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.

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.

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.

Multifocal Neuropathy: Expanding the Scope of Double Crush Syndrome.

PubMed

Cohen, Brian H; Gaspar, Michael P; Daniels, Alan H; Akelman, Edward; Kane, Patrick M

2016-12-01

Double crush syndrome (DCS), as it is classically defined, is a clinical condition composed of neurological dysfunction due to compressive pathology at multiple sites along a single peripheral nerve. The traditional definition of DCS is narrow in scope because many systemic pathologic processes, such as diabetes mellitus, drug-induced neuropathy, vascular disease and autoimmune neuronal damage, can have deleterious effects on nerve function. Multifocal neuropathy is a more appropriate term describing the multiple etiologies (including compressive lesions) that may synergistically contribute to nerve dysfunction and clinical symptoms. This paper examines the history of DCS and multifocal neuropathy, including the epidemiology and pathophysiology in addition to principles of evaluation and management. Copyright © 2016 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

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

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

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.

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.

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.

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

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

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.

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.

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

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

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.

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.

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.

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.

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

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.

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.

Comparing Two Methods for Reducing Variability in Voice Quality Measurements

ERIC Educational Resources Information Center

Kreiman, Jody; Gerratt, Bruce R.

2011-01-01

Purpose: Interrater disagreements in ratings of quality plague the study of voice. This study compared 2 methods for handling this variability. Method: Listeners provided multiple breathiness ratings for 2 sets of pathological voices, one including 20 male and 20 female voices unselected for quality and one including 20 breathy female voices.…

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.

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

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.

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

DTIC Science & Technology

2015-02-01

distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Athletes in contact sports who have sustained multiple concussive traumatic brain...who have sustained multiple concussive traumatic brain injuries 15-17 may also be at risk for this condition. Currently, there are no methods to...repetitive concussive TBI in mice has been optimal. Ongoing efforts include development of more sensitive methods to detect tau, and combinations of

[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.

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

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

Whole Slide Imaging Versus Microscopy for Primary Diagnosis in Surgical Pathology

PubMed Central

Mukhopadhyay, Sanjay; Feldman, Michael D.; Abels, Esther; Ashfaq, Raheela; Beltaifa, Senda; Cacciabeve, Nicolas G.; Cathro, Helen P.; Cheng, Liang; Cooper, Kumarasen; Dickey, Glenn E.; Gill, Ryan M.; Heaton, Robert P.; Kerstens, René; Lindberg, Guy M.; Malhotra, Reenu K.; Mandell, James W.; Manlucu, Ellen D.; Mills, Anne M.; Mills, Stacey E.; Moskaluk, Christopher A.; Nelis, Mischa; Patil, Deepa T.; Przybycin, Christopher G.; Reynolds, Jordan P.; Rubin, Brian P.; Saboorian, Mohammad H.; Salicru, Mauricio; Samols, Mark A.; Sturgis, Charles D.; Turner, Kevin O.; Wick, Mark R.; Yoon, Ji Y.; Zhao, Po

2018-01-01

Most prior studies of primary diagnosis in surgical pathology using whole slide imaging (WSI) versus microscopy have focused on specific organ systems or included relatively few cases. The objective of this study was to demonstrate that WSI is noninferior to microscopy for primary diagnosis in surgical pathology. A blinded randomized noninferiority study was conducted across the entire range of surgical pathology cases (biopsies and resections, including hematoxylin and eosin, immunohistochemistry, and special stains) from 4 institutions using the original sign-out diagnosis (baseline diagnosis) as the reference standard. Cases were scanned, converted to WSI and randomized. Sixteen pathologists interpreted cases by microscopy or WSI, followed by a wash-out period of ≥4 weeks, after which cases were read by the same observers using the other modality. Major discordances were identified by an adjudication panel, and the differences between major discordance rates for both microscopy (against the reference standard) and WSI (against the reference standard) were calculated. A total of 1992 cases were included, resulting in 15,925 reads. The major discordance rate with the reference standard diagnosis was 4.9% for WSI and 4.6% for microscopy. The difference between major discordance rates for microscopy and WSI was 0.4% (95% confidence interval, −0.30% to 1.01%). The difference in major discordance rates for WSI and microscopy was highest in endocrine pathology (1.8%), neoplastic kidney pathology (1.5%), urinary bladder pathology (1.3%), and gynecologic pathology (1.2%). Detailed analysis of these cases revealed no instances where interpretation by WSI was consistently inaccurate compared with microscopy for multiple observers. We conclude that WSI is noninferior to microscopy for primary diagnosis in surgical pathology, including biopsies and resections stained with hematoxylin and eosin, immunohistochemistry and special stains. This conclusion is valid across a wide variety of organ systems and specimen types. PMID:28961557

Whole Slide Imaging Versus Microscopy for Primary Diagnosis in Surgical Pathology: A Multicenter Blinded Randomized Noninferiority Study of 1992 Cases (Pivotal Study).

PubMed

Mukhopadhyay, Sanjay; Feldman, Michael D; Abels, Esther; Ashfaq, Raheela; Beltaifa, Senda; Cacciabeve, Nicolas G; Cathro, Helen P; Cheng, Liang; Cooper, Kumarasen; Dickey, Glenn E; Gill, Ryan M; Heaton, Robert P; Kerstens, René; Lindberg, Guy M; Malhotra, Reenu K; Mandell, James W; Manlucu, Ellen D; Mills, Anne M; Mills, Stacey E; Moskaluk, Christopher A; Nelis, Mischa; Patil, Deepa T; Przybycin, Christopher G; Reynolds, Jordan P; Rubin, Brian P; Saboorian, Mohammad H; Salicru, Mauricio; Samols, Mark A; Sturgis, Charles D; Turner, Kevin O; Wick, Mark R; Yoon, Ji Y; Zhao, Po; Taylor, Clive R

2018-01-01

Most prior studies of primary diagnosis in surgical pathology using whole slide imaging (WSI) versus microscopy have focused on specific organ systems or included relatively few cases. The objective of this study was to demonstrate that WSI is noninferior to microscopy for primary diagnosis in surgical pathology. A blinded randomized noninferiority study was conducted across the entire range of surgical pathology cases (biopsies and resections, including hematoxylin and eosin, immunohistochemistry, and special stains) from 4 institutions using the original sign-out diagnosis (baseline diagnosis) as the reference standard. Cases were scanned, converted to WSI and randomized. Sixteen pathologists interpreted cases by microscopy or WSI, followed by a wash-out period of ≥4 weeks, after which cases were read by the same observers using the other modality. Major discordances were identified by an adjudication panel, and the differences between major discordance rates for both microscopy (against the reference standard) and WSI (against the reference standard) were calculated. A total of 1992 cases were included, resulting in 15,925 reads. The major discordance rate with the reference standard diagnosis was 4.9% for WSI and 4.6% for microscopy. The difference between major discordance rates for microscopy and WSI was 0.4% (95% confidence interval, -0.30% to 1.01%). The difference in major discordance rates for WSI and microscopy was highest in endocrine pathology (1.8%), neoplastic kidney pathology (1.5%), urinary bladder pathology (1.3%), and gynecologic pathology (1.2%). Detailed analysis of these cases revealed no instances where interpretation by WSI was consistently inaccurate compared with microscopy for multiple observers. We conclude that WSI is noninferior to microscopy for primary diagnosis in surgical pathology, including biopsies and resections stained with hematoxylin and eosin, immunohistochemistry and special stains. This conclusion is valid across a wide variety of organ systems and specimen types.

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.

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

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.

Using the Periscope Live Video-Streaming Application for Global Pathology Education: A Brief Introduction.

PubMed

Fuller, Maren Y; Mukhopadhyay, Sanjay; Gardner, Jerad M

2016-07-21

Periscope is a live video-streaming smartphone application (app) that allows any individual with a smartphone to broadcast live video simultaneously to multiple smartphone users around the world. The aim of this review is to describe the potential of this emerging technology for global pathology education. To our knowledge, since the launch of the Periscope app (2015), only a handful of educational presentations by pathologists have been streamed as live video via Periscope. This review includes links to these initial attempts, a step-by-step guide for those interested in using the app for pathology education, and a summary of the pros and cons, including ethical/legal issues. We hope that pathologists will appreciate the potential of Periscope for sharing their knowledge, expertise, and research with a live (and potentially large) audience without the barriers associated with traditional video equipment and standard classroom/conference settings.

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

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.

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.

Atypical progression of multiple myeloma with extensive extramedullary disease.

PubMed Central

Jowitt, S N; Jacobs, A; Batman, P A; Sapherson, D A

1994-01-01

Multiple myeloma is a neoplastic disorder caused by the proliferation of a transformed B lymphoid progenitor cell that gives rise to a clone of immunoglobulin-secreting cells. Other plasma cell tumours include solitary plasmacytoma of bone (SPB) and extramedullary plasmacytomas (EMP). Despite an apparent common origin there exist pathological and clinical differences between these neoplasms and the association between them is not completely understood. A case of IgG multiple myeloma that presented with typical clinical and laboratory features, including a bone marrow infiltrated by well differentiated plasma cells, is reported. The tumour had an unusual evolution, with the development of extensive extramedullary disease while maintaining mature histological features. Images PMID:8163701

Multiple Schwannomas of the Spine: Review of the Schwannomatosis or Congenital Neurilemmomatosis: A Case Report.

PubMed

Lee, Sang-Hoon; Kim, Se-Hoon; Kim, Bum-Joon; Lim, Dong-Jun

2015-06-01

Schwannomas are the most common benign nerve sheath tumors originating in Schwann cells. With special conditions like neurofibromatosis type 2 or entity called schwannomatosis, patients develop multiple schwannomas. But in clinical setting, distinguishing schwannomatosis from neurofibromatosis type 2 is challengeable. We describe 58-year-old male who presented with severe neuropathic pain, from schwannomatosis featuring multiple schwannomas of spine and trunk, and underwent surgical treatment. We demonstrate his radiologic and clinical findings, and discuss about important clinical features of this condition. To confirm schwannomatosis, we performed brain magnetic resonance imaging, and took his familial history. Staged surgery was done for pathological confirmation and relief of the pain. Schwannomatosis and neurofibromatosis type 2 are similar but different disease. There are diagnostic hallmarks of these conditions, including familial history, pathology, and brain imaging. Because of different prognosis, the two diseases must be distinguished, so diagnostic tests that are mentioned above should be performed in caution.

Multiple Schwannomas of the Spine: Review of the Schwannomatosis or Congenital Neurilemmomatosis: A Case Report

PubMed Central

Lee, Sang-Hoon; Kim, Bum-Joon; Lim, Dong-Jun

2015-01-01

Schwannomas are the most common benign nerve sheath tumors originating in Schwann cells. With special conditions like neurofibromatosis type 2 or entity called schwannomatosis, patients develop multiple schwannomas. But in clinical setting, distinguishing schwannomatosis from neurofibromatosis type 2 is challengeable. We describe 58-year-old male who presented with severe neuropathic pain, from schwannomatosis featuring multiple schwannomas of spine and trunk, and underwent surgical treatment. We demonstrate his radiologic and clinical findings, and discuss about important clinical features of this condition. To confirm schwannomatosis, we performed brain magnetic resonance imaging, and took his familial history. Staged surgery was done for pathological confirmation and relief of the pain. Schwannomatosis and neurofibromatosis type 2 are similar but different disease. There are diagnostic hallmarks of these conditions, including familial history, pathology, and brain imaging. Because of different prognosis, the two diseases must be distinguished, so diagnostic tests that are mentioned above should be performed in caution. PMID:26217390

Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder: Current Status and Working Hypotheses

ERIC Educational Resources Information Center

Vaidya, Chandan J.; Stollstorff, Melanie

2008-01-01

Cognitive neuroscience studies of Attention Deficit Hyperactivity Disorder (ADHD) suggest multiple loci of pathology with respect to both cognitive domains and neural circuitry. Cognitive deficits extend beyond executive functioning to include spatial, temporal, and lower-level "nonexecutive" functions. Atypical functional anatomy extends beyond…

Risk Factors and Pathological Substrates Associated with Agitation/Aggression in Alzheimer's Disease: A Preliminary Study using NACC Data.

PubMed

Sennik, Simrin; Schweizer, Tom A; Fischer, Corinne E; Munoz, David G

2017-01-01

Neuropsychiatric symptoms are common manifestations of Alzheimer's disease (AD). A number of studies have targeted psychosis, i.e., hallucinations and delusions in AD, but few have assessed agitation/aggression in AD. To investigate the risk factors and pathological substrates associated with presence [A(+)] and absence [A(-)] of agitation/aggression (A) in autopsy-confirmed AD. Data was collected from the UDS data as of 2015 on the NACC database. Patients were stratified as intermediate (IAD) or high (HAD) pathological load of AD. Clinical diagnoses were not considered; additional pathological diagnoses were treated as variables. Analysis of data did not include a control group or corrections for multiple comparisons. 1,716 patients met the eligibility criteria; 31.2% of the IAD and 47.8% of the HAD patients were A(+), indicating an association with severity of pathology (p = 0.001). Risk factors for A(+) included: age at initial visit, age at death, years of education, smoking (in females), recent cardiac events (in males), and clinical history of traumatic brain injury (TBI) (in males). A history of hypertension was not related to A(+). In terms of comorbidity, clinical diagnosis of Lewy body dementia syndrome was associated with A(+) but the association was not confirmed when pathological diagnosis based on demonstration of Lewy bodies was used as the criterion. The additional presence of phosphorylated TDP-43, but not tau pathologies, was associated with A(+)HAD. Vascular lesions, including lacunes, large arterial infarcts, and severity of atherosclerosis were negatively associated with A(+). Associated symptoms included delusions, hallucinations, and depression, but not irritability, aberrant motor behavior, sleep and night time behavioral changes, or changes in appetite and eating habits. Smoking, TBI, and phosphorylated TDP-43 are associated with A(+)AD in specific groups, respectively. A(+) is directly associated with AD pathology load and inversely with vascular lesions.

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

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.

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.

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.

Cushing Syndrome in Carney Complex: Clinical, Pathologic, and Molecular Genetic Findings in the 17 Affected Mayo Clinic Patients.

PubMed

Lowe, Kathleen M; Young, William F; Lyssikatos, Charalampos; Stratakis, Constantine A; Carney, J Aidan

2017-02-01

Carney complex (CNC) is a rare dominantly inherited multiorgan tumoral disorder that includes Cushing syndrome (CS). To establish the Mayo Clinic experience with the CS component, including its clinical, laboratory, and pathologic findings, we performed a retrospective search of the patient and pathologic databases of Mayo Clinic in Rochester, MN, for patients with CNC and clinical or laboratory findings of CS. Thirty-seven patients with CNC were identified. Twenty-nine had clinical, pathologic, or laboratory evidence of an adrenocortical disorder. Seventeen had classic CS; 15 underwent bilateral, subtotal, or partial unilateral adrenalectomy, and 2 had no treatment. Pathologically, the glands were normal sized or slightly enlarged with multiple small (1 to 4 mm), brown, black, and yellow micronodules (primary pigmented nodular adrenocortical disease; PPNAD). Three glands each had a mass: a 2 cm adenoma, a 1.5 cm macronodule, and an unencapsulated 1.8 cm myelolipoma. Fourteen of the patients were alive at follow-up, and 3 were deceased; 2 of the latter had PPNAD at autopsy, and the third had PPNAD at surgery. Twelve patients without clinical features of classic CS had abnormal adrenocortical testing results; none developed classic CS during follow-up (mean, 10 y). Autopsy findings in 1 showed bilateral vacuolated cell cortical hyperplasia.

Cognitive impairment, decline and fluctuations in older community-dwelling subjects with Lewy bodies

PubMed Central

Arvanitakis, Z.; Yu, L.; Boyle, P. A.; Leurgans, S. E.; Bennett, D. A.

2012-01-01

Lewy bodies are common in the ageing brain and often co-occur with Alzheimer’s disease pathology. There is little known regarding the independent role of Lewy body pathology in cognition impairment, decline and fluctuations in community-dwelling older persons. We examined the contribution of Lewy body pathology to dementia, global cognition, cognitive domains, cognitive decline and fluctuations in 872 autopsied subjects (mean age = 87.9 years) from the Rush Religious Order Study (n = 491) and Memory and Aging Project (n = 381) longitudinal community-based clinical–pathological studies. Dementia was based on a clinical evaluation; annual cognitive performance tests were used to create a measure of global cognition and five cognitive domains. Lewy body type was determined by using α-synuclein immunostained sections of substantia nigra, limbic and neocortical regions. Statistical models included multiple regression models for dementia and cognition and mixed effects models for decline. Cognitive fluctuations were estimated by comparing standard deviations of individual residuals from mean trajectories of decline in those with and without Lewy bodies. All models controlled for age, sex, education, Alzheimer’s disease pathology and infarcts. One hundred and fifty-seven subjects (18%) exhibited Lewy body pathology (76 neocortical-type, 54 limbic-type and 27 nigra-predominant). One hundred and three (66%) subjects with Lewy body pathology had a pathologic diagnosis of Alzheimer’s disease. Neocortical-type, but not nigral-predominant or limbic-type Lewy body pathology was related to an increased odds of dementia (odds ratio = 3.21; 95% confidence interval = 1.78–5.81) and lower cognition (P < 0.001) including episodic memory function (P < 0.001) proximate to death. Neocortical-type Lewy body pathology was also related to a faster decline in global cognition (P < 0.001), decline in all five specific cognitive domains (all P-values < 0.001), and to fluctuations in decline of working and semantic memory (P-values < 0.001). Limbic-type Lewy body pathology was related to lower and faster decline in visuospatial skills (P = 0.042). The relationship of Lewy body pathology to cognition and dementia was not modified by Alzheimer’s disease pathology. Neocortical-type Lewy body pathology is associated with increased odds of dementia; lower and more rapid decline in all cognitive domains including episodic memory and fluctuations in decline in semantic and working memory. Limbic-type Lewy body pathology is specifically associated with lower and more rapid decline in visuospatial skills. The effect of Lewy body pathology on cognition appears to be independent of Alzheimer’s disease pathology. PMID:23065790

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

Bilateral primary xanthoma of the humeri with pathologic fractures: A case report

PubMed Central

Ali, Sayed; Fedenko, Alex; Syed, Ali B; Matcuk, George; Patel, Dakshesh; Gottsegen, Chris; White, Eric

2013-01-01

Xanthomas are rare bone tumors that occur more often in the appendicular skeleton and typically appear radiographically benign, with a narrow zone of transition and a sclerotic rim. We report the case of a 57-year-old woman with hyperlipidemia presenting with bilateral shoulder pain after minor trauma. Radiographic and histopathologic investigation demonstrated intraosseous xanthoma with atypical features, including multifocality, a wide zone of transition and pathologic fractures-characteristics more commonly associated with aggressive lesions such as multiple myeloma or metastasis. The diagnosis, imaging, and histological appearance of xanthoma of bone are reviewed. PMID:24198913

[Osteoarticular coccidioidomicosis. Clinical and pathological study of 36 Mexican patients].

PubMed

Torres-Nájera, Manuel; de la Garza-Galván, Sergio; Cerda-Flores, Ricardo M; Nocedal-Rustrián, Fausto C; Calderón-Garcidueñas, Ana Laura

2006-01-01

Coccidioidomycosis (CM) is primarily a lung disease. Systemic spread occurs in 1% of cases and one of its manifestation is osteoarthritis. To describe the clinical and pathological characteristics of 36 patients with osteoarthritis by Coccidioides immitis (COA). The surgical pathology records of two medical institutions were reviewed; patients with clinical diagnosis of osteoarthritis and definitive histopathological diagnosis of COA were included in the study. Results were analyzed by contingence tables (RXC) and chi2 test. Twenty six adults (19 men, seven women) and 10 children (seven males, three females) were studied. The chi2 analysis demonstrated a predominance of disease in men (72.2%, p = 0.008). There was no difference between males and females in relation to history of mycotic disease or diagnosis of lung disease after the diagnosis of COA. Bone involvement (76% of cases) was more frequent that pure joint lesions and the predominant radiological lesion was of lytic type. 30.5% of patients (11 cases) had multiple bone lesions and eight of them were men with multiple vertebral bone lesions. The COA was the only manifestation of disease in 83% of the patients. Therefore is important to consider this etiology in patients of endemic area. The clinical and radiological spectrum of COA is wide and may include a dentigerous and synovial cyst or simulates metastatic disease. The recognition of the clinical manifestations of COA may contribute to an opportune diagnosis and treatment.

Methodological quality and reporting of systematic reviews in hand and wrist pathology.

PubMed

Wasiak, J; Shen, A Y; Ware, R; O'Donohoe, T J; Faggion, C M

2017-10-01

The objective of this study was to assess methodological and reporting quality of systematic reviews in hand and wrist pathology. MEDLINE, EMBASE and Cochrane Library were searched from inception to November 2016 for relevant studies. Reporting quality was evaluated using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and methodological quality using a measurement tool to assess systematic reviews, the Assessment of Multiple Systematic Reviews (AMSTAR). Descriptive statistics and linear regression were used to identify features associated with improved methodological quality. A total of 91 studies were included in the analysis. Most reviews inadequately reported PRISMA items regarding study protocol, search strategy and bias and AMSTAR items regarding protocol, publication bias and funding. Systematic reviews published in a plastics journal, or which included more authors, were associated with higher AMSTAR scores. A large proportion of systematic reviews within hand and wrist pathology literature score poorly with validated methodological assessment tools, which may affect the reliability of their conclusions. I.

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.

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.

Lumbar foraminal stenosis, the hidden stenosis including at L5/S1.

PubMed

Orita, Sumihisa; Inage, Kazuhide; Eguchi, Yawara; Kubota, Go; Aoki, Yasuchika; Nakamura, Junichi; Matsuura, Yusuke; Furuya, Takeo; Koda, Masao; Ohtori, Seiji

2016-10-01

In patients with lower back and leg pain, lumbar foraminal stenosis (LFS) is one of the most important pathologies, especially for predominant radicular symptoms. LFS pathology can develop as a result of progressing spinal degeneration and is characterized by exacerbation with foraminal narrowing caused by lumbar extension (Kemp's sign). However, there is a lack of critical clinical findings for LFS pathology. Therefore, patients with robust and persistent leg pain, which is exacerbated by lumbar extension, should be suspected of LFS. Radiological diagnosis is performed using multiple radiological modalities, such as magnetic resonance imaging, including plain examination and novel protocols such as diffusion tensor imaging, as well as dynamic X-ray, and computed tomography. Electrophysiological testing can also aid diagnosis. Treatment options include both conservative and surgical approaches. Conservative treatment includes medication, rehabilitation, and spinal nerve block. Surgery should be considered when the pathology is refractory to conservative treatment and requires direct decompression of the exiting nerve root, including the dorsal root ganglia. In cases with decreased intervertebral height and/or instability, fusion surgery should also be considered. Recent advancements in minimally invasive lumbar lateral interbody fusion procedures enable effective and less invasive foraminal enlargement compared with traditional fusion surgeries such as transforaminal lumbar interbody fusion. The lumbosacral junction can cause L5 radiculopathy with greater incidence than other lumbar levels as a result of anatomical and epidemiological factors, which should be better addressed when treating clinical lower back pain.

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.

Which ante mortem clinical features predict progressive supranuclear palsy pathology?

PubMed

Respondek, Gesine; Kurz, Carolin; Arzberger, Thomas; Compta, Yaroslau; Englund, Elisabet; Ferguson, Leslie W; Gelpi, Ellen; Giese, Armin; Irwin, David J; Meissner, Wassilios G; Nilsson, Christer; Pantelyat, Alexander; Rajput, Alex; van Swieten, John C; Troakes, Claire; Josephs, Keith A; Lang, Anthony E; Mollenhauer, Brit; Müller, Ulrich; Whitwell, Jennifer L; Antonini, Angelo; Bhatia, Kailash P; Bordelon, Yvette; Corvol, Jean-Christophe; Colosimo, Carlo; Dodel, Richard; Grossman, Murray; Kassubek, Jan; Krismer, Florian; Levin, Johannes; Lorenzl, Stefan; Morris, Huw; Nestor, Peter; Oertel, Wolfgang H; Rabinovici, Gil D; Rowe, James B; van Eimeren, Thilo; Wenning, Gregor K; Boxer, Adam; Golbe, Lawrence I; Litvan, Irene; Stamelou, Maria; Höglinger, Günter U

2017-07-01

Progressive supranuclear palsy (PSP) is a neuropathologically defined disease presenting with a broad spectrum of clinical phenotypes. To identify clinical features and investigations that predict or exclude PSP pathology during life, aiming at an optimization of the clinical diagnostic criteria for PSP. We performed a systematic review of the literature published since 1996 to identify clinical features and investigations that may predict or exclude PSP pathology. We then extracted standardized data from clinical charts of patients with pathologically diagnosed PSP and relevant disease controls and calculated the sensitivity, specificity, and positive predictive value of key clinical features for PSP in this cohort. Of 4166 articles identified by the database inquiry, 269 met predefined standards. The literature review identified clinical features predictive of PSP, including features of the following 4 functional domains: ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction. No biomarker or genetic feature was found reliably validated to predict definite PSP. High-quality original natural history data were available from 206 patients with pathologically diagnosed PSP and from 231 pathologically diagnosed disease controls (54 corticobasal degeneration, 51 multiple system atrophy with predominant parkinsonism, 53 Parkinson's disease, 73 behavioral variant frontotemporal dementia). We identified clinical features that predicted PSP pathology, including phenotypes other than Richardson's syndrome, with varying sensitivity and specificity. Our results highlight the clinical variability of PSP and the high prevalence of phenotypes other than Richardson's syndrome. The features of variant phenotypes with high specificity and sensitivity should serve to optimize clinical diagnosis of PSP. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

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

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.

Benchmarking in pathology: development of an activity-based costing model.

PubMed

Burnett, Leslie; Wilson, Roger; Pfeffer, Sally; Lowry, John

2012-12-01

Benchmarking in Pathology (BiP) allows pathology laboratories to determine the unit cost of all laboratory tests and procedures, and also provides organisational productivity indices allowing comparisons of performance with other BiP participants. We describe 14 years of progressive enhancement to a BiP program, including the implementation of 'avoidable costs' as the accounting basis for allocation of costs rather than previous approaches using 'total costs'. A hierarchical tree-structured activity-based costing model distributes 'avoidable costs' attributable to the pathology activities component of a pathology laboratory operation. The hierarchical tree model permits costs to be allocated across multiple laboratory sites and organisational structures. This has enabled benchmarking on a number of levels, including test profiles and non-testing related workload activities. The development of methods for dealing with variable cost inputs, allocation of indirect costs using imputation techniques, panels of tests, and blood-bank record keeping, have been successfully integrated into the costing model. A variety of laboratory management reports are produced, including the 'cost per test' of each pathology 'test' output. Benchmarking comparisons may be undertaken at any and all of the 'cost per test' and 'cost per Benchmarking Complexity Unit' level, 'discipline/department' (sub-specialty) level, or overall laboratory/site and organisational levels. We have completed development of a national BiP program. An activity-based costing methodology based on avoidable costs overcomes many problems of previous benchmarking studies based on total costs. The use of benchmarking complexity adjustment permits correction for varying test-mix and diagnostic complexity between laboratories. Use of iterative communication strategies with program participants can overcome many obstacles and lead to innovations.

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

Preparing Addiction Specialists to Include Case Management and Vocational Rehabilitation Services in the Treatment Model for Problem Gamblers

ERIC Educational Resources Information Center

Glenn, Margaret K.; Diaz, Sebastian R.; Hawley, Carolyn

2009-01-01

Professionals in the field of addictions view problems associated with recovery management across multiple domains. This exploratory study utilized concept mapping and pattern matching methodology to conceptualize the resulting 7 domains of concern for treatment and aftercare of problem and pathological gamblers. The information can be used by…

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.

[Delivery in multiple pregnancies].

PubMed

Colla, F; D'Addato, F; Grio, R

2001-04-01

A knowledge of clinical physiognomy in pathologies related to multiple births is indispensable for improving maternal and feto-neonatal prognosis. This study is a contribution to the solution of this problem. A meta-analysis of data for multiple births at Department B of the Gynecology and Obstetrics Clinic at the University of Turi during the decade 1989-1998 was carried out, focusing on the arrangement and presentation of fetuses, the various types of birth, the gestational age at which birth occurred, the weight of neonates, neonatal mortality and maternal morbidity. Out of 11,523 births, there were a total of 194 (1.68%) multiple births, including 190 sets of twins and 4 triplets. 154 (79.38%) premature births were reported; 20 occurred <32(nd) week (10.29%). There was a high incidence of podalic presentation (26.30%) and shoulder presentation (5.61%) among twins; 202 were delivered using a cesarian section (51.53%) and 190 by vaginal birth (48.47%), of which 172 (90.52%) spontaneously. Surgical birth was an important means of extracting fetuses rapidly from a pathological environment. two hundred and sixty-two neonates (66.84%) were LBW (<2500 g), including 28 (7.14%) VLBW (>1500 g). The perinatal mortality rate was 3.82%. Maternal complications mainly occurred during the placental state, in the immediate postpartum and in puerperio. The authors feel that a more careful medical and social assistance, preventive hospitalisation, early recognition of the risk, constant monitoring for the optimal timing of birth, and lastly, qualified medical assistance during labour (expert gynecologist, trained obstetric staff) with other medical personnel (anesthetist, neonatal specialist) represent winning strategies to solve the problems arising during multiple pregnancies.

Financial and Health Literacy Predict Incident Alzheimer's Disease Dementia and Pathology.

PubMed

Yu, Lei; Wilson, Robert S; Schneider, Julie A; Bennett, David A; Boyle, Patricia A

2017-01-01

Domain specific literacy is a multidimensional construct that requires multiple resources including cognitive and non-cognitive factors. We test the hypothesis that domain specific literacy is associated with Alzheimer's disease (AD) dementia and AD pathology after controlling for cognition. Participants were community-based older persons who completed a baseline literacy assessment, underwent annual clinical evaluations for up to 8 years, and agreed to organ donation after death. Financial and health literacy was measured using 32 questions and cognition was measured using 19 tests. Annual diagnosis of AD dementia followed standard criteria. AD pathology was examined postmortem by quantifying plaques and tangles. Cox models examined the association of literacy with incident AD dementia. Performance of model prediction for incident AD dementia was assessed using indices for integrated discrimination improvement and continuous net reclassification improvement. Linear regression models examined the independent association of literacy with AD pathology in autopsied participants. All 805 participants were free of dementia at baseline and 102 (12.7%) developed AD dementia during the follow-up. Lower literacy was associated with higher risk for incident AD dementia (p < 0.001), and the association persisted after controlling for cognition (hazard ratio = 1.50, p = 0.004). The model including the literacy measure had better predictive performance than the one with demographics and cognition only. Lower literacy also was associated with higher burden of AD pathology after controlling for cognition (β= 0.07, p = 0.035). Literacy predicts incident AD dementia and AD pathology in community-dwelling older persons, and the association is independent of traditional measures of cognition.

Harnessing the immune system for treatment and detection of tau pathology.

PubMed

Congdon, Erin E; Krishnaswamy, Senthilkumar; Sigurdsson, Einar M

2014-01-01

The tau protein is an attractive target for therapy and diagnosis. We started a tau immunotherapy program about 13 years ago and have since demonstrated that active and passive immunotherapies diminish tau pathology and improve function, including cognition, in different mouse models. These findings have been confirmed and extended by several groups. We routinely detect neuronal, and to a lesser extent microglial, antibody uptake correlating with tau pathology. Antibodies bind tau aggregates in the endosomal/lysosomal system, enhancing clearance presumably by promoting their disassembly. Extracellular clearance has recently been shown by others, using antibodies that apparently are not internalized. As most pathological tau is neuronal, intracellular targeting may be more efficacious. However, extracellular tau may be more accessible to antibodies, with tau-antibody complexes a target for microglial phagocytosis. The extent of involvement of each pathway may depend on numerous factors including antibody properties, degree of pathology, and experimental model. On the imaging front, multiple tau ligands derived from β-sheet dyes have been developed by several groups, some with promising results in clinical PET tests. Postmortem analysis should clarify their tau specificity, as in theory and based on histological staining, those are likely to have some affinity for various amyloids. We are developing antibody-derived tau probes that should be more specific, and have in mouse models shown in vivo detection and binding to pathological tau after peripheral injection. These are exciting times for research on tau therapies and diagnostic agents that hopefully can be applied to humans in the near future.

Financial and health literacy predict incident AD dementia and AD pathology

PubMed Central

Yu, Lei; Wilson, Robert S.; Schneider, Julie A.; Bennett, David A.; Boyle, Patricia A.

2017-01-01

Background Domain specific literacy is a multidimensional construct that requires multiple resources including cognitive and non-cognitive factors. Objective We test the hypothesis that domain specific literacy is associated with AD dementia and AD pathology after controlling for cognition. Methods Participants were community based older persons who completed a baseline literacy assessment, underwent annual clinical evaluations for up to 8 years and agreed to organ donation after death. Financial and health literacy was measured using 32 questions and cognition was measured using 19 tests. Annual diagnosis of AD dementia followed standard criteria. AD pathology was examined post-mortem by quantifying plaques and tangles. Cox models examined the association of literacy with incident AD dementia. Performance of model prediction for incident AD dementia was assessed using indices for integrated discrimination improvement and continuous net reclassification improvement. Linear regression models examined the independent association of literacy with AD pathology in autopsied participants. Results All 805 participants were free of dementia at baseline and 102 (12.7%) developed AD dementia during the follow-up. Lower literacy was associated with higher risk for incident AD dementia (p<0.001), and the association persisted after controlling for cognition (Hazard Ratio=1.50, p=0.004). The model including the literacy measure had better predictive performance than the one with demographics and cognition only. Lower literacy also was associated with higher burden of AD pathology after controlling for cognition (β=0.07, p=0.035). Conclusion Literacy predicts incident AD dementia and AD pathology in community-dwelling older persons, and the association is independent of traditional measures of cognition. PMID:28157101

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.

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.

Obesity and Cardiometabolic Defects in Heart Failure Pathology.

PubMed

Halade, Ganesh V; Kain, Vasundhara

2017-09-12

Obesity is a major global epidemic that sets the stage for diverse multiple pathologies, including cardiovascular disease. The obesity-related low-grade chronic inflamed milieu is more pronounced in aging and responsive to cardiac dysfunction in heart failure pathology. Metabolic dysregulation of obesity integrates with immune reservoir in spleen and kidney network. Therefore, an integrative systems biology approach is necessary to delay progressive cardiac alternations. The purpose of this comprehensive review is to largely discuss the impact of obesity on the cardiovascular pathobiology in the context of problems and challenges, with major emphasis on the diversified models, and to study cardiac remodeling in obesity. The information in this article is immensely helpful in teaching advanced undergraduate, graduate, and medical students about the advancement and impact of obesity on cardiovascular health. © 2017 American Physiological Society. Compr Physiol 7:1463-1477, 2017. Copyright © 2017 John Wiley & Sons, Inc.

Core components of a comprehensive quality assurance program in anatomic pathology.

PubMed

Nakhleh, Raouf E

2009-11-01

In this article the core components of a comprehensive quality assurance and improvement plan are outlined. Quality anatomic pathology work comes with focus on accurate, timely, and complete reports. A commitment to continuous quality improvement and a systems approach with a persistent effort helps to achieve this end. Departments should have a quality assurance and improvement plan that includes a risk assessment of real and potential problems facing the laboratory. The plan should also list the individuals responsible for carrying out the program with adequate resources, a defined timetable, and annual assessment for progress and future directions. Quality assurance monitors should address regulatory requirements and be organized by laboratory division (surgical pathology, cytology, etc) as well as 5 segments (preanalytic, analytic, postanalytic phases of the test cycle, turn-around-time, and customer satisfaction). Quality assurance data can also be used to evaluate individual pathologists using multiple parameters with peer group comparison.

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).

Unknown risk: co-exposure to lead and other heavy metals among children living in small-scale mining communities in Zamfara State, Nigeria.

PubMed

Bartrem, Casey; Tirima, Simba; von Lindern, Ian; von Braun, Margrit; Worrell, Mary Claire; Mohammad Anka, Shehu; Abdullahi, Aishat; Moller, Gregory

2014-08-01

The lead poisoning crisis in Zamfara State, Northern Nigeria has been called the worst such case in modern history and it presents unique challenges for risk assessment and management of co-exposure to multiple heavy metals. More than 400 children have died in Zamfara as a result of ongoing lead intoxication since early in 2010. A review of the common toxic endpoints of the major heavy metals advances analysis of co-exposures and their common pathologies. Environmental contamination in Bagega village, examined by X-ray fluorescence of soils, includes lead, mercury, cadmium, arsenic and manganese. Co-exposure risk is explored by scoring common toxic endpoints and hazard indices to calculate a common pathology hazard risk ranking of Pb > As > Hg > Cd > Mn. Zamfara presents an extreme picture of both lead and multiple heavy metal mortality and morbidity, but similar situations have become increasingly prevalent worldwide.

The clinico-radiological paradox of cognitive function and MRI burden of white matter lesions in people with multiple sclerosis: A systematic review and meta-analysis.

PubMed

Mollison, Daisy; Sellar, Robin; Bastin, Mark; Mollison, Denis; Chandran, Siddharthan; Wardlaw, Joanna; Connick, Peter

2017-01-01

Moderate correlation exists between the imaging quantification of brain white matter lesions and cognitive performance in people with multiple sclerosis (MS). This may reflect the greater importance of other features, including subvisible pathology, or methodological limitations of the primary literature. To summarise the cognitive clinico-radiological paradox and explore the potential methodological factors that could influence the assessment of this relationship. Systematic review and meta-analysis of primary research relating cognitive function to white matter lesion burden. Fifty papers met eligibility criteria for review, and meta-analysis of overall results was possible in thirty-two (2050 participants). Aggregate correlation between cognition and T2 lesion burden was r = -0.30 (95% confidence interval: -0.34, -0.26). Wide methodological variability was seen, particularly related to key factors in the cognitive data capture and image analysis techniques. Resolving the persistent clinico-radiological paradox will likely require simultaneous evaluation of multiple components of the complex pathology using optimum measurement techniques for both cognitive and MRI feature quantification. We recommend a consensus initiative to support common standards for image analysis in MS, enabling benchmarking while also supporting ongoing innovation.

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.

Treatment for Multiple Aspergillus Spondylitis Including a Hip Joint

PubMed Central

Oh, In-Soo; Seo, Jun-Yeong; Kim, Yoon-Chung

2009-01-01

Multiple aspergillus spondylitis (AS) is a life threatening infection that occurs more commonly in immunocompromised patients, and is commonly treated with antifungal agents. However, there is relatively little information available on the treatment of multiple AS. The authors encountered a 46-year-old man suffering from low back and neck pain with radiculomyelopathy after a liver transplant. The patient had concomitant multiple AS in the cervico-thoraco-lumbar spine and right hip joint, as confirmed by radiologic imaging studies. The pathological examination of a biopsy specimen revealed fungal hyphae at the cervical and lumbar spine. Anterior decompression and interbody fusion were performed for the cervical and lumbar lesions, which showed instability and related neurological symptoms. Additional antifungal therapy was also performed. The patient was treated successfully with remission of his symptoms. PMID:20404956

Treatment for multiple Aspergillus spondylitis including a hip joint.

PubMed

Oh, In-Soo; Seo, Jun-Yeong; Ha, Kee-Yong; Kim, Yoon-Chung

2009-12-01

Multiple aspergillus spondylitis (AS) is a life threatening infection that occurs more commonly in immunocompromised patients, and is commonly treated with antifungal agents. However, there is relatively little information available on the treatment of multiple AS. The authors encountered a 46-year-old man suffering from low back and neck pain with radiculomyelopathy after a liver transplant. The patient had concomitant multiple AS in the cervico-thoraco-lumbar spine and right hip joint, as confirmed by radiologic imaging studies. The pathological examination of a biopsy specimen revealed fungal hyphae at the cervical and lumbar spine. Anterior decompression and interbody fusion were performed for the cervical and lumbar lesions, which showed instability and related neurological symptoms. Additional antifungal therapy was also performed. The patient was treated successfully with remission of his symptoms.

[A case of fat embolism syndrome associated with pathological femoral fracture caused by metastatic adenocarcinoma of the lung].

PubMed

Sato, Takashi; Soejima, Kenzo; Nakayama, Sohei; Satomi, Ryosuke; Sayama, Koichi; Asano, Koichiro

2010-10-01

A 76-year-old woman with multiple bone metastases from lung adenocarcinoma was admitted due to a pathological femoral fracture. On the night after admission, her consciousness deteriorated rapidly and she developed progressive respiratory failure. Computed tomography of the chest revealed diffuse ground glass opacities in both lungs, and magnetic resonance imaging of the brain showed multiple acute infarctions. Her condition improved after several days of supportive treatment with oxygen, corticosteroids and diuretics. Fat embolism syndrome should be considered as a differential diagnosis if consciousness disturbance and respiratory failure occur in patients with metastatic bone carcinoma and pathological long bone fractures.

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

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.

Multiple Endocrine Neoplasia Type 2B Unmasked by 18 F-FDG PET/CT and 131 I-MIBG SPECT/CT.

PubMed

Sun, Xun; Arnous, Maher Mohamad Rajab; Lan, Xiaoli

2017-04-01

F-FDG PET/CT was performed to detect an occult malignancy in a 26-year-old woman with complicated medical history which included paroxysmal hypertension and significantly elevated tumor marker. The images revealed lesions in the thyroid, lymph nodes, and bilateral adrenal glands. Further I-MIBG SPECT/CT revealed intense activity in the lesion in the left adrenal gland, which was consistent with pheochromocytoma. The pathology examination after subsequent neck biopsy demonstrated medullary thyroid carcinoma. A diagnosis of multiple endocrine neoplasia type 2B was eventually made.

Green Tea Extracts Epigallocatechin-3-gallate for Different Treatments

PubMed Central

Chu, Chenyu; Deng, Jia

2017-01-01

Epigallocatechin-3-gallate (EGCG), a component extracted from green tea, has been proved to have multiple effects on human pathological and physiological processes, and its mechanisms are discrepant in cancer, vascularity, bone regeneration, and nervous system. Although there are multiple benefits associated with EGCG, more and more challenges are still needed to get through. For example, EGCG shows low bioactivity via oral administration. This review focuses on effects of EGCG, including anti-cancer, antioxidant, anti-inflammatory, anticollagenase, and antifibrosis effects, to express the potential of EGCG and necessity of further studies in this field. PMID:28884125

The role of follow-up ultrasound and clinical parameters after abdominal MDCT in patients with multiple trauma.

PubMed

Geyer, Lucas L; Körner, M; Linsenmaier, U; Wirth, S; Reiser, M F; Meindl, T

2014-05-01

Beside its value during the initial trauma work-up (focused assessment with sonography for trauma), ultrasound (US) is recommended for early follow-up examinations of the abdomen in multiple injured patients. However, multidetector CT (MDCT) has proven to reliably diagnose traumatic lesions of abdominal organs, to depict their extent, and to assess their clinical relevance. To evaluate the diagnostic impact of follow-up US studies after MDCT of the abdomen and to identify possible clinical parameters indicating the need of a follow-up US. During a 30-month period, patients with suspected multiple trauma were allocated. Patients with admission to the ICU, an initial abdominal MDCT scan, and an US follow-up examination after 6 and 24 h were included. Two patient cohorts were defined: patients with normal abdominal MDCT (group 1), patients with trauma-related pathologic abdominal MDCT (group 2). In all patients, parameters indicating alteration of vital functions or hemorrhage within the first 24 h were obtained by reviewing the medical charts. Forty-four of 193 patients were included: 24 were categorized in group 1 (mean age, 41.1 years; range, 21-90 years), 20 in group 2 (mean age, 36.6 years; range, 16-71 years). In group 1, US did not provide new information compared to emergency MDCT. In group 2, there were no contradictory 6- and 24-h follow-up US findings. In patients with positive MDCT findings and alterations of clinical parameters, US did not detect progression of a previously diagnosed pathology or any late manifestation of such a lesion. In none of the patients with negative abdominal MDCT and pathological clinical parameters US indicated an abdominal injury. Routine US follow-up does not yield additional information after abdominal trauma. In patients with MDCT-proven organ lesions, follow-up MDCT should be considered if indicated by abnormal clinical and/or laboratory findings.

Development of Web tools to predict axillary lymph node metastasis and pathological response to neoadjuvant chemotherapy in breast cancer patients.

PubMed

Sugimoto, Masahiro; Takada, Masahiro; Toi, Masakazu

2014-12-09

Nomograms are a standard computational tool to predict the likelihood of an outcome using multiple available patient features. We have developed a more powerful data mining methodology, to predict axillary lymph node (AxLN) metastasis and response to neoadjuvant chemotherapy (NAC) in primary breast cancer patients. We developed websites to use these tools. The tools calculate the probability of AxLN metastasis (AxLN model) and pathological complete response to NAC (NAC model). As a calculation algorithm, we employed a decision tree-based prediction model known as the alternative decision tree (ADTree), which is an analog development of if-then type decision trees. An ensemble technique was used to combine multiple ADTree predictions, resulting in higher generalization abilities and robustness against missing values. The AxLN model was developed with training datasets (n=148) and test datasets (n=143), and validated using an independent cohort (n=174), yielding an area under the receiver operating characteristic curve (AUC) of 0.768. The NAC model was developed and validated with n=150 and n=173 datasets from a randomized controlled trial, yielding an AUC of 0.787. AxLN and NAC models require users to input up to 17 and 16 variables, respectively. These include pathological features, including human epidermal growth factor receptor 2 (HER2) status and imaging findings. Each input variable has an option of "unknown," to facilitate prediction for cases with missing values. The websites developed facilitate the use of these tools, and serve as a database for accumulating new datasets.

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

MassImager: A software for interactive and in-depth analysis of mass spectrometry imaging data.

PubMed

He, Jiuming; Huang, Luojiao; Tian, Runtao; Li, Tiegang; Sun, Chenglong; Song, Xiaowei; Lv, Yiwei; Luo, Zhigang; Li, Xin; Abliz, Zeper

2018-07-26

Mass spectrometry imaging (MSI) has become a powerful tool to probe molecule events in biological tissue. However, it is a widely held viewpoint that one of the biggest challenges is an easy-to-use data processing software for discovering the underlying biological information from complicated and huge MSI dataset. Here, a user-friendly and full-featured MSI software including three subsystems, Solution, Visualization and Intelligence, named MassImager, is developed focusing on interactive visualization, in-situ biomarker discovery and artificial intelligent pathological diagnosis. Simplified data preprocessing and high-throughput MSI data exchange, serialization jointly guarantee the quick reconstruction of ion image and rapid analysis of dozens of gigabytes datasets. It also offers diverse self-defined operations for visual processing, including multiple ion visualization, multiple channel superposition, image normalization, visual resolution enhancement and image filter. Regions-of-interest analysis can be performed precisely through the interactive visualization between the ion images and mass spectra, also the overlaid optical image guide, to directly find out the region-specific biomarkers. Moreover, automatic pattern recognition can be achieved immediately upon the supervised or unsupervised multivariate statistical modeling. Clear discrimination between cancer tissue and adjacent tissue within a MSI dataset can be seen in the generated pattern image, which shows great potential in visually in-situ biomarker discovery and artificial intelligent pathological diagnosis of cancer. All the features are integrated together in MassImager to provide a deep MSI processing solution at the in-situ metabolomics level for biomarker discovery and future clinical pathological diagnosis. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

MiR-191 Regulates Primary Human Fibroblast Proliferation and Directly Targets Multiple Oncogenes

PubMed Central

Polioudakis, Damon; Abell, Nathan S.; Iyer, Vishwanath R.

2015-01-01

miRNAs play a central role in numerous pathologies including multiple cancer types. miR-191 has predominantly been studied as an oncogene, but the role of miR-191 in the proliferation of primary cells is not well characterized, and the miR-191 targetome has not been experimentally profiled. Here we utilized RNA induced silencing complex immunoprecipitations as well as gene expression profiling to construct a genome wide miR-191 target profile. We show that miR-191 represses proliferation in primary human fibroblasts, identify multiple proto-oncogenes as novel miR-191 targets, including CDK9, NOTCH2, and RPS6KA3, and present evidence that miR-191 extensively mediates target expression through coding sequence (CDS) pairing. Our results provide a comprehensive genome wide miR-191 target profile, and demonstrate miR-191’s regulation of primary human fibroblast proliferation. PMID:25992613

Pathologic Progression, Possible Origin, and Management of Multiple Primary Intracranial Neuroendocrine Carcinomas.

PubMed

Cao, Jingwei; Xu, Wenzhe; Du, Zhenhui; Sun, Bin; Li, Feng; Liu, Yuguang

2017-10-01

Primary intracranial neuroendocrine carcinomas (NECs) are extremely rare malignant tumors with no previous reports of multiple ones in the literatures. The clinical presentation, preoperative and reexamined magnetic resonance imaging findings, as well as histopathologic studies of a 56-year-old female subject with multiple intracranial NECs mimicking multiple intracranial meningiomas, who underwent 3 operations with left parietal craniotomy, right occipital parietal craniotomy, and left frontal craniotomy, separately and chronologically, are presented in this article. Noteworthy, the first and second tumors were confirmed as NECs exhibiting histologic characteristics of typical anaplastic meningiomas with features of whorl formation, while the third tumor was a typical NEC with features of organoid cancer nests. In other words, the first 2 lesions were diagnosed as meningioma as opposed to NEC. It was only after the third surgery that the pathology for the first 2 cases was reviewed and had a revised diagnosis. After the third surgical resection, the patient further received whole brain radiotherapy and systemic chemotherapy (temozolomide combined with YH-16). At her 10-month follow-up, the patient achieved a good outcome. Multiple primary intracranial NECs are extremely rare. The tumor might be of arachnoidal or leptomeningeal origin, with histologic patterns that might lead to transformation and/or progression. Maximal surgical resection is warranted for symptomatic mass effect. Postoperative adjuvant treatments including radiotherapy and chemotherapy should be a recommended therapeutic modality. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Relation of genomic variants for Alzheimer disease dementia to common neuropathologies

PubMed Central

Yu, Lei; Buchman, Aron S.; Schneider, Julie A.; De Jager, Philip L.; Bennett, David A.

2016-01-01

Objective: To investigate the associations of previously reported Alzheimer disease (AD) dementia genomic variants with common neuropathologies. Methods: This is a postmortem study including 1,017 autopsied participants from 2 clinicopathologic cohorts. Analyses focused on 22 genomic variants associated with AD dementia in large-scale case-control genome-wide association study (GWAS) meta-analyses. The neuropathologic traits of interest were a pathologic diagnosis of AD according to NIA-Reagan criteria, macroscopic and microscopic infarcts, Lewy bodies (LB), and hippocampal sclerosis. For each variant, multiple logistic regression was used to investigate its association with neuropathologic traits, adjusting for age, sex, and subpopulation structure. We also conducted power analyses to estimate the sample sizes required to detect genome-wide significance (p < 5 × 10−8) for pathologic AD for all variants. Results: APOE ε4 allele was associated with greater odds of pathologic AD (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.67–5.46, p = 1.9 × 10−13), while ε2 allele was associated with lower odds of pathologic AD (OR 0.42, 95% CI 0.30–0.61, p = 3.1 × 10−6). Four additional genomic variants including rs6656401 (CR1), rs1476679 (ZCWPW1), rs35349669 (INPP5D), and rs17125944 (FERMT2) had p values less than 0.05. Remarkably, half of the previously reported AD dementia variants are not likely to be detected for association with pathologic AD with a sample size in excess of the largest GWAS meta-analyses of AD dementia. Conclusions: Many recently discovered genomic variants for AD dementia are not associated with the pathology of AD. Some genomic variants for AD dementia appear to be associated with other common neuropathologies. PMID:27371493

Relation of genomic variants for Alzheimer disease dementia to common neuropathologies.

PubMed

Farfel, Jose M; Yu, Lei; Buchman, Aron S; Schneider, Julie A; De Jager, Philip L; Bennett, David A

2016-08-02

To investigate the associations of previously reported Alzheimer disease (AD) dementia genomic variants with common neuropathologies. This is a postmortem study including 1,017 autopsied participants from 2 clinicopathologic cohorts. Analyses focused on 22 genomic variants associated with AD dementia in large-scale case-control genome-wide association study (GWAS) meta-analyses. The neuropathologic traits of interest were a pathologic diagnosis of AD according to NIA-Reagan criteria, macroscopic and microscopic infarcts, Lewy bodies (LB), and hippocampal sclerosis. For each variant, multiple logistic regression was used to investigate its association with neuropathologic traits, adjusting for age, sex, and subpopulation structure. We also conducted power analyses to estimate the sample sizes required to detect genome-wide significance (p < 5 × 10(-8)) for pathologic AD for all variants. APOE ε4 allele was associated with greater odds of pathologic AD (odds ratio [OR] 3.82, 95% confidence interval [CI] 2.67-5.46, p = 1.9 × 10(-13)), while ε2 allele was associated with lower odds of pathologic AD (OR 0.42, 95% CI 0.30-0.61, p = 3.1 × 10(-6)). Four additional genomic variants including rs6656401 (CR1), rs1476679 (ZCWPW1), rs35349669 (INPP5D), and rs17125944 (FERMT2) had p values less than 0.05. Remarkably, half of the previously reported AD dementia variants are not likely to be detected for association with pathologic AD with a sample size in excess of the largest GWAS meta-analyses of AD dementia. Many recently discovered genomic variants for AD dementia are not associated with the pathology of AD. Some genomic variants for AD dementia appear to be associated with other common neuropathologies. © 2016 American Academy of Neurology.

Patients With Chondrolabral Pathology Have Bilateral Functional Impairments 12 to 24 Months After Unilateral Hip Arthroscopy: A Cross-sectional Study.

PubMed

Kemp, Joanne L; Risberg, May Arna; Schache, Anthony G; Makdissi, Michael; Pritchard, Michael G; Crossley, Kay M

2016-11-01

Study Design Cross-sectional study. Background Functional task performance in patients with chondrolabral pathology following hip arthroscopy is unknown. Objectives To investigate in people with chondrolabral pathology following hip arthroscopy (1) the bilateral differences in functional task performance compared to controls, (2) the association of hip muscle strength with functional task performance, and (3) the association of functional task performance scores with good outcome, as measured by International Hip Outcome Tool score. Methods Seventy-one patients who had unilateral hip arthroscopy for hip pain and 60 controls were recruited. Patient-reported outcomes included the 4 subscales of the International Hip Outcome Tool. Hip muscle strength measures included abduction, adduction, extension, flexion, external rotation, and internal rotation. Functional tasks assessed included the single hop test, the side bridge test, and the single-leg rise test. For aim 1, analyses of covariance tests were used. For aim 2, stepwise multiple linear regression analyses were used. For aim 3, receiver operating characteristic curve analyses were used. Results Compared to controls, the chondrolabral pathology group had significantly worse performance on both legs for each of the functional tasks (P<.001). Greater hip abduction strength was moderately associated with better performance on functional tasks in the chondrolabral pathology group (adjusted R 2 range, 0.197-0.407; P<.001). Cutoff values associated with good outcome were 0.37 (hop distance/height) for the single hop, 16 repetitions for the single-leg rise, and 34 seconds for the side bridge test. Conclusion Patients with hip chondrolabral pathology had reduced functional task performance bilaterally 12 to 24 months after unilateral hip arthroscopy when compared to controls. Level of Evidence Therapy/symptom prevalence, level 3b. J Orthop Sports Phys Ther 2016;46(11):947-956. doi:10.2519/jospt.2016.6577.

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

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

DTIC Science & Technology

2015-02-01

13. SUPPLEMENTARY NOTES 14. ABSTRACT Athletes in contact sports who have sustained multiple concussive traumatic brain injuries are at high risk for...multiple concussive traumatic brain injuries 15-17 may also be at risk for this condition. Currently, there are no methods to identify progressive tau...after traumatic brain injury. Progress to date: To date, none of the attempts to model progressive tau pathology after repetitive concussive TBI in

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

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

Myopathology of Adult and Paediatric Mitochondrial Diseases

PubMed Central

Phadke, Rahul

2017-01-01

Mitochondria are dynamic organelles ubiquitously present in nucleated eukaryotic cells, subserving multiple metabolic functions, including cellular ATP generation by oxidative phosphorylation (OXPHOS). The OXPHOS machinery comprises five transmembrane respiratory chain enzyme complexes (RC). Defective OXPHOS gives rise to mitochondrial diseases (mtD). The incredible phenotypic and genetic diversity of mtD can be attributed at least in part to the RC dual genetic control (nuclear DNA (nDNA) and mitochondrial DNA (mtDNA)) and the complex interaction between the two genomes. Despite the increasing use of next-generation-sequencing (NGS) and various omics platforms in unravelling novel mtD genes and pathomechanisms, current clinical practice for investigating mtD essentially involves a multipronged approach including clinical assessment, metabolic screening, imaging, pathological, biochemical and functional testing to guide molecular genetic analysis. This review addresses the broad muscle pathology landscape including genotype–phenotype correlations in adult and paediatric mtD, the role of immunodiagnostics in understanding some of the pathomechanisms underpinning the canonical features of mtD, and recent diagnostic advances in the field. PMID:28677615

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.

Factors associated with resistance to dementia despite high Alzheimer disease pathology.

PubMed

Erten-Lyons, D; Woltjer, R L; Dodge, H; Nixon, R; Vorobik, R; Calvert, J F; Leahy, M; Montine, T; Kaye, J

2009-01-27

Autopsy series have shown that some elderly people remain with normal cognitive function during life despite having high burdens of pathologic lesions associated with Alzheimer disease (AD) at death. Understanding why these individuals show no cognitive decline, despite high AD pathologic burdens, may be key to discovery of neuroprotective mechanisms. A total of 36 subjects who on autopsy had Braak stage V or VI and moderate or frequent neuritic plaque scores based on Consortium to Establish a Registry for Alzheimer's Disease (CERAD) standards were included. Twelve had normal cognitive function and 24 a diagnosis of AD before death. Demographic characteristics, clinical and pathologic data, as well as antemortem brain volumes were compared between the groups. In multiple regression analysis, antemortem hippocampal and total brain volumes were significantly larger in the group with normal cognitive function after adjusting for gender, age at MRI, time from MRI to death, Braak stage, CERAD neuritic plaque score, and overall presence of vascular disease. Larger brain and hippocampal volumes were associated with preserved cognitive function during life despite a high burden of Alzheimer disease (AD) pathologic lesions at death. A better understanding of processes that lead to preservation of brain volume may provide important clues for the discovery of mechanisms that protect the elderly from AD.

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

Clinical applications of CO2 laser resurfacing in the treatment of various pathologic skin disorders

NASA Astrophysics Data System (ADS)

Giler, Shamai

1997-12-01

CO2 laser skin resurfacing devices are widely used in cosmetic surgery for the treatment of facial rhytides, acne scars and aging skin. This technique is also useful in the treatment of various benign and premalignant or multiple pathological skin conditions and disorders originating in the epidermal, dermal and skin appendages, vascular lesions, epidermal nevi, infected wounds and ulcers, and keloids. Various surgical techniques have been developed in our clinic using laser resurfacing in the treatment of more than 2,000 patients with various skin pathologic disorders. We describe our experience with the various techniques used. The precise depth control and ablation properties combined with the hemostatic and sterilizing effects of the CO2 laser beam, reduction of the possibility of bleeding, infection and damage to healthy tissues, make the CO2 laser resurfacing techniques the treatment of choice for cosmetic surgery and treatment of benign, premalignant and multiple pathologic skin conditions.

VEGF-independent angiogenic pathways induced by PDGF-C

PubMed Central

Kumar, Anil; Zhang, Fan; Lee, Chunsik; Li, Yang; Tang, Zhongshu; Arjunan, Pachiappan

2010-01-01

VEGF is believed to be a master regulator in both developmental and pathological angiogenesis. The role of PDGF-C in angiogenesis, however, is only at the beginning of being revealed. We and others have shown that PDGF-C is a critical player in pathological angiogenesis because of its pleiotropic effects on multiple cellular targets. The angiogenic pathways induced by PDGF-C are, to a large extent, VEGF-independent. These pathways may include, but not limited to, the direct effect of PDGF-C on vascular cells, the effect of PDGF-C on tissue stroma fibroblasts, and its effect on macrophages. Taken together, the pleiotropic, versatile and VEGF-independent angiogenic nature of PDGF-C has placed it among the most important target genes for antiangiogenic therapy. PMID:20871734

Familial Prion Disease with Alzheimer Disease-Like Tau Pathology and Clinical Phenotype

PubMed Central

Jayadev, Suman; Nochlin, David; Poorkaj, Parvoneh; Steinbart, Ellen J.; Mastrianni, James A.; Montine, Thomas J.; Ghetti, Bernardino; Schellenberg, Gerard D.; Bird, Thomas D.; Leverenz, James B.

2011-01-01

Objective To describe the Alzheimer disease (AD)-like clinical and pathological features, including marked neurofibrillary tangle (NFT) pathology, of a familial prion disease due to a rare nonsense mutation of the prion gene (PRNP). Methods Longitudinal clinical assessments were available for the proband and her mother. After death, both underwent neuropathological evaluation. PRNP was sequenced after failure to find immunopositive Aβ deposits in the proband and the documentation of prion protein (PrP) immunopositive pathology. Results The proband presented at age 42 years with a 3-year history of progressive short-term memory impairment and depression. Neuropsychological testing found impaired memory performance, with relatively preserved attention and construction. She was diagnosed with AD and died at age 47 years. Neuropathologic evaluation revealed extensive limbic and neocortical NFT formation and neuritic plaques consistent with a Braak stage of VI. The NFTs were immunopositive, with multiple tau antibodies, and electron microscopy revealed paired helical filaments. However, the neuritic plaques were immunonegative for Aβ, whereas immunostaining for PrP was positive. The mother of the proband had a similar presentation, including depression, and had been diagnosed clinically and pathologically as AD. Reevaluation of her brain tissue confirmed similar tau and PrP immunostaining findings. Genetic analysis revealed that both the proband and her mother had a rare PRNP mutation (Q160X) that resulted in the production of truncated PrP. Interpretation We suggest that PRNP mutations that result in a truncation of PrP lead to a prolonged clinical course consistent with a clinical diagnosis of AD and severe AD-like NFTs. PMID:21416485

Hip instability: a review of hip dysplasia and other contributing factors

PubMed Central

Kraeutler, Matthew J.; Garabekyan, Tigran; Pascual-Garrido, Cecilia; Mei-Dan, Omer

2016-01-01

Summary Background Hip instability has classically been associated with developmental dysplasia of the hip (DDH) in newborns and children. However, numerous factors may contribute to hip instability in children, adolescents, and adults. Purpose This review aims to concisely present the literature on hip instability in patients of all ages in order to guide health care professionals in the appropriate diagnosis and treatment of the various disorders which may contribute to an unstable hip. Methods We reviewed the literature on the diagnosis and surgical management of hip dysplasia and other causes of hip instability. Conclusions Multiple intra- and extra-articular variables may contribute to hip instability, including acetabular bony coverage, femoral torsion, femoroacetabular impingement, and soft tissue laxity. Physical examination and advanced imaging studies are essential to accurately diagnose the pathology contributing to a patient’s unstable hip. Conservative management, including activity modification and physical therapy, may be used as a first-line treatment in patients with intra-articular hip pathology. Patients who continue to experience symptoms of pain or instability should proceed with arthroscopic or open surgical treatment aimed at correcting the underlying pathology. Level of evidence V. PMID:28066739

Large Amplitude Cortical Evoked Potentials in Nonepileptic Patients. Reviving an Old Neurophysiologic Tool to Help Detect CNS Pathology.

PubMed

Martín-Palomeque, Guillermo; Castro-Ortiz, Antonio; Pamplona-Valenzuela, Pilar; Saiz-Sepúlveda, Miguel Á; Cabañes-Martínez, Lidia; López, Jaime R

2017-01-01

Although large amplitude evoked potentials (EPs) are typically associated with progressive myoclonic epilepsy patients, giant EPs imply central nervous system (CNS) hyperexcitability and can be seen in various nonepileptic disorders. We performed a retrospective chart review including history, physical examination, imaging and diagnostic studies of nonepileptic patients with large amplitude somatosensory evoked potentials (SSEPs) and visual evoked potentials (VEPs) during 2007 to 2013. Large amplitude EPs were defined as follows: VEPs (N75-P100) >18 μV; and SSEPs (N20-P25) >6.4 μV. Recording montage for VEPs was Oz-Cz and SSEPs C3'/C4'-Fz. Fifty-two patients (33 females, 19 males; age range, 9-90 years) were identified. No CNS pathology was detected in 7 patients. All remaining patients were diagnosed with new CNS disorders including: vascular (37%); myelopathies (13%); demyelinating (11%); space occupying lesions (8.7%); syringomyelia (8.7%); hydrocephalus (6.5%); Vitamin B-12 deficiency (4.3%); multiple system atrophy (4.3%); and toxins (2.2%). This study supports the notion that large amplitude EP implies CNS hyperexcitability and CNS disease. These results confirm the utility of EP studies in patients with suspected CNS pathology.

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.

[Correlations of 18F-Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Imaging Parameters with the Pathological Differentiation of Head and Neck Squamous Cell Carcinoma and Their Diagnostic Efficiencies].

PubMed

Dang, Hao Dan; Chen, Yu; Shi, Xiao Hua; Hou, Bo; Xing, Hai Qun; Zhang, Tao; Chen, Xing Ming; Zhang, Zhu Hua; Xue, Hua Dan; Jin, Zheng Yu

2018-04-28

Objective To evaluate the correlation of the positron emission tomography/magnetic resonance imaging (PET/MR) parameters with the pathological differentiation of head and neck squamous cell carcinoma(HNSCC) and the diagnostic efficiencies of PET/MR parameters. Methods Patients with clinical suspicion of HNSCC were included and underwent PET/MR scan. HNSCC was pathologically confirmed in all these patients. The PET/MR examination included PET and MR sequences of diffusion-weighted imaging (DWI) and T2-and T1-weighted imaging. The multiple parameters of PET/MR included the mean values of apparent diffusion coefficient(ADC mean ) and the maximum and mean values of standardized uptake value (SUV max and SUV mean ) were measured and estimated. The correlations of all the parameters and distribution between the different tumor differentiation groups were analyzed. Logistic regression was utilized to build the model as the PET/MR combined parameter for predicting the differentiation by multiple parameters of PET/MR. The receiver operating characteristic curve was calculated for each parameter and the combination. Results Totally 23 patients were included in this study:9 patients (9 males and 0 female) had well-differentiated tumor,with an average age of (61.0±6.8)years;14 cases had moderately-differentiated (n=10) or poorly-differentiated tumors (n=4),with an average age of (62.0±9.1) years. All the patients were males. There was statistical correlation between SUV mean and SUV max (P<0.001);however,ADC mean showed no statistical correlation with SUV max and with SUV mean (P=0.42,P=0.13). ADC mean and SUV mean showed significant difference between well-differentiated group and moderately-poorly-differentiated group (P=0.005,P=0.007). Compared with the individual parameters,the combination of PET/MR parameters with SUV mean and ADC mean had higher efficacy in predicting tumor differentiation,with an area under curve of 0.84. Conclusions The distributions of ADC mean ,SUV max and SUV mean differ among HNSCC with different pathological differentiation. Compared with the individual parameters,the combination of the PET/MR parameters has higher efficiency in predicting tumor differentiation.

Chronic Inflammatory Demyelinating Polyradiculoneuropathy: From Bench to Bedside

PubMed Central

Peltier, Amanda C.; Donofrio, Peter D.

2015-01-01

Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) is the most common treatable chronic autoimmune neuropathy. Multiple diagnostic criteria have been established, with the primary goal of identifying neurophysiologic hallmarks of acquired demyelination. Treatment modalities have expanded to include numerous immuno-modulatory therapies, although the best evidence continues to be for corticosteroids, plasma exchange, and intravenous immunoglobulins (IVIg). This review describes the pathology, epidemiology, pathogenesis, diagnosis, and treatment of CIDP. PMID:23117943

Trigeminal Neuralgia

PubMed Central

Yadav, Yad Ram; Nishtha, Yadav; Sonjjay, Pande; Vijay, Parihar; Shailendra, Ratre; Yatin, Khare

2017-01-01

Trigeminal neuralgia (TN) is a sudden, severe, brief, stabbing, and recurrent pain within one or more branches of the trigeminal nerve. Type 1 as intermittent and Type 2 as constant pain represent distinct clinical, pathological, and prognostic entities. Although multiple mechanism involving peripheral pathologies at root (compression or traction), and dysfunctions of brain stem, basal ganglion, and cortical pain modulatory mechanisms could have role, neurovascular conflict is the most accepted theory. Diagnosis is essentially clinically; magnetic resonance imaging is useful to rule out secondary causes, detect pathological changes in affected root and neurovascular compression (NVC). Carbamazepine is the drug of choice; oxcarbazepine, baclofen, lamotrigine, phenytoin, and topiramate are also useful. Multidrug regimens and multidisciplinary approaches are useful in selected patients. Microvascular decompression is surgical treatment of choice in TN resistant to medical management. Patients with significant medical comorbidities, without NVC and multiple sclerosis are generally recommended to undergo gamma knife radiosurgery, percutaneous balloon compression, glycerol rhizotomy, and radiofrequency thermocoagulation procedures. Partial sensory root sectioning is indicated in negative vessel explorations during surgery and large intraneural vein. Endoscopic technique can be used alone for vascular decompression or as an adjuvant to microscope. It allows better visualization of vascular conflict and entire root from pons to ganglion including ventral aspect. The effectiveness and completeness of decompression can be assessed and new vascular conflicts that may be missed by microscope can be identified. It requires less brain retraction. PMID:29114270

Characteristics of Rosai-Dorfman Disease Primarily Involved in the Central Nervous System: 3 Case Reports and Review of Literature.

PubMed

Luo, Zhengxiang; Zhang, Yansong; Zhao, Penglai; Lu, Hucheng; Yang, Kun; Zhang, Yuhai; Zeng, Yanjun

2017-01-01

This study aimed to summarize the clinical characteristics of Rosai-Dorfman disease primarily involving the central nervous system and to explore diagnosis and treatment. We analyzed the clinical, imaging, and pathologic characteristics; treatment; and prognosis in 3 cases of Rosai-Dorfman disease primarily involving the central nervous system. We also performed a literature review. The largest of multiple intracranial lesions was totally resected, and steroid administration and radiotherapy were performed in phases for the remaining lesions. During the 1-year follow-up period, the excised lesion did not recur, and no obvious variations were observed in the other lesions. Subtotal resection was performed of the largest of another group of multiple intracranial lesions, and the residual did not show any obvious variations during the 1-year follow-up period. The isolated lesion was totally resected and did not recur during a 2-year follow-up period. Rosai-Dorfman disease with multiple lesions primarily involving the central nervous system is rare. Imaging characteristics are similar to meningiomas, and the pathological features include lymphocytes and plasma cells reaching tissue cells with large volume and abundant cytoplasm. Surgery is the preferred treatment, as the effects of steroid administration and radiotherapy are not apparent. Copyright © 2016 Elsevier Inc. All rights reserved.

A combined post-mortem magnetic resonance imaging and quantitative histological study of multiple sclerosis pathology

PubMed Central

Kolasinski, James; Chance, Steven A.; DeLuca, Gabriele C.; Esiri, Margaret M.; Chang, Eun-Hyuk; Palace, Jacqueline A.; McNab, Jennifer A.; Jenkinson, Mark; Miller, Karla L.; Johansen-Berg, Heidi

2012-01-01

Multiple sclerosis is a chronic inflammatory neurological condition characterized by focal and diffuse neurodegeneration and demyelination throughout the central nervous system. Factors influencing the progression of pathology are poorly understood. One hypothesis is that anatomical connectivity influences the spread of neurodegeneration. This predicts that measures of neurodegeneration will correlate most strongly between interconnected structures. However, such patterns have been difficult to quantify through post-mortem neuropathology or in vivo scanning alone. In this study, we used the complementary approaches of whole brain post-mortem magnetic resonance imaging and quantitative histology to assess patterns of multiple sclerosis pathology. Two thalamo-cortical projection systems were considered based on their distinct neuroanatomy and their documented involvement in multiple sclerosis: lateral geniculate nucleus to primary visual cortex and mediodorsal nucleus of the thalamus to prefrontal cortex. Within the anatomically distinct thalamo-cortical projection systems, magnetic resonance imaging derived cortical thickness was correlated significantly with both a measure of myelination in the connected tract and a measure of connected thalamic nucleus cell density. Such correlations did not exist between these markers of neurodegeneration across different thalamo-cortical systems. Magnetic resonance imaging lesion analysis depicted clearly demarcated subcortical lesions impinging on the white matter tracts of interest; however, quantitation of the extent of lesion-tract overlap failed to demonstrate any appreciable association with the severity of markers of diffuse pathology within each thalamo-cortical projection system. Diffusion-weighted magnetic resonance imaging metrics in both white matter tracts were correlated significantly with a histologically derived measure of tract myelination. These data demonstrate for the first time the relevance of functional anatomical connectivity to the spread of multiple sclerosis pathology in a ‘tract-specific’ pattern. Furthermore, the persisting relationship between metrics from post-mortem diffusion-weighted magnetic resonance imaging and histological measures from fixed tissue further validates the potential of imaging for future neuropathological studies. PMID:23065787

Pathologic C-spine fracture with low risk mechanism and normal physical exam.

PubMed

Hunter, Andrew; McGreevy, Jolion; Linden, Judith

2017-09-01

Cervical spinal fracture is a rare, but potentially disabling complication of trauma to the neck. Clinicians often rely on clinical decision rules and guidelines to decide whether or not imaging is necessary when a patient presents with neck pain. Validated clinical guidelines include the Canadian C-Spine Rule and the Nexus criteria. Studies suggest that the risks of a pathologic fracture from a simple rear end collision are negligible. We present a case of an individual who presented to an emergency department (ED) after a low speed motor vehicle collision complaining of lateral neck pain and had multiple subsequent visits for the same complaint with negative exam findings. Ultimately, he was found to have a severely pathologic cervical spine fracture with notable cord compression. Our objective is to discuss the necessity to incorporate clinical decision rules with physician gestalt and the need to take into account co-morbidities of a patient presenting after a minor MVC. Copyright © 2017 Elsevier Inc. All rights reserved.

Human sexual behavior related to pathology and activity of the brain.

PubMed

Komisaruk, Barry R; Rodriguez Del Cerro, Maria Cruz

2015-01-01

Reviewed in this chapter are: (1) correlations among human sexual behavior, brain pathology, and brain activity, including caveats regarding the interpretation of "cause and effect" among these factors, and the degree to which "hypersexuality" and reported changes in sexual orientation correlated with brain pathology are uniquely sexual or are attributable to a generalized disinhibition of brain function; (2) the effects, in some cases inhibitory, in others facilitatory, on sexual behavior and motivation, of stroke, epileptic seizures, traumatic brain injury, and brain surgery; and (3) insights into sexual motivation and behavior recently gained from functional brain imaging research and its interpretive limitations. We conclude from the reviewed research that the neural orchestra underlying the symphony of human sexuality comprises, rather than brain "centers," multiple integrated brain systems, and that there are more questions than answers in our understanding of the control of human sexual behavior by the brain - a level of understanding that is still in embryonic form. © 2015 Elsevier B.V. All rights reserved.

A review of multi-threat medical countermeasures against chemical warfare and terrorism.

PubMed

Cowan, Fred M; Broomfield, Clarence A; Stojiljkovic, Milos P; Smith, William J

2004-11-01

The Multi-Threat Medical Countermeasure (MTMC) hypothesis has been proposed with the aim of developing a single countermeasure drug with efficacy against different pathologies caused by multiple classes of chemical warfare agents. Although sites and mechanisms of action and the pathologies caused by different chemical insults vary, common biochemical signaling pathways, molecular mediators, and cellular processes provide targets for MTMC drugs. This article will review the MTMC hypothesis for blister and nerve agents and will expand the scope of the concept to include other chemicals as well as briefly consider biological agents. The article will also consider how common biochemical signaling pathways, molecular mediators, and cellular processes that contribute to clinical pathologies and syndromes may relate to the toxicity of threat agents. Discovery of MTMC provides the opportunity for the integration of diverse researchers and clinicians, and for the exploitation of cutting-edge technologies and drug discovery. The broad-spectrum nature of MTMC can augment military and civil defense to combat chemical warfare and chemical terrorism.

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.

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

The Potential of Nano-Vehicle Mediated Therapy in Vasculitis and Multiple Sclerosis.

PubMed

In't Veld, R Huis; Da Silva, C G; Kaijzel, E L; Chan, A B; Cruz, L J

2017-01-01

The induction of immune tolerance towards self-antigens presents as a viable future strategy in the treatment of auto-immune diseases, including vasculitis and multiple sclerosis (MS). As specific targets are currently lacking for vasculitis due to incomplete understanding of the pathologies underlying this disease, current treatment options are based on modalities that induce general immune suppression. However, many immune suppressants used in the clinic are known to display wide biodistribution and are thus often accompanied by several adverse effects. Nano-vehicles (NVs) possess the ability to overcome such limitations by enabling more specific delivery of their content through modifications with targeting moieties. In this review, we describe the latest insights in the pathology of vasculitis that may function as potential targets for NV carrier systems, allowing more specific delivery of currently used immune suppressants. In addition, we describe the existing strategies to induce artificial immune tolerance and explore the feasibility of inducing regulatory T cell (Treg) mediated tolerance for MS, possibly mediated by NVs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

Watershed microinfarct pathology and cognition in older persons.

PubMed

Kapasi, Alifiya; Leurgans, Sue E; James, Bryan D; Boyle, Patricia A; Arvanitakis, Zoe; Nag, Sukriti; Bennett, David A; Buchman, Aron S; Schneider, Julie A

2018-05-30

Brain microinfarcts are common in aging and are associated with cognitive impairment. Anterior and posterior watershed border zones lie at the territories of the anterior, middle, and posterior cerebral arteries, and are more vulnerable to hypoperfusion than brain regions outside the watershed areas. However, little is known about microinfarcts in these regions and how they relate to cognition in aging. Participants from the Rush Memory and Aging Project, a community-based clinical-pathologic study of aging, underwent detailed annual cognitive evaluations. We examined 356 consecutive autopsy cases (mean age-at-death, 91 years [SD = 6.16]; 28% men) for microinfarcts from 3 watershed brain regions (2 anterior and 1 posterior) and 8 brain regions outside the watershed regions. Linear regression models were used to examine the association of cortical watershed microinfarcts with cognition, including global cognition and 5 cognitive domains. Microinfarcts in any region were present in 133 (37%) participants, of which 50 had microinfarcts in watershed regions. Persons with multiple microinfarcts in cortical watershed regions had lower global cognition (estimate = -0.56, standard error (SE) = 0.26, p = 0.03) and lower cognitive function in the specific domains of working memory (estimate = -0.58, SE = 0.27, p = 0.03) and visuospatial abilities (estimate = -0.57, SE = 0.27, p = 0.03), even after controlling for microinfarcts in other brain regions, demographics, and age-related pathologies. Neither the presence nor multiplicity of microinfarcts in brain regions outside the cortical watershed regions were related to global cognition or any of the 5 cognitive domains. These findings suggest that multiple microinfarcts in watershed regions contribute to age-related cognitive impairment. Copyright © 2018 Elsevier Inc. All rights reserved.

How Does Psychosocial Behavior Contribute to Cognitive Health in Old Age?

PubMed Central

Wilson, Robert S.; Bennett, David A.

2017-01-01

With the aging of the U.S. population, the number of cognitively disabled persons is expected to substantially increase in coming decades, underscoring the urgent need for effective interventions. Here, we review the current evidence linking psychosocial factors to late-life cognitive loss and consider the study design needed to illuminate the biologic bases of the associations. We then examine an ongoing study that includes several of the key design elements, the Rush Memory and Aging Project. In this longitudinal clinical-pathological cohort study, indicators of personality, social connectedness, and psychological well-being were shown to predict late-life cognitive outcomes. Participants who died underwent a uniform neuropathologic examination to quantify common dementia-related pathologies. Some psychosocial indicators were associated with cerebral infarction; some indicators modified the association of neurodegenerative pathologies with cognitive loss; and the association of some indicators with cognitive outcomes appears to be independent of the pathologies traditionally associated with late-life dementia. These findings suggest that psychosocial behavior influences late-life cognitive health through multiple neurobiologic mechanisms. A better understanding of these mechanisms may lead to novel strategies for preserving cognitive health in old age. PMID:28545247

Acute and chronically increased immunoreactivity to phosphorylation-independent but not pathological TDP-43 after a single traumatic brain injury in humans

PubMed Central

Johnson, Victoria E.; Stewart, William; Trojanowski, John Q.

2012-01-01

The pathologic phosphorylation and sub-cellular translocation of neuronal transactive response-DNA binding protein (TDP-43) was identified as the major disease protein in frontotemporal lobar degeneration (FTLD) with ubiquitinated inclusions, now termed FTLD-TDP, and amyotrophic lateral sclerosis (ALS). More recently, TDP-43 proteinopathy has been reported in dementia pugilistica or chronic traumatic encephalopathy caused by repetitive traumatic brain injury (TBI). While a single TBI has been linked to the development of Alzheimer’s disease and an increased frequency of neurofibrillary tangles, TDP-43 proteinopathy has not been examined with survival following a single TBI. Using immunohistochemistry specific for both pathological phosphorylated TDP-43 (p-TDP-43) and phosphorylation-independent TDP-43 (pi-TDP-43), we examined acute (n = 23: Survival < 2 weeks) and long-term (n = 39; 1–47 years survival) survivors of a single TBI versus age-matched controls (n = 47). Multiple regions were examined including the hippocampus, medial temporal lobe, cingulate gyrus, superior frontal gyrus and brainstem. No association was found between a history of single TBI and abnormally phosphorylated TDP-43 (p-TDP-43) inclusions. Specifically, just 3 of 62 TBI cases displayed p-TDP-43 pathology versus 2 of 47 control cases. However, while aggregates of p-TDP-43 were not increased acutely or long-term following TBI, immunoreactivity to phosphorylation-independent TDP-43 was commonly increased in the cytoplasm following TBI with both acute and long-term survival. Moreover, while single TBI can induce multiple long-term neurodegenerative changes, the absence of TDP-43 proteinopathy may indicate a fundamental difference in the processes induced following single TBI from those of repetitive TBI. PMID:22101322

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.

Brain Organochlorines and Lewy Pathology: The Honolulu-Asia Aging Study

PubMed Central

Ross, G. Webster; Duda, John E.; Abbott, Robert D.; Pellizzari, Edo; Petrovitch, Helen; Miller, Diane B.; O’Callaghan, James P.; Tanner, Caroline M.; Noorigian, Joseph V.; Masaki, Kamal; Launer, Lenore; White, Lon R.

2012-01-01

Background Although organochlorines have been reported more frequently in Parkinson’s disease (PD) brains than controls, the association with brain Lewy pathology is unknown. Honolulu-Asia Aging Study (HAAS) participants, exposed to organochlorines from a variety of sources during mid-life, represent a population well suited to determine the relationship of brain organochlorines with Lewy pathology in decedents from the longitudinal HAAS. Methods Study design included the measurement of 21 organochlorine levels in frozen occipital lobe samples from HAAS decedents. Alpha-synuclein immunostaining performed on 225 brains was used to identify Lewy bodies and Lewy neurites. Results With the potential for spurious associations to appear between Lewy pathology and 17 organochlorine compounds found to be present in at least one brain, initial assessments identified heptachlor epoxide isomer b, methoxychlor, and benzene hexachloride b as being most important. Prevalence of Lewy pathology was 75% (6/8) among brains with any 2 of the 3 compounds, 48.8% (79/162) among those with 1, and 32.7% (18/55) for those with neither (P=0.007 test for trend). While findings persisted after removing cases with PD and dementia with Lewy bodies, and when adjustments were made for age at death, body mass index, pack-years of cigarette smoking, and coffee intake (p=0.013), results were insignificant when correcting for multiple testing. Conclusions While consistent with earlier accounts of an association between organochlorines and clinical PD, associations with Lewy pathology warrant further study. PMID:22976848

The Neuropsychopharmacology of Pathological Gambling.

PubMed

Zakeri, Kourosh; Potenza, Marc N

2012-02-01

Pathological gambling (PG) is an impulse control disorder with prevalence estimates in the range of 0.2-2% in the general population. PG can significantly impact one's ability to function as it may negatively influence social, financial, and occupational aspects of life. Historically, PG has received relatively little attention from researchers and clinicians, and few treatments, particularly pharmacological, have been both validated and widely employed. Given the clinical relevance of PG, it is important that researchers examine pharmacological and behavioral treatments for their safety and efficacy and that clinicians use empirically validated therapies. Multiple neurochemicals, including serotonin, dopamine, norepinephrine, and opioids, and related neurocircuitry, particularly ventral cortico-striatal pathways, have been implicated in PG. The neurobiological rationale for therapies, particularly pharmacological ones, is reviewed with a perspective on the generation of improved prevention and treatment strategies for PG.

The Enduring Challenge of Determining Pneumonia Etiology in Children: Considerations for Future Research Priorities

PubMed Central

Hammitt, Laura L.; Murdoch, David R.; O’Brien, Katherine L.; Scott, J. Anthony G.

2017-01-01

Abstract Pneumonia kills more children each year worldwide than any other disease. Nonetheless, accurately determining the causes of childhood pneumonia has remained elusive. Over the past century, the focus of pneumonia etiology research has shifted from studies of lung aspirates and postmortem specimens intent on identifying pneumococcal disease to studies of multiple specimen types distant from the lung that are tested for multiple pathogens. Some major challenges facing modern pneumonia etiology studies include the use of nonspecific and variable case definitions, poor access to pathologic lung tissue and to specimens from fatal cases, poor diagnostic accuracy of assays (especially when testing nonpulmonary specimens), and the interpretation of results when multiple pathogens are detected in a given individual. The future of childhood pneumonia etiology research will likely require integrating data from complementary approaches, including applications of advanced molecular diagnostics and vaccine probe studies, as well as a renewed emphasis on lung aspirates from radiologically confirmed pneumonia and postmortem examinations. PMID:28575369

GSK-3α is a central regulator of age-related pathologies in mice

PubMed Central

Zhou, Jibin; Freeman, Theresa A.; Ahmad, Firdos; Shang, Xiying; Mangano, Emily; Gao, Erhe; Farber, John; Wang, Yajing; Ma, Xin-Liang; Woodgett, James; Vagnozzi, Ronald J.; Lal, Hind; Force, Thomas

2013-01-01

Aging is regulated by conserved signaling pathways. The glycogen synthase kinase-3 (GSK-3) family of serine/threonine kinases regulates several of these pathways, but the role of GSK-3 in aging is unknown. Herein, we demonstrate premature death and acceleration of age-related pathologies in the Gsk3a global KO mouse. KO mice developed cardiac hypertrophy and contractile dysfunction as well as sarcomere disruption and striking sarcopenia in cardiac and skeletal muscle, a classical finding in aging. We also observed severe vacuolar degeneration of myofibers and large tubular aggregates in skeletal muscle, consistent with impaired clearance of insoluble cellular debris. Other organ systems, including gut, liver, and the skeletal system, also demonstrated age-related pathologies. Mechanistically, we found marked activation of mTORC1 and associated suppression of autophagy markers in KO mice. Loss of GSK-3α, either by pharmacologic inhibition or Gsk3a gene deletion, suppressed autophagy in fibroblasts. mTOR inhibition rescued this effect and reversed the established pathologies in the striated muscle of the KO mouse. Thus, GSK-3α is a critical regulator of mTORC1, autophagy, and aging. In its absence, aging/senescence is accelerated in multiple tissues. Strategies to maintain GSK-3α activity and/or inhibit mTOR in the elderly could retard the appearance of age-related pathologies. PMID:23549082

[Pathological and biochemical studies of 30 Niigata autopsy cases related to Minamata disease].

PubMed

Eto, Komyo; Takahashi, Hitoshi; Kakita, Akiyoshi; Tokunaga, Hidehiro; Yasutake, Akira; Nakano, Atsuhiro; Sawada, Masumi; Kinjo, Yoshihide

2007-01-01

To reevaluate pathologically and biochemically 30 autopsy cases related to Minamata disease (MD) in Niigata Prefecture (NP) and compare the findings with those of autopsy cases related to MD in Kumamoto Prefecture (KP). Recently, a set of pathological materials of these 30 autopsy cases has been sent from the Brain Research Institute at the University of Niigata to the National Institute for Minamata Disease (NIMD). The materials from each autopsy case were reexamined at the NIMD. There were no postnatal and fetal cases of MD in the NP autopsy materials. The contents of total mercury (T-Hg), methylmercury (Me-Hg), inorganic mercury (I-Hg) and selenium were measured in the organs of cerebrum, cerebellum, liver and kidney. The contents of T-Hg, Me-Hg and I-Hg were much higher in two cases than in controls. The pathological findings leading to the diagnosis of MD in the NP cases were essentially the same as those in KP, including the peripheral nerve lesions. In the most severely affected case of MD in NP, formation of multiple vacuoles of various sizes was observed in the cerebellar cortex, which was never encountered in the KP cases. The KP lesions were similar to that observed in an acute case of Me-Hg-treated common marmoset studied in the NIMD. The pathological features were essentially the same between the adult cases of MD in NP and KP.

Does standardised structured reporting contribute to quality in diagnostic pathology? The importance of evidence-based datasets.

PubMed

Ellis, D W; Srigley, J

2016-01-01

Key quality parameters in diagnostic pathology include timeliness, accuracy, completeness, conformance with current agreed standards, consistency and clarity in communication. In this review, we argue that with worldwide developments in eHealth and big data, generally, there are two further, often overlooked, parameters if our reports are to be fit for purpose. Firstly, population-level studies have clearly demonstrated the value of providing timely structured reporting data in standardised electronic format as part of system-wide quality improvement programmes. Moreover, when combined with multiple health data sources through eHealth and data linkage, structured pathology reports become central to population-level quality monitoring, benchmarking, interventions and benefit analyses in public health management. Secondly, population-level studies, particularly for benchmarking, require a single agreed international and evidence-based standard to ensure interoperability and comparability. This has been taken for granted in tumour classification and staging for many years, yet international standardisation of cancer datasets is only now underway through the International Collaboration on Cancer Reporting (ICCR). In this review, we present evidence supporting the role of structured pathology reporting in quality improvement for both clinical care and population-level health management. Although this review of available evidence largely relates to structured reporting of cancer, it is clear that the same principles can be applied throughout anatomical pathology generally, as they are elsewhere in the health system.

Daily Tobacco Smoking in Treatment-Seeking Pathological Gamblers: Clinical Correlates and Co-occurring Psychiatric Disorders.

PubMed

Grant, Jon E; Kim, Suck Won; Odlaug, Brian L; Potenza, Marc N

2008-01-01

Tobacco smoking and pathological gambling (PG) frequently co-occur. Little is known, however, about the clinical correlates and co-occurring psychiatric disorders in treatment-seeking pathological gamblers with and without daily tobacco smoking. Among a sample of 465 consecutive treatment-seeking subjects with current DSM-IV PG, those with daily tobacco smoking were compared to those without daily tobacco smoking on measures of gambling symptom severity (South Oaks Gambling Screen [SOGS] and the Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling [PG-YBOCS]), types of gambling, social and legal problems, and co-occurring disorders. Two hundred and nine (44.9%) of the 465 subjects with PG reported current daily tobacco smoking. Gamblers with daily tobacco smoking as compared to those without had higher SOGS scores, had more severe PG-YBOCS behavior scores, endorsed more DSM-IV PG criteria, lost more money gambling, and were more likely to engage in non-strategic gambling, and were less likely to have a co-occurring mood disorder. Gamblers with daily tobacco smoking and a current substance use disorder reported a greater percentage of income lost to gambling during the past year. Daily tobacco smoking in PG is common and associated with multiple important clinical features including more severe gambling and financial problems. These findings suggest that pathological gamblers with daily tobacco smoking might need unique or enhanced treatment strategies.

Clinicopathological and molecular stability and methylation analyses of gastric papillary adenocarcinoma.

PubMed

Uesugi, Noriyuki; Sugai, Tamotsu; Sugimoto, Ryo; Eizuka, Makoto; Fujita, Yasuko; Sato, Ayaka; Osakabe, Mitsumasa; Ishida, Kazuyuki; Koeda, Keisuke; Sasaki, Akira; Matsumoto, Takayuki

2017-10-01

The molecular alterations and pathological features of gastric papillary adenocarcinoma (GPA) remain unknown. We examined GPA samples and compared their molecular and pathological characteristics with those of gastric tubular adenocarcinoma (GTA). Additionally, we identified pathological and molecular features of GPA that vary with microsatellite stability. In the present study, samples from 63 GPA patients and 47 GTA patients were examined using a combination of polymerase chain reaction (PCR)-microsatellite assays and PCR-pyrosequencing in order to detect microsatellite instability (microsatellite instability, MSI; microsatellite stable, MSS), methylation status (low methylation, intermediate methylation and high methylation level), and chromosomal AI in multiple cancer-related loci. Additionally, the expression levels of TP53 and Her2 were evaluated using immunohistochemistry. GTA and GPA are statistically different in their frequency of pathological features, including mucinous, poorly differentiated and invasive micropapillary components. Clear genetic patterns differentiating GPA and GTA could not be identified with a hierarchical cluster analysis, but microsatellite stability was linked with TP53 and Her2 overexpression. Methylation status in GPA was also associated with the development of high microsatellite instability. However, no pathological differences were associated with microsatellite stability. We suggest that although molecular alterations in a subset of GPAs are closely associated with microsatellite stability, they play a minor role in GPA carcinogenesis. Copyright © 2017 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

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.

Standardizing the definition of adverse pathology for lower risk men undergoing radical prostatectomy.

PubMed

Kozminski, Michael A; Tomlins, Scott; Cole, Adam; Singhal, Udit; Lu, Louis; Skolarus, Ted A; Palapattu, Ganesh S; Montgomery, Jeffrey S; Weizer, Alon Z; Mehra, Rohit; Hollenbeck, Brent K; Miller, David C; He, Chang; Feng, Felix Y; Morgan, Todd M

2016-09-01

Numerous definitions of adverse pathology at radical prostatectomy (RP) have been proposed and implemented for both research and clinical care, and there is tremendous variation in the specific criteria used to define adverse pathology in these settings. Given the current landscape in which magnetic resonance imaging criteria and biomarker cutoffs are validated for disparate adverse pathology definitions, we sought to identify which of these is most closely tied to biochemical recurrence (BCR) after RP. A total of 2,837 patients who underwent RP at a single institution for localized prostate cancer (PCa) were included. We evaluated the following existing definitions of adverse pathology at RP: (1) Gleason score ≥7, (2) primary Gleason pattern ≥4, (3) Gleason score ≥7 or pathologic stage T3-4, (4) pathologic stage T3-4, (5) primary Gleason pattern ≥4 or pathologic stage T3-4. The primary outcome measure was BCR. Multiple statistical techniques were used to assess BCR prediction. Of the 5 definitions assessed, 1 (primary Gleason pattern ≥4 or pathologic stage T3-4, 540 patients [19% of cohort]) consistently outperformed the other definitions across all statistical measures. Additionally, a total of only 13 (6.6%) and 34 (10.3%) men with very-low-risk and low-risk cancer per National Comprehensive Cancer Network guideline, respectively, met this definition of adverse pathology at the time of RP. Varying definitions of adverse pathology differ in their prognostic performance. The criteria defined by either primary Gleason pattern ≥4 or pT3-4 disease appears to most accurately predict BCR in this subset of patients with lower risk PCa at the time of diagnosis. Additionally, men with very-low-risk or low-risk PCa per National Comprehensive Cancer Network guidelines are relatively unlikely to have adverse pathology at the time of surgical resection. These data may help inform the use of imaging and molecular markers as well as the intensity of surveillance in men with newly diagnosed PCa. Copyright © 2016 Elsevier Inc. 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.

An unusual autopsy case of cytokine storm-derived influenza-associated encephalopathy without typical histopathological findings: autopsy case report.

PubMed

Nara, Akina; Nagai, Hisashi; Yamaguchi, Rutsuko; Yoshida, Ken-ichi; Iwase, Hirotaro; Mizuguchi, Masashi

2015-03-01

Cytokine storm-derived influenza-associated encephalopathy is a severe complication, affecting not only the brain but also multiple systemic organs including the heart and lungs. Hundreds of Japanese children are afflicted by influenza-associated encephalopathy every year. Influenza-associated encephalopathy can be diagnosed by pathological changes, such as advanced brain edema and disruption of astrocytic projections, which is known as clasmatodendrosis. In the present case, despite the absence of significant histopathological findings in the brain, the diagnosis of influenza-associated encephalopathy was made on the basis of autopsy findings such as brain swelling, pathological findings including diffuse alveolar damage, and increase in the concentrations of interleukin-6 in both the serum and cerebrospinal fluid. In this case, the interval from high fever to death was approximately 7 hours and may have been too short for histopathological features to develop. This is an unusual autopsy case of cytokine storm-derived influenza-associated encephalopathy without typical histopathological findings.

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.

Pathological periodontal pockets are associated with raised diastolic blood pressure in obese adolescents.

PubMed

Zeigler, Cecilia C; Wondimu, Biniyam; Marcus, Claude; Modéer, Thomas

2015-03-24

Obesity, a well-known risk factor for developing cardiovascular disease (CVD), is associated with chronic periodontitis in adults. This cross-sectional pilot study on obese adolescents was designed to investigate whether periodontal disease in terms of pathological periodontal pockets is associated with raised blood pressure and other risk markers for CVD. The study included 75 obese subjects between 12 to 18 years of age, mean 14.5. Subjects answered a questionnaire regarding health, oral hygiene habits and sociodemographic factors. A clinical examination included Visible Plaque Index (VPI %), Gingival inflammation (BOP %) and the occurrence of pathological pockets exceeding 4 mm (PD ≥ 4 mm). Blood serum were collected and analyzed. The systolic and diastolic blood pressures were registered. Adolescents with pathological periodontal pockets (PD ≥ 4 mm; n = 14) had significantly higher BOP >25% (P = 0.002), higher diastolic blood pressure (P = 0.008), higher levels of Interleukin (IL)-6 (P < 0.001), Leptin (P = 0.018), Macrophage Chemoattractant Protein-1 (MCP-1) (P = 0.049) and thyroid stimulating hormone (TSH) (P = 0.004) in blood serum compared with subjects without pathological periodontal pockets (PD ≥ 4 mm; n = 61). The bivariate linear regression analysis demonstrated that PD ≥ 4 mm (P = 0.008) and systolic blood pressure (P < 0.001) were significantly associated with the dependent variable "diastolic blood pressure". The association between PD ≥ 4 mm and diastolic blood pressure remained significant (P = 0.006) even after adjusting for potential confounders BMI-sds, age, gender, mother's country of birth, BOP >25%, IL-6, IL-8, Leptin, MCP-1, TSH and total cholesterol in the multiple regression analysis. In conclusion, this study indicates an association between pathological periodontal pockets and diastolic blood pressure in obese adolescents. The association was unaffected by other risk markers for cardiovascular events or periodontal disease. The results call for collaboration between pediatric dentists and medical physicians in preventing obesity development and its associated disorders.

Multimodal Characterization of the Late Effects of Traumatic Brain Injury: A Methodological Overview of the Late Effects of Traumatic Brain Injury Project.

PubMed

Edlow, Brian L; Keene, C Dirk; Perl, Daniel P; Iacono, Diego; Folkerth, Rebecca D; Stewart, William; Mac Donald, Christine L; Augustinack, Jean; Diaz-Arrastia, Ramon; Estrada, Camilo; Flannery, Elissa; Gordon, Wayne A; Grabowski, Thomas J; Hansen, Kelly; Hoffman, Jeanne; Kroenke, Christopher; Larson, Eric B; Lee, Patricia; Mareyam, Azma; McNab, Jennifer A; McPhee, Jeanne; Moreau, Allison L; Renz, Anne; Richmire, KatieRose; Stevens, Allison; Tang, Cheuk Y; Tirrell, Lee S; Trittschuh, Emily H; van der Kouwe, Andre; Varjabedian, Ani; Wald, Lawrence L; Wu, Ona; Yendiki, Anastasia; Young, Liza; Zöllei, Lilla; Fischl, Bruce; Crane, Paul K; Dams-O'Connor, Kristen

2018-05-03

Epidemiological studies suggest that a single moderate-to-severe traumatic brain injury (TBI) is associated with an increased risk of neurodegenerative disease, including Alzheimer's disease (AD) and Parkinson's disease (PD). Histopathological studies describe complex neurodegenerative pathologies in individuals exposed to single moderate-to-severe TBI or repetitive mild TBI, including chronic traumatic encephalopathy (CTE). However, the clinicopathological links between TBI and post-traumatic neurodegenerative diseases such as AD, PD, and CTE remain poorly understood. Here, we describe the methodology of the Late Effects of TBI (LETBI) study, whose goals are to characterize chronic post-traumatic neuropathology and to identify in vivo biomarkers of post-traumatic neurodegeneration. LETBI participants undergo extensive clinical evaluation using National Institutes of Health TBI Common Data Elements, proteomic and genomic analysis, structural and functional magnetic resonance imaging (MRI), and prospective consent for brain donation. Selected brain specimens undergo ultra-high resolution ex vivo MRI and histopathological evaluation including whole-mount analysis. Co-registration of ex vivo and in vivo MRI data enables identification of ex vivo lesions that were present during life. In vivo signatures of postmortem pathology are then correlated with cognitive and behavioral data to characterize the clinical phenotype(s) associated with pathological brain lesions. We illustrate the study methods and demonstrate proof of concept for this approach by reporting results from the first LETBI participant, who despite the presence of multiple in vivo and ex vivo pathoanatomic lesions had normal cognition and was functionally independent until her mid-80s. The LETBI project represents a multidisciplinary effort to characterize post-traumatic neuropathology and identify in vivo signatures of postmortem pathology in a prospective study.

Emergence of pathogenic and multiple-antibiotic-resistant Macrococcus caseolyticus in commercial broiler chickens.

PubMed

Li, Gen; Du, Xusheng; Zhou, Defang; Li, Chengui; Huang, Libo; Zheng, Qiankun; Cheng, Ziqiang

2018-05-25

Macrococcus caseolyticus is generally considered to be a non-pathogenic bacterium that does not cause human or animal diseases. However, recently, a strain of M. caseolyticus (SDLY strain) that causes high mortality rates was isolated from commercial broiler chickens in China. The main pathological changes caused by SDLY included caseous exudation in cranial cavities, inflammatory infiltration, haemorrhages and multifocal necrosis in various organs. The whole genome of the SDLY strain was sequenced and was compared with that of the non-pathogenic JCSC5402 strain of M. caseolyticus. The results showed that the SDLY strain harboured a large quantity of mutations, antibiotic resistance genes and numerous insertions and deletions of virulence genes. In particular, among the inserted genes, there is a cluster of eight connected genes associated with the synthesis of capsular polysaccharide. This cluster encodes a transferase and capsular polysaccharide synthase, promotes the formation of capsules and causes changes in pathogenicity. Electron microscopy revealed a distinct capsule surrounding the SDLY strain. The pathogenicity test showed that the SDLY strain could cause significant clinical symptoms and pathological changes in both SPF chickens and mice. In addition, these clinical symptoms and pathological changes were the same as those observed in field cases. Furthermore, the anti-microbial susceptibility test demonstrated that the SDLY strain exhibits multiple-antibiotic resistance. The emergence of pathogenic M. caseolyticus indicates that more attention should be paid to the effects of this micro-organism on both poultry and public health. © 2018 Blackwell Verlag GmbH.

Resveratrol and Alzheimer's Disease: Mechanistic Insights.

PubMed

Ahmed, Touqeer; Javed, Sehrish; Javed, Sana; Tariq, Ameema; Šamec, Dunja; Tejada, Silvia; Nabavi, Seyed Fazel; Braidy, Nady; Nabavi, Seyed Mohammad

2017-05-01

Alzheimer's disease (AD) is the leading cause of dementia in the elderly and is characterized by progressive cognitive and memory deficits. The pathological hallmarks of AD include extracellular senile plaques and intracellular neurofibrillary tangles. Although several mechanisms have been used to explain the underlying pathogenesis of AD, current treatment regimens remain inadequate. The neuroprotective effects of the polyphenolic stilbene resveratrol (3,5,4'-trihydroxy-trans-stilbene) have been investigated in several in vitro and in vivo models of AD. The current review discusses the multiple potential mechanisms of action of resveratrol on the pathobiology of AD. Moreover, due to the limited pharmacokinetic parameters of resveratrol, multiple strategies aimed at increasing the bioavailability of resveratrol have also been addressed.

Arthroscopic management of posterior instability: evolution of technique and results.

PubMed

Savoie, Felix H; Holt, M Shaun; Field, Larry D; Ramsey, J Randall

2008-04-01

The purpose of this study was to evaluate the effectiveness of arthroscopic posterior shoulder reconstruction. We treated 136 shoulders in 131 patients with a diagnosis of primary posterior instability who failed 6 months of vigorous rehabilitation by operative stabilization between 1989 and 2001. Inclusion criterion was primary posterior instability that failed an extensive rehabilitative program with functional impairment and pain. Exclusion criterion was less than 12 months of follow-up and Suretac (Smith & Nephew, Andover, MA) or laser stabilization, leaving 92 shoulders in 90 patients available for the study (69 male, 21 female). Follow-up ranged from 12 to 132 months (average, 28 months). Each patient underwent diagnostic arthroscopy and surgical repair at the same time using one of several primary procedures. The procedure used was based on the pathologic entity noted at the time of surgery. At an average follow-up of 28 months, 97% of the shoulders were stable and considered a success based on the Neer-Foster rating scale. Posterior pathology varied, and a reverse Bankart lesion alone was found 51% of the time, a stretched posterior capsule 67% of the time, and a combination of a reverse Bankart lesion and capsular stretching 16% of the time. The rotator interval was obviously damaged in 61% of cases. Multiple accompanying lesions were found, including anterior-superior labral tears and SLAP tears (20%), superior glenohumeral ligament injury (7%), middle glenohumeral ligament injury (38%), anteroinferior glenohumaral ligament injury (37%), and an enlarged axillary pouch (20%). No essential lesion is present for posterior instability. Multiple varied pathologies will be present in a shoulder presenting with posterior instability. Arthroscopic surgery allows inspection of the joint and anatomic-specific repairs based on pathology. Careful attention to all the supporting structures of the shoulder, including the rotator interval, the anterior-superior labrum, and its attached superior glenohumeral ligament, the coracohumeral ligament, the inferior glenohumeral ligament complex, and the infraspinatus, in addition to the posterior labrum and capsule, allows excellent outcomes to be achieved with arthroscopic posterior reconstruction techniques. Level IV, therapeutic case series.

Correlates of motivation to change in pathological gamblers completing cognitive-behavioral group therapy.

PubMed

Gómez-Peña, Mónica; Penelo, Eva; Granero, Roser; Fernández-Aranda, Fernando; Alvarez-Moya, Eva; Santamaría, Juan José; Moragas, Laura; Neus Aymamí, Maria; Gunnard, Katarina; Menchón, José M; Jimenez-Murcia, Susana

2012-07-01

The present study analyzes the association between the motivation to change and the cognitive-behavioral group intervention, in terms of dropouts and relapses, in a sample of male pathological gamblers. The specific objectives were as follows: (a) to estimate the predictive value of baseline University of Rhode Island Change Assessment scale (URICA) scores (i.e., at the start of the study) as regards the risk of relapse and dropout during treatment and (b) to assess the incremental predictive ability of URICA scores, as regards the mean change produced in the clinical status of patients between the start and finish of treatment. The relationship between the URICA and the response to treatment was analyzed by means of a pre-post design applied to a sample of 191 patients who were consecutively receiving cognitive-behavioral group therapy. The statistical analysis included logistic regression models and hierarchical multiple linear regression models. The discriminative ability of the models including the four URICA scores regarding the likelihood of relapse and dropout was acceptable (area under the receiver operating haracteristic curve: .73 and .71, respectively). No significant predictive ability was found as regards the differences between baseline and posttreatment scores (changes in R(2) below 5% in the multiple regression models). The availability of useful measures of motivation to change would enable treatment outcomes to be optimized through the application of specific therapeutic interventions. © 2012 Wiley Periodicals, Inc.

Frequency of Cholelithiasis and Biliary Pathology in the Easter Island Rapanui and Non-Rapanui Populations.

PubMed

Bravo, Eduardo; Contardo, Jorge; Cea, Jerson

2016-01-01

Chile is one of the countries with the highest prevalence of cholelithiasis worldwide, considering the Mapuche ethnicity as a risk factor for developing this pathology. Moreover, cholelithiasis is the main risk factor for developing gallbladder cancer, being the fifth cause of cancer death in Chile. The purpose of this study was to compare the frequency of cholelithiasis and biliary pathology among the population belonging to Rapanui ethnicity and non-Rapanui population living on Easter Island. In this retrospective case-control study, a total of 609 abdominal ultrasonographs performed consecutively in Hanga Roa Hospital during the period August 2012 to January 2015 were analyzed. Multiple logistic regression was used to obtain odds ratio (OR) and 95% confidence intervals (95% CI) of cholelithiasis and biliary pathology, adjusting for age, gender and referral diagnostic hypothesis. In the Rapanui population the frequency for cholelithiasis and biliary pathology was 6.4% and 13%, meanwhile for the non-Rapanui population it was 13% and 22% respectively. Compared to the non-Rapanui Chilean population, the Rapanui ethnicity presented an OR of 0.53 (95% CI: 0.29-0.95) for cholelithiasis and OR of 0.52 (95% CI: 0.33-0.82) for biliary pathology. We found statistically significant ethnic differences in the frequency of cholelithiasis and biliary disease among the population of Rapanui and non-Rapanui ethnicity, so that this could be a protective factor for the development of biliary pathology, given the Chilean population context. Other studies including community population to determine the real prevalence of cholelithiasis and analyze the protective role of Rapanui ethnicity on this disease are necessary.

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.

The JCR:LA-cp rat: a novel rodent model of cystic medial necrosis.

PubMed

Pung, Yuh Fen; Chilian, William M; Bennett, Martin R; Figg, Nichola; Kamarulzaman, Mohd Hamzah

2017-03-01

Although there are multiple rodent models of the metabolic syndrome, very few develop vascular complications. In contrast, the JCR:LA-cp rat develops both metabolic syndrome and early atherosclerosis in predisposed areas. However, the pathology of the normal vessel wall has not been described. We examined JCR:LA control (+/+) or cp/cp rats fed normal chow diet for 6 or 18 mo. JCR:LA-cp rats developed multiple features of advanced cystic medial necrosis including "cysts," increased collagen formation and proteoglycan deposition around cysts, apoptosis of vascular smooth muscle cells, and spotty medial calcification. These appearances began within 6 mo and were extensive by 18 mo. JCR:LA-cp rats had reduced medial cellularity, increased medial thickness, and vessel hypoxia that was most marked in the adventitia. In conclusion, the normal chow-fed JCR:LA-cp rat represents a novel rodent model of cystic medial necrosis, associated with multiple metabolic abnormalities, vascular smooth muscle cell apoptosis, and vessel hypoxia. NEW & NOTEWORTHY Triggers for cystic medial necrosis (CMN) have been difficult to study due to lack of animal models to recapitulate the pathologies seen in humans. Our study is the first description of CMN in the rat. Thus the JCR:LA-cp rat represents a useful model to investigate the underlying molecular changes leading to the development of CMN. Copyright © 2017 the American Physiological Society.

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

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

James Homer Wright: a biography of the enigmatic creator of the Wright stain on the occasion of its centennial.

PubMed

Lee, Robert E; Young, Robert H; Castleman, Benjamin

2002-01-01

James Homer Wright (1869-1928), the eldest son of a Pittsburgh glass merchant, was educated in Baltimore and practiced pathology in Boston from 1893 until his death in 1928. In 1896, when not quite 27 years old, he assumed directorship of the newly founded Pathology Laboratory at the Massachusetts General Hospital, a post he held for the next 30 years. He is remembered eponymously by the blood cell stain that bears his name and the Homer Wright pseudorosettes of neuroblastoma, but he made many additional contributions to pathology. These include the following: determination of the cellular lineage of multiple myeloma, identification of the megakaryocyte as the cell of origin of blood platelets, recognition of the cell of origin of the neuroblastoma, demonstration of spirochetes in syphilitic aneurysms of the aorta, and clarification of misconceptions about actinomycosis. Additionally, Wright coauthored, with Dr. Frank B. Mallory, the book Pathological Technique, which was a staple of laboratories for >40 years and exemplifies Wright's wide-ranging interests in, and contributions to, practical aspects of pathology including staining, culture and frozen section techniques, photography, and development of the rotary microtome. He received Honorary Doctor of Science Degrees from Harvard University, the University of Maryland (his alma mater), and the University of Missouri. He was the recipient of the Gross prize in 1905 for his publication on actinomycosis and the Boylston Medical Prize in 1908 for his discovery of the origin of platelets, and he was inducted into the American Academy of Arts and Sciences in 1915. Although shy and somewhat austere in the workplace, a different side was shown by his anonymously sending flowers to a young Norwegian opera singer whom he subsequently married. The pathology laboratories of the Massachusetts General Hospital were named the "James Homer Wright Pathology Laboratories" in 1956. Today James Homer Wright is remembered and honored 100 years after his description of the stain that, along with the pseudorosettes of neuroblastoma, carry his name into eternity and ensure his great contributions will never be forgotten.

Vasoregression: A Shared Vascular Pathology Underlying Macrovascular And Microvascular Pathologies?

PubMed Central

Gupta, Akanksha

2015-01-01

Abstract Vasoregression is a common phenomenon underlying physiological vessel development as well as pathological microvascular diseases leading to peripheral neuropathy, nephropathy, and vascular oculopathies. In this review, we describe the hallmarks and pathways of vasoregression. We argue here that there is a parallel between characteristic features of vasoregression in the ocular microvessels and atherosclerosis in the larger vessels. Shared molecular pathways and molecular effectors in the two conditions are outlined, thus highlighting the possible systemic causes of local vascular diseases. Our review gives us a system-wide insight into factors leading to multiple synchronous vascular diseases. Because shared molecular pathways might usefully address the diagnostic and therapeutic needs of multiple common complex diseases, the literature analysis presented here is of broad interest to readership in integrative biology, rational drug development and systems medicine. PMID:26669709

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.

The multiple roles of EG-VEGF/PROK1 in normal and pathological placental angiogenesis.

PubMed

Alfaidy, Nadia; Hoffmann, Pascale; Boufettal, Houssine; Samouh, Naima; Aboussaouira, Touria; Benharouga, Mohamed; Feige, Jean-Jacques; Brouillet, Sophie

2014-01-01

Placentation is associated with several steps of vascular adaptations throughout pregnancy. These vascular changes occur both on the maternal and fetal sides, consisting of maternal uterine spiral arteries remodeling and placental vasculogenesis and angiogenesis, respectively. Placental angiogenesis is a pivotal process for efficient fetomaternal exchanges and placental development. This process is finely controlled throughout pregnancy, and it involves ubiquitous and pregnancy-specific angiogenic factors. In the last decade, endocrine gland derived vascular endothelial growth factor (EG-VEGF), also called prokineticin 1 (PROK1), has emerged as specific placental angiogenic factor that controls many aspects of normal and pathological placental angiogenesis such as recurrent pregnancy loss (RPL), gestational trophoblastic diseases (GTD), fetal growth restriction (FGR), and preeclampsia (PE). This review recapitulates EG-VEGF mediated-angiogenesis within the placenta and at the fetomaternal interface and proposes that its deregulation might contribute to the pathogenesis of several placental diseases including FGR and PE. More importantly this paper argues for EG-VEGF clinical relevance as a potential biomarker of the onset of pregnancy pathologies and discusses its potential usefulness for future therapeutic directions.

Déjà vu experiences are rarely associated with pathological dissociation.

PubMed

Adachi, Naoto; Akanuma, Nozomi; Akanu, Nozomi; Adachi, Takuya; Takekawa, Yoshikazu; Adachi, Yasushi; Ito, Masumi; Ikeda, Hiroshi

2008-05-01

We investigated the relation between déjà vu and dissociative experiences in nonclinical subjects. In 227 adult volunteers, déjà vu and dissociative experiences were evaluated by means of the inventory of déjà vu experiences assessment and dissociative experiences scale (DES). Déjà vu experiences occurred in 162 (71.4%) individuals. In univariate correlation analysis, the frequency of déjà vu experiences, as well as 5 other inventory of déjà vu experiences assessment symptoms and age at the time of evaluation, correlated significantly with the DES score. After exclusion of intercorrelative effects using multiple regression analysis, déjà vu experiences did not remain in the model. The DES score was best correlated with a model that included age, jamais vu, depersonalization, and precognitive dreams. Two indices for pathological dissociation (DES-taxon and DES > or = 30) were not associated with déjà vu experiences. Our findings suggest that déjà vu experiences are unlikely to be core pathological dissociative experiences.

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.

Selective Memory to Apoptotic Cell-Derived Self-Antigens with Implications for Systemic Lupus Erythematosus Development.

PubMed

Duhlin, Amanda; Chen, Yunying; Wermeling, Fredrik; Sedimbi, Saikiran K; Lindh, Emma; Shinde, Rahul; Halaby, Marie Jo; Kaiser, Ylva; Winqvist, Ola; McGaha, Tracy L; Karlsson, Mikael C I

2016-10-01

Autoimmune diseases are characterized by pathogenic immune responses to self-antigens. In systemic lupus erythematosus (SLE), many self-antigens are found in apoptotic cells (ACs), and defects in removal of ACs from the body are linked to a risk for developing SLE. This includes pathological memory that gives rise to disease flares. In this study, we investigated how memory to AC-derived self-antigens develops and the contribution of self-memory to the development of lupus-related pathology. Multiple injections of ACs without adjuvant into wild-type mice induce a transient primary autoimmune response without apparent anti-nuclear Ab reactivity or kidney pathology. Interestingly, as the transient Ab response reached baseline, a single boost injection fully recalled the immune response to ACs, and this memory response was furthermore transferable into naive mice. Additionally, the memory response contains elements of pathogenicity, accompanied by selective memory to selective Ags. Thus, we provide evidence for a selective self-memory that underlies progression of the response to self-antigens with implications for SLE development therapy. Copyright © 2016 by The American Association of Immunologists, Inc.

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.

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.

Real time non invasive imaging of fatty acid uptake in vivo

PubMed Central

Henkin, Amy H.; Cohen, Allison S.; Dubikovskaya, Elena A.; Park, Hyo Min; Nikitin, Gennady F.; Auzias, Mathieu G.; Kazantzis, Melissa; Bertozzi, Carolyn R.; Stahl, Andreas

2012-01-01

Detection and quantification of fatty acid fluxes in animal model systems following physiological, pathological, or pharmacological challenges is key to our understanding of complex metabolic networks as these macronutrients also activate transcription factors and modulate signaling cascades including insulin-sensitivity. To enable non-invasive, real-time, spatiotemporal quantitative imaging of fatty acid fluxes in animals, we created a bioactivatable molecular imaging probe based on long-chain fatty acids conjugated to a reporter molecule (luciferin). We show that this probe faithfully recapitulates cellular fatty acid uptake and can be used in animal systems as a valuable tool to localize and quantitate in real-time lipid fluxes such as intestinal fatty acid absorption and brown adipose tissue activation. This imaging approach should further our understanding of basic metabolic processes and pathological alterations in multiple disease models. PMID:22928772

Clinical features, endoscopic polypectomy and STK11 gene mutation in a nine-month-old Peutz-Jeghers syndrome Chinese infant

PubMed Central

Huang, Zhi-Heng; Song, Zai; Zhang, Ping; Wu, Jie; Huang, Ying

2016-01-01

AIM: To investigate multiple polyps in a Chinese Peutz-Jeghers syndrome (PJS) infant. METHODS: A nine-month-old PJS infant was admitted to our hospital for recurrent prolapsed rectal polyps for one month. The clinical characteristics, a colonoscopic image, the pathological characteristics of the polyps and X-ray images of the intestinal perforation were obtained. Serine threonine-protein kinase 11 (STK11) gene analysis was also performed using a DNA sample from this infant. RESULTS: Here we describe the youngest known Chinese infant with PJS. Five polyps, including a giant polyp of approximately 4 cm × 2 cm in size, were removed from the infant’s intestine. Laparotomy was performed to repair a perforation caused by pneumoperitoneum. The pathological results showed that this child had PJS. Molecular analysis of the STK11 gene further revealed a novel frameshift mutation (c.64_65het_delAT) in exon 1 in this PJS infant. CONCLUSION: The appropriate treatment method for multiple polyps in an infant must be carefully considered. Our results also show that the STK11 gene mutation is the primary cause of PJS. PMID:27004004

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.

Spinal Cord Injury Causes Chronic Liver Pathology in Rats

PubMed Central

Sauerbeck, Andrew D.; Laws, J. Lukas; Bandaru, Veera V.R.; Popovich, Phillip G.; Haughey, Norman J.

2015-01-01

Abstract Traumatic spinal cord injury (SCI) causes major disruption to peripheral organ innervation and regulation. Relatively little work has investigated these post-SCI systemic changes, however, despite considerable evidence that multiple organ system dysfunction contributes to chronic impairments in health. Because metabolic dysfunction is common after SCI and the liver is a pivotal site for metabolic homeostasis, we sought to determine if liver pathology occurs as a result of SCI in a rat spinal contusion model. Histologic evidence showed excess lipid accumulation in the liver for at least 21 days post-injury after cervical or midthoracic SCI. Lipidomic analysis revealed an acute increase in hepatic ceramides as well as chronically elevated lactosylceramide. Post-SCI hepatic changes also included increased proinflammatory gene expression, including interleukin (IL)-1α, IL-1β, chemokine ligand-2, and tumor necrosis factor-α mRNA. These were coincident with increased CD68+ macrophages in the liver through 21 days post-injury. Serum alanine transaminase, used clinically to detect liver damage, was significantly increased at 21 days post-injury, suggesting that early metabolic and inflammatory damage preceded overt liver pathology. Surprisingly, liver inflammation was even detected after lumbar SCI. Collectively, these results suggest that SCI produces chronic liver injury with symptoms strikingly similar to those of nonalcoholic steatohepatitis (fatty liver disease). These clinically significant hepatic changes after SCI are known to contribute to systemic inflammation, cardiovascular disease, and metabolic syndrome, all of which are more prevalent in persons with SCI. Targeting acute and prolonged hepatic pathology may improve recovery and reduce long-term complications after SCI. PMID:25036371

An Organ System Approach to Explore the Antioxidative, Anti-Inflammatory, and Cytoprotective Actions of Resveratrol

PubMed Central

Bath, Sundeep

2015-01-01

Resveratrol is a phenolic phytochemical, with a stilbene backbone, derived from edible plants such as grape and peanut. It is a bioactive molecule with physiological effects on multiple organ systems. Its effects range from the neuroprotective to the nephroprotective, including cardiovascular, neuronal, and antineoplastic responses as a part of its broad spectrum of action. In this review, we examine the effects of resveratrol on the following organ systems: the central nervous system, including neurological pathology such as Parkinson's and Alzheimer's disease; the cardiovascular system, including disorders such as atherosclerosis, ischemia-reperfusion injury, and cardiomyocyte hypertrophy; the kidneys, including primary and secondary nephropathies and nephrolithiasis; multiple forms of cancer; and metabolic syndromes including diabetes. We emphasize commonalities in extracellular matrix protein alterations and intracellular signal transduction system induction following resveratrol treatment. We summarize the known anti-inflammatory, antioxidative, and cytoprotective effects of resveratrol across disparate organ systems. Additionally, we analyze the available literature regarding the pharmacokinetics of resveratrol formulations used in these studies. Finally, we critically examine select clinical trials documenting a lack of effect following resveratrol treatment. PMID:26180596

Implementation of an education development project in pathology to improve student competency-lessons learnt.

PubMed

Negi, Gita; Harsh, Meena; Chauhan, Vijendra D; Kalra, Vinita; Agarwal, Pradeep; Kusum, Anuradha

2015-08-01

Basic medical sciences and clinical teachings are not coordinated in the present medical education system. They are not taught keeping in mind the outcomes required at the time of actual handling of patients in the community. An educational development project was implemented in the Department of Pathology with the aim that it will result in the student learning to link the pathophysiology of the disease to clinical scenarios and become fully competent for lifelong medical practice. The pathology teaching of the second professional batch was modified by starting with defining the desired outcomes/competencies in the student's knowledge, skills, and attitude which were then addressed by lectures, demonstrations, practical classes and small group activities where case scenarios and laboratory reports were included. The outcome was assessed by Objectively Structured Clinical/Practical Examination and multiple choice questions. Force field analysis, faculty and student interviews, and questionnaires were used to assess the factors affecting its implementation and impact. Totally 80 students of the 2(nd) Professional MBBS were exposed to a competency-based education development project. It was found that the system was appreciated by faculty and students, especially the integration with clinical scenarios. There were many factors which influenced the execution of this program, including motivation level of students and faculty, time, logistics and meticulous planning. There was a significant improvement in student's performance and satisfaction. Many factors including prior planning were a major determinant for the success of this education development project.

Tissue Physiology and Pathology of Aromatase

PubMed Central

Stocco, Carlos

2011-01-01

Summary Aromatase is expressed in multiple tissues, indicating a crucial role for locally produced oestrogens in the differentiation, regulation and normal function of several organs and processes. This review is an overview of the role of aromatase in different tissues under normal physiological conditions and its contribution to the development of some oestrogen-related pathologies. PMID:22108547

The structural and functional role of myelin fast-migrating cerebrosides: pathological importance in multiple sclerosis

PubMed Central

Podbielska, Maria; Levery, Steven B; Hogan, Edward L

2011-01-01

A family of neutral glycosphingolipids containing a 3-O-acetyl-sphingosine galactosylceramide (3-SAG) has been characterized. Seven new derivatives of galactosylceramide (GalCer), designated as fast-migrating cerebrosides (FMCs) by TLC retention factor, have been identified. The simplest compounds – FMC-1 and FMC-2 – of this series have been characterized as the 3-SAG containing nonhydroxy and hydroxy fatty acyl, respectively. The next two – FMC-3 and FMC-4 – add 6-O-acetyl-galactose and the most complex glycosphingolipids, FMC-5, -6 and -7, are 2,3,4,6-tetra-O-acetyl-3-SAG. These hydrophobic myelin lipid biomarkers coappear with GalCer during myelinogenesis and disappear along with GalCer in de- or dys-myelinating disorders. Myelin lipid antigens, including FMCs, are keys to myelin biology, opening the possibility of new and novel immune modulatory tools for treatment of autoimmune diseases including multiple sclerosis. PMID:22701512

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.

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.

The Relationship of Cerebral Vessel Pathology to Brain Microinfarcts

PubMed Central

Arvanitakis, Zoe; Capuano, Ana W.; Leurgans, Sue E.; Buchman, Aron S.; Bennett, David A.; Schneider, Julie A.

2016-01-01

The relationship of cerebral vessel pathology to brain microinfarcts is not fully understood. We examined associations of cerebral vessel pathology with microinfarcts among community-dwelling persons who came to autopsy. Brain specimens were derived from 1,066 deceased subjects (mean age-at-death = 88 years, 65% women) participating in a cohort study of aging. Microinfarcts were classified by number, age, and location. Severity of vessel pathologies was graded semi-quantitatively. Almost a third of subjects (n=300; 28%) had at least one chronic microinfarct, including 128 cortical only, 120 subcortical only, and 47 with both. Moderate-to-severe atherosclerosis was present in 430 (41%) subjects, arteriolosclerosis in 382 (36%), and amyloid angiopathy in 374 (35%). The odds of one or multiple microinfarct(s) was increased for more severe atherosclerosis (OR =1.22; 95%CI: 1.03–1.45), arteriolosclerosis (OR =1.18; 95%CI: 1.02–1.37), and amyloid angiopathy (OR =1.13; 95%CI: 1.00–1.28). Separately, the odds of subcortical microinfarct(s) was increased for atherosclerosis (OR =1.49; 95%CI: 1.20–1.84) and arteriolosclerosis (OR =1.39; 95%CI: 1.16–1.67) but not amyloid angiopathy; whereas the odds of cortical microinfarct(s) was increased for amyloid angiopathy (OR =1.26; 95%CI: 1.09–1.46) only. While cerebral vessel pathologies are associated with microinfarct burden, atherosclerosis and arteriolosclerosis are associated with subcortical microinfarcts, and amyloid angiopathy with cortical microinfarcts. PMID:26844934

The Enduring Challenge of Determining Pneumonia Etiology in Children: Considerations for Future Research Priorities.

PubMed

Feikin, Daniel R; Hammitt, Laura L; Murdoch, David R; O'Brien, Katherine L; Scott, J Anthony G

2017-06-15

Pneumonia kills more children each year worldwide than any other disease. Nonetheless, accurately determining the causes of childhood pneumonia has remained elusive. Over the past century, the focus of pneumonia etiology research has shifted from studies of lung aspirates and postmortem specimens intent on identifying pneumococcal disease to studies of multiple specimen types distant from the lung that are tested for multiple pathogens. Some major challenges facing modern pneumonia etiology studies include the use of nonspecific and variable case definitions, poor access to pathologic lung tissue and to specimens from fatal cases, poor diagnostic accuracy of assays (especially when testing nonpulmonary specimens), and the interpretation of results when multiple pathogens are detected in a given individual. The future of childhood pneumonia etiology research will likely require integrating data from complementary approaches, including applications of advanced molecular diagnostics and vaccine probe studies, as well as a renewed emphasis on lung aspirates from radiologically confirmed pneumonia and postmortem examinations. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Lysosomal response in relation to α-synuclein pathology differs between Parkinson's disease and multiple system atrophy.

PubMed

Puska, Gina; Lutz, Mirjam I; Molnar, Kinga; Regelsberger, Günther; Ricken, Gerda; Pirker, Walter; Laszlo, Lajos; Kovacs, Gabor G

2018-06-01

Intracellular deposition of pathologically altered α-synuclein mostly in neurons characterises Parkinson's disease (PD), while its accumulation predominantly in oligodendrocytes is a feature of multiple system atrophy (MSA). Recently a prion-like spreading of pathologic α-synuclein has been suggested to play a role in the pathogenesis of PD and MSA. This implicates a role of protein processing systems, including lysosomes, supported also by genetic studies in PD. However, particularly for MSA, the mechanism of cell-to-cell propagation of α-synuclein is yet not fully understood. To evaluate the significance of lysosomal response, we systematically compared differently affected neuronal populations in PD, MSA, and non-diseased brains using morphometric immunohistochemistry (cathepsin D), double immunolabelling (cathepsin D/α-synuclein) laser confocal microscopy, and immunogold electron microscopy for the disease associated α-synuclein. We found that i) irrespective of the presence of neuronal inclusions, the volume density of cathepsin D immunoreactivity significantly increases in affected neurons of the pontine base in MSA brains; ii) volume density of cathepsin D immunoreactivity increases in nigral neurons in PD without inclusions and with non-ubiquitinated pre-aggregates of α-synuclein, but not in neurons with Lewy bodies; iii) cathepsin D immunoreactivity frequently colocalises with α-synuclein pre-aggregates in nigral neurons in PD; iv) ultrastructural observations confirm disease-associated α-synuclein in neuronal and astrocytic lysosomes in PD; v) lysosome-associated α-synuclein is observed in astroglia and rarely in oligodendroglia and in neurons in MSA. Our observations support a crucial role for the neuronal endosomal-lysosomal system in the processing of α-synuclein in PD. We suggest a distinct contribution of lysosomes to the pathogenesis of MSA, including the possibility of oligodendroglial and eventually neuronal uptake of exogenous α-synuclein in MSA. Copyright © 2018 Elsevier Inc. All rights reserved.

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...

The tissue microarray data exchange specification: Extending TMA DES to provide flexible scoring and incorporate virtual slides

PubMed Central

Wright, Alexander; Lyttleton, Oliver; Lewis, Paul; Quirke, Philip; Treanor, Darren

2011-01-01

Background: Tissue MicroArrays (TMAs) are a high throughput technology for rapid analysis of protein expression across hundreds of patient samples. Often, data relating to TMAs is specific to the clinical trial or experiment it is being used for, and not interoperable. The Tissue Microarray Data Exchange Specification (TMA DES) is a set of eXtensible Markup Language (XML)-based protocols for storing and sharing digitized Tissue Microarray data. XML data are enclosed by named tags which serve as identifiers. These tag names can be Common Data Elements (CDEs), which have a predefined meaning or semantics. By using this specification in a laboratory setting with increasing demands for digital pathology integration, we found that the data structure lacked the ability to cope with digital slide imaging in respect to web-enabled digital pathology systems and advanced scoring techniques. Materials and Methods: By employing user centric design, and observing behavior in relation to TMA scoring and associated data, the TMA DES format was extended to accommodate the current limitations. This was done with specific focus on developing a generic tool for handling any given scoring system, and utilizing data for multiple observations and observers. Results: DTDs were created to validate the extensions of the TMA DES protocol, and a test set of data containing scores for 6,708 TMA core images was generated. The XML was then read into an image processing algorithm to utilize the digital pathology data extensions, and scoring results were easily stored alongside the existing multiple pathologist scores. Conclusions: By extending the TMA DES format to include digital pathology data and customizable scoring systems for TMAs, the new system facilitates the collaboration between pathologists and organizations, and can be used in automatic or manual data analysis. This allows complying systems to effectively communicate complex and varied scoring data. PMID:21572508

Evolutionary concepts in biobanking - the BC BioLibrary

PubMed Central

2009-01-01

Background Medical research to improve health care faces a major problem in the relatively limited availability of adequately annotated and collected biospecimens. This limitation is creating a growing gap between the pace of scientific advances and successful exploitation of this knowledge. Biobanks are an important conduit for transfer of biospecimens (tissues, blood, body fluids) and related health data to research. They have evolved outside of the historical source of tissue biospecimens, clinical pathology archives. Research biobanks have developed advanced standards, protocols, databases, and mechanisms to interface with researchers seeking biospecimens. However, biobanks are often limited in their capacity and ability to ensure quality in the face of increasing demand. Our strategy to enhance both capacity and quality in research biobanking is to create a new framework that repatriates the activity of biospecimen accrual for biobanks to clinical pathology. Methods The British Columbia (BC) BioLibrary is a framework to maximize the accrual of high-quality, annotated biospecimens into biobanks. The BC BioLibrary design primarily encompasses: 1) specialized biospecimen collection units embedded within clinical pathology and linked to a biospecimen distribution system that serves biobanks; 2) a systematic process to connect potential donors with biobanks, and to connect biobanks with consented biospecimens; and 3) interdisciplinary governance and oversight informed by public opinion. Results The BC BioLibrary has been embraced by biobanking leaders and translational researchers throughout BC, across multiple health authorities, institutions, and disciplines. An initial pilot network of three Biospecimen Collection Units has been successfully established. In addition, two public deliberation events have been held to obtain input from the public on the BioLibrary and on issues including consent, collection of biospecimens and governance. Conclusion The BC BioLibrary framework addresses common issues for clinical pathology, biobanking, and translational research across multiple institutions and clinical and research domains. We anticipate that our framework will lead to enhanced biospecimen accrual capacity and quality, reduced competition between biobanks, and a transparent process for donors that enhances public trust in biobanking. PMID:19909513

InterLymph hierarchical classification of lymphoid neoplasms for epidemiologic research based on the WHO classification (2008): update and future directions

PubMed Central

Morton, Lindsay M.; Linet, Martha S.; Clarke, Christina A.; Kadin, Marshall E.; Vajdic, Claire M.; Monnereau, Alain; Maynadié, Marc; Chiu, Brian C.-H.; Marcos-Gragera, Rafael; Costantini, Adele Seniori; Cerhan, James R.; Weisenburger, Dennis D.

2010-01-01

After publication of the updated World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues in 2008, the Pathology Working Group of the International Lymphoma Epidemiology Consortium (InterLymph) now presents an update of the hierarchical classification of lymphoid neoplasms for epidemiologic research based on the 2001 WHO classification, which we published in 2007. The updated hierarchical classification incorporates all of the major and provisional entities in the 2008 WHO classification, including newly defined entities based on age, site, certain infections, and molecular characteristics, as well as borderline categories, early and “in situ” lesions, disorders with limited capacity for clinical progression, lesions without current International Classification of Diseases for Oncology, 3rd Edition codes, and immunodeficiency-associated lymphoproliferative disorders. WHO subtypes are defined in hierarchical groupings, with newly defined groups for small B-cell lymphomas with plasmacytic differentiation and for primary cutaneous T-cell lymphomas. We suggest approaches for applying the hierarchical classification in various epidemiologic settings, including strategies for dealing with multiple coexisting lymphoma subtypes in one patient, and cases with incomplete pathologic information. The pathology materials useful for state-of-the-art epidemiology studies are also discussed. We encourage epidemiologists to adopt the updated InterLymph hierarchical classification, which incorporates the most recent WHO entities while demonstrating their relationship to older classifications. PMID:20699439

InterLymph hierarchical classification of lymphoid neoplasms for epidemiologic research based on the WHO classification (2008): update and future directions.

PubMed

Turner, Jennifer J; Morton, Lindsay M; Linet, Martha S; Clarke, Christina A; Kadin, Marshall E; Vajdic, Claire M; Monnereau, Alain; Maynadié, Marc; Chiu, Brian C-H; Marcos-Gragera, Rafael; Costantini, Adele Seniori; Cerhan, James R; Weisenburger, Dennis D

2010-11-18

After publication of the updated World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues in 2008, the Pathology Working Group of the International Lymphoma Epidemiology Consortium (InterLymph) now presents an update of the hierarchical classification of lymphoid neoplasms for epidemiologic research based on the 2001 WHO classification, which we published in 2007. The updated hierarchical classification incorporates all of the major and provisional entities in the 2008 WHO classification, including newly defined entities based on age, site, certain infections, and molecular characteristics, as well as borderline categories, early and "in situ" lesions, disorders with limited capacity for clinical progression, lesions without current International Classification of Diseases for Oncology, 3rd Edition codes, and immunodeficiency-associated lymphoproliferative disorders. WHO subtypes are defined in hierarchical groupings, with newly defined groups for small B-cell lymphomas with plasmacytic differentiation and for primary cutaneous T-cell lymphomas. We suggest approaches for applying the hierarchical classification in various epidemiologic settings, including strategies for dealing with multiple coexisting lymphoma subtypes in one patient, and cases with incomplete pathologic information. The pathology materials useful for state-of-the-art epidemiology studies are also discussed. We encourage epidemiologists to adopt the updated InterLymph hierarchical classification, which incorporates the most recent WHO entities while demonstrating their relationship to older classifications.

[The role of endocannabinoid system in physiological and pathological processes in the eye].

PubMed

Nadolska, Krystyna; Goś, Roman

2008-01-01

Plant of Cannabis sativa/ marihuana except for its psychotropic effects possesses a range of pharmacological properties, that has been utilized for medical purposes over a period of millenia. Investigations concerning biochemical mechanism of action of the main and most active pharmacological compound of Cannabis sativa, cannabinoid 9-THC, contributed to the discovery of cannabinoid receptors both in the central nervous system (CNS) and peripheral tissues, that mediated actions of this substance. The discovery made possible identification of a new, endogenous signaling system reffered to as the endocannabinoid system. Besides cannabinoid receptors CB1 and CB2, the system includes it's endogenic ligands (endocannabinoids) and compounds that participate in their biosynthesis and inactivation. Structure and functioning of the endocannabinoid system is conservative in all vertebrates. It's activation with plant, synthetic and endogenous cannabinoids has an influence on multiple physiological and pathological processes within the eye.

Parallel states of pathological Wnt signaling in neonatal brain injury and colon cancer

PubMed Central

Fancy, Stephen P.J.; Harrington, Emily P.; Baranzini, Sergio E.; Silbereis, John C.; Shiow, Lawrence R.; Yuen, Tracy J.; Huang, Eric J.; Lomvardas, Stavros; Rowitch, David H.

2014-01-01

In colon cancer, mutation of the Wnt repressor Adenomatous polyposis coli (APC) leads to a state of aberrant and unrestricted “high-activity” signaling. However, relevance of high Wnt tone in non-genetic human disease is unknown. Here we demonstrate that distinct Wnt activity functional states determine oligodendrocyte precursor (OPC) differentiation and myelination. Murine OPCs with genetic Wnt dysregulation (high tone) express multiple genes in common with colon cancer including Lef1, SP5, Ets2, Rnf43 and Dusp4. Surprisingly, we find that OPCs in lesions of hypoxic human neonatal white matter injury upregulate markers of high Wnt activity and lack expression of APC. Finally, we show lack of Wnt repressor tone promotes permanent white matter injury after mild hypoxic insult. These findings suggest a state of pathological high-activity Wnt signaling in human disease tissues that lack pre-disposing genetic mutation. PMID:24609463

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

Clinical Manifestations and Overall Management Strategies for Duchenne Muscular Dystrophy.

PubMed

Tsuda, Takeshi

2018-01-01

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder that causes progressive weakness and wasting of skeletal muscular and myocardium in boys due to mutation of dystrophin. The structural integrity of each individual skeletal and cardiac myocyte is significantly compromised upon physical stress due to the absence of dystrophin. The progressive destruction of systemic musculature and myocardium causes affected patients to develop multiple organ disabilities, including loss of ambulation, physical immobility, neuromuscular scoliosis, joint contracture, restrictive lung disease, obstructive sleep apnea, and cardiomyopathy. There are some central nervous system-related medical problems, as dystrophin is also expressed in the neuronal tissues. Although principal management is to mainly delay the pathological process, an enhanced understanding of underlying pathological processes has significantly improved quality of life and longevity for DMD patients. Future research in novel molecular approach is warranted to answer unanswered questions.

Endoscopic findings and pathologic characteristics of gastric eosinophilic granuloma: A report of 18 patients

PubMed Central

Song, Wen-Chong; Yu, Jie-Ping; Shen, Lei; Xia, Hong; Luo, He-Sheng

2006-01-01

AIM: To investigate the endoscopic findings and patholo-gic characteristics of gastric eosinophilic granuloma (GEG). METHODS: A retrospective study of 18 cases of gastric eosinophilic granulomas was conducted. Gastroscopy was performed and all specimens of biopsies were stained by H&E and observed under light microscopy. RESULTS: Ulcer was the most frequent endoscopic appearance. The others included deformed pylorus and/or duodenal bulb, esophagitis, mucous hyperemia and/or mucosal erosion. Eosinophilic cell infiltration and generous hyperplasia of arterioles, venules and lymph vessels were found in the lesions of the patients. Interstitium had massive eosinophilic infiltrates and was made up of collagen fibers and fibroblasts. Lymphoid follicles were revealed in some sections of biopsies. CONCLUSION: GEG is lack of specific symptoms and physical signs. It can be misdiagnosed as gastric ulcer in most cases before biopsies. Endoscopy and endoscopic multiple deep biopsies in suspected areas are indispensable for correct diagnosis of GEG. PMID:17167848

Cystic Fibrosis: A Review of Associated Phenotypes, Use of Molecular Diagnostic Approaches, Genetic Characteristics, Progress, and Dilemmas.

PubMed

Brennan, Marie-Luise; Schrijver, Iris

2016-01-01

Cystic fibrosis (CF) is an autosomal recessive disease with significant associated morbidity and mortality. It is now appreciated that the broad phenotypic CF spectrum is not explained by obvious genotype-phenotype correlations, suggesting that CF transmembrane conductance regulator (CFTR)-related disease may occur because of multiple additive effects. These contributing effects include complex CFTR alleles, modifier genes, mutations in alternative genes that produce CF-like phenotypes, epigenetic factors, and environmental influences. Most patients in the United States are now diagnosed through newborn screening and use of molecular testing methods. We review the molecular testing approaches and laboratory guidelines for carrier screening, prenatal testing, newborn screening, and clinical diagnostic testing, as well as recent developments in CF treatment, and reasons for the lack of a molecular diagnosis in some patients. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

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

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

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

Perforant path synaptic loss correlates with cognitive impairment and Alzheimer's disease in the oldest-old.

PubMed

Robinson, John L; Molina-Porcel, Laura; Corrada, Maria M; Raible, Kevin; Lee, Edward B; Lee, Virginia M-Y; Kawas, Claudia H; Trojanowski, John Q

2014-09-01

Alzheimer's disease, which is defined pathologically by abundant amyloid plaques and neurofibrillary tangles concurrent with synaptic and neuronal loss, is the most common underlying cause of dementia in the elderly. Among the oldest-old, those aged 90 and older, other ageing-related brain pathologies are prevalent in addition to Alzheimer's disease, including cerebrovascular disease and hippocampal sclerosis. Although definite Alzheimer's disease pathology can distinguish dementia from normal individuals, the pathologies underlying cognitive impairment, especially in the oldest-old, remain poorly understood. We therefore conducted studies to determine the relative contributions of Alzheimer's disease pathology, cerebrovascular disease, hippocampal sclerosis and the altered expression of three synaptic proteins to cognitive status and global cognitive function. Relative immunohistochemistry intensity measures were obtained for synaptophysin, Synaptic vesicle transporter Sv2 (now known as SV2A) and Vesicular glutamate transporter 1 in the outer molecular layer of the hippocampal dentate gyrus on the first 157 participants of 'The 90+ Study' who came to autopsy, including participants with dementia (n = 84), those with cognitive impairment but no dementia (n = 37) and those with normal cognition (n = 36). Thal phase, Braak stage, cerebrovascular disease, hippocampal sclerosis and Pathological 43-kDa transactive response sequence DNA-binding protein (TDP-43) were also analysed. All measures were obtained blind to cognitive diagnosis. Global cognition was tested by the Mini-Mental State Examinaton. Logistic regression analysis explored the association between the pathological measures and the odds of being in the different cognitive groups whereas multiple regression analyses explored the association between pathological measures and global cognition scores. No measure clearly distinguished the control and cognitive impairment groups. Comparing the cognitive impairment and dementia groups, synaptophysin and SV2 were reduced, whereas Braak stage, TDP-43 and hippocampal sclerosis frequency increased. Thal phase and VGLUT1 did not distinguish the cognitive impairment and dementia groups. All measures distinguished the dementia and control groups and all markers associated with the cognitive test scores. When all markers were analysed simultaneously, a reduction in synaptophysin, a high Braak stage and the presence of TDP-43 and hippocampal sclerosis associated with global cognitive function. These findings suggest that tangle pathology, hippocampal sclerosis, TDP-43 and perforant pathway synaptic loss are the major contributors to dementia in the oldest-old. Although an increase in plaque pathology and glutamatergic synaptic loss may be early events associated with cognitive impairment, we conclude that those with cognitive impairment, but no dementia, are indistinguishable from cognitively normal subjects based on the measures reported here. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

Pericytes in kidney fibrosis.

PubMed

Ren, Shuyu; Duffield, Jeremy S

2013-07-01

Pericytes and perivascular fibroblasts have emerged as poorly appreciated yet extensive populations of mesenchymal cells in the kidney that play important roles in homeostasis and responses to injury. This review will update readers on the evolving understanding of the biology of these cells. Fate mapping has identified pericytes and perivascular fibroblasts as the major source of pathological fibrillar matrix-forming cells in interstitial kidney disease. In other organs similar cells have been described and independent fate mapping indicates that pericytes or perivascular cells are myofibroblast progenitors in multiple organs. Over the last year, new insights into the function of pericytes in kidney homeostasis has been uncovered and new molecular pathways that regulate detachment and their transdifferentiation into pathological myofibroblasts, including Wingless/Int, ephrin, transforming growth factor β, platelet derived growth factor, and Hedgehog signaling pathways, have been reported. In addition provocative studies indicate that microRNAs, which regulate posttranscriptional gene expression, may also play important roles in their transdifferentiation. Pericytes and perivascular fibroblasts are the major source of pathological collagen fiber-forming cells in interstitial kidney diseases. New avenues of research into their activation and differentiation has identified new drug candidates for the treatment of interstitial kidney disease.

Measurement of psychological disorders using cognitive diagnosis models.

PubMed

Templin, Jonathan L; Henson, Robert A

2006-09-01

Cognitive diagnosis models are constrained (multiple classification) latent class models that characterize the relationship of questionnaire responses to a set of dichotomous latent variables. Having emanated from educational measurement, several aspects of such models seem well suited to use in psychological assessment and diagnosis. This article presents the development of a new cognitive diagnosis model for use in psychological assessment--the DINO (deterministic input; noisy "or" gate) model--which, as an illustrative example, is applied to evaluate and diagnose pathological gamblers. As part of this example, a demonstration of the estimates obtained by cognitive diagnosis models is provided. Such estimates include the probability an individual meets each of a set of dichotomous Diagnostic and Statistical Manual of Mental Disorders (text revision [DSM-IV-TR]; American Psychiatric Association, 2000) criteria, resulting in an estimate of the probability an individual meets the DSM-IV-TR definition for being a pathological gambler. Furthermore, a demonstration of how the hypothesized underlying factors contributing to pathological gambling can be measured with the DINO model is presented, through use of a covariance structure model for the tetrachoric correlation matrix of the dichotomous latent variables representing DSM-IV-TR criteria. Copyright 2006 APA

Thiamine deficiency induces oxidative stress and exacerbates the plaque pathology in Alzheimer’s mouse model

PubMed Central

Karuppagounder, Saravanan S.; Xu, Hui; Shi, Qingli; Chen, Lian H.; Pedrini, Steve; Pechman, David; Baker, Harriet; Beal, M. Flint; Gandy, Sam E.; Gibson, Gary E.

2009-01-01

Mitochondrial dysfunction, oxidative stress and reductions in thiamine-dependent enzymes have been implicated in multiple neurological disorders including Alzheimer's disease (AD). Experimental thiamine deficiency (TD) is an established model for reducing the activities of thiamine-dependent enzymes in brain. TD diminishes thiamine dependent enzymes throughout the brain, but produces a time-dependent selective neuronal loss, glial activation, inflammation, abnormalities in oxidative metabolism and clusters of degenerating neurites in only specific thalamic regions. The present studies tested how TD alters brain pathology in Tg19959 transgenic mice over expressing a double mutant form of the amyloid precursor protein (APP). TD exacerbated amyloid plaque pathology in transgenic mice and enlarged the area occupied by plaques in cortex, hippocampus and thalamus by 50%, 200% and 200%, respectively. TD increased Aβ1–42 levels by about three-fold, β-CTF (C99) levels by 33% and β-secretase (BACE1) protein levels by 43%. TD induced inflammation in areas of plaque formation. Thus, the induction of mild impairment of oxidative metabolism, oxidative stress and inflammation induced by TD alters metabolism of APP and/or Aβ and promotes accumulation of plaques independent of neuron loss or neuritic clusters. PMID:18406011

Activation of inflammasome signaling mediates pathology of acute P. aeruginosa pneumonia

PubMed Central

Cohen, Taylor S.; Prince, Alice S.

2013-01-01

The respiratory tract is exceptionally well defended against infection from inhaled bacteria, with multiple proinflammatory signaling cascades recruiting phagocytes to clear airway pathogens. However, organisms that efficiently activate damaging innate immune responses, such as those mediated by the inflammasome and caspase-1, may cause pulmonary damage and interfere with bacterial clearance. The extracellular, opportunistic pathogen Pseudomonas aeruginosa expresses not only pathogen-associated molecular patterns that activate NF-κB signaling in epithelial and immune cells, but also flagella that activate the NLRC4 inflammasome. We demonstrate that induction of inflammasome signaling, ascribed primarily to the alveolar macrophage, impaired P. aeruginosa clearance and was associated with increased apoptosis/pyroptosis and mortality in a murine model of acute pneumonia. Strategies that limited inflammasome activation, including infection by fliC mutants, depletion of macrophages, deletion of NLRC4, reduction of IL-1β and IL-18 production, inhibition of caspase-1, and inhibition of downstream signaling in IL-1R– or IL-18R–null mice, all resulted in enhanced bacterial clearance and diminished pathology. These results demonstrate that the inflammasome provides a potential target to limit the pathological consequences of acute P. aeruginosa pulmonary infection. PMID:23478406

The advantages of a swept source optical coherence tomography system in the evaluation of occlusal disorders

NASA Astrophysics Data System (ADS)

Marcauteanu, Corina; Bradu, Adrian; Sinescu, Cosmin; Topala, Florin Ionel; Negrutiu, Meda Lavinia; Duma, Virgil Florin; Podoleanu, Adrian Gh.

2014-01-01

Occlusal disorders are characterized by multiple dental and periodontal signs. Some of these are reversible (such as excessive tooth mobility, fremitus, tooth pain, migration of teeth in the absence of periodontitis), some are not (pathological occlusal/incisal wear, abfractions, enamel cracks, tooth fractures, gingival recessions). In this paper we prove the advantages of a fast swept source OCT system in the diagnosis of pathological incisal wear, a key sign of the occlusal disorders. On 15 extracted frontal teeth four levels of pathological incisal wear facets were artificially created. After every level of induced defect, OCT scanning was performed. B scans were acquired and 3D reconstructions were generated. A swept source OCT instrument is used in this study. The swept source is has a central wavelength of 1050 nm and a sweeping rate of 100 kHz. A depth resolution determined by the swept source of 12 μm in air was experimentally measured. The pathological incisal wear is qualitatively observed on the B-scans as 2D images and 3D reconstructions (volumes). For quantitative evaluations of volumes, we used the Image J software. Our swept source OCT system has several advantages, including the ability to measure (in air) a minimal volume of 2352 μm3 and to collect high resolution volumetric images in 2.5 s. By calculating the areas of the amount of lost tissue corresponding to each difference of B-scans, the final volumes of incisal wear were obtained. This swept source OCT method is very useful for the dynamic evaluation of pathological incisal wear.

Physician satisfaction with surgical pathology reports: a 2-year College of American Pathologists Q-Tracks Study.

PubMed

Nakhleh, Raouf E; Souers, Rhona; Ruby, Stephen G

2008-11-01

There are multiple elements that can be measured to assess the quality of a surgical pathology laboratory. Overall customer satisfaction is an excellent "global" measure, because it highlights the unique insight of laboratory performance from the users' perspective. To measure customer satisfaction with surgical pathology reports. This study was based on a subscription Q-Tracks study. Voluntary participants were asked to distribute and collect a minimum of 25 surveys per quarter from their clients. Four parameters were graded, which included overall satisfaction, report turnaround time (TAT), completeness, and style on a scale of 1 (poor) to 5 (excellent). Each laboratory submitted quarterly data to the College of American Pathologists, where the data were tabulated and analyzed. Each laboratory could compare their performance in all 4 measures against the entire cohort or a selected subgroup of laboratories. Overall customer satisfaction with surgical pathology reports and 3 subcategories of report TAT, completeness, and style were the main outcome measures. This study ran during 2004 and 2005, with 41 and 33 participant laboratories, respectively. The median score for overall satisfaction, TAT, completeness, and style were 4.57, 4.31, 4.62, and 4.64 in 2004, and 4.64, 4.56, 4.65, and 4.68 in 2005, respectively. Most laboratories reported results for 4 quarters or fewer. There was no statistically significant change in overall satisfaction over time. Overall satisfaction scores for surgical pathology reports as well as satisfaction with report TAT, completeness, and style were high. Report TAT received the lowest scores of all parameters.

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

The surgical treatment of anterior knee pain due to infrapatellar fat pad pathology: A systematic review.

PubMed

Rooney, A; Wahba, A J; Smith, T O; Donell, S T

2015-06-01

Anterior knee pain (AKP) encompasses a range of pathologies. As a result, there are a number of therapeutic options used to treat AKP. The non-operative treatments have been analysed in a number of randomised controlled trials and systematic reviews. There is however a scarcity of such publications covering the surgical management of AKP. There are no systematic reviews that have investigated surgical interventions for AKP due to pathology of the infrapatellar fat pad (IFP). The aims of this study were to review the literature systematically, to establish which surgical procedures have been used to treat IFP disease and to determine their efficacy. The review was conducted in accordance with the PRISMA reporting guidelines. A search of the literature was performed on 1st January 2014 using multiple databases including CENTRAL, MEDLINE, EMBASE, PubMed, and Google Scholar. The quality of the studies was assessed using Oxford Evidence-Based Medicine Levels of Evidence guidelines and the GRADE approach. Twenty-four eligible studies were found and included. The critical appraisal identified that the current evidence-base has low methodology quality. The clinical findings indicated that there is a positive trend towards the surgical management of IFP disease for AKP symptoms. Excision of IFP tumours and resection of the IFP in Hoffa's disease can lead to improvements in symptoms and function. Truly robust evidence to support the surgical management of IFP pathology requires randomised controlled trials; however the expenses involved to design such trials means that they are unlikely to be undertaken for this uncommon disorder. Consequently well-designed and well-reported case series need to be undertaken to improve our current understanding that includes recording quantitative measures such as range of knee motion, VAS Pain scores and a validated scoring system. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Adenoid cystic carcinoma: An unusual presentation.

PubMed

Pushpanjali, M; Sujata, D Naga; Subramanyam, S Bala; Jyothsna, M

2014-05-01

The adenoid cystic carcinoma is a relatively rare epithelial tumor of the major and minor salivary glands, accounting for about 1% of all malignant tumor of the oral and maxillofacial regions. Peak incidence occurs between the 5(th) and 6(th) decades of life. The clinical and pathological findings typical of this tumor include slow growth, peri-neural invasion, multiple local recurrences and distant metastasis. Herein, we report a case of adenoid cystic carcinoma of oropharynx with unusual clinical presentation. The diagnosis of this case and importance of cytology in diagnosing such cases is discussed.

Adenoid cystic carcinoma: An unusual presentation

PubMed Central

Pushpanjali, M; Sujata, D Naga; Subramanyam, S Bala; Jyothsna, M

2014-01-01

The adenoid cystic carcinoma is a relatively rare epithelial tumor of the major and minor salivary glands, accounting for about 1% of all malignant tumor of the oral and maxillofacial regions. Peak incidence occurs between the 5th and 6th decades of life. The clinical and pathological findings typical of this tumor include slow growth, peri-neural invasion, multiple local recurrences and distant metastasis. Herein, we report a case of adenoid cystic carcinoma of oropharynx with unusual clinical presentation. The diagnosis of this case and importance of cytology in diagnosing such cases is discussed. PMID:25328314

Late effects of 2.2 GeV protons on the central nervous system.

NASA Technical Reports Server (NTRS)

Lippincott, S. W.; Calvo, W.

1971-01-01

Investigation of late pathological effects of high-energy (2.2 GeV) protons on the brain of rabbits, in a postirradiation period of up to 16 months following exposure at fluxes of 30, 100, and 1000 billion protons per sq cm. At the latter two irradiation-intensity levels, the kinds of brain lesions inflicted include large venous dilatation, thickening of vessel walls with deposit of amorphous PAS positive substance, thrombosis, perivascular infiltration of leukocytes and macrophages, mobilization of microglia cells, gliosis, demyelinization, and multiple small pseudocyst formation.

Neuro-immune interactions at barrier surfaces

PubMed Central

Veiga-Fernandes, Henrique; Mucida, Daniel

2016-01-01

Multidirectional interactions between the nervous and immune systems have been documented in homeostasis and pathologies ranging from multiple sclerosis to autism, and from leukemia to acute and chronic inflammation. Recent studies have addressed this crosstalk using cell-specific targeting, novel sequencing, imaging and analytical tools, shedding light on unappreciated mechanisms of neuro-immune regulation. This review focuses on neuro-immune interactions at barrier surfaces, mostly the gut, but also including the skin and the airways, areas densely populated by neurons and immune cells that constantly sense and adapt to tissue-specific environmental challenges. PMID:27153494

Childhood bone tuberculosis from Roman Pécs, Hungary.

PubMed

Hlavenková, L; Teasdale, M D; Gábor, O; Nagy, G; Beňuš, R; Marcsik, A; Pinhasi, R; Hajdu, T

2015-02-01

A child from a Roman necropolis in Pécs, Hungary (4th century CE) was initially diagnosed with severe spinal osteomyelitis. The post-cranial skeleton displayed bone alterations in the lower thoracic and upper lumbar segments, including vertebral body destruction, collapse and sharp kyphosis, and additional multiple rib lesions, suggesting a most likely diagnosis of pulmonary and spinal tuberculosis. This study discusses a number of selected diagnoses in the context of our pathological findings, complementing the macroscopic examination with radiological and biomolecular analyses. Copyright © 2014 Elsevier GmbH. All rights reserved.

Interactive web-based identification and visualization of transcript shared sequences.

PubMed

Azhir, Alaleh; Merino, Louis-Henri; Nauen, David W

2018-05-12

We have developed TraC (Transcript Consensus), a web-based tool for detecting and visualizing shared sequences among two or more mRNA transcripts such as splice variants. Results including exon-exon boundaries are returned in a highly intuitive, data-rich, interactive plot that permits users to explore the similarities and differences of multiple transcript sequences. The online tool (http://labs.pathology.jhu.edu/nauen/trac/) is free to use. The source code is freely available for download (https://github.com/nauenlab/TraC). Copyright © 2018 Elsevier Inc. All rights reserved.

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.

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.

Dendritic Spine Pathology in Schizophrenia

PubMed Central

Glausier, Jill R.; Lewis, David A.

2012-01-01

Schizophrenia is a neurodevelopmental disorder whose clinical features include impairments in perception, cognition and motivation. These impairments reflect alterations in neuronal circuitry within and across multiple brain regions that are due, at least in part, to deficits in dendritic spines, the site of most excitatory synaptic connections. Dendritic spine alterations have been identified in multiple brain regions in schizophrenia, but are best characterized in layer 3 of the neocortex, where pyramidal cell spine density is lower. These spine deficits appear to arise during development, and thus are likely the result of disturbances in the molecular mechanisms that underlie spine formation, pruning, and/or maintenance. Each of these mechanisms may provide insight into novel therapeutic targets for preventing or repairing the alterations in neural circuitry that mediate the debilitating symptoms of schizophrenia. PMID:22546337

Safety in the operating theatre--a transition to systems-based care.

PubMed

Weiser, Thomas G; Porter, Michael P; Maier, Ronald V

2013-03-01

All surgeons want the best, safest care for their patients, but providing this requires the complex coordination of multiple disciplines to ensure that all elements of care are timely, appropriate, and well organized. Quality-improvement initiatives are beginning to lead to improvements in the quality of care and coordination amongst teams in the operating room. As the population ages and patients present with more complex disease pathology, the demands for efficient systematization will increase. Although evidence suggests that postoperative mortality rates are declining, there is substantial room for improvement. Multiple quality metrics are used as surrogates for safe care, but surgical teams--including surgeons, anaesthetists, and nurses--must think beyond these simple interventions if they are to effectively communicate and coordinate in the face of increasing demands.

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

Computational Pathology: A Path Ahead.

PubMed

Louis, David N; Feldman, Michael; Carter, Alexis B; Dighe, Anand S; Pfeifer, John D; Bry, Lynn; Almeida, Jonas S; Saltz, Joel; Braun, Jonathan; Tomaszewski, John E; Gilbertson, John R; Sinard, John H; Gerber, Georg K; Galli, Stephen J; Golden, Jeffrey A; Becich, Michael J

2016-01-01

We define the scope and needs within the new discipline of computational pathology, a discipline critical to the future of both the practice of pathology and, more broadly, medical practice in general. To define the scope and needs of computational pathology. A meeting was convened in Boston, Massachusetts, in July 2014 prior to the annual Association of Pathology Chairs meeting, and it was attended by a variety of pathologists, including individuals highly invested in pathology informatics as well as chairs of pathology departments. The meeting made recommendations to promote computational pathology, including clearly defining the field and articulating its value propositions; asserting that the value propositions for health care systems must include means to incorporate robust computational approaches to implement data-driven methods that aid in guiding individual and population health care; leveraging computational pathology as a center for data interpretation in modern health care systems; stating that realizing the value proposition will require working with institutional administrations, other departments, and pathology colleagues; declaring that a robust pipeline should be fostered that trains and develops future computational pathologists, for those with both pathology and nonpathology backgrounds; and deciding that computational pathology should serve as a hub for data-related research in health care systems. The dissemination of these recommendations to pathology and bioinformatics departments should help facilitate the development of computational pathology.

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

Localized primary gastrointestinal diffuse large B cell lymphoma received a surgical approach: an analysis of prognostic factors and comparison of staging systems in 101 patients from a single institution.

PubMed

Zhang, Shengting; Wang, Li; Yu, Dong; Shen, Yang; Cheng, Shu; Zhang, Li; Qian, Ying; Shen, Zhixiang; Li, Qinyu; Zhao, Weili

2015-08-15

Diffuse large B cell lymphoma (DLBCL) represents the most common histological subtype of primary gastrointestinal lymphoma and is a heterogeneous group of disease. Prognostic characterization of individual patients is an essential prerequisite for a proper risk-based therapeutic choice. Clinical and pathological prognostic factors were identified, and predictive value of four previously described prognostic systems were assessed in 101 primary gastrointestinal DLBCL (PG-DLBCL) patients with localized disease, including Ann Arbor staging with Musshoff modification, International Prognostic Index (IPI), Lugano classification, and Paris staging system. Univariate factors correlated with inferior survival time were clinical parameters [age>60 years old, multiple extranodal/gastrointestinal involvement, elevated serum lactate dehydrogenase and β2-microglobulin, and decreased serum albumin], as well as pathological parameters (invasion depth beyond serosa, involvement of regional lymph node or adjacent tissue, Ki-67 index, and Bcl-2 expression). Major independent variables of adverse outcome indicated by multivariate analysis were multiple gastrointestinal involvement. In patients unfit for Rituximab but received surgery, radical surgery significantly prolonged the survival time, comparing with alleviative surgery. Addition of Rituximab could overcome the negative prognostic effect of alleviative surgery. Among the four prognostic systems, IPI and Lugano classification clearly separated patients into different risk groups. IPI was able to further stratify the early-stage patients of Lugano classification into groups with distinct prognosis. Radical surgery might be proposed for the patients unfit for Rituximab treatment, and a combination of clinical and pathological staging systems was more helpful to predict the disease outcome of PG-DLBCL patients.

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.

Computational Pathology

PubMed Central

Louis, David N.; Feldman, Michael; Carter, Alexis B.; Dighe, Anand S.; Pfeifer, John D.; Bry, Lynn; Almeida, Jonas S.; Saltz, Joel; Braun, Jonathan; Tomaszewski, John E.; Gilbertson, John R.; Sinard, John H.; Gerber, Georg K.; Galli, Stephen J.; Golden, Jeffrey A.; Becich, Michael J.

2016-01-01

Context We define the scope and needs within the new discipline of computational pathology, a discipline critical to the future of both the practice of pathology and, more broadly, medical practice in general. Objective To define the scope and needs of computational pathology. Data Sources A meeting was convened in Boston, Massachusetts, in July 2014 prior to the annual Association of Pathology Chairs meeting, and it was attended by a variety of pathologists, including individuals highly invested in pathology informatics as well as chairs of pathology departments. Conclusions The meeting made recommendations to promote computational pathology, including clearly defining the field and articulating its value propositions; asserting that the value propositions for health care systems must include means to incorporate robust computational approaches to implement data-driven methods that aid in guiding individual and population health care; leveraging computational pathology as a center for data interpretation in modern health care systems; stating that realizing the value proposition will require working with institutional administrations, other departments, and pathology colleagues; declaring that a robust pipeline should be fostered that trains and develops future computational pathologists, for those with both pathology and non-pathology backgrounds; and deciding that computational pathology should serve as a hub for data-related research in health care systems. The dissemination of these recommendations to pathology and bioinformatics departments should help facilitate the development of computational pathology. PMID:26098131

Current research in aging: a report from the 2015 Ageing Summit.

PubMed

Moyse, Emmanuel; Lahousse, Lies; Krantic, Slavica

2015-01-01

Ageing Summit, London, UK, 10-12 February 2015 The Ageing Summit 2015 held on 10-12 February 2015 in London (UK) provided an extensive update to our knowledge of the 'Biology of Ageing' and a forum to discuss the participants' latest research progress. The meeting was subdivided into four thematic sessions: cellular level research including the aging brain; slowing down progression, rejuvenation and self-repair; genetic and epigenetic regulation; and expression and pathology of age-related diseases. Each session included multiple key presentations, three to five short research communications and ongoing poster presentations. The meeting provided an exciting multidisciplinary overview of the aging process from cellular and molecular mechanisms to medico-social aspects of human aging.

Heterogeneous data fusion for brain tumor classification.

PubMed

Metsis, Vangelis; Huang, Heng; Andronesi, Ovidiu C; Makedon, Fillia; Tzika, Aria

2012-10-01

Current research in biomedical informatics involves analysis of multiple heterogeneous data sets. This includes patient demographics, clinical and pathology data, treatment history, patient outcomes as well as gene expression, DNA sequences and other information sources such as gene ontology. Analysis of these data sets could lead to better disease diagnosis, prognosis, treatment and drug discovery. In this report, we present a novel machine learning framework for brain tumor classification based on heterogeneous data fusion of metabolic and molecular datasets, including state-of-the-art high-resolution magic angle spinning (HRMAS) proton (1H) magnetic resonance spectroscopy and gene transcriptome profiling, obtained from intact brain tumor biopsies. Our experimental results show that our novel framework outperforms any analysis using individual dataset.

Imaging outcome measures for progressive multiple sclerosis trials

PubMed Central

Moccia, Marcello; de Stefano, Nicola; Barkhof, Frederik

2017-01-01

Imaging markers that are reliable, reproducible and sensitive to neurodegenerative changes in progressive multiple sclerosis (MS) can enhance the development of new medications with a neuroprotective mode-of-action. Accordingly, in recent years, a considerable number of imaging biomarkers have been included in phase 2 and 3 clinical trials in primary and secondary progressive MS. Brain lesion count and volume are markers of inflammation and demyelination and are important outcomes even in progressive MS trials. Brain and, more recently, spinal cord atrophy are gaining relevance, considering their strong association with disability accrual; ongoing improvements in analysis methods will enhance their applicability in clinical trials, especially for cord atrophy. Advanced magnetic resonance imaging (MRI) techniques (e.g. magnetization transfer ratio (MTR), diffusion tensor imaging (DTI), spectroscopy) have been included in few trials so far and hold promise for the future, as they can reflect specific pathological changes targeted by neuroprotective treatments. Position emission tomography (PET) and optical coherence tomography have yet to be included. Applications, limitations and future perspectives of these techniques in clinical trials in progressive MS are discussed, with emphasis on measurement sensitivity, reliability and sample size calculation. PMID:29041865

[A Case of Metachronous Multiple Thyroid Papillary Carcinoma with FAP].

PubMed

Tajima, Yusuke; Kumamoto, Kensuke; Yamamoto, Azusa; Chika, Noriyasu; Watanabe, Yuichiro; Matsuzawa, Takeaki; Ishibashi, Keiichiro; Mochiki, Erito; Iwama, Takeo; Akagi, Kiwamu; Ishida, Hideyuki

2015-11-01

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disorder, the result of a germ line mutation in the adenomatous polyposis coli (APC) gene. FAP can be associated with various extracolonic lesions, including thyroid cancer, which frequently occurs in women. We report the case of a 36-year-old woman diagnosed as having FAP with multiple metachronous thyroid papillary carcinomas. She underwent left thyroidectomy at the age of 19 years without a diagnosis of FAP. Multiple polyps in her stomach were detected by medical examination and more than 100 polyps in the colon were found by colonoscopy. She was referred to our hospital after a diagnosis of non-profuse FAP. Multiple tumors with a maximum diameter of 10mm were detected in the right lobe of the thyroid gland during the preoperative examination. Papillary carcinoma was suspected based on fine-needle aspiration cytology. We performed a right thyroidectomy after prophylactic colectomy. Pathological findings revealed a cribriform-morula variant of papillary thyroid carcinoma. The patient remains well after 2 year 6 months with no recurrence.

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.

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.

A Next-Generation Sequencing Strategy for Evaluating the Most Common Genetic Abnormalities in Multiple Myeloma.

PubMed

Jiménez, Cristina; Jara-Acevedo, María; Corchete, Luis A; Castillo, David; Ordóñez, Gonzalo R; Sarasquete, María E; Puig, Noemí; Martínez-López, Joaquín; Prieto-Conde, María I; García-Álvarez, María; Chillón, María C; Balanzategui, Ana; Alcoceba, Miguel; Oriol, Albert; Rosiñol, Laura; Palomera, Luis; Teruel, Ana I; Lahuerta, Juan J; Bladé, Joan; Mateos, María V; Orfão, Alberto; San Miguel, Jesús F; González, Marcos; Gutiérrez, Norma C; García-Sanz, Ramón

2017-01-01

Identification and characterization of genetic alterations are essential for diagnosis of multiple myeloma and may guide therapeutic decisions. Currently, genomic analysis of myeloma to cover the diverse range of alterations with prognostic impact requires fluorescence in situ hybridization (FISH), single nucleotide polymorphism arrays, and sequencing techniques, which are costly and labor intensive and require large numbers of plasma cells. To overcome these limitations, we designed a targeted-capture next-generation sequencing approach for one-step identification of IGH translocations, V(D)J clonal rearrangements, the IgH isotype, and somatic mutations to rapidly identify risk groups and specific targetable molecular lesions. Forty-eight newly diagnosed myeloma patients were tested with the panel, which included IGH and six genes that are recurrently mutated in myeloma: NRAS, KRAS, HRAS, TP53, MYC, and BRAF. We identified 14 of 17 IGH translocations previously detected by FISH and three confirmed translocations not detected by FISH, with the additional advantage of breakpoint identification, which can be used as a target for evaluating minimal residual disease. IgH subclass and V(D)J rearrangements were identified in 77% and 65% of patients, respectively. Mutation analysis revealed the presence of missense protein-coding alterations in at least one of the evaluating genes in 16 of 48 patients (33%). This method may represent a time- and cost-effective diagnostic method for the molecular characterization of multiple myeloma. Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Quantitative measures of walking and strength provide insight into brain corticospinal tract pathology in multiple sclerosis.

PubMed

Fritz, Nora E; Keller, Jennifer; Calabresi, Peter A; Zackowski, Kathleen M

2017-01-01

At least 85% of individuals with multiple sclerosis report walking dysfunction as their primary complaint. Walking and strength measures are common clinical measures to mark increasing disability or improvement with rehabilitation. Previous studies have shown an association between strength or walking ability and spinal cord MRI measures, and strength measures with brainstem corticospinal tract magnetization transfer ratio. However, the relationship between walking performance and brain corticospinal tract magnetization transfer imaging measures and the contribution of clinical measurements of walking and strength to the underlying integrity of the corticospinal tract has not been explored in multiple sclerosis. The objectives of this study were explore the relationship of quantitative measures of walking and strength to whole-brain corticospinal tract-specific MRI measures and to determine the contribution of quantitative measures of function in addition to basic clinical measures (age, gender, symptom duration and Expanded Disability Status Scale) to structural imaging measures of the corticospinal tract. We hypothesized that quantitative walking and strength measures would be related to brain corticospinal tract-specific measures, and would provide insight into the heterogeneity of brain pathology. Twenty-nine individuals with relapsing-remitting multiple sclerosis (mean(SD) age 48.7 (11.5) years; symptom duration 11.9(8.7); 17 females; median[range] Expanded Disability Status Scale 4.0 [1.0-6.5]) and 29 age and gender-matched healthy controls (age 50.8(11.6) years; 20 females) participated in clinical tests of strength and walking (Timed Up and Go, Timed 25 Foot Walk, Two Minute Walk Test ) as well as 3 T imaging including diffusion tensor imaging and magnetization transfer imaging. Individuals with multiple sclerosis were weaker (p = 0.0024) and walked slower (p = 0.0013) compared to controls. Quantitative measures of walking and strength were significantly related to corticospinal tract fractional anisotropy (r > 0.26; p < 0.04) and magnetization transfer ratio (r > 0.29; p < 0.03) measures. Although the Expanded Disability Status Scale was highly correlated with walking measures, it was not significantly related to either corticospinal tract fractional anisotropy or magnetization transfer ratio (p > 0.05). Walk velocity was a significant contributor to magnetization transfer ratio (p = 0.006) and fractional anisotropy (p = 0.011) in regression modeling that included both quantitative measures of function and basic clinical information. Quantitative measures of strength and walking are associated with brain corticospinal tract pathology. The addition of these quantitative measures to basic clinical information explains more of the variance in corticospinal tract fractional anisotropy and magnetization transfer ratio than the basic clinical information alone. Outcome measurement for multiple sclerosis clinical trials has been notoriously challenging; the use of quantitative measures of strength and walking along with tract-specific imaging methods may improve our ability to monitor disease change over time, with intervention, and provide needed guidelines for developing more effective targeted rehabilitation strategies.

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

Mitochondrial DNA as an inflammatory mediator in cardiovascular diseases.

PubMed

Nakayama, Hiroyuki; Otsu, Kinya

2018-03-06

Mitochondria play a central role in multiple cellular functions, including energy production, calcium homeostasis, and cell death. Currently, growing evidence indicates the vital roles of mitochondria in triggering and maintaining inflammation. Chronic inflammation without microbial infection - termed sterile inflammation - is strongly involved in the development of heart failure. Sterile inflammation is triggered by the activation of pattern recognition receptors (PRRs) that sense endogenous ligands called damage-associated molecular patterns (DAMPs). Mitochondria release multiple DAMPs including mitochondrial DNA, peptides, and lipids, which induce inflammation via the stimulation of multiple PRRs. Among the mitochondrial DAMPs, mitochondrial DNA (mtDNA) is currently highlighted as the DAMP that mediates the activation of multiple PRRs, including Toll-like receptor 9, Nod-like receptors, and cyclic GMP-AMP synthetase/stimulator of interferon gene pathways. These PRR signalling pathways, in turn, lead to the activation of nuclear factor-κB and interferon regulatory factor, which enhances the transcriptional activity of inflammatory cytokines and interferons, and induces the recruitment of inflammatory cells. As the heart is an organ comprising abundant mitochondria for its ATP consumption (needed to maintain constant cyclic contraction and relaxation), the generation of massive amounts of mitochondrial radical oxygen species and mitochondrial DAMPs are predicted to occur and promote cardiac inflammation. Here, we will focus on the role of mtDNA in cardiac inflammation and review the mechanism and pathological significance of mtDNA-induced inflammatory responses in cardiac diseases. © 2018 The Author(s).

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.

The value of cell-free DNA for molecular pathology.

PubMed

Stewart, Caitlin M; Kothari, Prachi D; Mouliere, Florent; Mair, Richard; Somnay, Saira; Benayed, Ryma; Zehir, Ahmet; Weigelt, Britta; Dawson, Sarah-Jane; Arcila, Maria E; Berger, Michael F; Tsui, Dana Wy

2018-04-01

Over the past decade, advances in molecular biology and genomics techniques have revolutionized the diagnosis and treatment of cancer. The technological advances in tissue profiling have also been applied to the study of cell-free nucleic acids, an area of increasing interest for molecular pathology. Cell-free nucleic acids are released from tumour cells into the surrounding body fluids and can be assayed non-invasively. The repertoire of genomic alterations in circulating tumour DNA (ctDNA) is reflective of both primary tumours and distant metastatic sites, and ctDNA can be sampled multiple times, thereby overcoming the limitations of the analysis of single biopsies. Furthermore, ctDNA can be sampled regularly to monitor response to treatment, to define the evolution of the tumour genome, and to assess the acquisition of resistance and minimal residual disease. Recently, clinical ctDNA assays have been approved for guidance of therapy, which is an exciting first step in translating cell-free nucleic acid research tests into clinical use for oncology. In this review, we discuss the advantages of cell-free nucleic acids as analytes in different body fluids, including blood plasma, urine, and cerebrospinal fluid, and their clinical applications in solid tumours and haematological malignancies. We will also discuss practical considerations for clinical deployment, such as preanalytical factors and regulatory requirements. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Improved classification and visualization of healthy and pathological hard dental tissues by modeling specular reflections in NIR hyperspectral images

NASA Astrophysics Data System (ADS)

Usenik, Peter; Bürmen, Miran; Fidler, Aleš; Pernuš, Franjo; Likar, Boštjan

2012-03-01

Despite major improvements in dental healthcare and technology, dental caries remains one of the most prevalent chronic diseases of modern society. The initial stages of dental caries are characterized by demineralization of enamel crystals, commonly known as white spots, which are difficult to diagnose. Near-infrared (NIR) hyperspectral imaging is a new promising technique for early detection of demineralization which can classify healthy and pathological dental tissues. However, due to non-ideal illumination of the tooth surface the hyperspectral images can exhibit specular reflections, in particular around the edges and the ridges of the teeth. These reflections significantly affect the performance of automated classification and visualization methods. Cross polarized imaging setup can effectively remove the specular reflections, however is due to the complexity and other imaging setup limitations not always possible. In this paper, we propose an alternative approach based on modeling the specular reflections of hard dental tissues, which significantly improves the classification accuracy in the presence of specular reflections. The method was evaluated on five extracted human teeth with corresponding gold standard for 6 different healthy and pathological hard dental tissues including enamel, dentin, calculus, dentin caries, enamel caries and demineralized regions. Principal component analysis (PCA) was used for multivariate local modeling of healthy and pathological dental tissues. The classification was performed by employing multiple discriminant analysis. Based on the obtained results we believe the proposed method can be considered as an effective alternative to the complex cross polarized imaging setups.

The Neurobiological Basis of Cognitive Impairment in Parkinson'S Disease

PubMed Central

Halliday, Glenda M.; Leverenz, James B.; Schneider, Jay S.; Adler, Charles H.

2014-01-01

The recent formalization of clinical criteria for PD with dementia (PD-D) codifies many studies on this topic, including those assessing biological correlates. These studies show that the emergence of PD-D occurs on the background of severe dopamine deficits with the main pathological drivers of cognitive decline being a synergistic effect between α -synuclein and Alzheimer's disease pathology. The presence of these pathologies correlates with a marked loss of limbic and cortically projecting dopamine, noradrenaline, serotonin and acetylcholine neurons, although the exact timing of these relationships remains to be determined. Genetic factors, such as triplications in the α-synuclein gene, lead to a clear increased risk of PD-D, while others, such as parkin mutations, are associated with a reduced risk of PD-D. The very recent formalization of clinical criteria for PD with mild cognitive impairment (PD-MCI) allows only speculation on its biological and genetic bases. Critical assessment of animal models shows that chronic low dose MPTP treatment in primates recapitulates PD-MCI over time, enhancing the current biological concept of PD-MCI as having enhanced dopamine deficiency in frontostriatal pathways as well as involvement of other neurotransmitter systems. Data from other animal models support multiple transmitter involvement in cognitive impairment in PD. While dopamine dysfunction has been highlighted because of its obvious role in PD, the role of the other neurotransmitter systems, neurodegenerative pathologies and genetic factors in PD-MCI remain to be fully elucidated. PMID:24757112

An Assessment of Pathology Resident Access to and Use of Technology: A Nationwide Survey.

PubMed

Vallangeon, Bethany D; Hawley, Jeffrey S; Sloane, Richard; Bean, Sarah M

2017-03-01

- Current technologies including digital slide scanners and handheld devices can revolutionize clinical practice and pathology graduate medical education (GME). The extent to which these technologies are used in pathology GME is unknown. - To determine the types of technologies used, usage amount, and how they are integrated into pathology residency/fellowship programs nationwide. - A 40-question online survey for residents/fellows was developed and administered via the Research Electronic Data Capture System after institutional review board approval. - Fifty-two program directors (37%) gave permission for participation. One-hundred seventy-one responses were received (18% response rate). Most respondents have access to personal technology (laptop = 78% [134 of 171]), smartphone = 81% [139 of 171], tablet = 49% [84 of 171]), and Web-based digital slide collections (82%, 141 of 171). Few residents are provided electronic devices by their programs (laptop = 22% [38 of 171], smartphone = 0.5% [1 of 171], and tablet = 12% [21 of 171]). Fifty-nine percent have access to digital slide scanners, 33% have access to a program-created database of digitized slides, and 52% use telepathology. Fifteen percent have access to asynchronous learning. Of those with access to video-recorded conferences, 89% review them. Program size was significantly positively correlated with resident access to program-provided laptops (P = .02) and tablets (P < .001), digital slide scanners (P = .01), and telepathology (P = .001). Of all devices, program-provided laptops are used most for professional work (60.5% use this device for more than 5 hours per day). - Most residents report access to multiple types of innovative technology, but incorporation of these tools within pathology training programs is highly variable. Opportunities for incorporating innovative technologies exist and could be further explored.

Insulin dysfunction and Tau pathology.

PubMed

El Khoury, Noura B; Gratuze, Maud; Papon, Marie-Amélie; Bretteville, Alexis; Planel, Emmanuel

2014-01-01

The neuropathological hallmarks of Alzheimer's disease (AD) include senile plaques of β-amyloid (Aβ) peptides (a cleavage product of the Amyloid Precursor Protein, or APP) and neurofibrillary tangles (NFT) of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF). NFT pathology is important since it correlates with the degree of cognitive impairment in AD. Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99%) is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease. Insulin dysfunction, manifested by diabetes mellitus (DM) might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM) and type 2 diabetes (T2DM) are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since Tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment. Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia.

Insulin dysfunction and Tau pathology

PubMed Central

El Khoury, Noura B.; Gratuze, Maud; Papon, Marie-Amélie; Bretteville, Alexis; Planel, Emmanuel

2013-01-01

The neuropathological hallmarks of Alzheimer's disease (AD) include senile plaques of β-amyloid (Aβ) peptides (a cleavage product of the Amyloid Precursor Protein, or APP) and neurofibrillary tangles (NFT) of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF). NFT pathology is important since it correlates with the degree of cognitive impairment in AD. Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99%) is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease. Insulin dysfunction, manifested by diabetes mellitus (DM) might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM) and type 2 diabetes (T2DM) are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since Tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment. Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia. PMID:24574966

The creation of virtual teeth with and without tooth pathology for a virtual learning environment in dental education.

PubMed

de Boer, I R; Wesselink, P R; Vervoorn, J M

2013-11-01

To describe the development and opportunities for implementation of virtual teeth with and without pathology for use in a virtual learning environment in dental education. The creation of virtual teeth begins by scanning a tooth with a cone beam CT. The resulting scan consists of multiple two-dimensional grey-scale images. The specially designed software program ColorMapEditor connects these two-dimensional images to create a three-dimensional tooth. With this software, any aspect of the tooth can be modified, including its colour, volume, shape and density, resulting in the creation of virtual teeth of any type. This article provides examples of realistic virtual teeth with and without pathology that can be used for dental education. ColorMapEditor offers infinite possibilities to adjust and add options for the optimisation of virtual teeth. Virtual teeth have unlimited availability for dental students, allowing them to practise as often as required. Virtual teeth can be made and adjusted to any shape with any type of pathology. Further developments in software and hardware technology are necessary to refine the ability to colour and shape the interior of the pulp chamber and surface of the tooth to enable not only treatment but also diagnostics and thus create a greater degree of realism. The creation and use of virtual teeth in dental education appears to be feasible but is still in development; it offers many opportunities for the creation of teeth with various pathologies, although an evaluation of its use in dental education is still required. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mutations in RAB39B cause X-linked intellectual disability and early-onset Parkinson disease with α-synuclein pathology.

PubMed

Wilson, Gabrielle R; Sim, Joe C H; McLean, Catriona; Giannandrea, Maila; Galea, Charles A; Riseley, Jessica R; Stephenson, Sarah E M; Fitzpatrick, Elizabeth; Haas, Stefan A; Pope, Kate; Hogan, Kirk J; Gregg, Ronald G; Bromhead, Catherine J; Wargowski, David S; Lawrence, Christopher H; James, Paul A; Churchyard, Andrew; Gao, Yujing; Phelan, Dean G; Gillies, Greta; Salce, Nicholas; Stanford, Lynn; Marsh, Ashley P L; Mignogna, Maria L; Hayflick, Susan J; Leventer, Richard J; Delatycki, Martin B; Mellick, George D; Kalscheuer, Vera M; D'Adamo, Patrizia; Bahlo, Melanie; Amor, David J; Lockhart, Paul J

2014-12-04

Advances in understanding the etiology of Parkinson disease have been driven by the identification of causative mutations in families. Genetic analysis of an Australian family with three males displaying clinical features of early-onset parkinsonism and intellectual disability identified a ∼45 kb deletion resulting in the complete loss of RAB39B. We subsequently identified a missense mutation (c.503C>A [p.Thr168Lys]) in RAB39B in an unrelated Wisconsin kindred affected by a similar clinical phenotype. In silico and in vitro studies demonstrated that the mutation destabilized the protein, consistent with loss of function. In vitro small-hairpin-RNA-mediated knockdown of Rab39b resulted in a reduction in the density of α-synuclein immunoreactive puncta in dendritic processes of cultured neurons. In addition, in multiple cell models, we demonstrated that knockdown of Rab39b was associated with reduced steady-state levels of α-synuclein. Post mortem studies demonstrated that loss of RAB39B resulted in pathologically confirmed Parkinson disease. There was extensive dopaminergic neuron loss in the substantia nigra and widespread classic Lewy body pathology. Additional pathological features included cortical Lewy bodies, brain iron accumulation, tau immunoreactivity, and axonal spheroids. Overall, we have shown that loss-of-function mutations in RAB39B cause intellectual disability and pathologically confirmed early-onset Parkinson disease. The loss of RAB39B results in dysregulation of α-synuclein homeostasis and a spectrum of neuropathological features that implicate RAB39B in the pathogenesis of Parkinson disease and potentially other neurodegenerative disorders. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

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…

Multiple Personality and the Pathological Dissociation of Self.

ERIC Educational Resources Information Center

Price, Reese E.

This paper considers the condition of Multiple Personality Disorder (MPD), which is defined as a separation of alternating personalities by rigid boundaries and amnestic barriers. It is proposed that MPD represents the end of a continuum of a defensive dissociation of the self that can result when a child employs a dissociative splitting of self…

Different tracks for pathology informatics fellowship training: Experiences of and input from trainees in a large multisite fellowship program

PubMed Central

Levy, Bruce P.; McClintock, David S.; Lee, Roy E.; Lane, William J.; Klepeis, Veronica E.; Baron, Jason M.; Onozato, Maristela L.; Kim, JiYeon; Brodsky, Victor; Beckwith, Bruce; Kuo, Frank; Gilbertson, John R.

2012-01-01

Background: Pathology Informatics is a new field; a field that is still defining itself even as it begins the formalization, accreditation, and board certification process. At the same time, Pathology itself is changing in a variety of ways that impact informatics, including subspecialization and an increased use of data analysis. In this paper, we examine how these changes impact both the structure of Pathology Informatics fellowship programs and the fellows’ goals within those programs. Materials and Methods: As part of our regular program review process, the fellows evaluated the value and effectiveness of our existing fellowship tracks (Research Informatics, Clinical Two-year Focused Informatics, Clinical One-year Focused Informatics, and Clinical 1 + 1 Subspecialty Pathology and Informatics). They compared their education, informatics background, and anticipated career paths and analyzed them for correlations between those parameters and the fellowship track chosen. All current and past fellows of the program were actively involved with the project. Results: Fellows’ anticipated career paths correlated very well with the specific tracks in the program. A small set of fellows (Clinical – one or two year – Focused Informatics tracks) anticipated clinical careers primarily focused in informatics (Director of Informatics). The majority of the fellows, however, anticipated a career practicing in a Pathology subspecialty, using their informatics training to enhance that practice (Clinical 1 + 1 Subspecialty Pathology and Informatics Track). Significantly, all fellows on this track reported they would not have considered a Clinical Two-year Focused Informatics track if it was the only track offered. The Research and the Clinical One-year Focused Informatics tracks each displayed unique value for different situations. Conclusions: It seems a “one size fits all” fellowship structure does not fit the needs of the majority of potential Pathology Informatics candidates. Increasingly, these fellowships must be able to accommodate the needs of candidates anticipating a wide range of Pathology Informatics career paths, be able to accommodate Pathology's increasingly subspecialized structure, and do this in a way that respects the multiple fellowships needed to become a subspecialty pathologist and informatician. This is further complicated as Pathology Informatics begins to look outward and takes its place in the growing, and still ill-defined, field of Clinical Informatics, a field that is not confined to just one medical specialty, to one way of practicing medicine, or to one way of providing patient care. PMID:23024889

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.

Understanding the impact of relapses in the overall course of MS; refinement of the 2 stage natural history model.

PubMed

Scott, Thomas F

2017-04-15

Recent studies suggest a need for refinement of the traditional two phase model of relapse onset multiple sclerosis (RMS) to include dynamically changing subgroups within the broad category of secondary progressive MS (SPMS). These studies challenge the traditional notion that relapses play a minor role in comparison to a secondary progressive (perhaps degenerative) process. Patients fulfilling the broad definition for SPMS may take several courses, including variable rates and patterns of overall worsening. New paradigms or models for mapping the trajectory of disability in RMS and SPMS (clinical phenotyping), including periods of remission, may impact our understanding of the underlying pathology, and will be important in assessing treatments. Copyright © 2017 Elsevier B.V. All rights reserved.

Gorlin syndrome and bilateral ovarian fibroma

PubMed Central

Pirschner, Fernanda; Bastos, Pollyana Marçal; Contarato, George Luiz; Bimbato, Anna Carolina Bon Lima; Filho, Antônio Chambô

2012-01-01

INTRODUCTION Gorlin syndrome (GS), also known as nevoid basal cell carcinoma syndrome (NBCCS), is a rare hereditary, autosomal dominant disease that affects various systems. Its prevalence is estimated at 1/57,000 to 1/256,000 of the population. It is characterized by basal cell carcinomas, multiple odontogenic keratocysts, skeletal abnormalities and ovarian fibroma, among other disorders. PRESENTATION OF CASE To report the case of a young patient with Gorlin syndrome and bilateral ovarian fibroma. DISCUSSION A 20-year old patient with Gorlin syndrome presented with facial asymmetry, broad nasal root, dental abnormalities, micrognathism, convergent strabismus, multiple pigmented lesions on the trunk and face, pectus excavatum, kyphoscoliosis and a palpable mass in the abdomen occupying the entire pelvic region. CONCLUSION Gorlin–Goltz syndrome is a hereditary pathology that includes numerous clinical manifestations. Diagnosis is clinical and genetic confirmation is unnecessary. PMID:22771908

Cutaneous involvement in multiple myeloma (MM): A case series with clinicopathologic correlation.

PubMed

Malysz, Jozef; Talamo, Giampaolo; Zhu, Junjia; Clarke, Loren E; Bayerl, Michael G; Ali, Liaqat; Helm, Klaus F; Chung, Catherine G

2016-05-01

Disease-specific skin lesions are rare in patients with multiple myeloma (MM). We sought to further characterize the clinical and pathologic features of patients with cutaneous involvement with MM. We identified 13 patients with cutaneous lesions of MM. Cutaneous lesions consisted of pink, red, and violaceous papules, nodules, and/or plaques that varied in size. Histopathology revealed atypical plasma cells with occasional plasmablastic features. MM had aggressive biologic features and was at an advanced stage in the majority of patients. Despite aggressive management, including chemotherapy and stem-cell transplantation, most patients died of progressive disease within a few months after the development of cutaneous lesions. The study group was relatively small. Cutaneous involvement with MM is associated with aggressive biologic behavior and short survival. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Hormonal control of aging in rodents: The somatotropic axis

PubMed Central

Brown-Borg, Holly M.

2015-01-01

There is a growing body of literature focusing on the somatotropic axis and regulation of aging and longevity. Many of these reports derive data from multiple endocrine mutants, those that exhibit both elevated growth hormone (GH) and insulin-like growth factor I (IGF-1) or deficiencies in one or both of these hormones. In general, both spontaneous and genetically engineered GH and IGF-1 deficiencies have lead to small body size, delayed development of sexual maturation and age-related pathology, and life span extension. In contrast, characteristics of high circulating GH included larger body sizes, early puberty and reproductive senescence, increased cancer incidence and reduced life span when compared to wild-type animals with normal plasma hormone concentrations. This information, along with that found in multiple other species, implicates this anabolic pathway as the major regulator of longevity in animals. PMID:18674587

Nodular presentation of Dirofilaria repens infection in a cat mimicking a fibrosarcoma.

PubMed

Manzocchi, Simone; Lendner, Matthias; Piseddu, Eleonora; Sebastiani, Valeria; Morabito, Simona; Daugschies, Arwid; Pantchev, Nikola

2017-03-01

A cat with multiple subcutaneous nodules suggesting a soft tissue sarcoma by physical and computed tomographic examination was diagnosed as being affected by subcutaneous filariosis based on cytologic and ultrasonographic assessments. Nodules were surgically removed and extracted nematodes were identified by PCR as Dirofilaria repens. Furthermore, DNA of Dipetalonema dracunculoides (syn. Acantocheilonema dracunculoides) was detected by PCR, with no evidence of circulating microfilariae. To the best of the authors' knowledge, this represents the first report describing adults of D repens in multiple subcutaneous nodules in a cat. Cytopathologic examination allowed characterization of the parasitic nature of the nodules. Veterinary practitioners should be aware of the possible nodular presentation of D repens in cats and should include D repens in the differential diagnosis of subcutaneous neoformations in the cat. © 2016 American Society for Veterinary Clinical Pathology.

Positive or negative involvement of heat shock proteins in multiple sclerosis pathogenesis: an overview.

PubMed

Turturici, Giuseppina; Tinnirello, Rosaria; Sconzo, Gabriella; Asea, Alexzander; Savettieri, Giovanni; Ragonese, Paolo; Geraci, Fabiana

2014-12-01

Multiple sclerosis (MS) is the most diffuse chronic inflammatory disease of the central nervous system. Both immune-mediated and neurodegenerative processes apparently play roles in the pathogenesis of this disease. Heat shock proteins (HSPs) are a family of highly evolutionarily conserved proteins; their expression in the nervous system is induced in a variety of pathologic states, including cerebral ischemia, neurodegenerative diseases, epilepsy, and trauma. To date, investigators have observed protective effects of HSPs in a variety of brain disease models (e.g. of Alzheimer disease and Parkinson disease). In contrast, unequivocal data have been obtained for their roles in MS that depend on the HSP family and particularly on their localization (i.e. intracellular or extracellular). This article reviews our current understanding of the involvement of the principal HSP families in MS.

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.

Oxidatively modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and Alzheimer's disease: many pathways to neurodegeneration.

PubMed

Butterfield, D Allan; Hardas, Sarita S; Lange, Miranda L Bader

2010-01-01

Recently, the oxidoreductase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), has become a subject of interest as more and more studies reveal a surfeit of diverse GAPDH functions, extending beyond traditional aerobic metabolism of glucose. As a result of multiple isoforms and cellular locales, GAPDH is able to come in contact with a variety of small molecules, proteins, membranes, etc., that play important roles in normal and pathologic cell function. Specifically, GAPDH has been shown to interact with neurodegenerative disease-associated proteins, including the amyloid-beta protein precursor (AbetaPP). Studies from our laboratory have shown significant inhibition of GAPDH dehydrogenase activity in Alzheimer's disease (AD) brain due to oxidative modification. Although oxidative stress and damage is a common phenomenon in the AD brain, it would seem that inhibition of glycolytic enzyme activity is merely one avenue in which AD pathology affects neuronal cell development and survival, as oxidative modification can also impart a toxic gain-of-function to many proteins, including GAPDH. In this review, we examine the many functions of GAPDH with respect to AD brain; in particular, the apparent role(s) of GAPDH in AD-related apoptotic cell death is emphasized.

Telepathology. Long-distance diagnosis.

PubMed

Weinstein, R S; Bloom, K J; Rozek, L S

1989-04-01

Telepathology is defined as the practice of pathology at a distance, by visualizing an image on a video monitor rather than viewing a specimen directly through a microscope. Components of a telepathology system include the following: (1) a workstation equipped with a high-resolution video camera attached to a remote-controlled light microscope; (2) a pathologist workstation incorporating controls for manipulating the robotic microscope as well as a high-resolution video monitor; and (3) a telecommunications link. Progress has been made in designing and constructing telepathology workstations and fully motorized, computer-controlled light microscopes suitable for telepathology. In addition, components such as video signal digital encoders and decoders that produce remarkably stable, high-color fidelity, and high-resolution images have been incorporated into the workstations. Resolution requirements for the video microscopy component of telepathology have been formally examined in receiver operator characteristic (ROC) curve analyses. Test-of-concept demonstrations have been completed with the use of geostationary satellites as the broadband communication linkages for 750-line resolution video. Potential benefits of telepathology include providing a means of conveniently delivering pathology services in real-time to remote sites or underserviced areas, time-sharing of pathologists' services by multiple institutions, and increasing accessibility to specialty pathologists.

Emergent structure-function relations in emphysema and asthma.

PubMed

Winkler, Tilo; Suki, Béla

2011-01-01

Structure-function relationships in the respiratory system are often a result of the emergence of self-organized patterns or behaviors that are characteristic of certain respiratory diseases. Proper description of such self-organized behavior requires network models that include nonlinear interactions among different parts of the system. This review focuses on 2 models that exhibit self-organized behavior: a network model of the lung parenchyma during the progression of emphysema that is driven by mechanical force-induced breakdown, and an integrative model of bronchoconstriction in asthma that describes interactions among airways within the bronchial tree. Both models suggest that the transition from normal to pathologic states is a nonlinear process that includes a tipping point beyond which interactions among the system components are reinforced by positive feedback, further promoting the progression of pathologic changes. In emphysema, the progressive destruction of tissue is irreversible, while in asthma, it is possible to recover from a severe bronchoconstriction. These concepts may have implications for pulmonary medicine. Specifically, we suggest that structure-function relationships emerging from network behavior across multiple scales should be taken into account when the efficacy of novel treatments or drug therapy is evaluated. Multiscale, computational, network models will play a major role in this endeavor.

[A clinical and pathological study of coccidioidomycosis and pregnancy in four Mexican women].

PubMed

Calderón Garcidueñas, Ana Laura; Piña Osuna, Karina; Cerda Flores, Ricardo M

2004-09-01

In northeastern Mexican population prevalence of positive cutaneous reaction to coccidioidin varies from 30 to 49%. Pregnancy is a risk factor for disseminated coccidioidomycosis. 1) To describe the clinical spectrum of coccidioidomycosis in four women who acquired the disease during pregnancy or puerperium. 2) To discuss the autopsy findings. 3) To review the medical literature. From 1983 to 2000, files of the Pathology Department of a reference tertiary hospital in northeastern Mexico were reviewed. Four cases of 4,598 autopsies corresponded to pregnant women with coccidioidomycosis. Clinical and autopsy charts, and the histological material were studied. Clinical spectrum included a septicemia case with fetal lost, an atypical pneumonia, a chronic meningitis with neuropsychiatric alterations and a patient with hypertensive pregnancy disease with secondary renal insufficiency and repeated episodes of pneumonia. All patients at autopsy showed multiple granulomas with abundant mycotic spherules. Lung involvement included bilateral 2-10 mm nodules. In pregnant women of endemic areas or who had traveled to these zones during pregnancy, coccidioidomycosis should be considered in the differential diagnosis of febrile syndrome with pneumonia, specially if it is accompanied of bilateral nodular infiltrates in lung, with or without erythema nodosum or meningitis.

Identification and characterization of proteins isolated from microvesicles derived from human lung cancer pleural effusions.

PubMed

Park, Jung Ok; Choi, Do-Young; Choi, Dong-Sic; Kim, Hee Joung; Kang, Jeong Won; Jung, Jae Hun; Lee, Jeong Hwa; Kim, Jayoung; Freeman, Michael R; Lee, Kye Young; Gho, Yong Song; Kim, Kwang Pyo

2013-07-01

Microvesicles (MVs, also known as exosomes, ectosomes, microparticles) are released by various cancer cells, including lung, colorectal, and prostate carcinoma cells. MVs released from tumor cells and other sources accumulate in the circulation and in pleural effusion. Although recent studies have shown that MVs play multiple roles in tumor progression, the potential pathological roles of MV in pleural effusion, and their protein composition, are still unknown. In this study, we report the first global proteomic analysis of highly purified MVs derived from human nonsmall cell lung cancer (NSCLC) pleural effusion. Using nano-LC-MS/MS following 1D SDS-PAGE separation, we identified a total of 912 MV proteins with high confidence. Three independent experiments on three patients showed that MV proteins from PE were distinct from MV obtained from other malignancies. Bioinformatics analyses of the MS data identified pathologically relevant proteins and potential diagnostic makers for NSCLC, including lung-enriched surface antigens and proteins related to epidermal growth factor receptor signaling. These findings provide new insight into the diverse functions of MVs in cancer progression and will aid in the development of novel diagnostic tools for NSCLC. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pathology Reports

MedlinePlus

... pathology report will include the results of these tests. For example, the pathology report may include information obtained from ... markers or indicators of a specific cancer. For example, the Philadelphia chromosome ... ( 3 ). Some tests that might be performed on a tissue sample ...

[Clinical analysis of thoracoscopy of 30 coalworker's pneumoconiosiswith pleural effusion cases].

PubMed

Liang, Yandong; Jiang, Ruiling; Yu, Chunxiao; Huang, Cheng

2015-07-01

To investigate the diagnostic value of thoracoscopy on idiopathic coalworker's pneumoconiosis with pleural effusion in general medicine. Routine (general medicine) thoracoscopyof patients suffering from iIdiopathiccoalworker's pneumoconiosis with pleural effusion, pathological examination of lesions obtained (direct vision). Pathological examination revealed grayish-white miliary nodules with multiple protruding nodules, irregular focal pleura thickening, pulmonary congestion, edema, fibrous adhesion. Thorascopy produced a diagnostic rate of 93.3%. Confirmed cases includes 13 cases of tuberculous pleurisy, 11 cases of malignant pleural effusion, 4 cases of cardiac insufficiency with pleural effusion and 2 cases of idiopathic pleural effusion, with no serious complications. Thoracoscopy of idiopathic coalworker's pneumoconiosis with pleural effusion is a safe, accurate diagnostic methodin general medicine, and could benefit the establishment of a treatment method quickly, visual observation of the lesions of patients suffering from coalworker's pneumoconiosis with pleural effusion using thoracoscopy, and at the same time offer preliminary investigationof the correlation between the intensity and compactibilityof coal macule distribution and clinical stages of coalworker's Pneumoconiosis.

Clinical and pathological implications of miRNA in bladder cancer.

PubMed

Braicu, Cornelia; Cojocneanu-Petric, Roxana; Chira, Sergiu; Truta, Anamaria; Floares, Alexandru; Petrut, Bogdan; Achimas-Cadariu, Patriciu; Berindan-Neagoe, Ioana

2015-01-01

MicroRNAs (miRNAs) are small, noncoding RNA species with a length of 20-22 nucleotides that are recognized as essential regulators of relevant molecular mechanisms, including carcinogenesis. Current investigations show that miRNAs are detectable not only in different tissue types but also in a wide range of biological fluids, either free or trapped in circulating microvesicles. miRNAs were proven to be involved in cell communication, both in pathological and physiological processes. Evaluation of the global expression patterns of miRNAs provides key opportunities with important practical applications, taking into account that they modulate essential biological processes such as epithelial to mesenchymal transition, which is a mechanism relevant in bladder cancer. miRNAs collected from biological specimens can furnish valuable evidence with regard to bladder cancer oncogenesis, as they also have been linked to clinical outcomes in urothelial carcinoma. Therefore, a single miRNA or a signature of multiple miRNAs may improve risk stratification of patients and may supplement the histological diagnosis of urological tumors, particularly for bladder cancer.

Synoptic reporting in tumor pathology: advantages of a web-based system.

PubMed

Qu, Zhenhong; Ninan, Shibu; Almosa, Ahmed; Chang, K G; Kuruvilla, Supriya; Nguyen, Nghia

2007-06-01

The American College of Surgeons Commission on Cancer (ACS-CoC) mandates that pathology reports at ACS-CoC-approved cancer programs include all scientifically validated data elements for each site and tumor specimen. The College of American Pathologists (CAP) has produced cancer checklists in static text formats to assist reporting. To be inclusive, the CAP checklists are pages long, requiring extensive text editing and multiple intermediate steps. We created a set of dynamic tumor-reporting templates, using Microsoft Active Server Page (ASP.NET), with drop-down list and data-compile features, and added a reminder function to indicate missing information. Users can access this system on the Internet, prepare the tumor report by selecting relevant data from drop-down lists with an embedded tumor staging scheme, and directly transfer the final report into a laboratory information system by using the copy-and-paste function. By minimizing extensive text editing and eliminating intermediate steps, this system can reduce reporting errors, improve work efficiency, and increase compliance.

Posterior ankle impingement in athletes: Pathogenesis, imaging features and differential diagnoses.

PubMed

Hayashi, Daichi; Roemer, Frank W; D'Hooghe, Pieter; Guermazi, Ali

2015-11-01

Posterior ankle impingement is a clinical diagnosis which can be seen following a traumatic hyper-plantar flexion event and may lead to painful symptoms in athletes such as female dancers ('en pointe'), football players, javelin throwers and gymnasts. Symptoms of posterior ankle impingement are due to failure to accommodate the reduced interval between the posterosuperior aspect of the talus and tibial plafond during plantar flexion, and can be due to osseous or soft tissue lesions. There are multiple causes of posterior ankle impingement. Most commonly, the structural correlates of impingement relate to post-traumatic synovitis and intra-articular fibrous bands-scar tissue, capsular scarring, or bony prominences. The aims of this pictorial review article is to describe different types of posterior ankle impingement due to traumatic and non-traumatic osseous and soft tissue pathology in athletes, to describe diagnostic imaging strategies of these pathologies, and illustrate their imaging features, including relevant differential diagnoses. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Study of 103 cases of odontogenic cysts].

PubMed

Moctezuma-Bravo, Gustavo Sergio; Magallanes-González, Eduardo

2009-01-01

To describe characteristics of odontogenic cysts in a Mexican population. A retrospective study of 103 odontogenic cysts in 86 patients was done. The data were obtained from files of the Pathology Department of a General Hospital. We observed a frequency of the 8.13 % of odontogenic cysts (103) in 1266 pathological studies. The dentigerous cyst 56 % and odontogenic keratocyst 33 % were the most common odontogenic cysts. Sixty one percent of the cysts appeared in the second and third decades of life. In 71 cysts, 42 % appeared in the posterior region jaw, 29 % in the anterior region of the maxilla and 21 % in the posterior region of the maxilla. A 6.7 % developed a recurrence after treatment and a case of keratocyst of posterior region of the maxilla was associated with epidermoid carcinoma. The study included three women with the syndrome of carcinoma of the basal cell nevus, who presented multiple keratocysts. The dentigerous cysts and odontogenic keratocysts were the most frequent odontogenic cysts. They appeared mainly in the second and third decades of life.

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.

The computed tomography appearance of recurrent and chronic appendicitis.

PubMed

Rao, P M; Rhea, J T; Novelline, R A; McCabe, C J

1998-01-01

The objective of this study was to determine computed tomography (CT) appearance of recurrent and chronic appendicitis. In 100 consecutive appendiceal CT examinations of proven appendicitis, 18 patients met criteria for recurrent (multiple discrete episodes) or chronic (continuous symptoms > 3 weeks, pathological findings) appendicitis. CT findings were reviewed. Ten patients had recurrent appendicitis, 3 had chronic appendicitis, 3 had both, and 2 had pathological chronic appendicitis. CT findings in 18 recurrent/chronic cases were identical to 82 acute appendicitis cases, including pericecal stranding (both 100%), dilated (> 6 mm) appendix (88.9% versus 93.9%), apical thickening (66.7% versus 69.5%), adenopathy (66.7% versus 61.0%), appendolith(s) (50% versus 42.7%), arrowhead (27.8% versus 22.0%), abscess (11.1% versus 11.0%), phlegmon (11.1% versus 6.1%), and fluid (5.6% versus 19.5%). CT findings in recurrent and chronic appendicitis are the same as those in acute appendicitis. Appendiceal CT can be beneficial for evaluating patients with suspected recurrent or chronic appendicitis.

Research Priorities in Spasmodic Dysphonia

PubMed Central

Ludlow, Christy L.; Adler, Charles H.; Berke, Gerald S.; Bielamowicz, Steven A.; Blitzer, Andrew; Bressman, Susan B.; Hallett, Mark; Jinnah, H. A.; Juergens, Uwe; Martin, Sandra B.; Perlmutter, Joel S.; Sapienza, Christine; Singleton, Andrew; Tanner, Caroline M.; Woodson, Gayle E.

2009-01-01

OBJECTIVE To identify research priorities for increasing understanding of the pathogenesis, diagnosis and improved treatment of spasmodic dysphonia. STUDY DESIGN AND SETTING A multidisciplinary working group was formed including both scientists and clinicians from multiple disciplines, otolaryngology, neurology, speech pathology, genetics and neuroscience, to review currently available information on spasmodic dysphonia and to identify research priorities. RESULTS Operational definitions for spasmodic dysphonia at different levels of certainty were recommended for diagnosis and recommendations made for a multi-center multidisciplinary validation study. CONCLUSIONS The highest priority is to characterize the disorder and identify risk factors that may contribute to its onset. Future research should compare and contrast spasmodic dysphonia with other forms of focal dystonia. Development of animal models is recommended to explore hypotheses related to pathogenesis. Improved understanding of the pathophysiology of SD should provide the basis for developing new treatment options and exploratory clinical trials. SIGNIFICANCE This document should foster future research to improve the care of patients with this chronic debilitating voice and speech disorder by otolaryngology, neurology, and speech pathology. PMID:18922334

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.

Neuropathological Staging of Brain Pathology in Sporadic Parkinson's disease: Separating the Wheat from the Chaff.

PubMed

Braak, Heiko; Del Tredici, Kelly

2017-01-01

A relatively small number of especially susceptible nerve cell types within multiple neurotransmitter systems of the human central, peripheral, and enteric nervous systems (CNS, PNS, ENS) become involved in the degenerative process underlying sporadic Parkinson's disease (sPD). The six-stage model we proposed for brain pathology related to sPD (Neurobiol Aging 2003) was a retrospective study of incidental and clinically diagnosed cases performed on unconventionally thick tissue sections (100 μm) from a large number of brain regions.The staging model emphasized what we perceived to be a sequential development of increasing degrees of Lewy pathology in anatomically interconnected regions together with the loss of aminergic projection neurons in, but not limited to, the locus coeruleus and substantia nigra. The same weight was assigned to axonal and somatodendritic Lewy pathology, and the olfactory bulb was included for the first time in a sPD staging system. After years of research, it now appears that the earliest lesions could develop at nonnigral (dopamine agonist nonresponsive) sites, where the surrounding environment is potentially hostile: the olfactory bulb and, possibly, the ENS. The current lack of knowledge regarding the development of Lewy pathology within the peripheral autonomic nervous system, however, means that alternative extra-CNS sites of origin cannot be disregarded as possible candidates. The PD staging system not only caused controversy but contributed a framework for (1) assessing pathology in the spinal cord, ENS, and PNS in relationship to that evolving in the brain, (2) defining prodromal disease and cohorts of at-risk individuals, (3) developing potential prognostic biomarkers for very early disease, (4) testing novel hypotheses and experimental models of α-synuclein propagation and disease progression, and (5) finding causally-oriented therapies that intervene before the substantia nigra becomes involved. The identification of new disease mechanisms at the molecular and cellular levels indicates that physical contacts (transsynaptic) and transneuronal transmission between vulnerable nerve cells are somehow crucial to the pathogenesis of sPD.

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.

[Progress on mechanism of cell apoptosis induced by rubella virus].

PubMed

Li, Zhen-mei; Chu, Fu-lu; Liu, Ying; Wang, Zhi-yu

2013-09-01

Rubella virus (RV), a member of the family Togaviridae, can induce apoptosis of host cells in vitro. Protein kinases of the Ras-Raf-MEK-ERK pathway and PI3K-Akt pathway play essential roles in virus multiplication, cell survival and apoptosis. Proteins p53 and TAp63 that bind to specific DNA sequences stimulate Bax in a manner to produce functional pores that facilitate release of mitochondrial cytochrome c and downstream caspase activation. In this review, the molecular mechanisms of RV-induced cell apoptosis, including RV-infected cell lines, pathological changes in cell components and apoptosis signaling pathways are summarized.

A New Axi-Symmetric Element for Thin Walled Structures

NASA Astrophysics Data System (ADS)

Cardoso, Rui P. R.; Yoon, Jeong Whan; Dick, Robert E.

2010-06-01

A new axi-symmetric finite element for sheet metal forming applications is presented in this work. It uses the solid-shell element's concept with only a single element layer and multiple integration points along the thickness direction. The cross section of the element is composed of four nodes with two degrees of freedom each. The proposed formulation overcomes major locking pathologies including transverse shear locking, Poisson's locking and volumetric locking. Some examples are shown to demonstrate the performance and accuracy of the proposed element with special focus on the numerical simulations for the beverage can industry.

NEIBank: Genomics and bioinformatics resources for vision research

PubMed Central

Peterson, Katherine; Gao, James; Buchoff, Patee; Jaworski, Cynthia; Bowes-Rickman, Catherine; Ebright, Jessica N.; Hauser, Michael A.; Hoover, David

2008-01-01

NEIBank is an integrated resource for genomics and bioinformatics in vision research. It includes expressed sequence tag (EST) data and sequence-verified cDNA clones for multiple eye tissues of several species, web-based access to human eye-specific SAGE data through EyeSAGE, and comprehensive, annotated databases of known human eye disease genes and candidate disease gene loci. All expression- and disease-related data are integrated in EyeBrowse, an eye-centric genome browser. NEIBank provides a comprehensive overview of current knowledge of the transcriptional repertoires of eye tissues and their relation to pathology. PMID:18648525

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

Diagnostic criteria for vascular cognitive disorders: a VASCOG statement.

PubMed

Sachdev, Perminder; Kalaria, Raj; O'Brien, John; Skoog, Ingmar; Alladi, Suvarna; Black, Sandra E; Blacker, Deborah; Blazer, Dan G; Chen, Christopher; Chui, Helena; Ganguli, Mary; Jellinger, Kurt; Jeste, Dilip V; Pasquier, Florence; Paulsen, Jane; Prins, Niels; Rockwood, Kenneth; Roman, Gustavo; Scheltens, Philip

2014-01-01

Several sets of diagnostic criteria have been published for vascular dementia since the 1960s. The continuing ambiguity in vascular dementia definition warrants a critical reexamination. Participants at a special symposium of the International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) in 2009 critiqued the current criteria. They drafted a proposal for a new set of criteria, later reviewed through multiple drafts by the group, including additional experts and the members of the Neurocognitive Disorders Work Group of the fifth revision of Diagnostic and Statistical Manual (DSM-5) Task Force. Cognitive disorders of vascular etiology are a heterogeneous group of disorders with diverse pathologies and clinical manifestations, discussed broadly under the rubric of vascular cognitive disorders (VCD). The continuum of vascular cognitive impairment is recognized by the categories of Mild Vascular Cognitive Disorder, and Vascular Dementia or Major Vascular Cognitive Disorder. Diagnostic thresholds are defined. Clinical and neuroimaging criteria are proposed for establishing vascular etiology. Subtypes of VCD are described, and the frequent cooccurrence of Alzheimer disease pathology emphasized. The proposed criteria for VCD provide a coherent approach to the diagnosis of this diverse group of disorders, with a view to stimulating clinical and pathologic validation studies. These criteria can be harmonized with the DSM-5 criteria such that an international consensus on the criteria for VCD may be achieved.

Viewing relational aggression through multiple lenses: temperament, personality, and personality pathology.

PubMed

Tackett, Jennifer L; Kushner, Shauna C; Herzhoff, Kathrin; Smack, Avante J; Reardon, Kathleen W

2014-08-01

Dispositional trait frameworks offer great potential to elucidate the nature and development of psychopathology, including the construct of relational aggression. The present study sought to explore the dispositional context of relational aggression across three dispositional frameworks: temperament, personality, and personality pathology. Participants comprised a large community sample of youth, aged 6 to 18 years (N = 1,188; 51.2% female). Ratings of children's relational aggression, temperament, personality, and personality pathology traits were obtained through parent report (86.3% mothers). Results showed convergence and divergence across these three dispositional frameworks. Like other antisocial behavior subtypes, relational aggression generally showed connections with traits reflecting negative emotionality and poor self-regulation. Relational aggression showed stronger connections with temperament traits than with personality traits, suggesting that temperament frameworks may capture more relationally aggressive content. Findings at the lower order trait level help differentiate relational aggression from other externalizing problems by providing a more nuanced perspective (e.g., both sociability and shyness positively predicted relational aggression). In addition, there was little evidence of moderation of these associations by gender, age, or age2, and findings remained robust even after controlling for physical aggression. Results are discussed in the broader context of conceptualizing relational aggression in an overarching personality-psychopathology framework.

Microparticles: A New Perspective in Central Nervous System Disorders

PubMed Central

Schindler, Stephanie M.; Little, Jonathan P.

2014-01-01

Microparticles (MPs) are a heterogeneous population of small cell-derived vesicles, ranging in size from 0.1 to 1 μm. They contain a variety of bioactive molecules, including proteins, biolipids, and nucleic acids, which can be transferred between cells without direct cell-to-cell contact. Consequently, MPs represent a novel form of intercellular communication, which could play a role in both physiological and pathological processes. Growing evidence indicates that circulating MPs contribute to the development of cancer, inflammation, and autoimmune and cardiovascular diseases. Most cell types of the central nervous system (CNS) have also been shown to release MPs, which could be important for neurodevelopment, CNS maintenance, and pathologies. In disease, levels of certain MPs appear elevated; therefore, they may serve as biomarkers allowing for the development of new diagnostic tools for detecting the early stages of CNS pathologies. Quantification and characterization of MPs could also provide useful information for making decisions on treatment options and for monitoring success of therapies, particularly for such difficult-to-treat diseases as cerebral malaria, multiple sclerosis, and Alzheimer's disease. Overall, studies on MPs in the CNS represent a novel area of research, which promises to expand the knowledge on the mechanisms governing some of the physiological and pathophysiological processes of the CNS. PMID:24860829

Developmental Defects of Caenorhabditis elegans Lacking Branched-chain α-Ketoacid Dehydrogenase Are Mainly Caused by Monomethyl Branched-chain Fatty Acid Deficiency.

PubMed

Jia, Fan; Cui, Mingxue; Than, Minh T; Han, Min

2016-02-05

Branched-chain α-ketoacid dehydrogenase (BCKDH) catalyzes the critical step in the branched-chain amino acid (BCAA) catabolic pathway and has been the focus of extensive studies. Mutations in the complex disrupt many fundamental metabolic pathways and cause multiple human diseases including maple syrup urine disease (MSUD), autism, and other related neurological disorders. BCKDH may also be required for the synthesis of monomethyl branched-chain fatty acids (mmBCFAs) from BCAAs. The pathology of MSUD has been attributed mainly to BCAA accumulation, but the role of mmBCFA has not been evaluated. Here we show that disrupting BCKDH in Caenorhabditis elegans causes mmBCFA deficiency, in addition to BCAA accumulation. Worms with deficiency in BCKDH function manifest larval arrest and embryonic lethal phenotypes, and mmBCFA supplementation suppressed both without correcting BCAA levels. The majority of developmental defects caused by BCKDH deficiency may thus be attributed to lacking mmBCFAs in worms. Tissue-specific analysis shows that restoration of BCKDH function in multiple tissues can rescue the defects, but is especially effective in neurons. Taken together, we conclude that mmBCFA deficiency is largely responsible for the developmental defects in the worm and conceivably might also be a critical contributor to the pathology of human MSUD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Curriculum Guidelines for Pathology and Oral Pathology.

ERIC Educational Resources Information Center

Journal of Dental Education, 1985

1985-01-01

Guidelines for dental school pathology courses describe the interrelationships of general, systemic, and oral pathology; primary educational goals; prerequisites; a core curriculum outline and behavioral objectives for each type of pathology. Notes on sequencing, faculty, facilities, and occupational hazards are included. (MSE)

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.

[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.

Genetic architecture, epigenetic influence and environment exposure in the pathogenesis of Autism.

PubMed

Yu, Li; Wu, YiMing; Wu, Bai-Lin

2015-10-01

Autism spectrum disorder (ASD) is a spectral neurodevelopment disorder affecting approximately 1% of the population. ASD is characterized by impairments in reciprocal social interaction, communication deficits and restricted patterns of behavior. Multiple factors, including genetic/genomic, epigenetic/epigenomic and environmental, are thought to be necessary for autism development. Recent reviews have provided further insight into the genetic/genomic basis of ASD. It has long been suspected that epigenetic mechanisms, including DNA methylation, chromatin structures and long non-coding RNAs may play important roles in the pathology of ASD. In addition to genetic/genomic alterations and epigenetic/epigenomic influences, environmental exposures have been widely accepted as an important role in autism etiology, among which immune dysregulation and gastrointestinal microbiota are two prominent ones.

Endoplasmic Reticulum and the Unfolded Protein Response: Dynamics and Metabolic Integration

PubMed Central

Bravo, Roberto; Parra, Valentina; Gatica, Damián; Rodriguez, Andrea E.; Torrealba, Natalia; Paredes, Felipe; Wang, Zhao V.; Zorzano, Antonio; Hill, Joseph A.; Jaimovich, Enrique; Quest, Andrew F.G.; Lavandero, Sergio

2013-01-01

The endoplasmic reticulum (ER) is a dynamic intracellular organelle with multiple functions essential for cellular homeostasis, development, and stress responsiveness. In response to cellular stress, a well-established signaling cascade, the unfolded protein response (UPR), is activated. This intricate mechanism is an important means of reestablishing cellular homeostasis and alleviating the inciting stress. Now, emerging evidence has demonstrated that the UPR influences cellular metabolism through diverse mechanisms, including calcium and lipid transfer, raising the prospect of involvement of these processes in the pathogenesis of disease, including neurodegeneration, cancer, diabetes mellitus and cardiovascular disease. Here, we review the distinct functions of the ER and UPR from a metabolic point of view, highlighting their association with prevalent pathologies. PMID:23317820

Mitochondrial Dynamics in Diabetes

PubMed Central

Galloway, Chad A.; Jhun, Bong Sook; Yu, Tianzheng

2011-01-01

Abstract Mitochondria are at the center of cellular energy metabolism and regulate cell life and death. The cell biological aspect of mitochondria, especially mitochondrial dynamics, has drawn much attention through implications in human pathology, including neurological disorders and metabolic diseases. Mitochondrial fission and fusion are the main processes governing the morphological plasticity and are controlled by multiple factors, including mechanochemical enzymes and accessory proteins. Emerging evidence suggests that mitochondrial dynamics plays an important role in metabolism–secretion coupling in pancreatic β-cells as well as complications of diabetes. This review describes an overview of mechanistic and functional aspects of mitochondrial fission and fusion, and comments on the recent advances connecting mitochondrial dynamics with diabetes and diabetic complications. Antioxid. Redox Signal. 14, 439–457. PMID:20518704

Staging of intrahepatic cholangiocarcinoma

PubMed Central

Ronnekleiv-Kelly, Sean M.

2017-01-01

Intrahepatic cholangiocarcinoma (ICC) comprises approximately 5−30% of primary liver tumors, however it has been increasing over the last several decades. Up to and including the 6th edition of the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) edition staging system, ICC was staged the same as hepatocellular carcinoma. In the 7th edition AJCC/UICC manual, the staging system of ICC was revised such that a distinct classification was proposed. Pathologic features for prognosis included vascular invasion, tumor multiplicity, local extension, periductal infiltration and lymph nodal metastasis. Over the last decade, as the incidence of ICC has increased and surgery for this indication has become more common, more data has been published on the prognostic factors associated with long-term survival. PMID:28261593

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.

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.

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.

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.

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.

[Pathological diagnosis of pediatric Burkitt lymphoma involving bone marrow].

PubMed

Sun, Qi; Chen, Zhenping; Liu, Enbin; Li, Zhanqi; Yang, Qingying; Sun, Fujun; Ma, Yue; Zhang, Hongju; Zhang, Peihong; Ru, Kun

2015-02-01

To investigate pathologic and differential diagnostic features of pediatric Burkitt lymphoma (BL). A total of 20 cases of pediatric BL were retrospectively reviewed for their clinical and pathologic profiles. Bone marrow aspiration specimens were available in all cases and bone marrow biopsies were available for immunohistochemical study in 18 cases. Flow cytometry study was available in 16 cases. MYC translocation by FISH method was performed in 11 cases. Atypical lymphocytes with cytoplasmic vacuoles were found in bone marrow smears in all 20 cases and peripheral blood films in all 19 available cases. The bone marrow biopsies showed infiltration by uniform medium-sized atypical lymphocytes with multiple small nucleoli but without the starry-sky pattern in all 18 cases. Immunohistochemistry showed the following results in all 18 cases: positive for CD20, PAX-5, CD10, CD34 and TdT, but negative for bcl-2 and CD3 with Ki-67 > 95%.Flow cytometry showed CD19+CD20+CD10+FMC7+CD22+TdT-CD3- in 16 cases, including κ+ in 8 cases, λ+ in 7 cases, and κ-λ- in 1 case. MYC gene rearrangement by FISH was observed in 10 of the 11 cases. The histopathology of BL is distinct, including atypical lymphocytes with cytoplasmic vacuoles in bone marrow aspirate, lack of starry-sky patternin bone marrow biopsy. Generally, the diagnosis should be made with a combined immunophenotype and FISH approach. Pediatric BL must be distinguished from DLBCL and B-cell lymphoma, unclassifiable, which has intermediate features between DLBCL and Burkitt lymphoma.

Enteroviral Infection: The Forgotten Link to Amyotrophic Lateral Sclerosis?

PubMed Central

Xue, Yuan Chao; Feuer, Ralph; Cashman, Neil; Luo, Honglin

2018-01-01

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease that primarily attacks motor neurons in the brain and spinal cord, leading to progressive paralysis and ultimately death. Currently there is no effective therapy. The majority of ALS cases are sporadic, with no known family history; unfortunately the etiology remains largely unknown. Contribution of Enteroviruses (EVs), a family of positive-stranded RNA viruses including poliovirus, coxsackievirus, echovirus, enterovirus-A71 and enterovirus-D68, to the development of ALS has been suspected as they can target motor neurons, and patients with prior poliomyelitis show a higher risk of motor neuron disease. Multiple efforts have been made to detect enteroviral genome in ALS patient tissues over the past two decades; however the clinical data are controversial and a causal relationship has not yet been established. Recent evidence from in vitro and animal studies suggests that enterovirus-induced pathology remarkably resembles the cellular and molecular phenotype of ALS, indicating a possible link between enteroviral infection and ALS pathogenesis. In this review, we summarize the nature of enteroviral infection, including route of infection, cells targeted, and viral persistence within the central nervous system (CNS). We review the molecular mechanisms underlying viral infection and highlight the similarity between viral pathogenesis and the molecular and pathological features of ALS, and finally, discuss the potential role of enteroviral infection in frontotemporal dementia (FTD), a disease that shares common clinical, genetic, and pathological features with ALS, and the significance of anti-viral therapy as an option for the treatment of ALS. PMID:29593492

Localized hippocampus measures are associated with Alzheimer pathology and cognition independent of total hippocampal volume.

PubMed

Carmichael, Owen; Xie, Jing; Fletcher, Evan; Singh, Baljeet; DeCarli, Charles

2012-06-01

Hippocampal injury in the Alzheimer's disease (AD) pathological process is region-specific and magnetic resonance imaging (MRI)-based measures of localized hippocampus (HP) atrophy are known to detect region-specific changes associated with clinical AD, but it is unclear whether these measures provide information that is independent of that already provided by measures of total HP volume. Therefore, this study assessed the strength of association between localized HP atrophy measures and AD-related measures including cerebrospinal fluid (CSF) amyloid beta and tau concentrations, and cognitive performance, in statistical models that also included total HP volume as a covariate. A computational technique termed localized components analysis (LoCA) was used to identify 7 independent patterns of HP atrophy among 390 semiautomatically delineated HP from baseline magnetic resonance imaging of participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Among cognitively normal participants, multiple measures of localized HP atrophy were significantly associated with CSF amyloid concentration, while total HP volume was not. In addition, among all participants, localized HP atrophy measures and total HP volume were both independently and additively associated with CSF tau concentration, performance on numerous neuropsychological tests, and discrimination between normal, mild cognitive impairment (MCI), and AD clinical diagnostic groups. Together, these results suggest that regional measures of hippocampal atrophy provided by localized components analysis may be more sensitive than total HP volume to the effects of AD pathology burden among cognitively normal individuals and may provide information about HP regions whose deficits may have especially profound cognitive consequences throughout the AD clinical course. Copyright © 2012 Elsevier Inc. All rights reserved.

Aerophagia due to abdomino-phrenic dyssynergia in a 2-year-old child.

PubMed

Ercoli, Pablo; García, Belinda; Del Campo, Enrique; Pinillos, Sergio

2018-05-01

We report the case of a previously healthy 2-year-old child who presented with significant abdominal distension. After several interventions that proved ineffective, pathologic aerophagia was eventually diagnosed. In pediatrics, pathologic aerophagia is an uncommon disorder that almost exclusively affects children with an underlying neurological condition. It may lead to multiple diagnostic tests and unnecessary aggressive therapies. A recent case report associated aerophagia with a novel concept of abdomino-phrenic dyssynergia.

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

Epidemiology of Late Health Effects in Ukrainian Chornobyl Cleanup Workers.

PubMed

Bazyka, Dimitry; Prysyazhnyuk, Anatoly; Gudzenko, Natalya; Dyagil, Iryna; Belyi, David; Chumak, Vadim; Buzunov, Volodymyr

2018-07-01

This article summarizes the results of 30 y of follow-up of cancer and noncancer effects in Ukrainian cleanup workers after the Chornobyl accident. The number of power plant employees and first responders with acute radiation syndrome under follow-up by the National Research Center for Radiation Medicine decreased from 179 in 1986-1991 to 105 in 2011-2015. Cancers and leukemia (19) and cardiovascular diseases (21) were the main causes of deaths among acute radiation syndrome survivors (54) during the postaccident period. Increased radiation risks of leukemia in the Ukrainian cohort of 110,645 cleanup workers exposed to low doses are comparable to those among survivors of the atomic bomb explosions in Japan in 1945. Additionally, an excess of chronic lymphocytic leukemia was demonstrated in the cleanup workers cohort for 26 y after the exposure. A significant excess of multiple myeloma incidence [standardized incidence rate (SIR) 1.61 %, 95% confidence interval (CI) 1.01-2.21], thyroid cancer (SIR 4.18, 95% CI 3.76-4.59), female breast cancer (SIR 1.57 CI 1.40-1.73), and all cancers combined (SIR 1.07; 95% CI 1.05-1.09) was registered. High prevalence was demonstrated for cardio- and cerebrovascular diseases and mental health changes. However, the reasons for the increases require further investigation. To monitor other possible late effects of radiation exposure in Chornobyl cleanup workers, analytical cohort and case-control studies need to include cardiovascular pathology, specifically types of potentially radiogenic cancers using a molecular epidemiology approach. Possible effects for further study include increased rates of thyroid, breast, and lung cancers and multiple myeloma; reduction of radiation risks of leukemia to population levels; and increased morbidity and mortality of cleanup workers from cardio- and cerebrovascular pathology.

[Surgical indications in gallbladder polyps].

PubMed

Morera-Ocón, Francisco José; Ballestín-Vicente, Javier; Calatayud-Blas, Ana María; de Tursi-Rispoli, Leonardo Cataldo; Bernal-Sprekelsen, Juan Carlos

2013-05-01

The surgery of gallbladder polyps is not well defined due to the lack of evidence-based clinical guidelines. To analyse the management of polyps in Spain, and a review of the literature and treatment standards. The reports on cholecystectomy with gallbladder polyps (GBP) were extracted from the Pathology data base. Patients subjected to surgery with a diagnosis of GBP were identified in the Surgery data base. A single list was prepared and a review was made of the clinical histories, including, age, gender, clinical data, ultrasound report, and histopathology report. A total of 30 patients, with a median age of 51 years (range 22-83), 21 of whom were female, were included. The ultrasound diagnosis was GBP in 19 patients, GBP and calculi in 7 cases, and calculi with no polyps in 4 cases. Other diagnoses concurrent with GBP were multiple haemangiomas (3), large single simple cyst (1), and multiple simple cysts (1). Eleven patients had typical pain (biliary origin), 5 of which showed no calculi on ultrasound. Eight had non-specific pain, which persisted in 3 cases after the cholecystectomy. Pseudopolyps were found in 20 gallbladders, and true polyps in 4 cases. In 3 cases, polyps were not found in the pathology study. The ultrasound report must specify the size, shape, and number of polyps. Patients with biliary type pain would benefit from a cholecystectomy. The probability of malignancy is minimum if the GBP is less than 10mm and aged under 50 years, and a cholecystectomy is not required. A GBP greater than 10mm should be an indication of cholecystectomy. Copyright © 2011 AEC. Published by Elsevier España, S.L. All rights reserved.

Xenobiotics and the Glucocorticoid Receptor

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

Gulliver, Linda S M, E-mail: linda.gulliver@otago.

Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmunemore » processes. Many xenobiotics, if inadequately metabolized by xenobiotic metabolizing enzymes and not wholly eliminated, could have deleterious toxic effects with potentially lethal consequences. This review examines GR, the genomic and non-genomic actions of natural and synthetic GC and the body's handling of xenobiotic compounds, before reviewing what is presently known about GR's interactions with many of the more commonly encountered and some of the less well known GR-associated xenobiotics. GR promiscuity and crosstalk with other signaling pathways is discussed, alongside novel roles for GR that include mood disorder and addiction. A knowledge of GR interactions with xenobiotics is increasingly relevant when considering aging populations and the related prevalence of neoplastic disease, together with growing concerns around human exposure to mixtures of chemicals in the environment. Furthermore, escalating rates of obesity, Type 2 diabetes; autoimmune, allergy, addiction and mood disorder-related pathologies, require novel targeted interventions and GR appears a promising pharmacological candidate. - Highlights: • Biological impact of xenobiotics acting through Glucocorticoid Receptor. • Promiscuity of Glucocorticoid Receptor. • Involvement of Glucocorticoid Receptor in multiple pathologies. • Novel xenobiotic ligands for Glucocorticoid Receptor. • Potential for multifaceted Glucocorticoid Receptor-targeted pharmacological interventions.« less

"Boomerang Neuropathology" of Late-Onset Alzheimer's Disease is Shrouded in Harmful "BDDS": Breathing, Diet, Drinking, and Sleep During Aging.

PubMed

Daulatzai, Mak Adam

2015-07-01

Brain damage begins years before substantial neurodegeneration and Alzheimer's dementia. Crucial fundamental activities of life are breathing, eating, drinking, and sleeping. When these pivotal functions are maligned over a prolonged period, they impart escalating dyshomeostasis. The latter may lead to disastrous consequences including cognitive dysfunction and Alzheimer's disease (AD). The current theme here is that multiple pathophysiological derangements are promoted over a prolonged period by the very fundamental activities of life-when "rendered unhealthy." They may converge on several regulating/modulating factors (e.g., mitochondrial energy production, oxidative stress, innate immunity, and vascular function) and promote insidious neuropathology that culminates in cognitive decline in the aged. This is of course associated with the accumulation of amyloid beta and phosphorylated tau in the brain. Epidemiological, biomarker, and neuroimaging studies have provided significant copious evidence on the presence of indolent prodromal AD neuropathology many years prior to symptomatic onset. Progressive oxidative damage to specific gene promoters may result in gene silencing. A mechanistic link may possibly exist between epigenomic state, DNA damage, and chronically unhealthy/dysfunctional body systems. This paper, therefore, addresses and delineates the deleterious pathophysiological impact triggered by dysfunctional breathing, harmful diet, excess of alcohol consumption, and sleep deprivation; indeed, their impact may alter epigenetic state. It is mandatory, therefore, to abrogate cognitive decline and attenuate AD pathology through adoption of a healthy lifestyle, in conjunction with combination therapy with known moderators of cognitive decline. This strategy may thwart multiple concurrent and synergistic pathologies, including epigenetic dysfunction. A multi-factorial therapeutic intervention is required to overcome wide ranging neuropathology and multi-faceted disease process. Such an approach may attenuate neuropathology and ameliorate memory dysfunction.

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.

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.

Congenital microcephaly: A diagnostic challenge during Zika epidemics.

PubMed

Alvarado-Socarras, Jorge L; Idrovo, Álvaro J; Contreras-García, Gustavo A; Rodriguez-Morales, Alfonso J; Audcent, Tobey A; Mogollon-Mendoza, Adriana C; Paniz-Mondolfi, Alberto

2018-02-19

The multiple, wide and diverse etiologies of congenital microcephaly are complex and multifactorial. Recent advances in genetic testing have improved understanding of novel genetic causes of congenital microcephaly. The recent Zika virus (ZIKV) epidemic in Latin America has highlighted the need for a better understanding of the underlying pathological mechanisms of microcephaly including both infectious and non-infectious causes. The diagnostic approach to microcephaly needs to include potential infectious and genetic etiologies, as well as environmental in-utero exposures such as alcohol, toxins, and medications. Emerging genetic alterations linked to microcephaly include abnormal mitotic microtubule spindle structure and abnormal function of centrosomes. We discuss the diagnostic challenge of congenital microcephaly in the context of understanding the links with ZIKV emergence as a new etiological factor involved in this birth defect. Copyright © 2018 Elsevier Ltd. All rights reserved.

Gorlin syndrome and bilateral ovarian fibroma.

PubMed

Pirschner, Fernanda; Bastos, Pollyana Marçal; Contarato, George Luiz; Bimbato, Anna Carolina Bon Lima; Filho, Antônio Chambô

2012-01-01

Gorlin syndrome (GS), also known as nevoid basal cell carcinoma syndrome (NBCCS), is a rare hereditary, autosomal dominant disease that affects various systems. Its prevalence is estimated at 1/57,000 to 1/256,000 of the population. It is characterized by basal cell carcinomas, multiple odontogenic keratocysts, skeletal abnormalities and ovarian fibroma, among other disorders. To report the case of a young patient with Gorlin syndrome and bilateral ovarian fibroma. A 20-year old patient with Gorlin syndrome presented with facial asymmetry, broad nasal root, dental abnormalities, micrognathism, convergent strabismus, multiple pigmented lesions on the trunk and face, pectus excavatum, kyphoscoliosis and a palpable mass in the abdomen occupying the entire pelvic region. Gorlin-Goltz syndrome is a hereditary pathology that includes numerous clinical manifestations. Diagnosis is clinical and genetic confirmation is unnecessary. Copyright © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Immunohistochemistry for predictive biomarkers in non-small cell lung cancer.

PubMed

Mino-Kenudson, Mari

2017-10-01

In the era of targeted therapy, predictive biomarker testing has become increasingly important for non-small cell lung cancer. Of multiple predictive biomarker testing methods, immunohistochemistry (IHC) is widely available and technically less challenging, can provide clinically meaningful results with a rapid turn-around-time and is more cost efficient than molecular platforms. In fact, several IHC assays for predictive biomarkers have already been implemented in routine pathology practice. In this review, we will discuss: (I) the details of anaplastic lymphoma kinase (ALK) and proto-oncogene tyrosine-protein kinase ROS (ROS1) IHC assays including the performance of multiple antibody clones, pros and cons of IHC platforms and various scoring systems to design an optimal algorithm for predictive biomarker testing; (II) issues associated with programmed death-ligand 1 (PD-L1) IHC assays; (III) appropriate pre-analytical tissue handling and selection of optimal tissue samples for predictive biomarker IHC.

Defining the clinical course of multiple sclerosis

PubMed Central

Reingold, Stephen C.; Cohen, Jeffrey A.; Cutter, Gary R.; Sørensen, Per Soelberg; Thompson, Alan J.; Wolinsky, Jerry S.; Balcer, Laura J.; Banwell, Brenda; Barkhof, Frederik; Bebo, Bruce; Calabresi, Peter A.; Clanet, Michel; Comi, Giancarlo; Fox, Robert J.; Freedman, Mark S.; Goodman, Andrew D.; Inglese, Matilde; Kappos, Ludwig; Kieseier, Bernd C.; Lincoln, John A.; Lubetzki, Catherine; Miller, Aaron E.; Montalban, Xavier; O'Connor, Paul W.; Petkau, John; Pozzilli, Carlo; Rudick, Richard A.; Sormani, Maria Pia; Stüve, Olaf; Waubant, Emmanuelle; Polman, Chris H.

2014-01-01

Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined. PMID:24871874

Immunohistochemistry for predictive biomarkers in non-small cell lung cancer

PubMed Central

2017-01-01

In the era of targeted therapy, predictive biomarker testing has become increasingly important for non-small cell lung cancer. Of multiple predictive biomarker testing methods, immunohistochemistry (IHC) is widely available and technically less challenging, can provide clinically meaningful results with a rapid turn-around-time and is more cost efficient than molecular platforms. In fact, several IHC assays for predictive biomarkers have already been implemented in routine pathology practice. In this review, we will discuss: (I) the details of anaplastic lymphoma kinase (ALK) and proto-oncogene tyrosine-protein kinase ROS (ROS1) IHC assays including the performance of multiple antibody clones, pros and cons of IHC platforms and various scoring systems to design an optimal algorithm for predictive biomarker testing; (II) issues associated with programmed death-ligand 1 (PD-L1) IHC assays; (III) appropriate pre-analytical tissue handling and selection of optimal tissue samples for predictive biomarker IHC. PMID:29114473

Computed tomography and magnetic resonance imaging of multiple focal nodular hyperplasias of the liver with congenital absence of the portal vein in a Chinese girl: case report and review of the literature.

PubMed

Zhang, Kun; Wang, Qingjun; Wang, Haiyi; Ye, Huiyi; Guo, Aitao; Duan, Weidong

2014-11-26

Patients with congenital absence of the portal vein (CAPV) often suffer from additional medical complications such as hepatic tumors and cardiac malformations. Congenital absence of the portal vein (CAPV) is a rare malformation. We present a case of a 16-year-old Chinese girl with CAPV with multiple pathology-proven hepatic focal nodular hyperplasias (FNHs) and ventricular septal defect (VSD). The CT and MRI features of this case are described, and previously reported cases are reviewed. CAPV is a rare congenital anomaly and in such patients, clarifying the site of portosystemic shunts, liver disease, and other anomalies is critical for appropriate treatment selection and accurate prognosis determination. Close follow-up, including laboratory testing and radiologic imaging, is recommended for all CAPV patients.

Control of proliferation and cancer growth by the Hippo signaling pathway

PubMed Central

Ehmer, Ursula; Sage, Julien

2015-01-01

The control of cell division is essential for normal development and the maintenance of cellular homeostasis. Abnormal cell proliferation is associated with multiple pathological states, including cancer. While the Hippo/YAP signaling pathway was initially thought to control organ size and growth, increasing evidence indicates that this pathway also plays a major role in the control of proliferation independent of organ size control. In particular, accumulating evidence indicates that the Hippo/YAP signaling pathway functionally interacts with multiple other cellular pathways and serves as a central node in the regulation of cell division, especially in cancer cells. Here recent observations are highlighted that connect Hippo/YAP signaling to transcription, the basic cell cycle machinery, and the control of cell division. Furthermore, the oncogenic and tumor suppressive attributes of YAP/TAZ are reviewed which emphasizes the relevance of the Hippo pathway in cancer. PMID:26432795

Advancing drug delivery systems for the treatment of multiple sclerosis.

PubMed

Tabansky, Inna; Messina, Mark D; Bangeranye, Catherine; Goldstein, Jeffrey; Blitz-Shabbir, Karen M; Machado, Suly; Jeganathan, Venkatesh; Wright, Paul; Najjar, Souhel; Cao, Yonghao; Sands, Warren; Keskin, Derin B; Stern, Joel N H

2015-12-01

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease of the central nervous system. It is characterized by demyelination of neurons and loss of neuronal axons and oligodendrocytes. In MS, auto-reactive T cells and B cells cross the blood-brain barrier (BBB), causing perivenous demyelinating lesions that form multiple discrete inflammatory demyelinated plaques located primarily in the white matter. In chronic MS, cortical demyelination and progressive axonal transections develop. Treatment for MS can be stratified into disease-modifying therapies (DMTs) and symptomatic therapy. DMTs aim to decrease circulating immune cells or to prevent these cells from crossing the BBB and reduce the inflammatory response. There are currently 10 DMTs approved for the relapsing forms of MS; these vary with regard to their efficacy, route and frequency of administration, adverse effects, and toxicity profile. Better drug delivery systems are being developed in order to decrease adverse effects, increase drug efficacy, and increase patient compliance through the direct targeting of pathologic cells. Here, we address the uses and benefits of advanced drug delivery systems, including nanoparticles, microparticles, fusion antibodies, and liposomal formulations. By altering the properties of therapeutic particles and enhancing targeting, breakthrough drug delivery technologies potentially applicable to multiple disease treatments may rapidly emerge.

Automated classification and visualization of healthy and pathological dental tissues based on near-infrared hyper-spectral imaging

NASA Astrophysics Data System (ADS)

Usenik, Peter; Bürmen, Miran; Vrtovec, Tomaž; Fidler, Aleš; Pernuš, Franjo; Likar, Boštjan

2011-03-01

Despite major improvements in dental healthcare and technology, dental caries remains one of the most prevalent chronic diseases of modern society. The initial stages of dental caries are characterized by demineralization of enamel crystals, commonly known as white spots which are difficult to diagnose. If detected early enough, such demineralization can be arrested and reversed by non-surgical means through well established dental treatments (fluoride therapy, anti-bacterial therapy, low intensity laser irradiation). Near-infrared (NIR) hyper-spectral imaging is a new promising technique for early detection of demineralization based on distinct spectral features of healthy and pathological dental tissues. In this study, we apply NIR hyper-spectral imaging to classify and visualize healthy and pathological dental tissues including enamel, dentin, calculus, dentin caries, enamel caries and demineralized areas. For this purpose, a standardized teeth database was constructed consisting of 12 extracted human teeth with different degrees of natural dental lesions imaged by NIR hyper-spectral system, X-ray and digital color camera. The color and X-ray images of teeth were presented to a clinical expert for localization and classification of the dental tissues, thereby obtaining the gold standard. Principal component analysis was used for multivariate local modeling of healthy and pathological dental tissues. Finally, the dental tissues were classified by employing multiple discriminant analysis. High agreement was observed between the resulting classification and the gold standard with the classification sensitivity and specificity exceeding 85 % and 97 %, respectively. This study demonstrates that NIR hyper-spectral imaging has considerable diagnostic potential for imaging hard dental tissues.

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.

The microenvironment of proliferative diabetic retinopathy supports lymphatic neovascularization.

PubMed

Gucciardo, Erika; Loukovaara, Sirpa; Korhonen, Ani; Repo, Pauliina; Martins, Beatriz; Vihinen, Helena; Jokitalo, Eija; Lehti, Kaisa

2018-06-01

Proliferative diabetic retinopathy (PDR) is a major diabetic microvascular complication characterized by pathological angiogenesis. Several retinopathy animal models have been developed to study the disease mechanisms and putative targets. However, knowledge on the human proliferative disease remains incomplete, relying on steady-state results from thin histological neovascular tissue sections and vitreous samples. New translational models are thus required to comprehensively understand the disease pathophysiology and develop improved therapeutic interventions. We describe here a clinically relevant model, whereby the native multicellular PDR landscape and neo(fibro)vascular processes can be analysed ex vivo and related to clinical data. As characterized by three-dimensional whole-mount immunofluorescence and electron microscopy, heterogeneity in patient-derived PDR neovascular tissues included discontinuous capillaries coupled with aberrantly differentiated, lymphatic-like and tortuous endothelia. Spatially confined apoptosis and proliferation coexisted with inflammatory cell infiltration and unique vascular islet formation. Ex vivo-cultured explants retained multicellularity, islet patterning and capillary or fibrotic outgrowth in response to vitreoretinal factors. Strikingly, PDR neovascular tissues, whose matched vitreous samples enhanced lymphatic endothelial cell sprouting, contained lymphatic-like capillaries in vivo and developed Prox1 + capillaries and sprouts with lymphatic endothelial ultrastructures ex vivo. Among multiple vitreal components, vascular endothelial growth factor C was one factor found at lymphatic endothelium-activating concentrations. These results indicate that the ischaemia-induced and inflammation-induced human PDR microenvironment supports pathological neolymphovascularization, providing a new concept regarding PDR mechanisms and targeting options. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Concussion in Chronic Traumatic Encephalopathy

PubMed Central

Stein, Thor D.; Alvarez, Victor E.; McKee, Ann C.

2015-01-01

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease that occurs in association with repetitive mild traumatic brain injury. It is associated with a variety of clinical symptoms in multiple domains, and there is a distinct pattern of pathological changes. The abnormal tau pathology in CTE occurs uniquely in those regions of the brain that are likely most susceptible to stress concentration during trauma. CTE has been associated with a variety of types of repetitive head trauma, most frequently contact sports. In cases published to date, the mean length of exposure to repetitive head trauma was 15.4 years. The clinical symptoms of the disease began after a mean latency of 14.5 years with a mean age of death of 59.3 years. Most subjects had a reported history of concussions with a mean of 20.3. However, 16 % of published CTE subjects did not have a history of concussion suggesting that subconcussive hits are sufficient to lead to the development of CTE. Overall, the number of years of exposure, not the number of concussions, was significantly associated with worse tau pathology in CTE. This suggests that it is the chronic and repetitive nature of head trauma, irrespective of concussive symptoms, that is the most important driver of disease. CTE and exposure to repetitive head trauma is also associated with a variety of other neurodegenerations, including Alzheimer disease. In fact, amyloid β peptide deposition is altered and accelerated in CTE and is associated with worse disease. Here, we review the current exposure, clinical, and pathological associations of CTE. PMID:26260277

White matter tract abnormalities are associated with cognitive dysfunction in secondary progressive multiple sclerosis.

PubMed

Meijer, Kim A; Muhlert, Nils; Cercignani, Mara; Sethi, Varun; Ron, Maria A; Thompson, Alan J; Miller, David H; Chard, Declan; Geurts, Jeroen Jg; Ciccarelli, Olga

2016-10-01

While our knowledge of white matter (WM) pathology underlying cognitive impairment in relapsing remitting multiple sclerosis (MS) is increasing, equivalent understanding in those with secondary progressive (SP) MS lags behind. The aim of this study is to examine whether the extent and severity of WM tract damage differ between cognitively impaired (CI) and cognitively preserved (CP) secondary progressive multiple sclerosis (SPMS) patients. Conventional magnetic resonance imaging (MRI) and diffusion MRI were acquired from 30 SPMS patients and 32 healthy controls (HC). Cognitive domains commonly affected in MS patients were assessed. Linear regression was used to predict cognition. Diffusion measures were compared between groups using tract-based spatial statistics (TBSS). A total of 12 patients were classified as CI, and processing speed was the most commonly affected domain. The final regression model including demographic variables and radial diffusivity explained the greatest variance of cognitive performance (R 2  = 0.48, p = 0.002). SPMS patients showed widespread loss of WM integrity throughout the WM skeleton when compared with HC. When compared with CP patients, CI patients showed more extensive and severe damage of several WM tracts, including the fornix, superior longitudinal fasciculus and forceps major. Loss of WM integrity assessed using TBSS helps to explain cognitive decline in SPMS patients. © The Author(s), 2016.

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.

Pathogenesis of human papillomavirus-associated mucosal disease.

PubMed

Groves, Ian J; Coleman, Nicholas

2015-03-01

Human papillomaviruses (HPVs) are a necessary cause of carcinoma of the cervix and other mucosal epithelia. Key events in high-risk HPV (HRHPV)-associated neoplastic progression include persistent infection, deregulated expression of virus early genes in basal epithelial cells and genomic instability causing secondary host genomic imbalances. There are multiple mechanisms by which deregulated virus early gene expression may be achieved. Integration of virus DNA into host chromosomes is observed in the majority of cervical squamous cell carcinomas (SCCs), although in ∼15% of cases the virus remains extrachromosomal (episomal). Interestingly, not all integration events provide a growth advantage to basal cervical epithelial cells or lead to increased levels of the virus oncogenes E6 and E7, when compared with episome-containing basal cells. The factors that provide a competitive advantage to some integrants, but not others, are complex and include virus and host contributions. Gene expression from integrated and episomal HRHPV is regulated through host epigenetic mechanisms affecting the virus long control region (LCR), which appear to be of functional importance. New approaches to treating HRHPV-associated mucosal neoplasia include knockout of integrated HRHPV DNA, depletion of virus transcripts and inhibition of virus early gene transcription through targeting or use of epigenetic modifiers. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The cellular response to vascular endothelial growth factors requires co-ordinated signal transduction, trafficking and proteolysis

PubMed Central

Smith, Gina A.; Fearnley, Gareth W.; Tomlinson, Darren C.; Harrison, Michael A.; Ponnambalam, Sreenivasan

2015-01-01

VEGFs (vascular endothelial growth factors) are a family of conserved disulfide-linked soluble secretory glycoproteins found in higher eukaryotes. VEGFs mediate a wide range of responses in different tissues including metabolic homoeostasis, cell proliferation, migration and tubulogenesis. Such responses are initiated by VEGF binding to soluble and membrane-bound VEGFRs (VEGF receptor tyrosine kinases) and co-receptors. VEGF and receptor splice isoform diversity further enhances complexity of membrane protein assembly and function in signal transduction pathways that control multiple cellular responses. Different signal transduction pathways are simultaneously activated by VEGFR–VEGF complexes with membrane trafficking along the endosome–lysosome network further modulating signal output from multiple enzymatic events associated with such pathways. Balancing VEGFR–VEGF signal transduction with trafficking and proteolysis is essential in controlling the intensity and duration of different intracellular signalling events. Dysfunction in VEGF-regulated signal transduction is important in chronic disease states including cancer, atherosclerosis and blindness. This family of growth factors and receptors is an important model system for understanding human disease pathology and developing new therapeutics for treating such ailments. PMID:26285805

Residency choices by graduating medical students: why not pathology?

PubMed

Hung, Tawny; Jarvis-Selinger, Sandra; Ford, Jason C

2011-06-01

Pathology is an unpopular residency choice for medical students worldwide. In some countries, this has contributed to a crisis in pathologist human resources that has affected the quality of clinical laboratories. Several previous studies have used information from junior medical students and from residents to suggest ways of improving pathology recruitment. There are, however, no published studies of pathology residency choice that focus on the senior medical students who must be recruited. This study uses focus groups of senior medical students to explore both general and pathology-specific influences on residency choice. Several general influences are identified, including students' expectations for their future clinical practices, their own clinical rotation experiences, influences from other people including mentors, and their choice to reject certain fields. Several specific antipathology influences are also revealed, including negative stereotypes about pathologists, a perceived incompatibility of personality between most medical students (extroverted) and pathologists (introverted), and perceptions of pathologists as being in some ways nonmedical. The most important antipathology influence was that, from the students' perspective, pathology was utterly invisible in clinical practice. Most students did not consider and then reject a pathology residency: instead, pathology was completely ignored. Given the importance of clerkship electives in influencing medical student career choice, promoting clerkship experiences in pathology may improve recruitment. However, departments of pathology must first make pathology visible to students and teach them how pathologists contribute to clinical care. Copyright © 2011 Elsevier Inc. All rights reserved.

Revitalizing pathology laboratories in a gastrointestinal pathophysiology course using multimedia and team-based learning techniques.

PubMed

Carbo, Alexander R; Blanco, Paola G; Graeme-Cooke, Fiona; Misdraji, Joseph; Kappler, Steven; Shaffer, Kitt; Goldsmith, Jeffrey D; Berzin, Tyler; Leffler, Daniel; Najarian, Robert; Sepe, Paul; Kaplan, Jennifer; Pitman, Martha; Goldman, Harvey; Pelletier, Stephen; Hayward, Jane N; Shields, Helen M

2012-05-15

In 2008, we changed the gastrointestinal pathology laboratories in a gastrointestinal pathophysiology course to a more interactive format using modified team-based learning techniques and multimedia presentations. The results were remarkably positive and can be used as a model for pathology laboratory improvement in any organ system. Over a two-year period, engaging and interactive pathology laboratories were designed. The initial restructuring of the laboratories included new case material, Digital Atlas of Video Education Project videos, animations and overlays. Subsequent changes included USMLE board-style quizzes at the beginning of each laboratory, with individual readiness assessment testing and group readiness assessment testing, incorporation of a clinician as a co-teacher and role playing for the student groups. Student responses for pathology laboratory contribution to learning improved significantly compared to baseline. Increased voluntary attendance at pathology laboratories was observed. Spontaneous student comments noted the positive impact of the laboratories on their learning. Pathology laboratory innovations, including modified team-based learning techniques with individual and group self-assessment quizzes, multimedia presentations, and paired teaching by a pathologist and clinical gastroenterologist led to improvement in student perceptions of pathology laboratory contributions to their learning and better pathology faculty evaluations. These changes can be universally applied to other pathology laboratories to improve student satisfaction. Copyright © 2012 Elsevier GmbH. All rights reserved.

Extracellular vesicle communication pathways as regulatory targets of oncogenic transformation.

PubMed

Choi, Dongsic; Lee, Tae Hoon; Spinelli, Cristiana; Chennakrishnaiah, Shilpa; D'Asti, Esterina; Rak, Janusz

2017-07-01

Pathogenesis of human cancers bridges intracellular oncogenic driver events and their impact on intercellular communication. Among multiple mediators of this 'pathological connectivity' the role of extracellular vesicles (EVs) and their subsets (exosomes, ectosomes, oncosomes) is of particular interest for several reasons. The release of EVs from cancer cells represents a unique mechanism of regulated expulsion of bioactive molecules, a process that also mediates cell-to-cell transfer of lipids, proteins, and nucleic acids. Biological effects of these processes have been implicated in several aspects of cancer-related pathology, including tumour growth, invasion, angiogenesis, metastasis, immunity and thrombosis. Notably, the emerging evidence suggests that oncogenic mutations may impact several aspects of EV-mediated cell-cell communication including: (i) EV release rate and protein content; (ii) molecular composition of cancer EVs; (iii) the inclusion of oncogenic and mutant macromolecules in the EV cargo; (iv) EV-mediated release of genomic DNA; (v) deregulation of mechanisms responsible for EV biogenesis (vesiculome) and (vi) mechanisms of EV uptake by cancer cells. Intriguingly, EV-mediated intercellular transfer of mutant and oncogenic molecules between subpopulations of cancer cells, their indolent counterparts and stroma may exert profound biological effects that often resemble (but are not tantamount to) oncogenic transformation, including changes in cell growth, clonogenicity and angiogenic phenotype, or cause cell stress and death. However, several biological barriers likely curtail a permanent horizontal transformation of normal cells through EV-mediated mechanisms. The ongoing analysis and targeting of EV-mediated intercellular communication pathways can be viewed as a new therapeutic paradigm in cancer, while the analysis of oncogenic cargo contained in EVs released from cancer cells into biofluids is being developed for clinical use as a biomarker and companion diagnostics. Indeed, studies are underway to further explore the multiple links between molecular causality in cancer and various aspects of cellular vesiculation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Of Brain and Bone: The Unusual Case of Dr. A

PubMed Central

Narvid, J; Gorno-Tempini, ML; Slavotinek, A; DeArmond, SJ; Cha, YH; Miller, BL; Rankin, K.P

2009-01-01

Frontotemporal dementia (FTD) is a clinical syndrome characterized by progressive decline in social conduct and a focal pattern of frontal and temporal lobe damage. Its biological basis is still poorly understood but the focality of the brain degeneration provides a powerful model to study the cognitive and anatomical basis of social cognition. Here, we present Dr. A, a patient with a rare hereditary bone disease (hereditary multiple exostoses) and FTD (pathologically characterized as Pick’s disease), who presented with a profound behavioral disturbance characterized by acquired sociopathy. We conducted a detailed genetic, pathological, neuroimaging and cognitive study, including a battery of tests designed to investigate Dr. A’s abilities to understand emotional cues and to infer mental states and intentions to others (theory of mind). Dr. A’s genetic profile suggests the possibility that a mutation causing hereditary multiple exostoses, Ext2, may play a role in the pattern of neurodegeneration in frontotemporal dementia since knockout mice deficient in the Ext gene family member, Ext1, show severe CNS defects including loss of olfactory bulbs and abnormally small cerebral cortex. Dr. A showed significant impairment in emotion comprehension, second order theory of mind, attribution of intentions, and empathy despite preserved general cognitive abilities. Voxel-based morphometry on structural MRI images showed significant atrophy in the medial and right orbital frontal and anterior temporal regions with sparing of dorsolateral frontal cortex. This case demonstrates that social and emotional dysfunction in FTD can dissociate from preserved performance on classic executive functioning tasks. The specific pattern of anatomical damage shown by VBM emphasizes the importance of the network including the superior medial frontal gyrus as well as temporal polar areas, in regulation of social cognition and theory of mind. This case provides new evidence regarding the neural basis of social cognition and suggests a possible genetic link between bone disease and FTD. PMID:20183548

Co-occurrence of schwannomatosis and rhabdoid tumor predisposition syndrome 1.

PubMed

Kehrer-Sawatzki, Hildegard; Kordes, Uwe; Seiffert, Simone; Summerer, Anna; Hagel, Christian; Schüller, Ulrich; Farschtschi, Said; Schneppenheim, Reinhard; Bendszus, Martin; Godel, Tim; Mautner, Victor-Felix

2018-05-20

The clinical phenotype associated with germline SMARCB1 mutations has as yet not been fully documented. It is known that germline SMARCB1 mutations may cause rhabdoid tumor predisposition syndrome (RTPS1) or schwannomatosis. However, the co-occurrence of rhabdoid tumor and schwannomas in the same patient has not so far been reported. We investigated a family with members harboring a germline SMARCB1 deletion by means of whole-body MRI as well as high-resolution microstructural magnetic resonance neurography (MRN). Breakpoint-spanning PCRs were performed to characterize the SMARCB1 deletion and its segregation in the family. The index patient of this family was in complete continuous remission for an atypical teratoid/rhabdoid tumor (AT/RT) treated at the age of 2 years. However, at the age of 21 years, she exhibited paraparesis of her legs and MRI investigations revealed multiple intrathoracic and spinal schwannomas. Breakpoint-spanning PCRs indicated that the germline deletion segregating in the family encompasses 6.4-kb and includes parts of SMARCB1 intron 7, exons 8-9 and 3.3-kb located telomeric to exon 9 including the SMARCB1 3' UTR. The analysis of sequences at the deletion breakpoints showed that the deletion has been caused by replication errors including template-switching. The patient had inherited the deletion from her 56-year-old healthy mother who did not exhibit schwannomas or other tumors as determined by whole-body MRI. However, MRN of the peripheral nerves of the mother's extremities revealed multiple fascicular microlesions which have been previously identified as indicative of schwannomatosis-associated subclinical peripheral nerve pathology. The occurrence of schwannomatosis-associated clinical symptoms independent of the AT/RT as the primary disease should be considered in long-term survivors of AT/RT. Furthermore, our investigations indicate that germline SMARCB1 mutation carriers not presenting RTs or schwannomatosis-associated clinical symptoms may nevertheless exhibit peripheral nerve pathology as revealed by MRN. © 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Hand-Assisted Laparoscopic (HAL) Multiple Segmental Colorectal Resections: Are They Feasible and Safe?

PubMed

Taggarshe, Deepa; Attuwaybi, Bashir O; Matier, Brian; Visco, Jeffrey J; Butler, Bryan N

2015-04-01

The objective of this study was to evaluate the short-term outcomes of synchronous hand-assisted laparoscopic (HAL) segmental colorectal resections. The surgical options for synchronous colonic pathology include extensive colonic resection with single anastomosis, multiple synchronous segmental resections with multiple anastomoses, or staged resections. Traditionally, multiple open, synchronous, segmental resections have been performed. There is a lack of data on HAL multiple segmental colorectal resections. A retrospective chart review was compiled on all patients who underwent HAL synchronous segmental colorectal resections by all the colorectal surgeons from our Group during the period of 1999 to 2014. Demographics, operative details, and short-term outcomes are reported. During the period, 9 patients underwent HAL synchronous multiple segmental colorectal resections. There were 5 women and 4 men, with median age of 54 (24-83) years and median BMI of 24 (19.8-38.7) kg/m(2). Two patients were on long-term corticosteroid therapy. The median operative time was 210 (120-330) minutes and median operative blood loss was 200 (75-300) mLs. The median duration for return of bowel function was 2 days and the median length of stay was 3.5 days. We had 2 minor wound infections. There were no deaths. Synchronous segmental colorectal resections with anastomoses using the hand-assisted laparoscopic technique are safe. Early conversion to open and use of stomas are advisable in challenging cases.

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.

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.

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.

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

Bone marrow biopsy in monoclonal gammopathies: correlations between pathological findings and clinical data. The Cooperative Group for Study and Treatment of Multiple Myeloma.

PubMed Central

Riccardi, A; Ucci, G; Luoni, R; Castello, A; Coci, A; Magrini, U; Ascari, E

1990-01-01

Between January 1987 and October 1989, 561 consecutive untreated patients with monoclonal gammopathy of undetermined clinical importance (MGUS) (n = 295) or with multiple myeloma (n = 266) were evaluated in a multicentre trial. Both bone marrow biopsy and aspiration (performed at different anatomical sites) were required at presentation. Bone marrow biopsy data indicated that changes in bone marrow composition from MGUS to early multiple myeloma and to advanced multiple myeloma followed a precise pattern, including an increased percentage of bone marrow plasma cells (BMPC%), a shift from plasmocytic to plasmoblastic cytology, an increase in bone marrow cellularity and fibrosis, a change in bone marrow infiltration (becoming diffuse rather than interstitial), a decrease in residual haemopoiesis and an increase in osteoclasts. In multiple myeloma the BMPC% of biopsy specimens and aspirate were closely related, although in 5% of cases the difference between the two values was greater than 20%. Some histological features were remarkably associated with each other. For example, BMPC% was higher in cases with plasmoblastic cytology, heavy fibrosis, or reduced residual haemopoiesis. Anaemia was the clinical characteristic most influenced by bone marrow histology. The BMPC% was the only histological variable which affected the greatest number of clinical and laboratory characteristics, including, besides haemoglobin concentration, erythrocyte sedimentation rate, radiographic skeletal bone disease, and serum concentrations of monoclonal component, calcium, beta 2-microglobulin and thymidine kinase activity. These data indicate that comparative bone marrow histology in monoclonal gammopathies has clinical importance. Images PMID:2199532

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.

Military sexual trauma as a determinant in the development of mental and physical illness in male and female veterans.

PubMed

O'Brien, Betsy S; Sher, Leo

2013-01-01

Military Sexual Trauma (MST) is defined as sexual harassment and or sexual assault experienced by a military service member. It is much more widespread and common than reported. It is associated with pre-combat traumatic experiences and pathologic sequelae including mental and medical illness. An electronic search of the major behavioral science databases was conducted to retrieve studies detailing the social, epidemiological and clinical characteristics of MST and its relationship to psychiatric and medical illness. Studies indicate that military sexual trauma is related to an increase in psychiatric pathology, including posttraumatic stress disorder (PTSD), substance abuse and dependence, depression, anxiety, eating disorders and suicidal behavior. MST is also related to an increase in medical illness, primarily pain-related symptoms involving multiple organ systems, including gastrointestinal, neurological, genitourinary and musculoskeletal. MST is associated with an increased prevalence of mental and physical illness. Although there are some gender differences in the reported rates of MST and there may be some variables, such as prior traumatic experiences, that may make an individual more vulnerable to the psychiatric and medical sequela of MST, it is clear that MST is a major healthcare issue that affects both sexes and warrants further attention and an increase in clinical resources devoted to it. Some preventive measures for decreasing the prevalence of MST may include increasing education and legal prosecution of perpetrators in the military, and increasing access to mental health services for individuals who have suffered from MST.

[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.

Risk factors contributing to a poor prognosis of papillary thyroid carcinoma: validity of UICC/AJCC TNM classification and stage grouping.

PubMed

Ito, Yasuhiro; Miyauchi, Akira; Jikuzono, Tomoo; Higashiyama, Takuya; Takamura, Yuuki; Miya, Akihiro; Kobayashi, Kaoru; Matsuzuka, Fumio; Ichihara, Kiyoshi; Kuma, Kanji

2007-04-01

In 2002, the UICC/AJCC TNM classification for papillary thyroid carcinoma was revised. In this study, we examined the validity of this classification system by investigating the predictors of disease-free survival (DFS) and cause-specific survival (CSS) in patients. We examined various clinicopathological features, including the component of the TNM classification, for 1,740 patients who underwent initial and curative surgery for papillary carcinoma between 1987 and 1995. Clinical and pathological T4a, clinical N1b in the TNM classification, and patient age were recognized as independent predictors of not only DFS, but also CSS of patients. Tumor size, male gender, and central node metastasis independently affected DFS only. There were 1,005 pathological N1b patients, but pathological N1b did not independently affect either DFS or CSS. Regarding the stage grouping, clinical stage IVA including clinical N1b more clearly affected DFS and CSS than pathological stage IVA including pathological N1b. Clinical stage grouping was more useful than pathological stage grouping for predicting the prognosis of papillary carcinoma patients possibly because pathological stage overestimates the biological characteristics of many pathological N1b tumors.

Sonographic findings of hepatobiliary fascioliasis accompanied by extrahepatic expansion and ectopic lesions.

PubMed

Teke, Memik; Önder, Hakan; Çiçek, Mutalip; Hamidi, Cihad; Göya, Cemil; Çetinçakmak, Mehmet Güli; Hattapoğlu, Salih; Ülger, Burak Veli

2014-12-01

The aim of the study was to describe the sonographic findings of hepatobiliary fascioliasis with extrahepatic expansion and ectopic lesions. The study included 45 patients with fascioliasis. All diagnoses were confirmed via serologic enzyme-linked immunosorbent assays. Sonographic findings in the hepatobiliary system, extrahepatic expansion, and ectopic lesions were defined. The most common hepatic lesions were subcapsular localized, small, confluent, multiple hypoechoic nodules with poorly defined borders. We also detected ectopic lesion in 5 patients (11.1%) and live parasites in the gallbladder and bile duct in 11 (24.4%). The large spectrum of entities in the differential diagnosis of hepatobiliary fascioliasis may lead to misdiagnosis and incorrect treatment. However, the diagnosis can be made when the characteristic sonographic features are seen, such as heterogeneity of the liver with multiple poorly defined hypoechoic-isoechoic lesions and multiple echogenic nonshadowing particles in the gallbladder or common bile ducts. Nonetheless, the differential diagnosis of fascioliasis versus other hepatic lesions may still be difficult. In these situations, pathologic confirmation should be performed to exclude the possibility of malignancy. © 2013 by the American Institute of Ultrasound in Medicine.

Hemophagocytic syndrome in a cat with multiple myeloma.

PubMed

Dunbar, Mark D; Lyles, Sarah

2013-03-01

An 11-year-old, castrated male, Domestic Medium Hair cat was presented to the University of Florida Small Animal Hospital with a 2-week history of upper respiratory infection and increased serum globulins, as reported by the referring veterinarian. Physical examination was unremarkable other than melanosis of the left iris, with no evidence of ocular, nasal, or respiratory disease. Laboratory abnormalities included moderate nonregenerative anemia, mild leukopenia, mild hyperfibrinogenemia, severe hyperglobulinemia, mild hypoalbuminemia, and hypocholesterolemia. Abdominal radiographs and ultrasonographic examination revealed mild splenomegaly with no other abnormalities. Thoracic radiographs revealed no abnormalities. Cytologic evaluation of fine-needle aspirates from the spleen, liver, and bone marrow revealed numerous plasma cells and many vacuolated macrophages exhibiting marked phagocytosis of mature erythrocytes and platelets, occasionally metarubricytes and leukocytes, and rarely plasma cells. The cytologic interpretation was multiple myeloma and associated hemophagocytic syndrome (HPS). Serum protein electrophoresis revealed a monoclonal gammopathy, providing further evidence for a multiple myeloma. To the authors' knowledge, this is the first report of HPS secondary to neoplasia in a cat. © 2012 American Society for Veterinary Clinical Pathology.

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.

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.

Multiple metastatic malignant melanoma presenting intraluminal gallbladder bleeding.

PubMed

Onozawa, Hisashi; Saito, Motonobu; Yoshida, Sayaka; Sakuma, Takeshi; Matsuzaki, Masami; Katagata, Naoto; Watanabe, Fumiaki; Yamaguchi, Yoshiko; Takenoshita, Seiichi; Nomizu, Tadashi

2014-01-01

We report a case of malignant melanoma of unknown primary origin presenting metastasis in various organs as well as intraluminal gallbladder bleeding due to gallbladder metastasis. A 58-year-old woman was diagnosed with stage IV metastatic malignant melanoma. Because she exhibited acute cholecystitis and hemobilia due to malignant melanoma of the gallbladder, laparoscopic cholecystectomy was performed to relieve the symptoms. The resected gallbladder specimen showed a pedunculated black mass indicating malignant melanoma. Pathologic examination and immunohistochemical analysis revealed malignant melanoma of the gallbladder. Only a few cases of gallbladder malignant melanoma presenting hemobilia have been reported; here we present our case, including the experience of multidisciplinary treatment.

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

Arthroscopic Management of Anterior, Posterior, and Multidirectional Shoulder Instabilities.

PubMed

Field, Larry D; Ryu, Richard K N; Abrams, Jeffrey S; Provencher, Matthew

2016-01-01

Arthroscopic shoulder stabilization offers several potential advantages compared with open surgery, including the opportunity to more accurately evaluate the glenohumeral joint at the time of diagnostic assessment; comprehensively address multiple pathologic lesions that may be identified; and avoid potential complications unique to open stabilization, such as postoperative subscapularis failure. A thorough understanding of normal shoulder anatomy and biomechanics, along with the pathoanatomy responsible for anterior, posterior, and multidirectional shoulder instability patterns, is very important in the management of patients who have shoulder instability. The treating physician also must be familiar with diagnostic imaging and physical examination maneuvers that are required to accurately diagnose shoulder instability.

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.

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.

Imaging as a biomarker in drug discovery for Alzheimer’s disease: is MRI a suitable technology?

PubMed Central

2014-01-01

This review provides perspectives on the utility of magnetic resonance imaging (MRI) as a neuroimaging approach in the development of novel treatments for Alzheimer’s disease. These considerations were generated in a roundtable at a recent Wellcome Trust meeting that included experts from academia and industry. It was agreed that MRI, either structural or functional, could be used as a diagnostic, for assessing worsening of disease status, for monitoring vascular pathology, and for stratifying clinical trial populations. It was agreed also that MRI implementation is in its infancy, requiring more evidence of association with the disease states, test-retest data, better standardization across multiple clinical sites, and application in multimodal approaches which include other imaging technologies, such as positron emission tomography, electroencephalography, and magnetoencephalography. PMID:25484927

Recent advances in cytokines in cutaneous and systemic lupus erythematosus.

PubMed

Mikita, Naoya; Ikeda, Takaharu; Ishiguro, Mariko; Furukawa, Fukumi

2011-09-01

Lupus erythematosus (LE) includes a broad spectrum of diseases from a cutaneous-limited type to a systemic type. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease which affects multiple organs. Cutaneous lupus erythematosus (CLE) includes skin symptoms seen in SLE and cutaneous-limited LE. Although immune abnormalities, as well as heritable, hormonal and environmental factors, are involved in the pathology of LE, the actual pathogenesis is still unclear. Recently, the involvement of various cytokines has been shown in the pathogenesis of LE. Moreover, some trials with biological agents targeted specific cytokines are also ongoing for SLE. In this article, we review the contributions of major cytokines such as interferon, tumor necrosis factor-α and interleukin-18 to LE, especially SLE and CLE. © 2011 Japanese Dermatological Association.

Disseminated sinus histiocytosis with massive lymphadenopathy: its pathologic aspects.

PubMed

Buchino, J J; Byrd, R P; Kmetz, D R

1982-01-01

Sinus histiocytosis with massive lymphadenopathy (SHML) is generally regarded as a benign, self-limited, pseudolymphomatous process requiring little or no therapy. We studied a 13-year-old black boy with a ten-year clinical course of SHML that had varying, intermittent sites of extranodal involvement, including bone, submandibular gland, trachea, eye, and spinal cord. At the time of death, which was attributed to SHML, additional extranodal sites of involvement included thymus, kidney, heart, liver, and base of brain. Microscopic examination of the SHML lesions at the time of autopsy revealed varying stages of development, from proliferation to involution. This case illustrates that SHML may involve multiple organ systems, can kill, and that histologic evaluation of disease activity at one site cannot be used as an indicator of activity at another.

Primary biliary cirrhosis: From bench to bedside

PubMed Central

Kouroumalis, Elias; Notas, George

2015-01-01

Primary biliary cirrhosis (PBC) is a chronic non-suppurative destructive intrahepatic cholangitis leading to cirrhosis after a protractive non cirrhotic stage. The etiology and pathogenesis are largely unknown and autoimmne mechanisms have been implicated to explain the pathological lesions. Many epitopes and autoantigens have been reported as crucial in the pathophysiology of the disease and T and B cells abnormalities have been described, the exact pathways leading to the destruction of small intrahepatic ductules are mostly speculative. In this review we examined the various epidemiologal and geoepidemiological data as well as the complex pathogenetic aspects of this disease, focusing on recent in vivo and in vitro studies in this field. Initiation and progression of PBC is believed to be a multifactorial process with strong infuences from the patient’s genetic background and by various environmental factors. The role of innate and adaptive immunity, including cytokines, chemokines, macrophages and the involvement of apoptosis and reactive oxygen species are outlined in detailed. The current pathogenetic aspects are presented and a novel pathogenetic theory unifying the accumulated clinical information with in vitro and in vivo data is formulated. A review of clinical manifestations and immunological and pathological diagnosis was presented. Treatment modalities, including the multiple mechanisms of action of ursodeoxycholate were finally discussed. PMID:26261733

[Non-motor symptoms in Parkinson's disease: cognition and behavior].

PubMed

Bonnet, Anne Marie; Czernecki, Virginie

2013-09-01

Although the diagnosis of Parkinson disease is based on motor symptoms, it is now well known that non-motor symptoms are an integral part of this pathology, involving in fact multiple systems. These non-motor symptoms affect large population of patients and can appear sometimes before the motor disorders. The non-motor symptoms include mainly neuropsychological difficulties, neuropsychiatric symptoms, and autonomic disorders, but involve also pain and sleep disturbances for example. Depression may occur at any stage of the disease, and consists in major depressive disorder, minor depressive disorder, and dysthymia. During the course of the disease, 50% of patients experience anxiety. Apathy is present in up to 30-40% of patients, due to loss of motivation, appearing in emotional, intellectual and behavioral domains. Dopamine dysregulation syndrome and impulse control disorders are not rare, and in relation with dopaminergic therapies. Impulse control disorders include pathological gambling, hyper sexuality, compulsive shopping, and eating disorder. Visual hallucinations can occur in 30% of patients, mostly induced by dopaminergic therapies. Often, they have deeper impact on the quality of life than the motor symptoms themselves, which stay the focus of attention during consulting. Identifying those can help in providing better care with a positive impact on the quality of life of the patients.

Tissue and cellular tropism, pathology and pathogenesis of Ebola and Marburg viruses.

PubMed

Martines, Roosecelis Brasil; Ng, Dianna L; Greer, Patricia W; Rollin, Pierre E; Zaki, Sherif R

2015-01-01

Ebola viruses and Marburg viruses include some of the most virulent and fatal pathogens known to humans. These viruses cause severe haemorrhagic fevers, with case fatality rates in the range 25-90%. The diagnosis of filovirus using formalin-fixed tissues from fatal cases poses a significant challenge. The most characteristic histopathological findings are seen in the liver; however, the findings overlap with many other viral and non-viral haemorrhagic diseases. The need to distinguish filovirus infections from other haemorrhagic fevers, particularly in areas with multiple endemic viral haemorrhagic agents, is of paramount importance. In this review we discuss the current state of knowledge of filovirus infections and their pathogenesis, including histopathological findings, epidemiology, modes of transmission and filovirus entry and spread within host organisms. The pathogenesis of filovirus infections is complex and involves activation of the mononuclear phagocytic system, with release of pro-inflammatory cytokines, chemokines and growth factors, endothelial dysfunction, alterations of the innate and adaptive immune systems, direct organ and endothelial damage from unrestricted viral replication late in infection, and coagulopathy. Although our understanding of the pathogenesis of filovirus infections has rapidly increased in the past few years, many questions remain unanswered. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Blood microcirculation of ischemic pancreatitis

NASA Astrophysics Data System (ADS)

Dmitrieva, Irina V.; Arakelian, Sergei M.; Antonov, Olga V.

1998-06-01

Blood Microcirculation includes many of different components, which are joined by unique multiple system. Capillaries are one of the main link in this morpho-functional chain. Changes in any components of blood microcirculation are revealed by many of pathological processes in different organs and systems of the whole organism. We investigated 250 patients from 30 to 77 ages. Men included 149, women -- 101. The main diagnosis of all patients was the ischaemic pancreatitis. For verification of this diagnosis we used the whole spectrum of clinical, laboratorial and instrumental methods. These were the following: the definition of amylase of blood and urine, sonography and computer's tomography of pancreas, angiography of vessels of pancreas and Doppler's sonography of abdominal aorta and her branches: arteria mesenterica superior (AMS), truncus coeliacus (TC), arteria hepatica communis (AHC) and arteria lienalis (AL). We investigated the blood microcirculation of the mucous of the inferior lip, using Laser Dopplerography. The equipment for this research was LACC-01 with modified computer's program. The normal levels of blood microcirculation were from 120 to 180 Units. But patients with ischaemic pancreatitis had more lower level than in normal situation. This method are suggested as express diagnostic in the cases of abdominal ischaemic pathology. It can used as singel method or in combined with ultrasound Dopplerography.

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.

Diagnostic criteria for vascular cognitive disorders: a VASCOG statement

PubMed Central

Sachdev, Perminder; Kalaria, Raj; O’Brien, John; Skoog, Ingmar; Alladi, Suvarna; Black, Sandra E; Blacker, Deborah; Blazer, Dan; Chen, Christopher; Chui, Helena; Ganguli, Mary; Jellinger, Kurt; Jeste, Dilip V.; Pasquier, Florence; Paulsen, Jane; Prins, Niels; Rockwood, Kenneth; Roman, Gustavo; Scheltens, Philip

2014-01-01

Background Several sets of diagnostic criteria have been published for vascular dementia (VaD) since the 1960s. The continuing ambiguity in VaD definition warrants a critical re-examination. Methods Participants at a special symposium of the International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) in 2009 critiqued the current criteria. They drafted a proposal for a new set of criteria, later reviewed through multiple drafts by the group, including additional experts and the members of the Neurocognitive Disorders Work Group of the DSM-5 Task Force. Results Cognitive disorders of vascular etiology are a heterogeneous group of disorders with diverse pathologies and clinical manifestations, discussed broadly under the rubric of vascular cognitive disorders (VCD). The continuum of vascular cognitive impairment is recognized by the categories of Mild Vascular Cognitive Disorder, and Vascular Dementia or Major Vascular Cognitive Disorder. Diagnostic thresholds are defined. Clinical and neuroimaging criteria are proposed for establishing vascular etiology. Subtypes of VCD are described, and the frequent co-occurrence of Alzheimer’s disease pathology emphasized. Conclusions The proposed criteria for VCD provide a coherent approach to the diagnosis of this diverse group of disorders, with a view to stimulating clinical and pathological validation studies. These criteria can be harmonized with the DSM-5 criteria such that an international consensus on the criteria for VCD may be achieved. PMID:24632990

Corticobasal degeneration with olivopontocerebellar atrophy and TDP-43 pathology: an unusual clinicopathologic variant of CBD

PubMed Central

Kouri, Naomi; Oshima, Kenichi; Takahashi, Makio; Murray, Melissa E.; Ahmed, Zeshan; Parisi, Joseph E.; Yen, Shu-Hui C.; Dickson, Dennis W.

2013-01-01

CBD is a disorder affecting cognition and movement due to a progressive neurodegeneration associated with distinctive neuropathologic features, including abnormal phosphorylated tau protein in neurons and glia in cortex, basal ganglia, diencephalon and brainstem, as well as ballooned neurons and astrocytic plaques. We identified three cases of CBD with olivopontocerebellar atrophy (CBD-OPCA) that did not have α-synuclein-positive glial cytoplasmic inclusions of multiple system atrophy (MSA). Two patients had clinical features suggestive of progressive supranuclear palsy (PSP), and the third case had cerebellar ataxia thought to be due to idiopathic OPCA. Neuropathologic features of CBD-OPCA are compared to typical CBD, as well as MSA and PSP. CBD-OPCA and MSA had marked neuronal loss in pontine nuclei, inferior olivary nucleus, and Purkinje cell layer. Neuronal loss and grumose degeneration in the cerebellar dentate nucleus was comparable in CBD-OPCA and PSP. Image analysis of tau pathology showed greater infratentorial tau burden, especially in pontine base, in CBD-OPCA compared with typical CBD. Additionally, CBD-OPCA had TDP-43 immunoreactive neuronal and glial cytoplasmic inclusions and threads throughout the basal ganglia and in olivopontocerebellar system. CBD-OPCA met neuropathologic research diagnostic criteria for CBD and shared tau biochemical characteristics with typical CBD. These results suggest that CBD-OPCA is a distinct clinicopathologic variant of CBD with olivopontocerebellar TDP-43 pathology. PMID:23371366

Corticobasal degeneration with olivopontocerebellar atrophy and TDP-43 pathology: an unusual clinicopathologic variant of CBD.

PubMed

Kouri, Naomi; Oshima, Kenichi; Takahashi, Makio; Murray, Melissa E; Ahmed, Zeshan; Parisi, Joseph E; Yen, Shu-Hui C; Dickson, Dennis W

2013-05-01

Corticobasal degeneration (CBD) is a disorder affecting cognition and movement due to a progressive neurodegeneration associated with distinctive neuropathologic features, including abnormal phosphorylated tau protein in neurons and glia in cortex, basal ganglia, diencephalon, and brainstem, as well as ballooned neurons and astrocytic plaques. We identified three cases of CBD with olivopontocerebellar atrophy (CBD-OPCA) that did not have α-synuclein-positive glial cytoplasmic inclusions of multiple system atrophy (MSA). Two patients had clinical features suggestive of progressive supranuclear palsy (PSP), and the third case had cerebellar ataxia thought to be due to idiopathic OPCA. Neuropathologic features of CBD-OPCA are compared to typical CBD, as well as MSA and PSP. CBD-OPCA and MSA had marked neuronal loss in pontine nuclei, inferior olivary nucleus, and Purkinje cell layer. Neuronal loss and grumose degeneration in the cerebellar dentate nucleus were comparable in CBD-OPCA and PSP. Image analysis of tau pathology showed greater infratentorial tau burden, especially in pontine base, in CBD-OPCA compared with typical CBD. In addition, CBD-OPCA had TDP-43 immunoreactive neuronal and glial cytoplasmic inclusions and threads throughout the basal ganglia and in olivopontocerebellar system. CBD-OPCA met neuropathologic research diagnostic criteria for CBD and shared tau biochemical characteristics with typical CBD. These results suggest that CBD-OPCA is a distinct clinicopathologic variant of CBD with olivopontocerebellar TDP-43 pathology.

Immunophenotypic analysis of mast cells in mastocytosis: When and how to do it. Proposals of the Spanish Network on Mastocytosis (REMA).

PubMed

Escribano, Luis; Diaz-Agustin, Beatriz; López, Antonio; Núñez López, Rosa; García-Montero, Andrés; Almeida, Julia; Prados, Aranzazu; Angulo, Miguel; Herrero, Sonia; Orfao, Alberto

2004-03-01

Mastocytosis is a term used for a heterogeneous group of disorders characterized by an abnormal proliferation and accumulation of mast cells (MCs) in one or multiple tissues including skin, bone marrow, liver, spleen, and lymph nodes, among others. In recent years, multiparameter flow cytometric studies have shown that pathologic MCs from patients with mastocytosis display unique aberrant immunophenotypic characteristics as compared with normal MCs. Among other features, pathologic MCs show aberrant expression of CD25 and CD2 antigens and abnormally high levels of the CD11c and CD35 complement receptors, the CD59 complement regulatory molecule, the CD63 lysosomal membrane antigen, and the CD69 early-activation antigen. In addition, MCs from mastocytosis express abnormally low levels of CD117 and unexpectedly high light scatter and autofluorescence characteristics. These aberrant immunophenotypic features are of great relevance for the assessment of tissue involvement in mastocytosis with consequences in the diagnosis, classification, and follow-up of the disease and in its differential diagnosis with other entities. In this paper we provide the reader with information for the objective and reproducible identification of pathologic MCs by using quantitative multiparametric flow cytometry, information for their phenotypic characterization, and the criteria currently used for a correct interpretation of the immunophenotypic results obtained. Copyright 2004 Wiley-Liss, Inc.

Validating workplace performance assessments in health sciences students: a case study from speech pathology.

PubMed

McAllister, Sue; Lincoln, Michelle; Ferguson, Allison; McAllister, Lindy

2013-01-01

Valid assessment of health science students' ability to perform in the real world of workplace practice is critical for promoting quality learning and ultimately certifying students as fit to enter the world of professional practice. Current practice in performance assessment in the health sciences field has been hampered by multiple issues regarding assessment content and process. Evidence for the validity of scores derived from assessment tools are usually evaluated against traditional validity categories with reliability evidence privileged over validity, resulting in the paradoxical effect of compromising the assessment validity and learning processes the assessments seek to promote. Furthermore, the dominant statistical approaches used to validate scores from these assessments fall under the umbrella of classical test theory approaches. This paper reports on the successful national development and validation of measures derived from an assessment of Australian speech pathology students' performance in the workplace. Validation of these measures considered each of Messick's interrelated validity evidence categories and included using evidence generated through Rasch analyses to support score interpretation and related action. This research demonstrated that it is possible to develop an assessment of real, complex, work based performance of speech pathology students, that generates valid measures without compromising the learning processes the assessment seeks to promote. The process described provides a model for other health professional education programs to trial.

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.

Reliability of Frozen Section Examination in a Large Cohort of Testicular Masses: What Did We Learn?

PubMed

Matei, Deliu Victor; Vartolomei, Mihai Dorin; Renne, Giuseppe; Tringali, Valeria Maria Lucia; Russo, Andrea; Bianchi, Roberto; Cozzi, Gabriele; Bottero, Danilo; Musi, Gennaro; Mazzarol, Giovanni; Ferro, Matteo; de Cobelli, Ottavio

2017-08-01

Frozen section examination (FSE) for testicular masses is gaining popularity because of the possibility of performing testis-sparing surgery (TSS) on the basis of the FSE results. The aim of our study was to investigate the reliability of FSE in the diagnosis of testicular masses. From 1999 to 2016, 144 of 692 patients who underwent surgery in our tertiary center for testicular masses had FSE. The indications for FSE were: masses < 1 cm, nonpalpable, multiple, or with unusual presentation. Mean follow-up for patients was 25.5 months. The algorithm of surgery determined by FSE was: orchiectomy if malignant or nonconclusive pathology; TSS if benign or nontumor pathology. FSE data were analyzed retrospectively. Specificity and sensitivity of the method was calculated for benign, malignant, seminoma, and nonseminoma tumors. Intraoperative FSE was conducted on 21% of candidates for surgery on testicular masses. The sensitivity and specificity of FSE were 93% and 98%, respectively, for malignant tumors, and 90% and 99%, respectively, for benign tumors. The κ agreement coefficient between FSE and final histopathology was statistically significant (0.76). TSS was performed in 57 (40%) patients, including 6 of 23 monorchid patients. FSE correlates well with final histopathological diagnosis of testicular masses. Thus, it reliably identifies patients who might benefit from TSS. FSE should be considered always in small, nonpalpable, multiple, or uncommonly presenting masses in solitary testis or both testes. Copyright © 2017 Elsevier Inc. All rights reserved.

Differentiation of benign and malignant hilar bile duct stenosis.

PubMed

Liu, Xiaolei; Yang, Zhiying; Tan, Haidong; Shao, Chen; Liu, Liguo; Si, Shuang; Xu, Li; Sun, Yongliang

2016-06-15

Failure to differentiate benign and malignant hilar bile duct stenosis may lead to inappropriate treatment. We retrospectively analyzed the methods for differentiation. A total of 53 patients with hilar bile duct stenosis were included, comprising 41 malignant cases (hilar cholangiocarcinoma) and 12 benign cases (six primary sclerosing cholangitis and six IgG4-associated sclerosing cholangitis). Data of clinical histories, laboratory tests, imaging studies, and liver pathologies were collected, and comparison was made between benign and malignant groups. Compared with malignant group, patients in the benign group were more likely to have multiorgan involvement of clinical histories (P < 0.001). There was no difference on bilirubin, liver enzyme, and serum tumor marker between the two groups, whereas serum IgG4 levels were higher in the benign group (P = 0.003). Patients in the benign group were more likely to have pancreatic changes (P < 0.001) and multiple-segmental bile duct stenosis (P < 0.001) on imaging. Compared with the malignant group, patients in the benign group were more likely to show severe periportal inflammation in noninvolved liver (P < 0.001), fibrosis around intrahepatic bile duct (P < 0.001), and more IgG4-positive plasma cells (P < 0.001) on liver pathology. Benign lesion should be considered for patients with history of multiorgan involvement, pancreas changes, or multiple-segmental bile duct stenosis on imaging. Liver biopsy could be helpful for differential diagnosis before surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

How do immune cells support and shape the brain in health, disease, and aging?

PubMed

Schwartz, Michal; Kipnis, Jonathan; Rivest, Serge; Prat, Alexandre

2013-11-06

For decades, several axioms have prevailed with respect to the relationships between the CNS and circulating immune cells. Specifically, immune cell entry was largely considered to be pathological or to mark the beginning of pathology within the brain. Moreover, local inflammation associated with neurodegenerative diseases such Alzheimer's disease or amyotrophic lateral sclerosis, were considered similar in their etiology to inflammatory diseases, such as remitting relapsing-multiple sclerosis. The ensuing confusion reflected a lack of awareness that the etiology of the disease as well as the origin of the immune cells determines the nature of the inflammatory response, and that inflammation resolution is an active cellular process. The last two decades have seen a revolution in these prevailing dogmas, with a significant contribution made by the authors. Microglia and infiltrating monocyte-derived macrophages are now known to be functionally distinct and of separate origin. Innate and adaptive immune cells are now known to have protective/healing properties in the CNS, as long as their activity is regulated, and their recruitment is well controlled; their role is appreciated in maintenance of brain plasticity in health, aging, and chronic neurodevelopmental and neurodegenerative diseases. Moreover, it is now understood that the barriers of the brain are not uniform in their interactions with the circulating immune cells. The implications of these new findings to the basic understanding of CNS repair processes, brain aging, and a wide spectrum of CNS disorders, including acute injuries, Rett syndrome, Alzheimer's disease, and multiple sclerosis, will be discussed.

SANGUINATE (PEGylated Carboxyhemoglobin Bovine): Mechanism of Action and Clinical Update.

PubMed

Abuchowski, Abraham

2017-04-01

Historically, blood substitutes were under development that would provide oxygen carrying capacity as well as fluid replacement for both trauma and surgical indications. Their development was halted by the inability of the products to deliver therapeutic amounts of oxygen targeted to hypoxic tissue as well as from the inherent toxicity of the molecules. This led to the concept of an oxygen therapeutic that would be targeted for indications caused by anemia/ischemia/hypoxia but would not exhibit the toxicity that plagued earlier products. The complex pathophysiology of diseases such as sickle cell and hemorrhagic stroke not only has hypoxia as a pivotal event but also includes inflammation and vasoconstriction that perpetuate the oxygen deprivation. There is a need for an effective therapeutic that addresses the multiple events of inflammation and oxygen deprivation. SANGUINATE acts as a dual mode carbon monoxide (CO) and oxygen delivery therapeutic. SANGUINATE is designed not only to treat hypoxia but also to act on concurrent pathologies such as inflammation and reperfusion injury. This expands the potential therapeutic utility of SANGUINATE beyond anemia into indications such as early brain injury and delayed kidney graft function, where inflammation plays a pivotal pathological role as well as in indications such as sickle cell disease where the inflammation and hypoxia contribute to the development of comorbidities such as vaso-occlusive crisis. Clinical trials in multiple indications are underway. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

[The autoimmune rheumatic disease and laryngeal pathology].

PubMed

Osipenko, E V; Kotel'nikova, N M

Vocal disorders make up one of the autoimmune pathological conditions characterized by multiple organ system dysfunction. Laryngeal pathology in this condition has an autoimmune nature; it is highly diverse and poorly explored. The objective of the present work based on the analysis of the relevant literature publications was to study clinical manifestations of the autoimmune rheumatic disease affecting the larynx. 'Bamboo nodes' on the vocal folds is a rare manifestation of laryngeal autoimmune diseases. We found out references to 49 cases of this condition in the available literature. All the patients were women presenting with autoimmune diseases. The present review highlights the problems pertaining to etiology of 'bamboo nodes' on the vocal folds and the method for the treatment of this condition.

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.

“End-Stage” Neurofibrillary Tangle Pathology in Preclinical Alzheimer's Disease: Fact or Fiction?

PubMed Central

Abner, Erin L.; Kryscio, Richard J.; Schmitt, Frederick A.; SantaCruz, Karen S.; Jicha, Gregory A.; Lin, Yushun; Neltner, Janna M.; Smith, Charles D.; Van Eldik, Linda J.; Nelson, Peter T.

2011-01-01

Among individuals who were cognitively intact before death, autopsies may reveal some Alzheimer's disease-type pathology. The presence of end-stage pathology in cognitively intact persons would support the hypothesis that pathological markers are epiphenomena. We assessed advanced neurofibrillary (Braak stages V and VI) pathology focusing on nondemented individuals. Data from the National Alzheimer's Coordinating Center database (n = 4,690 included initially) and from the Nun Study (n = 526 included initially) were analyzed, with antemortem information about global cognition and careful postmortem studies available from each case. Global cognition (final Mini-Mental State Examination scores [MMSE] and clinical ‘dementia’ status) was correlated with neuropathology, including the severity of neurofibrillary pathology (Braak stages and neurofibrillary tangle counts in cerebral neocortex). Analyses support three major findings: 1. Braak stage V cases and Braak VI cases are significantly different from each other in terms of associated antemortem cognition; 2. There is an appreciable range of pathology within the category of Braak stage VI based on tangle counts such that brains with the most neurofibrillary tangles in neocortex always had profound antemortem cognitive impairment; and 3. There was no nondemented case with final MMSE score of 30 within a year of life and Braak stage VI pathology. It may be inappropriate to combine Braak stages V and VI cases, particularly in patients with early cognitive dysfunction, since the two pathological stages appear to differ dramatically in terms of both pathological severity and antemortem cognitive status. There is no documented example of truly end-stage neurofibrillary pathology coexisting with intact cognition. PMID:21471646

In vivo imaging of cortical pathology in multiple sclerosis using ultra-high field MRI

PubMed Central

Mainero, C; Benner, T; Radding, A; van der Kouwe, A; Jensen, R; Rosen, B R.; Kinkel, R P.

2009-01-01

Objective: We used ultra-high field MRI to visualize cortical lesion types described by neuropathology in 16 patients with multiple sclerosis (MS) compared with 8 age-matched controls; to characterize the contrast properties of cortical lesions including T2*, T2, T1, and phase images; and to investigate the relationship between cortical lesion types and clinical data. Methods: We collected, on a 7-T scanner, 2-dimensional fast low-angle shot (FLASH)-T2*-weighted spoiled gradient-echo, T2-weighted turbo spin-echo (TSE) images (0.33 × 033 × 1 mm3), and a 3-dimensional magnetization-prepared rapid gradient echo. Results: Overall, 199 cortical lesions were detected in patients on both FLASH-T2* and T2-TSE scans. Seven-tesla MRI allowed for characterization of cortical plaques into type I (leukocortical), type II (intracortical), and type III/IV (subpial extending partly or completely through the cortical width) lesions as described histopathologically. Types III and IV were the most frequent type of cortical plaques (50.2%), followed by type I (36.2%) and type II (13.6%) lesions. Each lesion type was more frequent in secondary progressive than in relapsing–remitting MS. This difference, however, was significant only for type III/IV lesions. T2*-weighted images showed the highest, while phase images showed the lowest, contrast-to-noise ratio for all cortical lesion types. In patients, the number of type III/IV lesions was associated with greater disability (p < 0.02 by Spearman test) and older age (p < 0.04 by Spearman test). Conclusions: Seven-tesla MRI detected different histologic cortical lesion types in our small multiple sclerosis (MS) sample, suggesting, if validated in a larger population, that it may prove a valuable tool to assess the contribution of cortical MS pathology to clinical disability. GLOSSARY ANOVA = analysis of variance; BN = background noise; CNR = contrast-to-noise ratio; DIR = double-inversion recovery; EDSS = Expanded Disability Status Scale; FLAIR = fluid-attenuated inversion recovery; FLASH = fast low-angle shot; GM = gray matter; MPRAGE = magnetization-prepared rapid gradient echo; MR = magnetic resonance; MS = multiple sclerosis; NACGM = normal-appearing cortical gray matter; RF = radiofrequency; ROI = region of interest; RRMS = relapsing–remitting multiple sclerosis; SNR = signal-to-noise ratio; SPMS = secondary progressive multiple sclerosis; TA = time of acquisition; TE = echo time; TR = repetition time; TSE = turbo spin-echo; WM = white matter. PMID:19641168

[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.

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...

[Programmed necrosis and necroptosis - molecular mechanisms].

PubMed

Giżycka, Agata; Chorostowska-Wynimko, Joanna

2015-12-16

Programmed necrosis has been proven vital for organism development and homeostasis maintenance. Its regulatory effects on functional activity of the immune system, as well as on pathways regulating the death mechanisms in cells with diminished apoptotic activity, including malignant cells, have been confirmed. There is also increasing evidence indicating necrosis involvement in many human pathologies. Contrary to previous beliefs, necrosis is not only a passive, pathological, gene-independent process. However, the current knowledge regarding molecular regulation of programmed necrosis is scarce. In part this is due to the multiplicity and complexity of signaling pathways involved in programmed necrosis, as well as the absence of specific cellular markers identifying this process, but also the ambiguous and imprecise international terminology. This review presents the current state of the art on molecular mechanisms of programmed necrosis. In particular, its specific and frequent form, necroptosis, is discussed. The role of RIP1 and RIP3 kinases in this process is presented, as well as the diverse pathways induced by ligation of tumor necrosis factor α, to its receptor, TNFR1, i.e. cell survival, apoptosis or necroptosis.

Clinical and pathological implications of miRNA in bladder cancer

PubMed Central

Braicu, Cornelia; Cojocneanu-Petric, Roxana; Chira, Sergiu; Truta, Anamaria; Floares, Alexandru; Petrut, Bogdan; Achimas-Cadariu, Patriciu; Berindan-Neagoe, Ioana

2015-01-01

MicroRNAs (miRNAs) are small, noncoding RNA species with a length of 20–22 nucleotides that are recognized as essential regulators of relevant molecular mechanisms, including carcinogenesis. Current investigations show that miRNAs are detectable not only in different tissue types but also in a wide range of biological fluids, either free or trapped in circulating microvesicles. miRNAs were proven to be involved in cell communication, both in pathological and physiological processes. Evaluation of the global expression patterns of miRNAs provides key opportunities with important practical applications, taking into account that they modulate essential biological processes such as epithelial to mesenchymal transition, which is a mechanism relevant in bladder cancer. miRNAs collected from biological specimens can furnish valuable evidence with regard to bladder cancer oncogenesis, as they also have been linked to clinical outcomes in urothelial carcinoma. Therefore, a single miRNA or a signature of multiple miRNAs may improve risk stratification of patients and may supplement the histological diagnosis of urological tumors, particularly for bladder cancer. PMID:25653521

[Clinical value of MRI united-sequences examination in diagnosis and differentiation of morphological sub-type of hilar and extrahepatic big bile duct cholangiocarcinoma].

PubMed

Yin, Long-Lin; Song, Bin; Guan, Ying; Li, Ying-Chun; Chen, Guang-Wen; Zhao, Li-Ming; Lai, Li

2014-09-01

To investigate MRI features and associated histological and pathological changes of hilar and extrahepatic big bile duct cholangiocarcinoma with different morphological sub-types, and its value in differentiating between nodular cholangiocarcinoma (NCC) and intraductal growing cholangiocarcinoma (IDCC). Imaging data of 152 patients with pathologically confirmed hilar and extrahepatic big bile duct cholangiocarcinoma were reviewed, which included 86 periductal infiltrating cholangiocarcinoma (PDCC), 55 NCC, and 11 IDCC. Imaging features of the three morphological sub-types were compared. Each of the subtypes demonstrated its unique imaging features. Significant differences (P < 0.05) were found between NCC and IDCC in tumor shape, dynamic enhanced pattern, enhancement degree during equilibrium phase, multiplicity or singleness of tumor, changes in wall and lumen of bile duct at the tumor-bearing segment, dilatation of tumor upstream or downstream bile duct, and invasion of adjacent organs. Imaging features reveal tumor growth patterns of hilar and extrahepatic big bile duct cholangiocarcinoma. MRI united-sequences examination can accurately describe those imaging features for differentiation diagnosis.

Obligatory role for GPER in cardiovascular aging and disease^

PubMed Central

Daniel, Christoph; Sharma, Geetanjali; Amann, Kerstin; Arterburn, Jeffrey B.; Barton, Matthias; Prossnitz, Eric R.

2016-01-01

Pharmacological activation of the heptahelical G protein-coupled receptor GPER by selective ligands counteracts multiple aspects of cardiovascular disease. We thus expected that genetic deletion or pharmacological inhibition of GPER would further aggravate such disease states, particularly with age. To the contrary, we found that genetic ablation of Gper in mice prevented cardiovascular pathologies associated with aging by reducing superoxide (.O2−) formation by NADPH oxidase (Nox) and reduced expression the Nox isoform Nox1. Blocking GPER activity pharmacologically with G36, a synthetic, small molecule, GPER-selective blocker (GRB), decreased Nox1 abundance and .O2− production to basal amounts in cells exposed to angiotensin II and in mice chronically infused with angiotensin II. Thus, this study revealed a role for GPER activity in regulating Nox1 abundance and associated .O2−-mediated structural and functional damage that contributes to disease pathology. Our results indicated that GRBs represent a new class of drugs that can indirectly reduce Nox activity and could be used for the treatment of chronic disease processes involving excessive .O2− formation, including arterial hypertension and diastolic heart failure. PMID:27803283

Gambling in Singapore: an overview of history, research, treatment and policy.

PubMed

Winslow, Munidasa; Cheok, Christopher; Subramaniam, Mythily

2015-09-01

This paper describes the current situation regarding gambling in Singapore in relation to its historical and cultural context. A computerized search was performed of two databases (PubMed and PsychINFO) and the reference lists from the papers searched manually to identify relevant studies. The findings were synthesized and their implications assessed. In addition to state lotteries and much informal gambling, Singapore has two large resort casinos, which rank third after Las Vegas and Macau in terms of gross revenues. The major ethnic subgroups in Singapore have different cultural connections to gambling, including the active involvement of the Chinese and religious prohibition among the Malay. A range of secondary prevention and treatment services has been developed to attempt to minimize potential negative impacts. Overall, the prevalence of pathological gambling and problem gambling has decreased in recent years: an estimated 0.2% are classified as probable pathological gamblers compared with 1.4% in 2011, 1.2% in 2008 and 2.1% in 2005. Singapore has experienced a reduction in problem gambling prevalence which may reflect the influence of multiple initiatives. © 2015 Society for the Study of Addiction.

Programmable 3D silk bone marrow niche for platelet generation ex vivo and modeling of megakaryopoiesis pathologies

PubMed Central

Di Buduo, Christian A.; Wray, Lindsay S.; Tozzi, Lorenzo; Malara, Alessandro; Chen, Ying; Ghezzi, Chiara E.; Smoot, Daniel; Sfara, Carla; Antonelli, Antonella; Spedden, Elise; Bruni, Giovanna; Staii, Cristian; De Marco, Luigi; Magnani, Mauro; Kaplan, David L.

2015-01-01

We present a programmable bioengineered 3-dimensional silk-based bone marrow niche tissue system that successfully mimics the physiology of human bone marrow environment allowing us to manufacture functional human platelets ex vivo. Using stem/progenitor cells, megakaryocyte function and platelet generation were recorded in response to variations in extracellular matrix components, surface topography, stiffness, coculture with endothelial cells, and shear forces. Millions of human platelets were produced and showed to be functional based on multiple activation tests. Using adult hematopoietic progenitor cells our system demonstrated the ability to reproduce key steps of thrombopoiesis, including alterations observed in diseased states. A critical feature of the system is the use of natural silk protein biomaterial allowing us to leverage its biocompatibility, nonthrombogenic features, programmable mechanical properties, and surface binding of cytokines, extracellular matrix components, and endothelial-derived proteins. This in turn offers new opportunities for the study of blood component production ex vivo and provides a superior tissue system for the study of pathologic mechanisms of human platelet production. PMID:25575540

Tau truncation is a productive posttranslational modification of neurofibrillary degeneration in Alzheimer's disease.

PubMed

Kovacech, B; Novak, M

2010-12-01

Deposits of the misfolded neuronal protein tau are major hallmarks of neurodegeneration in Alzheimer's disease (AD) and other tauopathies. The etiology of the transformation process of the intrinsically disordered soluble protein tau into the insoluble misordered aggregate has attracted much attention. Tau undergoes multiple modifications in AD, most notably hyperphosphorylation and truncation. Hyperphosphorylation is widely regarded as the hottest candidate for the inducer of the neurofibrillary pathology. However, the true nature of the impetus that initiates the whole process in the human brains remains unknown. In AD, several site-specific tau cleavages were identified and became connected to the progression of the disease. In addition, western blot analyses of tau species in AD brains reveal multitudes of various truncated forms. In this review we summarize evidence showing that tau truncation alone is sufficient to induce the complete cascade of neurofibrillary pathology, including hyperphosphorylation and accumulation of misfolded insoluble forms of tau. Therefore, proteolytical abnormalities in the stressed neurons and production of aberrant tau cleavage products deserve closer attention and should be considered as early therapeutic targets for Alzheimer's disease.

Pathogenesis of Congenital Rubella Virus Infection in Human Fetuses: Viral Infection in the Ciliary Body Could Play an Important Role in Cataractogenesis.

PubMed

Nguyen, Thong Van; Pham, Van Hung; Abe, Kenji

2015-01-01

Development of congenital rubella syndrome associated with rubella virus infection during pregnancy is clinically important, but the pathogenicity of the virus remains unclear. Pathological examination was conducted on 3 aborted fetuses with congenital rubella infection. At autopsy, all 3 aborted fetuses showed congenital cataract confirmed by gross observation. Rubella virus infection occurred via systemic organs including circulating hematopoietic stem cells confirmed by immunohistochemical and molecular investigations, and major histopathogical changes were found in the liver. It is noteworthy that the virus infected the ciliary body of the eye, suggesting a possible cause of cataracts. Our study based on the pathological examination demonstrated that the rubella virus infection occurred via systemic organs of human fetuses. This fact was confirmed by immunohistochemistry and direct detection of viral RNA in multiple organs. To the best of our knowledge, this study is the first report demonstrating that the rubella virus infection occurred via systemic organs of the human body. Importantly, virus infection of the ciliary body could play an important role in cataractogenesis.

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.

Biomarkers of Amyotrophic Lateral Sclerosis: Current Status and Interest of Oxysterols and Phytosterols

PubMed Central

Vejux, Anne; Namsi, Amira; Nury, Thomas; Moreau, Thibault; Lizard, Gérard

2018-01-01

Amyotrophic lateral sclerosis (ALS) is a non-demyelinating neurodegenerative disease in adults with motor disorders. Two forms exist: a sporadic form (90% of cases) and a family form due to mutations in more than 20 genes including the Superoxide dismutase 1, TAR DNA Binding Protein, Fused in Sarcoma, chromosome 9 open reading frame 72 and VAPB genes. The mechanisms associated with this pathology are beginning to be known: oxidative stress, glutamate excitotoxicity, protein aggregation, reticulum endoplasmic stress, neuroinflammation, alteration of RNA metabolism. In various neurodegenerative diseases, such as Alzheimer’s disease or multiple sclerosis, the involvement of lipids is increasingly suggested based on lipid metabolism modifications. With regard to ALS, research has also focused on the possible involvement of lipids. Lipid involvement was suggested for clinical arguments where changes in cholesterol and LDL/HDL levels were reported with, however, differences in positivity between studies. Since lipids are involved in the membrane structure and certain signaling pathways, it may be considered to look for oxysterols, mainly 25-hydroxycholesterol and its metabolites involved in immune response, or phytosterols to find suitable biomarkers for this pathology. PMID:29445325

Critical role of caveolin-1 in ocular neovascularization and multitargeted antiangiogenic effects of cavtratin via JNK

PubMed Central

Jiang, Yida; Lin, Xianchai; Tang, Zhongshu; Lee, Chunsik; Tian, Geng; Du, Yuxiang; Yin, Xiangke; Ren, Xiangrong; Huang, Lijuan; Ye, Zhimin; Chen, Wei; Zhang, Fan; Mi, Jia; Gao, Zhiqin; Wang, Shasha; Chen, Qishan; Xing, Liying; Wang, Bin; Cao, Yihai; Sessa, William C.; Ju, Rong; Liu, Yizhi; Li, Xuri

2017-01-01

Ocular neovascularization is a devastating pathology of numerous ocular diseases and is a major cause of blindness. Caveolin-1 (Cav-1) plays important roles in the vascular system. However, little is known regarding its function and mechanisms in ocular neovascularization. Here, using comprehensive model systems and a cell permeable peptide of Cav-1, cavtratin, we show that Cav-1 is a critical player in ocular neovascularization. The genetic deletion of Cav-1 exacerbated and cavtratin administration inhibited choroidal and retinal neovascularization. Importantly, combined administration of cavtratin and anti–VEGF-A inhibited neovascularization more effectively than monotherapy, suggesting the existence of other pathways inhibited by cavtratin in addition to VEGF-A. Indeed, we found that cavtratin suppressed multiple critical components of pathological angiogenesis, including inflammation, permeability, PDGF-B and endothelial nitric oxide synthase expression (eNOS). Mechanistically, we show that cavtratin inhibits CNV and the survival and migration of microglia and macrophages via JNK. Together, our data demonstrate the unique advantages of cavtratin in antiangiogenic therapy to treat neovascular diseases. PMID:28923916

PubMed

Monaca, C; Franco, P; Philip, P; Dauvilliers, Y

In the new international classification of sleep disorders (ICSD-3), narcolepsy is differentiated into two distinct pathologies: type 1 narcolepsy (NT1) and type 2 narcolepsy (NT2). NT1 is characterised by periods of an irrepressible need to sleep, cataplexy (a sudden loss of muscle tone triggered by emotion) and in some cases the presence of symptoms such as hypnagogic hallucinations, sleep paralysis and disturbed night-time sleep. Its physiopathology is based on the loss of hypocretin neurons in the hypothalamus, seemingly connected to an auto-immune process. By definition, cataplexy is absent and the hypocretin levels in the CSF are normal in NT2. Confirming the diagnosis requires polysomnography and multiple sleep latency tests. The choice of further investigations is based on the presence or absence of typical cataplexy. Further investigations include HLA typing, lumbar puncture to measure the hypocretin level in the CSF, or even brain imagery in the case of narcolepsy suspected to be secondary to an underlying pathology. In this consensus we propose recommendations for the work-up to be carried out during diagnosis and follow-up for patients suffering from narcolepsy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

In vivo longitudinal MRI and behavioral studies in experimental spinal cord injury.

PubMed

Sundberg, Laura M; Herrera, Juan J; Narayana, Ponnada A

2010-10-01

Comprehensive in vivo longitudinal studies that include multi-modal magnetic resonance imaging (MRI) and a battery of behavioral assays to assess functional outcome were performed at multiple time points up to 56 days post-traumatic spinal cord injury (SCI) in rodents. The MRI studies included high-resolution structural imaging for lesion volumetry, and diffusion tensor imaging (DTI) for probing the white matter integrity. The behavioral assays included open-field locomotion, grid walking, inclined plane, computerized activity box performance, and von Frey filament tests. Additionally, end-point histology was assessed for correlation with both the MRI and behavioral data. The temporal patterns of the lesions were documented on structural MRI. DTI studies showed significant changes in white matter that is proximal to the injury epicenter and persisted to day 56. White matter in regions up to 1 cm away from the injury epicenter that appeared normal on conventional MRI also exhibited changes that were indicative of tissue damage, suggesting that DTI is a more sensitive measure of the evolving injury. Correlations between DTI and histology after SCI could not be firmly established, suggesting that injury causes complex pathological changes in multiple tissue components that affect the DTI measures. Histological evidence confirmed a significant decrease in myelin and oligodendrocyte presence 56 days post-SCI. Multiple assays to evaluate aspects of functional recovery correlated with histology and DTI measures, suggesting that damage to specific white matter tracts can be assessed and tracked longitudinally after SCI.

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).

Does the presence of placental basal plate myometrial fibres increase the risk of subsequent morbidly adherent placenta: a case-control study.

PubMed

Miller, E S; Linn, R L; Ernst, L M

2016-12-01

Antenatal diagnosis of morbidly adherent placenta has been shown to improve outcomes, but existing predictors lack sensitivity. Our objective was to determine whether the presence of myometrial fibres attached to the placental basal plate (BPMYO) in an antecedent pregnancy is associated with subsequent morbidly adherent placenta. A case-control study. Departments of Obstetrics and Gynecology and Pathology, Northwestern University, Chicago, IL, USA. Women who had at least two pregnancies with placental pathological evaluation. Cases were defined as women with evidence of morbidly adherent placenta (both clinically and pathologically) in their most recent pregnancy whereas women without evidence of morbidly adherent placenta served as controls. Pathological specimens of placentas from previous pregnancies were evaluated for BPMYO. The presence of BPMYO on a previous placenta was evaluated to determine whether it could be used to improve the antenatal diagnosis of morbidly adherent placenta. Of the 25 cases of morbidly adherent placenta, 19 (76%) had BPMYO present on their previous placenta compared with 41 (41%) of controls (odds ratio 4.8, 95% CI 1.8-13.0). Adding BPMYO to a regression including other risk factors for morbidly adherent placenta (i.e. maternal age, number of previous caesarean sections, placenta praevia, previous multiple gestation, any previous curettage, and ultrasonographic suspicion of placenta accreta) significantly improved the sensitivity of antenatal diagnosis of morbidly adherent placenta (61% versus 39%, P < 0.001) without a change in specificity (97% versus 97%, P = 1.00). BPMYO on previous placental pathology is associated with an increased risk of morbidly adherent placenta in a subsequent pregnancy. These findings may shed light on the pathophysiology of accreta and inform future research on predictors of accreta. Previous basal plate myometrium improves the ability to detect subsequent morbidly adherent placenta. © 2015 Royal College of Obstetricians and Gynaecologists.

Multiview boosting digital pathology analysis of prostate cancer.

PubMed

Kwak, Jin Tae; Hewitt, Stephen M

2017-04-01

Various digital pathology tools have been developed to aid in analyzing tissues and improving cancer pathology. The multi-resolution nature of cancer pathology, however, has not been fully analyzed and utilized. Here, we develop an automated, cooperative, and multi-resolution method for improving prostate cancer diagnosis. Digitized tissue specimen images are obtained from 5 tissue microarrays (TMAs). The TMAs include 70 benign and 135 cancer samples (TMA1), 74 benign and 89 cancer samples (TMA2), 70 benign and 115 cancer samples (TMA3), 79 benign and 82 cancer samples (TMA4), and 72 benign and 86 cancer samples (TMA5). The tissue specimen images are segmented using intensity- and texture-based features. Using the segmentation results, a number of morphological features from lumens and epithelial nuclei are computed to characterize tissues at different resolutions. Applying a multiview boosting algorithm, tissue characteristics, obtained from differing resolutions, are cooperatively combined to achieve accurate cancer detection. In segmenting prostate tissues, the multiview boosting method achieved≥ 0.97 AUC using TMA1. For detecting cancers, the multiview boosting method achieved an AUC of 0.98 (95% CI: 0.97-0.99) as trained on TMA2 and tested on TMA3, TMA4, and TMA5. The proposed method was superior to single-view approaches, utilizing features from a single resolution or merging features from all the resolutions. Moreover, the performance of the proposed method was insensitive to the choice of the training dataset. Trained on TMA3, TMA4, and TMA5, the proposed method obtained an AUC of 0.97 (95% CI: 0.96-0.98), 0.98 (95% CI: 0.96-0.99), and 0.97 (95% CI: 0.96-0.98), respectively. The multiview boosting method is capable of integrating information from multiple resolutions in an effective and efficient fashion and identifying cancers with high accuracy. The multiview boosting method holds a great potential for improving digital pathology tools and research. Copyright © 2017 Elsevier B.V. All rights reserved.

Correlation between fecal calprotectin and inflammation in the surgical specimen of Crohn's disease.

PubMed

Pous-Serrano, Salvador; Frasson, Matteo; Cerrillo, Elena; Beltrán, Belén; Iborra, Marisa; Hervás, David; García-Granero, Eduardo; Nos, Pilar

2017-06-01

An accurate assessment of the inflammatory activity is crucial to establish the most appropriate treatment in Crohn's disease (CD). The present study aimed to evaluate the utility of preoperative fecal calprotectin (FC) measurement in small bowel CD and its relationship with inflammatory activity in surgical pathology specimens. This was a prospective observational study including all the patients with small bowel CD operated on at our center between March 2011 and September 2013. Preoperative laboratory and stool tests were performed. A meticulous exploration of entire small bowel was performed during surgery, and the resected bowel (or a sample of whole intestinal wall, if strictureplasty) was submitted for pathologic analyses. Chiorean's score was used to grade pathologic features (inflammation or fibrosis). In case of multiple lesions, the most inflammatory component was considered. Thirty-eight consecutive patients were included in the study, and 81 small bowel lesions were identified. Among inflammatory markers, only FC was significantly associated with the degree of histologic inflammation in the surgical specimen (P < 0.003). FC reflected histologic inflammatory activity with an area under the receiver-operating characteristic curve of 0.85 (CI: 0.70-0.99; P < 0.001). A cutoff value of 170 μg/g had 81% sensitivity and 85% specificity for diagnosis of moderate or severe inflammation. Ordinal regression analysis showed the probability of a greater or lesser degree of inflammation based on the value of preoperative FC. FC is an excellent biomarker of inflammatory activity in small bowel CD as it correlates with histologic inflammation in the surgical specimen. Copyright © 2017 Elsevier Inc. All rights reserved.

International Image Concordance Study to Compare a Point of Care Tampon Colposcope to a Standard-of-Care Colposcope

PubMed Central

Mueller, Jenna L.; Asma, Elizabeth; Lam, Christopher T.; Krieger, Marlee S.; Gallagher, Jennifer E.; Erkanli, Alaattin; Hariprasad, Roopa; Malliga, J.S.; Muasher, Lisa C.; Mchome, Bariki; Oneko, Olola; Taylor, Peyton; Venegas, Gino; Wanyoro, Anthony; Mehrotra, Ravi; Schmitt, John W.; Ramanujam, Nimmi

2017-01-01

Objective Barriers to cervical cancer screening in low resource settings include lack of accessible high quality services, high cost, and the need for multiple visits. To address these challenges, we developed a low cost intra-vaginal optical cervical imaging device, the Point of Care Tampon (POCkeT) colposcope, and evaluated whether its performance is comparable to a standard-of-care colposcope. Methods There were two protocols, which included 44 and 18 patients respectively. For the first protocol, white light cervical images were collected in vivo, blinded by device, and sent electronically to 8 physicians from high, middle and low income countries. For the second protocol, green light images were also collected and sent electronically to the highest performing physician from the first protocol who has experience in both a high and low income country. For each image, physicians completed a survey assessing cervix characteristics and severity of precancerous lesions. Corresponding pathology was obtained for all image pairs. Results For the first protocol, average percent agreement between devices was 70% across all physicians. POCkeT and standard-of-care colposcope images had 37% and 51% percent agreement respectively with pathology for high-grade squamous intraepithelial lesions (HSILs). Investigation of HSIL POCkeT images revealed decreased visibility of vascularization and lack of contrast in lesion margins. After changes were made for the second protocol, the two devices achieved similar agreement to pathology for HSIL lesions (55%). Conclusions Based on the exploratory study, physician interpretation of cervix images acquired using a portable, low cost, POCkeT colposcope was comparable to a standard-of-care colposcope. PMID:28263237

Disturbed self concept mediates the relationship between childhood maltreatment and adult personality pathology.

PubMed

Cohen, Lisa; Leibu, Olga; Tanis, Thachell; Ardalan, Firouz; Galynker, Igor

2016-07-01

Despite a robust literature documenting the relationship between childhood maltreatment and personality pathology in adulthood, there is far less clarity about the mechanism underlying this relationship. One promising candidate for such a linking mechanism is disturbance in the sense of self. This paper tests the hypothesis that disturbances in the sense of self mediate the relationship between childhood maltreatment and adult personality pathology. Specifically, we assess the self-related traits of stable self-image, self-reflective functioning, self-respect and feeling recognized. The sample included 113 non-psychotic psychiatric inpatients. Participants completed the Child Trauma Questionnaire (CTQ), the Personality Diagnostic Questionnaire-4 (PDQ-4+), and the self-reflexive functioning, stable self image, self-respect, and feeling recognized scales from the Severity Indices of Personality Problems (SIPP-118). A series of linear regressions was then performed to assess the direct and indirect effects of childhood trauma on personality disorder traits (PDQ-4+ total score), as mediated by self concept (SIPP-118 scales). Aroian tests assessed the statistical significance of each mediating effect. There was a significant mediating effect for all SIPP self concept variables, with a full mediating effect for the SIPP composite score and for SIPP feeling recognized and self-reflexive functioning, such that the direct effect of childhood trauma on personality did not retain significance after accounting for the effect of these variables. There was a partial mediating effect for SIPP stable self image and self-respect, such that the direct effect of the CTQ retained significance after accounting for these variables. SIPP feeling recognized had the strongest mediating effect. Multiple facets of self concept, particularly the degree to which an individual feels understood by other people, may mediate the relationship between childhood maltreatment and adult personality pathology. This underscores the importance of attending to disturbances in the sense of self in patients with personality pathology and a history of childhood maltreatment. These findings also support the centrality of disturbed self concept to the general construct of personality pathology. Copyright © 2016. Published by Elsevier Inc.

Entrustable Professional Activities for Pathology

PubMed Central

Domen, Ronald E.; Conran, Richard M.; Hoffman, Robert D.; Post, Miriam D.; Brissette, Mark D.; Raciti, Patricia M.; Cohen, David A.; Roberts, Cory A.; Rojiani, Amyn M.; Kong, Christina S.; Peterson, Jo Elle G.; Johnson, Kristen; Plath, Sue; Powell, Suzanne Zein-Eldin

2017-01-01

Competency-based medical education has evolved over the past decades to include the Accreditation Council for Graduate Medical Education Accreditation System of resident evaluation based on the Milestones project. Entrustable professional activities represent another means to determine learner proficiency and evaluate educational outcomes in the workplace and training environment. The objective of this project was to develop entrustable professional activities for pathology graduate medical education encompassing primary anatomic and clinical pathology residency training. The Graduate Medical Education Committee of the College of American Pathologists met over the course of 2 years to identify and define entrustable professional activities for pathology graduate medical education. Nineteen entrustable professional activities were developed, including 7 for anatomic pathology, 4 for clinical pathology, and 8 that apply to both disciplines with 5 of these concerning laboratory management. The content defined for each entrustable professional activity includes the entrustable professional activity title, a description of the knowledge and skills required for competent performance, mapping to relevant Accreditation Council for Graduate Medical Education Milestone subcompetencies, and general assessment methods. Many critical activities that define the practice of pathology fit well within the entrustable professional activity model. The entrustable professional activities outlined by the Graduate Medical Education Committee are meant to provide an initial framework for the development of entrustable professional activity–related assessment and curricular tools for pathology residency training. PMID:28725792

[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.

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.

Risk factors for the development of autism spectrum disorder in children with tuberous sclerosis complex: protocol for a systematic review.

PubMed

Mitchell, Rebecca; Barton, Sarah; Harvey, A Simon; Williams, Katrina

2017-03-08

Tuberous sclerosis complex (TSC) is an autosomal dominant condition, caused by mutations in either the TSC1 or TSC2 gene. It has widespread systemic manifestations and is associated with significant neurological morbidity. In addition to seizures and cerebral pathology including cortical tubers, subependymal nodules, subependymal giant cell astrocytoma and abnormal white matter, there are recognised neuropsychiatric difficulties including intellectual disability, autism spectrum disorder (ASD) and a range of learning and behaviour problems, recently conceptualised as "tuberous sclerosis-associated neuropsychiatric disorders", or "TAND". ASD in TSC is of particular importance because (1) it affects up to 50% of people with TSC and is a source of considerable difficulty for them and their families and (2) it provides a model for considering neurobiological pathways involved in ASD. Multiple factors are implicated in the development of ASD in TSC, including (1) seizures and related electrophysiological factors, (2) cerebral pathology, (3) genotype and (4) child characteristics. However, the neurobiological pathway remains unclear. We will conduct a systematic review to investigate and synthesise existing evidence about the role of these risk factors, individually and in combination, in leading to the development of ASD. Our review will report on all studies that include one or more of four predefined risk factors in the development of ASD in children with TSC. We will search five databases: MEDLINE, EMBASE, PubMed, The Cochrane Library and Web of Science (Conference Proceedings Citation Index). Studies will be selected for reporting after two authors independently (1) review all titles and abstracts, (2) read full text of all appropriate papers and (3) assess for bias using the Newcastle-Ottawa Scale recommended by the Guidelines for Meta-Analysis and Systematic Reviews of Observational Studies (MOOSE guidelines) and the ROBINS-I. To our knowledge, this is the first systematic review investigating multiple risk factors in the development of ASD in children with TSC. Clarifying the evidence in this area will be important to researchers in the field and to clinicians providing prognostic information to families. PROSPERO CRD42016042841.

Three-pronged assessment and diagnosis of personality disorder and its consequences: personality functioning, pathological traits, and psychosocial disability.

PubMed

Clark, Lee Anna; Ro, Eunyoe

2014-01-01

The alternative dimensional model of personality disorder (PD) in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5; American Psychiatric Association, 2013), Section III, has two main criteria: impairment in personality functioning and one or more pathological personality traits. The former is defined as disturbances in self-functioning (viz., identity, self-direction), and/or interpersonal functioning (viz., empathy, intimacy). Distinguishing personality functioning and traits is important conceptually, because simply having extreme traits is not necessarily pathological. However, adding personality functioning to PD diagnosis represents an empirical challenge, because the constructs overlap conceptually. Further, there is debate regarding whether diagnosis of mental disorder requires either distress or disability, concepts that also overlap with maladaptive-range personality traits and personality dysfunction. We investigated interrelations among these constructs using multiple self-report measures of each domain in a mixed community-patient sample (N = 402). We examined the structures of functioning (psychosocial disability and personality) and personality traits, first independently, then jointly. The disability/functioning measures yielded the 3 dimensions we have found previously (Ro & Clark, 2013). Trait measures had a hierarchical structure which, at the 5-factor level, reflected neuroticism/negative affectivity (N/NA), (low) sociability, disinhibition, (dis)agreeableness, and rigid goal engagement. When all measures were cofactored, a hierarchical structure again emerged which, at the 5-factor level, included (a) internalizing (N/NA and self-pathology vs. quality-of-life/satisfaction); (b) externalizing (social/interpersonal dysfunction, low sociability, and disagreeableness); (c) disinhibition; (d) poor basic functioning; and (e) rigid goal engagement. Results are discussed in terms of developing an integrated PD diagnostic model.

Odor identification as a biomarker of preclinical AD in older adults at risk

PubMed Central

Poirier, Judes; Etienne, Pierre; Tremblay-Mercier, Jennifer; Frenette, Joanne; Rosa-Neto, Pedro; Breitner, John C.S.

2017-01-01

Objective: To assess odor identification (OI) as an indicator of presymptomatic Alzheimer disease (AD) pathogenesis in cognitively normal aging individuals at increased risk of AD dementia. Methods: In 274 members of the PREVENT-AD cohort of healthy aging persons with a parental or multiple-sibling history of AD dementia, we assessed the cross-sectional association of OI with potential indicators of presymptomatic AD. Some 101 participants donated CSF, thus enabling assessment of AD pathology with the biomarkers total tau (t-tau), phospho-tau (P181-tau), and their ratios with β-amyloid (Aβ1-42). Adjusted analyses considered age, cognition, APOE ε4 status, education, and sex as covariates. We measured OI using the University of Pennsylvania Smell Identification Test and cognitive performance using the Repeatable Battery for Assessment of Neuropsychological Status. Standard kits provided assays of the AD biomarkers. Analyses used robust-fit linear regression models. Results: Reduced OI was associated with lower cognitive score and older age, as well as increased ratios of CSF t-tau and P181-tau to Aβ1-42 (all p < 0.02). However, the observed associations of OI with age and cognition were unapparent in adjusted models that restricted observations to CSF donors and included AD biomarkers. OI showed little association with CSF Aβ1-42 alone except in APOE ε4 carriers having lowest-quartile Aβ1-42 levels. Conclusions: These findings from healthy high-risk older individuals suggest that OI reflects degree of preclinical AD pathology, while its relationships with age and cognition result from the association of these latter variables with such pathology. Diminished OI may be a practical and affordable biomarker of AD pathology. PMID:28659431

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.

Canadian Consensus-based and Evidence-based Guidelines for Benign Endometrial Pathology Reporting in Biopsy Material.

PubMed

Parra-Herran, Carlos; Cesari, Matthew; Djordjevic, Bojana; Grondin, Katherine; Kinloch, Mary; Köbel, Martin; Pirzada, Amrah; Plotkin, Anna; Gilks, C Blake

2018-04-19

Standardized terminology has proven benefits in cancer reporting; in contrast, reporting of benign diagnoses in endometrial biopsy currently lacks such standardization. Unification and update on the lexicon can provide the structure and consistency needed for optimal patient care and quality assurance purposes. The Special Interest Group in Gynecologic Pathology of the Canadian Association of Pathologists-Association Canadienne des Pathologistes (CAP-ACP) embarked in an initiative to address the current need for consensus terminology in benign endometrial biopsy pathology reporting. Nine members of the Special Interest Group developed a guideline for structured diagnosis of benign endometrial pathology through critical appraisal of the available peer-reviewed literature and joint discussions. The first version of the document was circulated for feedback to a group of professionals in akin fields, the CAP-ACP Executive Committee and the CAP-ACP general membership. The final 1-page document included 17 diagnostic terms comprising the most common benign endometrial entities, as well as explanatory notes for pathologists. The proposed terminology was implemented in the practice of 5 pathologists from the group, who applied the guideline to all benign endometrial biopsies over a 2-wk period. A total of 212 benign endometrial biopsies were evaluated in this implementation step; the recommended terminology adequately covered the diagnosis in 203 cases (95.8%). A list of terminology for benign endometrial biopsy reporting, based on expert consensus and critical appraisal of the available literature, is presented. On the basis of our results of implementation at multiple centers, the proposed guideline can successfully cover the large majority of diagnostic scenarios. The document has the potential to positively impact patient care, promote quality assurance, and facilitate research initiatives aimed at improving histopathologic assessment of benign endometrium.

Reimagining the microscope in the 21(st) century using the scalable adaptive graphics environment.

PubMed

Mateevitsi, Victor; Patel, Tushar; Leigh, Jason; Levy, Bruce

2015-01-01

Whole-slide imaging (WSI), while technologically mature, remains in the early adopter phase of the technology adoption lifecycle. One reason for this current situation is that current methods of visualizing and using WSI closely follow long-existing workflows for glass slides. We set out to "reimagine" the digital microscope in the era of cloud computing by combining WSI with the rich collaborative environment of the Scalable Adaptive Graphics Environment (SAGE). SAGE is a cross-platform, open-source visualization and collaboration tool that enables users to access, display and share a variety of data-intensive information, in a variety of resolutions and formats, from multiple sources, on display walls of arbitrary size. A prototype of a WSI viewer app in the SAGE environment was created. While not full featured, it enabled the testing of our hypothesis that these technologies could be blended together to change the essential nature of how microscopic images are utilized for patient care, medical education, and research. Using the newly created WSI viewer app, demonstration scenarios were created in the patient care and medical education scenarios. This included a live demonstration of a pathology consultation at the International Academy of Digital Pathology meeting in Boston in November 2014. SAGE is well suited to display, manipulate and collaborate using WSIs, along with other images and data, for a variety of purposes. It goes beyond how glass slides and current WSI viewers are being used today, changing the nature of digital pathology in the process. A fully developed WSI viewer app within SAGE has the potential to encourage the wider adoption of WSI throughout pathology.

Three-Pronged Assessment and Diagnosis of Personality Disorder and its Consequences: Personality Functioning, Pathological Traits, and Psychosocial Disability

PubMed Central

Clark, Lee Anna; Ro, Eunyoe

2014-01-01

The alternative dimensional model of personality disorder (PD) in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5; American Psychiatric Association, 2013), Section III, has two main criteria: Impairment in personality functioning and one or more pathological personality traits. The former is defined as disturbances in self functioning (viz., identity, self-direction), and/or interpersonal functioning (viz., empathy, intimacy). Distinguishing personality functioning and traits is important conceptually, because simply having extreme traits is not necessarily pathological. However, adding personality functioning to PD diagnosis represents an empirical challenge, because the constructs overlap conceptually. Further, there is debate regarding whether diagnosis of mental disorder requires either distress or disability, concepts that also overlap with maladaptive-range personality traits and personality dysfunction. We investigated interrelations among these constructs using multiple self-report measures of each domain in a mixed community-patient sample (N = 402). We examined the structures of functioning (psychosocial disability and personality), and personality traits, first independently, then jointly. The disability/functioning measures yielded the three dimensions we have found previously (Ro & Clark, 2013). Trait measures had a hierarchical structure which, at the five-factor level, reflected neuroticism/negative affectivity (N/NA), (low) sociability, disinhibition, (dis)agreeableness, and rigid goal engagement. When all measures were co-factored, a hierarchical structure again emerged which, at the five-factor level, included (1) internalizing (N/NA and self-pathology vs. quality-of-life/satisfaction), (2) externalizing (social/interpersonal dysfunction, low sociability, and disagreeableness), (3) disinhibition, (4) poor basic functioning, and (5) rigid goal engagement. Results are discussed in terms of developing an integrated PD diagnostic model. PMID:24588062

Peripheral nerve pathology, including aberrant Schwann cell differentiation, is ameliorated by doxycycline in a laminin-α2-deficient mouse model of congenital muscular dystrophy

PubMed Central

Homma, Sachiko; Beermann, Mary Lou; Miller, Jeffrey Boone

2011-01-01

The most common form of childhood congenital muscular dystrophy, Type 1A (MDC1A), is caused by mutations in the human LAMA2 gene that encodes the laminin-α2 subunit. In addition to skeletal muscle deficits, MDC1A patients typically show a loss of peripheral nerve function. To identify the mechanisms underlying this loss of nerve function, we have examined pathology and cell differentiation in sciatic nerves and ventral roots of the laminin-α2-deficient (Lama2−/−) mice, which are models for MDC1A. We found that, compared with wild-type, sciatic nerves of Lama2−/− mice had a significant increase in both proliferating (Ki67+) cells and premyelinating (Oct6+) Schwann cells, but also had a significant decrease in both immature/non-myelinating [glial fibrillary acidic protein (GFAP)+] and myelinating (Krox20+) Schwann cells. To extend our previous work in which we found that doxycycline, which has multiple effects on mammalian cells, improves motor behavior and more than doubles the median life-span of Lama2−/− mice, we also determined how nerve pathology was affected by doxycycline treatment. We found that myelinating (Krox20+) Schwann cells were significantly increased in doxycycline-treated compared with untreated sciatic nerves. In addition, doxycycline-treated peripheral nerves had significantly less pathology as measured by assays such as amount of unmyelinated or disorganized axons. This study thus identified aberrant proliferation and differentiation of Schwann cells as key components of pathogenesis in peripheral nerves and provided proof-of-concept that pharmaceutical therapy can be of potential benefit for peripheral nerve dysfunction in MDC1A. PMID:21505075

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

Changes in Gene Expression and Metabolism in the Testes of the Rat following Spinal Cord Injury

PubMed Central

Fortune, Ryan D.; Grill, Raymond J.; Beeton, Christine; Tanner, Mark; Huq, Redwan

2017-01-01

Abstract Spinal cord injury (SCI) results in devastating changes to almost all aspects of a patient's life. In addition to a permanent loss of sensory and motor function, males also will frequently exhibit a profound loss of fertility through poorly understood mechanisms. We demonstrate that SCI causes measureable pathology in the testis both acutely (24 h) and chronically up to 1.5 years post-injury, leading to loss in sperm motility and viability. SCI has been shown in humans and rats to induce leukocytospermia, with the presence of inflammatory cytokines, anti-sperm antibodies, and reactive oxygen species found within the ejaculate. Using messenger RNA and metabolomic assessments, we describe molecular and cellular changes that occur within the testis of adult rats over an acute to chronic time period. From 24 h, 72 h, 28 days, and 90 days post-SCI, the testis reveal a distinct time course of pathological events. The testis show an acute drop in normal sexual organ processes, including testosterone production, and establishment of a pro-inflammatory environment. This is followed by a subacute initiation of an innate immune response and loss of cell cycle regulation, possibly due to apoptosis within the seminiferous tubules. At 1.5 years post-SCI, there is a chronic low level immune response as evidenced by an elevation in T cells. These data suggest that SCI elicits a wide range of pathological processes within the testes, the actions of which are not restricted to the acute phase of injury but rather extend chronically, potentially through the lifetime of the subject. The multiplicity of these pathological events suggest a single therapeutic intervention is unlikely to be successful. PMID:27750479

Myelin and oligodendrocyte lineage cells in white matter pathology and plasticity after traumatic brain injury.

PubMed

Armstrong, Regina C; Mierzwa, Amanda J; Sullivan, Genevieve M; Sanchez, Maria A

2016-11-01

Impact to the head or rapid head acceleration-deceleration can cause traumatic brain injury (TBI) with a characteristic pathology of traumatic axonal injury (TAI) and secondary damage in white matter tracts. Myelin and oligodendrocyte lineage cells have significant roles in the progression of white matter pathology after TBI and in the potential for plasticity and subsequent recovery. The myelination pattern of specific brain regions, such as frontal cortex, may also increase susceptibility to neurodegeneration and psychiatric symptoms after TBI. White matter pathology after TBI depends on the extent and distribution of axon damage, microhemorrhages and/or neuroinflammation. TAI occurs in a pattern of damaged axons dispersed among intact axons in white matter tracts. TAI accompanied by bleeding and/or inflammation produces focal regions of overt tissue destruction, resulting in loss of both axons and myelin. White matter regions with TAI may also exhibit demyelination of intact axons. Demyelinated axons that remain viable have the potential for remyelination and recovery of function. Indeed, animal models of TBI have demonstrated demyelination that is associated with evidence of remyelination, including oligodendrocyte progenitor cell proliferation, generation of new oligodendrocytes, and formation of thinner myelin. Changes in neuronal activity that accompany TBI may also involve myelin remodeling, which modifies conduction efficiency along intact myelinated fibers. Thus, effective remyelination and myelin remodeling may be neurobiological substrates of plasticity in neuronal circuits that require long-distance communication. This perspective integrates findings from multiple contexts to propose a model of myelin and oligodendrocyte lineage cell relevance in white matter injury after TBI. This article is part of the Special Issue entitled 'Oligodendrocytes in Health and Disease'. Published by Elsevier Ltd.

Introducing Euro-Glo, a rare earth metal chelate with numerous applications for the fluorescent localization of myelin and amyloid plaques in brain tissue sections.

PubMed

Schmued, Larry; Raymick, James

2017-03-01

The vast majority of fluorochromes are organic in nature and none of the few existing chelates have been applied as histological tracers for localizing brain anatomy and pathology. In this study we have developed and characterized a Europium chelate with the ability to fluorescently label normal and pathological myelin in control and toxicant-exposed rats, as well as the amyloid plaques in aged AD/Tg mice. This study demonstrates how Euro-Glo can be used for the detailed labeling of both normal myelination in the control rat as well as myelin pathology in the kainic acid exposed rat. In addition, this study demonstrates how E-G will label the shell of amyloid plaques in an AD/Tg mouse model of Alzheimer's disease a red color, while the plaque core appears blue in color. The observed E-G staining pattern is compared with that of well characterized tracers specific for the localization of myelin (Black-Gold II), degenerating neurons (Fluoro-Jade C), A-beta aggregates (Amylo-Glo) and glycolipids (PAS). This study represents the first time a rare earth metal (REM) chelate has been used as a histochemical tracer in the brain. This novel tracer, Euro-Glo (E-G), exhibits numerous advantages over conventional organic fluorophores including high intensity emission, high resistance to fading, compatibility with multiple labeling protocols, high Stoke's shift value and an absence of bleed-through of the signal through other filters. Euro-Glo represents the first fluorescent metal chelate to be used as a histochemical tracer, specifically to localize normal and pathological myelin as well as amyloid plaques. Copyright © 2016. Published by Elsevier B.V.

Somatic POLE exonuclease domain mutations are early events in sporadic endometrial and colorectal carcinogenesis, determining driver mutational landscape, clonal neoantigen burden and immune response.

PubMed

Temko, Daniel; Van Gool, Inge C; Rayner, Emily; Glaire, Mark; Makino, Seiko; Brown, Matthew; Chegwidden, Laura; Palles, Claire; Depreeuw, Jeroen; Beggs, Andrew; Stathopoulou, Chaido; Mason, John; Baker, Ann-Marie; Williams, Marc; Cerundolo, Vincenzo; Rei, Margarida; Taylor, Jenny C; Schuh, Anna; Ahmed, Ahmed; Amant, Frédéric; Lambrechts, Diether; Smit, Vincent Thbm; Bosse, Tjalling; Graham, Trevor A; Church, David N; Tomlinson, Ian

2018-03-31

Genomic instability, which is a hallmark of cancer, is generally thought to occur in the middle to late stages of tumourigenesis, following the acquisition of permissive molecular aberrations such as TP53 mutation or whole genome doubling. Tumours with somatic POLE exonuclease domain mutations are notable for their extreme genomic instability (their mutation burden is among the highest in human cancer), distinct mutational signature, lymphocytic infiltrate, and excellent prognosis. To what extent these characteristics are determined by the timing of POLE mutations in oncogenesis is unknown. Here, we have shown that pathogenic POLE mutations are detectable in non-malignant precursors of endometrial and colorectal cancer. Using genome and exome sequencing, we found that multiple driver mutations in POLE-mutant cancers show the characteristic POLE mutational signature, including those in genes conventionally regarded as initiators of tumourigenesis. In POLE-mutant cancers, the proportion of monoclonal predicted neoantigens was similar to that in other cancers, but the absolute number was much greater. We also found that the prominent CD8 + T-cell infiltrate present in POLE-mutant cancers was evident in their precursor lesions. Collectively, these data indicate that somatic POLE mutations are early, quite possibly initiating, events in the endometrial and colorectal cancers in which they occur. The resulting early onset of genomic instability may account for the striking immune response and excellent prognosis of these tumours, as well as their early presentation. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Reimagining the microscope in the 21st century using the scalable adaptive graphics environment

PubMed Central

Mateevitsi, Victor; Patel, Tushar; Leigh, Jason; Levy, Bruce

2015-01-01

Background: Whole-slide imaging (WSI), while technologically mature, remains in the early adopter phase of the technology adoption lifecycle. One reason for this current situation is that current methods of visualizing and using WSI closely follow long-existing workflows for glass slides. We set out to “reimagine” the digital microscope in the era of cloud computing by combining WSI with the rich collaborative environment of the Scalable Adaptive Graphics Environment (SAGE). SAGE is a cross-platform, open-source visualization and collaboration tool that enables users to access, display and share a variety of data-intensive information, in a variety of resolutions and formats, from multiple sources, on display walls of arbitrary size. Methods: A prototype of a WSI viewer app in the SAGE environment was created. While not full featured, it enabled the testing of our hypothesis that these technologies could be blended together to change the essential nature of how microscopic images are utilized for patient care, medical education, and research. Results: Using the newly created WSI viewer app, demonstration scenarios were created in the patient care and medical education scenarios. This included a live demonstration of a pathology consultation at the International Academy of Digital Pathology meeting in Boston in November 2014. Conclusions: SAGE is well suited to display, manipulate and collaborate using WSIs, along with other images and data, for a variety of purposes. It goes beyond how glass slides and current WSI viewers are being used today, changing the nature of digital pathology in the process. A fully developed WSI viewer app within SAGE has the potential to encourage the wider adoption of WSI throughout pathology. PMID:26110092

A Retrospective Analysis of Radiographic Jaw Findings in Young Women; Prevalence and Predictors

PubMed Central

El Khateeb, Sara M.; Abu-Hammad, Osama; Fadel, Hani; Dar-Odeh, Najla

2017-01-01

Aims and Objectives: To determine the prevalence and types of jaw pathologic findings as detected in panoramic radiographs of a sample of young women attending a teaching hospital in Al Madinah Al Munawarah, Saudi Arabia, and to determine the most important factors that predict the occurrence of jaw pathologic findings. Materials and Methods: The electronic clinical files of a representative sample of female patients who attended the outpatient dental clinics were retrieved. Patients were aged 18 to 25 years. Types of pathologic radiographic jaw findings and their prevalence were determined through screening of panoramic radiographs. Data were analyzed using the statistical analysis software [SPSS version 21 (IBM Corp.)]. Multiple linear regression was used to explore the significance of some types of dental lesions as predictor variables for the occurrence of jaw pathologic findings. Results: A total of 190 patients (mean age, 22.4 ± 2.46 years) were included in the study. Periapical lesions, retained roots, and alveolar bone loss were detected in 53.6%, 24.8%, and 17.4% of the participants, respectively. Other odontogenic abnormalities such as supernumerary and impacted teeth (6.4% and 33.7%, respectively) were also detected. Patients' age was found to be a good predictor for alveolar bone loss and number of periapical lesions (P ≤ 0.05). Conclusions: A high prevalence of periapical lesions, retained roots, and alveolar bone loss was found among a sample of young female dental attendees, as shown by their panoramic radiographs. Further studies are needed to explore potential risk factors for such a noticeable trend of poor oral health, and the needed strategies to counteract this trend. PMID:28316945

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

DTIC Science & Technology

2014-02-01

release; distribution unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Athletes in contact sports who have sustained multiple concussive traumatic...who have sustained multiple concussive traumatic brain injuries 15-17 may also be at risk for this condition. Currently, there are no methods to...11 Appendices……………………………………………………………………………... 12 4 INTRODUCTION: Athletes in contact sports who have sustained multiple concussive

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

DTIC Science & Technology

2014-02-01

multiple concussive traumatic brain injuries are at high risk for delayed, progressive neurological and psychiatric deterioration 1-9. This syndrome is...personnel 13, 14 and others who have sustained multiple concussive traumatic brain injuries 15-17 may also be at risk for this condition. Currently...11 Appendices……………………………………………………………………………... 12 4 INTRODUCTION: Athletes in contact sports who have sustained multiple concussive traumatic

Enhancement of hepatitis virus immunoassay outcome predictions in imbalanced routine pathology data by data balancing and feature selection before the application of support vector machines.

PubMed

Richardson, Alice M; Lidbury, Brett A

2017-08-14

Data mining techniques such as support vector machines (SVMs) have been successfully used to predict outcomes for complex problems, including for human health. Much health data is imbalanced, with many more controls than positive cases. The impact of three balancing methods and one feature selection method is explored, to assess the ability of SVMs to classify imbalanced diagnostic pathology data associated with the laboratory diagnosis of hepatitis B (HBV) and hepatitis C (HCV) infections. Random forests (RFs) for predictor variable selection, and data reshaping to overcome a large imbalance of negative to positive test results in relation to HBV and HCV immunoassay results, are examined. The methodology is illustrated using data from ACT Pathology (Canberra, Australia), consisting of laboratory test records from 18,625 individuals who underwent hepatitis virus testing over the decade from 1997 to 2007. Overall, the prediction of HCV test results by immunoassay was more accurate than for HBV immunoassay results associated with identical routine pathology predictor variable data. HBV and HCV negative results were vastly in excess of positive results, so three approaches to handling the negative/positive data imbalance were compared. Generating datasets by the Synthetic Minority Oversampling Technique (SMOTE) resulted in significantly more accurate prediction than single downsizing or multiple downsizing (MDS) of the dataset. For downsized data sets, applying a RF for predictor variable selection had a small effect on the performance, which varied depending on the virus. For SMOTE, a RF had a negative effect on performance. An analysis of variance of the performance across settings supports these findings. Finally, age and assay results for alanine aminotransferase (ALT), sodium for HBV and urea for HCV were found to have a significant impact upon laboratory diagnosis of HBV or HCV infection using an optimised SVM model. Laboratories looking to include machine learning via SVM as part of their decision support need to be aware that the balancing method, predictor variable selection and the virus type interact to affect the laboratory diagnosis of hepatitis virus infection with routine pathology laboratory variables in different ways depending on which combination is being studied. This awareness should lead to careful use of existing machine learning methods, thus improving the quality of laboratory diagnosis.

N-acetylcysteine (NAC) ameliorates Epstein-Barr virus latent membrane protein 1 induced chronic inflammation.

PubMed

Gao, Xiao; Lampraki, Eirini-Maria; Al-Khalidi, Sarwah; Qureshi, Muhammad Asif; Desai, Rhea; Wilson, Joanna Beatrice

2017-01-01

Chronic inflammation results when the immune system responds to trauma, injury or infection and the response is not resolved. It can lead to tissue damage and dysfunction and in some cases predispose to cancer. Some viruses (including Epstein-Barr virus (EBV)) can induce inflammation, which may persist even after the infection has been controlled or cleared. The damage caused by inflammation, can itself act to perpetuate the inflammatory response. The latent membrane protein 1 (LMP1) of EBV is a pro-inflammatory factor and in the skin of transgenic mice causes a phenotype of hyperplasia with chronic inflammation of increasing severity, which can progress to pre-malignant and malignant lesions. LMP1 signalling leads to persistent deregulated expression of multiple proteins throughout the mouse life span, including TGFα S100A9 and chitinase-like proteins. Additionally, as the inflammation increases, numerous chemokines and cytokines are produced which promulgate the inflammation. Deposition of IgM, IgG, IgA and IgE and complement activation form part of this process and through genetic deletion of CD40, we show that this contributes to the more tissue-destructive aspects of the phenotype. Treatment of the mice with N-acetylcysteine (NAC), an antioxidant which feeds into the body's natural redox regulatory system through glutathione synthesis, resulted in a significantly reduced leukocyte infiltrate in the inflamed tissue, amelioration of the pathological features and delay in the inflammatory signature measured by in vivo imaging. Reducing the degree of inflammation achieved through NAC treatment, had the knock on effect of reducing leukocyte recruitment to the inflamed site, thereby slowing the progression of the pathology. These data support the idea that NAC could be considered as a treatment to alleviate chronic inflammatory pathologies, including post-viral disease. Additionally, the model described can be used to effectively monitor and accurately measure therapies for chronic inflammation.

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.

Non-syndromic multiple supernumerary teeth in permanent dentition: a rare phenomenon

PubMed Central

Yadav, Rakesh Kumar; Rao, Jitendra; Yadav, Lakhya; Hasija, Mukesh

2013-01-01

Hyperdontia or supernumerary teeth in the absence of associated systemic condition or syndrome is an uncommon phenomenon. Non-syndromic supernumerary teeth need to have periodical radiographic observation. In the case of asymptomatic condition, as they impacted in the jaw, a careful examination is necessary because they may develop into pathological status such as dentigerous cysts. Surgical removal of such teeth is indicated if evidence of any pathologies, such as cystic lesion, resorption, delayed eruption, altered eruption and displacement of adjacent teeth, is evident or have occurred. PMID:23704431

Ureteritis Cystica: A Radiologic Pathologic Correlation

PubMed Central

Rothschild, Jennifer G; Wu, Guan

2011-01-01

Ureteritis cystica (UC) is a benign condition that commonly affects the ureter and can mimic other conditions such as transitional cell carcinoma, blood clots, air bubbles, radiolucent stones, fibroepithelial polyps, and sloughed renal papillae. Radiographically, UC is characterized by multiple small, round, lucent defects, which cause scalloping of the ureteral margins when seen in profile. The scalloping is produced by the projection of the submucosal cysts into the lumen and represents an important differential feature of this disease. We present a case of UC with a radiological pathological correlation. PMID:21966620

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.

A Suggested Molecular Pathology Curriculum for Residents: A Report of the Association for Molecular Pathology.

PubMed

Aisner, Dara L; Berry, Anna; Dawson, D Brian; Hayden, Randall T; Joseph, Loren; Hill, Charles E

2016-03-01

Molecular pathology is an essential element of pathology training. As more molecular tests have become available, there is an increasing need for pathology trainees to receive a strong foundation in molecular pathology. Appointed by the Training and Education Committee of the Association for Molecular Pathology, the Molecular Curriculum Task Force has developed a suggested curriculum in molecular pathology for residents. The foundations of molecular pathology are presented as a series of goals and objectives that residency programs can use to develop their educational programs. As pathologists continue to expand their roles to include regular clinical consultations in the realm of molecular testing, a strong foundation in molecular pathology and genomic medicine has become essential to the practice of pathology. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Mass murder in a university setting: analysis of the medical examiner's response.

PubMed

Fierro, Marcella F

2007-09-01

Seung-Hui Cho, a student at Virginia Polytechnic Institute and State University (Virginia Tech), shot and killed 33 students and faculty, including himself, on the morning of April 16, 2007. A retrospective review of the medical examiner system response to this multiple fatality event was undertaken to identify which procedures were and were not effective. Case records, spreadsheets, telephone call logs, notes, and after-action interviews of staff were reviewed and analyzed. Recommendations were developed to improve the management of the multiple components of a high-profile multiple fatality event. One autopsy took place on Monday, April 16, 12 on Tuesday, April 17, and 20 on Wednesday, April 18. Pathologists archived the biopsies of major organs in formalin. Slides were made of entrance wounds that exhibited residues. Blood for alcohols was collected from victims. Blood for alcohols, acid, base, and neutral drugs was collected from Cho for analysis. Standard forensic pathology procedures worked and timely postmortem examinations were completed. The victim identification component of the family assistance center must be established and staffed at the time of the initial response. Public information officers need training in morgue and medicolegal death management and in ways to effectively communicate with different audiences about multiple fatality management procedures.

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.

The application of multiple biophysical cues to engineer functional neocartilage for treatment of osteoarthritis. Part II: signal transduction.

PubMed

Brady, Mariea A; Waldman, Stephen D; Ethier, C Ross

2015-02-01

The unique mechanoelectrochemical environment of cartilage has motivated researchers to investigate the effect of multiple biophysical cues, including mechanical, magnetic, and electrical stimulation, on chondrocyte biology. It is well established that biophysical stimuli promote chondrocyte proliferation, differentiation, and maturation within "biological windows" of defined dose parameters, including mode, frequency, magnitude, and duration of stimuli (see companion review Part I: Cellular Response). However, the underlying molecular mechanisms and signal transduction pathways activated in response to multiple biophysical stimuli remain to be elucidated. Understanding the mechanisms of biophysical signal transduction will deepen knowledge of tissue organogenesis, remodeling, and regeneration and aiding in the treatment of pathologies such as osteoarthritis. Further, this knowledge will provide the tissue engineer with a potent toolset to manipulate and control cell fate and subsequently develop functional replacement cartilage. The aim of this article is to review chondrocyte signal transduction pathways in response to mechanical, magnetic, and electrical cues. Signal transduction does not occur along a single pathway; rather a number of parallel pathways appear to be activated, with calcium signaling apparently common to all three types of stimuli, though there are different modes of activation. Current tissue engineering strategies, such as the development of "smart" functionalized biomaterials that enable the delivery of growth factors or integration of conjugated nanoparticles, may further benefit from targeting known signal transduction pathways in combination with external biophysical cues.

Enucleation and limited pancreatic resection provide long-term cure for insulinoma in multiple endocrine neoplasia type 1.

PubMed

Bartsch, Detlef K; Albers, Max; Knoop, Richard; Kann, Peter H; Fendrich, Volker; Waldmann, Jens

2013-01-01

To assess the characteristics and long-term outcome after surgery in patients with multiple endocrine neoplasia type 1 (MEN1)-associated insulinoma. Retrospective analysis of prospectively collected data of MEN1 patients with organic hyperinsulinism at a tertiary referral center. Thirteen (17%) of 74 patients with MEN1 had organic hyperinsulinism. The median age at diagnosis was 27 (range 9-48) years. In 7 patients insulinoma was the first manifestation of the syndrome. All patients had at least one pancreatic neuroendocrine neoplasm (pNEN) upon imaging, including CT, MRI or endoscopic ultrasonography. Seven patients had solitary lesions upon imaging, 4 patients had one dominant tumor with coexisting multiple small pNENs, and 2 patients had multiple lesions without dominance. Eight patients had limited resections (1 segmental resection, 7 enucleations), 4 subtotal distal pancreatectomies, and 1 patient a partial duodenopancreatectomy. There was no postoperative mortality. Six patients experienced complications, including pancreatic fistula in 5 patients. Pathological examination revealed median three (range 1-14) macro-pNENs sized between 6 and 40 mm, and a total of 14 potentially benign insulinomas were detected in the 13 patients. After median follow-up of 156 months, only 1 patient developed recurrent hyperinsulinism after initial enucleation. Twelve patients developed new pNENs in the pancreatic remnant and 4 patients underwent reoperations (3 for metastatic ZES, 1 for recurrent hyperinsulinism). One of 5 patients with an initial extended pancreatic resection developed insulin-dependent diabetes mellitus. Enucleation and limited resection provide long-term cure for MEN1 insulinoma in patients with solitary or dominant tumors. Subtotal distal pancreatectomy should thus be preserved for patients with multiple pNENs without dominance given the risk of exocrine and endocrine pancreas insufficiency in the mostly young patients. © 2013 S. Karger AG, Basel.

Airway reconstruction: review of an approach to the advanced-stage laryngotracheal stenosis.

PubMed

Bitar, Mohamad Ahmad; Al Barazi, Randa; Barakeh, Rana

The management of laryngotracheal stenosis is complex and is influenced by multiple factors that can affect the ultimate outcome. Advanced lesions represent a special challenge to the treating surgeon to find the best remedying technique. To review the efficacy of our surgical reconstructive approach in managing advanced-stage laryngotracheal stenosis treated at a tertiary medical center. A retrospective review of all patients that underwent open laryngotracheal repair/reconstruction by the senior author between 2002 and 2014. Patients with mild/moderate stenosis (e.g. stage 1 or 2), or those who had an open reconstructive procedure prior to referral, were excluded. Patients who had only endoscopic treatment (e.g. laser, balloon dilatation) and were not subjected to an open reconstructive procedure at our institution, were not included in this study. Variables studied included patient demographics, clinical presentation, etiology of the laryngotracheal pathology, the location of stenosis, the stage of stenosis, the type of corrective or reconstructive procedure performed with the type of graft used (where applicable), the type and duration of stent used, the post-reconstruction complications, and the duration of follow-up. Outcome measures included decannulation rate, total number of reconstructive surgeries needed to achieve decannulation, and the number of post-operative endoscopies needed to reach a safe patent airway. Twenty five patients were included, aged 0.5 months to 45 years (mean 13.5 years, median 15 years) with 16 males and 9 females. Seventeen patients (68%) were younger than 18 years. Most patients presented with stridor, failure of decannulation, or respiratory distress. Majority had acquired etiology for their stenosis with only 24% having a congenital pathology. Thirty-two reconstructive procedures were performed resulting in decannulating 24 patients (96%), with 15/17 (88%) pediatric patients and 5/8 (62.5%) adult patients requiring only a single reconstructive procedure. Cartilage grafts were mostly used in children (84% vs. 38%) and stents were mostly silicone made, followed by endotracheal tubes. The number of endoscopies required ranged from 1 to 7 (mean 3). More co-morbidities existed in young children, resulting in failure to decannulate one patient. Adult patients had more complex pathologies requiring multiple procedures to achieve decannulation, with grafting less efficacious than in younger patients. The pediatric patients had double the incidence of granulation tissue compared to adults. The decannulated patients remained asymptomatic at a mean follow-up of 50.5 months. The review of our approach to open airway repair/reconstruction showed its efficacy in advanced-stage laryngotracheal stenosis. Good knowledge of a variety of reconstructive techniques is important to achieve good results in a variety of age groups. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

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.

[Diagnostic significance of pathologic synkinesis for detection of pyramidal pathology].

PubMed

Baliasnyĭ, M M

1991-01-01

Five types of pathological synkinesis (++blepharo-ocular, ++blepharo-facial, ++bucco-manual, ++digito-digital on the hands, ++pedo-digital) are described. They are of definite importance for revealing pyramidal pathology including its early stages as well as for objective evaluation and observation of the time-course of changes in the illness.

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.

Entrustable Professional Activities for Pathology: Recommendations From the College of American Pathologists Graduate Medical Education Committee.

PubMed

McCloskey, Cindy B; Domen, Ronald E; Conran, Richard M; Hoffman, Robert D; Post, Miriam D; Brissette, Mark D; Gratzinger, Dita A; Raciti, Patricia M; Cohen, David A; Roberts, Cory A; Rojiani, Amyn M; Kong, Christina S; Peterson, Jo Elle G; Johnson, Kristen; Plath, Sue; Powell, Suzanne Zein-Eldin

2017-01-01

Competency-based medical education has evolved over the past decades to include the Accreditation Council for Graduate Medical Education Accreditation System of resident evaluation based on the Milestones project. Entrustable professional activities represent another means to determine learner proficiency and evaluate educational outcomes in the workplace and training environment. The objective of this project was to develop entrustable professional activities for pathology graduate medical education encompassing primary anatomic and clinical pathology residency training. The Graduate Medical Education Committee of the College of American Pathologists met over the course of 2 years to identify and define entrustable professional activities for pathology graduate medical education. Nineteen entrustable professional activities were developed, including 7 for anatomic pathology, 4 for clinical pathology, and 8 that apply to both disciplines with 5 of these concerning laboratory management. The content defined for each entrustable professional activity includes the entrustable professional activity title, a description of the knowledge and skills required for competent performance, mapping to relevant Accreditation Council for Graduate Medical Education Milestone subcompetencies, and general assessment methods. Many critical activities that define the practice of pathology fit well within the entrustable professional activity model. The entrustable professional activities outlined by the Graduate Medical Education Committee are meant to provide an initial framework for the development of entrustable professional activity-related assessment and curricular tools for pathology residency training.

Opportunities for Improvement in Pathology Reporting of Childhood Nonrhabdomyosarcoma Soft Tissue Sarcomas:  A Report From Children's Oncology Group (COG) Study ARST0332.

PubMed

Black, Jennifer O; Coffin, Cheryl M; Parham, David M; Hawkins, Douglas S; Speights, Rose A; Spunt, Sheri L

2016-09-01

Treatment of soft tissue tumors in young patients relies on the diagnostic information conveyed in the pathology report. We examined pathology reports from Children's Oncology Group ARST0332 for inclusion of data elements required in published guidelines. Pathology reports for 551 eligible patients were examined for required data elements defined by the College of American Pathologists, including tissue type, procedure, tumor site, tumor maximum diameter, macroscopic extent of tumor, histologic type, mitotic rate, extent of necrosis, tumor grade, margin status, use of ancillary studies, and pathologic stage. Only 65 (12%) of 551 reports included all required data elements. Of reports containing synoptic templates, 57% were complete. This study reveals significant opportunity to improve the quality of pathology reports in young patients with soft tissue tumors. Use of templates or checklists improves completeness of reports. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Methods for the Detection of Autophagy in Mammalian Cells

PubMed Central

Zhang, Ziyan; Singh, Rajat; Aschner, Michael

2016-01-01

Macroautophagy (hereafter referred to as autophagy) is a degradation pathway that delivers cytoplasmic materials to lysosomes via double-membraned vesicles designated autophagosomes. Cytoplasmic constituents are sequestered into autophagosomes, which subsequently fuse with lysosomes, where the cargo is degraded. Autophagy is a crucial mechanism involved in many aspects of cell function, including cellular metabolism and energy balance; and alterations in autophagy have been linked to various human pathological processes. Thus, methods that accurately measure autophagic activity are necessary. In this unit, we introduce several approaches to analyze autophagy in mammalian cells, including immunoblotting analysis of LC3 and p62, detection of autophagosome formation by fluorescence microscopy, and monitoring autophagosome maturation by tandem mRFP-GFP fluorescence microscopy. Overall, we recommend a combined use of multiple methods to accurately assess the autophagic activity in any given biological setting. PMID:27479363

Mediator complex dependent regulation of cardiac development and disease.

PubMed

Grueter, Chad E

2013-06-01

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality. The risk factors for CVD include environmental and genetic components. Human mutations in genes involved in most aspects of cardiovascular function have been identified, many of which are involved in transcriptional regulation. The Mediator complex serves as a pivotal transcriptional regulator that functions to integrate diverse cellular signals by multiple mechanisms including recruiting RNA polymerase II, chromatin modifying proteins and non-coding RNAs to promoters in a context dependent manner. This review discusses components of the Mediator complex and the contribution of the Mediator complex to normal and pathological cardiac development and function. Enhanced understanding of the role of this core transcriptional regulatory complex in the heart will help us gain further insights into CVD. Copyright © 2013. Production and hosting by Elsevier Ltd.

Consequences of not treating children with laron syndrome (primary growth hormone insensitivity).

PubMed

Laron, Z

2001-01-01

The follow-up of a large cohort of patients with Laron syndrome (LS) from infancy to adult age has enabled us to determine the effects of long-term insulin-like growth factor-I (IGF-I) deficiency on auxological, biochemical, physiological and psychological parameters. We found that early and continuous IGF-I deficiency (the anabolic effector of growth hormone) causes dwarfism, acromicria, organomicria, marked obesity, insulin resistance, retardation of skeletal maturation and osteoporosis, as well as muscular and central nervous tissue underdevelopment, and a series of biochemical changes including hypercholesterolemia. These multiple pathologies impair the quality of life of these patients. It is concluded that patients with LS need IGF-I replacement treatment throughout life.

Computer vision elastography: speckle adaptive motion estimation for elastography using ultrasound sequences.

PubMed

Revell, James; Mirmehdi, Majid; McNally, Donal

2005-06-01

We present the development and validation of an image based speckle tracking methodology, for determining temporal two-dimensional (2-D) axial and lateral displacement and strain fields from ultrasound video streams. We refine a multiple scale region matching approach incorporating novel solutions to known speckle tracking problems. Key contributions include automatic similarity measure selection to adapt to varying speckle density, quantifying trajectory fields, and spatiotemporal elastograms. Results are validated using tissue mimicking phantoms and in vitro data, before applying them to in vivo musculoskeletal ultrasound sequences. The method presented has the potential to improve clinical knowledge of tendon pathology from carpel tunnel syndrome, inflammation from implants, sport injuries, and many others.

Multiorgan failure following mass wasp stings.

PubMed

Lin, Cheng-Jui; Wu, Chih-Jen; Chen, Han-Hsiang; Lin, Hsin-Chang

2011-05-01

Wasp bites usually bring temporary discomfort and pain, but on occasion, they can cause serious infections and fatal allergic reactions. We report on a patient who experienced massive wasp stings and developed multiple organ failure, including acute kidney, hepatic failure, and circulatory collapse 4 days later. He was treated with aggressive fluid resuscitation, inotropic agent, intravenous injection of steroids, broad-spectrum antibiotics, and hemodialysis. After intensive treatment, his liver function recovered one month later. Recovery of renal function was delayed, and the patient needed temporary regular hemodialysis. The pathology of kidney biopsy showed acute tubulointerstitial nephritis. This case shows that toxic reactions following massive wasp attacks may happen several days after the fact and result in severe, multiorgan system dysfunction.

Integrative, multimodal analysis of glioblastoma using TCGA molecular data, pathology images, and clinical outcomes.

PubMed

Kong, Jun; Cooper, Lee A D; Wang, Fusheng; Gutman, David A; Gao, Jingjing; Chisolm, Candace; Sharma, Ashish; Pan, Tony; Van Meir, Erwin G; Kurc, Tahsin M; Moreno, Carlos S; Saltz, Joel H; Brat, Daniel J

2011-12-01

Multimodal, multiscale data synthesis is becoming increasingly critical for successful translational biomedical research. In this letter, we present a large-scale investigative initiative on glioblastoma, a high-grade brain tumor, with complementary data types using in silico approaches. We integrate and analyze data from The Cancer Genome Atlas Project on glioblastoma that includes novel nuclear phenotypic data derived from microscopic slides, genotypic signatures described by transcriptional class and genetic alterations, and clinical outcomes defined by response to therapy and patient survival. Our preliminary results demonstrate numerous clinically and biologically significant correlations across multiple data types, revealing the power of in silico multimodal data integration for cancer research.

Posttransplant lymphoproliferative disorder in an 11-year-old immunosuppressed boy.

PubMed

Nelson, Alex; Dhamija, Radhika; Nickels, Katherine

2013-05-01

We present an 11-year-old boy who presented with symptoms of subacute facial nerve palsy after cardiac transplant. Neuroimaging revealed multiple ring-enhancing lesions that were most concerning for opportunistic organism abscesses and he was treated with broad-spectrum antifungal and antibacterial therapy. After noninvasive testing failed to identify a causative organism, he underwent brain biopsy. Pathology revealed posttransplant lymphoproliferative disease that was later determined to be isolated to the central nervous system. The patient was treated with reduction in his immunotherapy and chemotherapy including rituximab and methotrexate. This case exemplifies the importance of having a low threshold to consider posttransplant lymphoproliferative disease in posttransplant patients. Copyright © 2013 Elsevier Inc. All rights reserved.

A Retrospective Examination of Feline Leukemia Subgroup Characterization: Viral Interference Assays to Deep Sequencing.

PubMed

Chiu, Elliott S; Hoover, Edward A; VandeWoude, Sue

2018-01-10

Feline leukemia virus (FeLV) was the first feline retrovirus discovered, and is associated with multiple fatal disease syndromes in cats, including lymphoma. The original research conducted on FeLV employed classical virological techniques. As methods have evolved to allow FeLV genetic characterization, investigators have continued to unravel the molecular pathology associated with this fascinating agent. In this review, we discuss how FeLV classification, transmission, and disease-inducing potential have been defined sequentially by viral interference assays, Sanger sequencing, PCR, and next-generation sequencing. In particular, we highlight the influences of endogenous FeLV and host genetics that represent FeLV research opportunities on the near horizon.

The hypocretins/orexins: integrators of multiple physiological functions

PubMed Central

Li, Jingcheng; Hu, Zhian; Lecea, Luis

2014-01-01

The hypocretins (Hcrts), also known as orexins, are two peptides derived from a single precursor produced in the posterior lateral hypothalamus. Over the past decade, the orexin system has been associated with numerous physiological functions, including sleep/arousal, energy homeostasis, endocrine, visceral functions and pathological states, such as narcolepsy and drug abuse. Here, we review the discovery of Hcrt/orexins and their receptors and propose a hypothesis as to how the orexin system orchestrates these multifaceted physiological functions. Linked ArticlesThis article is part of a themed section on Orexin Receptors. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-2 PMID:24102345

MRI-guided Wire Localization Surgical Biopsy in an Adolescent Patient with a Difficult to Diagnose Case of Lymphoma

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

Thompson, Scott M., E-mail: Thompson.scott@mayo.edu; Gorny, Krzysztof R.; Jondal, Danielle E.

A 17-year-old previously healthy female presented with a progressive soft tissue infiltrative process involving the neck and thorax. Extensive diagnostic evaluation including multiple imaging, laboratory, and biopsy studies was nondiagnostic. Due to an urgent need to establish a diagnosis and several previous nondiagnostic biopsies, she was referred to interventional radiology for MRI-guided wire localization immediately prior to open surgical biopsy. Under general anesthesia, wires were placed in the areas of increased T2 signal within the bilateral splenius capitis muscles using intermittent MRI-guidance followed by immediate surgical biopsy down to the wires. Pathology confirmed the diagnosis of diffuse large B-cell lymphoma.

Alternative Interventions to Prevent Oxidative Damage following Ischemia/Reperfusion

PubMed Central

Rodríguez-Lara, Simón Quetzalcoatl; Ramírez-Lizardo, Ernesto Javier; Totsuka-Sutto, Sylvia Elena; Castillo-Romero, Araceli; García-Cobián, Teresa Arcelia

2016-01-01

Ischemia/reperfusion (I/R) lesions are a phenomenon that occurs in multiple pathological states and results in a series of events that end in irreparable damage that severely affects the recovery and health of patients. The principal therapeutic approaches include preconditioning, postconditioning, and remote ischemic preconditioning, which when used separately do not have a great impact on patient mortality or prognosis. Oxidative stress is known to contribute to the damage caused by I/R; however, there are no pharmacological approaches to limit or prevent this. Here, we explain the relationship between I/R and the oxidative stress process and describe some pharmacological options that may target oxidative stress-states. PMID:28116037

Transfer of interferon alfa into human breast milk.

PubMed

Kumar, A R; Hale, T W; Mock, R E

2000-08-01

Originally assumed to be antiviral substances, the efficacy of interferons in a number of pathologies, including malignancies, multiple sclerosis, and other immune syndromes, is increasingly recognized. This study provides data on the transfer of interferon alfa (2B) into human milk of a patient receiving massive intravenous doses for the treatment of malignant melanoma. Following an intravenous dose of 30 million IU, the amount of interferon transferred into human milk was only slightly elevated (1551 IU/mL) when compared to control milk (1249 IU/mL). These data suggest that even following enormous doses, interferon is probably too large in molecular weight to transfer into human milk in clinically relevant amounts.

Simultaneous imaging of cellular morphology and multiple biomarkers using an acousto-optic tunable filter-based bright field microscope.

PubMed

Wachman, Elliot S; Geyer, Stanley J; Recht, Joel M; Ward, Jon; Zhang, Bill; Reed, Murray; Pannell, Chris

2014-05-01

An acousto-optic tunable filter (AOTF)-based multispectral imaging microscope system allows the combination of cellular morphology and multiple biomarker stainings on a single microscope slide. We describe advances in AOTF technology that have greatly improved spectral purity, field uniformity, and image quality. A multispectral imaging bright field microscope using these advances demonstrates pathology results that have great potential for clinical use.

Sickle red cell adhesion: many issues and some answers.

PubMed

Kaul, D K

2008-01-01

Among multiple pathologies associated with sickle cell disease, sickle red cell-endothelial interaction has been implicated as a potential initiating mechanism in vaso-occlusive events that characterize this disease. Vast literature exists on various aspects of sickle red cell adhesion, but many issues remain unresolved, especially pertaining to the role of sickle red cell heterogeneity, the relative role of multiple adhesion mechanisms and targets of antiadhesive therapy. This review briefly analyzes these issues.

Relating Brain Damage to Brain Plasticity in Patients With Multiple Sclerosis

PubMed Central

Tomassini, Valentina; Johansen-Berg, Heidi; Jbabdi, Saad; Wise, Richard G.; Pozzilli, Carlo; Palace, Jacqueline; Matthews, Paul M.

2013-01-01

Background Failure of adaptive plasticity with increasing pathology is suggested to contribute to progression of disability in multiple sclerosis (MS). However, functional impairments can be reduced with practice, suggesting that brain plasticity is preserved even in patients with substantial damage. Objective Here, functional magnetic resonance imaging (fMRI) was used to probe systems-level mechanisms of brain plasticity associated with improvements in visuomotor performance in MS patients and related to measures of microstructural damage. Methods 23 MS patients and 12 healthy controls underwent brain fMRI during the first practice session of a visuomotor task (short-term practice) and after 2 weeks of daily practice with the same task (longer-term practice). Participants also underwent a structural brain MRI scan. Results Patients performed more poorly than controls at baseline. Nonetheless, with practice, patients showed performance improvements similar to controls and independent of the extent of MRI measures of brain pathology. Different relationships between performance improvements and activations were found between groups: greater short-term improvements were associated with lower activation in the sensorimotor, posterior cingulate, and parahippocampal cortices for patients, whereas greater long-term improvements correlated with smaller activation reductions in the visual cortex of controls. Conclusions Brain plasticity for visuomotor practice is preserved in MS patients despite a high burden of cerebral pathology. Cognitive systems different from those acting in controls contribute to this plasticity in patients. These findings challenge the notion that increasing pathology is accompanied by an outright failure of adaptive plasticity, supporting a neuroscientific rationale for recovery-oriented strategies even in chronically disabled patients. PMID:22328685

Analysis of Prognostic Factors and Patterns of Recurrence in Patients With Pathologic Stage III Endometrial Cancer

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

Patel, Samir; Portelance, Lorraine; Gilbert, Lucy

2007-08-01

Purpose: To retrospectively assess prognostic factors and patterns of recurrence in patients with pathologic Stage III endometrial cancer. Methods and Materials: Between 1989 and 2003, 107 patients with pathologic International Federation of Gynecology and Obstetrics Stage III endometrial adenocarcinoma confined to the pelvis were treated at our institution. Adjuvant radiotherapy (RT) was delivered to 68 patients (64%). The influence of multiple patient- and treatment-related factors on pelvic and distant control and overall survival (OS) was evaluated. Results: Median follow-up for patients at risk was 41 months. Five-year actuarial OS was significantly improved in patients treated with adjuvant RT (68%) comparedmore » with those with resection alone (50%; p = 0.029). Age, histology, grade, uterine serosal invasion, adnexal involvement, number of extrauterine sites, and treatment with adjuvant RT predicted for improved survival in univariate analysis. Multivariate analysis revealed that grade, uterine serosal invasion, and treatment with adjuvant RT were independent predictors of survival. Five-year actuarial pelvic control was improved significantly with the delivery of adjuvant RT (74% vs. 49%; p = 0.011). Depth of myometrial invasion and treatment with adjuvant RT were independent predictors of pelvic control in multivariate analysis. Conclusions: Multiple prognostic factors predicting for the outcome of pathologic Stage III endometrial cancer patients were identified in this analysis. In particular, delivery of adjuvant RT seems to be a significant independent predictor for improved survival and pelvic control, suggesting that pelvic RT should be routinely considered in the management of these patients.« less

Multiplex biomarker approach to cardiovascular diseases.

PubMed

Adamcova, Michaela; Šimko, Fedor

2018-04-12

Personalized medicine is partly based on biomarker-guided diagnostics, therapy and prognosis, which is becoming an unavoidable concept in modern cardiology. However, the clinical significance of single biomarker studies is rather limited. A promising novel approach involves combining multiple markers into a multiplex panel, which could refine the management of a particular patient with cardiovascular pathology. Two principally different assay formats have been developed to facilitate simultaneous quantification of multiple antigens: planar array assays and microbead assays. These approaches may help to better evaluate the complexity and dynamic nature of pathologic processes and offer substantial cost and sample savings compared with traditional enzyme-linked immunosorbent assay (ELISA) measurements. However, a multiplex multimarker approach cannot become a generally disseminated method until analytical problems are solved and further studies confirming improved clinical outcomes are accomplished. These drawbacks underlie the fact that a limited number of systematic studies are available regarding the use of a multiplex biomarker approach in cardiovascular medicine to date. Our perspective underscores the significant potential of the use of the multiplex approach in a wider conceptual framework under the close cooperation of clinical and experimental cardiologists, pathophysiologists and biochemists so that the personalized approach based on standardized multimarker testing may improve the management of various cardiovascular pathologies and become a ubiquitous partner of population-derived evidence-based medicine.

Rectal Carcinoma Model: A Novel Simulation in Pathology Training.

PubMed

Pongpaibul, Ananya; Chiravirakul, Prattana; Leksrisakul, Piyawadee; Silakorn, Phadungsak; Chumtap, Wangcha; Chongpipatchaipron, Somchai; Jaitrong, Peerasak; Jitvichai, Ekachai

2017-06-01

Until now, the apprenticeship training model is used to train pathology residents. Pathology residents are trained using patient specimens that are received during the course of normal daily pathology service. However, this training method could result in inconsistency in knowledge and experience among trainees because of variation in specimens that are received for analysis. The use of simulated specimens in pathology residency training could help ensure that all pathology residents receive consistent knowledge and experience. The aim of this study was to develop prototype rectal carcinoma model to be used as a simulation tool and to evaluate its effectiveness in pathology training. Five units of a prototype rectal carcinoma model were produced in latex rubber. The model was used as a simulation tool for training in 12 pathology residents and 7 pathologist assistants. Pretesting and posttesting of each participant was conducted by multiple choice question test. A questionnaire was also given to study participants to elicit their views regarding the fidelity of the model and the model's efficacy and usefulness relative to the gross examination technique. Among the 19 participants, the mean pretest score was 79.24% and the mean posttest score was 88.54% (P = 0.045). The fidelity of the model was rated as moderate to marked by all participants. Most participants (94.74%) rated the models efficacy and usefulness relative to the gross examination technique as being moderate to marked. The rectal carcinoma model introduced in this study was found to be an effective simulation tool for pathology training. The model had good fidelity on appearance and good efficacy as well as usefulness relative to the gross examination technique.

Robust skull stripping using multiple MR image contrasts insensitive to pathology.

PubMed

Roy, Snehashis; Butman, John A; Pham, Dzung L

2017-02-01

Automatic skull-stripping or brain extraction of magnetic resonance (MR) images is often a fundamental step in many neuroimage processing pipelines. The accuracy of subsequent image processing relies on the accuracy of the skull-stripping. Although many automated stripping methods have been proposed in the past, it is still an active area of research particularly in the context of brain pathology. Most stripping methods are validated on T 1 -w MR images of normal brains, especially because high resolution T 1 -w sequences are widely acquired and ground truth manual brain mask segmentations are publicly available for normal brains. However, different MR acquisition protocols can provide complementary information about the brain tissues, which can be exploited for better distinction between brain, cerebrospinal fluid, and unwanted tissues such as skull, dura, marrow, or fat. This is especially true in the presence of pathology, where hemorrhages or other types of lesions can have similar intensities as skull in a T 1 -w image. In this paper, we propose a sparse patch based Multi-cONtrast brain STRipping method (MONSTR), 2 where non-local patch information from one or more atlases, which contain multiple MR sequences and reference delineations of brain masks, are combined to generate a target brain mask. We compared MONSTR with four state-of-the-art, publicly available methods: BEaST, SPECTRE, ROBEX, and OptiBET. We evaluated the performance of these methods on 6 datasets consisting of both healthy subjects and patients with various pathologies. Three datasets (ADNI, MRBrainS, NAMIC) are publicly available, consisting of 44 healthy volunteers and 10 patients with schizophrenia. Other three in-house datasets, comprising 87 subjects in total, consisted of patients with mild to severe traumatic brain injury, brain tumors, and various movement disorders. A combination of T 1 -w, T 2 -w were used to skull-strip these datasets. We show significant improvement in stripping over the competing methods on both healthy and pathological brains. We also show that our multi-contrast framework is robust and maintains accurate performance across different types of acquisitions and scanners, even when using normal brains as atlases to strip pathological brains, demonstrating that our algorithm is applicable even when reference segmentations of pathological brains are not available to be used as atlases. Copyright © 2016 Elsevier Inc. All rights reserved.

Unifying mechanism for different fibrotic diseases

PubMed Central

Wernig, Gerlinde; Chen, Shih-Yu; Cui, Lu; Van Neste, Camille; Tsai, Jonathan M.; Kambham, Neeraja; Vogel, Hannes; Natkunam, Yaso; Gilliland, D. Gary; Nolan, Garry; Weissman, Irving L.

2017-01-01

Fibrotic diseases are not well-understood. They represent a number of different diseases that are characterized by the development of severe organ fibrosis without any obvious cause, such as the devastating diseases idiopathic pulmonary fibrosis (IPF) and scleroderma. These diseases have a poor prognosis comparable with endstage cancer and are uncurable. Given the phenotypic differences, it was assumed that the different fibrotic diseases also have different pathomechanisms. Here, we demonstrate that many endstage fibrotic diseases, including IPF; scleroderma; myelofibrosis; kidney-, pancreas-, and heart-fibrosis; and nonalcoholic steatohepatosis converge in the activation of the AP1 transcription factor c-JUN in the pathologic fibroblasts. Expression of the related AP1 transcription factor FRA2 was restricted to pulmonary artery hypertension. Induction of c-Jun in mice was sufficient to induce severe fibrosis in multiple organs and steatohepatosis, which was dependent on sustained c-Jun expression. Single cell mass cytometry revealed that c-Jun activates multiple signaling pathways in mice, including pAkt and CD47, which were also induced in human disease. αCD47 antibody treatment and VEGF or PI3K inhibition reversed various organ c-Jun–mediated fibroses in vivo. These data suggest that c-JUN is a central molecular mediator of most fibrotic conditions. PMID:28424250

A Federated Network for Translational Cancer Research Using Clinical Data and Biospecimens

PubMed Central

Becich, Michael J.; Bollag, Roni J.; Chavan, Girish; Corrigan, Julia; Dhir, Rajiv; Feldman, Michael D.; Gaudioso, Carmelo; Legowski, Elizabeth; Maihle, Nita J.; Mitchell, Kevin; Murphy, Monica; Sakthivel, Mayur; Tseytlin, Eugene; Weaver, JoEllen

2015-01-01

Advances in cancer research and personalized medicine will require significant new bridging infrastructures, including more robust biorepositories that link human tissue to clinical phenotypes and outcomes. In order to meet that challenge, four cancer centers formed the TIES Cancer Research Network, a federated network that facilitates data and biospecimen sharing among member institutions. Member sites can access pathology data that is de-identified and processed with the TIES natural language processing system, which creates a repository of rich phenotype data linked to clinical biospecimens. TIES incorporates multiple security and privacy best practices that, combined with legal agreements, network policies and procedures, enable regulatory compliance. The TIES Cancer Research Network now provides integrated access to investigators at all member institutions, where multiple investigator-driven pilot projects are underway. Examples of federated search across the network illustrate the potential impact on translational research, particularly for studies involving rare cancers, rare phenotypes, and specific biologic behaviors. The network satisfies several key desiderata including local control of data and credentialing, inclusion of rich phenotype information, and applicability to diverse research objectives. The TIES Cancer Research Network presents a model for a national data and biospecimen network. PMID:26670560

Best practices for veterinary toxicologic clinical pathology, with emphasis on the pharmaceutical and biotechnology industries.

PubMed

Tomlinson, Lindsay; Boone, Laura I; Ramaiah, Lila; Penraat, Kelley A; von Beust, Barbara R; Ameri, Mehrdad; Poitout-Belissent, Florence M; Weingand, Kurt; Workman, Heather C; Aulbach, Adam D; Meyer, Dennis J; Brown, Diane E; MacNeill, Amy L; Bolliger, Anne Provencher; Bounous, Denise I

2013-09-01

The purpose of this paper by the Regulatory Affairs Committee (RAC) of the American Society for Veterinary Clinical Pathology (ASVCP) is to review the current regulatory guidances (eg, guidelines) and published recommendations for best practices in veterinary toxicologic clinical pathology, particularly in the pharmaceutical and biotechnology industries, and to utilize the combined experience of ASVCP RAC to provide updated recommendations. Discussion points include (1) instrumentation, validation, and sample collection, (2) routine laboratory variables, (3) cytologic laboratory variables, (4) data interpretation and reporting (including peer review, reference intervals and statistics), and (5) roles and responsibilities of clinical pathologists and laboratory personnel. Revision and improvement of current practices should be in alignment with evolving regulatory guidance documents, new technology, and expanding understanding and utility of clinical pathology. These recommendations provide a contemporary guide for the refinement of veterinary toxicologic clinical pathology best practices. © 2013 American Society for Veterinary Clinical Pathology.

[The theory of multiple intelligences: a suitable neurocognitive context for the neuropsychological hypotheses on the factors and mechanisms of superiority].

PubMed

Sierra-Fitzgerald, O; Quevedo-Caicedo, J

The aim of this article is to relate two theories regarding the structure of the human mind. We suggest that the theory of multiple intelligences, a neurocognitive theory of the psychologist Howard Garnerd provides a suitable context for theoretical understanding and validation of the hypothesis of the pathology of superiority, a neuropsychological hypothesis formulated by the neuropsychologists Norman Geschwind and Albert Galaburda. Similarly, we show that, apart from being a context, the first theory enriches the second. We review the essential elements of both theories together with the arguments for them so that the reader may judge for himself. Similarly we review the factors determining intelligence; the association between neuropathology and intellectual dysfunction, general and specific, and the new directions in the understanding of human cognition. We propose to consider the first theory as a fertile ambit and broad methodological framework for investigation in neuropsychology. This simultaneously shows the relevance of including neuropsychological investigation in broader cognitive and neuropsychological theories and models.

Conflicting Role of Mycobacterium Species in Multiple Sclerosis

PubMed Central

Cossu, Davide; Yokoyama, Kazumasa; Hattori, Nobutaka

2017-01-01

Mycobacterium is a genus of aerobic and acid-fast bacteria, which include several pathogenic organisms that cause serious diseases in mammals. Previous studies have associated the immune response against mycobacteria with multiple sclerosis (MS), a chronic demyelinating disease of the central nervous system with unknown etiology. The role of mycobacteria in the pathological process has been controversial and often conflicting. We provide a detailed review of the mycobacteria that have been linked to MS over the last three decades, with a focus on Mycobacterium bovis bacille Calmette–Guérin vaccine for human and oral exposure to Mycobacterium avium subsp. paratuberculosis. We will also discuss the exposure and genetic susceptibility to mycobacterial infection, the protective role of vaccination, as well as the possible mechanisms involved in initiating or worsening MS symptoms, with particular emphasis on the molecular mimicry between mycobacterial and human proteins. Finally, we will introduce topics such as heat shock proteins and recognition by innate immunity, and toll-like receptor signaling-mediated responses to Mycobacterium exposure. PMID:28579973

Sensory ataxic neuropathy with ophthalmoparesis caused by POLG mutations.

PubMed

Milone, Margherita; Brunetti-Pierri, Nicola; Tang, Lin-Ya; Kumar, Neeraj; Mezei, Michelle M; Josephs, Keith; Powell, Suzanne; Simpson, Ericka; Wong, Lee-Jun C

2008-08-01

Mutations in POLG gene are responsible for a wide spectrum of clinical disorders with altered mitochondrial DNA (mtDNA) integrity, including mtDNA multiple deletions and depletion. Sensory ataxic neuropathy with ophthalmoparesis (SANDO) caused by mutations in POLG gene, fulfilling the clinical triad of sensory ataxic neuropathy, dysarthria and/or dysphagia and ophthalmoparesis, has described in a few reports. Here we described five cases of adult onset autosomal recessive sensory ataxic neuropathy with ophthalmoplegia. All patients had ataxia, neuropathy, myopathy, and progressive external ophthalmoplegia (PEO). The muscle pathology revealed ragged-red and cytochrome c oxidase (COX) negative fibers in three patients. However, deficiencies in the activities of mitochondrial respiratory chain enzyme complexes were not detected in any of the patients' muscle samples. Multiple deletions of mtDNA were detected in blood and muscle specimens but mtDNA depletion was not found. Due to these diagnostic difficulties, POLG-related syndromes are definitively diagnosed based on the presence of deleterious mutations in the POLG gene.

Targeting the hallmarks of cancer with therapy-induced endoplasmic reticulum (ER) stress

PubMed Central

Garg, Abhishek D; Maes, Hannelore; van Vliet, Alexander R; Agostinis, Patrizia

2015-01-01

The endoplasmic reticulum (ER) is at the center of a number of vital cellular processes such as cell growth, death, and differentiation, crosstalk with immune or stromal cells, and maintenance of proteostasis or homeostasis, and ER functions have implications for various pathologies including cancer. Recently, a number of major hallmarks of cancer have been delineated that are expected to facilitate the development of anticancer therapies. However, therapeutic induction of ER stress as a strategy to broadly target multiple hallmarks of cancer has been seldom discussed despite the fact that several primary or secondary ER stress-inducing therapies have been found to exhibit positive clinical activity in cancer patients. In the present review we provide a brief historical overview of the major discoveries and milestones in the field of ER stress biology with important implications for anticancer therapy. Furthermore, we comprehensively discuss possible strategies enabling the targeting of multiple hallmarks of cancer with therapy-induced ER stress. PMID:27308392

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.

Multiple and solitary skeletal muscle metastases on 18F-FDG PET/CT imaging.

PubMed

Nocuń, Anna; Chrapko, Beata

2015-11-01

The aim of this study was to investigate the features and patterns of skeletal muscle metastases (SMM) detected with F-fluorodeoxyglucose (F-FDG) PET/computed tomography (PET/CT). Our database was analyzed for patients with pathologically proven malignancy, who underwent F-FDG PET/CT in our institution. The patients with SMM were included in the study group on the basis of the final diagnosis confirmed by follow-up or histopathology. Images were acquired using a PET/CT system Biograph mCT S(64)-4R. CT was performed without contrast enhancement. The selected group included 31 patients (1.7% of the database, which consisted of 1805 patients). A total of 233 lesions were found. The prevalence of SMM evaluated in specific primary malignancies was the highest in melanoma (6.9%), followed by carcinoma of unknown primary (4.4%), colorectal cancer (4.1%) and lung cancer (2.8%). Three patterns of skeletal muscle metastatic involvement were observed: multiple SMM accompanied by other metastases (64.5%), solitary lesion associated with other metastases (29%) and isolated intramuscular lesions (two cases, 6.5%). Isolated SMM represented recurrence of the malignant disease. In patients with extraskeletal metastases, solitary or multiple SMM did not affect tumor staging. Solitary SMM are less common than multiple on F-FDG PET/CT imaging. SMM are usually associated with other metastases and do not affect tumor staging. The cases of isolated SMM are very rare. Nevertheless, in patients with a diagnosis of malignant disease, a solitary, F-FDG avid intramuscular focus should be suspected to represent metastasis.

The effectiveness of transdermal opioid in the management multiple rib fractures: randomized clinical trial.

PubMed

Solak, Okan; Oz, Gürhan; Kokulu, Serdar; Solak, Ozlem; Doğan, Gökçen; Esme, Hıdır; Ocalan, Kubilay; Baki, Elif Doğan

2013-09-01

The most commonly observed pathology in chest traumas is rib fracture, and the most important clinical symptom is severe pain. To investigate the effectiveness of intramuscular opioid (IMO), intravenous patient-controlled analgesia (IVPCA) and the Fentanyl transdermal therapeutic system (TTS) in the management of rib fracture pain. Prospective randomized clinical trial. In our prospective and randomised study, we included 45 patients with a diagnosis of multiple rib fractures. There were three groups and intercostal nerve blockage (ICB) in the first day and oral paracetamol for five days was administered to each group as standard. In Group IMO (n=15), 4×40 mg pethidine HCl was administered to the patients, while in Group IVPCA (n=15) this was 5 μg/mL continuous intravenous fentanyl and was 50 μg fentanyl TTS in Group TTS (n=15). The demographics, injury data and vital signs of the patients were recorded. Pain was scored using Visual Analogue Scale (VAS). The pain during lying down (VASl) and mobilisation (VASm) was detected. There were no differences between the three groups regarding age, sex, the trauma pattern, the number and distribution of costal fracture localisations, the presence of additional pathology, complications, thoracal catheter and the duration of thoracal catheter. No significant difference between the groups regarding systolic and diastolic arterial tension, number of breaths and beats in a minute was observed (p>0.05). We observed an improvement in the mean VAS score after treatment in all three groups. The mean VASl score significantly decreased after treatment in each group (p<0.05). The mean VASl and VASm scores measured on the 1(st), 2(nd), 3(rd), 4(th) and 5(th) days were found to be higher in Group IMO than in Groups IVPCA and TTS; however, these differences were not statistically significant (p>0.05). In the analgesia of patients with multiple rib fractures, TTS administration with ICB showed similar effectiveness with IVPCA administration with ICB. In the management of pain due to multiple rib fractures, TTS administration is a safe, non-invasive and effective procedure.