Traffic jam hypothesis: Relationship between endocytic dysfunction and Alzheimer's disease.

PubMed

Kimura, Nobuyuki; Yanagisawa, Katsuhiko

2017-07-08

Membrane trafficking pathways, like the endocytic pathway, carry out fundamental cellular processes that are essential for normal functioning. One such process is regulation of cell surface receptor signaling. A growing body of evidence suggests that β-amyloid protein (Aβ) plays a key role in Alzheimer's disease (AD) pathogenesis. Cleavage of Aβ from its precursor, β-amyloid precursor protein (APP), occurs through the endocytic pathway in neuronal cells. In early-stage AD, intraneuronal accumulation of abnormally enlarged endosomes is common, indicating that endosome trafficking is disrupted. Strikingly, genome-wide association studies reveal that several endocytosis-related genes are associated with AD onset. Also, recent studies demonstrate that alteration in endocytosis induces not only Aβ pathology but also the propagation of tau protein pathology, another key pathological feature of AD. Endocytic dysfunction can disrupt neuronal physiological functions, such as synaptic vesicle transport and neurotransmitter release. Thus, "traffic jams" in the endocytic pathway may be involved in AD pathogenesis and may serve as a novel target for the development of new therapeutics. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chordoma of the Head and Neck: A Review.

PubMed

Wasserman, Jason K; Gravel, Denis; Purgina, Bibianna

2018-06-01

Chordoma is a rare malignant bone tumor that can arise anywhere along the central neural axis and many involve head and neck sites, most commonly the skull base. The relative rarity of these tumors, combined with the complex anatomy of the head and neck, pose diagnostic challenges to pathologists. This article describes the pertinent clinical, pathologic, and molecular features of chordomas and describes how these features can be used to aid in formulating a differential diagnosis. Emphasis is placed on key diagnostic pitfalls and the importance of incorporating immunohistochemical information into the diagnosis.

Evidence that Meningeal Mast Cells Can Worsen Stroke Pathology in Mice

PubMed Central

Arac, Ahmet; Grimbaldeston, Michele A.; Nepomuceno, Andrew R.B.; Olayiwola, Oluwatobi; Pereira, Marta P.; Nishiyama, Yasuhiro; Tsykin, Anna; Goodall, Gregory J.; Schlecht, Ulrich; Vogel, Hannes; Tsai, Mindy; Galli, Stephen J.; Bliss, Tonya M.; Steinberg, Gary K.

2015-01-01

Stroke is the leading cause of adult disability and the fourth most common cause of death in the United States. Inflammation is thought to play an important role in stroke pathology, but the factors that promote inflammation in this setting remain to be fully defined. An understudied but important factor is the role of meningeal-located immune cells in modulating brain pathology. Although different immune cells traffic through meningeal vessels en route to the brain, mature mast cells do not circulate but are resident in the meninges. With the use of genetic and cell transfer approaches in mice, we identified evidence that meningeal mast cells can importantly contribute to the key features of stroke pathology, including infiltration of granulocytes and activated macrophages, brain swelling, and infarct size. We also obtained evidence that two mast cell-derived products, interleukin-6 and, to a lesser extent, chemokine (C-C motif) ligand 7, can contribute to stroke pathology. These findings indicate a novel role for mast cells in the meninges, the membranes that envelop the brain, as potential gatekeepers for modulating brain inflammation and pathology after stroke. PMID:25134760

Multi-channel MRI segmentation of eye structures and tumors using patient-specific features

PubMed Central

Ciller, Carlos; De Zanet, Sandro; Kamnitsas, Konstantinos; Maeder, Philippe; Glocker, Ben; Munier, Francis L.; Rueckert, Daniel; Thiran, Jean-Philippe

2017-01-01

Retinoblastoma and uveal melanoma are fast spreading eye tumors usually diagnosed by using 2D Fundus Image Photography (Fundus) and 2D Ultrasound (US). Diagnosis and treatment planning of such diseases often require additional complementary imaging to confirm the tumor extend via 3D Magnetic Resonance Imaging (MRI). In this context, having automatic segmentations to estimate the size and the distribution of the pathological tissue would be advantageous towards tumor characterization. Until now, the alternative has been the manual delineation of eye structures, a rather time consuming and error-prone task, to be conducted in multiple MRI sequences simultaneously. This situation, and the lack of tools for accurate eye MRI analysis, reduces the interest in MRI beyond the qualitative evaluation of the optic nerve invasion and the confirmation of recurrent malignancies below calcified tumors. In this manuscript, we propose a new framework for the automatic segmentation of eye structures and ocular tumors in multi-sequence MRI. Our key contribution is the introduction of a pathological eye model from which Eye Patient-Specific Features (EPSF) can be computed. These features combine intensity and shape information of pathological tissue while embedded in healthy structures of the eye. We assess our work on a dataset of pathological patient eyes by computing the Dice Similarity Coefficient (DSC) of the sclera, the cornea, the vitreous humor, the lens and the tumor. In addition, we quantitatively show the superior performance of our pathological eye model as compared to the segmentation obtained by using a healthy model (over 4% DSC) and demonstrate the relevance of our EPSF, which improve the final segmentation regardless of the classifier employed. PMID:28350816

The Use of Visual Arts as a Window to Diagnosing Medical Pathologies.

PubMed

Bramstedt, Katrina A

2016-08-01

Observation is a key step preceding diagnosis, prognostication, and treatment. Careful patient observation is a skill that is learned but rarely explicitly taught. Furthermore, proper clinical observation requires more than a glance; it requires attention to detail. In medical school, the art of learning to look can be taught using the medical humanities and especially visual arts such as paintings and film. Research shows that such training improves not only observation skills but also teamwork, listening skills, and reflective and analytical thinking. Overall, the use of visual arts in medical school curricula can build visual literacy: the capacity to identify and analyze facial features, emotions, and general bodily presentations, including contextual features such as clothing, hair, and body art. With the ability to formulate and convey a detailed "picture" of the patient, clinicians can integrate aesthetic and clinical knowledge, helping facilitate the diagnosing of medical pathologies. © 2016 American Medical Association. All Rights Reserved.

3D Pathology Volumetric Technique: A Method for Calculating Breast Tumour Volume from Whole-Mount Serial Section Images

PubMed Central

Clarke, G. M.; Murray, M.; Holloway, C. M. B.; Liu, K.; Zubovits, J. T.; Yaffe, M. J.

2012-01-01

Tumour size, most commonly measured by maximum linear extent, remains a strong predictor of survival in breast cancer. Tumour volume, proportional to the number of tumour cells, may be a more accurate surrogate for size. We describe a novel “3D pathology volumetric technique” for lumpectomies and compare it with 2D measurements. Volume renderings and total tumour volume are computed from digitized whole-mount serial sections using custom software tools. Results are presented for two lumpectomy specimens selected for tumour features which may challenge accurate measurement of tumour burden with conventional, sampling-based pathology: (1) an infiltrative pattern admixed with normal breast elements; (2) a localized invasive mass separated from the in situ component by benign tissue. Spatial relationships between key features (tumour foci, close or involved margins) are clearly visualized in volume renderings. Invasive tumour burden can be underestimated using conventional pathology, compared to the volumetric technique (infiltrative pattern: 30% underestimation; localized mass: 3% underestimation for invasive tumour, 44% for in situ component). Tumour volume approximated from 2D measurements (i.e., maximum linear extent), assuming elliptical geometry, was seen to overestimate volume compared to the 3D volumetric calculation (by a factor of 7x for the infiltrative pattern; 1.5x for the localized invasive mass). PMID:23320179

Dependent personality features in a complex case of borderline personality disorder.

PubMed

Nirestean, Tudor; Lukacs, Emese; Nirestean, Aurel; Gabos Grecu, Iosif

2016-11-01

Borderline personality disorder is a complex disease model as it encompasses a diversity of pathological personality traits and psychopathological symptoms. It is not surprising, therefore, that it is often manifested by personality disorders across all three clusters and accompanied by other mental (Axis I) disorders. This melange makes both psychological treatment and pharmacotherapy especially challenging, and this paper describes the case of a particularly complex case of a 33-year-old Romanian patient, who has a history of severe deprivation in childhood, mood and substance use disorder in association with borderline pathology. In the course of treatment from many sources and interventions, it has become clear that dependence is a key component of the pathology and has been rewarded with a degree of success in management. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Application of Immunohistochemistry and Molecular Diagnostics to Clinically Relevant Problems in Endometrial Cancer Bojana Djordjevic, Shannon Westin, Russell R. Broaddus

PubMed Central

Djordjevic, Bojana; Westin, Shannon; Broaddus, Russell R.

2012-01-01

Synopsis A number of different clinical scenarios are presented in which lab-based analyses beyond the usual diagnosis based on light microscopic examination of H&E stained slides – immunohistochemistry and PCR-based assays such as sequencing, mutation testing, microsatellite instability analysis, and determination of MLH1 methylation - are most helpful for guiding diagnosis and treatment of endometrial cancer. The central goal of this information is to provide a practical guide of key current and emerging issues in diagnostic endometrial cancer pathology that require the use of ancillary laboratory techniques, such as immunohistochemistry and molecular testing. The authors present the common diagnostic problems in endometrial carcinoma pathology, types of endometrial carcinoma, description of tissue testing and markers, pathological features, and targeted therapy. PMID:23687522

CT and MR Imaging Diagnosis and Staging of Hepatocellular Carcinoma: Part I. Development, Growth, and Spread: Key Pathologic and Imaging Aspects

PubMed Central

Choi, Jin-Young; Lee, Jeong-Min

2014-01-01

Computed tomography (CT) and magnetic resonance (MR) imaging play critical roles in the diagnosis and staging of hepatocellular carcinoma (HCC). The first article of this two-part review discusses key concepts of HCC development, growth, and spread, emphasizing those features with imaging correlates and hence most relevant to radiologists; state-of-the-art CT and MR imaging technique with extracellular and hepatobiliary contrast agents; and the imaging appearance of precursor nodules that eventually may transform into overt HCC. © RSNA, 2014 PMID:25153274

Mouse model of pulmonary cavitary tuberculosis and expression of matrix metalloproteinase-9.

PubMed

Ordonez, Alvaro A; Tasneen, Rokeya; Pokkali, Supriya; Xu, Ziyue; Converse, Paul J; Klunk, Mariah H; Mollura, Daniel J; Nuermberger, Eric L; Jain, Sanjay K

2016-07-01

Cavitation is a key pathological feature of human tuberculosis (TB), and is a well-recognized risk factor for transmission of infection, relapse after treatment and the emergence of drug resistance. Despite intense interest in the mechanisms underlying cavitation and its negative impact on treatment outcomes, there has been limited study of this phenomenon, owing in large part to the limitations of existing animal models. Although cavitation does not occur in conventional mouse strains after infection with Mycobacterium tuberculosis, cavitary lung lesions have occasionally been observed in C3HeB/FeJ mice. However, to date, there has been no demonstration that cavitation can be produced consistently enough to support C3HeB/FeJ mice as a new and useful model of cavitary TB. We utilized serial computed tomography (CT) imaging to detect pulmonary cavitation in C3HeB/FeJ mice after aerosol infection with M. tuberculosis Post-mortem analyses were performed to characterize lung lesions and to localize matrix metalloproteinases (MMPs) previously implicated in cavitary TB in situ A total of 47-61% of infected mice developed cavities during primary disease or relapse after non-curative treatments. Key pathological features of human TB, including simultaneous presence of multiple pathologies, were noted in lung tissues. Optical imaging demonstrated increased MMP activity in TB lesions and MMP-9 was significantly expressed in cavitary lesions. Tissue MMP-9 activity could be abrogated by specific inhibitors. In situ, three-dimensional analyses of cavitary lesions demonstrated that 22.06% of CD11b+ signal colocalized with MMP-9. C3HeB/FeJ mice represent a reliable, economical and tractable model of cavitary TB, with key similarities to human TB. This model should provide an excellent tool to better understand the pathogenesis of cavitation and its effects on TB treatments. © 2016. Published by The Company of Biologists Ltd.

Mouse model of pulmonary cavitary tuberculosis and expression of matrix metalloproteinase-9

PubMed Central

Ordonez, Alvaro A.; Tasneen, Rokeya; Pokkali, Supriya; Xu, Ziyue; Converse, Paul J.; Klunk, Mariah H.; Mollura, Daniel J.; Nuermberger, Eric L.

2016-01-01

ABSTRACT Cavitation is a key pathological feature of human tuberculosis (TB), and is a well-recognized risk factor for transmission of infection, relapse after treatment and the emergence of drug resistance. Despite intense interest in the mechanisms underlying cavitation and its negative impact on treatment outcomes, there has been limited study of this phenomenon, owing in large part to the limitations of existing animal models. Although cavitation does not occur in conventional mouse strains after infection with Mycobacterium tuberculosis, cavitary lung lesions have occasionally been observed in C3HeB/FeJ mice. However, to date, there has been no demonstration that cavitation can be produced consistently enough to support C3HeB/FeJ mice as a new and useful model of cavitary TB. We utilized serial computed tomography (CT) imaging to detect pulmonary cavitation in C3HeB/FeJ mice after aerosol infection with M. tuberculosis. Post-mortem analyses were performed to characterize lung lesions and to localize matrix metalloproteinases (MMPs) previously implicated in cavitary TB in situ. A total of 47-61% of infected mice developed cavities during primary disease or relapse after non-curative treatments. Key pathological features of human TB, including simultaneous presence of multiple pathologies, were noted in lung tissues. Optical imaging demonstrated increased MMP activity in TB lesions and MMP-9 was significantly expressed in cavitary lesions. Tissue MMP-9 activity could be abrogated by specific inhibitors. In situ, three-dimensional analyses of cavitary lesions demonstrated that 22.06% of CD11b+ signal colocalized with MMP-9. C3HeB/FeJ mice represent a reliable, economical and tractable model of cavitary TB, with key similarities to human TB. This model should provide an excellent tool to better understand the pathogenesis of cavitation and its effects on TB treatments. PMID:27482816

Relationships: empirical contribution. Understanding personality pathology in adolescents: the five factor model of personality and social information processing.

PubMed

Hessels, Christel; van den Hanenberg, Danique; de Castro, Bram Orobio; van Aken, Marcel A G

2014-02-01

This study seeks to integrate two research traditions that lie at the base of the understanding of personality pathology in adolescents. The first research tradition refers to normal personality according to the Five Factor Model (FFM). The second tradition specifies the key feature of personality disorder as the capacity to mentalize, which can be reflected in Social Information Processing (SIP). In a clinical sample of 96 adolescents, the authors investigated response generation, coping strategy, and memories of past frustrating experiences as part of SIP, as mediator in the relationship between personality and personality pathology, and a possible moderating role of personality on the relationship between SIP and personality pathology. The hypothesized mediation, by which the effects of personality dimensions on personality pathology was expected to be mediated by SIP variables, was found only for the effect of Neuroticism, most specifically on BPD, which appeared to be mediated by memories the patients had about past frustrating conflict situations with peers. Some moderating effects of personality on the relationship between SIP variables and personality pathology were found, suggesting that high Agreeableness and sometimes low Neuroticism can buffer this relationship. These results suggest that personality dimensions and social cognitions both independently and together play a role in adolescents' personality pathology.

Cardiotrophin 1 stimulates beneficial myogenic and vascular remodeling of the heart.

PubMed

Abdul-Ghani, Mohammad; Suen, Colin; Jiang, Baohua; Deng, Yupu; Weldrick, Jonathan J; Putinski, Charis; Brunette, Steve; Fernando, Pasan; Lee, Tom T; Flynn, Peter; Leenen, Frans H H; Burgon, Patrick G; Stewart, Duncan J; Megeney, Lynn A

2017-10-01

The post-natal heart adapts to stress and overload through hypertrophic growth, a process that may be pathologic or beneficial (physiologic hypertrophy). Physiologic hypertrophy improves cardiac performance in both healthy and diseased individuals, yet the mechanisms that propagate this favorable adaptation remain poorly defined. We identify the cytokine cardiotrophin 1 (CT1) as a factor capable of recapitulating the key features of physiologic growth of the heart including transient and reversible hypertrophy of the myocardium, and stimulation of cardiomyocyte-derived angiogenic signals leading to increased vascularity. The capacity of CT1 to induce physiologic hypertrophy originates from a CK2-mediated restraining of caspase activation, preventing the transition to unrestrained pathologic growth. Exogenous CT1 protein delivery attenuated pathology and restored contractile function in a severe model of right heart failure, suggesting a novel treatment option for this intractable cardiac disease.

Biological and Genomic Differences of ERG Oncoprotein-Stratified Prostate Cancers from African and Caucasian Americans

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-13-2-0096 TITLE: Biological and Genomic Differences of ERG Oncoprotein-Stratified Prostate Cancers from African and...Biological and Genomic Differences of ERG Oncoprotein-Stratified Prostate Cancers from African and Caucasian Americans Sb. GRANT NUMBER W81 XWH-13-2...differences in the distribution of key clinico-pathologic patient features and molecular determinants for both ERG positive and ERG negative prostate cancer

A new feature constituting approach to detection of vocal fold pathology

NASA Astrophysics Data System (ADS)

Hariharan, M.; Polat, Kemal; Yaacob, Sazali

2014-08-01

In the last two decades, non-invasive methods through acoustic analysis of voice signal have been proved to be excellent and reliable tool to diagnose vocal fold pathologies. This paper proposes a new feature vector based on the wavelet packet transform and singular value decomposition for the detection of vocal fold pathology. k-means clustering based feature weighting is proposed to increase the distinguishing performance of the proposed features. In this work, two databases Massachusetts Eye and Ear Infirmary (MEEI) voice disorders database and MAPACI speech pathology database are used. Four different supervised classifiers such as k-nearest neighbour (k-NN), least-square support vector machine, probabilistic neural network and general regression neural network are employed for testing the proposed features. The experimental results uncover that the proposed features give very promising classification accuracy of 100% for both MEEI database and MAPACI speech pathology database.

The Research of Feature Extraction Method of Liver Pathological Image Based on Multispatial Mapping and Statistical Properties

PubMed Central

Liu, Huiling; Xia, Bingbing; Yi, Dehui

2016-01-01

We propose a new feature extraction method of liver pathological image based on multispatial mapping and statistical properties. For liver pathological images of Hematein Eosin staining, the image of R and B channels can reflect the sensitivity of liver pathological images better, while the entropy space and Local Binary Pattern (LBP) space can reflect the texture features of the image better. To obtain the more comprehensive information, we map liver pathological images to the entropy space, LBP space, R space, and B space. The traditional Higher Order Local Autocorrelation Coefficients (HLAC) cannot reflect the overall information of the image, so we propose an average correction HLAC feature. We calculate the statistical properties and the average gray value of pathological images and then update the current pixel value as the absolute value of the difference between the current pixel gray value and the average gray value, which can be more sensitive to the gray value changes of pathological images. Lastly the HLAC template is used to calculate the features of the updated image. The experiment results show that the improved features of the multispatial mapping have the better classification performance for the liver cancer. PMID:27022407

Dynamic nuclear envelope phenotype in rats overexpressing mutated human torsinA protein.

PubMed

Yu-Taeger, Libo; Gaiser, Viktoria; Lotzer, Larissa; Roenisch, Tina; Fabry, Benedikt Timo; Stricker-Shaver, Janice; Casadei, Nicolas; Walter, Michael; Schaller, Martin; Riess, Olaf; Nguyen, Huu Phuc; Ott, Thomas; Grundmann-Hauser, Kathrin

2018-05-08

A three-base-pair deletion in the human TOR1A gene is causative for the most common form of primary dystonia, the early-onset dystonia type 1 (DYT1 dystonia). The pathophysiological consequences of this mutation are still unknown.To study the pathology of the mutant torsinA (TOR1A) protein, we have generated a transgenic rat line that overexpresses the human mutant protein under the control of the human TOR1A promoter. This new animal model was phenotyped with several approaches, including behavioral tests and neuropathological analyses. A motor phenotype and cellular and ultrastructural key features of torsinA pathology were found in this new transgenic rat line supporting that it can be used as a model system for investigating the disease development. Analyses of mutant TOR1A protein expression in various brain regions also showed a dynamic expression pattern and a reversible nuclear envelope pathology. These findings suggest the differential vulnerabilities of distinct neuronal subpopulations. Furthermore the reversibility of the nuclear envelope pathology might be a therapeutic target to treat the disease. © 2018. Published by The Company of Biologists Ltd.

Pathological mandibular fracture: A severe complication of periimplantitis

PubMed Central

Rodriguez-Campo, Francisco; Naval-Parra, Beatriz; Sastre-Pérez, Jesús

2015-01-01

Nowadays, dental implant treatment is a very common option for patients even in medical compromised conditons. Some complications related to them have been described. Periimplantitis (PI) is one of the biggest concerns complications of these kind of treatments, probably has a multifactorial aethiology. Usually the consequences of PI are the loss of the implants and prostheses, expenses of money and time for dentists and patients. Very often PI implies the necesity of repeating the treatment . Pathological mandibular fracture due to PI is a severe but infrequent complication after dental implant treatment, especially after PI. In this study we present three cases of mandibular pathologic fractures among patients with different medical and dental records but similar management: two of them had been treated years ago of oral squamous cell carcinoma with surgery and radiotherapy, the other patient received oral bisphosphonates for osteoporosis some years after implantation. We analized the causes, consequences and posible prevention of these fractures as well as the special features of this kind of mandibular fractures and the different existing treatments. Key words:Periimplantitis, pathological mandibular fracture, mandibular atrophy, bicortical implants. PMID:26155355

Pathological mandibular fracture: A severe complication of periimplantitis.

PubMed

Naval-Gías, Luis; Rodriguez-Campo, Francisco; Naval-Parra, Beatriz; Sastre-Pérez, Jesús

2015-04-01

Nowadays, dental implant treatment is a very common option for patients even in medical compromised conditons. Some complications related to them have been described. Periimplantitis (PI) is one of the biggest concerns complications of these kind of treatments, probably has a multifactorial aethiology. Usually the consequences of PI are the loss of the implants and prostheses, expenses of money and time for dentists and patients. Very often PI implies the necesity of repeating the treatment . Pathological mandibular fracture due to PI is a severe but infrequent complication after dental implant treatment, especially after PI. In this study we present three cases of mandibular pathologic fractures among patients with different medical and dental records but similar management: two of them had been treated years ago of oral squamous cell carcinoma with surgery and radiotherapy, the other patient received oral bisphosphonates for osteoporosis some years after implantation. We analized the causes, consequences and posible prevention of these fractures as well as the special features of this kind of mandibular fractures and the different existing treatments. Key words:Periimplantitis, pathological mandibular fracture, mandibular atrophy, bicortical implants.

Constrained clusters of gene expression profiles with pathological features.

PubMed

Sese, Jun; Kurokawa, Yukinori; Monden, Morito; Kato, Kikuya; Morishita, Shinichi

2004-11-22

Gene expression profiles should be useful in distinguishing variations in disease, since they reflect accurately the status of cells. The primary clustering of gene expression reveals the genotypes that are responsible for the proximity of members within each cluster, while further clustering elucidates the pathological features of the individual members of each cluster. However, since the first clustering process and the second classification step, in which the features are associated with clusters, are performed independently, the initial set of clusters may omit genes that are associated with pathologically meaningful features. Therefore, it is important to devise a way of identifying gene expression clusters that are associated with pathological features. We present the novel technique of 'itemset constrained clustering' (IC-Clustering), which computes the optimal cluster that maximizes the interclass variance of gene expression between groups, which are divided according to the restriction that only divisions that can be expressed using common features are allowed. This constraint automatically labels each cluster with a set of pathological features which characterize that cluster. When applied to liver cancer datasets, IC-Clustering revealed informative gene expression clusters, which could be annotated with various pathological features, such as 'tumor' and 'man', or 'except tumor' and 'normal liver function'. In contrast, the k-means method overlooked these clusters.

Correlating mammographic and pathologic findings in clinical decision support using natural language processing and data mining methods.

PubMed

Patel, Tejal A; Puppala, Mamta; Ogunti, Richard O; Ensor, Joe E; He, Tiancheng; Shewale, Jitesh B; Ankerst, Donna P; Kaklamani, Virginia G; Rodriguez, Angel A; Wong, Stephen T C; Chang, Jenny C

2017-01-01

A key challenge to mining electronic health records for mammography research is the preponderance of unstructured narrative text, which strikingly limits usable output. The imaging characteristics of breast cancer subtypes have been described previously, but without standardization of parameters for data mining. The authors searched the enterprise-wide data warehouse at the Houston Methodist Hospital, the Methodist Environment for Translational Enhancement and Outcomes Research (METEOR), for patients with Breast Imaging Reporting and Data System (BI-RADS) category 5 mammogram readings performed between January 2006 and May 2015 and an available pathology report. The authors developed natural language processing (NLP) software algorithms to automatically extract mammographic and pathologic findings from free text mammogram and pathology reports. The correlation between mammographic imaging features and breast cancer subtype was analyzed using one-way analysis of variance and the Fisher exact test. The NLP algorithm was able to obtain key characteristics for 543 patients who met the inclusion criteria. Patients with estrogen receptor-positive tumors were more likely to have spiculated margins (P = .0008), and those with tumors that overexpressed human epidermal growth factor receptor 2 (HER2) were more likely to have heterogeneous and pleomorphic calcifications (P = .0078 and P = .0002, respectively). Mammographic imaging characteristics, obtained from an automated text search and the extraction of mammogram reports using NLP techniques, correlated with pathologic breast cancer subtype. The results of the current study validate previously reported trends assessed by manual data collection. Furthermore, NLP provides an automated means with which to scale up data extraction and analysis for clinical decision support. Cancer 2017;114-121. © 2016 American Cancer Society. © 2016 American Cancer Society.

Ameloblastomas: Clinicopathological features from 70 cases diagnosed in a single Oral Pathology service in an 8-year period

PubMed Central

Filizzola, Andressa-Incerte; Bartholomeu-dos-Santos, Teresa-Cristina-Ribeiro

2014-01-01

Ameloblastomas are odontogenic tumors that can present some distinct clinicopathological profiles when comparing different populations and studies. Objectives: The aim of the present study was to analyze the clinicopathological features from a series of ameloblastomas diagnosed in a single Oral Pathology service in Brazil in an 8-year period. Study Design: The files were revised and all cases diagnosed as ameloblastomas in the period were retrieved. All hematoxylin and eosin stained histological slides were reviewed and all clinical and radiological information were obtained through a review of the laboratory forms. Data were descriptively analyzed and a comparison was performed with the different ameloblastomas subtypes. Results: Seventy ameloblastomas composed the final sample, including 57 (81%) solid/multicystic, 9 (13%) unicystic, 2 (3%) desmoplastic and 2 (3%) peripheral ameloblastomas. Mean age of the affected patients was in the forth decade of life and there was a slight male predominance. Most tumors presented as multilocular radiolucencies, were located in the posterior mandible and showed the follicular and plexiform histological patterns. There was no difference on the mean age of the patients affected by solid and unicystic ameloblastomas. Conclusions: The present results showed that the clinicopathological features of the ameloblastomas included in this Brazilian sample were similar to the features described in most other worldwide populations. Key words:Ameloblastoma, solid, unicystic, review, epidemiology, histology. PMID:25129244

Transitional neoplasms of the naso-lacrimal system: A review of the histopathology and histogenesis☆

PubMed Central

Heathcote, J. Godfrey

2012-01-01

Transitional papilloma (inverted papilloma, Schneiderian papilloma) is a relatively common, benign epithelial neoplasm of the sinonasal tract that also occurs in the lacrimal drainage system. The name transitional papilloma is recommended because it reflects the key histological features required for pathological diagnosis, as well as the histogenesis of the tumour. The histogenesis of the tumour is reviewed, together with its natural history, which is characterized by bone remodelling and destruction, a tendency to recur and to undergo malignant transformation. Biomarkers associated with these features have been identified in the sinonasal tumours and may also be of relevance to the lacrimal sac tumours, although the necessary studies have not yet been undertaken. PMID:23960982

Control of regulatory T cell lineage commitment and maintenance.

PubMed

Josefowicz, Steven Z; Rudensky, Alexander

2009-05-01

Foxp3-expressing regulatory T (Treg) cells suppress pathology mediated by immune responses against self and foreign antigens and commensal microorganisms. Sustained expression of the transcription factor Foxp3, a key distinguishing feature of Treg cells, is required for their differentiation and suppressor function. In addition, Foxp3 expression prevents deviation of Treg cells into effector T cell lineages and confers dependence of Treg cell survival and expansion on growth factors, foremost interleukin-2, provided by activated effector T cells. In this review we discuss Treg cell differentiation and maintenance with a particular emphasis on molecular regulation of Foxp3 expression, arguably a key to mechanistic understanding of biology of regulatory T cells.

Homeostatic and pathogenic extramedullary hematopoiesis

PubMed Central

Kim, Chang H

2010-01-01

Extramedullary hematopoiesis (EH) is defined as hematopoiesis occurring in organs outside of the bone marrow; it occurs in diverse conditions, including fetal development, normal immune responses, and pathological circumstances. During fetal development, before formation of mature marrow, EH occurs in the yolk sac, fetal liver, and spleen. EH also occurs during active immune responses to pathogens. Most frequently, this response occurs in the spleen and liver for the production of antigen-presenting cells and phagocytes. EH also occurs when the marrow becomes inhabitable for stem and progenitor cells in certain pathological conditions, including myelofibrosis, where marrow cells are replaced with collagenous connective tissue fibers. Thus, EH occurs either actively or passively in response to diverse changes in the hematopoietic environment. This article reviews the key features and regulators of the major types of EH. PMID:22282679

[Correction of indigestion in chronic biliary pancreatitis].

PubMed

Trukhan, D I; Tarasova, L V

2013-01-01

Chronic pancreatitis (CP) is one of the most urgent and investigated problems in gastroenterology. Despite the variety of the spectrum of etiologic, pathogenetic and provoking factors for CP, one of the leading causes of disease pathology is pathology of biliary tract. A key element in the treatment of CP is a correction of the digestive system, with biliary pancreatitis feature that distinguishes it from other forms of pancreatitis, is a combination of exocrine pancreatic insufficiency with chronic biliary insufficiency. The variety of biochemical and immunological effects of ursodeoxycholic acid (UDCA) can treat it with biliary pancreatitis as the drug of etiological, pathogenetic and substitution therapy. UDCA (Ursosan) in combination with modern mini-microspheroidal polyfermental drugs significantly improves the clinical efficacy of the correction of the digestive system in biliary pancreatitis.

Microbial imbalance and intestinal pathologies: connections and contributions

PubMed Central

Yang, Ye; Jobin, Christian

2014-01-01

Microbiome analysis has identified a state of microbial imbalance (dysbiosis) in patients with chronic intestinal inflammation and colorectal cancer. The bacterial phylum Proteobacteria is often overrepresented in these individuals, with Escherichia coli being the most prevalent species. It is clear that a complex interplay between the host, bacteria and bacterial genes is implicated in the development of these intestinal diseases. Understanding the basic elements of these interactions could have important implications for disease detection and management. Recent studies have revealed that E. coli utilizes a complex arsenal of virulence factors to colonize and persist in the intestine. Some of these virulence factors, such as the genotoxin colibactin, were found to promote colorectal cancer in experimental models. In this Review, we summarize key features of the dysbiotic states associated with chronic intestinal inflammation and colorectal cancer, and discuss how the dysregulated interplay between host and bacteria could favor the emergence of E. coli with pathological traits implicated in these pathologies. PMID:25256712

Comprehensive Computational Pathological Image Analysis Predicts Lung Cancer Prognosis.

PubMed

Luo, Xin; Zang, Xiao; Yang, Lin; Huang, Junzhou; Liang, Faming; Rodriguez-Canales, Jaime; Wistuba, Ignacio I; Gazdar, Adi; Xie, Yang; Xiao, Guanghua

2017-03-01

Pathological examination of histopathological slides is a routine clinical procedure for lung cancer diagnosis and prognosis. Although the classification of lung cancer has been updated to become more specific, only a small subset of the total morphological features are taken into consideration. The vast majority of the detailed morphological features of tumor tissues, particularly tumor cells' surrounding microenvironment, are not fully analyzed. The heterogeneity of tumor cells and close interactions between tumor cells and their microenvironments are closely related to tumor development and progression. The goal of this study is to develop morphological feature-based prediction models for the prognosis of patients with lung cancer. We developed objective and quantitative computational approaches to analyze the morphological features of pathological images for patients with NSCLC. Tissue pathological images were analyzed for 523 patients with adenocarcinoma (ADC) and 511 patients with squamous cell carcinoma (SCC) from The Cancer Genome Atlas lung cancer cohorts. The features extracted from the pathological images were used to develop statistical models that predict patients' survival outcomes in ADC and SCC, respectively. We extracted 943 morphological features from pathological images of hematoxylin and eosin-stained tissue and identified morphological features that are significantly associated with prognosis in ADC and SCC, respectively. Statistical models based on these extracted features stratified NSCLC patients into high-risk and low-risk groups. The models were developed from training sets and validated in independent testing sets: a predicted high-risk group versus a predicted low-risk group (for patients with ADC: hazard ratio = 2.34, 95% confidence interval: 1.12-4.91, p = 0.024; for patients with SCC: hazard ratio = 2.22, 95% confidence interval: 1.15-4.27, p = 0.017) after adjustment for age, sex, smoking status, and pathologic tumor stage. The results suggest that the quantitative morphological features of tumor pathological images predict prognosis in patients with lung cancer. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

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

A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways

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

Furuya, Shinji; Chappell, Grace A.; Iwata, Yasuhir

Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl{sub 4})-induced fibrosis with chronic intra-gastric alcohol feeding. Male C57BL/6J mice were administered a low dose of CCl{sub 4} (0.2 ml/kg 2 × week/6 weeks) followed by alcohol intragastrically (up to 25 g/kg/day formore » 3 weeks) and with continued CCl{sub 4}. We observed that combined treatment with CCl{sub 4} and alcohol resulted in severe liver injury, more pronounced than using each treatment alone. Importantly, severe kidney injury was evident only in the combined treatment group. This mouse model reproduced distinct pathological features consistent with AKI in human alcoholic hepatitis. Transcriptomic analysis of kidneys revealed profound effects in the combined treatment group, with enrichment for damage-associated pathways, such as apoptosis, inflammation, immune-response and hypoxia. Interestingly, Havcr1 and Lcn2, biomarkers of AKI, were markedly up-regulated. Overall, this study established a novel mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways. - Highlights: • Acute kidney injury (AKI) is a critical complication in alcoholic hepatitis • We developed a novel mouse model of fibrosis- and alcohol-associated AKI • This model reproduces key molecular and pathological features of human AKI • This animal model can help identify new targeted therapies for alcoholic hepatitis.« less

Identification of key regulators for the migration and invasion of rheumatoid synoviocytes through a systems approach

PubMed Central

You, Sungyong; Yoo, Seung-Ah; Choi, Susanna; Kim, Ji-Young; Park, Su-Jung; Ji, Jong Dae; Kim, Tae-Hwan; Kim, Ki-Jo; Cho, Chul-Soo; Hwang, Daehee; Kim, Wan-Uk

2014-01-01

Rheumatoid synoviocytes, which consist of fibroblast-like synoviocytes (FLSs) and synovial macrophages (SMs), are crucial for the progression of rheumatoid arthritis (RA). Particularly, FLSs of RA patients (RA-FLSs) exhibit invasive characteristics reminiscent of cancer cells, destroying cartilage and bone. RA-FLSs and SMs originate differently from mesenchymal and myeloid cells, respectively, but share many pathologic functions. However, the molecular signatures and biological networks representing the distinct and shared features of the two cell types are unknown. We performed global transcriptome profiling of FLSs and SMs obtained from RA and osteoarthritis patients. By comparing the transcriptomes, we identified distinct molecular signatures and cellular processes defining invasiveness of RA-FLSs and proinflammatory properties of RA-SMs, respectively. Interestingly, under the interleukin-1β (IL-1β)–stimulated condition, the RA-FLSs newly acquired proinflammatory signature dominant in RA-SMs without losing invasive properties. We next reconstructed a network model that delineates the shared, RA-FLS–dominant (invasive), and RA-SM–dominant (inflammatory) processes. From the network model, we selected 13 genes, including periostin, osteoblast-specific factor (POSTN) and twist basic helix–loop–helix transcription factor 1 (TWIST1), as key regulator candidates responsible for FLS invasiveness. Of note, POSTN and TWIST1 expressions were elevated in independent RA-FLSs and further instigated by IL-1β. Functional assays demonstrated the requirement of POSTN and TWIST1 for migration and invasion of RA-FLSs stimulated with IL-1β. Together, our systems approach to rheumatoid synovitis provides a basis for identifying key regulators responsible for pathological features of RA-FLSs and -SMs, demonstrating how a certain type of cells acquires functional redundancy under chronic inflammatory conditions. PMID:24374632

Automated classification of brain tumor type in whole-slide digital pathology images using local representative tiles.

PubMed

Barker, Jocelyn; Hoogi, Assaf; Depeursinge, Adrien; Rubin, Daniel L

2016-05-01

Computerized analysis of digital pathology images offers the potential of improving clinical care (e.g. automated diagnosis) and catalyzing research (e.g. discovering disease subtypes). There are two key challenges thwarting computerized analysis of digital pathology images: first, whole slide pathology images are massive, making computerized analysis inefficient, and second, diverse tissue regions in whole slide images that are not directly relevant to the disease may mislead computerized diagnosis algorithms. We propose a method to overcome both of these challenges that utilizes a coarse-to-fine analysis of the localized characteristics in pathology images. An initial surveying stage analyzes the diversity of coarse regions in the whole slide image. This includes extraction of spatially localized features of shape, color and texture from tiled regions covering the slide. Dimensionality reduction of the features assesses the image diversity in the tiled regions and clustering creates representative groups. A second stage provides a detailed analysis of a single representative tile from each group. An Elastic Net classifier produces a diagnostic decision value for each representative tile. A weighted voting scheme aggregates the decision values from these tiles to obtain a diagnosis at the whole slide level. We evaluated our method by automatically classifying 302 brain cancer cases into two possible diagnoses (glioblastoma multiforme (N = 182) versus lower grade glioma (N = 120)) with an accuracy of 93.1% (p < 0.001). We also evaluated our method in the dataset provided for the 2014 MICCAI Pathology Classification Challenge, in which our method, trained and tested using 5-fold cross validation, produced a classification accuracy of 100% (p < 0.001). Our method showed high stability and robustness to parameter variation, with accuracy varying between 95.5% and 100% when evaluated for a wide range of parameters. Our approach may be useful to automatically differentiate between the two cancer subtypes. Copyright © 2015 Elsevier B.V. All rights reserved.

Advanced imaging of tau pathology in Alzheimer Disease: New perspectives from super resolution microscopy and label-free nanoscopy.

PubMed

Schierle, Gabriele S Kaminski; Michel, Claire H; Gasparini, Laura

2016-08-01

Alzheimer's disease (AD) is the main cause of dementia in the elderly population. Over 30 million people worldwide are living with dementia and AD prevalence is projected to increase dramatically in the next two decades. In terms of neuropathology, AD is characterized by two major cerebral hallmarks: extracellular β-amyloid (Aβ) plaques and intracellular Tau inclusions, which start accumulating in the brain 15-20 years before the onset of symptoms. Within this context, the scientific community worldwide is undertaking a wide research effort to detect AD pathology at its earliest, before symptoms appear. Neuroimaging of Aβ by positron emission tomography (PET) is clinically available and is a promising modality for early detection of Aβ pathology and AD diagnosis. Substantive efforts are ongoing to develop advanced imaging techniques for early detection of Tau pathology. Here, we will briefly describe the key features of Tau pathology and its heterogeneity across various neurodegenerative diseases bearing cerebral Tau inclusions (i.e., tauopathies). We will outline the current status of research on Tau-specific PET tracers and their clinical development. Finally, we will discuss the potential application of novel super-resolution and label-free techniques for investigating Tau pathology at the experimental level and their potential application for AD diagnosis. Microsc. Res. Tech. 79:677-683, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The pathological consequences of impaired genome integrity in humans; disorders of the DNA replication machinery.

PubMed

O'Driscoll, Mark

2017-01-01

Accurate and efficient replication of the human genome occurs in the context of an array of constitutional barriers, including regional topological constraints imposed by chromatin architecture and processes such as transcription, catenation of the helical polymer and spontaneously generated DNA lesions, including base modifications and strand breaks. DNA replication is fundamentally important for tissue development and homeostasis; differentiation programmes are intimately linked with stem cell division. Unsurprisingly, impairments of the DNA replication machinery can have catastrophic consequences for genome stability and cell division. Functional impacts on DNA replication and genome stability have long been known to play roles in malignant transformation through a variety of complex mechanisms, and significant further insights have been gained from studying model organisms in this context. Congenital hypomorphic defects in components of the DNA replication machinery have been and continue to be identified in humans. These disorders present with a wide range of clinical features. Indeed, in some instances, different mutations in the same gene underlie different clinical presentations. Understanding the origin and molecular basis of these features opens a window onto the range of developmental impacts of suboptimal DNA replication and genome instability in humans. Here, I will briefly overview the basic steps involved in DNA replication and the key concepts that have emerged from this area of research, before switching emphasis to the pathological consequences of defects within the DNA replication network; the human disorders. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The Role of Tau in Neurodegenerative Diseases and Its Potential as a Therapeutic Target

PubMed Central

2012-01-01

The abnormal deposition of proteins in and around neurons is a common pathological feature of many neurodegenerative diseases. Among these pathological proteins, the microtubule-associated protein tau forms intraneuronal filaments in a spectrum of neurological disorders. The discovery that dominant mutations in the MAPT gene encoding tau are associated with familial frontotemporal dementia strongly supports abnormal tau protein as directly involved in disease pathogenesis. This and other evidence suggest that tau is a worthwhile target for the prevention or treatment of tau-associated neurodegenerative diseases, collectively called tauopathies. However, it is critical to understand the normal biological roles of tau, the specific molecular events that induce tau to become neurotoxic, the biochemical nature of pathogenic tau, the means by which pathogenic tau exerts neurotoxicity, and how tau pathology propagates. Based on known differences between normal and abnormal tau, a number of approaches have been taken toward the discovery of potential therapeutics. Key questions still remain open, such as the nature of the connection between the amyloid-β protein of Alzheimer's disease and tau pathology. Answers to these questions should help better understand the nature of tauopathies and may also reveal new therapeutic targets and strategies. PMID:24278740

Phenotype in patients with intellectual disability and pathological results in array CGH.

PubMed

Caballero Pérez, V; López Pisón, F J; Miramar Gallart, M D; González Álvarez, A; García Jiménez, M C; García Iñiguez, J P; Orden Rueda, C; Gil Hernández, I; Fuertes Rodrigo, C; Fernando Martínez, R; Rodríguez Valle, A; Alcaine Villarroya, M J

Global developmental delay (GDD) and intellectual disability (ID) are frequent reasons for consultation in paediatric neurology departments. Nowadays, array comparative genomic hybridisation (array-CGH) is one of the most widely used techniques for diagnosing these disorders. Our purpose was to determine the phenotypic features associated with pathological results in this genetic test. We conducted a blind study of the epidemiological, clinical, anthropometric, and morphological features of 80 patients with unexplained ID to determine which features were associated with pathological results in array-CGH. Pathological results were found in 27.5% of the patients. Factors associated with pathological results in array-CGH were a family history of GDD/ID (OR = 12.1), congenital malformations (OR = 5.33), having more than 3 facial dysmorphic features (OR = 20.9), and hypotonia (OR = 3.25). Our findings are consistent with those reported by other published series. We therefore conclude that the probability of having pathological results in array-CGH increases with the presence of any of the features mentioned above in patients with ID/GDD. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Mechanisms of fibrosis: therapeutic translation for fibrotic disease

PubMed Central

Wynn, Thomas A; Ramalingam, Thirumalai R

2012-01-01

Fibrosis is a pathological feature of most chronic inflammatory diseases. Fibrosis, or scarring, is defined by the accumulation of excess extracellular matrix components. If highly progressive, the fibrotic process eventually leads to organ malfunction and death. Fibrosis affects nearly every tissue in the body. Here we discuss how key components of the innate and adaptive immune response contribute to the pathogenesis of fibrosis. We also describe how cell-intrinsic changes in important structural cells can perpetuate the fibrotic response by regulating the differentiation, recruitment, proliferation and activation of extracellular matrix–producing myofibroblasts. Finally, we highlight some of the key mechanisms and pathways of fibrosis that are being targeted as potential therapies for a variety of important human diseases. PMID:22772564

Tubal telocytes: factor infertility reason?

PubMed

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

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

[Standardization of the terms for Chinese herbal functions based on functional targeting].

PubMed

Xiao, Bin; Tao, Ou; Gu, Hao; Wang, Yun; Qiao, Yan-Jiang

2011-03-01

Functional analysis concisely summarizes and concentrates on the therapeutic characteristics and features of Chinese herbal medicine. Standardization of the terms for Chinese herbal functions not only plays a key role in modern research and development of Chinese herbal medicine, but also has far-reaching clinical applications. In this paper, a new method for standardizing the terms for Chinese herbal function was proposed. Firstly, functional targets were collected. Secondly, the pathological conditions and the mode of action of every functional target were determined by analyzing the references. Thirdly, the relationships between the pathological condition and the mode of action were determined based on Chinese medicine theory and data. This three-step approach allows for standardization of the terms for Chinese herbal functions. Promoting the standardization of Chinese medicine terms will benefit the overall clinical application of Chinese herbal medicine.

Poly(A) code analyses reveal key determinants for tissue-specific mRNA alternative polyadenylation

PubMed Central

Weng, Lingjie; Li, Yi; Xie, Xiaohui; Shi, Yongsheng

2016-01-01

mRNA alternative polyadenylation (APA) is a critical mechanism for post-transcriptional gene regulation and is often regulated in a tissue- and/or developmental stage-specific manner. An ultimate goal for the APA field has been to be able to computationally predict APA profiles under different physiological or pathological conditions. As a first step toward this goal, we have assembled a poly(A) code for predicting tissue-specific poly(A) sites (PASs). Based on a compendium of over 600 features that have known or potential roles in PAS selection, we have generated and refined a machine-learning algorithm using multiple high-throughput sequencing-based data sets of tissue-specific and constitutive PASs. This code can predict tissue-specific PASs with >85% accuracy. Importantly, by analyzing the prediction performance based on different RNA features, we found that PAS context, including the distance between alternative PASs and the relative position of a PAS within the gene, is a key feature for determining the susceptibility of a PAS to tissue-specific regulation. Our poly(A) code provides a useful tool for not only predicting tissue-specific APA regulation, but also for studying its underlying molecular mechanisms. PMID:27095026

Intelligibility Evaluation of Pathological Speech through Multigranularity Feature Extraction and Optimization.

PubMed

Fang, Chunying; Li, Haifeng; Ma, Lin; Zhang, Mancai

2017-01-01

Pathological speech usually refers to speech distortion resulting from illness or other biological insults. The assessment of pathological speech plays an important role in assisting the experts, while automatic evaluation of speech intelligibility is difficult because it is usually nonstationary and mutational. In this paper, we carry out an independent innovation of feature extraction and reduction, and we describe a multigranularity combined feature scheme which is optimized by the hierarchical visual method. A novel method of generating feature set based on S -transform and chaotic analysis is proposed. There are BAFS (430, basic acoustics feature), local spectral characteristics MSCC (84, Mel S -transform cepstrum coefficients), and chaotic features (12). Finally, radar chart and F -score are proposed to optimize the features by the hierarchical visual fusion. The feature set could be optimized from 526 to 96 dimensions based on NKI-CCRT corpus and 104 dimensions based on SVD corpus. The experimental results denote that new features by support vector machine (SVM) have the best performance, with a recognition rate of 84.4% on NKI-CCRT corpus and 78.7% on SVD corpus. The proposed method is thus approved to be effective and reliable for pathological speech intelligibility evaluation.

Feature selection for examining behavior by pathology laboratories.

PubMed

Hawkins, S; Williams, G; Baxter, R

2001-08-01

Australia has a universal health insurance scheme called Medicare, which is managed by Australia's Health Insurance Commission. Medicare payments for pathology services generate voluminous transaction data on patients, doctors and pathology laboratories. The Health Insurance Commission (HIC) currently uses predictive models to monitor compliance with regulatory requirements. The HIC commissioned a project to investigate the generation of new features from the data. Feature generation has not appeared as an important step in the knowledge discovery in databases (KDD) literature. New interesting features for use in predictive modeling are generated. These features were summarized, visualized and used as inputs for clustering and outlier detection methods. Data organization and data transformation methods are described for the efficient access and manipulation of these new features.

ERP-based detection of brain pathology in rat models for preclinical Alzheimer's disease

NASA Astrophysics Data System (ADS)

Nouriziabari, Seyed Berdia

Early pathological features of Alzheimer's disease (AD) include the accumulation of hyperphosphorylated tau protein (HP-tau) in the entorhinal cortex and progressive loss of basal forebrain (BF) cholinergic neurons. These pathologies are known to remain asymptomatic for many years before AD is clinically diagnosed; however, they may induce aberrant brain processing which can be captured as an abnormality in event-related potentials (ERPs). Here, we examined cortical ERPs while a differential associative learning paradigm was applied to adult male rats with entorhinal HP-tau, pharmacological blockade of muscarinic acetylcholine receptors, or both conditions. Despite no impairment in differential associative and reversal learning, each pathological feature induced distinct abnormality in cortical ERPs to an extent that was sufficient for machine classifiers to accurately detect a specific type of pathology based on these ERP features. These results highlight a potential use of ERPs during differential associative learning as a biomarker for asymptomatic AD pathology.

The history of happiness.

PubMed

Stearns, Peter N

2012-01-01

In the 18th century, the Enlightenment ushered in the notion that happiness was the attainment of a worthy life. Since then the pursuit of happiness has spread to every aspect of behavior, from religion and politics to work and parenting. Today the happiness imperative creates pressures that, paradoxically, can make us miserable. Sadness is often mistaken for a pathology. Understanding the cultural commitment to good cheer as an artifact of modern history, not as an inherent feature of the human condition, opens new opportunities for understanding key facets of our social and personal experience.

Image analysis and machine learning in digital pathology: Challenges and opportunities.

PubMed

Madabhushi, Anant; Lee, George

2016-10-01

With the rise in whole slide scanner technology, large numbers of tissue slides are being scanned and represented and archived digitally. While digital pathology has substantial implications for telepathology, second opinions, and education there are also huge research opportunities in image computing with this new source of "big data". It is well known that there is fundamental prognostic data embedded in pathology images. The ability to mine "sub-visual" image features from digital pathology slide images, features that may not be visually discernible by a pathologist, offers the opportunity for better quantitative modeling of disease appearance and hence possibly improved prediction of disease aggressiveness and patient outcome. However the compelling opportunities in precision medicine offered by big digital pathology data come with their own set of computational challenges. Image analysis and computer assisted detection and diagnosis tools previously developed in the context of radiographic images are woefully inadequate to deal with the data density in high resolution digitized whole slide images. Additionally there has been recent substantial interest in combining and fusing radiologic imaging and proteomics and genomics based measurements with features extracted from digital pathology images for better prognostic prediction of disease aggressiveness and patient outcome. Again there is a paucity of powerful tools for combining disease specific features that manifest across multiple different length scales. The purpose of this review is to discuss developments in computational image analysis tools for predictive modeling of digital pathology images from a detection, segmentation, feature extraction, and tissue classification perspective. We discuss the emergence of new handcrafted feature approaches for improved predictive modeling of tissue appearance and also review the emergence of deep learning schemes for both object detection and tissue classification. We also briefly review some of the state of the art in fusion of radiology and pathology images and also combining digital pathology derived image measurements with molecular "omics" features for better predictive modeling. The review ends with a brief discussion of some of the technical and computational challenges to be overcome and reflects on future opportunities for the quantitation of histopathology. Copyright © 2016 Elsevier B.V. All rights reserved.

Content-based cell pathology image retrieval by combining different features

NASA Astrophysics Data System (ADS)

Zhou, Guangquan; Jiang, Lu; Luo, Limin; Bao, Xudong; Shu, Huazhong

2004-04-01

Content Based Color Cell Pathology Image Retrieval is one of the newest computer image processing applications in medicine. Recently, some algorithms have been developed to achieve this goal. Because of the particularity of cell pathology images, the result of the image retrieval based on single characteristic is not satisfactory. A new method for pathology image retrieval by combining color, texture and morphologic features to search cell images is proposed. Firstly, nucleus regions of leukocytes in images are automatically segmented by K-mean clustering method. Then single leukocyte region is detected by utilizing thresholding algorithm segmentation and mathematics morphology. The features that include color, texture and morphologic features are extracted from single leukocyte to represent main attribute in the search query. The features are then normalized because the numerical value range and physical meaning of extracted features are different. Finally, the relevance feedback system is introduced. So that the system can automatically adjust the weights of different features and improve the results of retrieval system according to the feedback information. Retrieval results using the proposed method fit closely with human perception and are better than those obtained with the methods based on single feature.

C/EBPβ regulates delta-secretase expression and mediates pathogenesis in mouse models of Alzheimer's disease.

PubMed

Wang, Zhi-Hao; Gong, Ke; Liu, Xia; Zhang, Zhentao; Sun, Xiaoou; Wei, Zheng Zachory; Yu, Shan Ping; Manfredsson, Fredric P; Sandoval, Ivette M; Johnson, Peter F; Jia, Jianping; Wang, Jian-Zhi; Ye, Keqiang

2018-05-03

Delta-secretase cleaves both APP and Tau to mediate the formation of amyloid plaques and neurofibrillary tangle in Alzheimer's disease (AD). However, how aging contributes to an increase in delta-secretase expression and AD pathologies remains unclear. Here we show that a CCAAT-enhancer-binding protein (C/EBPβ), an inflammation-regulated transcription factor, acts as a key age-dependent effector elevating both delta-secretase (AEP) and inflammatory cytokines expression in mediating pathogenesis in AD mouse models. We find that C/EBPβ regulates delta-secretase transcription and protein levels in an age-dependent manner. Overexpression of C/EBPβ in young 3xTg mice increases delta-secretase and accelerates the pathological features including cognitive dysfunctions, which is abolished by inactive AEP C189S. Conversely, depletion of C/EBPβ from old 3xTg or 5XFAD mice diminishes delta-secretase and reduces AD pathologies, leading to amelioration of cognitive impairment in these AD mouse models. Thus, our findings support that C/EBPβ plays a pivotal role in AD pathogenesis via increasing delta-secretase expression.

Pathology report assessment of incidental gallbladder carcinoma diagnosed from cholecystectomy specimens: results of a French multicentre survey.

PubMed

Chatelain, Denis; Fuks, David; Farges, Olivier; Attencourt, Christophe; Pruvot, François René; Regimbeau, Jean-Marc

2013-12-01

To assess the accuracy of pathology reports on gallbladder specimens from patients operated on for incidental gallbladder carcinoma. Demographic data, details on pathological reports including gross and microscopic features section were recorded in 100 selected patients with incidental gallbladder carcinoma diagnosed from 2004 to 2007. Pathology reports had a conventional format in 93% of cases, without any standardization. Turnaround time ranged from 1 to 35 days. Frozen sections were performed in 20% of cases. The reports failed to give information on prognostic histological factors: exact tumour site (missing in 55% of cases), depth of tumour infiltration within the gallbladder wall (missing in 10%), surgical margins (missing in 40% for the cystic duct margin), tumour differentiation (missing in 28%), vascular invasion (missing in 52%) and perineural invasion (missing in 51%). Lymph node status could be assessed in 44% of cases. Distances between the tumour and the cystic duct and circumferential margins were not specified in 68% and 84% of cases. Only 29% of the reports clearly stated the pTNM stage in the conclusion section. The pT stage with margin status and tumour site was only mentioned in 30% of the reports. Pathology reports on gallbladder carcinoma from participating centres frequently lacked important information on key prognostic histological factors. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2001-01-01

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

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.

Does the choice of display system influence perception and visibility of clinically relevant features in digital pathology images?

NASA Astrophysics Data System (ADS)

Kimpe, Tom; Rostang, Johan; Avanaki, Ali; Espig, Kathryn; Xthona, Albert; Cocuranu, Ioan; Parwani, Anil V.; Pantanowitz, Liron

2014-03-01

Digital pathology systems typically consist of a slide scanner, processing software, visualization software, and finally a workstation with display for visualization of the digital slide images. This paper studies whether digital pathology images can look different when presenting them on different display systems, and whether these visual differences can result in different perceived contrast of clinically relevant features. By analyzing a set of four digital pathology images of different subspecialties on three different display systems, it was concluded that pathology images look different when visualized on different display systems. The importance of these visual differences is elucidated when they are located in areas of the digital slide that contain clinically relevant features. Based on a calculation of dE2000 differences between background and clinically relevant features, it was clear that perceived contrast of clinically relevant features is influenced by the choice of display system. Furthermore, it seems that the specific calibration target chosen for the display system has an important effect on the perceived contrast of clinically relevant features. Preliminary results suggest that calibrating to DICOM GSDF calibration performed slightly worse than sRGB, while a new experimental calibration target CSDF performed better than both DICOM GSDF and sRGB. This result is promising as it suggests that further research work could lead to better definition of an optimized calibration target for digital pathology images resulting in a positive effect on clinical performance.

Parkinsonism in Spinocerebellar Ataxia

PubMed Central

Park, Hyeyoung; Kim, Han-Joon; Jeon, Beom S.

2015-01-01

Spinocerebellar ataxia (SCA) presents heterogeneous clinical phenotypes, and parkinsonism is reported in diverse SCA subtypes. Both levodopa responsive Parkinson disease (PD) like phenotype and atypical parkinsonism have been described especially in SCA2, SCA3, and SCA17 with geographic differences in prevalence. SCA2 is the most frequently reported subtype of SCA related to parkinsonism worldwide. Parkinsonism in SCA2 has unique genetic characteristics, such as low number of expansions and interrupted structures, which may explain the sporadic cases with low penetrance. Parkinsonism in SCA17 is more remarkable in Asian populations especially in Korea. In addition, an unclear cutoff of the pathologic range is the key issue in SCA17 related parkinsonism. SCA3 is more common in western cohorts. SCA6 and SCA8 have also been reported with a PD-like phenotype. Herein, we reviewed the epidemiologic, clinical, genetic, and pathologic features of parkinsonism in SCAs. PMID:25866756

Clinicopathologic features of patients with non-small cell lung cancer harboring the EML4-ALK fusion gene: a meta-analysis.

PubMed

Wang, Ying; Wang, Shumin; Xu, Shiguang; Qu, Jiaqi; Liu, Bo

2014-01-01

The frequencies of EML4-ALK fusion gene in non-small cell lung cancer (NSCLC) with different clinicopathologic features described by previous studies are inconsistent. The key demographic and pathologic features associated with EML4-ALK fusion gene have not been definitively established. This meta-analysis was conducted to compare the frequency of the EML4-ALK fusion gene in patients with different clinicopathologic features and to identify an enriched population of patients with NSCLC harboring EML4-ALK fusion gene. The Pubmed and Embase databases for all studies on EML4-ALK fusion gene in NSCLC patients were searched up to July 2014. A criteria list and exclusion criteria were established to screen the studies. The frequency of the EML4-ALK fusion gene and the clinicopathologic features, including smoking status, pathologic type, gender, and EGFR status were abstracted. Seventeen articles consisting of 4511 NSCLC cases were included in this meta-analysis. A significant lower EML4-ALK fusion gene positive rate was associated with smokers (pooled OR = 0.40, 95% CI = 0.30-0.54, P<0.00001). A significantly higher EML4-ALK fusion gene positivity rate was associated with adenocarcinomas (pooled OR = 2.53, 95% CI = 1.66-3.86, P<0.0001) and female (pooled OR = 0.61, 95% CI = 0.41-0.90, P = 0.01). We found that a significantly lower EML4-ALK fusion gene positivity rate was associated with EGFR mutation (pooled OR = 0.07, 95% CI = 0.03-0.19, P<0.00001). No publication bias was observed in any meta-analysis (all P value of Egger's test >0.05); however, because of the small sample size, no results were in the meta-analysis regarding EGFR gene status. This meta-analysis revealed that the EML4-ALK fusion gene is highly correlated with a never/light smoking history, female and the pathologic type of adenocarcinoma, and is largely mutually exclusive of EGFR.

Clinicopathologic Features of Patients with Non-Small Cell Lung Cancer Harboring the EML4-ALK Fusion Gene: A Meta-Analysis

PubMed Central

Wang, Shumin; Xu, Shiguang; Qu, Jiaqi

2014-01-01

Background The frequencies of EML4-ALK fusion gene in non-small cell lung cancer (NSCLC) with different clinicopathologic features described by previous studies are inconsistent. The key demographic and pathologic features associated with EML4-ALK fusion gene have not been definitively established. This meta-analysis was conducted to compare the frequency of the EML4-ALK fusion gene in patients with different clinicopathologic features and to identify an enriched population of patients with NSCLC harboring EML4-ALK fusion gene. Methods The Pubmed and Embase databases for all studies on EML4-ALK fusion gene in NSCLC patients were searched up to July 2014. A criteria list and exclusion criteria were established to screen the studies. The frequency of the EML4-ALK fusion gene and the clinicopathologic features, including smoking status, pathologic type, gender, and EGFR status were abstracted. Results Seventeen articles consisting of 4511 NSCLC cases were included in this meta-analysis. A significant lower EML4-ALK fusion gene positive rate was associated with smokers (pooled OR = 0.40, 95% CI = 0.30–0.54, P<0.00001). A significantly higher EML4-ALK fusion gene positivity rate was associated with adenocarcinomas (pooled OR = 2.53, 95% CI = 1.66–3.86, P<0.0001) and female (pooled OR = 0.61, 95% CI = 0.41–0.90, P = 0.01). We found that a significantly lower EML4-ALK fusion gene positivity rate was associated with EGFR mutation (pooled OR = 0.07, 95% CI = 0.03–0.19, P<0.00001). No publication bias was observed in any meta-analysis (all P value of Egger's test >0.05); however, because of the small sample size, no results were in the meta-analysis regarding EGFR gene status. Conclusion This meta-analysis revealed that the EML4-ALK fusion gene is highly correlated with a never/light smoking history, female and the pathologic type of adenocarcinoma, and is largely mutually exclusive of EGFR. PMID:25360721

Successful treatment of suspected organizing pneumonia in a patient without typical imaging and pathological characteristic: A case report.

PubMed

Ailing, Liu; Ning, Xu; Tao, Qu; Aijun, Li

2017-01-01

Organizing pneumonia (OP) is a clinicopathological entity characterized by granulation tissue plugs in the lumen of small airways, alveolar ducts, and alveoli. Diagnosis of OP needs the combination of clinical features, imaging and pathology. But it occurs often that there are no typical pathological features to support the diagnosis, which poses a challenge for clinicians' diagnosis and treatment. We diagnosed a case of OP without typical imaging and pathological characteristic and treated successfully. Finally we confirmed the pathological diagnosis. Not every OP case is supported by pathological evidence and typical imaging changes. It is important for us to judge and decide the diagnosis according to clinical experience.

Pathological criteria and practical issues in papillary lesions of the breast - a review.

PubMed

Ni, Yun-Bi; Tse, Gary M

2016-01-01

Papillary lesions of the breast include a broad spectrum of lesions, ranging from benign papilloma, papilloma with atypical ductal hyperplasia (ADH) or ductal carcinoma in situ (DCIS) to papillary carcinoma. The accurate diagnosis of mammary papillary lesions is a challenge for pathologists, owing to the overlapping features among these lesions. In this review, some of the diagnostic criteria of papillary lesions are discussed, with special emphasis on some key morphological features, namely fibrovascular cores, epithelial proliferation in a solid pattern, intraductal papilloma complicated by ADH or DCIS, and invasion and its mimics. The roles of immunohistochemistry, and the interpretation of myoepithelial cell markers, hormone receptors, and high molecular weight cytokeratin, are addressed. Finally, novel biomarkers and genetic aberrations in papillary lesions are summarized. © 2015 John Wiley & Sons Ltd.

Paired Helical Filaments from Alzheimer Disease Brain Induce Intracellular Accumulation of Tau Protein in Aggresomes*

PubMed Central

Santa-Maria, Ismael; Varghese, Merina; Ksiȩżak-Reding, Hanna; Dzhun, Anastasiya; Wang, Jun; Pasinetti, Giulio M.

2012-01-01

Abnormal folding of tau protein leads to the generation of paired helical filaments (PHFs) and neurofibrillary tangles, a key neuropathological feature in Alzheimer disease and tauopathies. A specific anatomical pattern of pathological changes developing in the brain suggests that once tau pathology is initiated it propagates between neighboring neuronal cells, possibly spreading along the axonal network. We studied whether PHFs released from degenerating neurons could be taken up by surrounding cells and promote spreading of tau pathology. Neuronal and non-neuronal cells overexpressing green fluorescent protein-tagged tau (GFP-Tau) were treated with isolated fractions of human Alzheimer disease-derived PHFs for 24 h. We found that cells internalized PHFs through an endocytic mechanism and developed intracellular GFP-Tau aggregates with attributes of aggresomes. This was particularly evident by the perinuclear localization of aggregates and redistribution of the vimentin intermediate filament network and retrograde motor protein dynein. Furthermore, the content of Sarkosyl-insoluble tau, a measure of abnormal tau aggregation, increased 3-fold in PHF-treated cells. An exosome-related mechanism did not appear to be involved in the release of GFP-Tau from untreated cells. The evidence that cells can internalize PHFs, leading to formation of aggresome-like bodies, opens new therapeutic avenues to prevent propagation and spreading of tau pathology. PMID:22496370

[The clinical and pathologic features of Charcot-Marie-Tooth disease].

PubMed

Xiao, Bo; Xie, Jusheng; Yang, Xiaosu; Wu, Zhiguo; Xiao, Jianfeng; Li, Jing

2002-11-01

To study the clinical and pathological features of Charcot-Marie-Tooth disease (CMT). The general clinical data, the changes of neuroelectrophysiology and the pathological features of neural and muscular biopsy of 20 CMT patients were comprehensively analyzed. The clinical manifestations in the two types of CMT were nearly the same, but the changes of neuroelectrophysiology and the pathological characteristics of the neural and muscular biopsy in the two types were obviously different. 16 cases of CMT type 1 were characterized by decreased sensory nerve conduction velocity (SNCV < 30 m/s) and are associated with demyelinating hypertrophic neuropathy. 4 cases of CMT tylpe 2 were characterized by normal SNCV and associated with axonopathy. Neuroelectrophysiology and neural and muscular biopsy are important for the diagnosis of CMT.

Bronchoalveolar carcinoma: clinical, radiologic, and pathologic factors and survival.

PubMed

Okubo, K; Mark, E J; Flieder, D; Wain, J C; Wright, C D; Moncure, A C; Grillo, H C; Mathisen, D J

1999-10-01

The principal feature of bronchoalveolar carcinoma is that it spreads along airways or aerogenously with multifocality, but many issues are unresolved. We studied 119 patients with pathologically confirmed bronchoalveolar carcinoma. Symptoms, smoking status, radiologic findings, the size of tumor, operative procedures, and complications were reviewed. We studied the pathologic features: presence or absence of aerogenous spread, patterns of growth, cell type, nuclear grade, mitosis, rate of bronchoalveolar carcinoma in adenocarcinoma, and lymphocyte infiltration. The correlation among clinical, radiologic, and pathologic findings was examined, and the factors affecting survival were analyzed. Symptomatic patients had more infiltrative radiographic features, and asymptomatic patients tended to have more mass-like features (P <.0001). Tumors with radiographically infiltrating lesions tended to have mucinous histologic features (P =.006). Tumors with mass lesions by radiograph tended to have nonmucinous and sclerosing histologic features (P =.003). Aerogenous spread was seen in 94% of specimens. The presence of a variety of cell types suggested multiple clonal origin. The overall survival in those patients undergoing resection was 69.1% at 5 years and 56.5% at 10 years. The significant factors affecting survival were radiologic presence of a mass or infiltrate, pathologic findings of the presence of sclerosis, association with a scar, the rate of bronchoalveolar carcinoma in adenocarcinoma, lymphocyte infiltration grade, nodal involvement, and status of complete resection. Mitosis or nuclear grade of tumor cells did not correlate with survival. Bronchoalveolar carcinoma showed good overall survival with appropriate surgical procedures. Certain radiologic or pathologic findings correlated with survival. These findings may enhance the ability to predict long-term survival.

Polyglutamine aggregation in Huntington and related diseases.

PubMed

Polling, Saskia; Hill, Andrew F; Hatters, Danny M

2012-01-01

Polyglutamine (polyQ)-expansions in different proteins cause nine neurodegenerative diseases. While polyQ aggregation is a key pathological hallmark of these diseases, how aggregation relates to pathogenesis remains contentious. In this chapter, we review what is known about the aggregation process and how cells respond and interact with the polyQ-expanded proteins. We cover detailed biophysical and structural studies to uncover the intrinsic features of polyQ aggregates and concomitant effects in the cellular environment. We also examine the functional consequences ofpolyQ aggregation and how cells may attempt to intervene and guide the aggregation process.

Radiology of pancreatic neoplasms: An update

PubMed Central

de la Santa, Luis Gijón; Retortillo, José Antonio Pérez; Miguel, Ainhoa Camarero; Klein, Lea Marie

2014-01-01

Diagnostic imaging is an important tool to evaluate pancreatic neoplasms. We describe the imaging features of pancreatic malignancies and their benign mimics. Accurate detection and staging are essential for ensuring appropriate selection of patients who will benefit from surgery and for preventing unnecessary surgeries in patients with unresectable disease. Ultrasound, multidetector computed tomography with multiplanar reconstruction and magnetic resonance imaging can help to do a correct diagnosis. Radiologists should be aware of the wide variety of anatomic variants and pathologic conditions that may mimic pancreatic neoplasms. The knowledge of the most important characteristic key findings may facilitate the right diagnosis. PMID:25232458

Radiology of pancreatic neoplasms: An update.

PubMed

de la Santa, Luis Gijón; Retortillo, José Antonio Pérez; Miguel, Ainhoa Camarero; Klein, Lea Marie

2014-09-15

Diagnostic imaging is an important tool to evaluate pancreatic neoplasms. We describe the imaging features of pancreatic malignancies and their benign mimics. Accurate detection and staging are essential for ensuring appropriate selection of patients who will benefit from surgery and for preventing unnecessary surgeries in patients with unresectable disease. Ultrasound, multidetector computed tomography with multiplanar reconstruction and magnetic resonance imaging can help to do a correct diagnosis. Radiologists should be aware of the wide variety of anatomic variants and pathologic conditions that may mimic pancreatic neoplasms. The knowledge of the most important characteristic key findings may facilitate the right diagnosis.

Persistent induction of goblet cell differentiation in the airways: Therapeutic approaches.

PubMed

Reid, Andrew T; Veerati, Punnam Chander; Gosens, Reinoud; Bartlett, Nathan W; Wark, Peter A; Grainge, Chris L; Stick, Stephen M; Kicic, Anthony; Moheimani, Fatemeh; Hansbro, Philip M; Knight, Darryl A

2018-05-01

Dysregulated induction of goblet cell differentiation results in excessive production and retention of mucus and is a common feature of several chronic airways diseases. To date, therapeutic strategies to reduce mucus accumulation have focused primarily on altering the properties of the mucus itself, or have aimed to limit the production of mucus-stimulating cytokines. Here we review the current knowledge of key molecular pathways that are dysregulated during persistent goblet cell differentiation and highlights both pre-existing and novel therapeutic strategies to combat this pathology. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Implementation and Validation of PACS Integrated Peer Review for Discrepancy Recording of Radiology Reporting.

PubMed

Olthof, A W; van Ooijen, P M A

2016-09-01

The purpose of this work is to demonstrate the possibility of implementation of a PACS-integrated peer review system based on RADPEER™ classification providing a step-wise implementation plan utilizing features already present in the standard PACS implementation and without the requirement of additional software development. Furthermore, we show the usage and effects of the system during the first 30 months of usage. To allow fast and easy implementation into the daily workflow the key-word feature of the PACS was used. This feature allows to add a key-word to an imaging examination for easy searching in the PACS database (e.g. by entering keywords for different kinds of pathology). For peer review we implemented a keyword structure including a code for each of the existing RADPEER™ scoring language terms and a keyword with the phrase "second reading" followed by the name of the individual radiologist. The use of the short-keys to enter the codes in relation to the peer review was a simple to use solution. During the study 599 reports were peer reviewed. The active participation in this study of the radiologists varies and ranges from 3 to 327 reviews per radiologist. The number of peer review is highest in CT and CR. There are no significant technical obstacles to implement a PACS-integrated RADPEER™ -system based on key-words allowing easy integration of peer review into the daily routine without the requirement of additional software. Peer review implemented in a non-random setting based on relevant priors could already help in increasing the quality of radiological reporting and serve as continuing education among peers. Decisiveness, tact and trust are needed to promote use of the system and collaborative discussion of the results by radiologist.

Idiopathic REM Sleep Behavior Disorder in the development of Parkinson’s Disease

PubMed Central

Boeve, Bradley F.

2016-01-01

Summary Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with Lewy body disease (LBD) pathology in central and peripheral nervous system structures. While the etiology of PD is not fully understood, recent clinicopathologic analyses by Braak and colleagues have led to the development of a staging system of LBD pathology in the evolution of prototypical PD. This system posits a relatively predictable topography of progression of LBD pathology in the central nervous system, from olfactory structures and the medulla, which then progresses rostrally from the medulla to the pons, then midbrain/substantia nigra, then limbic, and then neocortical structures. If this topography and temporal evolution of LBD pathology indeed occur, one could hypothesize that other manifestations of LBD which reflect degeneration of olfactory and pontomedullary structures may begin many years prior to the development of prominent nigral degeneration and the associated parkinsonian features of classic PD. One such manifestation of prodromal PD is rapid eye movement (REM) sleep behavior disorder (RBD), which is a parasomnia manifested by vivid dreams associated with dream enactment behavior during REM sleep. Animal and human studies have implicated lesions or dysfunction in REM sleep and motor control circuitry in the pontomedullary structures cause RBD phenomenology, and degeneration of these structures could explain the presence of RBD years or decades prior to the onset of parkinsonism in those who develop PD. This review incorporates the rapidly growing literature on RBD and other prodromal features of PD as it pertains to the Braak staging system, and presents a framework from which many hypotheses can be (and already are being) tested. An important outcome of this framework will be to determine the natural history of RBD and associated features in the evolution to PD in the current era of no disease-modifying therapies – these natural history data will permit the development of clinical trail methodology with key measures and adequate power to detect if such therapies delay the onset or prevent the development of PD and associated morbidity. PMID:23578773

[Immediate prediction of recovery, based on emotional impact of vertigo].

PubMed

Dal-Lago, Andrés H; Ceballos-Lizarraga, Ricardo; Carmona, Sergio

2014-01-01

This work presents deeper studies of comorbidity between anxiety and vestibular pathology. The aim of this work was to comprehend the reasons why patients do not feel «fully recovered» even though the treating professionals discharge them. We studied the features of personality that can favour the continuity of the condition. The questionnaire for measuring the emotional impact of vertigo makes it possible to determine if the patient has a psychological style with a tendency to develop pathological anxiety levels. Anxiety is a subjective characteristic determinant in difficulties with medical treatment. The questionnaire was applied to 198 patients in Argentina and Mexico in parallel. Each pathology was treated by standard medical procedures. The study focused on determining the correlation between «feeling fully recovered or not at the end of treatment» and the questionnaire scores obtained before the approach. In more than 80% of cases, high scores (>15 points) on the questionnaire were correlated with the difficulty presented by the patients for full recovery from the pathology after medical treatment. The objective assessments (duration and intensity of symptoms, time of onset of the disease, etc.) do not exactly predict possible difficulties during treatment of vertigo. Consequently, we consider the patient's subjective assessment of how the vestibular pathology affects him or her to be determinant. That key information allows us to predict the course of the illness and the probability of a full recovery. Copyright © 2013 Elsevier España, S.L. All rights reserved.

In vivo signatures of nonfluent/agrammatic primary progressive aphasia caused by FTLD pathology

PubMed Central

Caso, Francesca; Mandelli, Maria Luisa; Henry, Maya; Gesierich, Benno; Bettcher, Brianne M.; Ogar, Jennifer; Filippi, Massimo; Comi, Giancarlo; Magnani, Giuseppe; Sidhu, Manu; Trojanowski, John Q.; Huang, Eric J.; Grinberg, Lea T.; Miller, Bruce L.; Dronkers, Nina; Seeley, William W.

2014-01-01

Objective: To identify early cognitive and neuroimaging features of sporadic nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) caused by frontotemporal lobar degeneration (FTLD) subtypes. Methods: We prospectively collected clinical, neuroimaging, and neuropathologic data in 11 patients with sporadic nfvPPA with FTLD-tau (nfvPPA-tau, n = 9) or FTLD–transactive response DNA binding protein pathology of 43 kD type A (nfvPPA-TDP, n = 2). We analyzed patterns of cognitive and gray matter (GM) and white matter (WM) atrophy at presentation in the whole group and in each pathologic subtype separately. We also considered longitudinal clinical data. Results: At first evaluation, regardless of pathologic FTLD subtype, apraxia of speech (AOS) was the most common cognitive feature and atrophy involved the left posterior frontal lobe. Each pathologic subtype showed few distinctive features. At presentation, patients with nfvPPA-tau presented with mild to moderate AOS, mixed dysarthria with prominent hypokinetic features, clear agrammatism, and atrophy in the GM of the left posterior frontal regions and in left frontal WM. While speech and language deficits were prominent early, within 3 years of symptom onset, all patients with nfvPPA-tau developed significant extrapyramidal motor signs. At presentation, patients with nfvPPA-TDP had severe AOS, dysarthria with spastic features, mild agrammatism, and atrophy in left posterior frontal GM only. Selective mutism occurred early, when general neurologic examination only showed mild decrease in finger dexterity in the right hand. Conclusions: Clinical features in sporadic nfvPPA caused by FTLD subtypes relate to neurodegeneration of GM and WM in frontal motor speech and language networks. We propose that early WM atrophy in nfvPPA is suggestive of FTLD-tau pathology while early selective GM loss might be indicative of FTLD-TDP. PMID:24353332

A novel method for morphological pleomorphism and heterogeneity quantitative measurement: Named cell feature level co-occurrence matrix.

PubMed

Saito, Akira; Numata, Yasushi; Hamada, Takuya; Horisawa, Tomoyoshi; Cosatto, Eric; Graf, Hans-Peter; Kuroda, Masahiko; Yamamoto, Yoichiro

2016-01-01

Recent developments in molecular pathology and genetic/epigenetic analysis of cancer tissue have resulted in a marked increase in objective and measurable data. In comparison, the traditional morphological analysis approach to pathology diagnosis, which can connect these molecular data and clinical diagnosis, is still mostly subjective. Even though the advent and popularization of digital pathology has provided a boost to computer-aided diagnosis, some important pathological concepts still remain largely non-quantitative and their associated data measurements depend on the pathologist's sense and experience. Such features include pleomorphism and heterogeneity. In this paper, we propose a method for the objective measurement of pleomorphism and heterogeneity, using the cell-level co-occurrence matrix. Our method is based on the widely used Gray-level co-occurrence matrix (GLCM), where relations between neighboring pixel intensity levels are captured into a co-occurrence matrix, followed by the application of analysis functions such as Haralick features. In the pathological tissue image, through image processing techniques, each nucleus can be measured and each nucleus has its own measureable features like nucleus size, roundness, contour length, intra-nucleus texture data (GLCM is one of the methods). In GLCM each nucleus in the tissue image corresponds to one pixel. In this approach the most important point is how to define the neighborhood of each nucleus. We define three types of neighborhoods of a nucleus, then create the co-occurrence matrix and apply Haralick feature functions. In each image pleomorphism and heterogeneity are then determined quantitatively. For our method, one pixel corresponds to one nucleus feature, and we therefore named our method Cell Feature Level Co-occurrence Matrix (CFLCM). We tested this method for several nucleus features. CFLCM is showed as a useful quantitative method for pleomorphism and heterogeneity on histopathological image analysis.

Co-Occurrence of Language and Behavioural Change in Frontotemporal Lobar Degeneration.

PubMed

Harris, Jennifer M; Jones, Matthew; Gall, Claire; Richardson, Anna M T; Neary, David; du Plessis, Daniel; Pal, Piyali; Mann, David M A; Snowden, Julie S; Thompson, Jennifer C

2016-01-01

We aimed to evaluate the co-occurrence of language and behavioural impairment in patients with frontotemporal lobar degeneration (FTLD) spectrum pathology. Eighty-one dementia patients with pathological confirmation of FTLD were identified. Anonymized clinical records from patients' first assessment were rated for language and behavioural features from frontotemporal dementia consensus criteria, primary progressive aphasia (PPA) criteria and 1998 FTLD criteria. Over 90% of patients with FTLD pathology exhibited a combination of at least one behavioural and one language feature. Changes in language, in particular, were commonly accompanied by behavioural change. Notably, the majority of patients who displayed language features characteristic of semantic variant PPA exhibited 'early perseverative, stereotyped or compulsive/ritualistic behaviour'. Moreover, 'executive/generation deficits with relative sparing of memory and visuospatial functions' occurred in most patients with core features of non-fluent variant PPA. Behavioural and language symptoms frequently co-occur in patients with FTLD pathology. Current classifications, which separate behavioural and language syndromes, do not reflect this co-occurrence.

Pathological speech signal analysis and classification using empirical mode decomposition.

PubMed

Kaleem, Muhammad; Ghoraani, Behnaz; Guergachi, Aziz; Krishnan, Sridhar

2013-07-01

Automated classification of normal and pathological speech signals can provide an objective and accurate mechanism for pathological speech diagnosis, and is an active area of research. A large part of this research is based on analysis of acoustic measures extracted from sustained vowels. However, sustained vowels do not reflect real-world attributes of voice as effectively as continuous speech, which can take into account important attributes of speech such as rapid voice onset and termination, changes in voice frequency and amplitude, and sudden discontinuities in speech. This paper presents a methodology based on empirical mode decomposition (EMD) for classification of continuous normal and pathological speech signals obtained from a well-known database. EMD is used to decompose randomly chosen portions of speech signals into intrinsic mode functions, which are then analyzed to extract meaningful temporal and spectral features, including true instantaneous features which can capture discriminative information in signals hidden at local time-scales. A total of six features are extracted, and a linear classifier is used with the feature vector to classify continuous speech portions obtained from a database consisting of 51 normal and 161 pathological speakers. A classification accuracy of 95.7 % is obtained, thus demonstrating the effectiveness of the methodology.

A clinico-pathological study of lupus nephritis based on the International Society of Nephrology-Renal Pathology Society 2003 classification system.

PubMed

Satish, Suchitha; Deka, Pallavi; Shetty, Manjunath Sanjeev

2017-01-01

Lupus nephritis (LN) is a major complication of systemic lupus erythematosus (SLE). Renal involvement is a major determinant of the prognosis of SLE. The histological classification of LN is a key factor in determining the renal survival of patients with LN. Prompt recognition and treatment of renal disease are important, as early response to therapy is correlated with better outcome and renal biopsy plays an important role in achieving this. The objective of this study was to correlate the clinical and laboratory findings with histopathological classes of LN as per the 2003 International Society of Nephrology-Renal Pathology Society (ISN/RPS) classification system. Fifty-six patients with SLE, undergoing a renal biopsy for renal dysfunction were studied. The comparison of data from multiple groups was made by Pearson's Chi-square test and between two groups by independent samples t -test. The values of P < 0.05 were considered statistically significant. Of the 56 cases studied, 51 (91.1%) were females. The most common presenting symptoms were edema, arthralgia, and hypertension. Class IV (55.4%) was the most common class. Thirty-nine (69.6%) cases showed full house immunostaining. Hypertension, hematuria, proteinuria, and tubulo-interstitial disease showed a significant correlation ( P < 0.05) with ISN/RPS classification, 2003. Assessment and management of patients with suspected LN are greatly facilitated through information obtained by renal biopsy. Since renal morphology may predict long-term prognosis, and no clinical or laboratory feature uniformly predicts prognosis, it is important to study the constellation of features in LN for better patient management.

The comparison of pathology in ferrets infected by H9N2 avian influenza viruses with different genomic features.

PubMed

Gao, Rongbao; Bai, Tian; Li, Xiaodan; Xiong, Ying; Huang, Yiwei; Pan, Ming; Zhang, Ye; Bo, Hong; Zou, Shumei; Shu, Yuelong

2016-01-15

H9N2 avian influenza virus circulates widely in poultry and has been responsible for sporadic human infections in several regions. Few studies have been conducted on the pathogenicity of H9N2 AIV isolates that have different genomic features. We compared the pathology induced by a novel reassortant H9N2 virus and two currently circulating H9N2 viruses that have different genomic features in ferrets. The results showed that the three viruses can induce infections with various amounts of viral shedding in ferrets. The novel H9N2 induced respiratory infection, but no pathological lesions were observed in lung tissues. The other two viruses induced mild to intermediate pathological lesions in lung tissues, although the clinical signs presented mildly in ferrets. The pathological lesions presented a diversity consistent with viral replication in ferrets. Copyright © 2015 Elsevier Inc. All rights reserved.

Targeted endothelial nanomedicine for common acute pathological conditions

PubMed Central

Shuvaev, Vladimir V.; Brenner, Jacob S.; Muzykantov, Vladimir R.

2017-01-01

Endothelium, a thin monolayer of specialized cells lining the lumen of blood vessels is the key regulatory interface between blood and tissues. Endothelial abnormalities are implicated in many diseases, including common acute conditions with high morbidity and mortality lacking therapy, in part because drugs and drug carriers have no natural endothelial affinity. Precise endothelial drug delivery may improve management of these conditions. Using ligands of molecules exposed to the bloodstream on the endothelial surface enables design of diverse targeted endothelial nanomedicine agents. Target molecules and binding epitopes must be accessible to drug carriers, carriers must be free of harmful effects, and targeting should provide desirable sub-cellular addressing of the drug cargo. The roster of current candidate target molecules for endothelial nanomedicine includes peptidases and other enzymes, cell adhesion molecules and integrins, localized in different domains of the endothelial plasmalemma and differentially distributed throughout the vasculature. Endowing carriers with an affinity to specific endothelial epitopes enables an unprecedented level of precision of control of drug delivery: binding to selected endothelial cell phenotypes, cellular addressing and duration of therapeutic effects. Features of nanocarrier design such as choice of epitope and ligand control delivery and effect of targeted endothelial nanomedicine agents. Pathological factors modulate endothelial targeting and uptake of nanocarriers. Selection of optimal binding sites and design features of nanocarriers are key controllable factors that can be iteratively engineered based on their performance from in vitro to pre-clinical in vivo experimental models. Targeted endothelial nanomedicine agents provide antioxidant, anti-inflammatory and other therapeutic effects unattainable by non-targeted counterparts in animal models of common acute severe human disease conditions. The results of animal studies provide the basis for the challenging translation endothelial nanomedicine into the clinical domain. PMID:26435455

Role of Polyamines in Asthma Pathophysiology

PubMed Central

2018-01-01

Asthma is a complex disease of airways, where the interactions of immune and structural cells result in disease outcomes with airway remodeling and airway hyper-responsiveness. Polyamines, which are small-sized, natural super-cations, interact with negatively charged intracellular macromolecules, and altered levels of polyamines and their interactions have been associated with different pathological conditions including asthma. Elevated levels of polyamines have been reported in the circulation of asthmatic patients as well as in the lungs of a murine model of asthma. In various studies, polyamines were found to potentiate the pathogenic potential of inflammatory cells, such as mast cells and granulocytes (eosinophils and neutrophils), by either inducing the release of their pro-inflammatory mediators or prolonging their life span. Additionally, polyamines were crucial in the differentiation and alternative activation of macrophages, which play an important role in asthma pathology. Importantly, polyamines cause airway smooth muscle contraction and thus airway hyper-responsiveness, which is the key feature in asthma pathophysiology. High levels of polyamines in asthma and their active cellular and macromolecular interactions indicate the importance of the polyamine pathway in asthma pathogenesis; therefore, modulation of polyamine levels could be a suitable approach in acute and severe asthma management. This review summarizes the possible roles of polyamines in different pathophysiological features of asthma. PMID:29316647

Unconventional features of C9ORF72 expanded repeat in amyotrophic lateral sclerosis and frontotemporal lobar degeneration.

PubMed

Vatovec, Sabina; Kovanda, Anja; Rogelj, Boris

2014-10-01

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are devastating neurodegenerative diseases that form two ends of a complex disease spectrum. Aggregation of RNA binding proteins is one of the hallmark pathologic features of ALS and FTDL and suggests perturbance of the RNA metabolism in their etiology. Recent identification of the disease-associated expansions of the intronic hexanucleotide repeat GGGGCC in the C9ORF72 gene further substantiates the case for RNA involvement. The expanded repeat, which has turned out to be the single most common genetic cause of ALS and FTLD, may enable the formation of complex DNA and RNA structures, changes in RNA transcription, and processing and formation of toxic RNA foci, which may sequester and inactivate RNA binding proteins. Additionally, the transcribed expanded repeat can undergo repeat-associated non-ATG-initiated translation resulting in accumulation of a series of dipeptide repeat proteins. Understanding the basis of the proposed mechanisms and shared pathways, as well as interactions with known key proteins such as TAR DNA-binding protein (TDP-43) are needed to clarify the pathology of ALS and/or FTLD, and make possible steps toward therapy development. Copyright © 2014 Elsevier Inc. All rights reserved.

Using typical endoscopic features to diagnose esophageal squamous papilloma.

PubMed

Wong, Ming-Wun; Bair, Ming-Joug; Shih, Shou-Chuan; Chu, Cheng-Hsin; Wang, Horng-Yuan; Wang, Tsang-En; Chang, Chen-Wang; Chen, Ming-Jen

2016-02-21

To better understand some of the superficial tiny lesions that are recognized as squamous papilloma of the esophagus (SPE) and receive a different pathological diagnosis. All consecutive patients with esophageal polypoid lesions detected by routine endoscopy at our Endoscopy Centre between October 2009 and June 2014 were retrospectively analysed. We enrolled patients with SPE or other superficial lesions to investigate four key endoscopic appearances (whitish color, exophytic growth, wart-like shape, and surface vessels) and used narrow band imaging (NBI) to distinguish their differences. These series endoscopic images of each patient were retrospectively reviewed by three experienced endoscopists with no prior access to the images. All lesion specimens obtained by forceps biopsy were fixed in formalin and processed for pathological examination. The following data were collected from patient medical records: gender, age, indications for esophagogastroduodenoscopy, and endoscopic characteristics including lesion location, number, color, size, surface morphology, surrounding mucosa, and surface vessels under NBI. Clinicopathological features were also compared. During the study period, 41 esophageal polypoid lesions from 5698 endoscopic examinations were identified retrospectively. These included 24 patients with pathologically confirmed SPE, 11 patients with squamous hyperplasia, three patients with glycogenic acanthosis, two patients with ectopic sebaceous glands, and one patient with a xanthoma. In the χ (2) test, exophytic growth (P = 0.003), a wart-like shape (P < 0.001), and crossing surface vessels under NBI (P = 0.001) were more frequently observed in SPE than in other lesion types. By contrast, there was no significant difference regarding the appearance of a whitish color between SPE and other lesion types (P = 0.872). The most sensitive characteristic was wart-like projections (81.3%) and the most specific was exophytic growth (87.5%). Promising positive predictive values of 84.2%, 80.8%, and 82.6% were noted for exophytic growth, wart-like projections, and surface vessel crossing on NBI, respectively. The use of three key typical endoscopic appearances--exophytic growth, a wart-like shape, and vessel crossing on the lesion surface under NBI--has a promising positive predictive value of 88.2%. This diagnostic triad is useful for the endoscopic diagnosis of SPE.

Using typical endoscopic features to diagnose esophageal squamous papilloma

PubMed Central

Wong, Ming-Wun; Bair, Ming-Joug; Shih, Shou-Chuan; Chu, Cheng-Hsin; Wang, Horng-Yuan; Wang, Tsang-En; Chang, Chen-Wang; Chen, Ming-Jen

2016-01-01

AIM: To better understand some of the superficial tiny lesions that are recognized as squamous papilloma of the esophagus (SPE) and receive a different pathological diagnosis. METHODS: All consecutive patients with esophageal polypoid lesions detected by routine endoscopy at our Endoscopy Centre between October 2009 and June 2014 were retrospectively analysed. We enrolled patients with SPE or other superficial lesions to investigate four key endoscopic appearances (whitish color, exophytic growth, wart-like shape, and surface vessels) and used narrow band imaging (NBI) to distinguish their differences. These series endoscopic images of each patient were retrospectively reviewed by three experienced endoscopists with no prior access to the images. All lesion specimens obtained by forceps biopsy were fixed in formalin and processed for pathological examination. The following data were collected from patient medical records: gender, age, indications for esophagogastroduodenoscopy, and endoscopic characteristics including lesion location, number, color, size, surface morphology, surrounding mucosa, and surface vessels under NBI. Clinicopathological features were also compared. RESULTS: During the study period, 41 esophageal polypoid lesions from 5698 endoscopic examinations were identified retrospectively. These included 24 patients with pathologically confirmed SPE, 11 patients with squamous hyperplasia, three patients with glycogenic acanthosis, two patients with ectopic sebaceous glands, and one patient with a xanthoma. In the χ2 test, exophytic growth (P = 0.003), a wart-like shape (P < 0.001), and crossing surface vessels under NBI (P = 0.001) were more frequently observed in SPE than in other lesion types. By contrast, there was no significant difference regarding the appearance of a whitish color between SPE and other lesion types (P = 0.872). The most sensitive characteristic was wart-like projections (81.3%) and the most specific was exophytic growth (87.5%). Promising positive predictive values of 84.2%, 80.8%, and 82.6% were noted for exophytic growth, wart-like projections, and surface vessel crossing on NBI, respectively. CONCLUSION: The use of three key typical endoscopic appearances - exophytic growth, a wart-like shape, and vessel crossing on the lesion surface under NBI - has a promising positive predictive value of 88.2%. This diagnostic triad is useful for the endoscopic diagnosis of SPE. PMID:26900297

Optimization of a 3D Dynamic Culturing System for In Vitro Modeling of Frontotemporal Neurodegeneration-Relevant Pathologic Features

PubMed Central

Tunesi, Marta; Fusco, Federica; Fiordaliso, Fabio; Corbelli, Alessandro; Biella, Gloria; Raimondi, Manuela T.

2016-01-01

Frontotemporal lobar degeneration (FTLD) is a severe neurodegenerative disorder that is diagnosed with increasing frequency in clinical setting. Currently, no therapy is available and in addition the molecular basis of the disease are far from being elucidated. Consequently, it is of pivotal importance to develop reliable and cost-effective in vitro models for basic research purposes and drug screening. To this respect, recent results in the field of Alzheimer’s disease have suggested that a tridimensional (3D) environment is an added value to better model key pathologic features of the disease. Here, we have tried to add complexity to the 3D cell culturing concept by using a microfluidic bioreactor, where cells are cultured under a continuous flow of medium, thus mimicking the interstitial fluid movement that actually perfuses the body tissues, including the brain. We have implemented this model using a neuronal-like cell line (SH-SY5Y), a widely exploited cell model for neurodegenerative disorders that shows some basic features relevant for FTLD modeling, such as the release of the FTLD-related protein progranulin (PRGN) in specific vesicles (exosomes). We have efficiently seeded the cells on 3D scaffolds, optimized a disease-relevant oxidative stress experiment (by targeting mitochondrial function that is one of the possible FTLD-involved pathological mechanisms) and evaluated cell metabolic activity in dynamic culture in comparison to static conditions, finding that SH-SY5Y cells cultured in 3D scaffold are susceptible to the oxidative damage triggered by a mitochondrial-targeting toxin (6-OHDA) and that the same cells cultured in dynamic conditions kept their basic capacity to secrete PRGN in exosomes once recovered from the bioreactor and plated in standard 2D conditions. We think that a further improvement of our microfluidic system may help in providing a full device where assessing basic FTLD-related features (including PRGN dynamic secretion) that may be useful for monitoring disease progression over time or evaluating therapeutic interventions. PMID:27445790

Evaluation of wavelet spectral features in pathological detection and discrimination of yellow rust and powdery mildew in winter wheat with hyperspectral reflectance data

NASA Astrophysics Data System (ADS)

Shi, Yue; Huang, Wenjiang; Zhou, Xianfeng

2017-04-01

Hyperspectral absorption features are important indicators of characterizing plant biophysical variables for the automatic diagnosis of crop diseases. Continuous wavelet analysis has proven to be an advanced hyperspectral analysis technique for extracting absorption features; however, specific wavelet features (WFs) and their relationship with pathological characteristics induced by different infestations have rarely been summarized. The aim of this research is to determine the most sensitive WFs for identifying specific pathological lesions from yellow rust and powdery mildew in winter wheat, based on 314 hyperspectral samples measured in field experiments in China in 2002, 2003, 2005, and 2012. The resultant WFs could be used as proxies to capture the major spectral absorption features caused by infestation of yellow rust or powdery mildew. Multivariate regression analysis based on these WFs outperformed conventional spectral features in disease detection; meanwhile, a Fisher discrimination model exhibited considerable potential for generating separable clusters for each infestation. Optimal classification returned an overall accuracy of 91.9% with a Kappa of 0.89. This paper also emphasizes the WFs and their relationship with pathological characteristics in order to provide a foundation for the further application of this approach in monitoring winter wheat diseases at the regional scale.

Dual pathology of corticobasal degeneration and Parkinson's disease in a patient with clinical features of progressive supranuclear palsy.

PubMed

Mooney, Tomin; Tampiyappa, Anthony; Robertson, Thomas; Grimley, Rohan; Burke, Chris; Ng, Kenneth; Patrikios, Peter

2011-01-01

Corticobasal degeneration and Parkinson's disease are pathologically distinct disorders with unique histological and biochemical features of a tauopathy and a-synucleinopathy respectively. We report the first case of co-occurrence of these pathologies in the same patient. Convergence of such distinctly separate neuropathology in the same brain highlights the need for extensive brain banking and further research in supporting the hypothesis that tauopathies and a-synucleinopathies might share common pathogenic mechanisms.

Bone marrow failure in childhood: central pathology review of a nationwide registry.

PubMed

Ito, Masafumi

2017-01-01

Refractory cytopenia of childhood (RCC) was proposed as a provisional entity in the 2008 WHO classification of myelodysplastic syndromes (MDS). It is defined as a childhood MDS featuring persistent cytopenia without increase blasts in bone marrow (BM) or peripheral blood (PB). Because the majority of RCC cases feature hypocellularity and pancytopenia, it is quite challenging to differentiate RCC from acquired aplastic anemia (AA) and many kinds of inherited bone marrow failure syndromes (IBMFS). Diagnosis of RCC requires BM histology of characteristic features such as isolated erythroid islet with left shift, abnormal localization and micromegakaryocytes. The Japanese Society of Pediatric Hematology/Oncology has opened the central registry review system since 2009 to evaluate childhood cases of bone marrow failure (BMF). It has reviewed cytology and BM pathology of all registered BMF cases, which number more than 1,700. In the evaluation of BMF, BM pathology is important to assess the mechanism of hematopoiesis. Pathological dysplasia should be differentiated from cytological dysplasia. A central review system is important for rare diseases, such as pediatric BMF. Standardization of pathological diagnosis should be established upon consensus findings, descriptions, and diagnostic approaches. In this review, the pathology of pediatric BMF syndromes is summarized.

[Pathological features of myositis with myositis -specific autoantibodies].

PubMed

Shimizu, Jun; Mimori, Tsuneyo

2014-01-01

Myositis is a heterogeneous group of systemic autoimmune disorders characterized by inflammation of skeletal muscle. Historically, myositis has been defined using clinical features including muscle weakness, skin disease, internal organ involvement, and an association with cancer in adults. From a clinicopathologic approach, myositis has been classified into pathologically distinct subsets, polymyositis, dermatomyositis(DM), necrotizing autoimmune myositis, amyopathic DM, and non-specific myositis. Although the characteristic pathological changes are believed to be important in pathological mechanisms of each subset of myositis, in clinical practices, the percentages of the patients with typical pathological findings are usually not high. On the other hand, with the recent discovery of new myositis-specific autoantibodies (MSAs), it has been revealed that around 60% of patients with IIMs have been shown to have a anti-myositis-specific autoantibody, including anti-synthetase, anti-Mi-2, anti-MDA5, anti-TIF1 and anti-SRP antibodies. Because of striking association between unique MSAs and distinct clinical phenotypes, these antibodies are thought to be important not only for classifications of IIMs, but also as factors involved in the mechanism underlying their pathogenesis. This review reports recent progress in understanding of pathological features of myositis with MSAs.

The Characteristics of Herpes Simplex Virus Type 1 Infection in Rhesus Macaques and the Associated Pathological Features.

PubMed

Fan, Shengtao; Cai, Hongzhi; Xu, Xingli; Feng, Min; Wang, Lichun; Liao, Yun; Zhang, Ying; He, Zhanlong; Yang, Fengmei; Yu, Wenhai; Wang, Jingjing; Zhou, Jumin; Li, Qihan

2017-01-30

As one of the major pathogens for human herpetic diseases, herpes simplex virus type 1 (HSV1) causes herpes labialis, genital herpes and herpetic encephalitis. Our aim here was to investigate the infectious process of HSV1 in rhesus macaques and the pathological features induced during this infection. Clinical symptoms that manifested in the rhesus macaque during HSV1 infection included vesicular lesions and their pathological features. Viral distribution in the nervous tissues and associated pathologic changes indicated the typical systematic pathological processes associated with viral distribution of HSV1.Interestingly, vesicular lesions recurred in oral skin or in mucosa associated with virus shedding in macaques within four to five months post-infection,and viral latency-associated transcript (LAT) mRNA was found in the trigeminal ganglia (TG)on day 365 post-infection. Neutralization testing and enzyme-linked immunospot (ELISpot) detection of specific T cell responses confirmed the specific immunity induced by HSV1 infection. Thus, rhesus macaques could serve as an infectious model for HSV1 due to their typical clinical symptoms and the pathological recurrence associated with viral latency in nervous tissues.

Alterations of the microvascular network in the sclerotic hippocampus of patients with temporal lobe epilepsy.

PubMed

Alonso-Nanclares, Lidia; DeFelipe, Javier

2014-09-01

Hippocampal sclerosis is the most frequent pathology encountered in resected tissue obtained from patients with temporal lobe epilepsy. The main hallmarks of hippocampal sclerosis are neuronal loss and gliosis. Several authors have proposed that an increase in blood vessel density is a further indicator, based on interpretations from staining of markers related to both blood-brain barrier disruption and the formation of new blood vessels. However, previous studies performed in our laboratory using correlative light and electron microscopy revealed that many of these "blood vessels" are in fact atrophic vascular structures with a reduced or virtually absent lumen and are often filled with processes of reactive astrocytes. Thus, "normal" vasculature within the sclerotic CA1 field is drastically reduced. Since this decrease is consistently observed in the human sclerotic CA1, this feature can be considered another key pathological indicator of hippocampal sclerosis associated with temporal lobe epilepsy. Copyright © 2013 Elsevier Inc. All rights reserved.

Classification of electroencephalograph signals using time-frequency decomposition and linear discriminant analysis

NASA Astrophysics Data System (ADS)

Szuflitowska, B.; Orlowski, P.

2017-08-01

Automated detection system consists of two key steps: extraction of features from EEG signals and classification for detection of pathology activity. The EEG sequences were analyzed using Short-Time Fourier Transform and the classification was performed using Linear Discriminant Analysis. The accuracy of the technique was tested on three sets of EEG signals: epilepsy, healthy and Alzheimer's Disease. The classification error below 10% has been considered a success. The higher accuracy are obtained for new data of unknown classes than testing data. The methodology can be helpful in differentiation epilepsy seizure and disturbances in the EEG signal in Alzheimer's Disease.

[The case of completed pregnancy of the patient with Dandy-Walker malformation].

PubMed

Beliaeva, E V; Lapshina, L V; Shaposhnikova, E V; Molgachev, A A

2018-01-01

Dandy-Walker malformation is a rare disease of the central nervous system pathology (congenital malformations of the fossa cranii posterior). The key features of this syndrome are an enlargement of the fourth ventricle; complete absence of the cerebellar vermis, the posterior midline area of cerebellar cortex responsible for coordination of the axial musculature; and cyst formation near the internal base of the skull. Pregnant patients with Dandy-Walker malformation are at high risk and are managed by multidisciplinary teams including neurologists and obstetricians. We present a case report of full-term pregnancy and uncomplicated delivery in a women with Dandy-Walker malformation.

Revisiting the metabolic syndrome: the emerging role of aquaglyceroporins.

PubMed

da Silva, Inês Vieira; Rodrigues, Joana S; Rebelo, Irene; Miranda, Joana P G; Soveral, Graça

2018-06-01

The metabolic syndrome (MetS) includes a group of medical conditions such as insulin resistance (IR), dyslipidemia and hypertension, all associated with an increased risk for cardiovascular disease. Increased visceral and ectopic fat deposition are also key features in the development of IR and MetS, with pathophysiological sequels on adipose tissue, liver and muscle. The recent recognition of aquaporins (AQPs) involvement in adipose tissue homeostasis has opened new perspectives for research in this field. The members of the aquaglyceroporin subfamily are specific glycerol channels implicated in energy metabolism by facilitating glycerol outflow from adipose tissue and its systemic distribution and uptake by liver and muscle, unveiling these membrane channels as key players in lipid balance and energy homeostasis. Being involved in a variety of pathophysiological mechanisms including IR and obesity, AQPs are considered promising drug targets that may prompt novel therapeutic approaches for metabolic disorders such as MetS. This review addresses the interplay between adipose tissue, liver and muscle, which is the basis of the metabolic syndrome, and highlights the involvement of aquaglyceroporins in obesity and related pathologies and how their regulation in different organs contributes to the features of the metabolic syndrome.

[Clinico-pathologic Characteristics of Adult Patients with Atypical Infectious Mononucleosis].

PubMed

Yu, Ya-Ping; Song, Ping; An, Zhi-Ming; Zhou, Xiao-Gang; Li, Feng; Wang, Li-Ping; Mei, Jian-Gang; Zhai, Yong-Ping

2016-12-01

To investigate the clinicopathologic characteristics of adult patients with atypical infectious mononucleosis(IM). From January 2003 to December 2013, a total of 5 cases of atypical IM misdiagnosed as lymphoma were selected, and the clinico-pathological characteristics and efficacy of treatment were analyzed. Biopsy of lymph node or tonsil was performed to evaluate the possibility of lymphoma. Peripheral blood EBV antibody and EBV-DNA were examined by ELISA and real-time fluorescence quantitative PCR, respectively. All the cases were considered as lymphoma on the basis of morphological features in initial evaluation before relapse. These features included a florid immunoblastic proliferation, distortion of the underlying nodal or tonsillar architecture and the presence of necrosis. The immunophenotypic features, EBV encoded RNA (EBER) in situ hybridization and the gene rearrangement of immunoglobulin or T cell receptor may be helpful for the distinction of atypical IM from lymphoma. IM as EBV-related lymphoproliferative process shows marked clinical and histological diversity. Atypical case of IM may mimic many different type of lymphoma in clinical and pathologic features, and the misdiagnosis should be avoided by using molecular and pathological examination.

Veterinary software application for comparison of thermograms for pathology evaluation

NASA Astrophysics Data System (ADS)

Pant, Gita; Umbaugh, Scott E.; Dahal, Rohini; Lama, Norsang; Marino, Dominic J.; Sackman, Joseph

2017-09-01

The bilateral symmetry property in mammals allows for the detection of pathology by comparison of opposing sides. For any pathological disorder, thermal patterns differ compared to the normal body part. A software application for veterinary clinics has been under development to input two thermograms of body parts on both sides, one normal and the other unknown, and the application compares them based on extracted features and appropriate similarity and difference measures and outputs the likelihood of pathology. Here thermographic image data from 19° C to 40° C was linearly remapped to create images with 256 gray level values. Features were extracted from these images, including histogram, texture and spectral features. The comparison metrics used are the vector inner product, Tanimoto, Euclidean, city block, Minkowski and maximum value metric. Previous research with the anterior cruciate ligament (ACL) pathology in dogs suggested any thermogram variation below a threshold of 40% of Euclidean distance is normal and above 40% is abnormal. Here the 40% threshold was applied to a new ACL image set and achieved a sensitivity of 75%, an improvement from the 55% sensitivity of the previous work. With the new data set it was determined that using a threshold of 20% provided a much improved 92% sensitivity metric. However, this will require further research to determine the corresponding specificity success rate. Additionally, it was found that the anterior view provided better results than the lateral view. It was also determined that better results were obtained with all three feature sets than with just the histogram and texture sets. Further experiments are ongoing with larger image datasets, and pathologies, new features and comparison metric evaluation for determination of more accurate threshold values to separate normal and abnormal images.

VEGF-D promotes pulmonary oedema in hyperoxic acute lung injury.

PubMed

Sato, Teruhiko; Paquet-Fifield, Sophie; Harris, Nicole C; Roufail, Sally; Turner, Debra J; Yuan, Yinan; Zhang, You-Fang; Fox, Stephen B; Hibbs, Margaret L; Wilkinson-Berka, Jennifer L; Williams, Richard A; Stacker, Steven A; Sly, Peter D; Achen, Marc G

2016-06-01

Leakage of fluid from blood vessels, leading to oedema, is a key feature of many diseases including hyperoxic acute lung injury (HALI), which can occur when patients are ventilated with high concentrations of oxygen (hyperoxia). The molecular mechanisms driving vascular leak and oedema in HALI are poorly understood. VEGF-D is a protein that promotes blood vessel leak and oedema when overexpressed in tissues, but the role of endogenous VEGF-D in pathological oedema was unknown. To address these issues, we exposed Vegfd-deficient mice to hyperoxia. The resulting pulmonary oedema in Vegfd-deficient mice was substantially reduced compared to wild-type, as was the protein content of bronchoalveolar lavage fluid, consistent with reduced vascular leak. Vegf-d and its receptor Vegfr-3 were more highly expressed in lungs of hyperoxic, versus normoxic, wild-type mice, indicating that components of the Vegf-d signalling pathway are up-regulated in hyperoxia. Importantly, VEGF-D and its receptors were co-localized on blood vessels in clinical samples of human lungs exposed to hyperoxia; hence, VEGF-D may act directly on blood vessels to promote fluid leak. Our studies show that Vegf-d promotes oedema in response to hyperoxia in mice and support the hypothesis that VEGF-D signalling promotes vascular leak in human HALI. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

ASTROCYTE PATHOLOGY IN MAJOR DEPRESSIVE DISORDER: INSIGHTS FROM HUMAN POSTMORTEM BRAIN TISSUE

PubMed Central

Rajkowska, Grazyna; Stockmeier, Craig A.

2013-01-01

The present paper reviews astrocyte pathology in major depressive disorder (MDD) and proposes that reductions in astrocytes and related markers are key features in the pathology of MDD. Astrocytes are the most numerous and versatile of all types of glial cells. They are crucial to the neuronal microenvironment by regulating glucose metabolism, neurotransmitter uptake (particularly for glutamate), synaptic development and maturation and the blood brain barrier. Pathology of astrocytes has been consistently noted in MDD as well as in rodent models of depressive-like behavior. This review summarizes evidence from human postmortem tissue showing alterations in the expression of protein and mRNA for astrocyte markers such as glial fibrillary acidic protein (GFAP), gap junction proteins (connexin 40 and 43), the water channel aquaporin-4 (AQP4), a calcium-binding protein S100B and glutamatergic markers including the excitatory amino acid transporters 1 and 2 (EAAT1, EAAT2) and glutamine synthetase. Moreover, preclinical studies are presented that demonstrate the involvement of GFAP and astrocytes in animal models of stress and depressive-like behavior and the influence of different classes of antidepressant medications on astrocytes. In light of the various astrocyte deficits noted in MDD, astrocytes may be novel targets for the action of antidepressant medications. Possible functional consequences of altered expression of astrocytic markers in MDD are also discussed. Finally, the unique pattern of cell pathology in MDD, characterized by prominent reductions in the density of astrocytes and in the expression of their markers without obvious neuronal loss, is contrasted with that found in other neuropsychiatric and neurodegenerative disorders. PMID:23469922

Microvascular Pathology and Morphometrics of Sporadic and Hereditary Small Vessel Diseases of the Brain

PubMed Central

Craggs, Lucinda JL; Yamamoto, Yumi; Deramecourt, Vincent; Kalaria, Raj N

2014-01-01

Small vessel diseases (SVDs) of the brain are likely to become increasingly common in tandem with the rise in the aging population. In recent years, neuroimaging and pathological studies have informed on the pathogenesis of sporadic SVD and several single gene (monogenic) disorders predisposing to subcortical strokes and diffuse white matter disease. However, one of the limitations toward studying SVD lies in the lack of consistent assessment criteria and lesion burden for both clinical and pathological measures. Arteriolosclerosis and diffuse white matter changes are the hallmark features of both sporadic and hereditary SVDs. The pathogenesis of the arteriopathy is the key to understanding the differential progression of disease in various SVDs. Remarkably, quantification of microvascular abnormalities in sporadic and hereditary SVDs has shown that qualitatively the processes involved in arteriolar degeneration are largely similar in sporadic SVD compared with hereditary disorders such as cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Important significant regional differences in lesion location within the brain may enable one to distinguish SVDs, where frontal lobe involvement appears consistently with almost every SVD, but others bear specific pathologies in other lobes, such as the temporal pole in CADASIL and the pons in pontine autosomal dominant microangiopathy and leukoencephalopathy or PADMAL. Additionally, degenerative changes in the vascular smooth muscle cells, the cerebral endothelium and the basal lamina are often rapid and more aggressive in genetic disorders. Further quantification of other microvascular elements and even neuronal cells is needed to fully characterize SVD pathogenesis and to differentiate the usefulness of vascular interventions and treatments on the resulting pathology. PMID:25323665

“Kerrr” black hole: The lord of the string

NASA Astrophysics Data System (ADS)

Smailagic, Anais; Spallucci, Euro

2010-04-01

Kerrr in the title is not a typo. The third “r” stands for regular, in the sense of pathology-free rotating black hole. We exhibit a long search-for, exact, Kerr-like, solution of the Einstein equations with novel features: (i) no curvature ring singularity; (ii) no “anti-gravity” universe with causality violating time-like closed world-lines; (iii) no “super-luminal” matter disk. The ring singularity is replaced by a classical, circular, rotating string with Planck tension representing the inner engine driving the rotation of all the surrounding matter. The resulting geometry is regular and smoothly interpolates among inner Minkowski space, borderline de Sitter and outer Kerr universe. The key ingredient to cure all unphysical features of the ordinary Kerr black hole is the choice of a “non-commutative geometry inspired” matter source as the input for the Einstein equations, in analogy with spherically symmetric black holes described in earlier works.

Recurrent granulomatous mastitis mimicking inflammatory breast cancer

PubMed Central

Ergin, Ahmet Bahadir; Cristofanilli, Massimo; Daw, Hamed; Tahan, Gulgun; Gong, Yun

2011-01-01

Granulomatous mastitis (GM) is an uncommon benign breast lesion. Diagnosis is a matter of exclusion from other inflammatory, infectious and granulomatous aetiologies. Here, we presented an atypical GM case, which had clinical and radiologic features overlapping with inflammatory breast cancer (IBC). The disease had multiple recurrences. The patient is a 40-year-old Caucasian woman with a sudden onset of left breast swelling accompanied by diffuse skin redness, especially of the subareolar region and malodorous yellow nipple discharge from the left nipple. The disease progressed on antibiotic treatment and recurred after local resection. A similar lesion developed even after bilateral mastectomy. GM may show clinical/radiologic features suggestive of IBC. Multiple recurrences can be occasionally encountered. GM after recurrence could be much more alarming clinically. Pathology confirmation is the key for accurate diagnosis and a multidisciplinary approach is important to rule out IBC. PMID:22715267

ProFound: Source Extraction and Application to Modern Survey Data

NASA Astrophysics Data System (ADS)

Robotham, A. S. G.

2018-04-01

ProFound detects sources in noisy images, generates segmentation maps identifying the pixels belonging to each source, and measures statistics like flux, size, and ellipticity. These inputs are key requirements of ProFit (ascl:1612.004), our galaxy profiling package; these two packages used in unison semi-automatically profile large samples of galaxies. The key novel feature introduced in ProFound is that all photometry is executed on dilated segmentation maps that fully contain the identifiable flux, rather than using more traditional circular or ellipse-based photometry. Also, to be less sensitive to pathological segmentation issues, the de-blending is made across saddle points in flux. ProFound offers good initial parameter estimation for ProFit, and also segmentation maps that follow the sometimes complex geometry of resolved sources, whilst capturing nearly all of the flux. A number of bulge-disc decomposition projects are already making use of the ProFound and ProFit pipeline.

An improved high order texture features extraction method with application to pathological diagnosis of colon lesions for CT colonography

NASA Astrophysics Data System (ADS)

Song, Bowen; Zhang, Guopeng; Lu, Hongbing; Wang, Huafeng; Han, Fangfang; Zhu, Wei; Liang, Zhengrong

2014-03-01

Differentiation of colon lesions according to underlying pathology, e.g., neoplastic and non-neoplastic, is of fundamental importance for patient management. Image intensity based textural features have been recognized as a useful biomarker for the differentiation task. In this paper, we introduce high order texture features, beyond the intensity, such as gradient and curvature, for that task. Based on the Haralick texture analysis method, we introduce a virtual pathological method to explore the utility of texture features from high order differentiations, i.e., gradient and curvature, of the image intensity distribution. The texture features were validated on database consisting of 148 colon lesions, of which 35 are non-neoplastic lesions, using the random forest classifier and the merit of area under the curve (AUC) of the receiver operating characteristics. The results show that after applying the high order features, the AUC was improved from 0.8069 to 0.8544 in differentiating non-neoplastic lesion from neoplastic ones, e.g., hyperplastic polyps from tubular adenomas, tubulovillous adenomas and adenocarcinomas. The experimental results demonstrated that texture features from the higher order images can significantly improve the classification accuracy in pathological differentiation of colorectal lesions. The gain in differentiation capability shall increase the potential of computed tomography (CT) colonography for colorectal cancer screening by not only detecting polyps but also classifying them from optimal polyp management for the best outcome in personalized medicine.

A multiscale product approach for an automatic classification of voice disorders from endoscopic high-speed videos.

PubMed

Unger, Jakob; Schuster, Maria; Hecker, Dietmar J; Schick, Bernhard; Lohscheller, Joerg

2013-01-01

Direct observation of vocal fold vibration is indispensable for a clinical diagnosis of voice disorders. Among current imaging techniques, high-speed videoendoscopy constitutes a state-of-the-art method capturing several thousand frames per second of the vocal folds during phonation. Recently, a method for extracting descriptive features from phonovibrograms, a two-dimensional image containing the spatio-temporal pattern of vocal fold dynamics, was presented. The derived features are closely related to a clinically established protocol for functional assessment of pathologic voices. The discriminative power of these features for different pathologic findings and configurations has not been assessed yet. In the current study, a collective of 220 subjects is considered for two- and multi-class problems of healthy and pathologic findings. The performance of the proposed feature set is compared to conventional feature reduction routines and was found to clearly outperform these. As such, the proposed procedure shows great potential for diagnostical issues of vocal fold disorders.

Predictability in Pathological Gambling? Applying the Duplication of Purchase Law to the Understanding of Cross-Purchases Between Regular and Pathological Gamblers.

PubMed

Lam, Desmond; Mizerski, Richard

2017-06-01

The objective of this study is to explore the gambling participations and game purchase duplication of light regular, heavy regular and pathological gamblers by applying the Duplication of Purchase Law. Current study uses data collected by the Australian Productivity Commission for eight different types of games. Key behavioral statistics on light regular, heavy regular, and pathological gamblers were computed and compared. The key finding is that pathological gambling, just like regular gambling, follows the Duplication of Purchase Law, which states that the dominant factor of purchase duplication between two brands is their market shares. This means that gambling between any two games at pathological level, like any regular consumer purchases, exhibits "law-like" regularity based on the pathological gamblers' participation rate of each game. Additionally, pathological gamblers tend to gamble more frequently across all games except lotteries and instant as well as make greater cross-purchases compared to heavy regular gamblers. A better understanding of the behavioral traits between regular (particularly heavy regular) and pathological gamblers can be useful to public policy makers and social marketers in order to more accurately identify such gamblers and better manage the negative impacts of gambling.

Longitudinal Validation of General and Specific Structural Features of Personality Pathology

PubMed Central

Wright, Aidan G.C.; Hopwood, Christopher J.; Skodol, Andrew E.; Morey, Leslie C.

2016-01-01

Theorists have long argued that personality disorder (PD) is best understood in terms of general impairments shared across the disorders as well as more specific instantiations of pathology. A model based on this theoretical structure was proposed as part of the DSM-5 revision process. However, only recently has this structure been subjected to formal quantitative evaluation, with little in the way of validation efforts via external correlates or prospective longitudinal prediction. We used the Collaborative Longitudinal Study of Personality Disorders dataset to: (1) estimate structural models that parse general from specific variance in personality disorder features, (2) examine patterns of growth in general and specific features over the course of 10 years, and (3) establish concurrent and dynamic longitudinal associations in PD features and a host of external validators including basic personality traits and psychosocial functioning scales. We found that general PD exhibited much lower absolute stability and was most strongly related to broad markers of psychosocial functioning, concurrently and longitudinally, whereas specific features had much higher mean stability and exhibited more circumscribed associations with functioning. However, both general and specific factors showed recognizable associations with normative and pathological traits. These results can inform efforts to refine the conceptualization and diagnosis of personality pathology. PMID:27819472

Tumor size measured by preoperative ultrasonography and postoperative pathologic examination in papillary thyroid carcinoma: relative differences according to size, calcification and coexisting thyroiditis.

PubMed

Yoon, Young Hoon; Kwon, Ki Ryun; Kwak, Seo Young; Ryu, Kyeung A; Choi, Bobae; Kim, Jin-Man; Koo, Bon Seok

2014-05-01

Ultrasonography (US) is a useful diagnostic modality for evaluation of the size and features of thyroid nodules. Tumor size is a key indicator of the surgical extent of thyroid cancer. We evaluated the difference in tumor sizes measured by preoperative US and postoperative pathologic examination in papillary thyroid carcinoma (PTC). We reviewed the medical records of 172 consecutive patients, who underwent thyroidectomy for PTC treatment. We compared tumor size, as measured by preoperative US, with that in postoperative specimens. And we analyzed a number of factors potentially influencing the size measurement, including cancer size, calcification and coexisting thyroiditis. The mean size of the tumor measured by preoperative US was 11.4, and 10.2 mm by postoperative pathologic examination. The mean percentage difference (US-pathology/US) of tumor sizes measured by preoperative US and postoperative pathologic examination was 9.9 ± 19.3%, which was statistically significant (p < 0.001). When the effect of tumor size (≤10.0 vs. 10.1-20.0 vs. >20.0 mm) and the presence of calcification or coexisting thyroiditis on the tumor size discrepancy between the two measurements was analyzed, the mean percentage differences according to tumor size (9.1 vs. 11.2% vs. 9.8%, p = 0.842), calcification (9.2 vs. 10.2%, p = 0.756) and coexisting thyroiditis (17.6 vs. 9.5%, p = 0.223) did not show statistical significance. Tumor sizes measured in postoperative pathology were ~90% of those measured by preoperative US in PTC; this was not affected by tumor size, the presence of calcification or coexisting thyroiditis. When the surgical extent of PTC treatment according to tumor size measured by US is determined, the relative difference between tumor sizes measured by preoperative US and postoperative pathologic examination should be considered.

T cell-derived IL-10 and its impact on the regulation of host responses during malaria.

PubMed

Freitas do Rosario, Ana Paula; Langhorne, Jean

2012-05-15

Despite intense research, malaria still is the one of the most devastating diseases killing more people than any other parasitic infection. In an attempt to control the infection, the host immune system produces a potent pro-inflammatory response. However, this response is also associated with complications, such as severe anaemia, hypoglycaemia and cerebral malaria. This pronounced production of pro-inflammatory cytokines response is a common feature of malaria caused by parasites infecting humans as well as rodents and primates. A balance between pro- and anti-inflammatory responses may be fundamental to the elimination of the parasite without inducing excessive host pathology. IL-10 is a key cytokine that has been shown to have an important regulatory function in establishing this balance in malaria. Here we discuss which cells can produce IL-10 during infection, and present an overview of the evidence showing that T-cell derived IL-10 plays an important role in regulating malaria pathology. Many different subsets of T cells can produce IL-10, however, evidence is accumulating that it is effector Th1 CD4(+) T cells which provide the crucial source that down-regulates inflammatory pathology during blood-stage malaria infections. Copyright © 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Anisotropic tubular filtering for automatic detection of acid-fast bacilli in Ziehl-Neelsen stained sputum smear samples

NASA Astrophysics Data System (ADS)

Raza, Shan-e.-Ahmed; Marjan, M. Q.; Arif, Muhammad; Butt, Farhana; Sultan, Faisal; Rajpoot, Nasir M.

2015-03-01

One of the main factors for high workload in pulmonary pathology in developing countries is the relatively large proportion of tuberculosis (TB) cases which can be detected with high throughput using automated approaches. TB is caused by Mycobacterium tuberculosis, which appears as thin, rod-shaped acid-fast bacillus (AFB) in Ziehl-Neelsen (ZN) stained sputum smear samples. In this paper, we present an algorithm for automatic detection of AFB in digitized images of ZN stained sputum smear samples under a light microscope. A key component of the proposed algorithm is the enhancement of raw input image using a novel anisotropic tubular filter (ATF) which suppresses the background noise while simultaneously enhancing strong anisotropic features of AFBs present in the image. The resulting image is then segmented using color features and candidate AFBs are identified. Finally, a support vector machine classifier using morphological features from candidate AFBs decides whether a given image is AFB positive or not. We demonstrate the effectiveness of the proposed ATF method with two different feature sets by showing that the proposed image analysis pipeline results in higher accuracy and F1-score than the same pipeline with standard median filtering for image enhancement.

IL-17A GENE TRANSFER INDUCES BONE LOSS AND EPIDERMAL HYPERPLASIA ASSOCIATED WITH PSORIATIC ARTHRITIS

PubMed Central

ADAMOPOULOS, IANNIS E.; SUZUKI, ERIKA; CHAO, CHENG-CHI; GORMAN, DAN; ADDA, SARVESH; MAVERAKIS, EMANUAL; ZARBALIS, KONSTANTINOS; GEISSLER, RICHARD; ASIO, AGELIO; BLUMENSCHEIN, WENDY M; McCLANAHAN, TERRILL; DE WAAL MALEFYT, RENE; GERSHWIN, M. ERIC; BOWMAN, EDWARD P.

2014-01-01

Background Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by clinical features that include bone loss and epidermal hyperplasia. Aberrant cytokine expression has been linked to joint and skin pathology; however, it is unclear which cytokines are critical for disease initiation. IL-17A participates in many pathologic immune responses; however, its role in PsA has not been fully elucidated. Objective To determine the role of IL-17A in epidermal hyperplasia and bone destruction associated with psoriatic arthritis. Design An in vivo gene transfer approach was used to investigate the role of IL-17A in animal models of inflammatory (Collagen-induced arthritis) and non-inflammatory (RANKL-gene transfer) bone loss. Results IL-17A gene transfer induced the expansion of IL-17RA+CD11b+Gr1low osteoclast precursors and a concomitant elevation of biomarkers indicative of bone resorption. This occurred at a time preceding noticeable joint inflammation suggesting that IL-17A is critical for the induction of pathological bone resorption through direct activation of osteoclast precursors. Moreover, IL-17A induced a second myeloid population CD11b+Gr1high neutrophil-like cells which was associated with cutaneous pathology including epidermal hyperplasia, parakeratosis, and Munro’s microabscesses formation. Conclusion Collectively, these data support that IL-17A can play a key role in the pathogenesis of inflammation-associated arthritis and/or skin disease, as observed in PsA. PMID:24567524

Fluorescence lifetime technique for surgical imaging, guidance and augmented reality (Conference Presentation)

NASA Astrophysics Data System (ADS)

Marcu, Laura

2017-02-01

The surgeon's limited ability to accurately delineate the tumor margin during surgical interventions is one key challenge in clinical management of cancer. New methods for guiding tumor resection decisions are needed. Numerous studies have shown that tissue autofluorescence properties have the potential to asses biochemical features associates with distinct pathologies in tissue and to distinguish various cancers from normal tissues. However, despite these promising reports, autofluorescence techniques were sparsely adopted in clinical settings. Moreover, when adopted they were primarily used for pre-operative diagnosis rather than guiding interventions. To address this need, we have researched and engineered instrumentation that utilizes label-free fluorescence lifetime contrast to characterize tissue biochemical features in vivo in patients and methodologies conducive to real-time (few seconds) diagnosis of tissue pathologies during surgical procedures. This presentation overviews clinically-compatible multispectral fluorescence lifetime imaging techniques developed in our laboratory and their ability to operate as stand-alone tools, integrated in a biopsy needle and in conjunction with the da Vinci surgical robot. We present pre-clinical and clinical studies in patients that demonstrate the potential of these techniques for intraoperative assessment of brain tumors and head and neck cancer. Current results demonstrate that intrinsic fluorescence signals can provide useful contrast for delineation distinct types of tissues including tumors intraoperatively. Challenges and solutions in the clinical implementation of these techniques are discussed.

Spatial-Temporal [{sup 18}F]FDG-PET Features for Predicting Pathologic Response of Esophageal Cancer to Neoadjuvant Chemoradiation Therapy

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

Tan, Shan; Department of Control Science and Engineering, Huazhong University of Science and Technology, Wuhan; Kligerman, Seth

2013-04-01

Purpose: To extract and study comprehensive spatial-temporal {sup 18}F-labeled fluorodeoxyglucose ([{sup 18}F]FDG) positron emission tomography (PET) features for the prediction of pathologic tumor response to neoadjuvant chemoradiation therapy (CRT) in esophageal cancer. Methods and Materials: Twenty patients with esophageal cancer were treated with trimodal therapy (CRT plus surgery) and underwent [{sup 18}F]FDG-PET/CT scans both before (pre-CRT) and after (post-CRT) CRT. The 2 scans were rigidly registered. A tumor volume was semiautomatically delineated using a threshold standardized uptake value (SUV) of ≥2.5, followed by manual editing. Comprehensive features were extracted to characterize SUV intensity distribution, spatial patterns (texture), tumor geometry, andmore » associated changes resulting from CRT. The usefulness of each feature in predicting pathologic tumor response to CRT was evaluated using the area under the receiver operating characteristic curve (AUC) value. Results: The best traditional response measure was decline in maximum SUV (SUV{sub max}; AUC, 0.76). Two new intensity features, decline in mean SUV (SUV{sub mean}) and skewness, and 3 texture features (inertia, correlation, and cluster prominence) were found to be significant predictors with AUC values ≥0.76. According to these features, a tumor was more likely to be a responder when the SUV{sub mean} decline was larger, when there were relatively fewer voxels with higher SUV values pre-CRT, or when [{sup 18}F]FDG uptake post-CRT was relatively homogeneous. All of the most accurate predictive features were extracted from the entire tumor rather than from the most active part of the tumor. For SUV intensity features and tumor size features, changes were more predictive than pre- or post-CRT assessment alone. Conclusion: Spatial-temporal [{sup 18}F]FDG-PET features were found to be useful predictors of pathologic tumor response to neoadjuvant CRT in esophageal cancer.« less

Progressive aphasia secondary to Alzheimer disease pathology: A clinicopathologic and MRI study

PubMed Central

Josephs, Keith A.; Whitwell, Jennifer L.; Duffy, Joseph R.; Vanvoorst, Wendy A.; Strand, Edyth A.; Hu, William T.; Boeve, Bradley F.; Graff-Radford, Neill R.; Parisi, Joseph E.; Knopman, David S.; Dickson, Dennis W.; Jack, Clifford R.; Petersen, Ronald C.

2009-01-01

Background The pathology causing progressive aphasia is typically a variant of frontotemporal lobar degeneration, especially with ubiquitin-positive-inclusions (FTLD-U). Less commonly the underlying pathology is Alzheimer disease (AD). Objective To compare clinicopathological and MRI features of subjects with progressive aphasia and AD pathology, to subjects with aphasia and FTLD-U pathology, and subjects with typical AD. Methods We identified 5 subjects with aphasia and AD pathology and 5 with aphasia and FTLD-U pathology with an MRI from a total of 216 aphasia subjects. Ten subjects with typical AD clinical features and AD pathology were also identified. All subjects with AD pathology underwent pathological re-analysis with TDP-43 immunohistochemistry. Voxel-based morphometry (VBM) was used to assess patterns of grey matter atrophy in the aphasia cases with AD pathology, aphasia cases with FTLD-U, and typical AD cases with AD pathology, compared to a normal control group. Results All aphasic subjects had fluent speech output. However, those with AD pathology had better processing speed than those with FTLD-U pathology. Immunohistochemistry with TDP-43 antibodies was negative. VBM revealed grey matter atrophy predominantly in the temporoparietal cortices with notable sparing of the hippocampus in the aphasia with AD subjects. In comparison, the aphasic subjects with FTLD-U showed sparing of the parietal lobe. Typical AD subjects showed temporoparietal and hippocampal atrophy. Conclusions A temporoparietal pattern of atrophy on MRI in patients with progressive fluent aphasia and relatively preserved processing speed is suggestive of underlying AD pathology rather than FTLD-U. PMID:18166704

The Diagnostic Dilemma of Pathological Appearance and Performance Enhancing Drug Use

PubMed Central

Hildebrandt, Tom; Lai, Justine K.; Langenbucher, James W.; Schneider, Melanie; Yehuda, Rachel; Pfaff, Donald W.

2010-01-01

Appearance and performance enhancing drug (APED) use includes the use of a range of pharmacologically distinct substances and concurrent investment in outward appearance or achievement, dietary control, and frequent exercise. A number of existing reviews and conceptual papers have defined pathological forms of APED use within the APED class of anabolic-androgenic steroids (AASs) and using the framework of AAS dependence. We review published data on APED use including human studies of AAS users and identified three defining phenomenological features associated with increased health risk and pathology. These features included (1) polypharmacy or the concurrent use of several pharmacologically distinct substances used to change outward appearance or increase likelihood of personal achievement; (2) significant body image disturbance; (3) rigid practices and preoccupations with diet and exercise. Investigations into the latent structure of APED use suggest these features cluster together in a homogenous group of APED users who have the highest health risk and most psychopathology. These features are discussed in the context of AAS dependence and problems with defining classic tolerance-withdrawal symptoms among APED users. Suggestions for a resolution and outline for future research needed to determine the best system for identifying and diagnosing pathological APED use are discussed. PMID:21115306

Meeting Report: Tissue-based Image Analysis.

PubMed

Saravanan, Chandra; Schumacher, Vanessa; Brown, Danielle; Dunstan, Robert; Galarneau, Jean-Rene; Odin, Marielle; Mishra, Sasmita

2017-10-01

Quantitative image analysis (IA) is a rapidly evolving area of digital pathology. Although not a new concept, the quantification of histological features on photomicrographs used to be cumbersome, resource-intensive, and limited to specialists and specialized laboratories. Recent technological advances like highly efficient automated whole slide digitizer (scanner) systems, innovative IA platforms, and the emergence of pathologist-friendly image annotation and analysis systems mean that quantification of features on histological digital images will become increasingly prominent in pathologists' daily professional lives. The added value of quantitative IA in pathology includes confirmation of equivocal findings noted by a pathologist, increasing the sensitivity of feature detection, quantification of signal intensity, and improving efficiency. There is no denying that quantitative IA is part of the future of pathology; however, there are also several potential pitfalls when trying to estimate volumetric features from limited 2-dimensional sections. This continuing education session on quantitative IA offered a broad overview of the field; a hands-on toxicologic pathologist experience with IA principles, tools, and workflows; a discussion on how to apply basic stereology principles in order to minimize bias in IA; and finally, a reflection on the future of IA in the toxicologic pathology field.

Gliomagenesis and neural stem cells: Key role of hypoxia and concept of tumor "neo-niche".

PubMed

Diabira, Sylma; Morandi, Xavier

2008-01-01

Gliomas represent the most common primary brain tumors and the most devastating pathology of the central nervous system. Despite progress in conventional treatments, the prognosis remains dismal. Recent studies have suggested that a glioma brain tumor may arise from a "cancer stem cell". To understand this theory we summarize studies of the concepts of neural stem cell, and its specialized microenvironment, namely the niche which can regulate balanced self-renewal, differentiation and stem cell quiescence. We summarize the molecular mechanism known or postulated to be involved in the disregulation of normal stem cells features allowing them to undergo neoplasic transformation. We seek data pointing out the key role of hypoxia in normal homeostasis of stem cells and in the initiation, development and aggressiveness of gliomas. We develop the concept of tumor special microenvironment and we propose the new concept of neo-niche, surrounding the glioma, in which hypoxia could be a key factor to recruit and deregulate different stem cells for gliogenesis process. Substantial advances in treatment would come from obtaining better knowledge of molecular impairs of this disease.

Assessment of orofacial characteristics and oral pathology associated with cri-du-chat syndrome.

PubMed

Rodríguez-Caballero, A; Torres-Lagares, D; Yáñez-Vico, R-M; Gutiérrez-Pérez, J-L; Machuca-Portillo, G

2012-03-01

To obtain a deeper insight into the difficulties individuals with cri-du-chat syndrome experience by means of the analysis of the most common features and oral pathology observed in the subjects enrolled in the study. Intra-oral and extra-oral features of a total of 33 patients with cri-du-chat syndrome (the larger sample so far analyzed) through their clinical and photographic examination. Models, orthopantomographies, and teleradiographies have been collected to establish a pattern as accurate as possible of the oral pathology associated with these patients. The present descriptive study shows that patients with cri-du-chat syndrome present with a series of orofacial features such as mandibular retrognathism, high palate, and variable malocclusion, more commonly anterior open-bite. Most patients also present with perioral muscle relaxation with labial incompetence and short philtrum. As regards oral pathology, these patients suffer dental erosions provoked by gastroesophageal reflux and attritions because of intense day-and-night bruxism. The odontologists' familiarity with the orofacial pathology associated with cri-du-chat syndrome and with the specific needs such disorder conveys should improve the quality of the buccodental treatment these professionals may offer to these patients. © 2011 John Wiley & Sons A/S.

Telephone-quality pathological speech classification using empirical mode decomposition.

PubMed

Kaleem, M F; Ghoraani, B; Guergachi, A; Krishnan, S

2011-01-01

This paper presents a computationally simple and effective methodology based on empirical mode decomposition (EMD) for classification of telephone quality normal and pathological speech signals. EMD is used to decompose continuous normal and pathological speech signals into intrinsic mode functions, which are analyzed to extract physically meaningful and unique temporal and spectral features. Using continuous speech samples from a database of 51 normal and 161 pathological speakers, which has been modified to simulate telephone quality speech under different levels of noise, a linear classifier is used with the feature vector thus obtained to obtain a high classification accuracy, thereby demonstrating the effectiveness of the methodology. The classification accuracy reported in this paper (89.7% for signal-to-noise ratio 30 dB) is a significant improvement over previously reported results for the same task, and demonstrates the utility of our methodology for cost-effective remote voice pathology assessment over telephone channels.

Caffeoyl glucosides from Nandina domestica inhibit LPS-induced endothelial inflammatory responses.

PubMed

Kulkarni, Roshan R; Lee, Wonhwa; Jang, Tae Su; Lee, JungIn; Kwak, Soyoung; Park, Mi Seon; Lee, Hyun-Shik; Bae, Jong-Sup; Na, MinKyun

2015-11-15

Endothelial dysfunction is a key pathological feature of many inflammatory diseases, including sepsis. In the present study, a new caffeoyl glucoside (1) and two known caffeoylated compounds (2 and 3) were isolated from the fruits of Nandina domestica Thunb. (Berberidaceae). The compounds were investigated for their effects against lipopolysaccharide (LPS)-mediated endothelial inflammatory responses. At 20 μM, 1 and 2 inhibited LPS-induced hyperpermeability, adhesion, and migration of leukocytes across a human endothelial cell monolayer in a dose-dependent manner suggesting that 1 and 2 may serve as potential scaffolds for the development of therapeutic agents to treat vascular inflammatory disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

ER stress signaling and neurodegeneration: At the intersection between Alzheimer's disease and Prion-related disorders.

PubMed

Torres, Mauricio; Matamala, José Manuel; Duran-Aniotz, Claudia; Cornejo, Victor Hugo; Foley, Andrew; Hetz, Claudio

2015-09-02

Alzheimer's and Prion diseases are two neurodegenerative conditions sharing different pathophysiological characteristics. Disease symptoms are associated with the abnormal accumulation of protein aggregates, which are generated by the misfolding and oligomerization of specific proteins. Recent functional studies uncovered a key role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in the occurrence of synaptic dysfunction and neurodegeneration in Prion-related disorders and Alzheimer's disease. Here we review common pathological features of both diseases, emphasizing the link between amyloid formation, its pathogenesis and alterations in ER proteostasis. The potential benefits of targeting the UPR as a therapeutic strategy is also discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

Multi-detector CT angiography of the aortic valve—Part 2: disease specific findings

PubMed Central

Ganeshan, Arul

2014-01-01

The aortic valve and adjacent structures should be routinely evaluated on all thoracic cross-sectional imaging studies. Echocardiography and magnetic resonance imaging (MRI) are the main imaging techniques used for assessment of the aortic valve and related pathology but multi-detector computed tomography (MDCT) can offer valuable complimentary information in some clinical scenarios. MDCT is the definite means of assessing aortic valvular calcification, acute aortic syndrome and for non-invasive assessment of the coronary arteries. MDCT also has an emerging role in the planning and follow-up of trans-catheter aortic valve replacement. This article reviews the spectrum of aortic valve disease highlighting the key MDCT imaging features. PMID:25202663

Pathologic features of early inflammatory bowel disease.

PubMed

Finkelstein, Sydney D; Sasatomi, Eizaburo; Regueiro, Miguel

2002-03-01

Often the pathologic changes of IBD are subtle and may not be present in a proportion of biopsy specimens. In cases of early disease, the changes may be missed, and additional specimens should be taken after a period of time. Modifying factors, such as prebiopsy treatment and coexisting disease, should be considered. A forum to review cases and allow for communication between gastroenterologists and pathologists is especially useful for clinicopathologic correlation and assignment of a working diagnosis to each case. Careful attention to the pathologic features of early UC and CD would be most useful when evaluating new therapies for IBD.

Mouse model of necrotic tuberculosis granulomas develops hypoxic lesions.

PubMed

Harper, Jamie; Skerry, Ciaran; Davis, Stephanie L; Tasneen, Rokeya; Weir, Mariah; Kramnik, Igor; Bishai, William R; Pomper, Martin G; Nuermberger, Eric L; Jain, Sanjay K

2012-02-15

Preclinical evaluation of tuberculosis drugs is generally limited to mice. However, necrosis and hypoxia, key features of human tuberculosis lesions, are lacking in conventional mouse strains. We used C3HeB/FeJ mice, which develop necrotic lesions in response to Mycobacterium tuberculosis infection. Positron emission tomography in live infected animals, postmortem pimonidazole immunohistochemistry, and bacterial gene expression analyses were used to assess whether tuberculosis lesions in C3HeB/FeJ are hypoxic. Efficacy of combination drug treatment, including PA-824, active against M. tuberculosis under hypoxic conditions, was also evaluated. Tuberculosis lesions in C3HeB/FeJ (but not BALB/c) were found to be hypoxic and associated with up-regulation of known hypoxia-associated bacterial genes (P < .001). Contrary to sustained activity reported elsewhere in BALB/c mice, moxifloxacin and pyrazinamide (MZ) combination was not bactericidal beyond 3 weeks in C3HeB/FeJ. Although PA-824 added significant activity, the novel combination of PA-824 and MZ was less effective than the standard first-line regimen in C3HeB/FeJ. We demonstrate that tuberculosis lesions in C3HeB/FeJ are hypoxic. Activities of some key tuberculosis drug regimens in development are represented differently in C3HeB/FeJ versus BALB/c mice. Because C3HeB/FeJ display key features of human tuberculosis, this strain warrants evaluation as a more pathologically relevant model for preclinical studies.

A comparative study for chest radiograph image retrieval using binary texture and deep learning classification.

PubMed

Anavi, Yaron; Kogan, Ilya; Gelbart, Elad; Geva, Ofer; Greenspan, Hayit

2015-08-01

In this work various approaches are investigated for X-ray image retrieval and specifically chest pathology retrieval. Given a query image taken from a data set of 443 images, the objective is to rank images according to similarity. Different features, including binary features, texture features, and deep learning (CNN) features are examined. In addition, two approaches are investigated for the retrieval task. One approach is based on the distance of image descriptors using the above features (hereon termed the "descriptor"-based approach); the second approach ("classification"-based approach) is based on a probability descriptor, generated by a pair-wise classification of each two classes (pathologies) and their decision values using an SVM classifier. Best results are achieved using deep learning features in a classification scheme.

Ovarian torsion: diagnostic features on CT and MRI with pathologic correlation.

PubMed

Duigenan, Shauna; Oliva, Esther; Lee, Susanna I

2012-02-01

The CT and MRI features of ovarian torsion are illustrated with gross pathologic correlation. Ovarian enlargement with or without an underlying mass is the finding most frequently associated with torsion, but it is nonspecific. A twisted pedicle, although not often detected on imaging, is pathognomonic when seen. Subacute ovarian hemorrhage and abnormal enhancement is usually seen, and both features show characteristic patterns on CT and MRI. Ipsilateral uterine deviation can also be seen. Diagnostic pitfalls that may mimic ovarian torsion and observations for discriminating them are discussed.

Dawn of the digital diagnosis assisting system, can it open a new age for pathology?

NASA Astrophysics Data System (ADS)

Saito, Akira; Cosatto, Eric; Kiyuna, Tomoharu; Sakamoto, Michiie

2013-03-01

Digital pathology is developing based on the improvement and popularization of WSI (whole slide imaging) scanners. WSI scanners are widely expected to be used as the next generation microscope for diagnosis; however, their usage is currently mostly limited to education and archiving. Indeed, there are still many hindrances in using WSI scanners for diagnosis (not research purpose), two of the main reasons being the perceived high cost and small gain in productivity obtained by switching from the microscope to a WSI system and the lack of WSI standardization. We believe that a key factor for advancing digital pathology is the creation of computer assisted diagnosis systems (CAD). Such systems require high-resolution digitization of slides and provide a clear added value to the often costly conversion to WSI. We (NEC Corporation) are creating a CAD system, named e-Pathologist ®. This system is currently used at independent pathology labs for quality control (QC/QA), double-checking pathologists diagnosis and preventing missed cancers. At the end of 2012, about 80,000 slides, 200,000 tissues of gastric and colorectal samples will have been analyzed by e-Pathologist ®. Through the development of e-Pathologist ®, it has become clear that a computer program should be inspired by the pathologist diagnosis process, yet it should not be a mere copy or simulation of it. Indeed pathologists often approach the diagnosis of slides in a "holistic" manner, examining them at various magnifications, panning and zooming in a seemingly haphazard way that they often have a hard time to precisely describe. Hence there has been no clear recipe emerging from numerous interviews with pathologists on how to exactly computer code a diagnosis expert system. Instead, we focused on extracting a small set of histopathological features that were consistently indicated as important by the pathologists and then let the computer figure out how to interpret in a quantitative way the presence or absence of these features over the entire slide. Using the overall pathologists diagnosis (into a class of disease), we train the computer system using advanced machine learning techniques to predict the disease based on the extracted features. By considering the diagnosis of several expert pathologists during the training phase, we insure that the machine is learning a "gold standard" that will be applied consistently and objectively for all subsequent diagnosis, making them more predictable and reliable. Considering the future of digital pathology, it is essential for a CAD system to produce effective and accurate clinical data. To this effect, there remain many hurdles, including standardization as well as more research into seeking clinical evidences from "computer-friendly" objective measurements of histological images. Currently the most commonly used staining method is H&E (Hematoxylin and Eosin), but it is extremely difficult to standardize the H&E staining process. Current pathology criteria, category, definitions, and thresholds are all on based pathologists subjective observations. Digital pathology is an emerging field and researchers should bear responsibility not only for developing new algorithms, but also for understanding the meaning of measured quantitative data.

A comparative study of the svm and k-nn machine learning algorithms for the diagnosis of respiratory pathologies using pulmonary acoustic signals

PubMed Central

2014-01-01

Background Pulmonary acoustic parameters extracted from recorded respiratory sounds provide valuable information for the detection of respiratory pathologies. The automated analysis of pulmonary acoustic signals can serve as a differential diagnosis tool for medical professionals, a learning tool for medical students, and a self-management tool for patients. In this context, we intend to evaluate and compare the performance of the support vector machine (SVM) and K-nearest neighbour (K-nn) classifiers in diagnosis respiratory pathologies using respiratory sounds from R.A.L.E database. Results The pulmonary acoustic signals used in this study were obtained from the R.A.L.E lung sound database. The pulmonary acoustic signals were manually categorised into three different groups, namely normal, airway obstruction pathology, and parenchymal pathology. The mel-frequency cepstral coefficient (MFCC) features were extracted from the pre-processed pulmonary acoustic signals. The MFCC features were analysed by one-way ANOVA and then fed separately into the SVM and K-nn classifiers. The performances of the classifiers were analysed using the confusion matrix technique. The statistical analysis of the MFCC features using one-way ANOVA showed that the extracted MFCC features are significantly different (p < 0.001). The classification accuracies of the SVM and K-nn classifiers were found to be 92.19% and 98.26%, respectively. Conclusion Although the data used to train and test the classifiers are limited, the classification accuracies found are satisfactory. The K-nn classifier was better than the SVM classifier for the discrimination of pulmonary acoustic signals from pathological and normal subjects obtained from the RALE database. PMID:24970564

A comparative study of the SVM and K-nn machine learning algorithms for the diagnosis of respiratory pathologies using pulmonary acoustic signals.

PubMed

Palaniappan, Rajkumar; Sundaraj, Kenneth; Sundaraj, Sebastian

2014-06-27

Pulmonary acoustic parameters extracted from recorded respiratory sounds provide valuable information for the detection of respiratory pathologies. The automated analysis of pulmonary acoustic signals can serve as a differential diagnosis tool for medical professionals, a learning tool for medical students, and a self-management tool for patients. In this context, we intend to evaluate and compare the performance of the support vector machine (SVM) and K-nearest neighbour (K-nn) classifiers in diagnosis respiratory pathologies using respiratory sounds from R.A.L.E database. The pulmonary acoustic signals used in this study were obtained from the R.A.L.E lung sound database. The pulmonary acoustic signals were manually categorised into three different groups, namely normal, airway obstruction pathology, and parenchymal pathology. The mel-frequency cepstral coefficient (MFCC) features were extracted from the pre-processed pulmonary acoustic signals. The MFCC features were analysed by one-way ANOVA and then fed separately into the SVM and K-nn classifiers. The performances of the classifiers were analysed using the confusion matrix technique. The statistical analysis of the MFCC features using one-way ANOVA showed that the extracted MFCC features are significantly different (p < 0.001). The classification accuracies of the SVM and K-nn classifiers were found to be 92.19% and 98.26%, respectively. Although the data used to train and test the classifiers are limited, the classification accuracies found are satisfactory. The K-nn classifier was better than the SVM classifier for the discrimination of pulmonary acoustic signals from pathological and normal subjects obtained from the RALE database.

MR imaging features and staging of neuroendocrine carcinomas of the uterine cervix with pathological correlations.

PubMed

Duan, Xiaohui; Ban, Xiaohua; Zhang, Xiang; Hu, Huijun; Li, Guozhao; Wang, Dongye; Wang, Charles Qian; Zhang, Fang; Shen, Jun

2016-12-01

To determine MR imaging features and staging accuracy of neuroendocrine carcinomas (NECs) of the uterine cervix with pathological correlations. Twenty-six patients with histologically proven NECs, 60 patients with squamous cell carcinomas (SCCs), and 30 patients with adenocarcinomas of the uterine cervix were included. The clinical data, pathological findings, and MRI findings were reviewed retrospectively. MRI features of cervical NECs, SCCs, and adenocarcinomas were compared, and MRI staging of cervical NECs was compared with the pathological staging. Cervical NECs showed a higher tendency toward a homogeneous signal intensity on T2-weighted imaging and a homogeneous enhancement pattern, as well as a lower ADC value of tumour and a higher incidence of lymphadenopathy, compared with SCCs and adenocarcinomas (P < 0.05). An ADC value cutoff of 0.90 × 10 -3  mm 2 /s was robust for differentiation between cervical NECs and other cervical cancers, with a sensitivity of 63.3 % and a specificity of 95 %. In 21 patients who underwent radical hysterectomy and lymphadenectomy, the overall accuracy of tumour staging by MR imaging was 85.7 % with reference to pathology staging. Homogeneous lesion texture and low ADC value are likely suggestive features of cervical NECs and MR imaging is reliable for the staging of cervical NECs. • Cervical NECs show a tendency of lesion homogeneity and lymphadenopathy • Low ADC values are found in cervical NECs • MRI is an accurate imaging modality for the cervical NEC staging.

The Videofluorographic Swallowing Study in Rheumatologic Diseases: A Comprehensive Review

PubMed Central

Di Piazza, Ambra; Costanzo, Massimo; Scopelliti, Laura; Salvaggi, Francesco; Cupido, Francesco; Salerno, Sergio; Lo Casto, Antonio; Midiri, Massimo; Lo Re, Giuseppe; Lagalla, Roberto

2017-01-01

Autoimmune connective tissue diseases are a heterogeneous group of pathologies that affect about 10% of world population with chronic evolution in 20%–80%. Inflammation in autoimmune diseases may lead to serious damage to other organs including the gastrointestinal tract. Gastrointestinal tract involvement in these patients may also due to both a direct action of antibodies against organs and pharmacological therapies. Dysphagia is one of the most important symptom, and it is caused by failure of the swallowing function and may lead to aspiration pneumonia, malnutrition, dehydration, weight loss, and airway obstruction. The videofluorographic swallowing study is a key diagnostic tool in the detection of swallowing disorders, allowing to make an early diagnosis and to reduce the risk of gastrointestinal and pulmonary complications. This technique helps to identify both functional and structural anomalies of the anatomic chain involved in swallowing function. The aim of this review is to systematically analyze the basis of the pathological involvement of the swallowing function for each rheumatological disease and to show the main features of the videofluorographic study that may be encountered in these patients. PMID:28706536

Mitochondrial Aspects of Synaptic Dysfunction in Alzheimer’s Disease

PubMed Central

Cai, Qian; Tammineni, Prasad

2016-01-01

Alzheimer’s disease (AD) is characterized by brain deposition of amyloid plaques and tau neurofibrillary tangles along with steady cognitive decline. Synaptic damage, an early pathological event, correlates strongly with cognitive deficits and memory loss. Mitochondria are essential organelles for synaptic function. Neurons utilize specialized mechanisms to drive mitochondrial trafficking to synapses in which mitochondria buffer Ca2+ and serve as local energy sources by supplying ATP to sustain neurotransmitter release. Mitochondrial abnormalities are one of the earliest and prominent features in AD patient brains. Amyloid-β (Aβ) and tau both trigger mitochondrial alterations. Accumulating evidence suggests that mitochondrial perturbation acts as a key factor that is involved in synaptic failure and degeneration in AD. The importance of mitochondria in supporting synaptic function has made them a promising target of new therapeutic strategy for AD. Here, we review the molecular mechanisms regulating mitochondrial function at synapses, highlight recent findings on the disturbance of mitochondrial dynamics and transport in AD, and discuss how these alterations impact synaptic vesicle release and thus contribute to synaptic pathology associated with AD. PMID:27767992

Using Networks To Understand Medical Data: The Case of Class III Malocclusions

PubMed Central

Scala, Antonio; Auconi, Pietro; Scazzocchio, Marco; Caldarelli, Guido; McNamara, James A.; Franchi, Lorenzo

2012-01-01

A system of elements that interact or regulate each other can be represented by a mathematical object called a network. While network analysis has been successfully applied to high-throughput biological systems, less has been done regarding their application in more applied fields of medicine; here we show an application based on standard medical diagnostic data. We apply network analysis to Class III malocclusion, one of the most difficult to understand and treat orofacial anomaly. We hypothesize that different interactions of the skeletal components can contribute to pathological disequilibrium; in order to test this hypothesis, we apply network analysis to 532 Class III young female patients. The topology of the Class III malocclusion obtained by network analysis shows a strong co-occurrence of abnormal skeletal features. The pattern of these occurrences influences the vertical and horizontal balance of disharmony in skeletal form and position. Patients with more unbalanced orthodontic phenotypes show preponderance of the pathological skeletal nodes and minor relevance of adaptive dentoalveolar equilibrating nodes. Furthermore, by applying Power Graphs analysis we identify some functional modules among orthodontic nodes. These modules correspond to groups of tightly inter-related features and presumably constitute the key regulators of plasticity and the sites of unbalance of the growing dentofacial Class III system. The data of the present study show that, in their most basic abstraction level, the orofacial characteristics can be represented as graphs using nodes to represent orthodontic characteristics, and edges to represent their various types of interactions. The applications of this mathematical model could improve the interpretation of the quantitative, patient-specific information, and help to better targeting therapy. Last but not least, the methodology we have applied in analyzing orthodontic features can be applied easily to other fields of the medical science. PMID:23028552

Update on conjunctival pathology

PubMed Central

Mudhar, Hardeep Singh

2017-01-01

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

[Two anniversaries in Czech forensic medicine].

PubMed

Nečas, P; Hejna, P

2012-10-01

The authors commemorate the 100th anniversary of the publication of Slavíks textbook Forensic Pathology for Medical and Legal Students and the 125th anniversary of the 1st Czech forensic autopsy. They introduce professor V. Slavík and describe his personal qualities and expertise. The content of the textbook is described. The topicality of Slavíks explanations and the tradition of Czech forensic pathology are discussed. Key words: forensic pathology - history of Czech forensic pathology - textbooks of forensic pathology.

Features and machine learning classification of connected speech samples from patients with autopsy proven Alzheimer's disease with and without additional vascular pathology.

PubMed

Rentoumi, Vassiliki; Raoufian, Ladan; Ahmed, Samrah; de Jager, Celeste A; Garrard, Peter

2014-01-01

Mixed vascular and Alzheimer-type dementia and pure Alzheimer's disease are both associated with changes in spoken language. These changes have, however, seldom been subjected to systematic comparison. In the present study, we analyzed language samples obtained during the course of a longitudinal clinical study from patients in whom one or other pathology was verified at post mortem. The aims of the study were twofold: first, to confirm the presence of differences in language produced by members of the two groups using quantitative methods of evaluation; and secondly to ascertain the most informative sources of variation between the groups. We adopted a computational approach to evaluate digitized transcripts of connected speech along a range of language-related dimensions. We then used machine learning text classification to assign the samples to one of the two pathological groups on the basis of these features. The classifiers' accuracies were tested using simple lexical features, syntactic features, and more complex statistical and information theory characteristics. Maximum accuracy was achieved when word occurrences and frequencies alone were used. Features based on syntactic and lexical complexity yielded lower discrimination scores, but all combinations of features showed significantly better performance than a baseline condition in which every transcript was assigned randomly to one of the two classes. The classification results illustrate the word content specific differences in the spoken language of the two groups. In addition, those with mixed pathology were found to exhibit a marked reduction in lexical variation and complexity compared to their pure AD counterparts.

An atlas of radiological interpretation

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

Calder, J.F.; Chessell, G.

1988-01-01

This book is concerned with pathologic entities and their impact on the skeleton. The book is divided into nine chapters. After a discussion of normal anatomic features, the authors discuss trauma, avascular necrosis and osteochondritis, bone infections, diseases of the joints, bone tumors, reticuloses and hemopoietic disorders, endocrine and metabolic bone diseases, and congenital abnormalities. A line drawing accompanies every radiograph to contrast the pathologic findings with the normal anatomic features.

Pathological narcissism and acute anxiety symptoms after trauma: a study of Israeli civilians exposed to war.

PubMed

Besser, Avi; Zeigler-Hill, Virgil; Pincus, Aaron L; Neria, Yuval

2013-01-01

Diathesis-stress models of posttraumatic stress disorder (PTSD) hypothesize that exposure to trauma may interact with individual differences in the development of PTSD. Previous studies have not assessed immediate responses to a proximate stressor, but the current "natural laboratory" study was designed to empirically test the role that individual differences in pathological narcissism may play in the development of acute anxiety symptoms among civilians facing rocket and missile fire. We assessed demographic features, trauma exposure severity, narcissistic personality features, and acute anxiety symptoms (PTSD and General Anxiety Disorder [GAD]) among 342 Israeli female adults during the November 2012 eruption of violence in the Middle East. Results demonstrate an association between exposure severity and acute anxiety symptoms (both PTSD and GAD) for individuals with high levels of pathological narcissism but not for those with low levels of pathological narcissism. These results suggest that individuals with narcissistic personality features are at high risk for the development of acute anxiety symptoms following exposure to uncontrollable and life-threatening mass trauma. The findings underscore the role of intra-personal resources in the immediate psychological aftermath of war by highlighting the increased risk associated with narcissistic personality features. Theoretical and clinical implications of the findings are discussed.

Pathology of Chronic Chagas Cardiomyopathy in the United States:  A Detailed Review of 13 Cardiectomy Cases.

PubMed

Kransdorf, Evan P; Fishbein, Mike C; Czer, Lawrence S C; Patel, Jignesh K; Velleca, Angela; Tazelaar, Henry D; Roy, R Raina; Steidley, D Eric; Kobashigawa, Jon A; Luthringer, Daniel J

2016-08-01

The pathologic features of chronic Chagas cardiomyopathy may not be widely appreciated in the United States. We sought to describe the gross, microscopic, immunohistochemical, and molecular pathology features useful to diagnose chronic Chagas cardiomyopathy. The features from a case series of cardiectomy specimens of patients undergoing heart transplantation (12 patients) or mechanical circulatory support device implantation (one patient) for chronic Chagas cardiomyopathy at three institutions in the United States are reported and analyzed. Gross findings included enlarged and dilated ventricles (100% of cases), mural thrombi (54%), epicardial plaques (42%), and left ventricular aneurysm (36%). Microscopic evaluation revealed myocarditis (100% of cases) characterized by mononuclear cell infiltration, fibrosis (100%), nonnecrotizing granulomas (62%), and giant cells (38%). Two specimens (15%) showed rare intracellular amastigotes. Immunohistochemical assays for Trypanosoma cruzi organisms were negative in all cardiectomy specimens, whereas tissue polymerase chain reaction was positive in six (54%) of 11 cases. The gross and microscopic features of chronic Chagas cardiomyopathy in the United States appear similar to those reported in endemic countries. Importantly, tissue polymerase chain reaction may be useful to confirm the diagnosis. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A Joint Time-Frequency and Matrix Decomposition Feature Extraction Methodology for Pathological Voice Classification

NASA Astrophysics Data System (ADS)

Ghoraani, Behnaz; Krishnan, Sridhar

2009-12-01

The number of people affected by speech problems is increasing as the modern world places increasing demands on the human voice via mobile telephones, voice recognition software, and interpersonal verbal communications. In this paper, we propose a novel methodology for automatic pattern classification of pathological voices. The main contribution of this paper is extraction of meaningful and unique features using Adaptive time-frequency distribution (TFD) and nonnegative matrix factorization (NMF). We construct Adaptive TFD as an effective signal analysis domain to dynamically track the nonstationarity in the speech and utilize NMF as a matrix decomposition (MD) technique to quantify the constructed TFD. The proposed method extracts meaningful and unique features from the joint TFD of the speech, and automatically identifies and measures the abnormality of the signal. Depending on the abnormality measure of each signal, we classify the signal into normal or pathological. The proposed method is applied on the Massachusetts Eye and Ear Infirmary (MEEI) voice disorders database which consists of 161 pathological and 51 normal speakers, and an overall classification accuracy of 98.6% was achieved.

A novel murmur-based heart sound feature extraction technique using envelope-morphological analysis

NASA Astrophysics Data System (ADS)

Yao, Hao-Dong; Ma, Jia-Li; Fu, Bin-Bin; Wang, Hai-Yang; Dong, Ming-Chui

2015-07-01

Auscultation of heart sound (HS) signals serves as an important primary approach to diagnose cardiovascular diseases (CVDs) for centuries. Confronting the intrinsic drawbacks of traditional HS auscultation, computer-aided automatic HS auscultation based on feature extraction technique has witnessed explosive development. Yet, most existing HS feature extraction methods adopt acoustic or time-frequency features which exhibit poor relationship with diagnostic information, thus restricting the performance of further interpretation and analysis. Tackling such a bottleneck problem, this paper innovatively proposes a novel murmur-based HS feature extraction method since murmurs contain massive pathological information and are regarded as the first indications of pathological occurrences of heart valves. Adapting discrete wavelet transform (DWT) and Shannon envelope, the envelope-morphological characteristics of murmurs are obtained and three features are extracted accordingly. Validated by discriminating normal HS and 5 various abnormal HS signals with extracted features, the proposed method provides an attractive candidate in automatic HS auscultation.

Pathology Gross Photography: The Beginning of Digital Pathology.

PubMed

Rampy, B Alan; Glassy, Eric F

2015-06-01

The underutilized practice of photographing anatomic pathology specimens from surgical pathology and autopsies is an invaluable benefit to patients, clinicians, pathologists, and students. Photographic documentation of clinical specimens is essential for the effective practice of pathology. When considering what specimens to photograph, all grossly evident pathology, absent yet expected pathologic features, and gross-only specimens should be thoroughly documented. Specimen preparation prior to photography includes proper lighting and background, wiping surfaces of blood, removing material such as tubes or bandages, orienting the specimen in a logical fashion, framing the specimen to fill the screen, positioning of probes, and using the right-sized scale. Copyright © 2015 Elsevier Inc. All rights reserved.

Solid-State NMR Structure of a Pathogenic Fibril of Full-Length Human α-Synuclein

PubMed Central

Tuttle, Marcus D.; Comellas, Gemma; Nieuwkoop, Andrew J.; Covell, Dustin J.; Berthold, Deborah A.; Kloepper, Kathryn D.; Courtney, Joseph M.; Kim, Jae K.; Barclay, Alexander M.; Kendall, Amy; Wan, William; Stubbs, Gerald; Schwieters, Charles D.; Lee, Virginia M. Y.; George, Julia M.; Rienstra, Chad M.

2016-01-01

Misfolded α-synuclein amyloid fibrils are the principal components of Lewy bodies and neurites, hallmarks of Parkinson’s disease (PD). Here we present a high-resolution structure of an α-synuclein fibril, in a form that induces robust pathology in primary neuronal culture, determined by solid-state NMR spectroscopy and validated by electron microscopy and X-ray fiber diffraction. Over 200 unique long-range distance restraints define a consensus structure with common amyloid features including parallel in-register β-sheets and hydrophobic core residues, but also substantial complexity, arising from diverse structural features: an intermolecular salt bridge, a glutamine ladder, close backbone interactions involving small residues, and several steric zippers stabilizing a novel, orthogonal Greek-key topology. These characteristics contribute to the robust propagation of this fibril form, as evidenced by structural similarity of early-onset PD mutants. The structure provides a framework for understanding the interactions of α-synuclein with other proteins and small molecules to diagnose and treat PD. PMID:27018801

Interpersonal traits of psychopathy linked to reduced integrity of the uncinate fasciculus.

PubMed

Wolf, Richard C; Pujara, Maia S; Motzkin, Julian C; Newman, Joseph P; Kiehl, Kent A; Decety, Jean; Kosson, David S; Koenigs, Michael

2015-10-01

Psychopathy is a personality disorder characterized by callous lack of empathy, impulsive antisocial behavior, and criminal recidivism. Here, we performed the largest diffusion tensor imaging (DTI) study of incarcerated criminal offenders to date (N = 147) to determine whether psychopathy severity is linked to the microstructural integrity of major white matter tracts in the brain. Consistent with the results of previous studies in smaller samples, we found that psychopathy was associated with reduced fractional anisotropy in the right uncinate fasciculus (UF; the major white matter tract connecting ventral frontal and anterior temporal cortices). We found no such association in the left UF or in adjacent frontal or temporal white matter tracts. Moreover, the right UF finding was specifically related to the interpersonal features of psychopathy (glib superficial charm, grandiose sense of self-worth, pathological lying, manipulativeness), rather than the affective, antisocial, or lifestyle features. These results indicate a neural marker for this key dimension of psychopathic symptomatology. © 2015 Wiley Periodicals, Inc.

Interpersonal traits of psychopathy linked to reduced integrity of the uncinate fasciculus

PubMed Central

Wolf, Richard C.; Pujara, Maia S.; Motzkin, Julian C.; Newman, Joseph P.; Kiehl, Kent A.; Decety, Jean; Kosson, David S.; Koenigs, Michael

2015-01-01

Psychopathy is a personality disorder characterized by callous lack of empathy, impulsive antisocial behavior, and criminal recidivism. Here we performed the largest diffusion tensor imaging (DTI) study of incarcerated criminal offenders to date (N = 147) to determine whether psychopathy severity is linked to the microstructural integrity of major white matter tracts in the brain. Consistent with the results of previous studies in smaller samples, we found that psychopathy was associated with reduced fractional anisotropy in the right uncinate fasciculus (the major white matter tract connecting ventral frontal and anterior temporal cortices). We found no such association in the left uncinate fasciculus or in adjacent frontal or temporal white matter tracts. Moreover, the right uncinate fasciculus finding was specifically related to the interpersonal features of psychopathy (glib superficial charm, grandiose sense of self-worth, pathological lying, manipulativeness), rather than the affective, antisocial, or lifestyle features. These results indicate a neural marker for this key dimension of psychopathic symptomatology. PMID:26219745

The pathology and pathophysiology of vascular dementia.

PubMed

Kalaria, Raj N

2017-12-19

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

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.

"Big eye" surgery: the ethics of medicalizing Asian features.

PubMed

Aquino, Yves Saint James

2017-06-01

The popularity of surgical modifications of race-typical features among Asian women has generated debates on the ethical implications of the practice. Focusing on blepharoplasty as a representative racial surgery, this article frames the ethical discussion by viewing Asian cosmetic surgery as an example of medicalization, which can be interpreted in two forms: treatment versus enhancement. In the treatment form, medicalization occurs by considering cosmetic surgery as remedy for pathologized Asian features; the pathologization usually occurs in reference to western features as the norm. In the enhancement form, medicalization occurs by using medical means to improve physical features to achieve a certain type of beauty or physical appearance. Each type of medicalization raises slightly different ethical concerns. The problem with treatment medicalization lies in the pathologization of Asian features, which is oppressive as it continues to reinforce racial norms of appearance and negative stereotypes. Enhancement medicalization is ethically problematic because cosmetic surgery tends to conflate beauty and health as medical goals of surgery, overemphasizing the value of appearance that can further displace women's control over their own bodies. I conclude that in both forms of medicalization, cosmetic surgery seems to narrowly frame a complex psychosocial issue involving physical appearance as a matter that can be simply solved through surgical means.

Neuroimmune mechanisms of stress: sex differences, developmental plasticity, and implications for pharmacotherapy of stress-related disease

PubMed Central

Deak, Terrence; Quinn, Matt; Cidlowski, John A.; Victoria, Nicole C.; Murphy, Anne Z.; Sheridan, John F.

2016-01-01

The last decade has witnessed profound growth in studies examining the role of fundamental neuroimmune processes as key mechanisms that might form a natural bridge between normal physiology and pathological outcomes. Rooted in core concepts from psychoneuroimmunology, this review utilizes a succinct, exemplar-driven approach of several model systems that contribute significantly to our knowledge of the mechanisms by which neuroimmune processes interact with stress physiology. Specifically, we review recent evidence showing that (i) stress challenges produce time-dependent and stressor-specific patterns of cytokine/chemokine expression in the CNS; (ii) inflammation-related genes exhibit unique expression profiles in males and females depending upon individual, cooperative, or antagonistic interactions between steroid hormone receptors (Estrogen and Glucocorticoid receptors); (iii) adverse social experiences incurred through repeated social defeat engage a dynamic process of immune cell migration from the bone marrow to brain and prime neuroimmune function; and (iv) early developmental exposure to an inflammatory stimulus (carageenin injection into the hindpaw) has a lasting influence on stress reactivity across the lifespan. As such, the present review provides a theoretical framework for understanding the role that neuroimmune mechanisms might play in stress plasticity and pathological outcomes, while at the same time pointing toward features of the individual (sex, developmental experience, stress history) that might ultimately be used for the development of personalized strategies for therapeutic intervention in stress-related pathologies. PMID:26176590

Neuroimmune mechanisms of stress: sex differences, developmental plasticity, and implications for pharmacotherapy of stress-related disease.

PubMed

Deak, Terrence; Quinn, Matt; Cidlowski, John A; Victoria, Nicole C; Murphy, Anne Z; Sheridan, John F

2015-01-01

The last decade has witnessed profound growth in studies examining the role of fundamental neuroimmune processes as key mechanisms that might form a natural bridge between normal physiology and pathological outcomes. Rooted in core concepts from psychoneuroimmunology, this review utilizes a succinct, exemplar-driven approach of several model systems that contribute significantly to our knowledge of the mechanisms by which neuroimmune processes interact with stress physiology. Specifically, we review recent evidence showing that (i) stress challenges produce time-dependent and stressor-specific patterns of cytokine/chemokine expression in the CNS; (ii) inflammation-related genes exhibit unique expression profiles in males and females depending upon individual, cooperative or antagonistic interactions between steroid hormone receptors (estrogen and glucocorticoid receptors); (iii) adverse social experiences incurred through repeated social defeat engage a dynamic process of immune cell migration from the bone marrow to brain and prime neuroimmune function and (iv) early developmental exposure to an inflammatory stimulus (carageenin injection into the hindpaw) has a lasting influence on stress reactivity across the lifespan. As such, the present review provides a theoretical framework for understanding the role that neuroimmune mechanisms might play in stress plasticity and pathological outcomes, while at the same time pointing toward features of the individual (sex, developmental experience, stress history) that might ultimately be used for the development of personalized strategies for therapeutic intervention in stress-related pathologies.

Lewy Body Disease: Clinical and Pathological "Overlap Syndrome" Between Synucleinopathies (Parkinson Disease) and Tauopathies (Alzheimer Disease).

PubMed

Foguem, Clovis; Manckoundia, Patrick

2018-04-08

Lewy body disease (LBD) is a neurodegenerative disease resulting in dementia. It shares clinical and pathological features with Parkinson disease (PD), the most frequent synucleinopathy, Parkinson disease dementia (PDD), and Alzheimer disease (AD), a tauopathy. Even though the diagnostic criteria for these neurodegenerative diseases are clearly established, and recently revised for LBD, their precise clinical diagnosis is often difficult because LBD, PD, PDD, and AD share epidemiological, clinical, and pathological characteristics. This manuscript discusses current understanding of overlapping symptoms and the particular features of LBD, PD, and AD. It also describes features that could facilitate the diagnosis of each of these diseases. We concluded that the concept of neurodegenerative "overlap" syndrome, which includes the accepted diagnosis of LBD, may be taken in account and should contribute to clarifying LBD and definitions of close differential diagnoses. This should allow clinicians to suspect LBD at an earlier stage and provide better patient care.

The adenoid as a key factor in upper airway infections.

PubMed

van Cauwenberge, P B; Bellussi, L; Maw, A R; Paradise, J L; Solow, B

1995-06-01

The adenoids (and the nasopharynx) play a key role in the normal functioning and in various pathologies of the upper respiratory tract. In this paper the role of adenoidal pathology and the beneficial effect of adenoidectomy in some upper respiratory tract and facial anomalies and diseases are discussed; otitis media with effusion, recurrent acute otitis media, sinusitis, snoring and sleep apnea and abnormal patterns in the midface growth and development.

Next-generation endomyocardial biopsy: the potential of confocal and super-resolution microscopy.

PubMed

Crossman, David J; Ruygrok, Peter N; Hou, Yu Feng; Soeller, Christian

2015-03-01

Confocal laser scanning microscopy and super-resolution microscopy provide high-contrast and high-resolution fluorescent imaging, which has great potential to increase the diagnostic yield of endomyocardial biopsy (EMB). EMB is currently the gold standard for identification of cardiac allograft rejection, myocarditis, and infiltrative and storage diseases. However, standard analysis is dominated by low-contrast bright-field light and electron microscopy (EM); this lack of contrast makes quantification of pathological features difficult. For example, assessment of cardiac allograft rejection relies on subjective grading of H&E histology, which may lead to diagnostic variability between pathologists. This issue could be solved by utilising the high contrast provided by fluorescence methods such as confocal to quantitatively assess the degree of lymphocytic infiltrate. For infiltrative diseases such as amyloidosis, the nanometre resolution provided by EM can be diagnostic in identifying disease-causing fibrils. The recent advent of super-resolution imaging, particularly direct stochastic optical reconstruction microscopy (dSTORM), provides high-contrast imaging at resolution approaching that of EM. Moreover, dSTORM utilises conventional fluorescence dyes allowing for the same structures to be routinely imaged at the cellular scale and then at the nanoscale. The key benefit of these technologies is that the high contrast facilitates quantitative digital analysis and thereby provides a means to robustly assess critical pathological features. Ultimately, this technology has the ability to provide greater accuracy and precision to EMB assessment, which could result in better outcomes for patients.

Computational Neuropsychology and Bayesian Inference.

PubMed

Parr, Thomas; Rees, Geraint; Friston, Karl J

2018-01-01

Computational theories of brain function have become very influential in neuroscience. They have facilitated the growth of formal approaches to disease, particularly in psychiatric research. In this paper, we provide a narrative review of the body of computational research addressing neuropsychological syndromes, and focus on those that employ Bayesian frameworks. Bayesian approaches to understanding brain function formulate perception and action as inferential processes. These inferences combine 'prior' beliefs with a generative (predictive) model to explain the causes of sensations. Under this view, neuropsychological deficits can be thought of as false inferences that arise due to aberrant prior beliefs (that are poor fits to the real world). This draws upon the notion of a Bayes optimal pathology - optimal inference with suboptimal priors - and provides a means for computational phenotyping. In principle, any given neuropsychological disorder could be characterized by the set of prior beliefs that would make a patient's behavior appear Bayes optimal. We start with an overview of some key theoretical constructs and use these to motivate a form of computational neuropsychology that relates anatomical structures in the brain to the computations they perform. Throughout, we draw upon computational accounts of neuropsychological syndromes. These are selected to emphasize the key features of a Bayesian approach, and the possible types of pathological prior that may be present. They range from visual neglect through hallucinations to autism. Through these illustrative examples, we review the use of Bayesian approaches to understand the link between biology and computation that is at the heart of neuropsychology.

Computational Neuropsychology and Bayesian Inference

PubMed Central

Parr, Thomas; Rees, Geraint; Friston, Karl J.

2018-01-01

Computational theories of brain function have become very influential in neuroscience. They have facilitated the growth of formal approaches to disease, particularly in psychiatric research. In this paper, we provide a narrative review of the body of computational research addressing neuropsychological syndromes, and focus on those that employ Bayesian frameworks. Bayesian approaches to understanding brain function formulate perception and action as inferential processes. These inferences combine ‘prior’ beliefs with a generative (predictive) model to explain the causes of sensations. Under this view, neuropsychological deficits can be thought of as false inferences that arise due to aberrant prior beliefs (that are poor fits to the real world). This draws upon the notion of a Bayes optimal pathology – optimal inference with suboptimal priors – and provides a means for computational phenotyping. In principle, any given neuropsychological disorder could be characterized by the set of prior beliefs that would make a patient’s behavior appear Bayes optimal. We start with an overview of some key theoretical constructs and use these to motivate a form of computational neuropsychology that relates anatomical structures in the brain to the computations they perform. Throughout, we draw upon computational accounts of neuropsychological syndromes. These are selected to emphasize the key features of a Bayesian approach, and the possible types of pathological prior that may be present. They range from visual neglect through hallucinations to autism. Through these illustrative examples, we review the use of Bayesian approaches to understand the link between biology and computation that is at the heart of neuropsychology. PMID:29527157

Common threads in cardiac fibrosis, infarct scar formation, and wound healing.

PubMed

Czubryt, Michael P

2012-11-01

Wound healing, cardiac fibrosis, and infarct scar development, while possessing distinct features, share a number of key functional similarities, including extracellular matrix synthesis and remodeling by fibroblasts and myofibroblasts. Understanding the underlying mechanisms that are common to these processes may suggest novel therapeutic approaches for pathologic situations such as fibrosis, or defective wound healing such as hypertrophic scarring or keloid formation. This manuscript will briefly review the major steps of wound healing, and will contrast this process with how cardiac infarct scar formation or interstitial fibrosis occurs. The feasibility of targeting common pro-fibrotic growth factor signaling pathways will be discussed. Finally, the potential exploitation of novel regulators of wound healing and fibrosis (ski and scleraxis), will be examined.

S-Glutathionylation of Keap1: a new role for glutathione S-transferase pi in neuronal protection.

PubMed

Carvalho, Andreia Neves; Marques, Carla; Guedes, Rita C; Castro-Caldas, Margarida; Rodrigues, Elsa; van Horssen, Jack; Gama, Maria João

2016-05-01

Oxidative stress is a key pathological feature of Parkinson's disease (PD). Glutathione S-transferase pi (GSTP) is a neuroprotective antioxidant enzyme regulated at the transcriptional level by the antioxidant master regulator nuclear factor-erythroid 2-related factor 2 (Nrf2). Here, we show for the first time that upon MPTP-induced oxidative stress, GSTP potentiates S-glutathionylation of Kelch-like ECH-associated protein 1 (Keap1), an endogenous repressor of Nrf2, in vivo. S-glutathionylation of Keap1 leads to Nrf2 activation and subsequently increases expression of GSTP. This positive feedback regulatory loop represents a novel mechanism by which GSTP elicits antioxidant protection in the brain. © 2016 Federation of European Biochemical Societies.

Lysine acetyltransferase inhibitors: structure-activity relationships and potential therapeutic implications.

PubMed

Fiorentino, Francesco; Mai, Antonello; Rotili, Dante

2018-05-01

Lysine acetylation is a post-translational modification of both histone and nonhistone proteins that is catalyzed by lysine acetyltransferases and plays a key role in numerous biological contexts. The dysregulation of this enzyme activity is implicated in many human pathologies such as cancer, neurological and inflammatory disorders. Many lysine acetyltransferase inhibitors (KATi) have been developed so far, but there is still the need for new, more potent, metabolically stable and selective KATi as chemical tools for studying KAT biology and/or as potential therapeutic agents. This review will examine the features of KAT enzymes and related diseases, with particular emphasis on KATi (bisubstrate analogs, natural compounds and synthetic derivatives), analyzing their mechanism of action, structure-activity relationships, pharmacokinetic/pharmacodynamic properties and potential future applications.

European consensus on the histopathology of inflammatory bowel disease.

PubMed

Magro, F; Langner, C; Driessen, A; Ensari, A; Geboes, K; Mantzaris, G J; Villanacci, V; Becheanu, G; Borralho Nunes, P; Cathomas, G; Fries, W; Jouret-Mourin, A; Mescoli, C; de Petris, G; Rubio, C A; Shepherd, N A; Vieth, M; Eliakim, R

2013-11-01

The histologic examination of endoscopic biopsies or resection specimens remains a key step in the work-up of affected inflammatory bowel disease (IBD) patients and can be used for diagnosis and differential diagnosis, particularly in the differentiation of UC from CD and other non-IBD related colitides. The introduction of new treatment strategies in inflammatory bowel disease (IBD) interfering with the patients' immune system may result in mucosal healing, making the pathologists aware of the impact of treatment upon diagnostic features. The European Crohn's and Colitis Organisation (ECCO) and the European Society of Pathology (ESP) jointly elaborated a consensus to establish standards for histopathology diagnosis in IBD. The consensus endeavors to address: (i) procedures required for a proper diagnosis, (ii) features which can be used for the analysis of endoscopic biopsies, (iii) features which can be used for the analysis of surgical samples, (iv) criteria for diagnosis and differential diagnosis, and (v) special situations including those inherent to therapy. Questions that were addressed include: how many features should be present for a firm diagnosis? What is the role of histology in patient management, including search for dysplasia? Which features if any, can be used for assessment of disease activity? The statements and general recommendations of this consensus are based on the highest level of evidence available, but significant gaps remain in certain areas. Copyright © 2013 European Crohn's and Colitis Organisation. All rights reserved.

Anatomic features of enhancing renal masses predict malignant and high-grade pathology: a preoperative nomogram using the RENAL Nephrometry score.

PubMed

Kutikov, Alexander; Smaldone, Marc C; Egleston, Brian L; Manley, Brandon J; Canter, Daniel J; Simhan, Jay; Boorjian, Stephen A; Viterbo, Rosalia; Chen, David Y T; Greenberg, Richard E; Uzzo, Robert G

2011-08-01

Counseling patients with enhancing renal mass currently occurs in the context of significant uncertainty regarding tumor pathology. We evaluated whether radiographic features of renal masses could predict tumor pathology and developed a comprehensive nomogram to quantitate the likelihood of malignancy and high-grade pathology based on these features. We retrospectively queried Fox Chase Cancer Center's prospectively maintained database for consecutive renal masses where a Nephrometry score was available. All patients in the cohort underwent either partial or radical nephrectomy. The individual components of Nephrometry were compared with histology and grade of resected tumors. We used multiple logistic regression to develop nomograms predicting the malignancy of tumors and likelihood of high-grade disease among malignant tumors. Nephrometry score was available for 525 of 1750 renal masses. Nephrometry score correlated with both tumor grade (p < 0.0001) and histology (p < 0.0001), such that small endophytic nonhilar tumors were more likely to represent benign pathology. Conversely, large interpolar and hilar tumors more often represented high-grade cancers. The resulting nomogram from these data offers a useful tool for the preoperative prediction of tumor histology (area under the curve [AUC]: 0.76) and grade (AUC: 0.73). The model was subjected to out-of-sample cross-validation; however, lack of external validation is a limitation of the study. The current study is the first to objectify the relationship between tumor anatomy and pathology. Using the Nephrometry score, we developed a tool to quantitate the preoperative likelihood of malignant and high-grade pathology of an enhancing renal mass. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Glioma grading using cell nuclei morphologic features in digital pathology images

NASA Astrophysics Data System (ADS)

Reza, Syed M. S.; Iftekharuddin, Khan M.

2016-03-01

This work proposes a computationally efficient cell nuclei morphologic feature analysis technique to characterize the brain gliomas in tissue slide images. In this work, our contributions are two-fold: 1) obtain an optimized cell nuclei segmentation method based on the pros and cons of the existing techniques in literature, 2) extract representative features by k-mean clustering of nuclei morphologic features to include area, perimeter, eccentricity, and major axis length. This clustering based representative feature extraction avoids shortcomings of extensive tile [1] [2] and nuclear score [3] based methods for brain glioma grading in pathology images. Multilayer perceptron (MLP) is used to classify extracted features into two tumor types: glioblastoma multiforme (GBM) and low grade glioma (LGG). Quantitative scores such as precision, recall, and accuracy are obtained using 66 clinical patients' images from The Cancer Genome Atlas (TCGA) [4] dataset. On an average ~94% accuracy from 10 fold crossvalidation confirms the efficacy of the proposed method.

Diagnosis of breast masses from dynamic contrast-enhanced and diffusion-weighted MR: a machine learning approach.

PubMed

Cai, Hongmin; Peng, Yanxia; Ou, Caiwen; Chen, Minsheng; Li, Li

2014-01-01

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is increasingly used for breast cancer diagnosis as supplementary to conventional imaging techniques. Combining of diffusion-weighted imaging (DWI) of morphology and kinetic features from DCE-MRI to improve the discrimination power of malignant from benign breast masses is rarely reported. The study comprised of 234 female patients with 85 benign and 149 malignant lesions. Four distinct groups of features, coupling with pathological tests, were estimated to comprehensively characterize the pictorial properties of each lesion, which was obtained by a semi-automated segmentation method. Classical machine learning scheme including feature subset selection and various classification schemes were employed to build prognostic model, which served as a foundation for evaluating the combined effects of the multi-sided features for predicting of the types of lesions. Various measurements including cross validation and receiver operating characteristics were used to quantify the diagnostic performances of each feature as well as their combination. Seven features were all found to be statistically different between the malignant and the benign groups and their combination has achieved the highest classification accuracy. The seven features include one pathological variable of age, one morphological variable of slope, three texture features of entropy, inverse difference and information correlation, one kinetic feature of SER and one DWI feature of apparent diffusion coefficient (ADC). Together with the selected diagnostic features, various classical classification schemes were used to test their discrimination power through cross validation scheme. The averaged measurements of sensitivity, specificity, AUC and accuracy are 0.85, 0.89, 90.9% and 0.93, respectively. Multi-sided variables which characterize the morphological, kinetic, pathological properties and DWI measurement of ADC can dramatically improve the discriminatory power of breast lesions.

Mouse strain and injection site are crucial for detecting linked suppression in transplant recipients by trans-vivo DTH assay.

PubMed

Burlingham, W J; Jankowska-Gan, E

2007-02-01

Chemokine-driven accumulation of lymphocytes, mononuclear and polymorphonuclear proinflammatory cells in antigenic tissue sites is a key feature of several types of T-cell-dependent autoimmunity and transplant rejection pathology. It is now clear that the immune system expends considerable energy to control this process, exemplified by the sequential layers of regulatory cell input, both innate and adaptive, designed to prevent a classical Type IV or 'delayed-type' hypersensitivity (DTH) reaction from occurring in the visual field of the eye. Yet, despite an abundance of in vitro assays currently available to the human T-cell immunologist, none of them adequately models the human DTH response and its various control features. The theme of this article is that it is relatively easy to model the effector side of the human DTH response with xenogeneic adoptive transfer models. However, we show that in order to detect inhibition of a recall DTH in response to colocalized donor antigen (linked suppression)--a characteristic feature of peripheral tolerance to an organ transplant--both the challenge site and the immunocompetence of the mouse adoptive host are critical factors limiting the sensitivity of the trans-vivo DTH test.

[Features of neurologic semiotics at chronic obstructive pulmonary disease].

PubMed

Litvinenko, I V; Baranov, V L; Kolcheva, Iu A

2011-01-01

Chronic obstructive pulmonary disease (COPD) is actual pathology, when it forms the mixed hypoxemia. In the conditions of a chronic hypoxemia structures of organism with high level of metabolic processes, namely brain tissues, suffer. Character of defeat of the central nervous system at that pathology is insufficiently studied. In this article we studied and analysed the presence of such changes as depression, anxiety, cognitive impairment and features of neurologic semiotics at COPD in 50 patients.

Ultrasound and MRI of Pediatric Ocular Masses with Histopathologic Correlation

PubMed Central

Brennan, Rachel C.; Wilson, Matthew W.; Kaste, Sue; Helton, Kathleen J.; McCarville, M. Beth

2012-01-01

We review our experience with unusual ocular pathologies mimicking retinoblastoma that were referred to our institution over the past two decades. After presenting the imaging anatomy of the normal eye, we discuss pertinent clinical and pathological features, and illustrate the ultrasound and magnetic resonance imaging appearance of retinoblastoma, medulloepithelioma, uveal melanoma, persistent fetal vasculature, Coats disease, corneal dermoid, retinal dysplasia and toxocara granuloma. Features useful in discriminating between these entities are emphasized. PMID:22466750

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.

Phonologic errors as a clinical marker of the logopenic variant of PPA.

PubMed

Leyton, Cristian E; Ballard, Kirrie J; Piguet, Olivier; Hodges, John R

2014-05-06

To disentangle the clinical heterogeneity of nonsemantic variants of primary progressive aphasia (PPA) and to identify a coherent linguistic-anatomical marker for the logopenic variant of PPA (lv-PPA). Key speech and language features of 14 cases of lv-PPA and 18 cases of nonfluent/agrammatic variant of PPA were systematically evaluated and scored by an independent rater blinded to diagnosis. Every case underwent a structural MRI and a Pittsburgh compound B (PiB)-PET scan, a putative biomarker of Alzheimer disease. Key speech and language features that showed association with the PiB-PET status were entered into a hierarchical cluster analysis. The linguistic features and patterns of cortical thinning in each resultant cluster were analyzed. The cluster analysis revealed 3 coherent clinical groups, each of which was linked to a specific PiB-PET status. The first cluster was linked to high PiB retention and characterized by phonologic errors and cortical thinning focused on the left superior temporal gyrus. The second and third clusters were characterized by grammatical production errors and motor speech disorders, respectively, and were associated with low PiB brain retention. A fourth cluster, however, demonstrated nonspecific language deficits and unpredictable PiB-PET status. These findings suggest that despite the clinical and pathologic heterogeneity of nonsemantic variants, discrete clinical syndromes can be distinguished and linked to specific likelihood of PiB-PET status. Phonologic errors seem to be highly predictive of high amyloid burden in PPA and can provide a specific clinical marker for lv-PPA.

Oral lymphoepithelial cyst: A clinicopathological study of 26 cases and review of the literature.

PubMed

Sykara, Maria; Ntovas, Panagiotis; Kalogirou, Eleni-Marina; Tosios, Konstantinos I; Sklavounou, Alexandra

2017-08-01

Τo describe the clinicopathological features of 26 oral lymphoepithelial cysts (LECs) and review the literature. Twenty-six cases of oral LECs diagnosed during a 37-year period were retrospectively collected. The patients' gender and age, as well as the main clinical features of the cysts were retrieved from the requisition forms. The main microscopic features were recorded after reevaluation of all cases. Pubmed and Google Scholar electronic databases were searched with the key word "oral LEC". Inclusion criteria were the microscopic confirmation of LEC diagnosis and the report at least two of three main clinical features (gender, age and cyst's location). The 26 oral LECs represented 0.08% of 31,564 biopsies accessioned during the study period. They affected 25 patients, 14 females and 11 males with a mean age of 33.04±9.81 years. They appeared as smooth (92%) nodules, with soft (24%) or firm (76%) consistency and normal (28%), yellow to normal (20%), yellow (32%) or white (20%) hue, in the tongue (69.23%) or the floor of mouth (30.77%). They were covered by parakeratinized squamous (92.31%) or non-keratinized (7.69%) epithelium and contained desquamated epithelial cells, amorphous eosinophilic material and/or inflammatory cells (100%). The lymphoid tissue surrounded the cystic cavity partially (34.62%) or completely (65.38%), often in a follicular pattern with prominent germinal centers (53.85%). Literature review yielded 316 cases of oral LECs derived from 25 case reports, 3 case studies/retrospective studies with detailed information for each case and 7 studies with summarized data. Oral LEC is a pathologic entity with discrete clinical presentation that is, however, commonly misdiagnosed in clinical practice as other, mostly benign, entities. Its pathogenesis remains obscure, as its clinicopathologic features are consistent with both theories suggested up to date. Key words: Oral lymphoepithelial cyst; developmental cyst; non odontogenic cyst; lymphoid tissue; oral tonsil.

Oral lymphoepithelial cyst: A clinicopathological study of 26 cases and review of the literature

PubMed Central

Sykara, Maria; Ntovas, Panagiotis; Tosios, Konstantinos I.; Sklavounou, Alexandra

2017-01-01

Introduction Τo describe the clinicopathological features of 26 oral lymphoepithelial cysts (LECs) and review the literature. Material and Methods Twenty-six cases of oral LECs diagnosed during a 37-year period were retrospectively collected. The patients’ gender and age, as well as the main clinical features of the cysts were retrieved from the requisition forms. The main microscopic features were recorded after reevaluation of all cases. Pubmed and Google Scholar electronic databases were searched with the key word “oral LEC”. Inclusion criteria were the microscopic confirmation of LEC diagnosis and the report at least two of three main clinical features (gender, age and cyst’s location). Results The 26 oral LECs represented 0.08% of 31,564 biopsies accessioned during the study period. They affected 25 patients, 14 females and 11 males with a mean age of 33.04±9.81 years. They appeared as smooth (92%) nodules, with soft (24%) or firm (76%) consistency and normal (28%), yellow to normal (20%), yellow (32%) or white (20%) hue, in the tongue (69.23%) or the floor of mouth (30.77%). They were covered by parakeratinized squamous (92.31%) or non-keratinized (7.69%) epithelium and contained desquamated epithelial cells, amorphous eosinophilic material and/or inflammatory cells (100%). The lymphoid tissue surrounded the cystic cavity partially (34.62%) or completely (65.38%), often in a follicular pattern with prominent germinal centers (53.85%). Literature review yielded 316 cases of oral LECs derived from 25 case reports, 3 case studies/retrospective studies with detailed information for each case and 7 studies with summarized data. Conclusions Oral LEC is a pathologic entity with discrete clinical presentation that is, however, commonly misdiagnosed in clinical practice as other, mostly benign, entities. Its pathogenesis remains obscure, as its clinicopathologic features are consistent with both theories suggested up to date. Key words:Oral lymphoepithelial cyst; developmental cyst; non odontogenic cyst; lymphoid tissue; oral tonsil. PMID:28936296

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.

Indexing and filing of pathological illustrations.

PubMed Central

Brown, R A; Fawkes, R S; Beck, J S

1975-01-01

An inexpensive feature card retrieval system has been combined with the Systematised Nomenclature of Pathology (SNOP) to provide simple but efficient means of indexing and filing 2 in. x 2 in. transparencies within a department of pathology. Using this system 2400 transparencies and the associated index cards can be conveniently stored in one drawer of a standard filing cabinet. Images PMID:1123438

Thermographic image analysis for classification of ACL rupture disease, bone cancer, and feline hyperthyroid, with Gabor filters

NASA Astrophysics Data System (ADS)

Alvandipour, Mehrdad; Umbaugh, Scott E.; Mishra, Deependra K.; Dahal, Rohini; Lama, Norsang; Marino, Dominic J.; Sackman, Joseph

2017-05-01

Thermography and pattern classification techniques are used to classify three different pathologies in veterinary images. Thermographic images of both normal and diseased animals were provided by the Long Island Veterinary Specialists (LIVS). The three pathologies are ACL rupture disease, bone cancer, and feline hyperthyroid. The diagnosis of these diseases usually involves radiology and laboratory tests while the method that we propose uses thermographic images and image analysis techniques and is intended for use as a prescreening tool. Images in each category of pathologies are first filtered by Gabor filters and then various features are extracted and used for classification into normal and abnormal classes. Gabor filters are linear filters that can be characterized by the two parameters wavelength λ and orientation θ. With two different wavelength and five different orientations, a total of ten different filters were studied. Different combinations of camera views, filters, feature vectors, normalization methods, and classification methods, produce different tests that were examined and the sensitivity, specificity and success rate for each test were produced. Using the Gabor features alone, sensitivity, specificity, and overall success rates of 85% for each of the pathologies was achieved.

Correlation of hemorrhage, axonal damage, and blood-tissue barrier disruption in brain and retina of Malawian children with fatal cerebral malaria.

PubMed

Greiner, Jesse; Dorovini-Zis, Katerina; Taylor, Terrie E; Molyneux, Malcolm E; Beare, Nicholas A V; Kamiza, Steve; White, Valerie A

2015-01-01

The retinal and brain histopathological findings in children who died from cerebral malaria (CM) have been recently described. Similar changes occur in both structures, but the findings have not been directly compared in the same patients. In this study, we compared clinical retinal findings and retinal and cerebral histopathological changes in a series of patients in Blantyre, Malawi, who died of CM. The features systematically compared in the same patient were: (1) clinical, gross and microscopic retinal hemorrhages with microscopic cerebral hemorrhages, (2) retinal and cerebral hemorrhage-associated and -unassociated axonal damage, and fibrinogen leakage, and (3) differences in the above features between the pathological categories of CM without microvascular pathology (CM1) and CM with microvascular pathology (CM2) in retina and brain. Forty-seven patients were included: seven CM1, 28 CM2, and 12 controls. In the 35 malaria cases retinal and cerebral pathology correlated in all features except for non-hemorrhage associated fibrinogen leakage. Regarding CM1 and CM2 cases, the only differences were in the proportion of patients with hemorrhage-associated cerebral pathology, and this was expected, based on the definitions of CM1 and CM2. The retina did not show this difference. Non-hemorrhage associated pathology was similar for the two groups. As postulated, histopathological features of hemorrhages, axonal damage and non-hemorrhage associated fibrinogen leakage correlated in the retina and brain of individual patients, although the difference in hemorrhages between the CM1 and CM2 groups was not consistently observed in the retina. These results help to underpin the utility of ophthalmoscopic examination and fundus findings to help in diagnosis and assessment of cerebral malaria patients, but may not help in distinguishing between CM1 and CM2 patients during life.

Specific features of cytological and colposcopical pattern in pregnant women with benign cervix uteri pathology in anamnesis.

PubMed

Bysaha, Nataliya Yu

2016-01-01

a tendency of increasing incidence of the cervix uteri precancer and cancer in women of reproductive age is noticed recently being related to the growth of number of the sexually-transmitted infections. The cervix uteri pathology incidence in women of fertile age is 20-25%. to study the specific features of the cytological and colposcopical pattern in pregnant patients with benign cervix uteri pathology in the anamnesis and the character of its change post partum. we have examined 195 women during their pregnancy and 3-5 months post partum. All pregnant women, alongside with generally accepted clinical and laboratory examinations, were subjected to the simple and extended colposcopy, cytology of the targeted smears and, according to indications, the histological studies of bioptate. according to the results of the colcoscopical studies and the signs of the cervix uteri pathology found, the patients were divided into several groups. A control group included 49 pregnant women. The clinical and instrumental examination of 146 women with cervix uteri pathology has been carried out both during pregnancy and post partum. the structure of the clinical forms of benign and premalignant changes in the cervix uteri epithelium in pregnant patients has been found. Specific features of the cytological and colposcopical pattern in pregnant patients with benign cervix uteri pathology in anamnesis have been studied. The relationship between the parity of pregnancy, delivery, route of delivery and regress of both benign and premalignant changes in the cervix uteri epithelium 3-5 months post partum has been determined.

Hereditary factors are unlikely behind unusual pattern of early - Onset colorectal cancer in Egyptians: A study of family history and pathology features in Egyptians with large bowel cancer (cross-sectional study).

PubMed

Abou-Zeid, Ahmed A; Jumuah, Wael A; Ebied, Essam F; Abd El Samee Atia, Karim Sabry; El Ghamrini, Yasser; Somaie, Dina A

2017-08-01

Colorectal cancer in Egypt has a higher incidence in young patients compared to western countries, where the disease is more prevalent in the old age group. This difference has been attributed to higher incidence of hereditary cancers in young Egyptian patients. The aim of this study is to compare the family history criteria and pathology features of tumors in young (≤40 years) and old (>40 years) Egyptian patients with adenocarcinoma of the colon and rectum. This is the analysis of our prospectively collected data on the pathology features of tumors in 313 consecutive patients (133 young, 180 old) with colorectal cancer presenting to the Department of Surgery within an eight-year period. A detailed family history was obtained from 258 patients (112 young, 146 old). 41 young and 48 old patients reported family history of cancer, the difference was not statistically significant. Ten young patients (9%) reported a family history of colorectal cancer in a first degree relative (3 fitting into Amsterdam criteria, 7 fitting into less strict criteria) which was not significantly different from the old age group. The pathologic features of tumors in both groups resembled sporadic rather than hereditary cancer and there was no significant difference between groups in tumor location, degree of differentiation, mucin production, synchronous and metachronous colorectal tumors or polyps and grossly stricturing or ulcerating tumors. Extracolonic tumors developed in one young and two old patients. The characteristics of large bowel cancer in young Egyptian patients do not differ significantly from those in older patients. Despite the high incidence of large bowel cancer in young Egyptian patients, family history and pathologic features of tumors do not support a hereditary origin of colorectal cancer in this age group in Egypt. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Computerized macular pathology diagnosis in spectral domain optical coherence tomography scans based on multiscale texture and shape features.

PubMed

Liu, Yu-Ying; Ishikawa, Hiroshi; Chen, Mei; Wollstein, Gadi; Duker, Jay S; Fujimoto, James G; Schuman, Joel S; Rehg, James M

2011-10-21

To develop an automated method to identify the normal macula and three macular pathologies (macular hole [MH], macular edema [ME], and age-related macular degeneration [AMD]) from the fovea-centered cross sections in three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) images. A sample of SD-OCT macular scans (macular cube 200 × 200 or 512 × 128 scan protocol; Cirrus HD-OCT; Carl Zeiss Meditec, Inc., Dublin, CA) was obtained from healthy subjects and subjects with MH, ME, and/or AMD (dataset for development: 326 scans from 136 subjects [193 eyes], and dataset for testing: 131 scans from 37 subjects [58 eyes]). A fovea-centered cross-sectional slice for each of the SD-OCT images was encoded using spatially distributed multiscale texture and shape features. Three ophthalmologists labeled each fovea-centered slice independently, and the majority opinion for each pathology was used as the ground truth. Machine learning algorithms were used to identify the discriminative features automatically. Two-class support vector machine classifiers were trained to identify the presence of normal macula and each of the three pathologies separately. The area under the receiver operating characteristic curve (AUC) was calculated to assess the performance. The cross-validation AUC result on the development dataset was 0.976, 0.931, 0939, and 0.938, and the AUC result on the holdout testing set was 0.978, 0.969, 0.941, and 0.975, for identifying normal macula, MH, ME, and AMD, respectively. The proposed automated data-driven method successfully identified various macular pathologies (all AUC > 0.94). This method may effectively identify the discriminative features without relying on a potentially error-prone segmentation module.

Computerized Macular Pathology Diagnosis in Spectral Domain Optical Coherence Tomography Scans Based on Multiscale Texture and Shape Features

PubMed Central

Liu, Yu-Ying; Chen, Mei; Wollstein, Gadi; Duker, Jay S.; Fujimoto, James G.; Schuman, Joel S.; Rehg, James M.

2011-01-01

Purpose. To develop an automated method to identify the normal macula and three macular pathologies (macular hole [MH], macular edema [ME], and age-related macular degeneration [AMD]) from the fovea-centered cross sections in three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) images. Methods. A sample of SD-OCT macular scans (macular cube 200 × 200 or 512 × 128 scan protocol; Cirrus HD-OCT; Carl Zeiss Meditec, Inc., Dublin, CA) was obtained from healthy subjects and subjects with MH, ME, and/or AMD (dataset for development: 326 scans from 136 subjects [193 eyes], and dataset for testing: 131 scans from 37 subjects [58 eyes]). A fovea-centered cross-sectional slice for each of the SD-OCT images was encoded using spatially distributed multiscale texture and shape features. Three ophthalmologists labeled each fovea-centered slice independently, and the majority opinion for each pathology was used as the ground truth. Machine learning algorithms were used to identify the discriminative features automatically. Two-class support vector machine classifiers were trained to identify the presence of normal macula and each of the three pathologies separately. The area under the receiver operating characteristic curve (AUC) was calculated to assess the performance. Results. The cross-validation AUC result on the development dataset was 0.976, 0.931, 0939, and 0.938, and the AUC result on the holdout testing set was 0.978, 0.969, 0.941, and 0.975, for identifying normal macula, MH, ME, and AMD, respectively. Conclusions. The proposed automated data-driven method successfully identified various macular pathologies (all AUC > 0.94). This method may effectively identify the discriminative features without relying on a potentially error-prone segmentation module. PMID:21911579

Vision-based gait impairment analysis for aided diagnosis.

PubMed

Ortells, Javier; Herrero-Ezquerro, María Trinidad; Mollineda, Ramón A

2018-02-12

Gait is a firsthand reflection of health condition. This belief has inspired recent research efforts to automate the analysis of pathological gait, in order to assist physicians in decision-making. However, most of these efforts rely on gait descriptions which are difficult to understand by humans, or on sensing technologies hardly available in ambulatory services. This paper proposes a number of semantic and normalized gait features computed from a single video acquired by a low-cost sensor. Far from being conventional spatio-temporal descriptors, features are aimed at quantifying gait impairment, such as gait asymmetry from several perspectives or falling risk. They were designed to be invariant to frame rate and image size, allowing cross-platform comparisons. Experiments were formulated in terms of two databases. A well-known general-purpose gait dataset is used to establish normal references for features, while a new database, introduced in this work, provides samples under eight different walking styles: one normal and seven impaired patterns. A number of statistical studies were carried out to prove the sensitivity of features at measuring the expected pathologies, providing enough evidence about their accuracy. Graphical Abstract Graphical abstract reflecting main contributions of the manuscript: at the top, a robust, semantic and easy-to-interpret feature set to describe impaired gait patterns; at the bottom, a new dataset consisting of video-recordings of a number of volunteers simulating different patterns of pathological gait, where features were statistically assessed.

High-Performance Computational Analysis of Glioblastoma Pathology Images with Database Support Identifies Molecular and Survival Correlates.

PubMed

Kong, Jun; Wang, Fusheng; Teodoro, George; Cooper, Lee; Moreno, Carlos S; Kurc, Tahsin; Pan, Tony; Saltz, Joel; Brat, Daniel

2013-12-01

In this paper, we present a novel framework for microscopic image analysis of nuclei, data management, and high performance computation to support translational research involving nuclear morphometry features, molecular data, and clinical outcomes. Our image analysis pipeline consists of nuclei segmentation and feature computation facilitated by high performance computing with coordinated execution in multi-core CPUs and Graphical Processor Units (GPUs). All data derived from image analysis are managed in a spatial relational database supporting highly efficient scientific queries. We applied our image analysis workflow to 159 glioblastomas (GBM) from The Cancer Genome Atlas dataset. With integrative studies, we found statistics of four specific nuclear features were significantly associated with patient survival. Additionally, we correlated nuclear features with molecular data and found interesting results that support pathologic domain knowledge. We found that Proneural subtype GBMs had the smallest mean of nuclear Eccentricity and the largest mean of nuclear Extent, and MinorAxisLength. We also found gene expressions of stem cell marker MYC and cell proliferation maker MKI67 were correlated with nuclear features. To complement and inform pathologists of relevant diagnostic features, we queried the most representative nuclear instances from each patient population based on genetic and transcriptional classes. Our results demonstrate that specific nuclear features carry prognostic significance and associations with transcriptional and genetic classes, highlighting the potential of high throughput pathology image analysis as a complementary approach to human-based review and translational research.

Vemurafenib resistance signature by proteome analysis offers new strategies and rational therapeutic concepts.

PubMed

Paulitschke, Verena; Berger, Walter; Paulitschke, Philipp; Hofstätter, Elisabeth; Knapp, Bernhard; Dingelmaier-Hovorka, Ruth; Födinger, Dagmar; Jäger, Walter; Szekeres, Thomas; Meshcheryakova, Anastasia; Bileck, Andrea; Pirker, Christine; Pehamberger, Hubert; Gerner, Christopher; Kunstfeld, Rainer

2015-03-01

The FDA-approved BRAF inhibitor vemurafenib achieves outstanding clinical response rates in patients with melanoma, but early resistance is common. Understanding the pathologic mechanisms of drug resistance and identification of effective therapeutic alternatives are key scientific challenges in the melanoma setting. Using proteomic techniques, including shotgun analysis and 2D-gel electrophoresis, we identified a comprehensive signature of the vemurafenib-resistant M24met in comparison with the vemurafenib-sensitive A375 melanoma cell line. The resistant cells were characterized by loss of differentiation, induction of transformation, enhanced expression of the lysosomal compartment, increased potential for metastasis, migration, adherence and Ca2(+) ion binding, enhanced expression of the MAPK pathway and extracellular matrix proteins, and epithelial-mesenchymal transformation. The main features were verified by shotgun analysis with QEXACTIVE orbitrap MS, electron microscopy, lysosomal staining, Western blotting, and adherence assay in a VM-1 melanoma cell line with acquired vemurafenib resistance. On the basis of the resistance profile, we were able to successfully predict that a novel resveratrol-derived COX-2 inhibitor, M8, would be active against the vemurafenib-resistant but not the vemurafenib-sensitive melanoma cells. Using high-throughput methods for cell line and drug characterization may thus offer a new way to identify key features of vemurafenib resistance, facilitating the design of effective rational therapeutic alternatives. ©2015 American Association for Cancer Research.

Colour in digital pathology: a review.

PubMed

Clarke, Emily L; Treanor, Darren

2017-01-01

Colour is central to the practice of pathology because of the use of coloured histochemical and immunohistochemical stains to visualize tissue features. Our reliance upon histochemical stains and light microscopy has evolved alongside a wide variation in slide colour, with little investigation into the implications of colour variation. However, the introduction of the digital microscope and whole-slide imaging has highlighted the need for further understanding and control of colour. This is because the digitization process itself introduces further colour variation which may affect diagnosis, and image analysis algorithms often use colour or intensity measures to detect or measure tissue features. The US Food and Drug Administration have released recent guidance stating the need to develop a method of controlling colour reproduction throughout the digitization process in whole-slide imaging for primary diagnostic use. This comprehensive review introduces applied basic colour physics and colour interpretation by the human visual system, before discussing the importance of colour in pathology. The process of colour calibration and its application to pathology are also included, as well as a summary of the current guidelines and recommendations regarding colour in digital pathology. © 2016 John Wiley & Sons Ltd.

Cellular, synaptic and biochemical features of resilient cognition in Alzheimer’s disease

PubMed Central

Arnold, Steven. E.; Louneva, Natalia; Cao, Kajia; Wang, Li-San; Han, Li-Ying; Wolk, David A.; Negash, Selamawit; Leurgans, Sue E.; Schneider, Julie A.; Buchman, Aron S.; Wilson, Robert S.; Bennett, David A.

2012-01-01

While neuritic plaques and neurofibrillary tangles in older adults are correlated with cognitive impairment and severity of dementia, it has long been recognized that the relationship is imperfect as some people exhibit normal cognition despite high levels of AD pathology. We compared the cellular, synaptic and biochemical composition of midfrontal cortices in female subjects from the Religious Orders Study who were stratified into three subgroups: 1) pathological AD with normal cognition (“AD-Resilient”), 2) pathological AD with AD-typical dementia (“AD-Dementia)” and 3) pathologically normal with normal cognition (“Normal Comparison”). The AD-Resilient group exhibited preserved densities of synaptophysin-labeled presynaptic terminals and synaptopodin-labeled dendritic spines compared to the AD-Dementia group, and increased densities of GFAP astrocytes compared to both the AD-Dementia and Normal Comparison group. Further, in a discovery antibody microarray protein analysis we identified a number of candidate protein abnormalities that were associated with diagnostic group. These data characterize cellular and synaptic features and identify novel biochemical targets that may be associated with resilient cognitive brain aging in the setting of pathological AD. PMID:22554416

Histopathology and immunohistochemistry in the diagnosis of bioterrorism agents.

PubMed

Guarner, Jeannette; Zaki, Sherif R

2006-01-01

From October to November 2001, the inhalational and cutaneous anthrax cases that occurred in the U.S. underscored the importance of recognizing the clinical and pathological features of infectious agents that can be used in acts of terrorism. Early confirmation of bio-terrorist acts can only be performed by making organism-specific diagnosis of cases with clinical and pathologic syndromes that could be caused by possible bioterrorism weapons. Recognition and diagnosis of these cases is central to establish adequate responses. This review will examine the events that occurred during the anthrax bio-terrorist attack with specific emphasis on the role of pathology and immunohistochemistry and will describe the histopathologic features of category A bioterrorism agents (anthrax, plague, tularemia, botulism, smallpox, and viral hemorrhagic fevers).

Texture Analysis of Recurrence Plots Based on Wavelets and PSO for Laryngeal Pathologies Detection.

PubMed

Souza, Taciana A; Vieira, Vinícius J D; Correia, Suzete E N; Costa, Silvana L N C; de A Costa, Washington C; Souza, Micael A

2015-01-01

This paper deals with the discrimination between healthy and pathological speech signals using recurrence plots and wavelet transform with texture features. Approximation and detail coefficients are obtained from the recurrence plots using Haar wavelet transform, considering one decomposition level. The considered laryngeal pathologies are: paralysis, Reinke's edema and nodules. Accuracy rates above 86% were obtained by means of the employed method.

Chronic ethanol consumption in mice alters hepatocyte lipid droplet properties

USDA-ARS?s Scientific Manuscript database

Background: Hepatosteatosis is a common pathological feature of impaired hepatic metabolism following chronic alcohol consumption. Although often benign and reversible, it is widely believed that steatosis is a risk factor for development of advanced liver pathologies, including steatohepatitis and ...

The molecular mechanisms on glomangiopericytoma invasion

PubMed Central

2013-01-01

Purpose To observed the imaging and pathological features of the glomangiopericytoma. Experimental design In this paper we report a typical case of glomangiopericytoma arising in the skull base area and summarize the clinical manifestations, imaging and pathological features of such diseases. Results Immunohistochemical staining confirmed the tumor cells were strongly positive to Vim, SMA, MSA and negative to CD31, CD34. Partial cells were positive to FVIII. The imaging can’t confirm the diagnosis but indicate the the tumor has intact envelope.The cells in the tumor envelope is positive to Vim and negative SMA and FVIII. These findings were compatible with glomangiopericytoma and the cells in the tumor envelope is not glomangiopericytoma cells. Conclusion In view of the clinical and pathological features of the glomangiopericytoma, we believe that the surgery is the best treatment so far and the tumor can be resected completely. The above results can be preliminary reason to explain the low recurrence of such diseases. PMID:24074285

An approach based on wavelet analysis for feature extraction in the a-wave of the electroretinogram.

PubMed

Barraco, R; Persano Adorno, D; Brai, M

2011-12-01

Most biomedical signals are non-stationary. The knowledge of their frequency content and temporal distribution is then useful in a clinical context. The wavelet analysis is appropriate to achieve this task. The present paper uses this method to reveal hidden characteristics and anomalies of the human a-wave, an important component of the electroretinogram since it is a measure of the functional integrity of the photoreceptors. We here analyse the time-frequency features of the a-wave both in normal subjects and in patients affected by Achromatopsia, a pathology disturbing the functionality of the cones. The results indicate the presence of two or three stable frequencies that, in the pathological case, shift toward lower values and change their times of occurrence. The present findings are a first step toward a deeper understanding of the features of the a-wave and possible applications to diagnostic procedures in order to recognise incipient photoreceptoral pathologies. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Redox Regulation of Endothelial Cell Fate

PubMed Central

Song, Ping; Zou, Ming-Hui

2014-01-01

Endothelial cells (ECs) are present throughout blood vessels and have variable roles in both physiological and pathological settings. EC fate is altered and regulated by several key factors in physiological or pathological conditions. Reactive nitrogen species and reactive oxygen species derived from NAD(P)H oxidases, mitochondria, or nitric oxide-producing enzymes are not only cytotoxic but also compose a signaling network in the redox system. The formation, actions, key molecular interactions, and physiological and pathological relevance of redox signals in ECs remain unclear. We review the identities, sources, and biological actions of oxidants and reductants produced during EC function or dysfunction. Further, we discuss how ECs shape key redox sensors and examine the biological functions, transcriptional responses, and post-translational modifications evoked by the redox system in ECs. We summarize recent findings regarding the mechanisms by which redox signals regulate the fate of ECs and address the outcome of altered EC fate in health and disease. Future studies will examine if the redox biology of ECs can be targeted in pathophysiological conditions. PMID:24633153

A method for normalizing pathology images to improve feature extraction for quantitative pathology.

PubMed

Tam, Allison; Barker, Jocelyn; Rubin, Daniel

2016-01-01

With the advent of digital slide scanning technologies and the potential proliferation of large repositories of digital pathology images, many research studies can leverage these data for biomedical discovery and to develop clinical applications. However, quantitative analysis of digital pathology images is impeded by batch effects generated by varied staining protocols and staining conditions of pathological slides. To overcome this problem, this paper proposes a novel, fully automated stain normalization method to reduce batch effects and thus aid research in digital pathology applications. Their method, intensity centering and histogram equalization (ICHE), normalizes a diverse set of pathology images by first scaling the centroids of the intensity histograms to a common point and then applying a modified version of contrast-limited adaptive histogram equalization. Normalization was performed on two datasets of digitized hematoxylin and eosin (H&E) slides of different tissue slices from the same lung tumor, and one immunohistochemistry dataset of digitized slides created by restaining one of the H&E datasets. The ICHE method was evaluated based on image intensity values, quantitative features, and the effect on downstream applications, such as a computer aided diagnosis. For comparison, three methods from the literature were reimplemented and evaluated using the same criteria. The authors found that ICHE not only improved performance compared with un-normalized images, but in most cases showed improvement compared with previous methods for correcting batch effects in the literature. ICHE may be a useful preprocessing step a digital pathology image processing pipeline.

Classification of pulmonary pathology from breath sounds using the wavelet packet transform and an extreme learning machine.

PubMed

Palaniappan, Rajkumar; Sundaraj, Kenneth; Sundaraj, Sebastian; Huliraj, N; Revadi, S S

2017-06-08

Auscultation is a medical procedure used for the initial diagnosis and assessment of lung and heart diseases. From this perspective, we propose assessing the performance of the extreme learning machine (ELM) classifiers for the diagnosis of pulmonary pathology using breath sounds. Energy and entropy features were extracted from the breath sound using the wavelet packet transform. The statistical significance of the extracted features was evaluated by one-way analysis of variance (ANOVA). The extracted features were inputted into the ELM classifier. The maximum classification accuracies obtained for the conventional validation (CV) of the energy and entropy features were 97.36% and 98.37%, respectively, whereas the accuracies obtained for the cross validation (CRV) of the energy and entropy features were 96.80% and 97.91%, respectively. In addition, maximum classification accuracies of 98.25% and 99.25% were obtained for the CV and CRV of the ensemble features, respectively. The results indicate that the classification accuracy obtained with the ensemble features was higher than those obtained with the energy and entropy features.

A mouse model for creatine transporter deficiency reveals early onset cognitive impairment and neuropathology associated with brain aging.

PubMed

Baroncelli, Laura; Molinaro, Angelo; Cacciante, Francesco; Alessandrì, Maria Grazia; Napoli, Debora; Putignano, Elena; Tola, Jonida; Leuzzi, Vincenzo; Cioni, Giovanni; Pizzorusso, Tommaso

2016-10-01

Mutations in the creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CCDS1), an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement and autistic-like behavioural disturbances, language and speech impairment. Since no data are available about the neural and molecular underpinnings of this disease, we performed a longitudinal analysis of behavioural and pathological alterations associated with CrT deficiency in a CCDS1 mouse model. We found precocious cognitive and autistic-like defects, mimicking the early key features of human CCDS1. Moreover, mutant mice displayed a progressive impairment of short and long-term declarative memory denoting an early brain aging. Pathological examination showed a prominent loss of GABAergic synapses, marked activation of microglia, reduction of hippocampal neurogenesis and the accumulation of autofluorescent lipofuscin. Our data suggest that brain Cr depletion causes both early intellectual disability and late progressive cognitive decline, and identify novel targets to design intervention strategies aimed at overcoming brain CCDS1 alterations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

WINCS Harmoni: Closed-loop dynamic neurochemical control of therapeutic interventions

NASA Astrophysics Data System (ADS)

Lee, Kendall H.; Lujan, J. Luis; Trevathan, James K.; Ross, Erika K.; Bartoletta, John J.; Park, Hyung Ook; Paek, Seungleal Brian; Nicolai, Evan N.; Lee, Jannifer H.; Min, Hoon-Ki; Kimble, Christopher J.; Blaha, Charles D.; Bennet, Kevin E.

2017-04-01

There has been significant progress in understanding the role of neurotransmitters in normal and pathologic brain function. However, preclinical trials aimed at improving therapeutic interventions do not take advantage of real-time in vivo neurochemical changes in dynamic brain processes such as disease progression and response to pharmacologic, cognitive, behavioral, and neuromodulation therapies. This is due in part to a lack of flexible research tools that allow in vivo measurement of the dynamic changes in brain chemistry. Here, we present a research platform, WINCS Harmoni, which can measure in vivo neurochemical activity simultaneously across multiple anatomical targets to study normal and pathologic brain function. In addition, WINCS Harmoni can provide real-time neurochemical feedback for closed-loop control of neurochemical levels via its synchronized stimulation and neurochemical sensing capabilities. We demonstrate these and other key features of this platform in non-human primate, swine, and rodent models of deep brain stimulation (DBS). Ultimately, systems like the one described here will improve our understanding of the dynamics of brain physiology in the context of neurologic disease and therapeutic interventions, which may lead to the development of precision medicine and personalized therapies for optimal therapeutic efficacy.

Post-traumatic stress symptoms in pathological gambling: Potential evidence of anti-reward processes.

PubMed

Green, Cheryl L; Nahhas, Ramzi W; Scoglio, Arielle A; Elman, Igor

2017-03-01

Background Excessive gambling is considered to be a part of the addiction spectrum. Stress-like emotional states are a key feature both of pathological gambling (PG) and of substance addiction. In substance addiction, stress symptomatology has been attributed in part to "anti-reward" allostatic neuroadaptations, while a potential involvement of anti-reward processes in the course of PG has not yet been investigated. Methods To that end, individuals with PG (n = 22) and mentally healthy subjects (n = 13) were assessed for trauma exposure and post-traumatic stress symptomatology (PTSS) using the Life Events Checklist and the Civilian Mississippi Scale, respectively. Results In comparison with healthy subjects, individuals with PG had significantly greater PTSS scores including greater physiological arousal sub-scores. The number of traumatic events and their recency were not significantly different between the groups. In the PG group, greater gambling severity was associated with more PTSS, but neither with traumatic events exposure nor with their recency. Conclusions Our data replicate prior reports on the role of traumatic stress in the course of PG and extend those findings by suggesting that the link may be derived from the anti-reward-type neuroadaptation rather than from the traumatic stress exposure per se.

Intolerance of uncertainty, causal uncertainty, causal importance, self-concept clarity and their relations to generalized anxiety disorder.

PubMed

Kusec, Andrea; Tallon, Kathleen; Koerner, Naomi

2016-06-01

Although numerous studies have provided support for the notion that intolerance of uncertainty plays a key role in pathological worry (the hallmark feature of generalized anxiety disorder (GAD)), other uncertainty-related constructs may also have relevance for the understanding of individuals who engage in pathological worry. Three constructs from the social cognition literature, causal uncertainty, causal importance, and self-concept clarity, were examined in the present study to assess the degree to which these explain unique variance in GAD, over and above intolerance of uncertainty. N = 235 participants completed self-report measures of trait worry, GAD symptoms, and uncertainty-relevant constructs. A subgroup was subsequently classified as low in GAD symptoms (n = 69) or high in GAD symptoms (n = 54) based on validated cut scores on measures of trait worry and GAD symptoms. In logistic regressions, only elevated intolerance of uncertainty and lower self-concept clarity emerged as unique correlates of high (vs. low) GAD symptoms. The possible role of self-concept uncertainty in GAD and the utility of integrating social cognition theories and constructs into clinical research on intolerance of uncertainty are discussed.

Quantifying Novice and Expert Differences in Visual Diagnostic Reasoning in Veterinary Pathology Using Eye-Tracking Technology.

PubMed

Warren, Amy L; Donnon, Tyrone L; Wagg, Catherine R; Priest, Heather; Fernandez, Nicole J

2018-01-18

Visual diagnostic reasoning is the cognitive process by which pathologists reach a diagnosis based on visual stimuli (cytologic, histopathologic, or gross imagery). Currently, there is little to no literature examining visual reasoning in veterinary pathology. The objective of the study was to use eye tracking to establish baseline quantitative and qualitative differences between the visual reasoning processes of novice and expert veterinary pathologists viewing cytology specimens. Novice and expert participants were each shown 10 cytology images and asked to formulate a diagnosis while wearing eye-tracking equipment (10 slides) and while concurrently verbalizing their thought processes using the think-aloud protocol (5 slides). Compared to novices, experts demonstrated significantly higher diagnostic accuracy (p<.017), shorter time to diagnosis (p<.017), and a higher percentage of time spent viewing areas of diagnostic interest (p<.017). Experts elicited more key diagnostic features in the think-aloud protocol and had more efficient patterns of eye movement. These findings suggest that experts' fast time to diagnosis, efficient eye-movement patterns, and preference for viewing areas of interest supports system 1 (pattern-recognition) reasoning and script-inductive knowledge structures with system 2 (analytic) reasoning to verify their diagnosis.

New Trends of Emerging Technologies in Digital Pathology.

PubMed

Bueno, Gloria; Fernández-Carrobles, M Milagro; Deniz, Oscar; García-Rojo, Marcial

2016-01-01

The future paradigm of pathology will be digital. Instead of conventional microscopy, a pathologist will perform a diagnosis through interacting with images on computer screens and performing quantitative analysis. The fourth generation of virtual slide telepathology systems, so-called virtual microscopy and whole-slide imaging (WSI), has allowed for the storage and fast dissemination of image data in pathology and other biomedical areas. These novel digital imaging modalities encompass high-resolution scanning of tissue slides and derived technologies, including automatic digitization and computational processing of whole microscopic slides. Moreover, automated image analysis with WSI can extract specific diagnostic features of diseases and quantify individual components of these features to support diagnoses and provide informative clinical measures of disease. Therefore, the challenge is to apply information technology and image analysis methods to exploit the new and emerging digital pathology technologies effectively in order to process and model all the data and information contained in WSI. The final objective is to support the complex workflow from specimen receipt to anatomic pathology report transmission, that is, to improve diagnosis both in terms of pathologists' efficiency and with new information. This article reviews the main concerns about and novel methods of digital pathology discussed at the latest workshop in the field carried out within the European project AIDPATH (Academia and Industry Collaboration for Digital Pathology). © 2016 S. Karger AG, Basel.

Androgen receptor and immune inflammation in benign prostatic hyperplasia and prostate cancer

PubMed Central

Izumi, Kouji; Li, Lei; Chang, Chawnshang

2014-01-01

Both benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are frequent diseases in middle-aged to elderly men worldwide. While both diseases are linked to abnormal growth of the prostate, the epidemiological and pathological features of these two prostate diseases are different. BPH nodules typically arise from the transitional zone, and, in contrast, PCa arises from the peripheral zone. Androgen deprivation therapy alone may not be sufficient to cure these two prostatic diseases due to its undesirable side effects. The alteration of androgen receptor-mediated inflammatory signals from infiltrating immune cells and prostate stromal/epithelial cells may play key roles in those unwanted events. Herein, this review will focus on the roles of androgen/androgen receptor signals in the inflammation-induced progression of BPH and PCa. PMID:26594314

[Molecular medicine in thyroid surgery].

PubMed

Moretti, Sonia; Barbi, Flavia; Tavano, Maria; Calzolari, Filippo; Misso, Claudia; Lucchini, Roberta; Monacelli, Massimo; D'Ajello, Michele; Puxeddu, Efisio; Avenia, Nicola

2008-01-01

Cancer originates from a single cell which, through the acquisition of mutations in genes for key growth and survival factors, undergoes clonal expansion. Study of the genome allowed the detection of genes whose mutation is involved in tumour formation. In detail, in most thyroid neoplasms we are now able to identify the genes which cause cancer initiation. Moreover, correlations between mutations and clinico-pathological features of the tumours have been revealed. Thus, the genetic study of tumours is not anymore only a scientific curiosity, but a useful tool for the formulation of the more efficacious therapeutic and follow-up strategies. In this review we will summarize the more recent molecular medicine acquisitions in the thyroid cancer field and will describe their present and eventually future impact on the activity of the endocrine surgeon.

Perivascular Spaces, Glymphatic Dysfunction, and Small Vessel Disease

PubMed Central

Mestre, Humberto; Kostrikov, Serhii; Mehta, Rupal I.; Nedergaard, Maiken

2017-01-01

Cerebral small vessel diseases (SVD) range broadly in etiology but share a remarkably overlapping pathology. Features of SVD including enlarged perivascular spaces and formation of abluminal protein deposits cannot be completely explained by the putative pathophysiology. The recently discovered glymphatic system provides a new perspective to potentially address these gaps. This work provides a comprehensive review of the known factors that regulate glymphatic function and the disease mechanisms underlying glymphatic impairment emphasizing the role that aquaporin-4 (AQP4)-lined perivascular spaces, cerebrovascular pulsatility, and metabolite clearance play in normal CNS physiology. This review also discusses the implications that glymphatic impairment may have on SVD inception and progression with the aim of exploring novel therapeutic targets and highlighting the key questions that remain to be answered. PMID:28798076

Color mapping of one specific velocity of a biological fluid flows with complex geometry using optical coherence tomography

NASA Astrophysics Data System (ADS)

Potlov, A. Yu.; Frolov, S. V.; Proskurin, S. G.

2018-04-01

The method of Doppler color mapping of one specific (previously chosen) velocity in a turbulent flow inside biological tissues using optical coherence tomography is described. The key features of the presented method are: the raw data are separated into three parts, corresponding to the unmoving biological tissue, the positively and negatively directed biological fluid flows; the further independent signal processing procedure yields the structure image and two images of the chosen velocity, which are then normalised, encoded and joined. The described method can be used to obtain in real time the anatomical maps of the chosen velocities in normal and pathological states. The described method can be applied not only in optical coherence tomography, but also in endoscopic and Doppler ultrasonic medical imaging systems.

An analysis-by-synthesis approach to the estimation of vocal cord polyp features.

PubMed

Koizumi, T; Taniguchi, S; Itakura, F

1993-09-01

This paper deals with a new noninvasive method of estimating vocal cord polyp features through hoarse-voice analysis. A noteworthy feature of this method is that it enables us not only to discriminate hoarse voices caused by pathological vocal cords with a single golf-ball-like polyp from normal voices, but also to estimate polyp features such as the mass and dimension of polyp through the use of a novel model of pathological vocal cords which has been devised to simulate the subtle movement of the vocal cords. A synthetic hoarse voice produced with a hoarse-voice synthesizer is compared with a natural hoarse voice caused by the vocal cord polyp in terms of a distance measure and the polyp features are estimated by minimizing the distance measure. Some estimates of polyp dimension that have been obtained by applying this procedure to hoarse voices are found to compare favorably with actual polyp dimensions, demonstrating that the procedure is effective for estimating the features of golf-ball-like vocal cord polyps.

Hepatic perivascular epithelioid cell tumor (PEComa): dynamic CT, MRI, ultrasonography, and pathologic features--analysis of 7 cases and review of the literature.

PubMed

Tan, Yan; Xiao, En-hua

2012-10-01

To evaluate the dynamic CT, MRI, ultrasonography, and pathologic features of hepatic perivascular epithelioid cell tumor (PEComa), improving the understanding and diagnosis of the tumor. A retrospective analysis of CT, MRI, ultrasonography, and pathologic features of 7 hepatic PEComas diagnosed by pathology during 1st January 2005 to 1st September 2011 in our hospital. The performance of dynamic CT, MRI, and ultrasonography revealed that lesions were regular masses with well-defined borders, the maximum diameters were 2.5-8.5 cm (mean = 4 cm), density was homogeneous, contrast-enhanced CT and MRI showed the lesions were significantly and heterogeneously enhanced on arterial phase, less enhanced on portal venous phase, and slightly hypodense on delayed phase. One patient had multiple hepatic lesions and had delayed enhancement. There were no backgrounds of hepatitis and cirrhosis, enlarged lymph nodes, or distant metastases. Pathology showed the gross appearance of the tumor was smooth. Tumor cells were round or polygonal, with clear boundaries and clear membranes, and had abundant translucent cytoplasm. Nuclei were round, with medium size. Tumor cells were epithelial-like cells and arranged in dense sheets. Immunohistochemistry showed that most of them were positive in HMB45 and MelanA, S-100, SMA, while negative in CgA, Syn, CK, CD117, CD10, and CD34. Dynamic CT, MRI, ultrasonography, and pathology of PEComa had some characteristics of benign tumor's performance. Enhanced scan showed PEComa quickly enhanced on arterial phase and enhanced less on portal venous phase. Knowing these characteristics could help to improve the understanding and diagnosis of hepatic PEComa.

Learning pathology using collaborative vs. individual annotation of whole slide images: a mixed methods trial.

PubMed

Sahota, Michael; Leung, Betty; Dowdell, Stephanie; Velan, Gary M

2016-12-12

Students in biomedical disciplines require understanding of normal and abnormal microscopic appearances of human tissues (histology and histopathology). For this purpose, practical classes in these disciplines typically use virtual microscopy, viewing digitised whole slide images in web browsers. To enhance engagement, tools have been developed to enable individual or collaborative annotation of whole slide images within web browsers. To date, there have been no studies that have critically compared the impact on learning of individual and collaborative annotations on whole slide images. Junior and senior students engaged in Pathology practical classes within Medical Science and Medicine programs participated in cross-over trials of individual and collaborative annotation activities. Students' understanding of microscopic morphology was compared using timed online quizzes, while students' perceptions of learning were evaluated using an online questionnaire. For senior medical students, collaborative annotation of whole slide images was superior for understanding key microscopic features when compared to individual annotation; whilst being at least equivalent to individual annotation for junior medical science students. Across cohorts, students agreed that the annotation activities provided a user-friendly learning environment that met their flexible learning needs, improved efficiency, provided useful feedback, and helped them to set learning priorities. Importantly, these activities were also perceived to enhance motivation and improve understanding. Collaborative annotation improves understanding of microscopic morphology for students with sufficient background understanding of the discipline. These findings have implications for the deployment of annotation activities in biomedical curricula, and potentially for postgraduate training in Anatomical Pathology.

Iris recognition based on key image feature extraction.

PubMed

Ren, X; Tian, Q; Zhang, J; Wu, S; Zeng, Y

2008-01-01

In iris recognition, feature extraction can be influenced by factors such as illumination and contrast, and thus the features extracted may be unreliable, which can cause a high rate of false results in iris pattern recognition. In order to obtain stable features, an algorithm was proposed in this paper to extract key features of a pattern from multiple images. The proposed algorithm built an iris feature template by extracting key features and performed iris identity enrolment. Simulation results showed that the selected key features have high recognition accuracy on the CASIA Iris Set, where both contrast and illumination variance exist.

Pediatric Benign Soft Tissue Oral and Maxillofacial Pathology.

PubMed

Glickman, Alexandra; Karlis, Vasiliki

2016-02-01

Despite the many types of oral pathologic lesions found in infants and children, the most commonly encountered are benign soft tissue lesions. The clinical features, diagnostic criteria, and treatment algorithms of pathologies in the age group from birth to 18 years of age are summarized based on their prevalence in each given age distribution. Treatment modalities include both medical and surgical management. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

Glucocerebrosidase Mutations in Parkinson Disease.

PubMed

O'Regan, Grace; deSouza, Ruth-Mary; Balestrino, Roberta; Schapira, Anthony H

2017-01-01

Following the discovery of a higher than expected incidence of Parkinson Disease (PD) in Gaucher disease, a lysosomal storage disorder, mutations in the glucocerebrocidase (GBA) gene, which encodes a lysosomal enzyme involved in sphingolipid degradation were explored in the context of idiopathic PD. GBA mutations are now known to be the single largest risk factor for development of idiopathic PD. Clinically, on imaging and pharmacologically, GBA PD is almost identical to idiopathic PD, other than certain features that can be identified in the specialist research setting but not in routine clinical practice. In patients with a known GBA mutation, it is possible to monitor for prodromal signs of PD. The clinical similarity with idiopathic PD and the chance to identify PD at a pre-clinical stage provides a unique opportunity to research therapeutic options for early PD, before major irreversible neurodegeneration occurs. However, to date, the molecular mechanisms which lead to this increased PD risk in GBA mutation carriers are not fully elucidated. Experimental models to define the molecular mechanisms and test therapeutic options include cell culture, transgenic mice and other in vivo models amenable to genetic manipulation, such as drosophilia. Some key pathological pathways of interest in the context of GBA mutations include alpha synuclein aggregation, lysosomal-autophagy axis changes and endoplasmic reticulum stress. Therapeutic agents that exploit these pathways are being developed and include the small molecule chaperone Ambroxol. This review aims to summarise the main features of GBA-PD and provide insights into the pathological relevance of GBA mutations on molecular pathways and the therapeutic implications for PD resulting from investigation of the role of GBA in PD.

How are memory complaints in functional memory disorder related to measures of affect, metamemory and cognition?

PubMed

Metternich, Birgitta; Schmidtke, Klaus; Hüll, Michael

2009-05-01

Memory complaints are a common finding in outpatients, especially in psychosomatic and neurological practice. In a substantial group of patients persistent memory complaints are found in the absence of abnormal neuropsychology. Different labels such as "functional memory complaint" have been suggested for this phenomenon. We characterise a group of patients with such memory complaints, which we termed functional memory disorder (FMD). The aim of the present study is to describe patients with FMD. Thirty-nine patients with FMD were compared to 38 control subjects. Data were collected on the German version of the Rey Auditory Verbal Learning test and the Zahlenverbindungstest (cognitive speed), subscales of the Metamemory in Adulthood questionnaire (MIA), the Perceived Stress Questionnaire (PSQ), the Global Severity Index (GSI) of the Symptom Checklist, the Beck Depression Inventory (BDI), and other psychological questionnaire measures. We found significant group differences on all psychological questionnaire measures, with more pathological scores in the patient group. GSI and PSQ were the best predictors of memory self-efficacy. MIA-Memory Self-Efficacy (MSE), MIA-Achievement, and BDI were the best predictors of group membership (FMD vs. control group). When MSE was excluded, MIA-Achievement and BDI or GSI were the only predictors of group membership. Neuropsychological measures predicted neither MSE nor group membership. Pathological scores on measures of metamemory, stress, and depression are typical of FMD. Low MSE and a high memory-related achievement motivation seem to be key features of FMD. Other important features are increased perceived stress, general psychosomatic complaint, and elevated depression scores. Neuropsychological test performance is not associated with FMD symptoms.

Image microarrays (IMA): Digital pathology's missing tool

PubMed Central

Hipp, Jason; Cheng, Jerome; Pantanowitz, Liron; Hewitt, Stephen; Yagi, Yukako; Monaco, James; Madabhushi, Anant; Rodriguez-canales, Jaime; Hanson, Jeffrey; Roy-Chowdhuri, Sinchita; Filie, Armando C.; Feldman, Michael D.; Tomaszewski, John E.; Shih, Natalie NC.; Brodsky, Victor; Giaccone, Giuseppe; Emmert-Buck, Michael R.; Balis, Ulysses J.

2011-01-01

Introduction: The increasing availability of whole slide imaging (WSI) data sets (digital slides) from glass slides offers new opportunities for the development of computer-aided diagnostic (CAD) algorithms. With the all-digital pathology workflow that these data sets will enable in the near future, literally millions of digital slides will be generated and stored. Consequently, the field in general and pathologists, specifically, will need tools to help extract actionable information from this new and vast collective repository. Methods: To address this limitation, we designed and implemented a tool (dCORE) to enable the systematic capture of image tiles with constrained size and resolution that contain desired histopathologic features. Results: In this communication, we describe a user-friendly tool that will enable pathologists to mine digital slides archives to create image microarrays (IMAs). IMAs are to digital slides as tissue microarrays (TMAs) are to cell blocks. Thus, a single digital slide could be transformed into an array of hundreds to thousands of high quality digital images, with each containing key diagnostic morphologies and appropriate controls. Current manual digital image cut-and-paste methods that allow for the creation of a grid of images (such as an IMA) of matching resolutions are tedious. Conclusion: The ability to create IMAs representing hundreds to thousands of vetted morphologic features has numerous applications in education, proficiency testing, consensus case review, and research. Lastly, in a manner analogous to the way conventional TMA technology has significantly accelerated in situ studies of tissue specimens use of IMAs has similar potential to significantly accelerate CAD algorithm development. PMID:22200030

The Pathology of Chronic Obstructive Pulmonary Disease: Progress in the 20th and 21st Centuries.

PubMed

Berg, Kyra; Wright, Joanne L

2016-12-01

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and is the fourth leading cause of death worldwide. There has been significant progress in the pathologic description and pathophysiologic analysis of COPD in the 20th and 21st centuries. We review the history, progression, and significance of pathologic alterations in COPD, including emphysematous changes, airway alterations, and vascular alterations. We also indicate what pathologic features of COPD the practicing pathologist should be describing in standard surgical and autopsy specimens.

Fluorescence and reflectance properties of hemoglobin-pigmented skin disorders

NASA Astrophysics Data System (ADS)

Troyanova, P.; Borisova, E.; Avramov, L.

2007-06-01

There has been growing interest in clinical application of laser-induced autofluorescence (LIAF) and reflectance spectroscopy (RS) to differentiate disease from normal surrounding tissue, including skin pathologies. Pigmented cutaneous lesions diagnosis plays important role in clinical practice, as malignant melanoma, which is characterized with greatest mortality from all skin cancer types, must be carefully discriminated form other colorized pathologies. The goals of this work were investigation of cutaneous hemoglobin-pigmented lesions (heamangioma, angiokeratoma, and fibroma) by the methods of LIAFS and RS. Spectra from healthy skin areas near to the lesion were detected to be used posteriori in analysis. Fluorescence and reflectance of cutaneous hemoglobin-pigmented lesions are used to develop criterion for differentiation from other pigmented pathologies. Origins of the spectral features obtained are discussed and determination of lesion types is achieved using selected spectral features. The spectral results, obtained were used to develop multispectral diagnostic algorithms based on the most prominent spectral features from the fluorescence and reflectance spectra of the lesions investigated. In comparison between normal skin and different cutaneous lesion types and between lesion types themselves sensitivities and specificities higher than 90 % were achieved. These results show a perspective possibility to differentiate hemoglobin-pigmented lesions from other pigmented pathologies using non-invasive and real time discrimination procedure.

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.

[Age characteristics of the cardiovascular system, depending on the thyroid function in type 2 diabetes mellitus].

PubMed

Ignateva, P A; Ballyuzek, M F; Shpakov, A O

To study the features of cardiovascular system in patients with diabetes mellitus type 2 considering the thyroid pathology and age, 264 patients were examined. They were divided into three groups: 1st - patients with diffuse-nodular changes in the thyroid gland, 2nd - patients with autoimmune thyroid disease, 3rd - a control group of patients without thyroid disease. The patients of different ages were examined in each of these groups. All patients were in euthyroid state. It was established that identified in diabetes mellitus type 2 thyroid pathology and the thyroid disease contribute special features to the clinical picture for combined diabetic and cardiovascular pathology even in a euthyroid state including the age features. The laboratory and instrumental researches showed that the patients with combined diabetes and thyroid pathology have a higher incidence of atrial fibrillation, ischemic heart disease, and ventricular arrhythmias of high grades. They also were noticed to have a more adverse form of the left ventricle remodeling, also the combination of diastolic and systolic dysfunctions were found to be more frequent. It was concluded about the necessity of early diagnosis and correction of the cardiovascular disorders and thyroid systems in type 2 diabetes mellitus patients, including euthyroid patients.

A Perspective on DNA Microarrays in Pathology Research and Practice

PubMed Central

Pollack, Jonathan R.

2007-01-01

DNA microarray technology matured in the mid-1990s, and the past decade has witnessed a tremendous growth in its application. DNA microarrays have provided powerful tools for pathology researchers seeking to describe, classify, and understand human disease. There has also been great expectation that the technology would advance the practice of pathology. This review highlights some of the key contributions of DNA microarrays to experimental pathology, focusing in the area of cancer research. Also discussed are some of the current challenges in translating utility to clinical practice. PMID:17600117

Regulation of immunity and inflammation by hypoxia in immunological niches.

PubMed

Taylor, Cormac T; Colgan, Sean P

2017-12-01

Immunological niches are focal sites of immune activity that can have varying microenvironmental features. Hypoxia is a feature of physiological and pathological immunological niches. The impact of hypoxia on immunity and inflammation can vary depending on the microenvironment and immune processes occurring in a given niche. In physiological immunological niches, such as the bone marrow, lymphoid tissue, placenta and intestinal mucosa, physiological hypoxia controls innate and adaptive immunity by modulating immune cell proliferation, development and effector function, largely via transcriptional changes driven by hypoxia-inducible factor (HIF). By contrast, in pathological immunological niches, such as tumours and chronically inflamed, infected or ischaemic tissues, pathological hypoxia can drive tissue dysfunction and disease development through immune cell dysregulation. Here, we differentiate between the effects of physiological and pathological hypoxia on immune cells and the consequences for immunity and inflammation in different immunological niches. Furthermore, we discuss the possibility of targeting hypoxia-sensitive pathways in immune cells for the treatment of inflammatory disease.

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.

CD147 expression predicts biochemical recurrence after prostatectomy independent of histologic and pathologic features.

PubMed

Bauman, Tyler M; Ewald, Jonathan A; Huang, Wei; Ricke, William A

2015-07-25

CD147 is an MMP-inducing protein often implicated in cancer progression. The purpose of this study was to investigate the expression of CD147 in prostate cancer (PCa) progression and the prognostic ability of CD147 in predicting biochemical recurrence after prostatectomy. Plasma membrane-localized CD147 protein expression was quantified in patient samples using immunohistochemistry and multispectral imaging, and expression was compared to clinico-pathological features (pathologic stage, Gleason score, tumor volume, preoperative PSA, lymph node status, surgical margins, biochemical recurrence status). CD147 specificity and expression were confirmed with immunoblotting of prostate cell lines, and CD147 mRNA expression was evaluated in public expression microarray datasets of patient prostate tumors. Expression of CD147 protein was significantly decreased in localized tumors (pT2; p = 0.02) and aggressive PCa (≥pT3; p = 0.004), and metastases (p = 0.001) compared to benign prostatic tissue. Decreased CD147 was associated with advanced pathologic stage (p = 0.009) and high Gleason score (p = 0.02), and low CD147 expression predicted biochemical recurrence (HR 0.55; 95 % CI 0.31-0.97; p = 0.04) independent of clinico-pathologic features. Immunoblot bands were detected at 44 kDa and 66 kDa, representing non-glycosylated and glycosylated forms of CD147 protein, and CD147 expression was lower in tumorigenic T10 cells than non-tumorigenic BPH-1 cells (p = 0.02). Decreased CD147 mRNA expression was associated with increased Gleason score and pathologic stage in patient tumors but is not associated with recurrence status. Membrane-associated CD147 expression is significantly decreased in PCa compared to non-malignant prostate tissue and is associated with tumor progression, and low CD147 expression predicts biochemical recurrence after prostatectomy independent of pathologic stage, Gleason score, lymph node status, surgical margins, and tumor volume in multivariable analysis.

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.

The modern role of transoesophageal echocardiography in the assessment of valvular pathologies

PubMed Central

Bull, Sacha; Newton, James

2017-01-01

Despite significant advancements in the field of cardiovascular imaging, transoesophageal echocardiography remains the key imaging modality in the management of valvular pathologies. This paper provides echocardiographers with an overview of the modern role of TOE in the diagnosis and management of valvular disease. We describe how the introduction of 3D techniques has changed the detection and grading of valvular pathologies and concentrate on its role as a monitoring tool in interventional cardiology. In addition, we focus on the echocardiographic and Doppler techniques used in the assessment of prosthetic valves and provide guidance for the evaluation of prosthetic valves. Finally, we summarise quantitative methods used for the assessment of valvular stenosis and regurgitation and highlight the key areas where echocardiography remains superior over other novel imaging modalities. PMID:28096184

The modern role of transoesophageal echocardiography in the assessment of valvular pathologies.

PubMed

Wamil, Malgorzata; Bull, Sacha; Newton, James

2017-01-17

Despite significant advancements in the field of cardiovascular imaging, transoesophageal echocardiography remains the key imaging modality in the management of valvular pathologies. This paper provides echocardiographers with an overview of the modern role of TOE in the diagnosis and management of valvular disease. We describe how the introduction of 3D techniques has changed detection and grading of valvular pathologies and concentrate on its role as a monitoring tool in interventional cardiology. In addition, we focus on the echocardiographic and Doppler techniques used in the assessment of prosthetic valves, and provide guidance for evaluation of prosthetic valves. Finally, we summarise quantitative methods used for the assessment of valvular stenosis and regurgitation and highlight the key areas where echocardiography remains superior over other novel imaging modalities. © 2017 The authors.

Imaging Characteristics of Pathologically Proven Thymic Hyperplasia: Identifying Features That Can Differentiate True From Lymphoid Hyperplasia

PubMed Central

Araki, Tetsuro; Sholl, Lynette M.; Gerbaudo, Victor H.; Hatabu, Hiroto; Nishino, Mizuki

2014-01-01

OBJECTIVE The purpose of this article is to investigate the imaging characteristics of pathologically proven thymic hyperplasia and to identify features that can differentiate true hyperplasia from lymphoid hyperplasia. MATERIALS AND METHODS Thirty-one patients (nine men and 22 women; age range, 20–68 years) with pathologically confirmed thymic hyperplasia (18 true and 13 lymphoid) who underwent preoperative CT (n = 27), PET/CT (n = 5), or MRI (n = 6) were studied. The length and thickness of each thymic lobe and the transverse and anterior-posterior diameters and attenuation of the thymus were measured on CT. Thymic morphologic features and heterogeneity on CT and chemical shift on MRI were evaluated. Maximum standardized uptake values were measured on PET. Imaging features between true and lymphoid hyperplasia were compared. RESULTS No significant differences were observed between true and lymphoid hyperplasia in terms of thymic length, thickness, diameters, morphologic features, and other qualitative features (p > 0.16). The length, thickness, and diameters of thymic hyperplasia were significantly larger than the mean values of normal glands in the corresponding age group (p < 0.001). CT attenuation of lymphoid hyperplasia was significantly higher than that of true hyperplasia among 15 patients with contrast-enhanced CT (median, 47.9 vs 31.4 HU; Wilcoxon p = 0.03). The receiver operating characteristic analysis yielded greater than 41.2 HU as the optimal threshold for differentiating lymphoid hyperplasia from true hyperplasia, with 83% sensitivity and 89% specificity. A decrease of signal intensity on opposed-phase images was present in all four cases with in- and opposed-phase imaging. The mean maximum standardized uptake value was 2.66. CONCLUSION CT attenuation of the thymus was significantly higher in lymphoid hyperplasia than in true hyperplasia, with an optimal threshold of greater than 41.2 HU in this cohort of patients with pathologically confirmed thymic hyperplasia. PMID:24555583

Secondary tumors involving the thyroid gland: A multi-institutional analysis of 28 cases diagnosed on fine-needle aspiration.

PubMed

HooKim, Kim; Gaitor, Jennifer; Lin, Oscar; Reid, Michelle D

2015-11-01

Fine-needle aspiration (FNA) is routinely used to evaluate primary thyroid lesions (PTLs), however, its role in diagnosing secondary thyroid neoplasms (STNs) has not been extensively studied. The goal was to examine the clinical and cytopathologic features of STNs diagnosed on FNA. The clinico-pathologic features of 28 STNs were analyzed. All PTLs, lymphomas, and locally invasive tumors were excluded. There were 28 STNs (0.18% incidence) out of 15,800 thyroid FNAs (12 males, 16 females, 32 - 85 years), all occurring metachronously (3 weeks-20 years, average 78.3 months) comprising 24 (85.7%) metastatic carcinomas (14 [50%] renal; 4 [14.3%] head and neck squamous cell carcinomas, 3 [10.7%] breast, and 1 [3.6%] colorectal, uterine serous carcinoma, and lung adenosquamous carcinoma, respectively), 3 sarcomas (10.7%) and 1 melanoma (3.6%). STNs are rare and diverse tumors which may occur decades after primary malignancy. Renal carcinomas are the most common. Prior history of malignancy, high index of suspicion, and attention to key distinguishing cytologic clues are critical for accurate diagnosis. © 2015 Wiley Periodicals, Inc.

Evidence of aortic dissection and Marfan syndrome in a mummy from the Capuchin Catacombs of Palermo, Sicily.

PubMed

Panzer, Stephanie; Thompson, Randall C; Hergan, Klaus; Zink, Albert R; Piombino-Mascali, Dario

2018-06-08

The authors report on the assessment of an anthropogenic mummy of a young man from the Capuchin Catacombs of Palermo, Sicily, tentatively dated from the mid- to late 19 th century AD. The mummy was investigated by full-body CT examination. CT images clearly showed aortic dissection classified as Stanford-A. Due to the relation of aortic dissection to inherited connective tissue diseases in young people, such as Marfan syndrome, conspicuous and pathological findings possibly indicating the presence of underlying Marfan syndrome were assessed. Several systemic features were scored that supported the presence of underlying Marfan syndrome in this mummy. These findings were: pectus carinatum and chest asymmetry, dural ectasia, protrusio acetabuli, dolichocephaly, down-slanting palpebral fissures, malar hypoplasia and (probable) reduced elbow extension. Aortic dissection, a cardinal feature of Marfan syndrome, turned out to be the diagnostic key for the paleoradiological diagnosis of this disease. The demonstrated CT findings contribute to the spectrum of cardiovascular diseases and inherited connective tissue disease in the fields of paleopathology and paleoradiology. Copyright © 2018 Elsevier Inc. All rights reserved.

Radiomics Evaluation of Histological Heterogeneity Using Multiscale Textures Derived From 3D Wavelet Transformation of Multispectral Images.

PubMed

Chaddad, Ahmad; Daniel, Paul; Niazi, Tamim

2018-01-01

Colorectal cancer (CRC) is markedly heterogeneous and develops progressively toward malignancy through several stages which include stroma (ST), benign hyperplasia (BH), intraepithelial neoplasia (IN) or precursor cancerous lesion, and carcinoma (CA). Identification of the malignancy stage of CRC pathology tissues (PT) allows the most appropriate therapeutic intervention. This study investigates multiscale texture features extracted from CRC pathology sections using 3D wavelet transform (3D-WT) filter. Multiscale features were extracted from digital whole slide images of 39 patients that were segmented in a pre-processing step using an active contour model. The capacity for multiscale texture to compare and classify between PTs was investigated using ANOVA significance test and random forest classifier models, respectively. 12 significant features derived from the multiscale texture (i.e., variance, entropy, and energy) were found to discriminate between CRC grades at a significance value of p  < 0.01 after correction. Combining multiscale texture features lead to a better predictive capacity compared to prediction models based on individual scale features with an average (±SD) classification accuracy of 93.33 (±3.52)%, sensitivity of 88.33 (± 4.12)%, and specificity of 96.89 (± 3.88)%. Entropy was found to be the best classifier feature across all the PT grades with an average of the area under the curve (AUC) value of 91.17, 94.21, 97.70, 100% for ST, BH, IN, and CA, respectively. Our results suggest that multiscale texture features based on 3D-WT are sensitive enough to discriminate between CRC grades with the entropy feature, the best predictor of pathology grade.

Key Features of the Intragraft Microenvironment that Determine Long-Term Survival Following Transplantation

PubMed Central

Bruneau, Sarah; Woda, Craig Bryan; Daly, Kevin Patrick; Boneschansker, Leonard; Jain, Namrata Gargee; Kochupurakkal, Nora; Contreras, Alan Gabriel; Seto, Tatsuichiro; Briscoe, David Michael

2012-01-01

In this review, we discuss how changes in the intragraft microenvironment serve to promote or sustain the development of chronic allograft rejection. We propose two key elements within the microenvironment that contribute to the rejection process. The first is endothelial cell proliferation and angiogenesis that serve to create abnormal microvascular blood flow patterns as well as local tissue hypoxia, and precedes endothelial-to-mesenchymal transition. The second is the overexpression of local cytokines and growth factors that serve to sustain inflammation and, in turn, function to promote a leukocyte-induced angiogenesis reaction. Central to both events is overexpression of vascular endothelial growth factor (VEGF), which is both pro-inflammatory and pro-angiogenic, and thus drives progression of the chronic rejection microenvironment. In our discussion, we focus on how inflammation results in angiogenesis and how leukocyte-induced angiogenesis is pathological. We also discuss how VEGF is a master control factor that fosters the development of the chronic rejection microenvironment. Overall, this review provides insight into the intragraft microenvironment as an important paradigm for future direction in the field. PMID:22566935

Nutraceutical Properties of Olive Oil Polyphenols. An Itinerary from Cultured Cells through Animal Models to Humans

PubMed Central

Rigacci, Stefania; Stefani, Massimo

2016-01-01

The increasing interest in the Mediterranean diet hinges on its healthy and anti-ageing properties. The composition of fatty acids, vitamins and polyphenols in olive oil, a key component of this diet, is considered a key feature of its healthy properties. Therefore, it is of significance that the Rod of Asclepius lying on a world map surrounded by olive tree branches has been chosen by the World Health Organization as a symbol of both peace and well-being. This review travels through most of the current and past research, recapitulating the biochemical and physiological correlations of the beneficial properties of olive tree (Olea europaea) polyphenols and their derivatives found in olive oil. The factors influencing the content and beneficial properties of olive oil polyphenols will also be taken into account together with their bioavailability. Finally, the data on the clinical and epidemiological relevance of olive oil and its polyphenols for longevity and against age- and lifestyle-associated pathologies such as cancer, cardiovascular, metabolic and neurodegenerative diseases are reviewed. PMID:27258251

An autopsy study of combined pulmonary fibrosis and emphysema: correlations among clinical, radiological, and pathological features

PubMed Central

2014-01-01

Background Clinical evaluation to differentiate the characteristic features of pulmonary fibrosis and emphysema is often difficult in patients with combined pulmonary fibrosis and emphysema (CPFE), but diagnosis of pulmonary fibrosis is important for evaluating treatment options and the risk of acute exacerbation of interstitial pneumonia of such patients. As far as we know, it is the first report describing a correlation among clinical, radiological, and whole-lung pathological features in an autopsy cases of CPFE patients. Methods Experts retrospectively reviewed the clinical charts and examined chest computed tomography (CT) images and pathological findings of an autopsy series of 22 CPFE patients, and compared these with findings from 8 idiopathic pulmonary fibrosis (IPF) patients and 17 emphysema-alone patients. Results All patients had a history of heavy smoking. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC%) was significantly lower in the emphysema-alone group than the CPFE and IPF-alone groups. The percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) was significantly lower in the CPFE group than the IPF- and emphysema-alone groups. Usual interstitial pneumonia (UIP) pattern was observed radiologically in 15 (68.2%) CPFE and 8 (100%) IPF-alone patients and was pathologically observed in all patients from both groups. Pathologically thick-cystic lesions involving one or more acini with dense wall fibrosis and occasional fibroblastic foci surrounded by honeycombing and normal alveoli were confirmed by post-mortem observation as thick-walled cystic lesions (TWCLs). Emphysematous destruction and enlargement of membranous and respiratory bronchioles with fibrosis were observed in the TWCLs. The cystic lesions were always larger than the cysts of honeycombing. The prevalence of both radiological and pathological TWCLs was 72.7% among CPFE patients, but no such lesions were observed in patients with IPF or emphysema alone (p = 0.001). The extent of emphysema in CPFE patients with TWCLs was greater than that in patients without such lesions. Honeycombing with emphysema was also observed in 11 CPFE patients. Conclusions TWCLs were only observed in the CPFE patients. They were classified as lesions with coexistent fibrosing interstitial pneumonia and emphysema, and should be considered an important pathological and radiological feature of CPFE. PMID:24972672

The pathological features of idiopathic interstitial pneumonia-associated pulmonary adenocarcinomas.

PubMed

Kojima, Yoko; Okudela, Koji; Matsumura, Mai; Omori, Takahiro; Baba, Tomohisa; Sekine, Akimasa; Woo, Tetsukan; Umeda, Shigeaki; Takemura, Tamiko; Mitsui, Hideaki; Suzuki, Takehisa; Tateishi, Yoko; Iwasawa, Tae; Arai, Hiromasa; Tajiri, Michihiko; Ogura, Takashi; Kameda, Yoichi; Masuda, Munetaka; Ohashi, Kenich

2017-03-01

To investigate the pathological features of idiopathic interstitial pneumonia (IIP)-associated pulmonary adenocarcinoma. Surgically resected adenocarcinomas associated with IIP (the IIP group) and adenocarcinomas without IIP (the non-IIP group) were subjected to analysis. Adenocarcinomas in the IIP group were subdivided into two groups: one group included tumours connected to bronchiolar metaplasia in honeycomb lesions (the H-IIP group), and the other included tumours unrelated to honeycomb lesions (the NH-IIP group). Histomorphological appearance and immunohistochemical expression were compared among the H-IIP group, the NH-IIP group, and the non-IIP group. Most of the tumour cells in the H-IIP group had a tall, columnar shape that showed similar features to proximal bronchial epithelium, whereas tumour cells in the NH-IIP group and the non-IIP group had a club-like shape that showed similar features to respiratory bronchiolar/alveolar epithelium. Adenocarcinomas in the H-IIP group tended to be negative for thyroid transcription factor-1 (TTF-1) and positive for hepatocyte nuclear factor-4α (HNF-4α). The frequency of EGFR mutations was significantly lower in adenocarcinomas in the H-IIP group, although the frequencies of KRAS and ALK mutations did not differ among the three groups. Idiopathic interstitial pneumonia-associated pulmonary adenocarcinomas, especially those arising from honeycomb lesions, have distinct pathological features. © 2016 John Wiley & Sons Ltd.

Clinical features of pathologic childhood aerophagia: early recognition and essential diagnostic criteria.

PubMed

Hwang, Jin-Bok; Choi, Won Joung; Kim, Jun Sik; Lee, Sang Yun; Jung, Chul-Ho; Lee, Young Hwan; Kam, Sin

2005-11-01

This study investigated the early recognition and diagnosis of pathologic childhood aerophagia to avoid unnecessary diagnostic approaches and serious complications. Between 1995 and 2003, data from 42 consecutive patients with pathologic childhood aerophagia, aged 2 to 16 years, were reviewed. An esophageal air sign was defined as an abnormal air shadow on the proximal esophagus adjacent to the trachea on a full-inflated chest radiograph. Of the 42 patients, the chief complaints were abdominal distention (52.4%), recurrent abdominal pain syndrome (21.4%), chronic diarrhea (11.9%), acute abdominal pain (7.1%) and others (7.2%). Mean symptom duration before diagnosis was 10.6 months (range, 1 to 60 months), and it exceeded 12 months for 16 (38.1%) patients. The clinical features common to all patients were abdominal distention that increased progressively during the day, increased flatus on sleep, increased bowel sound on auscultation and an air-distended stomach with increased gas in the small and large bowel by radiography. Visible or audible air swallowing (26.2%) and repetitive belching (9.5%) were also noted. Esophageal air sign was observed in 76.2% of the patients and in 9.7% of the controls (P=0.0001). The subgroups of pathologic childhood aerophagia divided by underlying associations were pathologic childhood aerophagia without severe mental retardation (76.2%), which consisted of psychological stresses and uncertain condition, and pathologic childhood aerophagia with severe mental retardation (23.8%). The common manifestations of pathologic childhood aerophagia may be its essential diagnostic criteria, and esophageal air sign may be useful for the early recognition of pathologic childhood aerophagia. Our observations show that the diagnostic clinical profiles suggested by Rome II criteria should be detailed and made clearer if they are to serve as diagnostic criteria for pathologic childhood aerophagia.

Pathology in Greece.

PubMed

Sakellariou, S; Patsouris, E

2015-11-01

Pathology is the field of medicine that studies diseases. Ancient Greece hosted some of the earliest societies that laid the structural foundations of pathology. Initially, knowledge was based on observations but later on the key elements of pathology were established based on the dissection of animals and the autopsy of human cadavers. Christianized Greece under Ottoman rule (1453-1821) was not conducive to the development of pathology. After liberation, however, a series of events took place that paved the way for the establishment and further development of the specialty. The appointment in 1849 of two Professors of Pathology at the Medical School of Athens for didactical purposes proved to be the most important step in fostering the field of pathology in modern Greece. Presently in Greece there are seven university departments and 74 pathology laboratories in public hospitals, employing 415 specialized pathologists and 90 residents. The First Department of Pathology at the Medical School of Athens University is the oldest (1849) and largest in Greece, encompassing most pathology subspecialties.

A comparative study on pathological features of transgenic rat lines expressing either three or four repeat misfolded tau.

PubMed

Valachova, Bernadeta; Brezovakova, Veronika; Bugos, Ondrej; Jadhav, Santosh; Smolek, Tomas; Novak, Petr; Zilka, Norbert

2018-08-01

Human tauopathies represent a heterogeneous group of neurodegenerative disorders characterized by distinct clinical features, typical histopathological structures, and defined ratio(s) of three-repeat and four-repeat tau isoforms within pathological aggregates. How the optional microtubule-binding repeat of tau influences this differentiation of pathologies is understudied. We have previously generated and characterized transgenic rodent models expressing human truncated tau aa151-391 with either three (SHR24) or four microtubule-binding repeats (SHR72). Here, we compare the behavioral and neuropathological hallmarks of these two transgenic lines using a battery of tests for sensorimotor, cognitive, and neurological functions over the age range of 3.5-15 months. Progression of sensorimotor and neurological deficits was similar in both transgenic lines; however, the lifespan of transgenic line SHR72 expressing truncated four-repeat tau was markedly shorter than SHR24. Moreover, the expression of three or four-repeat tau induced distinct neurofibrillary pathology in these lines. Transgenic lines displayed different distribution of tau pathology and different type of neurofibrillary tangles. Our results suggest that three- and four-repeat isoforms of tau may display different modes of action in the diseased brain. © 2018 Wiley Periodicals, Inc.

Dimensional assessment of personality pathology in patients with eating disorders.

PubMed

Goldner, E M; Srikameswaran, S; Schroeder, M L; Livesley, W J; Birmingham, C L

1999-02-22

This study examined patients with eating disorders on personality pathology using a dimensional method. Female subjects who met DSM-IV diagnostic criteria for eating disorder (n = 136) were evaluated and compared to an age-controlled general population sample (n = 68). We assessed 18 features of personality disorder with the Dimensional Assessment of Personality Pathology - Basic Questionnaire (DAPP-BQ). Factor analysis and cluster analysis were used to derive three clusters of patients. A five-factor solution was obtained with limited intercorrelation between factors. Cluster analysis produced three clusters with the following characteristics: Cluster 1 members (constituting 49.3% of the sample and labelled 'rigid') had higher mean scores on factors denoting compulsivity and interpersonal difficulties; Cluster 2 (18.4% of the sample) showed highest scores in factors denoting psychopathy, neuroticism and impulsive features, and appeared to constitute a borderline psychopathology group; Cluster 3 (32.4% of the sample) was characterized by few differences in personality pathology in comparison to the normal population sample. Cluster membership was associated with DSM-IV diagnosis -- a large proportion of patients with anorexia nervosa were members of Cluster 1. An empirical classification of eating-disordered patients derived from dimensional assessment of personality pathology identified three groups with clinical relevance.

Youth with Psychopathy Features Are Not a Discrete Class: A Taxometric Analysis

ERIC Educational Resources Information Center

Murrie, Daniel C.; Marcus, David K.; Douglas, Kevin S.; Lee, Zina; Salekin, Randall T.; Vincent, Gina

2007-01-01

Background: Recently, researchers have sought to measure psychopathy-like features among youth in hopes of identifying children who may be progressing toward a particularly destructive form of adult pathology. However, it remains unclear whether psychopathy-like personality features among youth are best conceptualized as dimensional (distributed…

From telepathology to virtual pathology institution: the new world of digital pathology.

PubMed

Kayser, K; Kayser, G; Radziszowski, D; Oehmann, A

Telepathology has left its childhood. Its technical development is mature, and its use for primary (frozen section) and secondary (expert consultation) diagnosis has been expanded to a great amount. This is in contrast to a virtual pathology laboratory, which is still under technical constraints. Similar to telepathology, which can also be used for e-learning and e-training in pathology, as exemplarily is demonstrated on Digital Lung Pathology (Klaus.Kayser@charite.de) at least two kinds of virtual pathology laboratories will be implemented in the near future: a) those with distributed pathologists and distributed (> or = 1) laboratories associated to individual biopsy stations/surgical theatres, and b) distributed pathologists (usually situated in one institution) and a centralized laboratory, which digitizes complete histological slides. Both scenarios are under intensive technical investigations. The features of virtual pathology comprise a virtual pathology institution (mode a) that accepts a complete case with the patient's history, clinical findings, and (pre-selected) images for first diagnosis. The diagnostic responsibility is that of a conventional institution. The Internet serves as platform for information transfer, and an open server such as the iPATH (http://telepath.patho.unibas.ch) for coordination and performance of the diagnostic procedure. The size and number of transferred images have to be limited, and usual different magnifications have to be used. The sender needs to possess experiences in image sampling techniques, which present with the most significant information. A group of pathologists is "on duty", or selects one member for a predefined duty period. The diagnostic statement of the pathologist(s) on duty is retransmitted to the sender with full responsibility. The first experiences of a virtual pathology institution group working with the iPATH server working with a small hospital of the Salomon islands are promising. A centralized virtual pathology institution (mode b) depends upon the digitalization of a complete slide, and the transfer of large sized images to different pathologists working in one institution. The technical performance of complete slide digitalization is still under development. Virtual pathology can be combined with e-learning and e-training, that will serve for a powerful daily-work-integrated pathology system. At present, e-learning systems are "stand-alone" solutions distributed on CD or via Internet. A characteristic example is the Digital Lung Pathology CD, which includes about 60 different rare and common lung diseases with some features of electronic communication. These features include access to scientific library systems (PubMed), distant measurement servers (EuroQuant), automated immunohisto-chemistry measurements, or electronic journals (Elec J Pathol Histol, www.pathology-online.org). It combines e-learning and e-training with some acoustic support. A new and complete database based upon this CD will combine e-learning and e-teaching with the actual workflow in a virtual pathology institution (mode a). The technological problems are solved and do not depend upon technical constraints such as slide scanning systems. At present, telepathology serves as promoter for a complete new landscape in diagnostic pathology, the so-called virtual pathology institution. Industrial and scientific efforts will probably allow an implementation of this technique within the next two years with exciting diagnostic and scientific perspectives.

A method for normalizing pathology images to improve feature extraction for quantitative pathology

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

Tam, Allison; Barker, Jocelyn; Rubin, Daniel

Purpose: With the advent of digital slide scanning technologies and the potential proliferation of large repositories of digital pathology images, many research studies can leverage these data for biomedical discovery and to develop clinical applications. However, quantitative analysis of digital pathology images is impeded by batch effects generated by varied staining protocols and staining conditions of pathological slides. Methods: To overcome this problem, this paper proposes a novel, fully automated stain normalization method to reduce batch effects and thus aid research in digital pathology applications. Their method, intensity centering and histogram equalization (ICHE), normalizes a diverse set of pathology imagesmore » by first scaling the centroids of the intensity histograms to a common point and then applying a modified version of contrast-limited adaptive histogram equalization. Normalization was performed on two datasets of digitized hematoxylin and eosin (H&E) slides of different tissue slices from the same lung tumor, and one immunohistochemistry dataset of digitized slides created by restaining one of the H&E datasets. Results: The ICHE method was evaluated based on image intensity values, quantitative features, and the effect on downstream applications, such as a computer aided diagnosis. For comparison, three methods from the literature were reimplemented and evaluated using the same criteria. The authors found that ICHE not only improved performance compared with un-normalized images, but in most cases showed improvement compared with previous methods for correcting batch effects in the literature. Conclusions: ICHE may be a useful preprocessing step a digital pathology image processing pipeline.« less

RNA-Binding Proteins in Female Reproductive Pathologies.

PubMed

Khalaj, Kasra; Miller, Jessica E; Fenn, Christian R; Ahn, SooHyun; Luna, Rayana L; Symons, Lindsey; Monsanto, Stephany P; Koti, Madhuri; Tayade, Chandrakant

2017-06-01

RNA-binding proteins are key regulatory molecules involved primarily in post-transcriptional gene regulation of RNAs. Post-transcriptional gene regulation is critical for adequate cellular growth and survival. Recent reports have shown key interactions between these RNA-binding proteins and other regulatory elements, such as miRNAs and long noncoding RNAs, either enhancing or diminishing their response to RNA stabilization. Many RNA-binding proteins have been reported to play a functional role in mediation of cytokines involved in inflammation and immune dysfunction, and some have been classified as global post-transcriptional regulators of inflammation. The ubiquitous expression of RNA-binding proteins in a wide variety of cell types and their unique mechanisms of degradative action provide evidence that they are involved in reproductive tract pathologies. Aberrant inflammation and immune dysfunction are major contributors to the pathogenesis and disease pathophysiology of many reproductive pathologies, including ovarian and endometrial cancers in the female reproductive tract. Herein, we discuss various RNA-binding proteins and their unique contributions to female reproductive pathologies with a focus on those mediated by aberrant inflammation and immune dysfunction. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

MR enterography in nonresponsive adult celiac disease: Correlation with endoscopic, pathologic, serologic, and genetic features.

PubMed

Radmard, Amir Reza; Hashemi Taheri, Amir Pejman; Salehian Nik, Elham; Kooraki, Soheil; Kolahdoozan, Shadi; Mirminachi, Babak; Sotoudeh, Masoud; Ekhlasi, Golnaz; Malekzadeh, Reza; Shahbazkhani, Bijan

2017-10-01

To assess small bowel abnormalities on magnetic resonance enterography (MRE) in adult patients with nonresponsive celiac disease (CD) and investigate their associations with endoscopic, histopathologic, serologic, and genetic features. This prospective study was carried out between September 2012 and August 2013. After approval by the Ethics Committee of our institution, informed consent was acquired from all participants. Forty consecutive patients with nonresponsive CD, aged 17-76 years, underwent MRE using a 1.5T unit. Sequences included T 2 -HASTE, True-FISP, pre- and postcontrast VIBE to assess the quantitative (number of ileal and jejunal folds) and qualitative (fold pattern abnormalities, mural thickening, increased enhancement, bowel dilatation, or intussusception) measures. Endoscopic manifestations were categorized as normal/mild vs. severe. Histopathological results were divided into mild and severe. Genotyping of HLA-DQ2 and DQ8 was performed. Serum levels of tissue-transglutaminase, endomysial, and gliadin antibodies were also determined. Logistic regression analysis and receiver operating characteristic (ROC) curve were used. Twenty-nine (72.5%) cases showed abnormal MRE. Reversed jejunoileal fold pattern had significant association with severe endoscopic (odds ratio [OR] = 8.38, 95% confidence interval [CI] 1.73-40.5) and pathologic features (OR = 7.36, 95% CI 1.33-40.54). An increased number of ileal folds/inch was significantly associated with severe MARSH score and positive HLA-DQ8. (P < 0.001 and P = 0.026, respectively). Ileal fold number had the highest areas under the curve for prediction of severe endoscopic (AUC: 0.75, P = 0.009) and pathologic (AUC: 0.84, P < 0.001) findings and positive anti-transglutaminase antibody (AUC: 0.85, P = 0.027). Fold pattern reversal on MRE is highly associated with endoscopic and pathologic features of refractory celiac disease (RCD). Increased ileal folds showed higher correlation with endoscopic-pathologic features, HLA-DQ8, and anti-transglutaminase level. MRE might be more sensitive for detection of increased ileal folds in CD rather than reduction of duodenal and jejunal folds due to better distension of ileal loops. 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1096-1106. © 2017 International Society for Magnetic Resonance in Medicine.

Machine learning approach for the outcome prediction of temporal lobe epilepsy surgery.

PubMed

Armañanzas, Rubén; Alonso-Nanclares, Lidia; Defelipe-Oroquieta, Jesús; Kastanauskaite, Asta; de Sola, Rafael G; Defelipe, Javier; Bielza, Concha; Larrañaga, Pedro

2013-01-01

Epilepsy surgery is effective in reducing both the number and frequency of seizures, particularly in temporal lobe epilepsy (TLE). Nevertheless, a significant proportion of these patients continue suffering seizures after surgery. Here we used a machine learning approach to predict the outcome of epilepsy surgery based on supervised classification data mining taking into account not only the common clinical variables, but also pathological and neuropsychological evaluations. We have generated models capable of predicting whether a patient with TLE secondary to hippocampal sclerosis will fully recover from epilepsy or not. The machine learning analysis revealed that outcome could be predicted with an estimated accuracy of almost 90% using some clinical and neuropsychological features. Importantly, not all the features were needed to perform the prediction; some of them proved to be irrelevant to the prognosis. Personality style was found to be one of the key features to predict the outcome. Although we examined relatively few cases, findings were verified across all data, showing that the machine learning approach described in the present study may be a powerful method. Since neuropsychological assessment of epileptic patients is a standard protocol in the pre-surgical evaluation, we propose to include these specific psychological tests and machine learning tools to improve the selection of candidates for epilepsy surgery.

Machine Learning Approach for the Outcome Prediction of Temporal Lobe Epilepsy Surgery

PubMed Central

DeFelipe-Oroquieta, Jesús; Kastanauskaite, Asta; de Sola, Rafael G.; DeFelipe, Javier; Bielza, Concha; Larrañaga, Pedro

2013-01-01

Epilepsy surgery is effective in reducing both the number and frequency of seizures, particularly in temporal lobe epilepsy (TLE). Nevertheless, a significant proportion of these patients continue suffering seizures after surgery. Here we used a machine learning approach to predict the outcome of epilepsy surgery based on supervised classification data mining taking into account not only the common clinical variables, but also pathological and neuropsychological evaluations. We have generated models capable of predicting whether a patient with TLE secondary to hippocampal sclerosis will fully recover from epilepsy or not. The machine learning analysis revealed that outcome could be predicted with an estimated accuracy of almost 90% using some clinical and neuropsychological features. Importantly, not all the features were needed to perform the prediction; some of them proved to be irrelevant to the prognosis. Personality style was found to be one of the key features to predict the outcome. Although we examined relatively few cases, findings were verified across all data, showing that the machine learning approach described in the present study may be a powerful method. Since neuropsychological assessment of epileptic patients is a standard protocol in the pre-surgical evaluation, we propose to include these specific psychological tests and machine learning tools to improve the selection of candidates for epilepsy surgery. PMID:23646148

Cone beam computed tomography of plastinated hearts for instruction of radiological anatomy.

PubMed

Chang, Chih-Wei; Atkinson, Gregory; Gandhi, Niket; Farrell, Michael L; Labrash, Steven; Smith, Alice B; Norton, Neil S; Matsui, Takashi; Lozanoff, Scott

2016-09-01

Radiological anatomy education is an important aspect of the medical curriculum. The purpose of this study was to establish and demonstrate the use of plastinated anatomical specimens, specifically human hearts, for use in radiological anatomy education. Four human hearts were processed with routine plastination procedures at room temperature. Specimens were subjected to cone beam computed tomography and a graphics program (ER3D) was applied to generate 3D cardiac models. A comparison was conducted between plastinated hearts and their corresponding computer models based on a list of morphological cardiac features commonly studied in the gross anatomy laboratory. Results showed significant correspondence between plastinations and CBCT-generated 3D models (98 %; p < .01) for external structures and 100 % for internal cardiac features, while 85 % correspondence was achieved between plastinations and 2D CBCT slices. Complete correspondence (100 %) was achieved between key observations on the plastinations and internal radiological findings typically required of medical student. All pathologic features seen on the plastinated hearts were also visualized internally with the CBCT-generated models and 2D slices. These results suggest that CBCT-derived slices and models can be successfully generated from plastinated material and provide accurate representations for radiological anatomy education.

Quantitative Analysis of Intracellular Motility Based on Optical Flow Model

PubMed Central

Li, Heng

2017-01-01

Analysis of cell mobility is a key issue for abnormality identification and classification in cell biology research. However, since cell deformation induced by various biological processes is random and cell protrusion is irregular, it is difficult to measure cell morphology and motility in microscopic images. To address this dilemma, we propose an improved variation optical flow model for quantitative analysis of intracellular motility, which not only extracts intracellular motion fields effectively but also deals with optical flow computation problem at the border by taking advantages of the formulation based on L1 and L2 norm, respectively. In the energy functional of our proposed optical flow model, the data term is in the form of L2 norm; the smoothness of the data changes with regional features through an adaptive parameter, using L1 norm near the edge of the cell and L2 norm away from the edge. We further extract histograms of oriented optical flow (HOOF) after optical flow field of intracellular motion is computed. Then distances of different HOOFs are calculated as the intracellular motion features to grade the intracellular motion. Experimental results show that the features extracted from HOOFs provide new insights into the relationship between the cell motility and the special pathological conditions. PMID:29065574

Exploring cognitive integration of basic science and its effect on diagnostic reasoning in novices.

PubMed

Lisk, Kristina; Agur, Anne M R; Woods, Nicole N

2016-06-01

Integration of basic and clinical science knowledge is increasingly being recognized as important for practice in the health professions. The concept of 'cognitive integration' places emphasis on the value of basic science in providing critical connections to clinical signs and symptoms while accounting for the fact that clinicians may not spontaneously articulate their use of basic science knowledge in clinical reasoning. In this study we used a diagnostic justification test to explore the impact of integrated basic science instruction on novices' diagnostic reasoning process. Participants were allocated to an integrated basic science or clinical science training group. The integrated basic science group was taught the clinical features along with the underlying causal mechanisms of four musculoskeletal pathologies while the clinical science group was taught only the clinical features. Participants completed a diagnostic accuracy test immediately after initial learning, and one week later a diagnostic accuracy and justification test. The results showed that novices who learned the integrated causal mechanisms had superior diagnostic accuracy and better understanding of the relative importance of key clinical features. These findings further our understanding of cognitive integration by providing evidence of the specific changes in clinical reasoning when basic and clinical sciences are integrated during learning.

Borderline personality pathology in young people at ultra high risk of developing a psychotic disorder.

PubMed

Ryan, Jaymee; Graham, Anne; Nelson, Barnaby; Yung, Alison

2017-06-01

The association between borderline personality disorder and the ultra high risk (UHR) for psychosis state is unclear. The following study aimed to investigate the type of attenuated psychotic symptoms and prevalence of borderline personality pathology in a sample of UHR young people. Additionally, the study aimed to explore whether borderline personality pathology influenced the transition rate to psychosis. Medical records from Orygen Youth Health between 2007 and 2009 were examined. There were 180 patients who met UHR criteria and were included for analysis. Most patients were females (62.8%) and age ranged from 15 to 24 years. A quarter (25.2%) of UHR patients endorsed items consistent with borderline personality pathology. UHR patients with borderline personality pathology experienced a range of attenuated psychotic symptoms and could not be statistically differentiated from UHR patients with less significant or without borderline personality pathology. Borderline personality pathology did not increase or decrease the risk of developing a psychotic disorder. The absence of depression was the only predictor of psychosis. Many UHR patients present with concurrent borderline personality features. The psychotic experiences reported by UHR patients with borderline personality features were not limited to paranoid ideation, supporting the idea that borderline personality disorder may include a wider range of psychotic symptoms than previously thought. It is further possible that the psychotic symptoms experienced in this group could also be indicative of an emerging psychotic disorder. © 2015 Wiley Publishing Asia Pty Ltd.

The spectrum of muscle histopathologic findings in 42 weak scleroderma patients

PubMed Central

Paik, Julie J.; Wigley, Fredrick M.; Lloyd, Thomas E.; Corse, Andrea M.; Casciola-Rosen, Livia; Shah, Ami A.; Boin, Francesco; Hummers, Laura K.; Mammen, Andrew L.

2015-01-01

Objective To determine if distinct muscle pathological features exist in scleroderma subjects with weakness. Methods This retrospective study included weak scleroderma subjects with muscle biopsies available for review. Biopsies were systematically assessed for individual pathologic features including inflammation, necrosis, fibrosis, and acute neurogenic atrophy. Based on the aggregate individual features, biopsies were assigned a histopathologic category of polymyositis, dermatomyositis, necrotizing myopathy, non-specific myositis, “acute denervation”, “fibrosis only”, or “other”. Clinical data analyzed included autoantibody profiles, scleroderma subtype and disease duration, Medsger muscle severity scores, creatine kinase (CK), electromyography (EMG), and muscle magnetic resonance imaging (MRI). Results 42 subjects (79% female and 64% diffuse scleroderma) were included in this study. Necrosis (67%), inflammation (48%), acute neurogenic atrophy (48%), and fibrosis (33%) were the most prevalent pathologic features. The presence of fibrosis was strongly associated with anti-PM-Scl antibodies. Histopathologic categories included non-specific myositis (36%), necrotizing myopathy (21%), dermatomyositis (7%), “acute denervation” (7%), “fibrosis only” (7%), and polymyositis (5%). Disease duration of scleroderma at the time of muscle biopsy was shorter in polymyositis than other histopathologic categories. Patients with anti-PM-Scl and Scl-70 antibodies also had a shorter disease duration than those with other auto-antibody profiles. Conclusion Non-specific myositis and necrotizing myopathy were the most common histopathologic categories in weak scleroderma subjects. Surprisingly, nearly half of the subjects studied had histological evidence of acute motor denervation (acute neurogenic atrophy); this has not been previously reported. Taken together, these observations suggest that a variety of pathologic mechanisms may underlie the development of myopathy in scleroderma. PMID:25989455

[Clinical and pathological features of breast cancer in a population of Mexico].

PubMed

Maffuz-Aziz, Antonio; Labastida-Almendaro, Sonia; Espejo-Fonseca, Aura; Rodríguez-Cuevas, Sergio

Breast cancer is the most common among women in our country, and its treatment is based on prognostic factors to categorize patients into different risk groups. In this study, the clinical and pathological features that play a role as a prognostic factor in a representative population with breast cancer in México are described. A descriptive analysis of the clinical and pathological features of women diagnosed with breast cancer, in a period from June 2005 to May 2014; registered in a database and calculated by simple frequencies. A total of 4,411 patients were included, the average age at diagnosis was 53 years, 19.7% were diagnosed by mammography screening program and 80.3% derived from any signs or symptoms. Regarding the stages at diagnosis, 6.8% were carcinoma in situ, 36% at early stages (I and IIA), 45% locally advanced (IIB to IIIC), 7.7% metastatic and 3.9% unclassifiable. A 79% were ductal histology, lobular 7.8% and the rest, other types. Of ductal carcinomas, 9.1% were grade I, 54.1% grade II, and 34.6% grade III. Regarding the biological subtypes, 65.7% were luminal, 10.9% luminal Her positive, 8.7% pure Her 2 positive and 14.6% triple negative. In the present study, we described the clinical and pathologic features of a group of Mexican women with breast cancer that might reflect a national landscape, and represent the prognostic factors to determine groups of risk and treatment decisions. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Computer aided detection of tumor and edema in brain FLAIR magnetic resonance image using ANN

NASA Astrophysics Data System (ADS)

Pradhan, Nandita; Sinha, A. K.

2008-03-01

This paper presents an efficient region based segmentation technique for detecting pathological tissues (Tumor & Edema) of brain using fluid attenuated inversion recovery (FLAIR) magnetic resonance (MR) images. This work segments FLAIR brain images for normal and pathological tissues based on statistical features and wavelet transform coefficients using k-means algorithm. The image is divided into small blocks of 4×4 pixels. The k-means algorithm is used to cluster the image based on the feature vectors of blocks forming different classes representing different regions in the whole image. With the knowledge of the feature vectors of different segmented regions, supervised technique is used to train Artificial Neural Network using fuzzy back propagation algorithm (FBPA). Segmentation for detecting healthy tissues and tumors has been reported by several researchers by using conventional MRI sequences like T1, T2 and PD weighted sequences. This work successfully presents segmentation of healthy and pathological tissues (both Tumors and Edema) using FLAIR images. At the end pseudo coloring of segmented and classified regions are done for better human visualization.

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.

In phyllodes tumour of the breast expression of c-kit but not of ALDH1A1 is associated with adverse clinico-pathological features.

PubMed

Chougule, Abhijit; Bal, Amanjit; Das, Ashim; Kohli, Pavneet Singh; Singh, Gurpreet

2016-12-01

Attempts at identification of an ideal prognostic/predictive biomarker in phyllodes tumour (PT) have not been fruitful so far. Studies evaluating c-kit expression in PT have shown contradictory results. Recently aldehyde dehydrogenase 1A1 (ALDH1A1) was proposed as a stem cell marker for malignant PT but its expression has not been studied in benign and borderline tumours. We aimed to evaluate expression and prognostic significance of c-kit and ALDH1A1 in different grades of PT. Epithelial and stromal c-kit and ALDH1A1 expression were studied in 104 PT cases (86 primary and 18 recurrent tumours) and compared with different clinico-pathological features and recurrence rates. Stromal c-kit expression at 1 % cutoff correlated with increasing tumour grade, larger tumour size, hypercellularity, nuclear atypia, stromal overgrowth, infiltrative margins and mitotic count. These associations, however, were lost with higher (5 or 10 %) cutoffs. Conversely, decreased c-kit expression in the epithelial component correlated with increasing tumour grade, regardless of the cutoffs used. Stromal ALDH1A1 expression did not have significant associations with tumour grade or other adverse clinico-pathological features, regardless of different cutoffs. None of the cases showed significant epithelial ALDH1A1 expression. Expression of c-kit was associated with poorer overall survival (p = 0.011), while ALDH1A1 expression was associated with shorter recurrence-free survival (p = 0.036). In conclusion, c-kit expression was associated with higher tumour grade and adverse clinico-pathological features. However, these associations are cutoff dependent, partly explaining the variability in previously reported studies. ALDH1A1 expression did not have significant correlations with tumour grade and adverse clinico-pathological variables.

Dedifferentiated liposarcoma of the lower extremity with low-grade dedifferentiation and low-grade osteosarcomatous component.

PubMed

Zajicek, Anna K; Bridge, Julia A; Akers, Joshua W; McGarry, Sean V; Walker, Craig W

2017-02-01

Dedifferentiated liposarcoma can arise de novo or as a complication of a preexisting well-differentiated liposarcoma. We describe the radiologic and pathologic features of a long-standing liposarcoma with multiple recurrences in a 59-year-old male. Imaging demonstrated a heterogeneous fat-containing mass in the anterior thigh. The adjacent proximal femur showed irregular cortical new bone, eventually followed by intramedullary osteoblastic involvement and pathologic fracture. Histologic assessment at resection revealed dedifferentiated liposarcoma with low-grade osteosarcomatous component. The patient subsequently developed metastatic lesions in the lungs containing osteoid and osteoblastic bone metastases. We discuss the radiologic and pathologic features of this rare entity that, to our knowledge, has previously been reported to directly involve osseous structures in only one other case and discuss the potential pitfalls in diagnosis.

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

Hierarchical Diagnosis of Vocal Fold Disorders

NASA Astrophysics Data System (ADS)

Nikkhah-Bahrami, Mansour; Ahmadi-Noubari, Hossein; Seyed Aghazadeh, Babak; Khadivi Heris, Hossein

This paper explores the use of hierarchical structure for diagnosis of vocal fold disorders. The hierarchical structure is initially used to train different second-level classifiers. At the first level normal and pathological signals have been distinguished. Next, pathological signals have been classified into neurogenic and organic vocal fold disorders. At the final level, vocal fold nodules have been distinguished from polyps in organic disorders category. For feature selection at each level of hierarchy, the reconstructed signal at each wavelet packet decomposition sub-band in 5 levels of decomposition with mother wavelet of (db10) is used to extract the nonlinear features of self-similarity and approximate entropy. Also, wavelet packet coefficients are used to measure energy and Shannon entropy features at different spectral sub-bands. Davies-Bouldin criterion has been employed to find the most discriminant features. Finally, support vector machines have been adopted as classifiers at each level of hierarchy resulting in the diagnosis accuracy of 92%.

Neuroimaging and Anxiety: the Neural Substrates of Pathological and Non-pathological Anxiety.

PubMed

Taylor, James M; Whalen, Paul J

2015-06-01

Advances in the use of noninvasive neuroimaging to study the neural correlates of pathological and non-pathological anxiety have shone new light on the underlying neural bases for both the development and manifestation of anxiety. This review summarizes the most commonly observed neural substrates of the phenotype of anxiety. We focus on the neuroimaging paradigms that have shown promise in exposing this relevant brain circuitry. In this way, we offer a broad overview of how anxiety is studied in the neuroimaging laboratory and the key findings that offer promise for future research and a clearer understanding of anxiety.

Telephony-based voice pathology assessment using automated speech analysis.

PubMed

Moran, Rosalyn J; Reilly, Richard B; de Chazal, Philip; Lacy, Peter D

2006-03-01

A system for remotely detecting vocal fold pathologies using telephone-quality speech is presented. The system uses a linear classifier, processing measurements of pitch perturbation, amplitude perturbation and harmonic-to-noise ratio derived from digitized speech recordings. Voice recordings from the Disordered Voice Database Model 4337 system were used to develop and validate the system. Results show that while a sustained phonation, recorded in a controlled environment, can be classified as normal or pathologic with accuracy of 89.1%, telephone-quality speech can be classified as normal or pathologic with an accuracy of 74.2%, using the same scheme. Amplitude perturbation features prove most robust for telephone-quality speech. The pathologic recordings were then subcategorized into four groups, comprising normal, neuromuscular pathologic, physical pathologic and mixed (neuromuscular with physical) pathologic. A separate classifier was developed for classifying the normal group from each pathologic subcategory. Results show that neuromuscular disorders could be detected remotely with an accuracy of 87%, physical abnormalities with an accuracy of 78% and mixed pathology voice with an accuracy of 61%. This study highlights the real possibility for remote detection and diagnosis of voice pathology.

Facial emotion recognition and borderline personality pathology.

PubMed

Meehan, Kevin B; De Panfilis, Chiara; Cain, Nicole M; Antonucci, Camilla; Soliani, Antonio; Clarkin, John F; Sambataro, Fabio

2017-09-01

The impact of borderline personality pathology on facial emotion recognition has been in dispute; with impaired, comparable, and enhanced accuracy found in high borderline personality groups. Discrepancies are likely driven by variations in facial emotion recognition tasks across studies (stimuli type/intensity) and heterogeneity in borderline personality pathology. This study evaluates facial emotion recognition for neutral and negative emotions (fear/sadness/disgust/anger) presented at varying intensities. Effortful control was evaluated as a moderator of facial emotion recognition in borderline personality. Non-clinical multicultural undergraduates (n = 132) completed a morphed facial emotion recognition task of neutral and negative emotional expressions across different intensities (100% Neutral; 25%/50%/75% Emotion) and self-reported borderline personality features and effortful control. Greater borderline personality features related to decreased accuracy in detecting neutral faces, but increased accuracy in detecting negative emotion faces, particularly at low-intensity thresholds. This pattern was moderated by effortful control; for individuals with low but not high effortful control, greater borderline personality features related to misattributions of emotion to neutral expressions, and enhanced detection of low-intensity emotional expressions. Individuals with high borderline personality features may therefore exhibit a bias toward detecting negative emotions that are not or barely present; however, good self-regulatory skills may protect against this potential social-cognitive vulnerability. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

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

[The clinicopathological features of acute fibrinous and organizing pneumonia].

PubMed

Qiu, Yu-ying; Miao, Li-yun; Cai, Hou-rong; Xiao, Yong-long; Ye, Qing; Meng, Fan-qing; Feng, An-ning

2013-06-01

To improve understanding of the clinical, radiological and pathological characteristics of acute fibrinous and organizing pneumonia (AFOP). The clinical data of 5 AFOP patients were retrospectively analyzed. AFOP was diagnosed via percutaneous lung biopsy guided by chest computerized tomography (CT) in the Affiliated Drum Tower Hospital of Nanjing University Medical School during March 2011 to June 2012. The clinical, radiological and pathological characteristics of those patients were summarized. Among the 5 patients, 2 were male and 3 were female, aging 43-61 years. They were all subacute onset. The main clinical manifestations were dyspnea, productive cough, fever and chest pain with hypoxemia via blood gas analysis. Bilateral infiltrates with diffuse and pathy distribution were the predominant features in chest HRCT. The pathological examination revealed slightly widened alveolar septa, 1ymphocyte and plasma cell infiltration and the presence of intra-alveolar fibrin in the form of fibrin "balls" (organization) within the alveolar spaces. No neutrophil, and eosinophil infiltration and hyaline membrane formation were detected, which was different from other well-recognized histologic patterns of acute lung injury, such as diffuse alveolar damage, cryptogenic organizing pneumonia and eosinophilic pneumonia. All patients were treated by corticosteroids and showed significant clinical and radiological improvement. AFOP has nospecific features, and its diagnosis depends on pathological examination. Treatment with corticosteroids is optimal. However, whether it is a unique interstitial disease needs to be further clinically investigated.

An ICA-EBM-Based sEMG Classifier for Recognizing Lower Limb Movements in Individuals With and Without Knee Pathology.

PubMed

Naik, Ganesh R; Selvan, S Easter; Arjunan, Sridhar P; Acharyya, Amit; Kumar, Dinesh K; Ramanujam, Arvind; Nguyen, Hung T

2018-03-01

Surface electromyography (sEMG) data acquired during lower limb movements has the potential for investigating knee pathology. Nevertheless, a major challenge encountered with sEMG signals generated by lower limb movements is the intersubject variability, because the signals recorded from the leg or thigh muscles are contingent on the characteristics of a subject such as gait activity and muscle structure. In order to cope with this difficulty, we have designed a three-step classification scheme. First, the multichannel sEMG is decomposed into activities of the underlying sources by means of independent component analysis via entropy bound minimization. Next, a set of time-domain features, which would best discriminate various movements, are extracted from the source estimates. Finally, the feature selection is performed with the help of the Fisher score and a scree-plot-based statistical technique, prior to feeding the dimension-reduced features to the linear discriminant analysis. The investigation involves 11 healthy subjects and 11 individuals with knee pathology performing three different lower limb movements, namely, walking, sitting, and standing, which yielded an average classification accuracy of 96.1% and 86.2%, respectively. While the outcome of this study per se is very encouraging, with suitable improvement, the clinical application of such an sEMG-based pattern recognition system that distinguishes healthy and knee pathological subjects would be an attractive consequence.

Worry and Generalized Anxiety Disorder: A Review and Theoretical Synthesis of Evidence on Nature, Etiology, Mechanisms, and Treatment

PubMed Central

Newman, Michelle G.; Llera, Sandra J.; Erickson, Thane M.; Przeworski, Amy; Castonguay, Louis G.

2016-01-01

Generalized anxiety disorder (GAD) is associated with substantial personal and societal cost yet is the least successfully treated of the anxiety disorders. In this review, research on clinical features, boundary issues, and naturalistic course, as well as risk factors and maintaining mechanisms (cognitive, biological, neural, interpersonal, and developmental), are presented. A synthesis of these data points to a central role of emotional hyperreactivity, sensitivity to contrasting emotions, and dysfunctional attempts to cope with strong emotional shifts via worry. Consistent with the Contrast Avoidance model, evidence shows that worry evokes and sustains negative affect, thereby precluding sharp increases in negative emotion. We also review current treatment paradigms and suggest how the Contrast Avoidance model may help to target key fears and avoidance tendencies that serve to maintain pathology in GAD. PMID:23537486

Fas Versatile Signaling and Beyond: Pivotal Role of Tyrosine Phosphorylation in Context-Dependent Signaling and Diseases

PubMed Central

Chakrabandhu, Krittalak; Hueber, Anne-Odile

2016-01-01

The Fas/FasL system is known, first and foremost, as a potent apoptosis activator. While its proapoptotic features have been studied extensively, evidence that the Fas/FasL system can elicit non-death signals has also accumulated. These non-death signals can promote survival, proliferation, migration, and invasion of cells. The key molecular mechanism that determines the shift from cell death to non-death signals had remained unclear until the recent identification of the tyrosine phosphorylation in the death domain of Fas as the reversible signaling switch. In this review, we present the connection between the recent findings regarding the control of Fas multi-signals and the context-dependent signaling choices. This information can help explain variable roles of Fas signaling pathway in different pathologies. PMID:27799932

Perivascular spaces, glymphatic dysfunction, and small vessel disease.

PubMed

Mestre, Humberto; Kostrikov, Serhii; Mehta, Rupal I; Nedergaard, Maiken

2017-09-01

Cerebral small vessel diseases (SVDs) range broadly in etiology but share remarkably overlapping pathology. Features of SVD including enlarged perivascular spaces (EPVS) and formation of abluminal protein deposits cannot be completely explained by the putative pathophysiology. The recently discovered glymphatic system provides a new perspective to potentially address these gaps. This work provides a comprehensive review of the known factors that regulate glymphatic function and the disease mechanisms underlying glymphatic impairment emphasizing the role that aquaporin-4 (AQP4)-lined perivascular spaces (PVSs), cerebrovascular pulsatility, and metabolite clearance play in normal CNS physiology. This review also discusses the implications that glymphatic impairment may have on SVD inception and progression with the aim of exploring novel therapeutic targets and highlighting the key questions that remain to be answered. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Nondiabetic retinal pathology - prevalence in diabetic retinopathy screening.

PubMed

Nielsen, Nathan; Jackson, Claire; Spurling, Geoffrey; Cranstoun, Peter

2011-07-01

To determine the prevalence of photographic signs of nondiabetic retinal pathology in Australian general practice patients with diabetes. Three hundred and seven patients with diabetes underwent retinal photography at two general practices, one of which was an indigenous health centre. The images were assessed for signs of pathology by an ophthalmologist. Signs of nondiabetic retinal pathology were detected in 31% of subjects with adequate photographs. Features suspicious of glaucoma were detected in 7.7% of subjects. Other abnormalities detected included signs of age related macular degeneration (1.9%), epiretinal membranes (2.4%), vascular pathology (9.6%), chorioretinal lesions (2.9%), and congenital disc anomalies (2.9%). Indigenous Australian patients were more likely to have signs of retinal pathology and glaucoma. Signs of nondiabetic retinal pathology were frequently encountered. In high risk groups, general practice based diabetic retinopathy screening may reduce the incidence of preventable visual impairment, beyond the benefits of detection of diabetic retinopathy alone.

Modeling Pathologic Response of Esophageal Cancer to Chemoradiation Therapy Using Spatial-Temporal {sup 18}F-FDG PET Features, Clinical Parameters, and Demographics

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

Zhang, Hao; Tan, Shan; Department of Control Science and Engineering, Huazhong University of Science and Technology, Wuhan

2014-01-01

Purpose: To construct predictive models using comprehensive tumor features for the evaluation of tumor response to neoadjuvant chemoradiation therapy (CRT) in patients with esophageal cancer. Methods and Materials: This study included 20 patients who underwent trimodality therapy (CRT + surgery) and underwent {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) both before and after CRT. Four groups of tumor features were examined: (1) conventional PET/CT response measures (eg, standardized uptake value [SUV]{sub max}, tumor diameter); (2) clinical parameters (eg, TNM stage, histology) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associated changesmore » resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, cross-validations being used to avoid model overfitting. Prediction accuracy was assessed by area under the receiver operating characteristic curve (AUC), and precision was evaluated by confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). With the use of spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications)—results that were significantly better than when conventional PET/CT measures or clinical parameters and demographics alone were used. For groups with many tumor features (groups 3 and 4), the SVM model achieved significantly higher accuracy than did the LR model. Conclusions: The SVM model that used all features including spatial-temporal PET features accurately and precisely predicted pathologic tumor response to CRT in esophageal cancer.« less

Pathologic fracture in childhood and adolescent osteosarcoma: A single-institution experience.

PubMed

Haynes, Lindsay; Kaste, Sue C; Ness, Kirsten K; Wu, Jianrong; Ortega-Laureano, Lucia; Bishop, Michael; Neel, Michael; Rao, Bhaskar; Fernandez-Pineda, Israel

2017-04-01

Pathologic fractures occur in 5-10% of pediatric osteosarcoma (OS) cases and have historically been considered a contraindication to limb salvage. Our purpose was to describe the radiographic features of pathologic fracture and examine its impact on local recurrence rates, functional outcomes, and overall survival. We retrospectively analyzed patients at our institution from 1990 to 2015 with pathologic fracture at diagnosis or during neoadjuvant chemotherapy. We selected a control group of 50 OS patients of similar age and gender without pathologic fracture from 1990 to 2015. Functional outcomes were scored using Musculoskeletal Tumor Society criteria. Chi-square test was used for comparative analysis of groups. Thirty-six patients with 37 pathologic fractures form the study cohort. Of patients who received surgery, 18 of 34 patients with fracture underwent amputation compared to 8 of 48 patients in the nonfracture group (P = 0.007). Indications for amputation in fracture patients were tumor size (n = 7), neurovascular involvement (n = 6), and tumor progression during neoadjuvant chemotherapy (n = 5). Only one patient (2.9%) in the fracture group who underwent limb salvage suffered local recurrence. Of patients who received neoadjuvant chemotherapy, 25 of 34 fracture patients showed poor histological response compared to 24 of 47 nonfracture patients (P = 0.044). There was no statistically significant difference in overall survival (P = 0.96). Functional outcomes were significantly lower in fracture patients (median = 17.5) than nonfracture patients (median = 24) (P = 0.023). Radiographic features of pathologic fractures were highly variable in this population. Limb salvage surgery can be performed without increased risk of local recurrence. Patients with pathologic fracture suffer worse functional outcomes but no decrease in overall survival. © 2016 Wiley Periodicals, Inc.

Key findings from the International Ovarian Tumor Analysis (IOTA) study: an approach to the optimal ultrasound based characterisation of adnexal pathology

PubMed Central

Bourne, Tom; De Rijdt, Sylvie; Van Holsbeke, Caroline; Sayasneh, Ahmad; Valentin, Lil; Van Calster, Ben; Timmerman, Dirk

2015-01-01

Abstract The principal aim of the IOTA project has been to develop approaches to the evaluation of adnexal pathology using ultrasound that can be transferred to all examiners. Creating models that use simple, easily reproducible ultrasound characteristics is one approach. PMID:28191150

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

Bone Marrow Synoptic Reporting for Hematologic Neoplasms: Guideline From the College of American Pathologists Pathology and Laboratory Quality Center.

PubMed

Sever, Cordelia; Abbott, Charles L; de Baca, Monica E; Khoury, Joseph D; Perkins, Sherrie L; Reichard, Kaaren Kemp; Taylor, Ann; Terebelo, Howard R; Colasacco, Carol; Rumble, R Bryan; Thomas, Nicole E

2016-09-01

-There is ample evidence from the solid tumor literature that synoptic reporting improves accuracy and completeness of relevant data. No evidence-based guidelines currently exist for synoptic reporting for bone marrow samples. -To develop evidence-based recommendations to standardize the basic components of a synoptic report template for bone marrow samples. -The College of American Pathologists Pathology and Laboratory Quality Center convened a panel of experts in hematopathology to develop recommendations. A systematic evidence review was conducted to address 5 key questions. Recommendations were derived from strength of evidence, open comment feedback, and expert panel consensus. -Nine guideline statements were established to provide pathology laboratories with a framework by which to develop synoptic reporting templates for bone marrow samples. The guideline calls for specific data groups in the synoptic section of the pathology report; provides a list of evidence-based parameters for key, pertinent elements; and addresses ancillary testing. -A framework for bone marrow synoptic reporting will improve completeness of the final report in a manner that is clear, succinct, and consistent among institutions.

Congenital renal rhabdoid tumor with placental metastases: immunohistochemistry, cytogenetic, and ultrastructural findings.

PubMed

de Tar, Michael; Sanford Biggerstaff, Julie

2006-01-01

Malignant congenital tumors of fetal origin are rare lesions, the most common type being congenital neuroblastoma. Although prenatal diagnosis is possible in large tumors, occasionally the tumor will be diagnosed first by its metastatic involvement of the placenta. Placental metastases can reflect either maternal or fetal primary sites, and each has relatively specific patterns of placental involvement. We describe the clinical and pathologic features of a widely metastatic congenital renal rhabdoid tumor with its placental and autopsy findings, and include the immunohistochemical, cytogenetic, and ultrastructural features. The pathologic features of the placenta in congenital renal rhabdoid tumor with placental metastasis have not been previously described. The examination of the placenta in this case led to the initial diagnosis and obviated the need for additional diagnostic procedures.

Placental pathology in early intrauterine growth restriction associated with maternal hypertension.

PubMed

Veerbeek, J H W; Nikkels, P G J; Torrance, H L; Gravesteijn, J; Post Uiterweer, E D; Derks, J B; Koenen, S V; Visser, G H A; Van Rijn, B B; Franx, A

2014-09-01

To identify key pathological characteristics of placentas from pregnancies complicated by early intrauterine growth restriction, and to examine their relations with maternal hypertensive disease and umbilical artery Doppler waveform abnormalities. Single-center retrospective cohort study of singleton pregnancies with abnormal umbilical artery Doppler flow patterns resulting in a live birth <34 weeks of a baby with a weight <10th percentile for gestational age. Umbilical artery end diastolic flow was classified as being either present or absent/reversed (AREDF). Data were stratified into intrauterine growth restriction with or without hypertensive disease and pathological characteristics were compared between these various conditions according to predefined scoring criteria. Among 164 placentas studied, we found high rates of characteristic histopathological features that were associated with intrauterine growth restriction, including infarction (>5% in 42%), chronic villitis (21%), chronic chorioamnionitis (36%), membrane necrosis (20%), elevated nucleated red blood cells (89%), increased syncytial knotting (93%), increased villous maturation (98%), fetal thrombosis (32%) and distal villous hypoplasia (35%). Chronic inflammation of fetal membranes and syncytial knotting were more common in women with concomitant hypertensive disease as compared to women with normotensive IUGR (p < 0.05). Placentas from women with umbilical artery AREDF were more likely to show increased numbers of nucleated red blood cells and distal villous hypoplasia (p < 0.05). Placentas of women with early IUGR show high rates of several histological aberrations. Further, concomitant maternal hypertension is associated with characteristic inflammatory changes and umbilical artery AREDF with signs of chronic hypoxia. Copyright © 2014 Elsevier Ltd. All rights reserved.

Indications for distinct pathogenic mechanisms of asbestos and silica through gene expression profiling of the response of lung epithelial cells

PubMed Central

Perkins, Timothy N.; Peeters, Paul M.; Shukla, Arti; Arijs, Ingrid; Dragon, Julie; Wouters, Emiel F.M.; Reynaert, Niki L.; Mossman, Brooke T.

2015-01-01

Occupational and environmental exposures to airborne asbestos and silica are associated with the development of lung fibrosis in the forms of asbestosis and silicosis, respectively. However, both diseases display distinct pathologic presentations, likely associated with differences in gene expression induced by different mineral structures, composition and bio-persistent properties. We hypothesized that effects of mineral exposure in the airway epithelium may dictate deviating molecular events that may explain the different pathologies of asbestosis versus silicosis. Using robust gene expression-profiling in conjunction with in-depth pathway analysis, we assessed early (24 h) alterations in gene expression associated with crocidolite asbestos or cristobalite silica exposures in primary human bronchial epithelial cells (NHBEs). Observations were confirmed in an immortalized line (BEAS-2B) by QRT-PCR and protein assays. Utilization of overall gene expression, unsupervised hierarchical cluster analysis and integrated pathway analysis revealed gene alterations that were common to both minerals or unique to either mineral. Our findings reveal that both minerals had potent effects on genes governing cell adhesion/migration, inflammation, and cellular stress, key features of fibrosis. Asbestos exposure was most specifically associated with aberrant cell proliferation and carcinogenesis, whereas silica exposure was highly associated with additional inflammatory responses, as well as pattern recognition, and fibrogenesis. These findings illustrate the use of gene-profiling as a means to determine early molecular events that may dictate pathological processes induced by exogenous cellular insults. In addition, it is a useful approach for predicting the pathogenicity of potentially harmful materials. PMID:25351596

[Correlation of CD82 and hTERT expressions and HPV infection with penile cancer].

PubMed

Zhai, Jian-Po; Li, Ming; Wang, Qi-Yan; Wei, Dong; Xu, Ke-Xin

2011-09-01

To study the correlation of the expressions of CD82 and hTERT and HPV infection with the clinical pathological features of penile cancer and identify their prognostic significance in the lymphatic metastasis of the disease. A total of 44 patients underwent partial or radical penectomy and lymph node dissection. The expressions of CD82 and hTERT were determined by immunohistochemistry, and HPV infection was detected by PCR. The positive rates of CD82, hTERT, and HPV DNA in penile carcinoma were 47.7%, 38.6% and 25.9%, respectively. The amplified HPV DNA was HPV-16. The pathological stage and hTERT expression were positively correlated with inguinal lymph node metastasis of penile cancer (P = 0.032, P = 0.041), and so was the pathological stage with the expression of CD82 (P = 0.045), but neither the pathological stage, nor the expression of CD82 or the positive rate of HPV DNA showed any correlation with lymph node metastasis (P = 0.627, P = 0.094, P = 0.633). The pathological grade and hTERT expression are independent prognostic factors for lymph node metastasis in penile carcinoma. These features help the prognosis and identification of the patient at the risk of nodal metastasis.

Long-Term Mangiferin Extract Treatment Improves Central Pathology and Cognitive Deficits in APP/PS1 Mice.

PubMed

Infante-Garcia, Carmen; Ramos-Rodriguez, Juan Jose; Delgado-Olmos, Irene; Gamero-Carrasco, Carlos; Fernandez-Ponce, Maria Teresa; Casas, Lourdes; Mantell, Casimiro; Garcia-Alloza, Monica

2017-08-01

Alzheimer's disease (AD) is the most common cause of dementia; however, available treatments have had limited success. Therefore AD patients are in tremendous need of new pharmacological approaches that may delay or slow the progression of the disease. In addition to the classical neuropathological features, immunological and inflammatory processes are also involved in AD pathogenesis. Naturally occurring compounds, such as Mangifera indica Linn (MGF) extracts have previously been shown to significantly reduce peripheral inflammatory processes. In order to explore the role of MGF in AD central pathology, we have orally treated APP/PS1 mice for 22 weeks. While MGF did not affect amyloid pathology, tau hyperphosphorylation was significantly reduced in the cortex and hippocampus. Also, inflammatory processes, measured by microglia and astrocyte burdens, were diminished in MGF-treated mice. Moreover, neuronal morphological alterations, such as abnormal neurite curvature and dystrophies, highly increased in APP/PS1 mice, were significantly ameliorated by long-term MGF treatment. Reduction of all these pathological features were accompanied by compelling improvements of episodic and spatial memory in APP/PS1 mice treated with MGF. Altogether our data suggest that MGF may provide a useful tool to target different aspects of AD pathology and could lead to more effective future therapeutic or preventive strategies.

Dendritic cell and histiocytic neoplasms: biology, diagnosis, and treatment.

PubMed

Dalia, Samir; Shao, Haipeng; Sagatys, Elizabeth; Cualing, Hernani; Sokol, Lubomir

2014-10-01

Dendritic and histiocytic cell neoplasms are rare malignancies that make up less than 1% of all neoplasms arising in lymph nodes or soft tissues. These disorders have distinctive disease biology, clinical presentations, pathology, and unique treatment options. Morphology and immunohistochemistry evaluation by a hematopathologist remains key for differentiating between these neoplasms. In this review, we describe tumor biology, clinical features, pathology, and treatment of follicular dendritic cell sarcoma, interdigitating dendritic cell sarcoma, indeterminate dendritic cell sarcoma, histiocytic sarcoma, fibroblastic reticular cell tumors, and disseminated juvenile xanthogranuloma. A literature search for articles published between 1990 and 2013 was undertaken. Articles are reviewed and salient findings are systematically described. Patients with dendritic cell and histiocytic neoplasms have distinct but variable clinical presentations; however, because many tumors have recently been recognized, their true incidence is uncertain. Although the clinical features can present in many organs, most occur in the lymph nodes or skin. Most cases are unifocal and solitary presentations have good prognoses with surgical resection. The role of adjuvant therapy in these disorders remains unclear. In cases with disseminated disease, prognosis is poor and data on treatment options are limited, although chemotherapy and referral to a tertiary care center should be considered. Excisional biopsy is the preferred method of specimen collection for tissue diagnosis, and immunohistochemistry is the most important diagnostic method for differentiating these disorders from other entities. Dendritic cell and histiocytic cell neoplasms are rare hematological disorders with variable clinical presentations and prognoses. Immunohistochemistry remains important for diagnosis. Larger pooled analyses or clinical trials are needed to better understand optimal treatment options in these rare disorders. Whenever possible, patients should be referred to a tertiary care center for disease management.

Role of the P-Type ATPases, ATP7A and ATP7B in brain copper homeostasis.

PubMed

Telianidis, Jonathon; Hung, Ya Hui; Materia, Stephanie; Fontaine, Sharon La

2013-01-01

Over the past two decades there have been significant advances in our understanding of copper homeostasis and the pathological consequences of copper dysregulation. Cumulative evidence is revealing a complex regulatory network of proteins and pathways that maintain copper homeostasis. The recognition of copper dysregulation as a key pathological feature in prominent neurodegenerative disorders such as Alzheimer's, Parkinson's, and prion diseases has led to increased research focus on the mechanisms controlling copper homeostasis in the brain. The copper-transporting P-type ATPases (copper-ATPases), ATP7A and ATP7B, are critical components of the copper regulatory network. Our understanding of the biochemistry and cell biology of these complex proteins has grown significantly since their discovery in 1993. They are large polytopic transmembrane proteins with six copper-binding motifs within the cytoplasmic N-terminal domain, eight transmembrane domains, and highly conserved catalytic domains. These proteins catalyze ATP-dependent copper transport across cell membranes for the metallation of many essential cuproenzymes, as well as for the removal of excess cellular copper to prevent copper toxicity. A key functional aspect of these copper transporters is their copper-responsive trafficking between the trans-Golgi network and the cell periphery. ATP7A- and ATP7B-deficiency, due to genetic mutation, underlie the inherited copper transport disorders, Menkes and Wilson diseases, respectively. Their importance in maintaining brain copper homeostasis is underscored by the severe neuropathological deficits in these disorders. Herein we will review and update our current knowledge of these copper transporters in the brain and the central nervous system, their distribution and regulation, their role in normal brain copper homeostasis, and how their absence or dysfunction contributes to disturbances in copper homeostasis and neurodegeneration.

Role of the P-Type ATPases, ATP7A and ATP7B in brain copper homeostasis

PubMed Central

Telianidis, Jonathon; Hung, Ya Hui; Materia, Stephanie; Fontaine, Sharon La

2013-01-01

Over the past two decades there have been significant advances in our understanding of copper homeostasis and the pathological consequences of copper dysregulation. Cumulative evidence is revealing a complex regulatory network of proteins and pathways that maintain copper homeostasis. The recognition of copper dysregulation as a key pathological feature in prominent neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and prion diseases has led to increased research focus on the mechanisms controlling copper homeostasis in the brain. The copper-transporting P-type ATPases (copper-ATPases), ATP7A and ATP7B, are critical components of the copper regulatory network. Our understanding of the biochemistry and cell biology of these complex proteins has grown significantly since their discovery in 1993. They are large polytopic transmembrane proteins with six copper-binding motifs within the cytoplasmic N-terminal domain, eight transmembrane domains, and highly conserved catalytic domains. These proteins catalyze ATP-dependent copper transport across cell membranes for the metallation of many essential cuproenzymes, as well as for the removal of excess cellular copper to prevent copper toxicity. A key functional aspect of these copper transporters is their copper-responsive trafficking between the trans-Golgi network and the cell periphery. ATP7A- and ATP7B-deficiency, due to genetic mutation, underlie the inherited copper transport disorders, Menkes and Wilson diseases, respectively. Their importance in maintaining brain copper homeostasis is underscored by the severe neuropathological deficits in these disorders. Herein we will review and update our current knowledge of these copper transporters in the brain and the central nervous system, their distribution and regulation, their role in normal brain copper homeostasis, and how their absence or dysfunction contributes to disturbances in copper homeostasis and neurodegeneration. PMID:23986700

pH regulators in invadosomal functioning: proton delivery for matrix tasting.

PubMed

Brisson, Lucie; Reshkin, Stephan J; Goré, Jacques; Roger, Sébastien

2012-01-01

Invadosomes are actin-rich finger-like cellular structures sensing and interacting with the surrounding extracellular matrix (ECM) and involved in its proteolytic remodeling. Invadosomes are structures distinct from other adhesion complexes, and have been identified in normal cells that have to cross tissue barriers to fulfill their function such as leukocytes, osteoclasts and endothelial cells. They also represent features of highly aggressive cancer cells, allowing them to escape from the primary tumor, to invade surrounding tissues and to reach systemic circulation. They are localized to the ventral membrane of cells grown under 2-dimensional conditions and are supposed to be present all around cells grown in 3-dimensional matrices. Indeed invadosomes are key structures in physiological processes such as inflammation and the immune response, bone remodeling, tissue repair, but also in pathological conditions such as osteopetrosis and the development of metastases. Invadosomes are subdivided into podosomes, found in normal cells, and into invadopodia specific for cancer cells. While these two structures exhibit differences in organization, size, number and half-life, they share similarities in molecular composition, participation in cell-matrix adhesion and promoting matrix degradation. A key determinant in invadosomal function is the recruitment and release of proteases, such as matrix metalloproteinases (MMPs), serine proteases and cysteine cathepsins, together with their activation in a tightly controlled and highly acidic microenvironment. Therefore numerous pH regulators such as V-ATPases and Na(+)/H(+) exchangers, are found in invadosomes and are directly involved in their constitution as well as their functioning. This review focuses on the participation of pH regulators in invadosome function in physiological and pathological conditions, with a particular emphasis on ECM remodeling by osteoclasts during bone resorption and by cancer cells. Copyright © 2012 Elsevier GmbH. All rights reserved.

A Population-Based Analysis of Application of WHO Nomenclature in Pathology Reports of Pulmonary Neuroendocrine Tumors.

PubMed

Derks, Jules L; van Suylen, Robert Jan; Thunnissen, Erik; den Bakker, Michael A; Smit, Egbert F; Groen, Harry J M; Speel, Ernst J M; Dingemans, Anne-Marie C

2016-04-01

Pulmonary neuroendocrine tumors (pNETs) are difficult to classify. We performed a population-based analysis to investigate the application of pNET nomenclature in daily pathology practice. Conclusions from pathology reports (2003-2012) describing carcinoids, (large cell) neuroendocrine carcinomas (NECs), and carcinomas with neuroendocrine features/differentiation were retrieved from the Dutch Pathology Registry by queries on location and diagnosis and screened for terminology. Cases with a nonpulmonary or unknown origin and small cell lung cancer were excluded. Diagnoses were clustered into subgroups and the retrieved terminology was compared with the 2015 World Health Organization (WHO) diagnoses. By means of an online questionnaire, interpretation of the non-WHO nomenclature retrieved from pathology reports was evaluated (by 35 physicians and 19 pathologists). A total of 3216 unique pathology report conclusions with 55 different pNET diagnoses (n = 3052) and 20 uncertain diagnoses (n = 164) were analyzed. Non-WHO nomenclature was used in 15% of diagnoses (n = 488). Diagnoses could be clustered into carcinoids (n = 1086), NEC (n = 1316), carcinomas with neuroendocrine features/differentiation (n = 624), and unspecified pNETs (n = 26). Non-WHO nomenclature within these clusters was found for 7% of carcinoids, 20% of NECs, 13% of carcinomas with neuroendocrine features/differentiation, and 100% of unspecified pNETs and was observed more often in conclusions regarding biopsy or cytological specimens (62% and 12%) compared with resection specimens (26%). Analysis of the questionnaire results revealed that 4 of 19 diagnoses based on non-WHO nomenclature were uniformly interpreted (>50% agreement) by physicians, as were 10 of 19 diagnoses by pathologists. In 15% of pNETs other than small cell lung cancer, a non-WHO nomenclature diagnosis was provided, more frequently on the basis of smaller specimens. The interpretation was different between physicians and pathologists. Application of uniform nomenclature among all clinicians is advocated. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

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.

Neuropathologic features associated with Alzheimer disease diagnosis

PubMed Central

Grinberg, L.T.; Miller, B.; Kawas, C.; Yaffe, K.

2011-01-01

Objective: To examine whether the association between clinical Alzheimer disease (AD) diagnosis and neuropathology and the precision by which neuropathology differentiates people with clinical AD from those with normal cognition varies by age. Methods: We conducted a cross-sectional analysis of 2,014 older adults (≥70 years at death) from the National Alzheimer's Coordinating Center database with clinical diagnosis of normal cognition (made ≤1 year before death, n = 419) or AD (at ≥65 years, n = 1,595) and a postmortem neuropathologic examination evaluating AD pathology (neurofibrillary tangles, neuritic plaques) and non-AD pathology (diffuse plaques, amyloid angiopathy, Lewy bodies, macrovascular disease, microvascular disease). We used adjusted logistic regression to analyze the relationship between clinical AD diagnosis and neuropathologic features, area under the receiver operating characteristic curve (c statistic) to evaluate how precisely neuropathology differentiates between cognitive diagnoses, and an interaction to identify effect modification by age group. Results: In a model controlling for coexisting neuropathologic features, the relationship between clinical AD diagnosis and neurofibrillary tangles was significantly weaker with increasing age (p < 0.001 for interaction). The aggregate of all neuropathologic features more strongly differentiated people with clinical AD from those without in younger age groups (70–74 years: c statistic, 95% confidence interval: 0.93, 0.89–0.96; 75–84 years: 0.95, 0.87–0.95; ≥85 years: 0.83, 0.80–0.87). Non-AD pathology significantly improved precision of differentiation across all age groups (p < 0.004). Conclusion: Clinical AD diagnosis was more weakly associated with neurofibrillary tangles among the oldest old compared to younger age groups, possibly due to less accurate clinical diagnosis, better neurocompensation, or unaccounted pathology among the oldest old. PMID:22031532

Association of BRCA Mutation Types, Imaging Features, and Pathologic Findings in Patients With Breast Cancer With BRCA1 and BRCA2 Mutations.

PubMed

Ha, Su Min; Chae, Eun Young; Cha, Joo Hee; Kim, Hak Hee; Shin, Hee Jung; Choi, Woo Jung

2017-10-01

The purpose of this study is to retrospectively evaluate the relationships between the BRCA mutation types, imaging features, and pathologic findings of breast cancers in BRCA1 and BRCA2 mutation carriers. We identified patients with breast cancer with BRCA gene mutations from January 2000 to December 2014. After excluding patients who underwent lesion excision before MRI, 99 BRCA1 and 103 BRCA2 lesions in 187 women (mean age, 39.7 and 40.4 years, respectively) were enrolled. Mammographic, sonographic, and MRI scans were reviewed according to the BI-RADS lexicon (5th edition). Pathologic data were reviewed, including the immunohistochemistry findings. The relationships between the BRCA mutations and both imaging and pathologic findings were analyzed. The distribution of molecular subtypes of tumors significantly differed by the mutation type. BRCA1 tumors were associated with the triple-negative subtype, whereas BRCA2 tumors were associated with the luminal B subtype (p = 0.002). At MRI, breast cancers with BRCA1 mutations exhibited a circumscribed margin (p = 0.032) and rim enhancement (p = 0.013). No significant differences in mass shape or kinetic features were observed at MRI. Cancers in BRCA1 mutation carriers tended to develop in the posterior location in the breast (p = 0.034). At mammography, no significant difference in the prevalence of calcifications was observed according to the mutation type. At sonography, BRCA1 lesions were found to be associated with posterior acoustic enhancement (p < 0.0001). Breast cancers with BRCA1 mutations tend to exhibit benign morphologic features at MRI, mammography, and sonography, compared with BRCA2 mutations. Lesion location may represent another difference on imaging among various genetic phenotypes.

Soft-Tissue Sarcomas of the Abdomen and Pelvis: Radiologic-Pathologic Features, Part 1-Common Sarcomas: From the Radiologic Pathology Archives.

PubMed

Levy, Angela D; Manning, Maria A; Al-Refaie, Waddah B; Miettinen, Markku M

2017-01-01

Soft-tissue sarcomas are a diverse group of rare mesenchymal malignancies that can arise at any location in the body and affect all age groups. These sarcomas are most common in the extremities, trunk wall, retroperitoneum, and head and neck. In the adult population, soft-tissue sarcomas arising in the abdomen and pelvis are often large masses at the time of diagnosis because they are usually clinically silent or cause vague or mild symptoms until they invade or compress vital organs. In contrast, soft-tissue sarcomas arising from the abdominal wall come to clinical attention earlier in the course of disease because they cause a palpable mass, abdominal wall deformity, or pain that is more clinically apparent. The imaging features of abdominal and pelvic sarcomas and abdominal wall sarcomas can be nonspecific and overlap with more common pathologic conditions, making diagnosis difficult or, in some cases, delaying diagnosis. Liposarcoma (well-differentiated and dedifferentiated liposarcomas), leiomyosarcoma, and gastrointestinal stromal tumor (GIST) are the most common intra-abdominal primary sarcomas. Any soft-tissue sarcoma can arise in the abdominal wall. Knowledge of the classification and pathologic features of soft-tissue sarcomas, the anatomic locations where they occur, and their cross-sectional imaging features helps the radiologist establish the diagnosis or differential diagnosis so that patients with soft-tissue sarcomas can receive optimal treatment and management. In part 1 of this article, the most common soft-tissue sarcomas (liposarcoma, leiomyosarcoma, and GIST) are reviewed, with a discussion on anatomic locations, classification, clinical considerations, and differential diagnosis. Part 2 will focus on the remainder of the soft-tissue sarcomas occurring in the abdomen and pelvis.

Soft-Tissue Sarcomas of the Abdomen and Pelvis: Radiologic-Pathologic Features, Part 1—Common Sarcomas: From the Radiologic Pathology Archives

PubMed Central

Manning, Maria A.; Al-Refaie, Waddah B.; Miettinen, Markku M.

2017-01-01

Soft-tissue sarcomas are a diverse group of rare mesenchymal malignancies that can arise at any location in the body and affect all age groups. These sarcomas are most common in the extremities, trunk wall, retroperitoneum, and head and neck. In the adult population, soft-tissue sarcomas arising in the abdomen and pelvis are often large masses at the time of diagnosis because they are usually clinically silent or cause vague or mild symptoms until they invade or compress vital organs. In contrast, soft-tissue sarcomas arising from the abdominal wall come to clinical attention earlier in the course of disease because they cause a palpable mass, abdominal wall deformity, or pain that is more clinically apparent. The imaging features of abdominal and pelvic sarcomas and abdominal wall sarcomas can be nonspecific and overlap with more common pathologic conditions, making diagnosis difficult or, in some cases, delaying diagnosis. Liposarcoma (well-differentiated and dedifferentiated liposarcomas), leiomyosarcoma, and gastrointestinal stromal tumor (GIST) are the most common intra-abdominal primary sarcomas. Any soft-tissue sarcoma can arise in the abdominal wall. Knowledge of the classification and pathologic features of soft-tissue sarcomas, the anatomic locations where they occur, and their cross-sectional imaging features helps the radiologist establish the diagnosis or differential diagnosis so that patients with soft-tissue sarcomas can receive optimal treatment and management. In part 1 of this article, the most common soft-tissue sarcomas (liposarcoma, leiomyosarcoma, and GIST) are reviewed, with a discussion on anatomic locations, classification, clinical considerations, and differential diagnosis. Part 2 will focus on the remainder of the soft-tissue sarcomas occurring in the abdomen and pelvis. PMID:28287938

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

PubMed

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

2009-05-01

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

Dual pathology of the submandibular gland: plasmacytoma and pleomorphic adenoma.

PubMed

Menon, Shalini; Pujary, Kailesh; Valiathan, Manna

2014-03-03

Synchronous tumours of different histological types involving the salivary gland are very rare. There have been cases reported in the literature of such tumours occurring in the parotid gland. A 52-year-old man presented with a 4-year history of gradually increasing painless swelling in the right submandibular region. The ultrasound scan of the neck showed features suggestive of a submandibular sialadenitis. The right submandibular gland was then surgically excised and sent for histopathological examination. The features showed a unique dual pathology of the submandibular gland, that is, a plasmacytoma and a pleomorphic adenoma. Such a synchronous double pathology involving the submandibular gland has not been reported in the literature. A review of the literature suggests a good prognosis for the extramedullary plasmacytoma, provided multiple myeloma is ruled out. In 18 months of follow-up, the patient has been asymptomatic with a negative myeloma workup.

Dual pathology of the submandibular gland: plasmacytoma and pleomorphic adenoma

PubMed Central

Menon, Shalini; Pujary, Kailesh; Valiathan, Manna

2014-01-01

Synchronous tumours of different histological types involving the salivary gland are very rare. There have been cases reported in the literature of such tumours occurring in the parotid gland. A 52-year-old man presented with a 4-year history of gradually increasing painless swelling in the right submandibular region. The ultrasound scan of the neck showed features suggestive of a submandibular sialadenitis. The right submandibular gland was then surgically excised and sent for histopathological examination. The features showed a unique dual pathology of the submandibular gland, that is, a plasmacytoma and a pleomorphic adenoma. Such a synchronous double pathology involving the submandibular gland has not been reported in the literature. A review of the literature suggests a good prognosis for the extramedullary plasmacytoma, provided multiple myeloma is ruled out. In 18 months of follow-up, the patient has been asymptomatic with a negative myeloma workup. PMID:24591383

Clinical, pathological, and genetic features of limb-girdle muscular dystrophy type 2A with new calpain 3 gene mutations in seven patients from three Japanese families.

PubMed

Kawai, H; Akaike, M; Kunishige, M; Inui, T; Adachi, K; Kimura, C; Kawajiri, M; Nishida, Y; Endo, I; Kashiwagi, S; Nishino, H; Fujiwara, T; Okuno, S; Roudaut, C; Richard, I; Beckmann, J S; Miyoshi, K; Matsumoto, T

1998-11-01

We report on the clinical, pathological, and genetic features of 7 patients with limb-girdle muscular dystrophy type 2A (LGMD2A) from three Japanese families. The mean age of onset was 9.7+/-3.1 years (mean+/-SD), and loss of ambulance occurred at 38.5+/-2.1 years. Muscle atrophy was predominant in the pelvic and shoulder girdles, and proximal limb muscles. Muscle pathology revealed dystrophic changes. In two families, an identical G to C mutation at position 1080 the in calpain 3 gene was identified, and a frameshift mutation (1796insA) was found in the third family. The former mutation results in a W360R substitution in the proteolytic site of calpain 3, and the latter in a deletion of the Ca2+-binding domain.

Histopathological study of the mite biting (Dermanyssus gallinae) in poultry skin

PubMed Central

Hobbenaghi, Rahim; Tavassoli, Mousa; Alimehr, Manochehr; Shokrpoor, Sara; Ghorbanzadeghan, Mohammad

2012-01-01

The red mite of poultry, Dremanyssus gallinae, is the most important hematophagous ectoparasite of poultry. In this study, pathologic changes of its biting on the poultry skin have been investigated. Thirty-two (Control = 16 and Treatment = 16) four weeks old Ross broilers (308) were infested with the mite on skin of hock joins. Samples were collected after 1, 24, 72 hours and 10 days. The skin samples were fixed in 10% buffered formalin and histological sections were prepared using routine Hematoxylin & Eosin staining method. Results showed that in all cases, except within first hour of infestation, lymphocytic infiltration was always a constant pathologic feature. Necrosis of feather's follicles was a prominent pathologic feature ensued due to vascular disturbances and resulted in loss of feather. Hyperkeratosis, parakeratosis and acanthosis were observed after 72 hours. These findings reveal that mite biting induces local epidermal hyperplasia. PMID:25610570

Histopathological study of the mite biting (Dermanyssus gallinae) in poultry skin.

PubMed

Hobbenaghi, Rahim; Tavassoli, Mousa; Alimehr, Manochehr; Shokrpoor, Sara; Ghorbanzadeghan, Mohammad

2012-01-01

The red mite of poultry, Dremanyssus gallinae, is the most important hematophagous ectoparasite of poultry. In this study, pathologic changes of its biting on the poultry skin have been investigated. Thirty-two (Control = 16 and Treatment = 16) four weeks old Ross broilers (308) were infested with the mite on skin of hock joins. Samples were collected after 1, 24, 72 hours and 10 days. The skin samples were fixed in 10% buffered formalin and histological sections were prepared using routine Hematoxylin & Eosin staining method. Results showed that in all cases, except within first hour of infestation, lymphocytic infiltration was always a constant pathologic feature. Necrosis of feather's follicles was a prominent pathologic feature ensued due to vascular disturbances and resulted in loss of feather. Hyperkeratosis, parakeratosis and acanthosis were observed after 72 hours. These findings reveal that mite biting induces local epidermal hyperplasia.

Chronic neuropathologies of single and repetitive TBI: substrates of dementia?

PubMed Central

Smith, Douglas H.; Johnson, Victoria E.; Stewart, William

2014-01-01

Traumatic brain injury (TBI) has long been recognized to be a risk factor for dementia. This association has, however, only recently gained widespread attention through the increased awareness of ‘chronic traumatic encephalopathy’ (CTE) in athletes exposed to repetitive head injury. Originally termed ‘dementia pugilistica’ and linked to a career in boxing, descriptions of the neuropathological features of CTE include brain atrophy, cavum septum pellucidum, and amyloid-β, tau and TDP-43 pathologies, many of which might contribute to clinical syndromes of cognitive impairment. Similar chronic pathologies are also commonly found years after just a single moderate to severe TBI. However, little consensus currently exists on specific features of these post-TBI syndromes that might permit their confident clinical and/or pathological diagnosis. Moreover, the mechanisms contributing to neurodegeneration following TBI largely remain unknown. Here, we review the current literature and controversies in the study of chronic neuropathological changes after TBI. PMID:23458973

"English Disease": Historical Notes on Rickets, the Bone-Lung Link and Child Neglect Issues.

PubMed

Zhang, Mingyong; Shen, Fan; Petryk, Anna; Tang, Jingfeng; Chen, Xingzhen; Sergi, Consolato

2016-11-15

Nutritional or classical rickets (here labeled as "rickets") is a worldwide disease involving mostly infants and young children having inadequate sunlight exposure, often associated with a low dietary intake of Vitamin D. Rickets targets all layers of society independently of economic status with historical information spanning more than two millennia. Vitamin D is critical for the absorption of calcium and prevention of rickets in children as well as osteomalacia in adults. The initial and misleading paradigm of the 19th and 20th centuries that rickets may have been the consequence of infection has been, indeed, reversed following the identification of the Vitamin D molecule's important role in the function of the immune system. Although traditionally considered limited to osteopathology, Vitamin D deficiency is now known to be linked to infection, inflammation, and carcinogenesis. In this review, we consider the key historical (Whistler, pre-Whistler and post-Whistler descriptors) and social facts around rickets; highlight the osteo-pathological features of rickets and the pathology of the upper and lower respiratory tract, stressing the fact that lungs remain the main secondary organ affected by Vitamin D deficiency; and emphasize the public health role in identifying the cases of child neglect or abuse based on the evaluation of the costochondral region.

Regulator of calcineurin 1 mediates pathological vascular wall remodeling

PubMed Central

Esteban, Vanesa; Méndez-Barbero, Nerea; Jesús Jiménez-Borreguero, Luis; Roqué, Mercè; Novensá, Laura; Belén García-Redondo, Ana; Salaices, Mercedes; Vila, Luis; Arbonés, María L.

2011-01-01

Artery wall remodeling, a major feature of diseases such as hypertension, restenosis, atherosclerosis, and aneurysm, involves changes in the tunica media mass that reduce or increase the vessel lumen. The identification of molecules involved in vessel remodeling could aid the development of improved treatments for these pathologies. Angiotensin II (AngII) is a key effector of aortic wall remodeling that contributes to aneurysm formation and restenosis through incompletely defined signaling pathways. We show that AngII induces vascular smooth muscle cell (VSMC) migration and vessel remodeling in mouse models of restenosis and aneurysm. These effects were prevented by pharmacological inhibition of calcineurin (CN) or lentiviral delivery of CN-inhibitory peptides. Whole-genome analysis revealed >1,500 AngII-regulated genes in VSMCs, with just 11 of them requiring CN activation. Of these, the most sensitive to CN activation was regulator of CN 1 (Rcan1). Rcan1 was strongly activated by AngII in vitro and in vivo and was required for AngII-induced VSMC migration. Remarkably, Rcan1−/− mice were resistant to AngII-induced aneurysm and restenosis. Our results indicate that aneurysm formation and restenosis share mechanistic elements and identify Rcan1 as a potential therapeutic target for prevention of aneurysm and restenosis progression. PMID:21930771

Beyond the zebrafish: diverse fish species for modeling human disease

PubMed Central

Schartl, Manfred

2014-01-01

ABSTRACT In recent years, zebrafish, and to a lesser extent medaka, have become widely used small animal models for human diseases. These organisms have convincingly demonstrated the usefulness of fish for improving our understanding of the molecular and cellular mechanisms leading to pathological conditions, and for the development of new diagnostic and therapeutic tools. Despite the usefulness of zebrafish and medaka in the investigation of a wide spectrum of traits, there is evidence to suggest that other fish species could be better suited for more targeted questions. With the emergence of new, improved sequencing technologies that enable genomic resources to be generated with increasing efficiency and speed, the potential of non-mainstream fish species as disease models can now be explored. A key feature of these fish species is that the pathological condition that they model is often related to specific evolutionary adaptations. By exploring these adaptations, new disease-causing and disease-modifier genes might be identified; thus, diverse fish species could be exploited to better understand the complexity of disease processes. In addition, non-mainstream fish models could allow us to study the impact of environmental factors, as well as genetic variation, on complex disease phenotypes. This Review will discuss the opportunities that such fish models offer for current and future biomedical research. PMID:24271780

Post-traumatic stress symptoms in pathological gambling: Potential evidence of anti-reward processes

PubMed Central

Green, Cheryl L.; Nahhas, Ramzi W.; Scoglio, Arielle A.; Elman, Igor

2017-01-01

Background Excessive gambling is considered to be a part of the addiction spectrum. Stress-like emotional states are a key feature both of pathological gambling (PG) and of substance addiction. In substance addiction, stress symptomatology has been attributed in part to “anti-reward” allostatic neuroadaptations, while a potential involvement of anti-reward processes in the course of PG has not yet been investigated. Methods To that end, individuals with PG (n = 22) and mentally healthy subjects (n = 13) were assessed for trauma exposure and post-traumatic stress symptomatology (PTSS) using the Life Events Checklist and the Civilian Mississippi Scale, respectively. Results In comparison with healthy subjects, individuals with PG had significantly greater PTSS scores including greater physiological arousal sub-scores. The number of traumatic events and their recency were not significantly different between the groups. In the PG group, greater gambling severity was associated with more PTSS, but neither with traumatic events exposure nor with their recency. Conclusions Our data replicate prior reports on the role of traumatic stress in the course of PG and extend those findings by suggesting that the link may be derived from the anti-reward-type neuroadaptation rather than from the traumatic stress exposure per se. PMID:28274137

Mitochondrial genetic background modulates bioenergetics and susceptibility to acute cardiac volume overload.

PubMed

Fetterman, Jessica L; Zelickson, Blake R; Johnson, Larry W; Moellering, Douglas R; Westbrook, David G; Pompilius, Melissa; Sammy, Melissa J; Johnson, Michelle; Dunham-Snary, Kimberly J; Cao, Xuemei; Bradley, Wayne E; Zhang, Jinju; Wei, Chih-Chang; Chacko, Balu; Schurr, Theodore G; Kesterson, Robert A; Dell'italia, Louis J; Darley-Usmar, Victor M; Welch, Danny R; Ballinger, Scott W

2013-10-15

Dysfunctional bioenergetics has emerged as a key feature in many chronic pathologies such as diabetes and cardiovascular disease. This has led to the mitochondrial paradigm in which it has been proposed that mtDNA sequence variation contributes to disease susceptibility. In the present study we show a novel animal model of mtDNA polymorphisms, the MNX (mitochondrial-nuclear exchange) mouse, in which the mtDNA from the C3H/HeN mouse has been inserted on to the C57/BL6 nuclear background and vice versa to test this concept. Our data show a major contribution of the C57/BL6 mtDNA to the susceptibility to the pathological stress of cardiac volume overload which is independent of the nuclear background. Mitochondria harbouring the C57/BL6J mtDNA generate more ROS (reactive oxygen species) and have a higher mitochondrial membrane potential relative to those with C3H/HeN mtDNA, independent of nuclear background. We propose this is the primary mechanism associated with increased bioenergetic dysfunction in response to volume overload. In summary, these studies support the 'mitochondrial paradigm' for the development of disease susceptibility, and show that the mtDNA modulates cellular bioenergetics, mitochondrial ROS generation and susceptibility to cardiac stress.

Mitochondrial Genetic Background Modulates Bioenergetics and Susceptibility to Acute Cardiac Volume – Overload

PubMed Central

Fetterman, Jessica L.; Zelickson, Blake R.; Johnson, Larry W.; Moellering, Douglas R.; Westbrook, David G.; Pompilius, Melissa; Sammy, Melissa J.; Johnson, Michelle; Dunham-Snary, Kimberly J.; Cao, Xuemei; Bradley, Wayne E.; Zhang, Jinju; Wei, Chih-Chang; Chacko, Balu; Schurr, Theodore G.; Kesterson, Robert A.; Dell’Italia, Louis J.; Darley-Usmar, Victor M.; Welch, Danny R.; Ballinger, Scott W.

2013-01-01

Synopsis Dysfunctional bioenergetics has emerged as a key feature in many chronic pathologies such as diabetes and cardiovascular disease. This has led to the mitochondrial paradigm in which it has been proposed that mitochondrial DNA (mtDNA) sequence variation contributes to disease susceptibility. In this study we present a novel animal model of mtDNA polymorphisms, the mitochondrial nuclear exchange mouse (MNX), in which the mtDNA from C3H/HeN mouse has been inserted onto the C57/BL6 nuclear background and vice versa to test this concept. Our data show a major contribution of the C57/BL6 mtDNA to the susceptibility to the pathological stress of cardiac volume overload which is independent of the nuclear background. Mitochondria harboring the C57/BL6J mtDNA generate more reactive oxygen species (ROS) and have a higher mitochondrial membrane potential relative to those having the C3H/HeN mtDNA, independent of nuclear background. We propose this is the primary mechanism associated with increased bioenergetic dysfunction in response to volume overload. In summary, these studies support the “mitochondrial paradigm” for the development of disease susceptibility, and show that the mtDNA modulates, cellular bioenergetics, mitochondrial reactive oxygen species generation and susceptibility to cardiac stress. PMID:23924350

“English Disease”: Historical Notes on Rickets, the Bone–Lung Link and Child Neglect Issues

PubMed Central

Zhang, Mingyong; Shen, Fan; Petryk, Anna; Tang, Jingfeng; Chen, Xingzhen; Sergi, Consolato

2016-01-01

Nutritional or classical rickets (here labeled as “rickets”) is a worldwide disease involving mostly infants and young children having inadequate sunlight exposure, often associated with a low dietary intake of Vitamin D. Rickets targets all layers of society independently of economic status with historical information spanning more than two millennia. Vitamin D is critical for the absorption of calcium and prevention of rickets in children as well as osteomalacia in adults. The initial and misleading paradigm of the 19th and 20th centuries that rickets may have been the consequence of infection has been, indeed, reversed following the identification of the Vitamin D molecule’s important role in the function of the immune system. Although traditionally considered limited to osteopathology, Vitamin D deficiency is now known to be linked to infection, inflammation, and carcinogenesis. In this review, we consider the key historical (Whistler, pre-Whistler and post-Whistler descriptors) and social facts around rickets; highlight the osteo-pathological features of rickets and the pathology of the upper and lower respiratory tract, stressing the fact that lungs remain the main secondary organ affected by Vitamin D deficiency; and emphasize the public health role in identifying the cases of child neglect or abuse based on the evaluation of the costochondral region. PMID:27854286

Cross Sectional Imaging of Solitary Lesions of the Neurocranium.

PubMed

Schäfer, Max-Ludwig; Koch, Arend; Streitparth, Florian; Wiener, Edzard

2017-12-01

Background  Although a wide range of processes along the neurocranium are of a benign nature, there are often difficulties in the differential diagnosis. Method  In the review CT/MRI scans of the head were evaluated retrospectively regarding solitary lesions along the neurocranium. The majority of the lesions were histologically proven. Results  The purpose of the review is to present typical pathologies of the neurocranium and provide a systematic overview based on 12 entities, their locations, prevalence and radiological characteristics. Conclusion  Processes, which primarily originate from the neurocranium have to be differentiated from secondary processes infiltrating the neurocranium. For this important diagnostic feature, MRI is typically essential, while the definitive diagnosis is often made on the basis of the medical history and the typical appearance on computer tomography. Key Points   · There are often difficulties in the precise differential diagnosis of solitary lesions along the neurocranium. Typical solitary pathologies of the neurocranium based on 12 entities were presented. Both magnetic resonance imaging and computed tomography are often essential for an exact differential diagnosis.. Citation Format · Schäfer M, Koch A, Streitparth F et al. Cross Sectional Diagnosis of Solitary Lesions of the Neurocranium. Fortschr Röntgenstr 2017; 189: 1135 - 1144. © Georg Thieme Verlag KG Stuttgart · New York.

The Prognostic and Clinicopathological Roles of Sirtuin-3 in Various Cancers.

PubMed

Yu, Fei-Yuan; Xu, Qian; Wu, Dan-Dan; Lau, Andy T Y; Xu, Yan-Ming

2016-01-01

Sirtuin-3 (SIRT3) is a major mitochondrial NAD(+)-dependent deacetylase and plays a key role in the progression and development of human cancers. Although the prognostic and clinicopathological features of SIRT3 expression in various cancers have been investigated by different research groups, however, inconsistent and opposing results can be observed. In this study, we therefore performed a meta-analysis to evaluate the significance of SIRT3 expression in various cancers. Systematic literature searching was performed in PubMed, Embase, China National Knowledge Infrastructure, and Wanfang Data up to November 2015. Total effect analyses and subgroup analyses were performed to evaluate the relationship between SIRT3 expression and overall survival, cancer/non-cancer tissues, lymph node metastasis, pathological differentiation, tumor node metastasis (TNM) stage, tumor size, and gender, in various cancer patients. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to clarify the risk or hazard association. A total of 14 studies comprising 2165 cancer patients were included to assess the association between SIRT3 immunohistochemical expression and overall survival or clinicopathological characteristics. SIRT3 expression was significantly associated with overall survival in gastric cancer (HR = 0.62, 95% CI = 0.43-0.89, P = 0.009) and hepatocellular carcinoma patients (HR = 0.56, 95% CI = 0.42-0.74, P<0.0001), cancer/non-cancer tissues in hepatocellular carcinoma patients (OR = 0.04, 95% CI = 0.01-0.16, P<0.0001), lymph node metastasis in breast cancer patients (OR = 2.20, 95% CI = 1.49-3.26, P<0.0001), and also pathological differentiation in hepatocellular carcinoma patients (OR = 0.69, 95% CI = 0.48-0.98, P = 0.04) and gastric cancer patients (OR = 0.33, 95% CI = 0.21-0.50, P<0.00001), by subgroup analyses. Furthermore, SIRT3 expression was significantly associated with pathological differentiation in total effect analysis (OR = 0.46, 95% CI = 0.29-0.74, P = 0.001). No detectable relation between SIRT3 expression and other clinicopathological parameters were found. This meta-analysis indicates that SIRT3 expression level is associated with prognostic and clinical features in specific cancers.

Analysis and Prediction of Myristoylation Sites Using the mRMR Method, the IFS Method and an Extreme Learning Machine Algorithm.

PubMed

Wang, ShaoPeng; Zhang, Yu-Hang; Huang, GuoHua; Chen, Lei; Cai, Yu-Dong

2017-01-01

Myristoylation is an important hydrophobic post-translational modification that is covalently bound to the amino group of Gly residues on the N-terminus of proteins. The many diverse functions of myristoylation on proteins, such as membrane targeting, signal pathway regulation and apoptosis, are largely due to the lipid modification, whereas abnormal or irregular myristoylation on proteins can lead to several pathological changes in the cell. To better understand the function of myristoylated sites and to correctly identify them in protein sequences, this study conducted a novel computational investigation on identifying myristoylation sites in protein sequences. A training dataset with 196 positive and 84 negative peptide segments were obtained. Four types of features derived from the peptide segments following the myristoylation sites were used to specify myristoylatedand non-myristoylated sites. Then, feature selection methods including maximum relevance and minimum redundancy (mRMR), incremental feature selection (IFS), and a machine learning algorithm (extreme learning machine method) were adopted to extract optimal features for the algorithm to identify myristoylation sites in protein sequences, thereby building an optimal prediction model. As a result, 41 key features were extracted and used to build an optimal prediction model. The effectiveness of the optimal prediction model was further validated by its performance on a test dataset. Furthermore, detailed analyses were also performed on the extracted 41 features to gain insight into the mechanism of myristoylation modification. This study provided a new computational method for identifying myristoylation sites in protein sequences. We believe that it can be a useful tool to predict myristoylation sites from protein sequences. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Hypochondriasis as an early manifestation of dementia with Lewy bodies: an autopsied case report.

PubMed

Fujishiro, Hiroshige; Iritani, Shuji; Sekiguchi, Hirotaka; Habuchi, Chikako; Torii, Youta; Matsunaga, Shinji; Ozaki, Norio; Yoshida, Mari; Fujita, Kiyoshi

2016-03-01

Discrepancies between clinical and pathological diagnoses of dementia with Lewy bodies (DLB) may occur because the full disease progression remains unclear, especially during the early stage. Herein, we report the case of a 78-year-old Japanese man with hypochondriasis who had autopsy-confirmed limbic-type DLB pathology. He exhibited no core clinical features of DLB. We attempted to identify the clinicopathological correlations in the early stages of DLB. At the age of 77, he became hypochondriacal and exhibited progressive cognitive decline after the death of his wife. He was concerned about his poor physical condition, but hospital examinations did not identify any overtly abnormal findings. At 78 years of age, he consulted a neurologist with complaints of facial numbness and irritability. Neurological examination revealed no overt abnormality, and he scored 21 points on the Mini-Mental State Examination. Magnetic resonance imaging of the brain showed mild bilateral ventricular enlargement. The patient was clinically diagnosed as having possible Alzheimer's disease. Approximately 1 month after his consult, he died of acute pneumonia in a psychiatric hospital to which he had been admitted for severe aggressive behaviour. He exhibited no core clinical features pointing towards a clinical diagnosis of DLB. Neuropathological investigation revealed limbic-type Lewy body disease with concurrent minimum Alzheimer-type pathology, which corresponds to high-likelihood DLB pathology based on the Third Consortium DLB pathological criteria. The patient had minimum nigral degeneration, which is consistent with the absence of parkinsonism. This autopsied case suggests that some DLB patients exhibit hypochondriasis in the early stage of the disease, even if they lack the core clinical features of DLB. © 2015 The Authors. Psychogeriatrics © 2015 Japanese Psychogeriatric Society.

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.

A natural language processing program effectively extracts key pathologic findings from radical prostatectomy reports.

PubMed

Kim, Brian J; Merchant, Madhur; Zheng, Chengyi; Thomas, Anil A; Contreras, Richard; Jacobsen, Steven J; Chien, Gary W

2014-12-01

Natural language processing (NLP) software programs have been widely developed to transform complex free text into simplified organized data. Potential applications in the field of medicine include automated report summaries, physician alerts, patient repositories, electronic medical record (EMR) billing, and quality metric reports. Despite these prospects and the recent widespread adoption of EMR, NLP has been relatively underutilized. The objective of this study was to evaluate the performance of an internally developed NLP program in extracting select pathologic findings from radical prostatectomy specimen reports in the EMR. An NLP program was generated by a software engineer to extract key variables from prostatectomy reports in the EMR within our healthcare system, which included the TNM stage, Gleason grade, presence of a tertiary Gleason pattern, histologic subtype, size of dominant tumor nodule, seminal vesicle invasion (SVI), perineural invasion (PNI), angiolymphatic invasion (ALI), extracapsular extension (ECE), and surgical margin status (SMS). The program was validated by comparing NLP results to a gold standard compiled by two blinded manual reviewers for 100 random pathology reports. NLP demonstrated 100% accuracy for identifying the Gleason grade, presence of a tertiary Gleason pattern, SVI, ALI, and ECE. It also demonstrated near-perfect accuracy for extracting histologic subtype (99.0%), PNI (98.9%), TNM stage (98.0%), SMS (97.0%), and dominant tumor size (95.7%). The overall accuracy of NLP was 98.7%. NLP generated a result in <1 second, whereas the manual reviewers averaged 3.2 minutes per report. This novel program demonstrated high accuracy and efficiency identifying key pathologic details from the prostatectomy report within an EMR system. NLP has the potential to assist urologists by summarizing and highlighting relevant information from verbose pathology reports. It may also facilitate future urologic research through the rapid and automated creation of large databases.

Clinicopathological correlations in behavioural variant frontotemporal dementia.

PubMed

Perry, David C; Brown, Jesse A; Possin, Katherine L; Datta, Samir; Trujillo, Andrew; Radke, Anneliese; Karydas, Anna; Kornak, John; Sias, Ana C; Rabinovici, Gil D; Gorno-Tempini, Maria Luisa; Boxer, Adam L; De May, Mary; Rankin, Katherine P; Sturm, Virginia E; Lee, Suzee E; Matthews, Brandy R; Kao, Aimee W; Vossel, Keith A; Tartaglia, Maria Carmela; Miller, Zachary A; Seo, Sang Won; Sidhu, Manu; Gaus, Stephanie E; Nana, Alissa L; Vargas, Jose Norberto S; Hwang, Ji-Hye L; Ossenkoppele, Rik; Brown, Alainna B; Huang, Eric J; Coppola, Giovanni; Rosen, Howard J; Geschwind, Daniel; Trojanowski, John Q; Grinberg, Lea T; Kramer, Joel H; Miller, Bruce L; Seeley, William W

2017-12-01

Accurately predicting the underlying neuropathological diagnosis in patients with behavioural variant frontotemporal dementia (bvFTD) poses a daunting challenge for clinicians but will be critical for the success of disease-modifying therapies. We sought to improve pathological prediction by exploring clinicopathological correlations in a large bvFTD cohort. Among 438 patients in whom bvFTD was either the top or an alternative possible clinical diagnosis, 117 had available autopsy data, including 98 with a primary pathological diagnosis of frontotemporal lobar degeneration (FTLD), 15 with Alzheimer's disease, and four with amyotrophic lateral sclerosis who lacked neurodegenerative disease-related pathology outside of the motor system. Patients with FTLD were distributed between FTLD-tau (34 patients: 10 corticobasal degeneration, nine progressive supranuclear palsy, eight Pick's disease, three frontotemporal dementia with parkinsonism associated with chromosome 17, three unclassifiable tauopathy, and one argyrophilic grain disease); FTLD-TDP (55 patients: nine type A including one with motor neuron disease, 27 type B including 21 with motor neuron disease, eight type C with right temporal lobe presentations, and 11 unclassifiable including eight with motor neuron disease), FTLD-FUS (eight patients), and one patient with FTLD-ubiquitin proteasome system positive inclusions (FTLD-UPS) that stained negatively for tau, TDP-43, and FUS. Alzheimer's disease was uncommon (6%) among patients whose only top diagnosis during follow-up was bvFTD. Seventy-nine per cent of FTLD-tau, 86% of FTLD-TDP, and 88% of FTLD-FUS met at least 'possible' bvFTD diagnostic criteria at first presentation. The frequency of the six core bvFTD diagnostic features was similar in FTLD-tau and FTLD-TDP, suggesting that these features alone cannot be used to separate patients by major molecular class. Voxel-based morphometry revealed that nearly all pathological subgroups and even individual patients share atrophy in anterior cingulate, frontoinsula, striatum, and amygdala, indicating that degeneration of these regions is intimately linked to the behavioural syndrome produced by these diverse aetiologies. In addition to these unifying features, symptom profiles also differed among pathological subtypes, suggesting distinct anatomical vulnerabilities and informing a clinician's prediction of pathological diagnosis. Data-driven classification into one of the 10 most common pathological diagnoses was most accurate (up to 60.2%) when using a combination of known predictive factors (genetic mutations, motor features, or striking atrophy patterns) and the results of a discriminant function analysis that incorporated clinical, neuroimaging, and neuropsychological data. © 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.

Evaluating stability of histomorphometric features across scanner and staining variations: predicting biochemical recurrence from prostate cancer whole slide images

NASA Astrophysics Data System (ADS)

Leo, Patrick; Lee, George; Madabhushi, Anant

2016-03-01

Quantitative histomorphometry (QH) is the process of computerized extraction of features from digitized tissue slide images. Typically these features are used in machine learning classifiers to predict disease presence, behavior and outcome. Successful robust classifiers require features that both discriminate between classes of interest and are stable across data from multiple sites. Feature stability may be compromised by variation in slide staining and scanning procedures. These laboratory specific variables include dye batch, slice thickness and the whole slide scanner used to digitize the slide. The key therefore is to be able to identify features that are not only discriminating between the classes of interest (e.g. cancer and non-cancer or biochemical recurrence and non- recurrence) but also features that will not wildly fluctuate on slides representing the same tissue class but from across multiple different labs and sites. While there has been some recent efforts at understanding feature stability in the context of radiomics applications (i.e. feature analysis of radiographic images), relatively few attempts have been made at studying the trade-off between feature stability and discriminability for histomorphometric and digital pathology applications. In this paper we present two new measures, preparation-induced instability score (PI) and latent instability score (LI), to quantify feature instability across and within datasets. Dividing PI by LI yields a ratio for how often a feature for a specific tissue class (e.g. low grade prostate cancer) is different between datasets from different sites versus what would be expected from random chance alone. Using this ratio we seek to quantify feature vulnerability to variations in slide preparation and digitization. Since our goal is to identify stable QH features we evaluate these features for their stability and thus inclusion in machine learning based classifiers in a use case involving prostate cancer. Specifically we examine QH features which may predict 5 year biochemical recurrence for prostate cancer patients who have undergone radical prostatectomy from digital slide images of surgically excised tissue specimens, 5 year biochemical recurrence being a strong predictor of disease recurrence. In this study we evaluated the ability of our feature robustness indices to identify the most stable and predictive features of 5 year biochemical recurrence using digitized slide images of surgically excised prostate cancer specimens from 80 different patients across 4 different sites. A total of 242 features from 5 different feature families were investigated to identify the most stable QH features from our set. Our feature robustness indices (PI and LI) suggested that five feature families (graph, shape, co-occurring gland tensors, gland sub-graphs, texture) were susceptible to variations in slide preparation and digitization across various sites. The family least affected was shape features in which 19.3% of features varied across laboratories while the most vulnerable family, at 55.6%, was the gland disorder features. However the disorder features were the most stable within datasets being different between random halves of a dataset in an average of just 4.1% of comparisons while texture features were the most unstable being different at a rate of 4.7%. We also compared feature stability across two datasets before and after color normalization. Color normalization decreased feature stability with 8% and 34% of features different between the two datasets in two outcome groups prior to normalization and 49% and 51% different afterwards. Our results appear to suggest that evaluation of QH features across multiple sites needs to be undertaken to assess robustness and class discriminability alone should not represent the benchmark for selection of QH features to build diagnostic and prognostic digital pathology classifiers.

Secure image retrieval with multiple keys

NASA Astrophysics Data System (ADS)

Liang, Haihua; Zhang, Xinpeng; Wei, Qiuhan; Cheng, Hang

2018-03-01

This article proposes a secure image retrieval scheme under a multiuser scenario. In this scheme, the owner first encrypts and uploads images and their corresponding features to the cloud; then, the user submits the encrypted feature of the query image to the cloud; next, the cloud compares the encrypted features and returns encrypted images with similar content to the user. To find the nearest neighbor in the encrypted features, an encryption with multiple keys is proposed, in which the query feature of each user is encrypted by his/her own key. To improve the key security and space utilization, global optimization and Gaussian distribution are, respectively, employed to generate multiple keys. The experiments show that the proposed encryption can provide effective and secure image retrieval for each user and ensure confidentiality of the query feature of each user.

A practical guide to assessing clinical decision-making skills using the key features approach.

PubMed

Farmer, Elizabeth A; Page, Gordon

2005-12-01

This paper in the series on professional assessment provides a practical guide to writing key features problems (KFPs). Key features problems test clinical decision-making skills in written or computer-based formats. They are based on the concept of critical steps or 'key features' in decision making and represent an advance on the older, less reliable patient management problem (PMP) formats. The practical steps in writing these problems are discussed and illustrated by examples. Steps include assembling problem-writing groups, selecting a suitable clinical scenario or problem and defining its key features, writing the questions, selecting question response formats, preparing scoring keys, reviewing item quality and item banking. The KFP format provides educators with a flexible approach to testing clinical decision-making skills with demonstrated validity and reliability when constructed according to the guidelines provided.

Clinical Correlations With Lewy Body Pathology in LRRK2-Related Parkinson Disease

PubMed Central

Kalia, Lorraine V.; Lang, Anthony E.; Hazrati, Lili-Naz; Fujioka, Shinsuke; Wszolek, Zbigniew K.; Dickson, Dennis W.; Ross, Owen A.; Van Deerlin, Vivianna M.; Trojanowski, John Q.; Hurtig, Howard I.; Alcalay, Roy N.; Marder, Karen S.; Clark, Lorraine N.; Gaig, Carles; Tolosa, Eduardo; Ruiz-Martínez, Javier; Marti-Masso, Jose F.; Ferrer, Isidre; de Munain, Adolfo López; Goldman, Samuel M.; Schüle, Birgitt; Langston, J. William; Aasly, Jan O.; Giordana, Maria T.; Bonifati, Vincenzo; Puschmann, Andreas; Canesi, Margherita; Pezzoli, Gianni; De Paula, Andre Maues; Hasegawa, Kazuko; Duyckaerts, Charles; Brice, Alexis; Stoessl, A. Jon; Marras, Connie

2015-01-01

IMPORTANCE Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of genetic Parkinson disease (PD) known to date. The clinical features of manifesting LRRK2 mutation carriers are generally indistinguishable from those of patients with sporadic PD. However, some PD cases associated with LRRK2 mutations lack Lewy bodies (LBs), a neuropathological hallmark of PD. We investigated whether the presence or absence of LBs correlates with different clinical features in LRRK2-related PD. OBSERVATIONS We describe genetic, clinical, and neuropathological findings of 37 cases of LRRK2-related PD including 33 published and 4 unpublished cases through October 2013. Among the different mutations, the LRRK2 p.G2019S mutation was most frequently associated with LB pathology. Nonmotor features of cognitive impairment/dementia, anxiety, and orthostatic hypotension were correlated with the presence of LBs. In contrast, a primarily motor phenotype was associated with a lack of LBs. CONCLUSIONS AND RELEVANCE To our knowledge, this is the first report of clinicopathological correlations in a series of LRRK2-related PD cases. Findings from this selected group of patients with PD demonstrated that parkinsonian motor features can occur in the absence of LBs. However, LB pathology in LRRK2-related PD may be a marker for a broader parkinsonian symptom complex including cognitive impairment. PMID:25401511

Supervised learning methods for pathological arterial pulse wave differentiation: A SVM and neural networks approach.

PubMed

Paiva, Joana S; Cardoso, João; Pereira, Tânia

2018-01-01

The main goal of this study was to develop an automatic method based on supervised learning methods, able to distinguish healthy from pathologic arterial pulse wave (APW), and those two from noisy waveforms (non-relevant segments of the signal), from the data acquired during a clinical examination with a novel optical system. The APW dataset analysed was composed by signals acquired in a clinical environment from a total of 213 subjects, including healthy volunteers and non-healthy patients. The signals were parameterised by means of 39pulse features: morphologic, time domain statistics, cross-correlation features, wavelet features. Multiclass Support Vector Machine Recursive Feature Elimination (SVM RFE) method was used to select the most relevant features. A comparative study was performed in order to evaluate the performance of the two classifiers: Support Vector Machine (SVM) and Artificial Neural Network (ANN). SVM achieved a statistically significant better performance for this problem with an average accuracy of 0.9917±0.0024 and a F-Measure of 0.9925±0.0019, in comparison with ANN, which reached the values of 0.9847±0.0032 and 0.9852±0.0031 for Accuracy and F-Measure, respectively. A significant difference was observed between the performances obtained with SVM classifier using a different number of features from the original set available. The comparison between SVM and NN allowed reassert the higher performance of SVM. The results obtained in this study showed the potential of the proposed method to differentiate those three important signal outcomes (healthy, pathologic and noise) and to reduce bias associated with clinical diagnosis of cardiovascular disease using APW. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuropathology in movement disorders.

PubMed Central

Gibb, W R

1989-01-01

This review concentrates on the definition and classification of degenerative movement disorders in which Parkinsonian symptoms are often prominent. The pathological spectrum and clinical manifestations of Lewy body disease are described, and associations with Alzheimer's disease and motor neuron disease are explored. A classification of pallidonigral degenerations is based on clinical features, distribution of pathology, and morphological abnormalities; some of these patients have mild nigral degeneration and no Parkinsonian features. Many other juvenile and familial Parkinsonian cases are not included among the pallidonigral degenerations. Most of these latter syndromes have been organised into preliminary groups, in particular, autosomal dominant dystonia-Parkinson syndrome, juvenile Parkinsonian disorder and autosomal dominant Lewy body disease. Images PMID:2547027

Giant cell angiofibroma misdiagnosed as a vascular malformation and treated with absolute alcohol for one year: a case report and review of the literature.

PubMed

He, Yue; Zhang, Chenping; Liu, Guanglong; Tian, Zhuowei; Wang, Lizhen; Kalfarentzos, Evagelos

2014-04-24

To present the clinical, imaging, pathological and immunohistochemical features of giant cell angiofibroma (GCA). In this paper we report an atypical case of a GCA extending from the parotid to the parapharyngeal space. The lesion was being treated as a vascular malformation for one year prior to surgical removal. We summarize the clinical manifestations, imaging, pathological and molecular features of this rare disease.After complete surgical removal of the tumor, immunohistochemical analysis revealed strong positivity for the mesenchymal markers vimentin, CD34, CD31 and CD99 in neoplastic cells. Tumor proliferation antigen marker Ki67 was partly positive (<5% of cells). Tumor cells were negative for muscle-specific actin, epithelial membrane antigen, smooth muscle actin, cytokeratin pan, S100, desmin, glial fibrillary acidic protein, myogenin, MyoD1 and F8. The morphological and immunohistochemical profile was consistent with the diagnosis of GCA. GCA is a rare soft tissue tumor that can easily be misdiagnosed in the clinical preoperative setting. In view of the clinical, pathological and molecular features of the tumor, complete surgical removal is the current optimal treatment option, providing accurate diagnosis and low to minimal recurrence rate.

Ultrasound features in trisomy 13 (Patau syndrome) and trisomy 18 (Edwards syndrome) in a consecutive series of 47 cases.

PubMed

Kroes, I; Janssens, S; Defoort, P

2014-01-01

To determine and list the variety of the predominant appeal signs leading to referral and their accompanying features found during specialized ultrasound evaluation in foetuses with trisomy 13 and trisomy 18. In a period of thirty years, 1110 cases of foetal malformations were detected during specialized echographic evaluation. 47 Of these cases were foetuses with trisomy 13 or trisomy 18. We evaluated the predominant signs leading to referral, the difference and overlap in presenting signs between both syndromes and when the data were available, we also compared the echographic signs with the foetal pathology. In foetuses with trisomy 13 the most common malformations were craniofacial defects, cerebral malformations and genitourinary tract anomalies. The most common malformations associated with trisomy 18 were limb abnormalities and intrauterine growth restriction. Most malformations were predominant in trisomy 18, except for genitourinary tract anomalies. In most cases the sonographic signs correlated with the pathology findings. Trisomy 13 as well as trisomy 18 are characterized by a number of various malformations in the foetus. Most of the ultrasound features were predominant in foetuses with trisomy 18. Mostly the foetal pathology correlated with the sonographic evaluation.

[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.

Automatic intelligibility classification of sentence-level pathological speech

PubMed Central

Kim, Jangwon; Kumar, Naveen; Tsiartas, Andreas; Li, Ming; Narayanan, Shrikanth S.

2014-01-01

Pathological speech usually refers to the condition of speech distortion resulting from atypicalities in voice and/or in the articulatory mechanisms owing to disease, illness or other physical or biological insult to the production system. Although automatic evaluation of speech intelligibility and quality could come in handy in these scenarios to assist experts in diagnosis and treatment design, the many sources and types of variability often make it a very challenging computational processing problem. In this work we propose novel sentence-level features to capture abnormal variation in the prosodic, voice quality and pronunciation aspects in pathological speech. In addition, we propose a post-classification posterior smoothing scheme which refines the posterior of a test sample based on the posteriors of other test samples. Finally, we perform feature-level fusions and subsystem decision fusion for arriving at a final intelligibility decision. The performances are tested on two pathological speech datasets, the NKI CCRT Speech Corpus (advanced head and neck cancer) and the TORGO database (cerebral palsy or amyotrophic lateral sclerosis), by evaluating classification accuracy without overlapping subjects’ data among training and test partitions. Results show that the feature sets of each of the voice quality subsystem, prosodic subsystem, and pronunciation subsystem, offer significant discriminating power for binary intelligibility classification. We observe that the proposed posterior smoothing in the acoustic space can further reduce classification errors. The smoothed posterior score fusion of subsystems shows the best classification performance (73.5% for unweighted, and 72.8% for weighted, average recalls of the binary classes). PMID:25414544

Response monitoring of breast cancer patients receiving neoadjuvant chemotherapy using quantitative ultrasound, texture, and molecular features

PubMed Central

Gangeh, Mehrdad; Tadayyon, Hadi; Sadeghi-Naini, Ali; Gandhi, Sonal; Wright, Frances C.; Slodkowska, Elzbieta; Curpen, Belinda; Tran, William; Czarnota, Gregory J.

2018-01-01

Background Pathological response of breast cancer to chemotherapy is a prognostic indicator for long-term disease free and overall survival. Responses of locally advanced breast cancer in the neoadjuvant chemotherapy (NAC) settings are often variable, and the prediction of response is imperfect. The purpose of this study was to detect primary tumor responses early after the start of neoadjuvant chemotherapy using quantitative ultrasound (QUS), textural analysis and molecular features in patients with locally advanced breast cancer. Methods The study included ninety six patients treated with neoadjuvant chemotherapy. Breast tumors were scanned with a clinical ultrasound system prior to chemotherapy treatment, during the first, fourth and eighth week of treatment, and prior to surgery. Quantitative ultrasound parameters and scatterer-based features were calculated from ultrasound radio frequency (RF) data within tumor regions of interest. Additionally, texture features were extracted from QUS parametric maps. Prior to therapy, all patients underwent a core needle biopsy and histological subtypes and biomarker ER, PR, and HER2 status were determined. Patients were classified into three treatment response groups based on combination of clinical and pathological analyses: complete responders (CR), partial responders (PR), and non-responders (NR). Response classifications from QUS parameters, receptors status and pathological were compared. Discriminant analysis was performed on extracted parameters using a support vector machine classifier to categorize subjects into CR, PR, and NR groups at all scan times. Results Of the 96 patients, the number of CR, PR and NR patients were 21, 52, and 23, respectively. The best prediction of treatment response was achieved with the combination mean QUS values, texture and molecular features with accuracies of 78%, 86% and 83% at weeks 1, 4, and 8, after treatment respectively. Mean QUS parameters or clinical receptors status alone predicted the three response groups with accuracies less than 60% at all scan time points. Recurrence free survival (RFS) of response groups determined based on combined features followed similar trend as determined based on clinical and pathology. Conclusions This work demonstrates the potential of using QUS, texture and molecular features for predicting the response of primary breast tumors to chemotherapy early, and guiding the treatment planning of refractory patients. PMID:29298305

Acinar Cell Carcinoma of the Pancreas: Overview of Clinicopathologic Features and Insights into the Molecular Pathology.

PubMed

La Rosa, Stefano; Sessa, Fausto; Capella, Carlo

2015-01-01

Acinar cell carcinomas (ACCs) of the pancreas are rare pancreatic neoplasms accounting for about 1-2% of pancreatic tumors in adults and about 15% in pediatric subjects. They show different clinical symptoms at presentation, different morphological features, different outcomes, and different molecular alterations. This heterogeneous clinicopathological spectrum may give rise to difficulties in the clinical and pathological diagnosis with consequential therapeutic and prognostic implications. The molecular mechanisms involved in the onset and progression of ACCs are still not completely understood, although in recent years, several attempts have been made to clarify the molecular mechanisms involved in ACC biology. In this paper, we will review the main clinicopathological and molecular features of pancreatic ACCs of both adult and pediatric subjects to give the reader a comprehensive overview of this rare tumor type.

Coronary Microvascular Disease in Chronic Chagas Cardiomyopathy Including an Overview on History, Pathology, and Other Proposed Pathogenic Mechanisms

PubMed Central

Rossi, Marcos A.; Tanowitz, Herbert B.; Malvestio, Lygia M.; Celes, Mara R.; Campos, Erica C.; Blefari, Valdecir; Prado, Cibele M.

2010-01-01

This review focuses on the short and bewildered history of Brazilian scientist Carlos Chagas's discovery and subsequent developments, the anatomopathological features of chronic Chagas cardiomyopathy (CCC), an overview on the controversies surrounding theories concerning its pathogenesis, and studies that support the microvascular hypothesis to further explain the pathological features and clinical course of CCC. It is our belief that knowledge of this particular and remarkable cardiomyopathy will shed light not only on the microvascular involvement of its pathogenesis, but also on the pathogenetic processes of other cardiomyopathies, which will hopefully provide a better understanding of the various changes that may lead to an end-stage heart disease with similar features. This review is written to celebrate the 100th anniversary of the discovery of Chagas disease. PMID:20824217

A new set of wavelet- and fractals-based features for Gleason grading of prostate cancer histopathology images

NASA Astrophysics Data System (ADS)

Mosquera Lopez, Clara; Agaian, Sos

2013-02-01

Prostate cancer detection and staging is an important step towards patient treatment selection. Advancements in digital pathology allow the application of new quantitative image analysis algorithms for computer-assisted diagnosis (CAD) on digitized histopathology images. In this paper, we introduce a new set of features to automatically grade pathological images using the well-known Gleason grading system. The goal of this study is to classify biopsy images belonging to Gleason patterns 3, 4, and 5 by using a combination of wavelet and fractal features. For image classification we use pairwise coupling Support Vector Machine (SVM) classifiers. The accuracy of the system, which is close to 97%, is estimated through three different cross-validation schemes. The proposed system offers the potential for automating classification of histological images and supporting prostate cancer diagnosis.

An exploratory study of clinical measures associated with subsyndromal pathological gambling in patients with binge eating disorder.

PubMed

Yip, Sarah W; White, Marney A; Grilo, Carlos M; Potenza, Marc N

2011-06-01

Both binge eating disorder (BED) and pathological gambling (PG) are characterized by impairments in impulse control. Subsyndromal levels of PG have been associated with measures of adverse health. The nature and significance of PG features in individuals with BED is unknown. Ninety-four patients with BED (28 men and 66 women) were classified by gambling group based on inclusionary criteria for Diagnostic and Statistical Manual-IV (DSM-IV) PG and compared on a range of behavioral, psychological and eating disorder (ED) psychopathology variables. One individual (1.1% of the sample) met criteria for PG, although 18.7% of patients with BED displayed one or more DSM-IV criteria for PG, hereafter referred to as problem gambling features. Men were more likely than women to have problem gambling features. BED patients with problem gambling features were distinguished by lower self-esteem and greater substance problem use. After controlling for gender, findings of reduced self-esteem and increased substance problem use among patients with problem gambling features remained significant. In patients with BED, problem gambling features are associated with a number of heightened clinical problems.

A report on the clinical-pathological correlations of 788 gingival lesion

PubMed Central

Carbone, Mario; Broccoletti, Roberto; Carcieri, Paola; Conrotto, Davide; Carrozzo, Marco; Arduino, Paolo G.

2017-01-01

Background The diagnosis and treatment of a variety of non-plaque related gingival diseases have become an integrated aspect of everyday dentistry. The aim of this study was to analyse the relationship between clinical appearance and histopathological features of gingival lesions in a large Northern Italian population. Material and Methods A retrospective study of 788 cases of gingival and alveolar mucosal biopsies was set up. Statistical analysis was performed by calculating the odds ratio and 95% confidence interval (C.I.), in order to assess the degree of association between the clinical parameters considered (primary lesions) and the single pathologies, statistically evaluated by Mantel-Haenszel tests. The correlation between clinical and histological diagnosis was classified as follow: 1) expected data (ED): provisional clinical diagnosis; 2) real data (RD): final histopathology diagnosis; 3) concordant data (CD): correspondence between the expected data and real data. The correlation was calculated as follow: CC (complete concordance) = CD x 100 / ED, this expressing the percentage in which the clinical and the histological diagnosis overlapped. Results The most frequently observed and biopsied primary lesions resulted to be exophytic, followed by mucosal colour changes and finally by losses of substance. The statistically significant association between primary lesion and their manifestation in gingival pathologies was reported. Volume increases, for instance, were positively correlated to plasma cell epulis, pyogenic granuloma, fibrous reactive hyperplasia and hemangioma. Verrucous-papillary lesions were most often seen in verrucous carcinoma, verrucous leukoplakia and mild dysplasia. White lesion resulted to be related to leukoplakia or oral lichen planus. Red lesions resulted to be related only oral lichen planus. Erosive vesicle-bullous lesions were linked to disimmune pathologies. Ulcerative lesions were positively associated to oral squamous cell cancer. Finally, potentially malignant disorders have the most percentage high concordance. Among the malignant lesions, the correlation increased up to the squamous cell carcinoma and leukaemia. Conclusions This article presented the frequency and the clinico-pathological concordance of all primary lesions and the histopathological diagnosis of gingival lesions. For every primary lesion, it is possible to correlate a specific histopathological diagnosis in a statistical manner. This can be a valuable aid for not specialist clinicians who daily observe mucosae and have the opportunity to intercept major diseases. Key words:Gingival lesions; clinical appearance; histological analysis; clinico-pathological correlation. PMID:29053652

Pathological gambling: an impulse control disorder? Measurement of impulsivity using neurocognitive tests.

PubMed

Dannon, Pinhas N; Shoenfeld, Netta; Rosenberg, Oded; Kertzman, Semion; Kotler, Moshe

2010-04-01

Pathological gambling is classified in the DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders) and in the ICD-10 (International Classification of Disease) as an impulse control disorder. The association between impulsivity and pathological gambling remains a matter of debate: some researchers find high levels of impulsivity within pathological gamblers, others report no difference compared to controls, and yet others even suggest that it is lower. In this review we examine the relationship between pathological gambling and impulsivity assessed by various neurocognitive tests. These tests--the Stroop task, the Stop Signal Task, the Matching Familiar Figures Task, the Iowa Gambling Task, the Wisconsin Card Sorting Test, the Tower of London test, and the Continuous Performance Test--demonstrated less impulsivity in gambling behavior. The differences in performance between pathological gamblers and healthy controls on the neurocognitive tasks could be due to addictive behavior features rather than impulsive behavior.

Role of targeted magnetic resonance imaging sequences in the surgical management of anterior skull base pathology.

PubMed

Chawla, S; Bowman, J; Gandhi, M; Panizza, B

2017-01-01

The skull base is a highly complex anatomical region that provides passage for important nerves and vessels as they course into and out of the cranial cavity. Key to the management of pathology in this region is a thorough understanding of the anatomy, with its variations, and the relationship of various neurovascular structures to the pathology in question. Targeted high-resolution magnetic resonance imaging on high field strength magnets can enable the skull base surgeon to understand this intricate relationship and deal with the pathology from a position of relative advantage. With the help of case studies, this paper illustrates the application of specialised magnetic resonance techniques to study pathology of the orbital apex in particular. The fine anatomical detail provided gives surgeons the ability to design an endonasal endoscopic procedure appropriate to the anatomy of the pathology.

Could MRI Be Used To Image Kidney Fibrosis? A Review of Recent Advances and Remaining Barriers.

PubMed

Leung, General; Kirpalani, Anish; Szeto, Stephen G; Deeb, Maya; Foltz, Warren; Simmons, Craig A; Yuen, Darren A

2017-06-07

A key contributor to the progression of nearly all forms of CKD is fibrosis, a largely irreversible process that drives further kidney injury. Despite its importance, clinicians currently have no means of noninvasively assessing renal scar, and thus have historically relied on percutaneous renal biopsy to assess fibrotic burden. Although helpful in the initial diagnostic assessment, renal biopsy remains an imperfect test for fibrosis measurement, limited not only by its invasiveness, but also, because of the small amounts of tissue analyzed, its susceptibility to sampling bias. These concerns have limited not only the prognostic utility of biopsy analysis and its ability to guide therapeutic decisions, but also the clinical translation of experimental antifibrotic agents. Recent advances in imaging technology have raised the exciting possibility of magnetic resonance imaging (MRI)-based renal scar analysis, by capitalizing on the differing physical features of fibrotic and nonfibrotic tissue. In this review, we describe two key fibrosis-induced pathologic changes (capillary loss and kidney stiffening) that can be imaged by MRI techniques, and the potential for these new MRI-based technologies to noninvasively image renal scar. Copyright © 2017 by the American Society of Nephrology.

Microbiota, a key player in alcoholic liver disease.

PubMed

Cassard, Anne-Marie; Ciocan, Dragos

2017-12-22

Alcoholic liver disease (ALD) is a major cause of morbidity and mortality worldwide. Only 20% of heavy alcohol consumers develop alcoholic liver cirrhosis. The intestinal microbiota (IM) has been recently identified as a key player in the severity of liver injury in ALD. Common features of ALD include a decrease of gut epithelial tight junction protein expression, mucin production, and antimicrobial peptide levels. This disruption of the gut barrier, which is a prerequisite for ALD, leads to the passage of bacterial products into the blood stream (endotoxemia). Moreover, metabolites produced by bacteria, such as short chain fatty acids, volatile organic compounds (VOS), and bile acids (BA), are involved in ALD pathology. Probiotic treatment, IM transplantation, or the consumption of dietary fiber, such as pectin, which all alter the ratio of bacterial species, have been shown to improve liver injury in animal models of ALD and to be associated with an improvement in gut barrier function. Although the connections between the microbiota and the host in ALD are well established, the underlying mechanisms are still an active area of research. Targeting the microbiome through the use of prebiotic, probiotic, and postbiotic modalities could be an attractive new approach to manage ALD.

Could MRI Be Used To Image Kidney Fibrosis? A Review of Recent Advances and Remaining Barriers

PubMed Central

Leung, General; Kirpalani, Anish; Szeto, Stephen G.; Deeb, Maya; Foltz, Warren; Simmons, Craig A.

2017-01-01

A key contributor to the progression of nearly all forms of CKD is fibrosis, a largely irreversible process that drives further kidney injury. Despite its importance, clinicians currently have no means of noninvasively assessing renal scar, and thus have historically relied on percutaneous renal biopsy to assess fibrotic burden. Although helpful in the initial diagnostic assessment, renal biopsy remains an imperfect test for fibrosis measurement, limited not only by its invasiveness, but also, because of the small amounts of tissue analyzed, its susceptibility to sampling bias. These concerns have limited not only the prognostic utility of biopsy analysis and its ability to guide therapeutic decisions, but also the clinical translation of experimental antifibrotic agents. Recent advances in imaging technology have raised the exciting possibility of magnetic resonance imaging (MRI)–based renal scar analysis, by capitalizing on the differing physical features of fibrotic and nonfibrotic tissue. In this review, we describe two key fibrosis-induced pathologic changes (capillary loss and kidney stiffening) that can be imaged by MRI techniques, and the potential for these new MRI-based technologies to noninvasively image renal scar. PMID:28298435

Inclusion-Body Myositis Associated with Alzheimer's Disease

PubMed Central

Levacic, Danijela; Peddareddygari, Leema Reddy; Nochlin, David; Sharer, Leroy R.; Grewal, Raji P.

2013-01-01

Sporadic inclusion-body myositis (s-IBM) is a myopathy that is characterized by progressive weakness and muscle pathology demonstrating inflammation and rimmed vacuoles. In addition, similar to the pathology observed in the brains of patients with Alzheimer's disease, the deposition of beta-amyloid and phosphorylated tau proteins in muscle fibers has been reported. These shared pathologic features have prompted hypotheses suggesting a shared etiology of these two conditions. We report a case of a 73-year-old woman initially diagnosed with s-IBM who later developed Alzheimer's disease. PMID:23606855

Colorectal tumors: the histology report.

PubMed

Lanza, Giovanni; Messerini, Luca; Gafà, Roberta; Risio, Mauro

2011-03-01

Epithelial colorectal tumors are common pathologic entities. Their histology report should be comprehensive of a series of pathologic parameters essential for the correct clinical management of the patients. Diagnostic histologic criteria of adenomatous, serrated, inflammatory, and hamartomatous polyps and of polyposis syndromes are discussed. In addition, the pathologic features of early and advanced colorectal cancer are described and a checklist is given. Finally, molecular prognostic and predictive factors currently employed in the treatment of colorectal cancer are discussed. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd.. All rights reserved.

A Clinical and Pathological Overview of Vulvar Condyloma Acuminatum, Intraepithelial Neoplasia, and Squamous Cell Carcinoma

PubMed Central

Léonard, Boris; Kridelka, Frederic; Delbecque, Katty; Goffin, Frederic; Demoulin, Stéphanie; Doyen, Jean; Delvenne, Philippe

2014-01-01

Condyloma acuminatum, intraepithelial neoplasia, and squamous cell carcinoma are three relatively frequent vulvar lesions. Condyloma acuminatum is induced by low risk genotypes of human papillomavirus (HPV). Vulvar intraepithelial neoplasia (VIN) and squamous cell carcinoma have different etiopathogenic pathways and are related or not with high risk HPV types. The goal of this paper is to review the main pathological and clinical features of these lesions. A special attention has been paid also to epidemiological data, pathological classification, and clinical implications of these diseases. PMID:24719870

Mitochondrial DNA replication, nucleoside reverse-transcriptase inhibitors, and AIDS cardiomyopathy.

PubMed

Lewis, William

2003-01-01

Nucleoside reverse-transcriptase inhibitors (NRTIs) in combination with other antiretrovirals (HAART) are the cornerstones of current AIDS therapy, but extensive use brought mitochondrial side effects to light. Clinical experience, pharmacological, cell, and molecular biological evidence links altered mitochondrial (mt-) DNA replication to the toxicity of NRTIs in many tissues, and conversely, mtDNA replication defects and mtDNA depletion in target tissues are observed. Organ-specific pathological changes or diverse systemic effects result from and are frequently attributed to HAART in which NRTIs are included. The shared features of mtDNA depletion and energy depletion became key observations and related the clinical and in vivo experimental findings to inhibition of mtDNA replication by NRTI triphosphates in vitro. Subsequent to those findings, other observations suggested that mitochondrial energy deprivation is concomitant with or the result of mitochondrial oxidative stress in AIDS (from HIV, for example) or from NRTI therapy itself. Copyright 2003, Elsevier Science (USA)

Ultra-structural study of insulin granules in pancreatic β-cells of db/db mouse by scanning transmission electron microscopy tomography.

PubMed

Xue, Yanhong; Zhao, Wei; Du, Wen; Zhang, Xiang; Ji, Gang; Ying, Wang; Xu, Tao

2012-07-01

Insulin granule trafficking is a key step in the secretion of glucose-stimulated insulin from pancreatic β-cells. The main feature of type 2 diabetes (T2D) is the failure of pancreatic β-cells to secrete sufficient amounts of insulin to maintain normal blood glucose levels. In this work, we developed and applied tomography based on scanning transmission electron microscopy (STEM) to image intact insulin granules in the β-cells of mouse pancreatic islets. Using three-dimensional (3D) reconstruction, we found decreases in both the number and the grey level of insulin granules in db/db mouse pancreatic β-cells. Moreover, insulin granules were closer to the plasma membrane in diabetic β-cells than in control cells. Thus, 3D ultra-structural tomography may provide new insights into the pathology of insulin secretion in T2D.

Study of anti-cancer effects of chemotherapeutic agents and radiotherapy in breast cancer patients using fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Chithra, K.; Vijayaraghavan, S.; Prakasarao, Aruna; Singaravelu, Ganesan

2017-02-01

The analysis of the variations in the spectroscopic patterns of the key bio molecules using Native fluorescence spectroscopy, without exogenous labels, has emerged as a new trend in the characterization of the Physiological State and the Discrimination of Pathological from normal conditions of cells and tissues as the relative concentration of these bio-molecules serve as markers in evaluating the presence of cancer in the body. The aim of this unique study is to use these features of Optical spectroscopy in monitoring the behavior of cells to treatment and thus to evaluate the response to Chemotherapeutic agents and Radiation in Breast Cancer Patients. The results of the study conducted using NFS of Human blood plasma of biopsy proved Breast Cancer patients undergoing treatment are promising, enhancing the scope of Native fluorescence Spectroscopy emerging as a promising technology in the evaluation of Therapeutic Response in Breast Cancer Patients.

Hepatic steatosis and fibrosis: Non-invasive assessment

PubMed Central

Karanjia, Rustam N; Crossey, Mary M E; Cox, I Jane; Fye, Haddy K S; Njie, Ramou; Goldin, Robert D; Taylor-Robinson, Simon D

2016-01-01

Chronic liver disease is a major cause of morbidity and mortality worldwide and usually develops over many years, as a result of chronic inflammation and scarring, resulting in end-stage liver disease and its complications. The progression of disease is characterised by ongoing inflammation and consequent fibrosis, although hepatic steatosis is increasingly being recognised as an important pathological feature of disease, rather than being simply an innocent bystander. However, the current gold standard method of quantifying and staging liver disease, histological analysis by liver biopsy, has several limitations and can have associated morbidity and even mortality. Therefore, there is a clear need for safe and non-invasive assessment modalities to determine hepatic steatosis, inflammation and fibrosis. This review covers key mechanisms and the importance of fibrosis and steatosis in the progression of liver disease. We address non-invasive imaging and blood biomarker assessments that can be used as an alternative to information gained on liver biopsy. PMID:28018096

Glycogen synthase kinase-3 (GSK-3) inhibitors for the treatment of Alzheimer's disease.

PubMed

Medina, Miguel; Avila, Jesús

2010-01-01

Originally discovered because of its role in the regulation of glucose metabolism, Glycogen Synthase Kinase-3 (GSK-3) it is now recognised as a crucial player in a diverse series of cellular processes involved in Alzheimer's disease (AD) pathology. Besides having been identified as the major tau protein kinase, GSK-3 mediates Aβ neurotoxicity, plays an essential role in synaptic plasticity and memory, might be involved in Aβ formation, and it has an important role in inflammation and neuronal survival, all key features of AD neuropathology. Moreover, AD was one of the earliest disorders linked to GSK-3 dysfunction. Thus, the discovery of small molecule GSK-3 inhibitors has attracted significant attention to the protein both as therapeutic target for the therapeutic intervention in neurodegenerative diseases as well as a means to understand the molecular basis of these disorders.

Autoimmune Encephalitis: Pathophysiology and Imaging Review of an Overlooked Diagnosis.

PubMed

Kelley, B P; Patel, S C; Marin, H L; Corrigan, J J; Mitsias, P D; Griffith, B

2017-06-01

Autoimmune encephalitis is a relatively new category of immune-mediated disease involving the central nervous system that demonstrates a widely variable spectrum of clinical presentations, ranging from the relatively mild or insidious onset of cognitive impairment to more complex forms of encephalopathy with refractory seizure. Due to its diverse clinical features, which can mimic a variety of other pathologic processes, autoimmune encephalitis presents a diagnostic challenge to clinicians. Imaging findings in patients with these disorders can also be quite variable, but recognizing characteristic findings within limbic structures suggestive of autoimmune encephalitis can be a key step in alerting clinicians to the potential diagnosis and ensuring a prompt and appropriate clinical work-up. In this article, we review antibody-mediated encephalitis and its various subtypes with a specific emphasis on the role of neuroimaging in the diagnostic work-up. © 2017 by American Journal of Neuroradiology.

Narrowband UVB-induced lichen planus pemphigoide

PubMed Central

Mandy Chan, Wai Man; See Lee, Joyce Siong; Thiam Theng, Colin Seng; Chua, Sze Hon; Boon Oon, Hazel Hwee

2011-01-01

Lichen planus pemphigoides (LPP) is an autoimmune disease characterised by evolution of subepidermal blisters on normal and lichen planus affected skin. We describe a case of LPP in a 54-year-old Chinese woman. The patient presented with psoriasiform plaques and was diagnosed with guttate psoriasis. Narrowband ultraviolet B (NBUVB) therapy was commenced, and she experienced a generalised eruption of violaceous papules, bullae over the lower limbs, and Wickham's striae over the buccal mucosa. Histology from a plaque revealed interface dermatitis, while a specimen from a blister showed subepidermal bulla. Direct immunofluorescence showed linear deposition of IgG and C3 along the basement membrane. A diagnosis of LPP was made on clinicopathological grounds. This is the first case report of NBUVB alone in unmasking LPP. In this case report, we describe the pathological mechanism of NBUVB in the development of LPP and key features distinguishing LPP from bullous lupus erythematosus, bullous lichen planus, bullous pemphigoid, and psoriasis. PMID:25386295

Ferroptosis and Cell Death Analysis by Flow Cytometry.

PubMed

Chen, Daishi; Eyupoglu, Ilker Y; Savaskan, Nicolai

2017-01-01

Cell death and its recently discovered regulated form ferroptosis are characterized by distinct morphological, electrophysiological, and pharmacological features. In particular ferroptosis can be induced by experimental compounds and clinical drugs (i.e., erastin, sulfasalazine, sorafenib, and artesunate) in various cell types and cancer cells. Pharmacologically, this cell death process can be inhibited by iron chelators and lipid peroxidation inhibitors. Relevance of this specific cell death form has been found in different pathological conditions such as cancer, neurotoxicity, neurodegeneration, and ischemia. Distinguishing cell viability and cell death is essential for experimental and clinical applications and a key component in flow cytometry experiments. Dead cells can compromise the integrity of the data by nonspecific binding of antibodies and dyes. Therefore it is essential that dead cells are robustly and reproducibly identified and characterized by means of cytometry application. Here we describe a procedure to detect and quantify cell death and its specific form ferroptosis based on standard flow cytometry techniques.

Current issues in diagnostic breast pathology.

PubMed

Walker, Rosemary A; Hanby, Andy; Pinder, Sarah E; Thomas, Jeremy; Ellis, Ian O

2012-09-01

On behalf of the NHS Breast Screening Programme Pathology Coordinating Group we present recommendations for terminology and diagnostic criteria for a number of key areas of practice in breast pathology where terminology can be confusing and where accurate communication will ensure appropriate clinical management. These recommendations cover columnar cell lesions and the spectrum of changes that can be seen in these epithelial proliferations, lobular neoplasia, micrometastases and isolated tumour cells in axillary lymph nodes, the use of basal/myoepithelial markers in diagnostic practice and oestrogen receptor testing in ductal carcinoma in situ.

Demystifying MR Neurography of the Lumbosacral Plexus: From Protocols to Pathologies

PubMed Central

Muniz Neto, Francisco J.; Kihara Filho, Eduardo N.; Miranda, Frederico C.; Rosemberg, Laercio A.; Santos, Durval C. B.

2018-01-01

Magnetic resonance neurography is a high-resolution imaging technique that allows evaluating different neurological pathologies in correlation to clinical and the electrophysiological data. The aim of this article is to present a review on the anatomy of the lumbosacral plexus nerves, along with imaging protocols, interpretation pitfalls, and most common pathologies that should be recognized by the radiologist: traumatic, iatrogenic, entrapment, tumoral, infectious, and inflammatory conditions. An extensive series of clinical and imaging cases is presented to illustrate key-points throughout the article. PMID:29662907

Clinico-pathological features of kidney disease in diabetic cases.

PubMed

Furuichi, Kengo; Shimizu, Miho; Okada, Hirokazu; Narita, Ichiei; Wada, Takashi

2018-03-21

Diabetic kidney disease is the major cause of end-stage kidney disease in developed countries. However, the onset of kidney disorder and the progression pattern of kidney dysfunction and proteinuria greatly vary cases by cases. Therefore, risk classification with clinical data and pathological findings is important. Recent clinico-pathological study with kidney biopsy samples from diabetic patients revealed that pathological changes of diabetic nephropathy are characteristic and have special impacts on prognosis in each clinical stage. Moreover, comparison of the clinico-pathological findings of diabetic nephropathy with hypertensive nephrosclerosis revealed that there are few differences in their pathological findings in cases with low albuminuria and preserved estimated glomerular filtration rate (eGFR). Because it is so difficult to clearly distinguish pure kidney lesions caused by diabetes and kidney lesions due to effects other than diabetes, it is vital that these overlapped pathological findings be confirmed on kidney biopsy in cases of early stage diabetes. Further research is warranted regarding the pathogenesis of diabetic nephropathy and indication of kidney biopsy in diabetic cases.

Summary of third Nordic symposium on digital pathology.

PubMed

Lundström, Claes; Waltersson, Marie; Persson, Anders; Treanor, Darren

2016-01-01

Cross-disciplinary and cross-sectorial collaboration is a key success factor for turning the promise of digital pathology into actual clinical benefits. The Nordic symposium on digital pathology (NDP) was created to promote knowledge exchange in this area, among stakeholders in health care, industry, and academia. This article is a summary of the third NDP symposium in Linkφping, Sweden. The Nordic experiences, including several hospitals using whole-slide imaging for substantial parts of their primary reviews, formed a fertile base for discussions among the 190 NDP attendees originating from 15 different countries. This summary also contains results from a survey on adoption and validation aspects of clinical digital pathology use.

Summary of third Nordic symposium on digital pathology

PubMed Central

Lundström, Claes; Waltersson, Marie; Persson, Anders; Treanor, Darren

2016-01-01

Cross-disciplinary and cross-sectorial collaboration is a key success factor for turning the promise of digital pathology into actual clinical benefits. The Nordic symposium on digital pathology (NDP) was created to promote knowledge exchange in this area, among stakeholders in health care, industry, and academia. This article is a summary of the third NDP symposium in Linkφping, Sweden. The Nordic experiences, including several hospitals using whole-slide imaging for substantial parts of their primary reviews, formed a fertile base for discussions among the 190 NDP attendees originating from 15 different countries. This summary also contains results from a survey on adoption and validation aspects of clinical digital pathology use. PMID:27141318

Microvesicating effects of sulfur mustard on an in vitro human skin model.

PubMed

Hayden, Patrick J; Petrali, John P; Stolper, Gina; Hamilton, Tracey A; Jackson, George R; Wertz, Philip W; Ito, Susumu; Smith, William J; Klausner, Mitchell

2009-10-01

Bis-(beta-chloroethyl) sulfide (SM) is a potent skin vesicant previously used for chemical warfare. Progress in determination of the mechanistic basis of SM pathology, and development of prophylactic and/or therapeutic countermeasures to SM exposure has been hampered by lack of physiologically relevant models of human skin. The current work evaluated a newly developed tissue engineered full-thickness human skin model in a completely in vitro approach to investigation of SM-induced dermal pathology. The model was first characterized with regard to overall morphology, lipid composition, basement membrane (BM) composition and ultrastructural features that are important targets of SM pathologic activity. Well-developed BM ultrastructural features were observed at the dermal-epidermal junction (DEJ), thus demonstrating successful resolution of a primary deficiency of models previously evaluated for SM studies. Studies were then conducted to evaluate histopathological effects of SM on the model. Good replication of in vivo effects was observed, including apoptosis of basal keratinocytes (KC) and microblister formation at the DEJ. Tissue engineered skin models with well-developed basement membrane structures thus appear to be useful tools for in vitro mechanistic studies of SM vesicant activity and development of preventive/therapeutic approaches for SM pathology.

[Clinical and pathological features of Alport syndrome in children].

PubMed

Zhu, Chun-Hua; Huang, Song-Ming; Wu, Hong-Mei; Bao, Hua-Ying; Chen, Ying; Han, Yuan; Zhao, Fei; Zhang, Ai-Hua; Zhang, Wei-Zhen

2010-03-01

To study the clinical and pathological features of Alport syndrome in children. The clinical and histopathological data of 10 hospitalized children with Alport syndrome from February 2007 to February 2009 were retrospectively reviewed. There were 7 males and 3 females, with the age ranging from 2 years to 6 years and 7 months (mean 3 years and 2 months). Five of 10 cases had positive family history. X-linked dominant inheritance Alport syndrome was diagnosed in 8 cases, and autosomal recessive inheritance Alport syndrome in 2 cases. Recurrent gross hematuria was found in 5 cases, hematuria and proteinuria in 3 cases, massive proteinuria in 1 case, and nephritic syndrome in 1 case. Under the light microscope, 8 cases presented with mesangial proliferation glomerulonephritis, and 2 cases with focal segmental glomerulosclerosis. Immunofluorescence assay showed that all cases had IgM deposition in glomerulus. Only 1 case showed typical glomerular basement membrane (GBM) pathological changes. All cases showed abnormal alpha-chain distribution in renal collagen IV. The children with Alport syndrome have diverse clinical manifestations. Characteristic histopathological presentations could not be found under a light microscope, mesangial proliferation glomerulonephritis is the dominant pathological change, and IgM deposition in glomerulus is common. The GBM pathological change in children is not common. Immunofluorescence assay of alpha-chain in collagen IV is needed for the diagnosis of Alport syndrome.

Multi Texture Analysis of Colorectal Cancer Continuum Using Multispectral Imagery

PubMed Central

Chaddad, Ahmad; Desrosiers, Christian; Bouridane, Ahmed; Toews, Matthew; Hassan, Lama; Tanougast, Camel

2016-01-01

Purpose This paper proposes to characterize the continuum of colorectal cancer (CRC) using multiple texture features extracted from multispectral optical microscopy images. Three types of pathological tissues (PT) are considered: benign hyperplasia, intraepithelial neoplasia and carcinoma. Materials and Methods In the proposed approach, the region of interest containing PT is first extracted from multispectral images using active contour segmentation. This region is then encoded using texture features based on the Laplacian-of-Gaussian (LoG) filter, discrete wavelets (DW) and gray level co-occurrence matrices (GLCM). To assess the significance of textural differences between PT types, a statistical analysis based on the Kruskal-Wallis test is performed. The usefulness of texture features is then evaluated quantitatively in terms of their ability to predict PT types using various classifier models. Results Preliminary results show significant texture differences between PT types, for all texture features (p-value < 0.01). Individually, GLCM texture features outperform LoG and DW features in terms of PT type prediction. However, a higher performance can be achieved by combining all texture features, resulting in a mean classification accuracy of 98.92%, sensitivity of 98.12%, and specificity of 99.67%. Conclusions These results demonstrate the efficiency and effectiveness of combining multiple texture features for characterizing the continuum of CRC and discriminating between pathological tissues in multispectral images. PMID:26901134

Bladder cancer treatment response assessment with radiomic, clinical, and radiologist semantic features

NASA Astrophysics Data System (ADS)

Gordon, Marshall N.; Cha, Kenny H.; Hadjiiski, Lubomir M.; Chan, Heang-Ping; Cohan, Richard H.; Caoili, Elaine M.; Paramagul, Chintana; Alva, Ajjai; Weizer, Alon Z.

2018-02-01

We are developing a decision support system for assisting clinicians in assessment of response to neoadjuvant chemotherapy for bladder cancer. Accurate treatment response assessment is crucial for identifying responders and improving quality of life for non-responders. An objective machine learning decision support system may help reduce variability and inaccuracy in treatment response assessment. We developed a predictive model to assess the likelihood that a patient will respond based on image and clinical features. With IRB approval, we retrospectively collected a data set of pre- and post- treatment CT scans along with clinical information from surgical pathology from 98 patients. A linear discriminant analysis (LDA) classifier was used to predict the likelihood that a patient would respond to treatment based on radiomic features extracted from CT urography (CTU), a radiologist's semantic feature, and a clinical feature extracted from surgical and pathology reports. The classification accuracy was evaluated using the area under the ROC curve (AUC) with a leave-one-case-out cross validation. The classification accuracy was compared for the systems based on radiomic features, clinical feature, and radiologist's semantic feature. For the system based on only radiomic features the AUC was 0.75. With the addition of clinical information from examination under anesthesia (EUA) the AUC was improved to 0.78. Our study demonstrated the potential of designing a decision support system to assist in treatment response assessment. The combination of clinical features, radiologist semantic features and CTU radiomic features improved the performance of the classifier and the accuracy of treatment response assessment.

Automatic lumbar vertebrae detection based on feature fusion deep learning for partial occluded C-arm X-ray images.

PubMed

Yang Li; Wei Liang; Yinlong Zhang; Haibo An; Jindong Tan

2016-08-01

Automatic and accurate lumbar vertebrae detection is an essential step of image-guided minimally invasive spine surgery (IG-MISS). However, traditional methods still require human intervention due to the similarity of vertebrae, abnormal pathological conditions and uncertain imaging angle. In this paper, we present a novel convolutional neural network (CNN) model to automatically detect lumbar vertebrae for C-arm X-ray images. Training data is augmented by DRR and automatic segmentation of ROI is able to reduce the computational complexity. Furthermore, a feature fusion deep learning (FFDL) model is introduced to combine two types of features of lumbar vertebrae X-ray images, which uses sobel kernel and Gabor kernel to obtain the contour and texture of lumbar vertebrae, respectively. Comprehensive qualitative and quantitative experiments demonstrate that our proposed model performs more accurate in abnormal cases with pathologies and surgical implants in multi-angle views.

The Pathology of Reactive Lymphadenopathies: A Discussion of Common Reactive Patterns and Their Malignant Mimics.

PubMed

Slack, Graham W

2016-09-01

-Distinguishing between a reactive and a neoplastic lymphoid proliferation is a clinically significant task frequently performed by the surgical pathologist in routine practice. -To highlight common situations in lymph node pathology where reactive changes and lymphoma may be misdiagnosed. -Data sources are peer-reviewed journal articles, textbooks, and clinical experience. -This review aims to refresh and enhance the surgical pathologist's awareness of the shared and distinguishing features of select reactive and neoplastic lymphoproliferations, which in turn will allow the surgical pathologist to make more accurate diagnoses and avoid the pitfalls of misdiagnosis. This will be done by describing a selection of commonly encountered reactive histologic changes observed in lymph nodes, present the lymphomas with which they share overlapping features, outline the features that distinguish them, and describe an approach to making an accurate diagnosis and avoiding a misdiagnosis in each scenario.

Automatic Detection of Sand Ripple Features in Sidescan Sonar Imagery

DTIC Science & Technology

2014-07-09

Among the features used in forensic scientific fingerprint analysis are terminations or bifurcations of print ridges. Sidescan sonar imagery of ripple...always be pathological cases. The size of the blocks of pixels used in determining the ripple wavelength is evident in the output images on the right in

Granulomatous lobular mastitis.

PubMed

Going, J J; Anderson, T J; Wilkinson, S; Chetty, U

1987-05-01

The clinical and pathological features of nine cases of granulomatous mastitis were compared with those of 10 cases of duct ectasia/periductal mastitis (DE/PM), all of which were associated with active granulomatous inflammation. Granulomatous mastitis affects a younger age group, and although there is some overlap with DE/PM, it has distinctive pathological features, particularly a lobule centred distribution, for which the term "granulomatous lobular mastitis" is recommended. There is a strong tendency for persistence or recurrence. Our cases of granulomatous mastitis all occurred in parous women, five of them within three years of pregnancy. Awareness of this condition is important, because surgery does not offer the best treatment of recurrent disease, and trials of adequate drug treatment, including corticosteroids, are required.

Some problems of human adaptation and ecology under the aspect of general pathology

NASA Technical Reports Server (NTRS)

Kaznacheyev, V. P.

1980-01-01

The main problems of human adaptation at the level of the body and the population in connection with the features of current morbidity of the population and certain demographic processes are analyzed. The concepts of health and adaptation of the individual and human populations are determined. The importance of the anthropo-ecological approach to the investigation of the adaptation process of human populations is demonstrated. Certain features of the etiopathogenesis of diseases are considered in connection with the population-ecological regularities of human adaptation. The importance of research on general pathology aspects of adaptation and the ecology of man for planning, and organization of public health protection is discussed.

[Nasal NK/T cell lymphoma with outstanding performance of ocular symptoms].

PubMed

Liu, Lei; Zhao, Yulin; Wang, Jia; Ma, Fei

2012-09-01

To investigate the clinical features and misdiagnosis of nasal NK/T cell lymphoma with outstanding performance in ocular symptoms. Clinical data of 11 patients who had nasal NK/T cell lymphoma with the outstanding performances in ocular symptoms during 2009 to 2011 were retrospectively analyzed. The rate of misdiagnosis in the first diagnosis and first pathological diagnosis were 72.7% and 27.3% respectively. Nasal NK/T cell lymphoma with obvious ocular symptoms developed quickly and had almost special imaging findings. Nasal NK/T cell lymphoma with outstanding performance of ocular symptoms can be easily misdiagnosed. Comprehensive consideration of the clinical features, imaging findings and pathological examination do help to make accurate diagnosis early.

Intraosseous schwannoma in schwannomatosis.

PubMed

Kashima, T G; Gibbons, M R J P; Whitwell, D; Gibbons, C L M H; Bradley, K M; Ostlere, S J; Athanasou, N A

2013-12-01

This study investigates the clinical, radiological, and pathological features of two cases of intraosseous schwannoma that arose in patients with multiple soft tissue schwannomas. In both cases, the patients were adult females and the tibial bone was affected. Vestibular schwannomas were not identified, indicating that these were not cases of neurofibromatosis 2 (NF2). Radiographs showed a well-defined lytic lesion in the proximal tibia; in one case, this was associated with a pathological fracture. Histologically, both cases showed typical features of benign schwannoma. Molecular analysis of one of the excised tumors showed different alterations in the NF2 gene in keeping with a diagnosis of schwannomatosis. Our findings show for the first time that intraosseous schwannomas can occur in schwannomatosis.

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

PubMed

Ardestani, Amin; Lupse, Blaz; Maedler, Kathrin

2018-05-05

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

Anatomic pathology laboratory information systems: a review.

PubMed

Park, Seung Lyung; Pantanowitz, Liron; Sharma, Gaurav; Parwani, Anil Vasdev

2012-03-01

The modern anatomic pathology laboratory depends on a reliable information infrastructure to register specimens, record gross and microscopic findings, regulate laboratory workflow, formulate and sign out report(s), disseminate them to the intended recipients across the whole health system, and support quality assurance measures. This infrastructure is provided by the Anatomical Pathology Laboratory Information Systems (APLIS), which have evolved over decades and now are beginning to support evolving technologies like asset tracking and digital imaging. As digital pathology transitions from "the way of the future" to "the way of the present," the APLIS continues to be one of the key effective enablers of the scope and practice of pathology. In this review, we discuss the evolution, necessary components, architecture and functionality of the APLIS that are crucial to today's practicing pathologist and address the demands of emerging trends on the future APLIS.

Endocytic vesicle rupture is a conserved mechanism of cellular invasion by amyloid proteins.

PubMed

Flavin, William P; Bousset, Luc; Green, Zachary C; Chu, Yaping; Skarpathiotis, Stratos; Chaney, Michael J; Kordower, Jeffrey H; Melki, Ronald; Campbell, Edward M

2017-10-01

Numerous pathological amyloid proteins spread from cell to cell during neurodegenerative disease, facilitating the propagation of cellular pathology and disease progression. Understanding the mechanism by which disease-associated amyloid protein assemblies enter target cells and induce cellular dysfunction is, therefore, key to understanding the progressive nature of such neurodegenerative diseases. In this study, we utilized an imaging-based assay to monitor the ability of disease-associated amyloid assemblies to rupture intracellular vesicles following endocytosis. We observe that the ability to induce vesicle rupture is a common feature of α-synuclein (α-syn) assemblies, as assemblies derived from WT or familial disease-associated mutant α-syn all exhibited the ability to induce vesicle rupture. Similarly, different conformational strains of WT α-syn assemblies, but not monomeric or oligomeric forms, efficiently induced vesicle rupture following endocytosis. The ability to induce vesicle rupture was not specific to α-syn, as amyloid assemblies of tau and huntingtin Exon1 with pathologic polyglutamine repeats also exhibited the ability to induce vesicle rupture. We also observe that vesicles ruptured by α-syn are positive for the autophagic marker LC3 and can accumulate and fuse into large, intracellular structures resembling Lewy bodies in vitro. Finally, we show that the same markers of vesicle rupture surround Lewy bodies in brain sections from PD patients. These data underscore the importance of this conserved endocytic vesicle rupture event as a damaging mechanism of cellular invasion by amyloid assemblies of multiple neurodegenerative disease-associated proteins, and suggest that proteinaceous inclusions such as Lewy bodies form as a consequence of continued fusion of autophagic vesicles in cells unable to degrade ruptured vesicles and their amyloid contents.

Atherosclerosis and Alzheimer - diseases with a common cause? Inflammation, oxysterols, vasculature

PubMed Central

2014-01-01

Background Aging is accompanied by increasing vulnerability to pathologies such as atherosclerosis (ATH) and Alzheimer disease (AD). Are these different pathologies, or different presentations with a similar underlying pathoetiology? Discussion Both ATH and AD involve inflammation, macrophage infiltration, and occlusion of the vasculature. Allelic variants in common genes including APOE predispose to both diseases. In both there is strong evidence of disease association with viral and bacterial pathogens including herpes simplex and Chlamydophila. Furthermore, ablation of components of the immune system (or of bone marrow-derived macrophages alone) in animal models restricts disease development in both cases, arguing that both are accentuated by inflammatory/immune pathways. We discuss that amyloid β, a distinguishing feature of AD, also plays a key role in ATH. Several drugs, at least in mouse models, are effective in preventing the development of both ATH and AD. Given similar age-dependence, genetic underpinnings, involvement of the vasculature, association with infection, Aβ involvement, the central role of macrophages, and drug overlap, we conclude that the two conditions reflect different manifestations of a common pathoetiology. Mechanism Infection and inflammation selectively induce the expression of cholesterol 25-hydroxylase (CH25H). Acutely, the production of ‘immunosterol’ 25-hydroxycholesterol (25OHC) defends against enveloped viruses. We present evidence that chronic macrophage CH25H upregulation leads to catalyzed esterification of sterols via 25OHC-driven allosteric activation of ACAT (acyl-CoA cholesterol acyltransferase/SOAT), intracellular accumulation of cholesteryl esters and lipid droplets, vascular occlusion, and overt disease. Summary We postulate that AD and ATH are both caused by chronic immunologic challenge that induces CH25H expression and protection against particular infectious agents, but at the expense of longer-term pathology. PMID:24656052

Dysregulation of synaptic proteins, dendritic spine abnormalities and pathological plasticity of synapses as experience-dependent mediators of cognitive and psychiatric symptoms in Huntington's disease.

PubMed

Nithianantharajah, J; Hannan, A J

2013-10-22

Huntington's disease (HD) is an autosomal dominant tandem repeat expansion disorder involving cognitive, psychiatric and motor symptoms. The expanded trinucleotide (CAG) repeat leads to an extended polyglutamine tract in the huntingtin protein and a subsequent cascade of molecular and cellular pathogenesis. One of the key features of neuropathology, which has been shown to precede the eventual loss of neurons in the cerebral cortex, striatum and other areas, are changes to synapses, including the dendritic protrusions known as spines. In this review we will focus on synapse and spine pathology in HD, including molecular and experience-dependent aspects of pathogenesis. Dendritic spine pathology has been found in both the human HD brain at post mortem as well as various transgenic and knock-in animal models. These changes may help explain the symptoms in HD, and synaptopathy within the cerebral cortex may be particularly important in mediating the psychiatric and cognitive manifestations of this disease. The earliest stages of synaptic dysfunction in HD, as assayed in various mouse models, appears to involve changes in synaptic proteins and associated physiological abnormalities such as synaptic plasticity deficits. In mouse models, synaptic and cortical plasticity deficits have been directly correlated with the onset of cognitive deficits, implying a causal link. Furthermore, following the discovery that environmental enrichment can delay onset of affective, cognitive and motor deficits in HD transgenic mice, specific synaptic molecules shown to be dysregulated by the polyglutamine-induced toxicity were also found to be beneficially modulated by environmental stimulation. This identifies potential molecular targets for future therapeutic developments to treat this devastating disease. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Dopamine and Opioid Neurotransmission in Behavioral Addictions: A Comparative PET Study in Pathological Gambling and Binge Eating.

PubMed

Majuri, Joonas; Joutsa, Juho; Johansson, Jarkko; Voon, Valerie; Alakurtti, Kati; Parkkola, Riitta; Lahti, Tuuli; Alho, Hannu; Hirvonen, Jussi; Arponen, Eveliina; Forsback, Sarita; Kaasinen, Valtteri

2017-04-01

Although behavioral addictions share many clinical features with drug addictions, they show strikingly large variation in their behavioral phenotypes (such as in uncontrollable gambling or eating). Neurotransmitter function in behavioral addictions is poorly understood, but has important implications in understanding its relationship with substance use disorders and underlying mechanisms of therapeutic efficacy. Here, we compare opioid and dopamine function between two behavioral addiction phenotypes: pathological gambling (PG) and binge eating disorder (BED). Thirty-nine participants (15 PG, 7 BED, and 17 controls) were scanned with [ 11 C]carfentanil and [ 18 F]fluorodopa positron emission tomography using a high-resolution scanner. Binding potentials relative to non-displaceable binding (BP ND ) for [ 11 C]carfentanil and influx rate constant (K i ) values for [ 18 F]fluorodopa were analyzed with region-of-interest and whole-brain voxel-by-voxel analyses. BED subjects showed widespread reductions in [ 11 C]carfentanil BP ND in multiple subcortical and cortical brain regions and in striatal [ 18 F]fluorodopa K i compared with controls. In PG patients, [ 11 C]carfentanil BP ND was reduced in the anterior cingulate with no differences in [ 18 F]fluorodopa K i compared with controls. In the nucleus accumbens, a key region involved in reward processing, [ 11 C]Carfentanil BP ND was 30-34% lower and [ 18 F]fluorodopa K i was 20% lower in BED compared with PG and controls (p<0.002). BED and PG are thus dissociable as a function of dopaminergic and opioidergic neurotransmission. Compared with PG, BED patients show widespread losses of mu-opioid receptor availability together with presynaptic dopaminergic defects. These findings highlight the heterogeneity underlying the subtypes of addiction and indicate differential mechanisms in the expression of pathological behaviors and responses to treatment.

Transferrin receptor 1 upregulation in primary tumor and downregulation in benign kidney is associated with progression and mortality in renal cell carcinoma patients

PubMed Central

Greene, Christopher J.; Attwood, Kristopher; Sharma, Nitika J.; Gross, Kenneth W.; Smith, Gary J.; Xu, Bo; Kauffman, Eric C.

2017-01-01

The central dysregulated pathway of clear cell (cc) renal cell carcinoma (RCC), the von Hippel Lindau/hypoxia inducible factor-α axis, is a key regulator of intracellular iron levels, however the role of iron uptake in human RCC tumorigenesis and progression remains unknown. We conducted a thorough, large-scale investigation of the expression and prognostic significance of the primary iron uptake protein, transferrin receptor 1 (TfR1/CD71/TFRC), in RCC patients. TfR1 immunohistochemistry was performed in over 1500 cores from 574 renal cell tumor patient tissues (primary tumors, matched benign kidneys, metastases) and non-neoplastic tissues from 36 different body sites. TfR1 levels in RCC tumors, particularly ccRCC, were significantly associated with adverse clinical prognostic features (anemia, lower body mass index, smoking), worse tumor pathology (size, stage, grade, multifocality, sarcomatoid dedifferentiation) and worse survival outcomes, including after adjustments for tumor pathology. Highest TfR1 tissue levels in the non-gravid body were detected in benign renal tubule epithelium. Opposite to TfR1 changes in the primary tumor, TfR1 levels in benign kidney dropped during tumor progression and were inversely associated with worse survival outcomes, independent of tumor pathology. Quantitative measurement of TfR1 subcellular localization in cell lines demonstrated mixed cytoplasmic and membranous expression with increased TfR1 in clusters in ccRCC versus benign renal cell lines. Results of this study support an important role for TfR1 in RCC progression and identify TfR1 as a novel RCC biomarker and therapeutic target. PMID:29291011

Atherosclerosis and Alzheimer--diseases with a common cause? Inflammation, oxysterols, vasculature.

PubMed

Lathe, Richard; Sapronova, Alexandra; Kotelevtsev, Yuri

2014-03-21

Aging is accompanied by increasing vulnerability to pathologies such as atherosclerosis (ATH) and Alzheimer disease (AD). Are these different pathologies, or different presentations with a similar underlying pathoetiology? Both ATH and AD involve inflammation, macrophage infiltration, and occlusion of the vasculature. Allelic variants in common genes including APOE predispose to both diseases. In both there is strong evidence of disease association with viral and bacterial pathogens including herpes simplex and Chlamydophila. Furthermore, ablation of components of the immune system (or of bone marrow-derived macrophages alone) in animal models restricts disease development in both cases, arguing that both are accentuated by inflammatory/immune pathways. We discuss that amyloid β, a distinguishing feature of AD, also plays a key role in ATH. Several drugs, at least in mouse models, are effective in preventing the development of both ATH and AD. Given similar age-dependence, genetic underpinnings, involvement of the vasculature, association with infection, Aβ involvement, the central role of macrophages, and drug overlap, we conclude that the two conditions reflect different manifestations of a common pathoetiology. Infection and inflammation selectively induce the expression of cholesterol 25-hydroxylase (CH25H). Acutely, the production of 'immunosterol' 25-hydroxycholesterol (25OHC) defends against enveloped viruses. We present evidence that chronic macrophage CH25H upregulation leads to catalyzed esterification of sterols via 25OHC-driven allosteric activation of ACAT (acyl-CoA cholesterol acyltransferase/SOAT), intracellular accumulation of cholesteryl esters and lipid droplets, vascular occlusion, and overt disease. We postulate that AD and ATH are both caused by chronic immunologic challenge that induces CH25H expression and protection against particular infectious agents, but at the expense of longer-term pathology.

Similarities and differences between learning abilities, "pure" learning disabilities, "pure" ADHD and comorbid ADHD with learning disabilities.

PubMed

Mangina, Constantine A; Beuzeron-Mangina, Helen

2009-08-01

This research pursues the crucial question of the differentiation of preadolescents with "Pure" ADHD, comorbid ADHD with learning disabilities, "Pure" learning disabilities and age-matched normal controls. For this purpose, Topographic Mapping of Event-Related Brain Potentials (ERPs) to a Memory Workload Paradigm with visually presented words, Bilateral Electrodermal Activity during cognitive workload and Mangina-Test performance were used. The analysis of Topographic distribution of amplitudes revealed that normal preadolescents were significantly different from "Pure" ADHD (P<0.0001), "Pure" learning disabilities (P<0.0001), and comorbid ADHD with learning disabilities (P<0.0009), by displaying enhanced prefrontal and frontal negativities (N450). In contrast, preadolescents with "Pure" ADHD and comorbid ADHD with learning disabilities have shown a marked reduction of prefrontal and frontal negativities (N450). As for the "Pure" Learning Disabled preadolescents, very small positivities (P450) in prefrontal and frontal regions were obtained as compared to the other pathological groups. Bilateral Electrodermal Activity during cognitive workload revealed a significant main effect for groups (P<0.00001), Left versus Right (P=0.0029) and sessions (P=0.0136). A significant main effect for the Mangina-Test performance which separated the four groups was found (P<0.000001). Overall, these data support the existence of clear differences and similarities between the pathological preadolescent groups as opposed to age-matched normal controls. The psychophysiological differentiation of these groups, provides distinct biological markers which integrate central, autonomic and neuropsychometric variables by targeting the key features of these pathologies for diagnosis and intervention strategies and by providing knowledge for the understanding of normal neurocognitive processes and functions.

Wheeze sound analysis using computer-based techniques: a systematic review.

PubMed

Ghulam Nabi, Fizza; Sundaraj, Kenneth; Chee Kiang, Lam; Palaniappan, Rajkumar; Sundaraj, Sebastian

2017-10-31

Wheezes are high pitched continuous respiratory acoustic sounds which are produced as a result of airway obstruction. Computer-based analyses of wheeze signals have been extensively used for parametric analysis, spectral analysis, identification of airway obstruction, feature extraction and diseases or pathology classification. While this area is currently an active field of research, the available literature has not yet been reviewed. This systematic review identified articles describing wheeze analyses using computer-based techniques on the SCOPUS, IEEE Xplore, ACM, PubMed and Springer and Elsevier electronic databases. After a set of selection criteria was applied, 41 articles were selected for detailed analysis. The findings reveal that 1) computerized wheeze analysis can be used for the identification of disease severity level or pathology, 2) further research is required to achieve acceptable rates of identification on the degree of airway obstruction with normal breathing, 3) analysis using combinations of features and on subgroups of the respiratory cycle has provided a pathway to classify various diseases or pathology that stem from airway obstruction.

The relationship between personality organization as assessed by theory-driven profiles of the Dutch Short Form of the MMPI and self-reported features of personality organization.

PubMed

Eurelings-Bontekoe, Elisabeth H M; Luyten, Patrick; Remijsen, Mila; Koelen, Jurrijn

2010-11-01

In this study, we investigated the relationships between features of personality organization (PO) as assessed by theory driven profiles of the Dutch Short Form of the MMPI (DSFM; Luteijn & Kok, 1985) and 2 self-report measures of personality pathology, that is, the Dutch Inventory of Personality Organization (Berghuis, Kamphuis, Boedijn, & Verheul, 2009) and the Dutch Schizotypy Personality Questionnaire-Revised (Vollema & Hoijtink, 2000), in a sample of 190 outpatient psychiatric patients. Results showed that the single scales of all 3 measures segregated into 2 theoretically expected and meaningful dimensions, that is, a dimension assessing severity of personality pathology and an introversion/extraversion dimension. Theory-driven combinations of single DSFM subscales as a measure of level of PO distinguished characteristics of patients at various levels of PO in theoretically predicted ways. Results also suggest that structural personality pathology may not be fully captured by self-report measures.

Cerebral vascular amyloid seeds drive amyloid β-protein fibril assembly with a distinct anti-parallel structure

PubMed Central

Xu, Feng; Fu, Ziao; Dass, Sharmila; Kotarba, AnnMarie E.; Davis, Judianne; Smith, Steven O.; Van Nostrand, William E.

2016-01-01

Cerebrovascular accumulation of amyloid β-protein (Aβ), a condition known as cerebral amyloid angiopathy (CAA), is a common pathological feature of patients with Alzheimer's disease. Familial Aβ mutations, such as Dutch-E22Q and Iowa-D23N, can cause severe cerebrovascular accumulation of amyloid that serves as a potent driver of vascular cognitive impairment and dementia. The distinctive features of vascular amyloid that underlie its unique pathological properties remain unknown. Here, we use transgenic mouse models producing CAA mutants (Tg-SwDI) or overproducing human wild-type Aβ (Tg2576) to demonstrate that CAA-mutant vascular amyloid influences wild-type Aβ deposition in brain. We also show isolated microvascular amyloid seeds from Tg-SwDI mice drive assembly of human wild-type Aβ into distinct anti-parallel β-sheet fibrils. These findings indicate that cerebrovascular amyloid can serve as an effective scaffold to promote rapid assembly and strong deposition of Aβ into a unique structure that likely contributes to its distinctive pathology. PMID:27869115

Telangiectatic oncocytoma: a previously undescribed variant of renal oncocytoma.

PubMed

Xiao, Guang-Qian; Ko, Huai-Bin Mabel; Unger, Pamela

2013-07-01

To identify, describe, and investigate the clinical, radiologic, and pathologic features of 8 cases of telangiectatic oncocytoma. Fifty-three consecutive renal oncocytomas were reviewed for the telangiectatic pathologic features that were subsequently correlated with the demographic, clinical, and radiographic findings. Telangiectatic oncocytoma accounted for 15% of the 53 renal oncocytomas collected in the past 7 years in our institution. On radiology, almost all presented as an enhancing mass and were suspicious for or consistent with a renal malignant tumor. Grossly, the tumors ranged from 2.4 to 6.0 cm (mean, 3.5 cm) and macroscopically were hemorrhagic spongy or multicystic masses without a central stellate scar. Microscopically, they were characterized by variably sized blood-distended spaces (<0.1-mm to 2- to 3-mm blood lakes) lined by typical oncocytoma cells and without evidence of degenerative changes. With its unique radiologic and pathologic presentations in comparison with classic renal oncocytoma, it is important to recognize this new variant of renal oncocytoma.

Management of Cerebral Radiation Necrosis: A Retrospective Study of 12 Patients.

PubMed

Liao, Chenlong; Visocchi, Massimiliano; Zhang, Wenchuan; Yang, Min; Zhong, Wenxiang; Liu, Pengfei

2017-01-01

Cerebral radiation necrosis (RN) is a severe complication of radiotherapy for cerebral pathologies. This study discusses the radiographic and pathological features of 12 patients with RN and investigates the management strategy. Eleven patients with brain tumors, and one with cerebral cavernous angioma, treated by surgical resection or Gamma Knife alone before radiotherapy developed RN during follow-up. Surgical resection for the cerebral RN was performed in nine patients, and the other three patients received medical treatment. The clinical features, magnetic resonance imaging (MRI), surgical findings, and pathological sections are reviewed. The diagnosis of RN was confirmed by histological study in all the patients; those with surgical and medical treatment recovered. As a major complication of radiotherapy, from the clinical and neuroradiological points of view, RN may simulate tumor recurrence. Due to the increasing number of patients with RN who will need to be treated in future years, the definite diagnosis and appropriate treatment of RN remain critical.

The characteristic ultrasound features of specific types of ovarian pathology (Review)

PubMed Central

SAYASNEH, AHMAD; EKECHI, CHRISTINE; FERRARA, LAURA; KAIJSER, JEROEN; STALDER, CATRIONA; SUR, SHYAMALY; TIMMERMAN, DIRK; BOURNE, TOM

2015-01-01

Characterizing ovarian masses enables patients with malignancy to be appropriately triaged for treatment by subspecialist gynecological oncologists, which has been shown to optimize care and improve survival. Furthermore, correctly classifying benign masses facilitates the selection of patients with ovarian pathology that may either not require intervention, or be suitable for minimal access surgery if intervention is required. However, predicting whether a mass is benign or malignant is not the only clinically relevant information that we need to know before deciding on appropriate treatment. Knowing the specific histology of a mass is becoming of increasing importance as management options become more tailored to the individual patient. For example predicting a mucinous borderline tumor gives the opportunity for fertility sparing surgery, and will highlight the need for further gastrointestinal assessment. For benign disease, predicting the presence of an endometrioma and possible deeply infiltrating endometriosis is important when considering both who should perform and the extent of surgery. An examiner’s subjective assessment of the morphological and vascular features of a mass using ultrasonography has been shown to be highly effective for predicting whether a mass is benign or malignant. Many masses also have features that enable a reliable diagnosis of the specific pathology of a particular mass to be made. In this narrative review we aim to describe the typical morphological features seen on ultrasound of different adnexal masses and illustrate these by showing representative ultrasound images. PMID:25406094

Clinical and pathological features of amyotrophic lateral sclerosis caused by mutation in the C9ORF72 gene on chromosome 9p.

PubMed

Stewart, Heather; Rutherford, Nicola J; Briemberg, Hannah; Krieger, Charles; Cashman, Neil; Fabros, Marife; Baker, Matt; Fok, Alice; DeJesus-Hernandez, Mariely; Eisen, Andrew; Rademakers, Rosa; Mackenzie, Ian R A

2012-03-01

Two studies recently identified a GGGGCC hexanucleotide repeat expansion in a non-coding region of the chromosome 9 open-reading frame 72 gene (C9ORF72) as the cause of chromosome 9p-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In a cohort of 231 probands with ALS, we identified the C9ORF72 mutation in 17 familial (27.4%) and six sporadic (3.6%) cases. Patients with the mutation presented with typical motor features of ALS, although subjects with the C9ORF72 mutation had more frequent bulbar onset, compared to those without this mutation. Dementia was significantly more common in ALS patients and families with the C9ORF72 mutation and was usually early-onset FTD. There was striking clinical heterogeneity among the members of individual families with the mutation. The associated neuropathology was a combination of ALS with TDP-ir inclusions and FTLD-TDP. In addition to TDP-43-immunoreactive pathology, a consistent and specific feature of cases with the C9ORF72 mutation was the presence of ubiquitin-positive, TDP-43-negative inclusions in a variety of neuroanatomical regions, such as the cerebellar cortex. These findings support the C9ORF72 mutation as an important newly recognized cause of ALS, provide a more detailed characterization of the associated clinical and pathological features and further demonstrate the clinical and molecular overlap between ALS and FTD.

Metabolic syndrome and low high-density lipoprotein cholesterol are associated with adverse pathological features in patients with prostate cancer treated by radical prostatectomy.

PubMed

Lebdai, Souhil; Mathieu, Romain; Leger, Julie; Haillot, Olivier; Vincendeau, Sébastien; Rioux-Leclercq, Nathalie; Fournier, Georges; Perrouin-Verbe, Marie-Aimée; Doucet, Laurent; Azzouzi, Abdel Rahmene; Rigaud, Jérome; Renaudin, Karine; Charles, Thomas; Bruyere, Franck; Fromont, Gaelle

2018-02-01

Previous studies have suggested a link between metabolic syndrome (MetS) and prostate cancer (PCa). In the present study, we aimed to assess the association between MetS and markers of PCa aggressiveness on radical prostatectomy (RP). All patients consecutively treated for PCa by RP in 6 academic institutions between August 2013 and July 2016 were included. MetS was defined as at least 3 of 5 components (obesity, elevated blood pressure, diabetes, low high-density lipoprotein (HDL)-cholesterol, and hypertriglyceridemia). Demographic, biological, and clinical parameters were prospectively collected, including: age, biopsy results, preoperative serum prostate-specific antigen, surgical procedure, and pathological data of RP specimen. Locally advanced disease was defined as a pT-stage ≥3. International Society of Urological Pathology (ISUP) groups were used for pathological grading. Qualitative and quantitative variables were compared using chi-square and Wilcoxon tests; logistic regression analyses assessed the association of MetS and its components with pathological data. Statistical significance was defined as a P<0.05. Among 567 men, 249 (44%) had MetS. In a multivariate model including preoperative prostate-specific antigen, biopsy ISUP-score, clinical T-stage, age, and ethnicity: we found that MetS was an independent risk factor for positive margins, and ISUP group ≥4 on the RP specimen (odds ratio [OR] = 1.5; 95% CI: 1.1-2.3; P = 0.035; OR = 2.0; 95% CI: 1.1-4.0; P = 0.044, respectively). In addition, low HDL-cholesterol level was associated with locally advanced PCa (OR = 1.6; 95% CI: 1.1-2.4; P = 0.024). Risks of adverse pathological features increased with the number of MetS components: having ≥ 4 MetS components was significantly associated with higher risk of ISUP group ≥ 4 and higher risk of positive margins (OR = 1.9; 95% CI: 1.1-3.3; P = 0.017; OR = 1.8; 95% CI: 1.1-2.8; P = 0.007, respectively). MetS was an independent predictive factor for higher ISUP group and positive margins at RP. Low HDL-cholesterol alone, and having 4 and more MetS components were also associated with higher risk of adverse pathological features. Copyright © 2018. Published by Elsevier Inc.

Key Program Features to Enhance the School-to-Career Transition for Youth with Disabilities

ERIC Educational Resources Information Center

Doren, Bonnie; Yan, Min-Chi; Tu, Wei-Mo

2013-01-01

The purpose of the article was to identify key features within research-based school-to-career programs that were linked to positive employment outcomes for youth disabilities. Three key program features were identified and discussed that could be incorporated into the practices and programs of schools and communities to support the employment…

Lupus mastitis: a mimicker of breast carcinoma

PubMed Central

Warne, Richard Roger; Taylor, Donna; Segal, Amanda; Irish, Ashley

2011-01-01

The authors present a case of lupus mastitis which was initially diagnosed following an incisional biopsy of a breast lump, with similar pathology found 2 years later after an ultrasound guided biopsy of the same lump. The woman had been diagnosed 7 years before with systemic lupus erythematosus. The radiological and pathological features are presented in this report with discussion of similar cases in the literature. PMID:22669997

Gross feature recognition of Anatomical Images based on Atlas grid (GAIA): Incorporating the local discrepancy between an atlas and a target image to capture the features of anatomic brain MRI.

PubMed

Qin, Yuan-Yuan; Hsu, Johnny T; Yoshida, Shoko; Faria, Andreia V; Oishi, Kumiko; Unschuld, Paul G; Redgrave, Graham W; Ying, Sarah H; Ross, Christopher A; van Zijl, Peter C M; Hillis, Argye E; Albert, Marilyn S; Lyketsos, Constantine G; Miller, Michael I; Mori, Susumu; Oishi, Kenichi

2013-01-01

We aimed to develop a new method to convert T1-weighted brain MRIs to feature vectors, which could be used for content-based image retrieval (CBIR). To overcome the wide range of anatomical variability in clinical cases and the inconsistency of imaging protocols, we introduced the Gross feature recognition of Anatomical Images based on Atlas grid (GAIA), in which the local intensity alteration, caused by pathological (e.g., ischemia) or physiological (development and aging) intensity changes, as well as by atlas-image misregistration, is used to capture the anatomical features of target images. As a proof-of-concept, the GAIA was applied for pattern recognition of the neuroanatomical features of multiple stages of Alzheimer's disease, Huntington's disease, spinocerebellar ataxia type 6, and four subtypes of primary progressive aphasia. For each of these diseases, feature vectors based on a training dataset were applied to a test dataset to evaluate the accuracy of pattern recognition. The feature vectors extracted from the training dataset agreed well with the known pathological hallmarks of the selected neurodegenerative diseases. Overall, discriminant scores of the test images accurately categorized these test images to the correct disease categories. Images without typical disease-related anatomical features were misclassified. The proposed method is a promising method for image feature extraction based on disease-related anatomical features, which should enable users to submit a patient image and search past clinical cases with similar anatomical phenotypes.

The Emerging Relationship Between Interstitial Fluid-Cerebrospinal Fluid Exchange, Amyloid-β, and Sleep.

PubMed

Boespflug, Erin L; Iliff, Jeffrey J

2018-02-15

Amyloid-β (Aβ) plaques are a key histopathological hallmark of Alzheimer's disease (AD), and soluble Aβ species are believed to play an important role in the clinical development of this disease. Emerging biomarker data demonstrate that Aβ plaque deposition begins decades before the onset of clinical symptoms, suggesting that understanding the biological determinants of the earliest steps in the development of AD pathology may provide key opportunities for AD treatment and prevention. Although a clinical association between sleep disruption and AD has long been appreciated, emerging clinical studies and insights from the basic neurosciences have shed important new light on how sleep and Aβ homeostasis may be connected in the setting of AD. Aβ, like many interstitial solutes, is cleared in part through the exchange of brain interstitial fluid and cerebrospinal fluid along a brain-wide network of perivascular pathways recently termed the glymphatic system. Glymphatic function is primarily a feature of the sleeping brain, rather than the waking brain, and is slowed in the aging and posttraumatic brain. These changes may underlie the diurnal fluctuations in interstitial and cerebrospinal fluid Aβ levels observed in both the rodent and the human. These and other emerging studies suggest that age-related sleep disruption may be one key factor that renders the aging brain vulnerable to Aβ deposition and the development of AD. If this is true, sleep may represent a key modifiable risk factor or therapeutic target in the preclinical phases of AD. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Giant cell angiofibroma misdiagnosed as a vascular malformation and treated with absolute alcohol for one year: a case report and review of the literature

PubMed Central

2014-01-01

Purpose To present the clinical, imaging, pathological and immunohistochemical features of giant cell angiofibroma (GCA). Case presentation In this paper we report an atypical case of a GCA extending from the parotid to the parapharyngeal space. The lesion was being treated as a vascular malformation for one year prior to surgical removal. We summarize the clinical manifestations, imaging, pathological and molecular features of this rare disease. After complete surgical removal of the tumor, immunohistochemical analysis revealed strong positivity for the mesenchymal markers vimentin, CD34, CD31 and CD99 in neoplastic cells. Tumor proliferation antigen marker Ki67 was partly positive (<5% of cells). Tumor cells were negative for muscle-specific actin, epithelial membrane antigen, smooth muscle actin, cytokeratin pan, S100, desmin, glial fibrillary acidic protein, myogenin, MyoD1 and F8. The morphological and immunohistochemical profile was consistent with the diagnosis of GCA. Conclusion GCA is a rare soft tissue tumor that can easily be misdiagnosed in the clinical preoperative setting. In view of the clinical, pathological and molecular features of the tumor, complete surgical removal is the current optimal treatment option, providing accurate diagnosis and low to minimal recurrence rate. PMID:24758544

Automated Intelligibility Assessment of Pathological Speech Using Phonological Features

NASA Astrophysics Data System (ADS)

Middag, Catherine; Martens, Jean-Pierre; Van Nuffelen, Gwen; De Bodt, Marc

2009-12-01

It is commonly acknowledged that word or phoneme intelligibility is an important criterion in the assessment of the communication efficiency of a pathological speaker. People have therefore put a lot of effort in the design of perceptual intelligibility rating tests. These tests usually have the drawback that they employ unnatural speech material (e.g., nonsense words) and that they cannot fully exclude errors due to listener bias. Therefore, there is a growing interest in the application of objective automatic speech recognition technology to automate the intelligibility assessment. Current research is headed towards the design of automated methods which can be shown to produce ratings that correspond well with those emerging from a well-designed and well-performed perceptual test. In this paper, a novel methodology that is built on previous work (Middag et al., 2008) is presented. It utilizes phonological features, automatic speech alignment based on acoustic models that were trained on normal speech, context-dependent speaker feature extraction, and intelligibility prediction based on a small model that can be trained on pathological speech samples. The experimental evaluation of the new system reveals that the root mean squared error of the discrepancies between perceived and computed intelligibilities can be as low as 8 on a scale of 0 to 100.

The predictive value of magnetic resonance imaging of retinoblastoma for the likelihood of high-risk pathologic features.

PubMed

Hiasat, Jamila G; Saleh, Alaa; Al-Hussaini, Maysa; Al Nawaiseh, Ibrahim; Mehyar, Mustafa; Qandeel, Monther; Mohammad, Mona; Deebajah, Rasha; Sultan, Iyad; Jaradat, Imad; Mansour, Asem; Yousef, Yacoub A

2018-06-01

To evaluate the predictive value of magnetic resonance imaging in retinoblastoma for the likelihood of high-risk pathologic features. A retrospective study of 64 eyes enucleated from 60 retinoblastoma patients. Contrast-enhanced magnetic resonance imaging was performed before enucleation. Main outcome measures included demographics, laterality, accuracy, sensitivity, and specificity of magnetic resonance imaging in detecting high-risk pathologic features. Optic nerve invasion and choroidal invasion were seen microscopically in 34 (53%) and 28 (44%) eyes, respectively, while they were detected in magnetic resonance imaging in 22 (34%) and 15 (23%) eyes, respectively. The accuracy of magnetic resonance imaging in detecting prelaminar invasion was 77% (sensitivity 89%, specificity 98%), 56% for laminar invasion (sensitivity 27%, specificity 94%), 84% for postlaminar invasion (sensitivity 42%, specificity 98%), and 100% for optic cut edge invasion (sensitivity100%, specificity 100%). The accuracy of magnetic resonance imaging in detecting focal choroidal invasion was 48% (sensitivity 33%, specificity 97%), and 84% for massive choroidal invasion (sensitivity 53%, specificity 98%), and the accuracy in detecting extrascleral extension was 96% (sensitivity 67%, specificity 98%). Magnetic resonance imaging should not be the only method to stratify patients at high risk from those who are not, eventhough it can predict with high accuracy extensive postlaminar optic nerve invasion, massive choroidal invasion, and extrascleral tumor extension.

Ultrasound features in trisomy 13 (Patau syndrome) and trisomy 18 (Edwards syndrome) in a consecutive series of 47 cases

PubMed Central

Kroes, I.; Janssens, S.; Defoort, P.

2014-01-01

Objective: To determine and list the variety of the predominant appeal signs leading to referral and their accompanying features found during specialized ultrasound evaluation in foetuses with trisomy 13 and trisomy 18. Materials and Methods: In a period of thirty years, 1110 cases of foetal malformations were detected during specialized echographic evaluation. 47 Of these cases were foetuses with trisomy 13 or trisomy 18. We evaluated the predominant signs leading to referral, the difference and overlap in presenting signs between both syndromes and when the data were available, we also compared the echographic signs with the foetal pathology. Results: In foetuses with trisomy 13 the most common malformations were craniofacial defects, cerebral malformations and genitourinary tract anomalies. The most common malformations associated with trisomy 18 were limb abnormalities and intrauterine growth restriction. Most malformations were predominant in trisomy 18, except for genitourinary tract anomalies. In most cases the sonographic signs correlated with the pathology findings. Conclusion: Trisomy 13 as well as trisomy 18 are characterized by a number of various malformations in the foetus. Most of the ultrasound features were predominant in foetuses with trisomy 18. Mostly the foetal pathology correlated with the sonographic evaluation. PMID:25593701

Pathological Gleason prediction through gland ring morphometry in immunofluorescent prostate cancer images

NASA Astrophysics Data System (ADS)

Scott, Richard; Khan, Faisal M.; Zeineh, Jack; Donovan, Michael; Fernandez, Gerardo

2016-03-01

The Gleason score is the most common architectural and morphological assessment of prostate cancer severity and prognosis. There have been numerous quantitative techniques developed to approximate and duplicate the Gleason scoring system. Most of these approaches have been developed in standard H and E brightfield microscopy. Immunofluorescence (IF) image analysis of tissue pathology has recently been proven to be extremely valuable and robust in developing prognostic assessments of disease, particularly in prostate cancer. There have been significant advances in the literature in quantitative biomarker expression as well as characterization of glandular architectures in discrete gland rings. In this work we leverage a new method of segmenting gland rings in IF images for predicting the pathological Gleason; both the clinical and the image specific grade, which may not necessarily be the same. We combine these measures with nuclear specific characteristics as assessed by the MST algorithm. Our individual features correlate well univariately with the Gleason grades, and in a multivariate setting have an accuracy of 85% in predicting the Gleason grade. Additionally, these features correlate strongly with clinical progression outcomes (CI of 0.89), significantly outperforming the clinical Gleason grades (CI of 0.78). This work presents the first assessment of morphological gland unit features from IF images for predicting the Gleason grade.

[Pancreatic serous cystadenoma associated with pancreatic heterotopia].

PubMed

Mohamed, Hedfi; Dorra, Belghachem; Hela, Bouhafa; Cherif, Abdelhedi; Azza, Sridi; Karim, Sassi; Khadija, Bellil; Adnen, Chouchene

2016-01-01

Pancreatic heterotopias (HP) are rare. They can occur at any age with a slight male predominance. These lesions are usually asymptomatic and they are often found incidentally during upper or lower GI endoscopy or during the anatomo-pathological examination of an organ which was resected for other reasons; they can be isolated or associated with a digestive pathology. We report, through observation, the association of HP with serous cystadenoma of the pancreas discovered during examinations to identify the etiology of isolated abdominal pain. The aim of this study is to analyse clinical and histological features of this rare pathology.

Dual Pathology of Mandible

PubMed Central

Rajurkar, Suday G.; Deshpande, Mohan D.; Kazi, Noaman; Jadhav, Dhanashree; Ranadive, Pallavi; Ingole, Snehal

2017-01-01

Aneurysmal Bone cyst (ABC)is a rare benign lesion of the bone which is infrequent in craniofacial region (12%). Rapid growth pattern causing bone expansion and facial asymmetry is a characteristic feature of ABC. Giant cell lesion is another distinct pathological entity. Here we present to you a rare case of dual pathology in an 11 year old female patient who presented with a large expansile lesion in the left hemimandible. All radiographic investigations were suggestive of ABC, aspiration of the lesion resulted in blood aspirate. However only after a histologic examination the dual nature of the lesion was revealed. PMID:29264307

Dual Pathology of Mandible.

PubMed

Rajurkar, Suday G; Deshpande, Mohan D; Kazi, Noaman; Jadhav, Dhanashree; Ranadive, Pallavi; Ingole, Snehal

2017-01-01

Aneurysmal Bone cyst (ABC)is a rare benign lesion of the bone which is infrequent in craniofacial region (12%). Rapid growth pattern causing bone expansion and facial asymmetry is a characteristic feature of ABC. Giant cell lesion is another distinct pathological entity. Here we present to you a rare case of dual pathology in an 11 year old female patient who presented with a large expansile lesion in the left hemimandible. All radiographic investigations were suggestive of ABC, aspiration of the lesion resulted in blood aspirate. However only after a histologic examination the dual nature of the lesion was revealed.

Telangiectatic osteosarcoma of the spine: a case report.

PubMed

Amritanand, R; Venkatesh, K; Cherian, R; Shah, A; Sundararaj, G D

2008-09-01

Telangiectatic osteosarcoma (TOS) of the spine is rare accounting for only 0.08% of all primary osteosarcomas. Though a well described radio-pathological entity it is not often thought of as a cause of paraplegia. We describe the clinical, radiological and pathological features and discuss the treatment options of telangiectatic osteosarcoma of the dorsal spine presenting in a young man. The diagnostic pitfalls are discussed emphasising the fact that the diagnosis of TOS of the spine requires not only a multi modal approach of appropriate radiological and pathological tests but also an awareness of this condition.

Telangiectatic osteosarcoma of the spine: a case report

PubMed Central

Venkatesh, K.; Cherian, R.; Shah, A.; Sundararaj, G. D.

2008-01-01

Telangiectatic osteosarcoma (TOS) of the spine is rare accounting for only 0.08% of all primary osteosarcomas. Though a well described radio-pathological entity it is not often thought of as a cause of paraplegia. We describe the clinical, radiological and pathological features and discuss the treatment options of telangiectatic osteosarcoma of the dorsal spine presenting in a young man. The diagnostic pitfalls are discussed emphasising the fact that the diagnosis of TOS of the spine requires not only a multi modal approach of appropriate radiological and pathological tests but also an awareness of this condition. PMID:18421481

Stationary Wavelet Transform and AdaBoost with SVM Based Pathological Brain Detection in MRI Scanning.

PubMed

Nayak, Deepak Ranjan; Dash, Ratnakar; Majhi, Banshidhar

2017-01-01

This paper presents an automatic classification system for segregating pathological brain from normal brains in magnetic resonance imaging scanning. The proposed system employs contrast limited adaptive histogram equalization scheme to enhance the diseased region in brain MR images. Two-dimensional stationary wavelet transform is harnessed to extract features from the preprocessed images. The feature vector is constructed using the energy and entropy values, computed from the level- 2 SWT coefficients. Then, the relevant and uncorrelated features are selected using symmetric uncertainty ranking filter. Subsequently, the selected features are given input to the proposed AdaBoost with support vector machine classifier, where SVM is used as the base classifier of AdaBoost algorithm. To validate the proposed system, three standard MR image datasets, Dataset-66, Dataset-160, and Dataset- 255 have been utilized. The 5 runs of k-fold stratified cross validation results indicate the suggested scheme offers better performance than other existing schemes in terms of accuracy and number of features. The proposed system earns ideal classification over Dataset-66 and Dataset-160; whereas, for Dataset- 255, an accuracy of 99.45% is achieved. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Iris-based medical analysis by geometric deformation features.

PubMed

Ma, Lin; Zhang, D; Li, Naimin; Cai, Yan; Zuo, Wangmeng; Wang, Kuanguan

2013-01-01

Iris analysis studies the relationship between human health and changes in the anatomy of the iris. Apart from the fact that iris recognition focuses on modeling the overall structure of the iris, iris diagnosis emphasizes the detecting and analyzing of local variations in the characteristics of irises. This paper focuses on studying the geometrical structure changes in irises that are caused by gastrointestinal diseases, and on measuring the observable deformations in the geometrical structures of irises that are related to roundness, diameter and other geometric forms of the pupil and the collarette. Pupil and collarette based features are defined and extracted. A series of experiments are implemented on our experimental pathological iris database, including manual clustering of both normal and pathological iris images, manual classification by non-specialists, manual classification by individuals with a medical background, classification ability verification for the proposed features, and disease recognition by applying the proposed features. The results prove the effectiveness and clinical diagnostic significance of the proposed features and a reliable recognition performance for automatic disease diagnosis. Our research results offer a novel systematic perspective for iridology studies and promote the progress of both theoretical and practical work in iris diagnosis.

Analysis of breast thermograms using Gabor wavelet anisotropy index.

PubMed

Suganthi, S S; Ramakrishnan, S

2014-09-01

In this study, an attempt is made to distinguish the normal and abnormal tissues in breast thermal images using Gabor wavelet transform. Thermograms having normal, benign and malignant tissues are considered in this study and are obtained from public online database. Segmentation of breast tissues is performed by multiplying raw image and ground truth mask. Left and right breast regions are separated after removing the non-breast regions from the segmented image. Based on the pathological conditions, the separated breast regions are grouped as normal and abnormal tissues. Gabor features such as energy and amplitude in different scales and orientations are extracted. Anisotropy and orientation measures are calculated from the extracted features and analyzed. A distinctive variation is observed among different orientations of the extracted features. It is found that the anisotropy measure is capable of differentiating the structural changes due to varied metabolic conditions. Further, the Gabor features also showed relative variations among different pathological conditions. It appears that these features can be used efficiently to identify normal and abnormal tissues and hence, improve the relevance of breast thermography in early detection of breast cancer and content based image retrieval.

Radiomics analysis of DWI data to identify the rectal cancer patients qualified for local excision after neoadjuvant chemoradiotherapy

NASA Astrophysics Data System (ADS)

Tang, Zhenchao; Liu, Zhenyu; Zhang, Xiaoyan; Shi, Yanjie; Wang, Shou; Fang, Mengjie; Sun, Yingshi; Dong, Enqing; Tian, Jie

2018-02-01

The Locally advanced rectal cancer (LARC) patients were routinely treated with neoadjuvant chemoradiotherapy (CRT) firstly and received total excision afterwards. While, the LARC patients might relieve to T1N0M0/T0N0M0 stage after the CRT, which would enable the patients be qualified for local excision. However, accurate pathological TNM stage could only be obtained by the pathological examination after surgery. We aimed to conduct a Radiomics analysis of Diffusion weighted Imaging (DWI) data to identify the patients in T1N0M0/T0N0M0 stages before surgery, in hope of providing clinical surgery decision support. 223 routinely treated LARC patients in Beijing Cancer Hospital were enrolled in current study. DWI data and clinical characteristics were collected after CRT. According to the pathological TNM stage, the patients of T1N0M0 and T0N0M0 stages were labelled as 1 and the other patients were labelled as 0. The first 123 patients in chronological order were used as training set, and the rest patients as validation set. 563 image features extracted from the DWI data and clinical characteristics were used as features. Two-sample T test was conducted to pre-select the top 50% discriminating features. Least absolute shrinkage and selection operator (Lasso)-Logistic regression model was conducted to further select features and construct the classification model. Based on the 14 selected image features, the area under the Receiver Operating Characteristic (ROC) curve (AUC) of 0.8781, classification Accuracy (ACC) of 0.8432 were achieved in the training set. In the validation set, AUC of 0.8707, ACC (ACC) of 0.84 were observed.

Role of tumour molecular and pathology features to estimate colorectal cancer risk for first-degree relatives.

PubMed

Win, Aung Ko; Buchanan, Daniel D; Rosty, Christophe; MacInnis, Robert J; Dowty, James G; Dite, Gillian S; Giles, Graham G; Southey, Melissa C; Young, Joanne P; Clendenning, Mark; Walsh, Michael D; Walters, Rhiannon J; Boussioutas, Alex; Smyrk, Thomas C; Thibodeau, Stephen N; Baron, John A; Potter, John D; Newcomb, Polly A; Le Marchand, Loïc; Haile, Robert W; Gallinger, Steven; Lindor, Noralane M; Hopper, John L; Ahnen, Dennis J; Jenkins, Mark A

2015-01-01

To estimate risk of colorectal cancer (CRC) for first-degree relatives of CRC cases based on CRC molecular subtypes and tumour pathology features. We studied a cohort of 33,496 first-degree relatives of 4853 incident invasive CRC cases (probands) who were recruited to the Colon Cancer Family Registry through population cancer registries in the USA, Canada and Australia. We categorised the first-degree relatives into four groups: 28,156 of 4095 mismatch repair (MMR)-proficient probands, 2302 of 301 MMR-deficient non-Lynch syndrome probands, 1799 of 271 suspected Lynch syndrome probands and 1239 of 186 Lynch syndrome probands. We compared CRC risk for first-degree relatives stratified by the absence or presence of specific tumour molecular pathology features in probands across each of these four groups and for all groups combined. Compared with first-degree relatives of MMR-proficient CRC cases, a higher risk of CRC was estimated for first-degree relatives of CRC cases with suspected Lynch syndrome (HR 2.06, 95% CI 1.59 to 2.67) and with Lynch syndrome (HR 5.37, 95% CI 4.16 to 6.94), but not with MMR-deficient non-Lynch syndrome (HR 1.04, 95% CI 0.82 to 1.31). A greater risk of CRC was estimated for first-degree relatives if CRC cases were diagnosed before age 50 years, had proximal colon cancer or if their tumours had any of the following: expanding tumour margin, peritumoral lymphocytes, tumour-infiltrating lymphocytes or synchronous CRC. Molecular pathology features are potentially useful to refine screening recommendations for first-degree relatives of CRC cases and to identify which cases are more likely to be caused by genetic or other familial factors. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Genome-wide association meta-analysis of neuropathologic features of Alzheimer's disease and related dementias.

PubMed

Beecham, Gary W; Hamilton, Kara; Naj, Adam C; Martin, Eden R; Huentelman, Matt; Myers, Amanda J; Corneveaux, Jason J; Hardy, John; Vonsattel, Jean-Paul; Younkin, Steven G; Bennett, David A; De Jager, Philip L; Larson, Eric B; Crane, Paul K; Kamboh, M Ilyas; Kofler, Julia K; Mash, Deborah C; Duque, Linda; Gilbert, John R; Gwirtsman, Harry; Buxbaum, Joseph D; Kramer, Patricia; Dickson, Dennis W; Farrer, Lindsay A; Frosch, Matthew P; Ghetti, Bernardino; Haines, Jonathan L; Hyman, Bradley T; Kukull, Walter A; Mayeux, Richard P; Pericak-Vance, Margaret A; Schneider, Julie A; Trojanowski, John Q; Reiman, Eric M; Schellenberg, Gerard D; Montine, Thomas J

2014-09-01

Alzheimer's disease (AD) and related dementias are a major public health challenge and present a therapeutic imperative for which we need additional insight into molecular pathogenesis. We performed a genome-wide association study and analysis of known genetic risk loci for AD dementia using neuropathologic data from 4,914 brain autopsies. Neuropathologic data were used to define clinico-pathologic AD dementia or controls, assess core neuropathologic features of AD (neuritic plaques, NPs; neurofibrillary tangles, NFTs), and evaluate commonly co-morbid neuropathologic changes: cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), hippocampal sclerosis of the elderly (HS), and vascular brain injury (VBI). Genome-wide significance was observed for clinico-pathologic AD dementia, NPs, NFTs, CAA, and LBD with a number of variants in and around the apolipoprotein E gene (APOE). GalNAc transferase 7 (GALNT7), ATP-Binding Cassette, Sub-Family G (WHITE), Member 1 (ABCG1), and an intergenic region on chromosome 9 were associated with NP score; and Potassium Large Conductance Calcium-Activated Channel, Subfamily M, Beta Member 2 (KCNMB2) was strongly associated with HS. Twelve of the 21 non-APOE genetic risk loci for clinically-defined AD dementia were confirmed in our clinico-pathologic sample: CR1, BIN1, CLU, MS4A6A, PICALM, ABCA7, CD33, PTK2B, SORL1, MEF2C, ZCWPW1, and CASS4 with 9 of these 12 loci showing larger odds ratio in the clinico-pathologic sample. Correlation of effect sizes for risk of AD dementia with effect size for NFTs or NPs showed positive correlation, while those for risk of VBI showed a moderate negative correlation. The other co-morbid neuropathologic features showed only nominal association with the known AD loci. Our results discovered new genetic associations with specific neuropathologic features and aligned known genetic risk for AD dementia with specific neuropathologic changes in the largest brain autopsy study of AD and related dementias.

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.

Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2.

PubMed

Silvestri, Valentina; Barrowdale, Daniel; Mulligan, Anna Marie; Neuhausen, Susan L; Fox, Stephen; Karlan, Beth Y; Mitchell, Gillian; James, Paul; Thull, Darcy L; Zorn, Kristin K; Carter, Natalie J; Nathanson, Katherine L; Domchek, Susan M; Rebbeck, Timothy R; Ramus, Susan J; Nussbaum, Robert L; Olopade, Olufunmilayo I; Rantala, Johanna; Yoon, Sook-Yee; Caligo, Maria A; Spugnesi, Laura; Bojesen, Anders; Pedersen, Inge Sokilde; Thomassen, Mads; Jensen, Uffe Birk; Toland, Amanda Ewart; Senter, Leigha; Andrulis, Irene L; Glendon, Gord; Hulick, Peter J; Imyanitov, Evgeny N; Greene, Mark H; Mai, Phuong L; Singer, Christian F; Rappaport-Fuerhauser, Christine; Kramer, Gero; Vijai, Joseph; Offit, Kenneth; Robson, Mark; Lincoln, Anne; Jacobs, Lauren; Machackova, Eva; Foretova, Lenka; Navratilova, Marie; Vasickova, Petra; Couch, Fergus J; Hallberg, Emily; Ruddy, Kathryn J; Sharma, Priyanka; Kim, Sung-Won; Teixeira, Manuel R; Pinto, Pedro; Montagna, Marco; Matricardi, Laura; Arason, Adalgeir; Johannsson, Oskar Th; Barkardottir, Rosa B; Jakubowska, Anna; Lubinski, Jan; Izquierdo, Angel; Pujana, Miguel Angel; Balmaña, Judith; Diez, Orland; Ivady, Gabriella; Papp, Janos; Olah, Edith; Kwong, Ava; Nevanlinna, Heli; Aittomäki, Kristiina; Perez Segura, Pedro; Caldes, Trinidad; Van Maerken, Tom; Poppe, Bruce; Claes, Kathleen B M; Isaacs, Claudine; Elan, Camille; Lasset, Christine; Stoppa-Lyonnet, Dominique; Barjhoux, Laure; Belotti, Muriel; Meindl, Alfons; Gehrig, Andrea; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Hahnen, Eric; Kast, Karin; Arnold, Norbert; Varon-Mateeva, Raymonda; Wand, Dorothea; Godwin, Andrew K; Evans, D Gareth; Frost, Debra; Perkins, Jo; Adlard, Julian; Izatt, Louise; Platte, Radka; Eeles, Ros; Ellis, Steve; Hamann, Ute; Garber, Judy; Fostira, Florentia; Fountzilas, George; Pasini, Barbara; Giannini, Giuseppe; Rizzolo, Piera; Russo, Antonio; Cortesi, Laura; Papi, Laura; Varesco, Liliana; Palli, Domenico; Zanna, Ines; Savarese, Antonella; Radice, Paolo; Manoukian, Siranoush; Peissel, Bernard; Barile, Monica; Bonanni, Bernardo; Viel, Alessandra; Pensotti, Valeria; Tommasi, Stefania; Peterlongo, Paolo; Weitzel, Jeffrey N; Osorio, Ana; Benitez, Javier; McGuffog, Lesley; Healey, Sue; Gerdes, Anne-Marie; Ejlertsen, Bent; Hansen, Thomas V O; Steele, Linda; Ding, Yuan Chun; Tung, Nadine; Janavicius, Ramunas; Goldgar, David E; Buys, Saundra S; Daly, Mary B; Bane, Anita; Terry, Mary Beth; John, Esther M; Southey, Melissa; Easton, Douglas F; Chenevix-Trench, Georgia; Antoniou, Antonis C; Ottini, Laura

2016-02-09

BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10(-12)). On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.

Pathologic features of mycobacteriosis in naturally infected Syngnathidae and novel transcriptome assembly in association with disease.

PubMed

Fogelson, S B; Fast, M D; Leary, J; Camus, A C

2017-11-01

Syngnathidae (seahorses, seadragons and pipefish) suffer significant losses from non-tuberculous mycobacteria. However, they produce markedly different lesions in response to the disease compared to other teleost species, notably infrequent granuloma formation. This study evaluated 270 syngnathid fish, from which 92 were diagnosed with mycobacteriosis by histopathology, culture or both. Microscopic lesions variably consisted of random foci of coagulative necrosis in multiple organs, containing high numbers of free bacteria and large aggregates or sheets of macrophages with cytoplasm laden with acid-fast bacilli. Mycobacterial associated granulomas were identified in only six seahorses. Five fish had positive cultures with no observed microscopic changes. RNA-seq of the head kidney was performed to investigate the transcriptome of two infected and six non-infected lined seahorses Hippocampus erectus. Assembled and annotated putative transcripts serve to enrich the database for this species, as well as provide baseline data for understanding the pathogenesis of mycobacteriosis in seahorses. Putative components of the innate immune system (IL-1β, IL-6, TNF, NOS, Toll-like receptor 1, MHC Class I, NF-κβ, transforming growth factor beta, MyD88) were identified in the RNA-seq data set. However, a homolog for a key component in the TH1 adaptive immune response, interferon-gamma, was not identified and may underlie the unique pathologic presentation. © 2017 John Wiley & Sons Ltd.

Targeted inactivation of the mouse locus encoding coagulation factor XIII-A: hemostatic abnormalities in mutant mice and characterization of the coagulation deficit.

PubMed

Lauer, Peter; Metzner, Hubert J; Zettlmeissl, Gerd; Li, Meng; Smith, Austin G; Lathe, Richard; Dickneite, Gerhard

2002-12-01

Blood coagulation factor XIII (FXIII) promotes cross-linking of fibrin during blood coagulation; impaired clot stabilization in human genetic deficiency is associated with marked pathologies of major clinical impact, including bleeding symptoms and deficient wound healing. To investigate the role of FXIII we employed homologous recombination to generate a targeted deletion of the inferred exon 7 of the FXIII-A gene. FXIII transglutaminase activity in plasma was reduced to about 50% in mice heterozygous for the mutant allele, and was abolished in homozygous null mice. Plasma fibrin gamma-dimerization was also indetectable in the homozygous deficient animals, confirming the absence of activatable FXIII. Homozygous mutant mice were fertile, although reproduction was impaired. Bleeding episodes, hematothorax, hematoperitoneum and subcutaneous hemorrhage in mutant mice were associated with reduced survival. Arrest of tail-tip bleeding in FXIII-A deficient mice was markedly and significantly delayed; replacement of mutant mice with human plasma FXIII (Fibrogammin P) restored bleeding time to within the normal range. Thrombelastography (TEG) experiments demonstrated impaired clot stabilization in FXIII-A mutant mice, replacement with human FXIII led to dose-dependent TEG normalization. The mutant mice thus reiterate some key features of the human genetic disorder: they will be valuable in assessing the role of FXIII in other associated pathologies and the development of new therapies.

A comparison of machine learning techniques for survival prediction in breast cancer

PubMed Central

2011-01-01

Background The ability to accurately classify cancer patients into risk classes, i.e. to predict the outcome of the pathology on an individual basis, is a key ingredient in making therapeutic decisions. In recent years gene expression data have been successfully used to complement the clinical and histological criteria traditionally used in such prediction. Many "gene expression signatures" have been developed, i.e. sets of genes whose expression values in a tumor can be used to predict the outcome of the pathology. Here we investigate the use of several machine learning techniques to classify breast cancer patients using one of such signatures, the well established 70-gene signature. Results We show that Genetic Programming performs significantly better than Support Vector Machines, Multilayered Perceptrons and Random Forests in classifying patients from the NKI breast cancer dataset, and comparably to the scoring-based method originally proposed by the authors of the 70-gene signature. Furthermore, Genetic Programming is able to perform an automatic feature selection. Conclusions Since the performance of Genetic Programming is likely to be improvable compared to the out-of-the-box approach used here, and given the biological insight potentially provided by the Genetic Programming solutions, we conclude that Genetic Programming methods are worth further investigation as a tool for cancer patient classification based on gene expression data. PMID:21569330

Forensic Pathology Education in Pathology Residency

PubMed Central

Ross, Wayne K.; Domen, Ronald E.

2017-01-01

Forensic pathology is a fundamental part of anatomic pathology training during pathology residency. However, the lack of information on forensic teaching suggests the highly variable nature of forensic education. A survey of pathology residency program directors was performed to determine key aspects of their respective forensic rotations and curriculum. A total of 38.3% of programs from across the country responded, and the survey results show 5.6% don’t require a forensic pathology rotation. In those that do, most forensic pathology rotations are 4 weeks long, are done at a medical examiner’s office, and require set prerequisites. A total of 21.1% of responding programs have residents who are not receiving documented evaluations for this rotation. While 39.6% of programs have a defined forensics curriculum, as many as 15% do not. Furthermore, nearly 43% of programs place no limit on counting forensic autopsies when applying for pathology board examinations. Our survey confirmed the inconsistent nature of forensic pathology training in resident education. Additionally, our curriculum was reorganized to create a more robust educational experience. A pre- and post-forensic lecture quiz and Resident In-Service Examination scores were analyzed to determine our curriculum’s impact and effectiveness. Analysis of our pre- and post-lecture quiz showed an improved overall average as well as an increase in Resident In-Service Examination scores, indicating improved general forensic pathology knowledge. Using this knowledge, along with changes in our curriculum, we generated a number of recommendations for improving forensic pathology education in pathology residency. PMID:28913415

3D printed pathological sectioning boxes to facilitate radiological-pathological correlation in hepatectomy cases.

PubMed

Trout, Andrew T; Batie, Matthew R; Gupta, Anita; Sheridan, Rachel M; Tiao, Gregory M; Towbin, Alexander J

2017-11-01

Radiogenomics promises to identify tumour imaging features indicative of genomic or proteomic aberrations that can be therapeutically targeted allowing precision personalised therapy. An accurate radiological-pathological correlation is critical to the process of radiogenomic characterisation of tumours. An accurate correlation, however, is difficult to achieve with current pathological sectioning techniques which result in sectioning in non-standard planes. The purpose of this work is to present a technique to standardise hepatic sectioning to facilitateradiological-pathological correlation. We describe a process in which three-dimensional (3D)-printed specimen boxes based on preoperative cross-sectional imaging (CT and MRI) can be used to facilitate pathological sectioning in standard planes immediately on hepatic resection enabling improved tumour mapping. We have applied this process in 13 patients undergoing hepatectomy and have observed close correlation between imaging and gross pathology in patients with both unifocal and multifocal tumours. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cholangiocarcinoma: classification, diagnosis, staging, imaging features, and management.

PubMed

Oliveira, Irai S; Kilcoyne, Aoife; Everett, Jamie M; Mino-Kenudson, Mari; Harisinghani, Mukesh G; Ganesan, Karthik

2017-06-01

Cholangiocarcinoma is a relatively uncommon malignant neoplasm with poor prognosis. The distinction between extrahepatic and intrahepatic subtypes is important as epidemiological features, biologic and pathologic characteristics, and clinical course are different for both entities. This review study focuses on the role imaging plays in the diagnosis, classification, staging, and post-treatment assessment of cholangiocarcinoma.

[Establishment of an iRFP and luciferase dual-color fluorescence-traced hepatocellular carcinoma transplantation model in nude mice].

PubMed

Li, Hongjun; Yang, Tianhua; Huang, Yanping; Liu, Mingzhu; Qin, Zhongqiang; Chu, Fei; Li, Zhenghong; Li, Yonghai

2017-11-01

Objective To establish a hepatocellular carcinoma xenograft model in nude mice which could stably express gene and be monitored dynamically. Methods We first constructed the lentiviral particles containing luciferase (Luc) and near-infrared fluorescent protein (iRFP) and puromycin resistance gene, and then transduced them into the HepG2 hepatoma cells. The cell line stably expressing Luc and iRFP genes were screened and inoculated into nude mice to establish xenograft tumor model. Tumor growth was monitored using in vivo imaging system. HE staining and immunohistochemistry were used to evaluate the pathological features and tumorigenic ability. Results HepG2 cells stably expressing iRFP and Luc were obtained; with the engineered cell line, xenograft model was successfully established with the features of proper tumor developing time and high rate of tumor formation as well as typical pathological features as showed by HE staining and immunohistochemistry. Conclusion Hepatocellular carcinoma model in nude mice with the features of stable gene expression and dynamical monitoring has been established successfully with the HepG2-iRFP-Luc cell line.

Analysis of pathology department Web sites and practical recommendations.

PubMed

Nero, Christopher; Dighe, Anand S

2008-09-01

There are numerous customers for pathology departmental Web sites, including pathology department staff, clinical staff, residency applicants, job seekers, and other individuals outside the department seeking department information. Despite the increasing importance of departmental Web sites as a means of distributing information, no analysis has been done to date of the content and usage of pathology department Web sites. In this study, we analyzed pathology department Web sites to examine the elements present on each site and to evaluate the use of search technology on these sites. Further, we examined the usage patterns of our own departmental Internet and internet Web sites to better understand the users of pathology Web sites. We reviewed selected departmental pathology Web sites and analyzed their content and functionality. Our institution's departmental pathology Web sites were modified to enable detailed information to be stored regarding users and usage patterns, and that information was analyzed. We demonstrate considerable heterogeneity in departmental Web sites with many sites lacking basic content and search features. In addition, we demonstrate that increasing the traffic of a department's informational Web sites may result in reduced phone inquiries to the laboratory. We propose recommendations for pathology department Web sites to maximize promotion of a department's mission. A departmental pathology Web site is an essential communication tool for all pathology departments, and attention to the users and content of the site can have operational impact.

Transient mutism and pathologic laughter in the course of cerebellitis.

PubMed

Dimova, Petia S; Bojinova, Veneta S; Milanov, Ivan G

2009-07-01

The phenomenon of cerebellar mutism with subsequent dysarthria is most commonly described as a part of posterior fossa syndrome after surgery for neoplasms in childhood. Pathologic laughter, on the other hand, is observed primarily in various neurologic diseases in adults. In the present case, a child manifested transient mutism and pathologic laughter during a severe cerebellitis. Headache, vertigo, and impaired consciousness developed during an acute respiratory infection. Thereafter, severe ataxia, mutism, and involuntary laughter became the main clinical features, as well as pyramidal signs. Magnetic resonance imaging revealed cerebellar swelling and T(2) hyperintensity. During steroid treatment, a gradual vanishing of the pathologic laughter and improvement of the motor and speech functions occurred. Recovery was slow and incomplete, and follow-up magnetic resonance imaging showed cerebellar atrophy. This case confirms that mutism is a rare, but possible, manifestation in acute parainfectious cerebellitis and provides a novel example of pathologic laughter during this disease in childhood.

Are pathological narcissism and psychopathy different constructs or different names for the same thing? A study based on Italian nonclinical adult participants.

PubMed

Fossati, Andrea; Pincus, Aaron L; Borroni, Serena; Munteanu, Arina Ferrari; Maffei, Cesare

2014-06-01

To understand the similarities and differences in personality traits and moral disengagement associated with pathological narcissism and psychopathy, 740 Italian active community members who voluntarily participated in the study were administered the Italian versions of the Pathological Narcissism Inventory, the Levenson Self-Report Psychopathy Scale, the HEXACO Personality Inventory, and the Moral Disengagement Scale. Hierarchical regression analyses showed that low Honesty-Humility and Antagonism (i.e., low Agreeableness) were personality traits common to both pathological narcissism and psychopathy, whereas low Conscientiousness was only related to psychopathy. Different associations with the HEXACO-PI scales and facets were observed for narcissistic grandiosity and narcissistic vulnerability, as well as for primary psychopathy and secondary psychopathy. Moral disengagement represented a common feature of pathological narcissism and psychopathy that was related to narcissistic vulnerability and to primary and secondary psychopathy, but not to narcissistic grandiosity.

MR imaging features associated with distant metastasis-free survival of patients with invasive breast cancer: a case-control study.

PubMed

Song, Sung Eun; Shin, Sung Ui; Moon, Hyeong-Gon; Ryu, Han Suk; Kim, Kwangsoo; Moon, Woo Kyung

2017-04-01

Preoperative breast magnetic resonance (MR) imaging features of primary breast cancers may have the potential to act as prognostic biomarkers by providing morphologic and kinetic features representing inter- or intra-tumor heterogeneity. Recent radiogenomic studies reveal that several radiologist-annotated image features are associated with genes or signal pathways involved in tumor progression, treatment resistance, and distant metastasis (DM). We investigate whether preoperative breast MR imaging features are associated with worse DM-free survival in patients with invasive breast cancer. Of the 3536 patients with primary breast cancers who underwent preoperative MR imaging between 2003 and 2009, 147 patients with DM were identified and one-to-one matched with control patients (n = 147) without DM according to clinical-pathologic variables. Three radiologists independently reviewed the MR images of 294 patients, and the association of DM-free survival with MR imaging and clinical-pathologic features was assessed using Cox proportional hazard models. Of MR imaging features, rim enhancement (hazard ratio [HR], 1.83 [95% confidence interval, CI 1.29, 2.51]; p = 0.001) and peritumoral edema (HR, 1.48 [95% CI 1.03, 2.11]; p = 0.032) were the significant features associated with worse DM-free survival. The significant MR imaging features, however, were different between breast cancer subtypes and stages. Preoperative breast MR imaging features of rim enhancement and peritumoral edema may be used as prognostic biomarkers that help predict DM risk in patients with breast cancer, thereby potentially enabling improved personalized treatment and monitoring strategies for individual patients.

Teaching pediatric laboratory medicine to pathology residents.

PubMed

Pysher, Theodore J; Bach, Philip R; Geaghan, Sharon M; Hamilton, Marilyn S; Laposata, Michael; Lockitch, Gillian; Brugnara, Carlo; Coffin, Cheryl M; Pasquali, Marzia; Rinaldo, Piero; Roberts, William L; Rutledge, Joe C; Ashwood, Edward R; Blaylock, Robert C; Campos, Joseph M; Goldsmith, Barbara; Jones, Patricia M; Lim, Megan; Meikle, A Wayne; Perkins, Sherrie L; Perry, Deborah A; Petti, Cathy A; Rogers, Beverly B; Steele, Paul E; Weiss, Ronald L; Woods, Gail

2006-07-01

Laboratory data are essential to the medical care of fetuses, infants, children, and adolescents. However, the performance and interpretation of laboratory tests on specimens from these patients, which may constitute a significant component of the workload in general hospitals and integrated health care systems as well as specialized perinatal or pediatric centers, present unique challenges to the clinical pathologist and the laboratory. Therefore, pathology residents should receive training in pediatric laboratory medicine. Children's Health Improvement through Laboratory Diagnostics, a group of pathologists and laboratory scientists with interest and expertise in pediatric laboratory medicine, convened a task force to develop a list of curriculum topics, key resources, and training experiences in pediatric laboratory medicine for trainees in anatomic and clinical pathology or straight clinical pathology residency programs and in pediatric pathology fellowship programs. Based on the experiences of 11 training programs, we have compiled a comprehensive list of pediatric topics in the areas of clinical chemistry, endocrinology, hematology, urinalysis, coagulation medicine, transfusion medicine, immunology, microbiology and virology, biochemical genetics, cytogenetics and molecular diagnostics, point of care testing, and laboratory management. This report also includes recommendations for training experiences and a list of key texts and other resources in pediatric laboratory medicine. Clinical pathologists should be trained to meet the laboratory medicine needs of pediatric patients and to assist the clinicians caring for these patients with the selection and interpretation of laboratory studies. This review helps program directors tailor their curricula to more effectively provide this training.

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.

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.

Pathological features of glutaminase toxicity.

PubMed Central

Baskerville, A.; Hambleton, P.; Benbough, J. E.

1980-01-01

In an investigation of the toxicity of the anti-tumour enzyme glutaminase Rhesus monkeys, marmosets, rabbits and mice were given various doses of chemically modified glutaminase parenterally. The enzyme induced diarrhoea and dysentery and at all but the lowest doses caused illness which was fatal within 10 days. Pathological lesions produced were hepatic lipidosis and glycogen accumulation, and, in the primates, acute necrotizing colitis. Images Fig. 1 Fig. 2 PMID:6775661

Trends in Pathology Graduate Medical Education Programs and Positions, 2001 to 2017.

PubMed

Petriceks, Aldis H; Salmi, Darren

2018-01-01

The US medical workforce is facing an impending physician shortage. This shortage holds special concern for pathologists, as many senior practitioners are set to retire in the coming years. Indeed, studies indicate a "pathologist gap" may grow through 2030. As such, it is important to understand current and future trends in US pathology. One key factor is graduate medical education. In this study, we analyzed data from the Accreditation Council of Graduate Medical Education, to determine the change in pathology graduate medical education programs and positions, from 2001 to 2017. We found that pathology programs and positions have increased since the 2001 to 2002 academic year, even after adjusting for population growth. However, this increase is much lower than that of total graduate medical education. Furthermore, many pathology subspecialties have declined in population-adjusted levels. Other subspecialties, such as selective pathology, have grown disproportionately. Our findings may be valuable for understanding the state of US pathology, now and in the future. They imply that more resources-or technological innovations-may be needed for specific pathology programs, in hopes of closing the pathologist gap for both this specialty and its subspecialties.

Virtual microscopy and digital pathology in training and education.

PubMed

Hamilton, Peter W; Wang, Yinhai; McCullough, Stephen J

2012-04-01

Traditionally, education and training in pathology has been delivered using textbooks, glass slides and conventional microscopy. Over the last two decades, the number of web-based pathology resources has expanded dramatically with centralized pathological resources being delivered to many students simultaneously. Recently, whole slide imaging technology allows glass slides to be scanned and viewed on a computer screen via dedicated software. This technology is referred to as virtual microscopy and has created enormous opportunities in pathological training and education. Students are able to learn key histopathological skills, e.g. to identify areas of diagnostic relevance from an entire slide, via a web-based computer environment. Students no longer need to be in the same room as the slides. New human-computer interfaces are also being developed using more natural touch technology to enhance the manipulation of digitized slides. Several major initiatives are also underway introducing online competency and diagnostic decision analysis using virtual microscopy and have important future roles in accreditation and recertification. Finally, researchers are investigating how pathological decision-making is achieved using virtual microscopy and modern eye-tracking devices. Virtual microscopy and digital pathology will continue to improve how pathology training and education is delivered. © 2012 The Authors APMIS © 2012 APMIS.

Deep learning with non-medical training used for chest pathology identification

NASA Astrophysics Data System (ADS)

Bar, Yaniv; Diamant, Idit; Wolf, Lior; Greenspan, Hayit

2015-03-01

In this work, we examine the strength of deep learning approaches for pathology detection in chest radiograph data. Convolutional neural networks (CNN) deep architecture classification approaches have gained popularity due to their ability to learn mid and high level image representations. We explore the ability of a CNN to identify different types of pathologies in chest x-ray images. Moreover, since very large training sets are generally not available in the medical domain, we explore the feasibility of using a deep learning approach based on non-medical learning. We tested our algorithm on a dataset of 93 images. We use a CNN that was trained with ImageNet, a well-known large scale nonmedical image database. The best performance was achieved using a combination of features extracted from the CNN and a set of low-level features. We obtained an area under curve (AUC) of 0.93 for Right Pleural Effusion detection, 0.89 for Enlarged heart detection and 0.79 for classification between healthy and abnormal chest x-ray, where all pathologies are combined into one large class. This is a first-of-its-kind experiment that shows that deep learning with large scale non-medical image databases may be sufficient for general medical image recognition tasks.

Mucor irregularis infection and lethal midline granuloma: a case report and review of published literature.

PubMed

Li, Dong Ming; Lun, Li De

2012-12-01

Mucor irregularis (Rhizomucor variabilis) infection and lethal midline granuloma (LMG) are characterized by progressive swelling, ulceration, and destruction of the central face that is usually fatal. Pathological features are inflammation, necrosis, and granulation. LMG has been called by various names, and in recent years, it has been known as NK/T cell lymphoma. However, diagnosis still relies on the progressive necrosis course rather than malignancy in histology. The disease has long challenged physicians, particularly when it worsens with radiotherapy or chemotherapy but sometimes achieves total remission without anti-malignancy therapies. We describe a 35-year-old man who had typical clinical-pathological symptoms of LMG, which turned out to be primary M. irregularis infection; that was diagnosed by positive tissue culture and fungal elements in histology. The patient was successfully treated with antifungal therapy (liposomal amphotericin B, total 4,600 mg and amphotericin B total 277 mg, over a duration of 70 days). We hereby review current knowledge about the epidemiology, clinical manifestations, radiographic characteristics, and pathologic features of LMG with those of M. irregularis infection and their associations. We conclude that primary M. irregulars infection can mimic the clinico-pathological symptoms of LMG and the condition responds favorably to aggressive antifungal therapy.

Homo floresiensis Contextualized: A Geometric Morphometric Comparative Analysis of Fossil and Pathological Human Samples

PubMed Central

Baab, Karen L.; McNulty, Kieran P.; Harvati, Katerina

2013-01-01

The origin of hominins found on the remote Indonesian island of Flores remains highly contentious. These specimens may represent a new hominin species, Homo floresiensis, descended from a local population of Homo erectus or from an earlier (pre-H. erectus) migration of a small-bodied and small-brained hominin out of Africa. Alternatively, some workers suggest that some or all of the specimens recovered from Liang Bua are pathological members of a small-bodied modern human population. Pathological conditions proposed to explain their documented anatomical features include microcephaly, myxoedematous endemic hypothyroidism (“cretinism”) and Laron syndrome (primary growth hormone insensitivity). This study evaluates evolutionary and pathological hypotheses through comparative analysis of cranial morphology. Geometric morphometric analyses of landmark data show that the sole Flores cranium (LB1) is clearly distinct from healthy modern humans and from those exhibiting hypothyroidism and Laron syndrome. Modern human microcephalic specimens converge, to some extent, on crania of extinct species of Homo. However in the features that distinguish these two groups, LB1 consistently groups with fossil hominins and is most similar to H. erectus. Our study provides further support for recognizing the Flores hominins as a distinct species, H. floresiensis, whose affinities lie with archaic Homo. PMID:23874886

Analysis of spatial heterogeneity in normal epithelium and preneoplastic alterations in mouse prostate tumor models

PubMed Central

Valkonen, Mira; Ruusuvuori, Pekka; Kartasalo, Kimmo; Nykter, Matti; Visakorpi, Tapio; Latonen, Leena

2017-01-01

Cancer involves histological changes in tissue, which is of primary importance in pathological diagnosis and research. Automated histological analysis requires ability to computationally separate pathological alterations from normal tissue with all its variables. On the other hand, understanding connections between genetic alterations and histological attributes requires development of enhanced analysis methods suitable also for small sample sizes. Here, we set out to develop computational methods for early detection and distinction of prostate cancer-related pathological alterations. We use analysis of features from HE stained histological images of normal mouse prostate epithelium, distinguishing the descriptors for variability between ventral, lateral, and dorsal lobes. In addition, we use two common prostate cancer models, Hi-Myc and Pten+/− mice, to build a feature-based machine learning model separating the early pathological lesions provoked by these genetic alterations. This work offers a set of computational methods for separation of early neoplastic lesions in the prostates of model mice, and provides proof-of-principle for linking specific tumor genotypes to quantitative histological characteristics. The results obtained show that separation between different spatial locations within the organ, as well as classification between histologies linked to different genetic backgrounds, can be performed with very high specificity and sensitivity. PMID:28317907

Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project.

PubMed

Weisenburger, Dennis D; Savage, Kerry J; Harris, Nancy Lee; Gascoyne, Randy D; Jaffe, Elaine S; MacLennan, Kenneth A; Rüdiger, Thomas; Pileri, Stefano; Nakamura, Shigeo; Nathwani, Bharat; Campo, Elias; Berger, Francoise; Coiffier, Bertrand; Kim, Won-Seog; Holte, Harald; Federico, Massimo; Au, Wing Y; Tobinai, Kensei; Armitage, James O; Vose, Julie M

2011-03-24

The International Peripheral T-cell Lymphoma Project is a collaborative effort to better understand peripheral T-cell lymphoma (PTCL). A total of 22 institutions submitted clinical and pathologic material on 1314 cases. One objective was to analyze the clinical and pathologic features of 340 cases of PTCL, not otherwise specified. The median age of the patients was 60 years, and the majority (69%) presented with advanced stage disease. Most patients (87%) presented with nodal disease, but extranodal disease was present in 62%. The 5-year overall survival was 32%, and the 5-year failure-free survival was only 20%. The majority of patients (80%) were treated with combination chemotherapy that included an anthracycline, but there was no survival advantage. The International Prognostic Index (IPI) was predictive of both overall survival and failure-free survival (P < .001). Multivariate analysis of clinical and pathologic prognostic factors, respectively, when controlling for the IPI, identified bulky disease (≥ 10 cm), thrombocytopenia (< 150 × 10(9)/L), and a high number of transformed tumor cells (> 70%) as adverse predictors of survival, but only the latter was significant in final analysis. Thus, the IPI and a single pathologic feature could be used to stratify patients with PTCL-not otherwise specified for novel and risk-adapted therapies.

The changing role of the pathologist in the management of Barrett's oesophagus.

PubMed

Hopcroft, Suzanne A; Shepherd, Neil A

2014-10-01

Pathological specimens from columnar-lined oesophagus (CLO) comprise a considerable proportion of the workload of gastrointestinal pathologists in Western countries. There remain controversies concerning the diagnostic role of pathology. More recently, in the UK at least, the diagnosis has been regarded as primarily an endoscopic endeavour, with pathology being corroborative and only diagnostic when endoscopic features are equivocal or when there are additional features that make the endoscopic diagnosis unclear. There is also recognition that demonstration of intestinalisation or 'goblet cells' is not paramount, and should not be required for the diagnosis. There have been notable changes in the management of CLO neoplasia: pathologists are centrally involved in its management. Pathological assessment of endoscopic mucosal resection (EMR) specimens provides the most useful means of determining the management of early neoplasia and of determining indications for surgery. This represents an extraordinarily rapid change in management, in that, <10 years ago, laborious Seattle-type biopsy protocols were recommended, and high grade dysplasia was an indication for resectional surgery. Now, individual patient management is paramount: multi-professional meetings determine management after biopsy and EMR assessment. One significant change is that major resections are undertaken less often, in Western countries, for CLO neoplasia. © 2014 John Wiley & Sons Ltd.

Correlation of Clinicoserologic and Pathologic Classifications of Inflammatory Myopathies

PubMed Central

Fernandez, Carla; Bardin, Nathalie; De Paula, André Maues; Salort-Campana, Emmanuelle; Benyamine, Audrey; Franques, Jérôme; Schleinitz, Nicolas; Weiller, Pierre-Jean; Pouget, Jean; Pellissier, Jean-François; Figarella-Branger, Dominique

2013-01-01

Abstract The idiopathic inflammatory myopathies (IIM) are acquired muscle diseases characterized by muscle weakness and inflammation on muscle biopsy. Clinicoserologic classifications do not take muscle histology into account to distinguish the subsets of IIM. Our objective was to determine the pathologic features of each serologic subset of IIM and to correlate muscle biopsy results with the clinicoserologic classification defined by Troyanov et al, and with the final diagnoses. We retrospectively studied a cohort of 178 patients with clinicopathologic features suggestive of IIM with the exclusion of inclusion body myositis. At the end of follow-up, 156 of 178 cases were still categorized as IIM: pure dermatomyositis, n = 44; pure polymyositis, n = 14; overlap myositis, n = 68; necrotizing autoimmune myopathy, n = 8; cancer-associated myositis, n = 18; and unclassified IIM, n = 4. The diagnosis of IIM was ruled out in the 22 remaining cases. Pathologic dermatomyositis was the most frequent histologic picture in all serologic subsets of IIM, with the exception of patients with anti-Ku or anti-SRP autoantibodies, suggesting that it supports the histologic diagnosis of pure dermatomyositis, but also myositis of connective tissue diseases and cancer-associated myositis. Unspecified myositis was the second most frequent histologic pattern. It frequently correlated with overlap myositis, especially with anti-Ku or anti-PM-Scl autoantibodies. Pathologic polymyositis was rare and more frequently correlated with myositis mimickers than true polymyositis. The current study shows that clinicoserologic and pathologic data are complementary and must be taken into account when classifying patients with IIM patients. We propose guidelines for diagnosis according to both clinicoserologic and pathologic classifications, to be used in clinical practice. PMID:23269233

Twinkle artefact in the ultrasound diagnosis of superficial epidermoid cysts

PubMed Central

Clarke, Richard; Suresh, Priya; Thomas, Rose

2016-01-01

Aim The aim of the study was to evaluate whether the twinkle artefact is a valuable feature in the sonographic diagnosis of superficial epidermoid cysts. Materials and methods A retrospective search was undertaken of our institution’s Radiology Information System and pathology database to identify cases of superficial masses showing the twinkle artefact that proceeded to surgical excision. Results Eighteen superficial masses demonstrating the twinkle artefact were identified that were submitted for pathological analysis. Of these, 17 were confirmed to represent epidermoid cysts and only 1 case had an alternative diagnosis (proliferating trichilemmal cyst). Conclusion The presence of the twinkle artefact appears to be a specific and valuable ancillary sonographic feature for the diagnosis of superficial epidermoid cysts. PMID:27867407

An examination of the relationship between childhood emotional abuse and borderline personality disorder features: the role of difficulties with emotion regulation.

PubMed

Kuo, Janice R; Khoury, Jennifer E; Metcalfe, Rebecca; Fitzpatrick, Skye; Goodwill, Alasdair

2015-01-01

Childhood abuse has been consistently linked with borderline personality disorder (BPD) and recent studies suggest that some forms of childhood abuse might be uniquely related to both BPD and BPD features. In addition, difficulties with emotion regulation have been found to be associated with childhood abuse, BPD, as well as BPD features. The present study examined (1) whether frequency of childhood emotional abuse is uniquely associated with BPD feature severity when controlling for other forms of childhood abuse and (2) whether difficulties with emotion regulation accounts for the relationship between childhood emotional abuse and BPD feature severity. A sample of undergraduates (n=243) completed the Childhood Trauma Questionnaire - Short Form, Difficulties in Emotion Regulation Scale, and Borderline Symptom List-23. Multiple regression analyses and Structural Equation Modeling were conducted. Results indicated that frequency of childhood emotional abuse (and not sexual or physical abuse) was uniquely associated with BPD feature severity. In addition, while there was no direct path between childhood emotional abuse, childhood physical abuse, or childhood sexual abuse and BPD features, there was an indirect relationship between childhood emotional abuse and BPD features through difficulties with emotion regulation. These findings suggest that, of the different forms of childhood abuse, emotional abuse specifically, may have a developmental role in BPD pathology. Prevention and treatment of BPD pathology might benefit from the provision of emotion regulation strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

EG-VEGF: a key endocrine factor in placental development.

PubMed

Brouillet, Sophie; Hoffmann, Pascale; Feige, Jean-Jacques; Alfaidy, Nadia

2012-10-01

Endocrine gland-derived vascular endothelial growth factor (EG-VEGF), also named prokineticin 1, is the canonical member of the prokineticin family. Numerous reports suggest a direct involvement of this peptide in normal and pathological reproductive processes. Recent advances propose EG-VEGF as a key endocrine factor that controls many aspects of placental development and suggest its involvement in the development of preeclampsia (PE), the most threatening pathology of human pregnancy. This review describes the finely tuned action and regulation of EG-VEGF throughout human pregnancy, argues for its clinical relevance as a potential diagnostic marker of the onset of PE, and discusses future research directions for therapeutic targeting of EG-VEGF. Copyright © 2012 Elsevier Ltd. All rights reserved.

Towards a taxonomy for integrated care: a mixed-methods study

PubMed Central

Valentijn, Pim P.; Boesveld, Inge C.; van der Klauw, Denise M.; Ruwaard, Dirk; Struijs, Jeroen N.; Molema, Johanna J.W.; Bruijnzeels, Marc A.; Vrijhoef, Hubertus JM.

2015-01-01

Introduction Building integrated services in a primary care setting is considered an essential important strategy for establishing a high-quality and affordable health care system. The theoretical foundations of such integrated service models are described by the Rainbow Model of Integrated Care, which distinguishes six integration dimensions (clinical, professional, organisational, system, functional and normative integration). The aim of the present study is to refine the Rainbow Model of Integrated Care by developing a taxonomy that specifies the underlying key features of the six dimensions. Methods First, a literature review was conducted to identify features for achieving integrated service delivery. Second, a thematic analysis method was used to develop a taxonomy of key features organised into the dimensions of the Rainbow Model of Integrated Care. Finally, the appropriateness of the key features was tested in a Delphi study among Dutch experts. Results The taxonomy consists of 59 key features distributed across the six integration dimensions of the Rainbow Model of Integrated Care. Key features associated with the clinical, professional, organisational and normative dimensions were considered appropriate by the experts. Key features linked to the functional and system dimensions were considered less appropriate. Discussion This study contributes to the ongoing debate of defining the concept and typology of integrated care. This taxonomy provides a development agenda for establishing an accepted scientific framework of integrated care from an end-user, professional, managerial and policy perspective. PMID:25759607

Towards a taxonomy for integrated care: a mixed-methods study.

PubMed

Valentijn, Pim P; Boesveld, Inge C; van der Klauw, Denise M; Ruwaard, Dirk; Struijs, Jeroen N; Molema, Johanna J W; Bruijnzeels, Marc A; Vrijhoef, Hubertus Jm

2015-01-01

Building integrated services in a primary care setting is considered an essential important strategy for establishing a high-quality and affordable health care system. The theoretical foundations of such integrated service models are described by the Rainbow Model of Integrated Care, which distinguishes six integration dimensions (clinical, professional, organisational, system, functional and normative integration). The aim of the present study is to refine the Rainbow Model of Integrated Care by developing a taxonomy that specifies the underlying key features of the six dimensions. First, a literature review was conducted to identify features for achieving integrated service delivery. Second, a thematic analysis method was used to develop a taxonomy of key features organised into the dimensions of the Rainbow Model of Integrated Care. Finally, the appropriateness of the key features was tested in a Delphi study among Dutch experts. The taxonomy consists of 59 key features distributed across the six integration dimensions of the Rainbow Model of Integrated Care. Key features associated with the clinical, professional, organisational and normative dimensions were considered appropriate by the experts. Key features linked to the functional and system dimensions were considered less appropriate. This study contributes to the ongoing debate of defining the concept and typology of integrated care. This taxonomy provides a development agenda for establishing an accepted scientific framework of integrated care from an end-user, professional, managerial and policy perspective.

Eating disorder pathology among overweight treatment-seeking youth: clinical correlates and cross-sectional risk modeling.

PubMed

Eddy, Kamryn T; Tanofsky-Kraff, Marian; Thompson-Brenner, Heather; Herzog, David B; Brown, Timothy A; Ludwig, David S

2007-10-01

Preliminary research suggests that pediatric overweight is associated with increased eating disorder pathology, however, little is known about which overweight youth are most vulnerable to eating disorder pathology. We therefore investigated 122 overweight treatment-seeking youth to describe eating disorder pathology and mental health correlates, and to identify psychopathological constructs that may place overweight youth at increased risk for eating disorder pathology. Youth participated in a comprehensive assessment of eating disorders, mood and anxiety disorders, general psychopathology, and risk variables involving semi-structured clinical interviews and self- and parent-report questionnaires prior to the initiation of weight-loss treatment. Ten youth met criteria for an eating disorder, and over one-third endorsed recent binge eating. Eating disorder pathology was associated with depressive and anxious symptoms (p's<0.001). Structural equation modeling indicated increased negative affect, teasing experience, and thin-ideal internalization, and decreased perfectionism were associated with increased eating disorder pathology. Findings corroborate earlier work indicating that eating disorder pathology is elevated and clinically significant in overweight treatment-seeking youth, bolstering the need for mental health assessment of such individuals. Cross-sectional modeling proposed key variables that relate to eating disorder pathology in overweight treatment-seeking youth, which following prospective replication, may inform the development of effective interventions for overweight and eating disorders.

TU-C-12A-09: Modeling Pathologic Response of Locally Advanced Esophageal Cancer to Chemo-Radiotherapy Using Quantitative PET/CT Features, Clinical Parameters and Demographics

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

Zhang, H; Chen, W; Kligerman, S

2014-06-15

Purpose: To develop predictive models using quantitative PET/CT features for the evaluation of tumor response to neoadjuvant chemo-radiotherapy (CRT) in patients with locally advanced esophageal cancer. Methods: This study included 20 patients who underwent tri-modality therapy (CRT + surgery) and had {sup 18}F-FDG PET/CT scans before initiation of CRT and 4-6 weeks after completion of CRT but prior to surgery. Four groups of tumor features were examined: (1) conventional PET/CT response measures (SUVmax, tumor diameter, etc.); (2) clinical parameters (TNM stage, histology, etc.) and demographics; (3) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associatedmore » changes resulting from CRT; and (4) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, using cross-validations to avoid model over-fitting. Prediction accuracy was assessed via area under the receiver operating characteristic curve (AUC), and precision was evaluated via confidence intervals (CIs) of AUC. Results: When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). Using spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications), significantly better than using conventional PET/CT measures or clinical parameters and demographics alone. For groups with a large number of tumor features (groups 3 and 4), the SVM model achieved significantly higher accuracy than the LR model. Conclusion: The SVM model using all features including quantitative PET/CT features accurately and precisely predicted pathologic tumor response to CRT in esophageal cancer. This work was supported in part by National Cancer Institute Grant R21 CA131979 and R01 CA172638. Shan Tan was supported in part by the National Natural Science Foundation of China 60971112 and 61375018, and by Fundamental Research Funds for the Central Universities 2012QN086.« less

The virtuous pathologist. An ethical basis for laboratory medicine.

PubMed

Stempsey, W E

1989-06-01

The profession of pathology is a practice in the technical sense used by many philosophers. Such practices have internal goods, which, it is hoped, lead to the attainment of a certain end. The ultimate end of the practice of pathology must be the good of the patient in terms of restoring health. Key internal goods in pathology are technical competence, the proper pathologist-patient relationship, and the proper pathologist-clinician relationship. Virtues are predispositions to act so as to attain the end of the practice and further the internal goods. Technical growth in the practice of pathology must be accompanied by continued attempts to articulate the goals and internal goods of the practice. Only if pathologists are predisposed to act in accordance with proper goals will an ethical practice be assured.

Molecular association of pathogenetic contributors to pre-eclampsia (pre-eclampsia associome)

PubMed Central

2015-01-01

Background Pre-eclampsia is the most common complication occurring during pregnancy. In the majority of cases, it is concurrent with other pathologies in a comorbid manner (frequent co-occurrences in patients), such as diabetes mellitus, gestational diabetes and obesity. Providing bronchial asthma, pulmonary tuberculosis, certain neurodegenerative diseases and cancers as examples, we have shown previously that pairs of inversely comorbid pathologies (rare co-occurrences in patients) are more closely related to each other at the molecular genetic level compared with randomly generated pairs of diseases. Data in the literature concerning the causes of pre-eclampsia are abundant. However, the key mechanisms triggering this disease that are initiated by other pathological processes are thus far unknown. The aim of this work was to analyse the characteristic features of genetic networks that describe interactions between comorbid diseases, using pre-eclampsia as a case in point. Results The use of ANDSystem, Pathway Studio and STRING computer tools based on text-mining and database-mining approaches allowed us to reconstruct associative networks, representing molecular genetic interactions between genes, associated concurrently with comorbid disease pairs, including pre-eclampsia, diabetes mellitus, gestational diabetes and obesity. It was found that these associative networks statistically differed in the number of genes and interactions between them from those built for randomly chosen pairs of diseases. The associative network connecting all four diseases was composed of 16 genes (PLAT, ADIPOQ, ADRB3, LEPR, HP, TGFB1, TNFA, INS, CRP, CSRP1, IGFBP1, MBL2, ACE, ESR1, SHBG, ADA). Such an analysis allowed us to reveal differential gene risk factors for these diseases, and to propose certain, most probable, theoretical mechanisms of pre-eclampsia development in pregnant women. The mechanisms may include the following pathways: [TGFB1 or TNFA]-[IL1B]-[pre-eclampsia]; [TNFA or INS]-[NOS3]-[pre-eclampsia]; [INS]-[HSPA4 or CLU]-[pre-eclampsia]; [ACE]-[MTHFR]-[pre-eclampsia]. Conclusions For pre-eclampsia, diabetes mellitus, gestational diabetes and obesity, we showed that the size and connectivity of the associative molecular genetic networks, which describe interactions between comorbid diseases, statistically exceeded the size and connectivity of those built for randomly chosen pairs of diseases. Recently, we have shown a similar result for inversely comorbid diseases. This suggests that comorbid and inversely comorbid diseases have common features concerning structural organization of associative molecular genetic networks. PMID:25879409

Key feature of the catalytic cycle of TNF-α converting enzyme involves communication between distal protein sites and the enzyme catalytic core

PubMed Central

Solomon, Ariel; Akabayov, Barak; Frenkel, Anatoly; Milla, Marcos E.; Sagi, Irit

2007-01-01

Despite their key roles in many normal and pathological processes, the molecular details by which zinc-dependent proteases hydrolyze their physiological substrates remain elusive. Advanced theoretical analyses have suggested reaction models for which there is limited and controversial experimental evidence. Here we report the structure, chemistry and lifetime of transient metal–protein reaction intermediates evolving during the substrate turnover reaction of a metalloproteinase, the tumor necrosis factor-α converting enzyme (TACE). TACE controls multiple signal transduction pathways through the proteolytic release of the extracellular domain of a host of membrane-bound factors and receptors. Using stopped-flow x-ray spectroscopy methods together with transient kinetic analyses, we demonstrate that TACE's catalytic zinc ion undergoes dynamic charge transitions before substrate binding to the metal ion. This indicates previously undescribed communication pathways taking place between distal protein sites and the enzyme catalytic core. The observed charge transitions are synchronized with distinct phases in the reaction kinetics and changes in metal coordination chemistry mediated by the binding of the peptide substrate to the catalytic metal ion and product release. Here we report key local charge transitions critical for proteolysis as well as long sought evidence for the proposed reaction model of peptide hydrolysis. This study provides a general approach for gaining critical insights into the molecular basis of substrate recognition and turnover by zinc metalloproteinases that may be used for drug design. PMID:17360351

Dedifferentiated chondrosarcoma: Radiological features, prognostic factors and survival statistics in 23 patients

PubMed Central

Liu, Chenglei; Xi, Yan; Li, Mei; Jiao, Qiong; Zhang, Huizhen; Yang, Qingcheng; Yao, Weiwu

2017-01-01

Background Dedifferentiated chondrosarcoma is a rare, highly malignant tumor with a poor survival. There are many confusing issues concerning the imaging feature that can facilitate early diagnosis and the factors that might be related to outcomes. Methods Twenty-three patients with dedifferentiated chondrosarcoma confirmed by pathology were retrospectively reviewed from 2008 to 2015. The patients’ clinical information, images from radiographs (n = 17), CT (n = 19), and MRI (n = 17), histological features, treatment and prognosis were analyzed. Results There were 12 males and 11 females, and the mean age was 50.39 years old. Fourteen cases affected the axial bone (pelvis, spine), and 9 cases involved the appendicular bone. Seven (41.17%), 9 (47.36), and 12 (66.66%) lesions showed a biphasic nature on radiograph, CT and MRI, respectively. Of the lesions, 17.39% (4/23) were accompanied by pathological fractures. Histologically, the cartilage component was considered histological Grade1 in 12 patients and Grade 2 in 11 patients. The dedifferentiated component showed features of osteosarcoma in 8 cases, malignant fibrous histiocytoma in3 cases, myofibroblastic sarcoma in 1 case and spindle cell sarcoma in 11cases. Twenty-two cases were treated with surgical resection, and 17 cases achieved adequate (wide or radical) surgical margin. In 8 cases, surgery was combined with adjuvant chemotherapy. The overall median survival time was nine months; 17.4% of patients survived to five years. Conclusion Axial bone location, lung metastasis at diagnosis, inadequate surgical margin, incorrect diagnosis before surgery and pathological fractures was related to poorer outcome. Pre- or postoperative chemotherapy had no definitively effect on improved survival. PMID:28301537

Symmetric corticobasal degeneration (S-CBD).

PubMed

Hassan, Anhar; Whitwell, Jennifer L; Boeve, Bradley F; Jack, Clifford R; Parisi, Joseph E; Dickson, Dennis W; Josephs, Keith A

2010-03-01

Corticobasal degeneration (CBD) is a neurodegenerative disease characterized pathologically by neuronal loss, gliosis and tau deposition in neocortex, basal ganglia and brainstem. Typical clinical presentation is known as corticobasal syndrome (CBS) and involves the core features of progressive asymmetric rigidity and apraxia, accompanied by other signs of cortical and extrapyramidal dysfunction. Asymmetry is also emphasized on neuroimaging. To describe a series of cases of CBD with symmetric clinical features and to compare clinical and imaging features of these symmetric CBD cases (S-CBD) to typical cases of CBS with CBD pathology. All cases of pathologically confirmed CBD from the Mayo Clinic Rochester database were identified. Clinical records were reviewed and quantitative volumetric analysis of symmetric atrophy on head MRI using atlas based parcellation was performed. Subjects were classified as S-CBD if no differences had been observed between right- and left-sided cortical or extrapyramidal signs or symptoms. S-CBD cases were compared to 10 randomly selected typical CBS cases. Five cases (2 female) met criteria for S-CBD. None had limb dystonia, myoclonus, apraxia or alien limb phenomena. S-CBD cases had significantly less asymmetric atrophy when compared with CBS cases (p=0.009); they were also younger at onset (median 61 versus 66 years, p<0.05) and death (67 versus 73 years, p<0.05). Family history was present in 40% of S-CBD cases. CBD can have a symmetric presentation, clinically and radiologically, in which typical features of CBS, such as limb apraxia, myoclonus, dystonia and alien limb phenomenon, may be absent. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

A quantitative brain map of experimental cerebral malaria pathology.

PubMed

Strangward, Patrick; Haley, Michael J; Shaw, Tovah N; Schwartz, Jean-Marc; Greig, Rachel; Mironov, Aleksandr; de Souza, J Brian; Cruickshank, Sheena M; Craig, Alister G; Milner, Danny A; Allan, Stuart M; Couper, Kevin N

2017-03-01

The murine model of experimental cerebral malaria (ECM) has been utilised extensively in recent years to study the pathogenesis of human cerebral malaria (HCM). However, it has been proposed that the aetiologies of ECM and HCM are distinct, and, consequently, no useful mechanistic insights into the pathogenesis of HCM can be obtained from studying the ECM model. Therefore, in order to determine the similarities and differences in the pathology of ECM and HCM, we have performed the first spatial and quantitative histopathological assessment of the ECM syndrome. We demonstrate that the accumulation of parasitised red blood cells (pRBCs) in brain capillaries is a specific feature of ECM that is not observed during mild murine malaria infections. Critically, we show that individual pRBCs appear to occlude murine brain capillaries during ECM. As pRBC-mediated congestion of brain microvessels is a hallmark of HCM, this suggests that the impact of parasite accumulation on cerebral blood flow may ultimately be similar in mice and humans during ECM and HCM, respectively. Additionally, we demonstrate that cerebrovascular CD8+ T-cells appear to co-localise with accumulated pRBCs, an event that corresponds with development of widespread vascular leakage. As in HCM, we show that vascular leakage is not dependent on extensive vascular destruction. Instead, we show that vascular leakage is associated with alterations in transcellular and paracellular transport mechanisms. Finally, as in HCM, we observed axonal injury and demyelination in ECM adjacent to diverse vasculopathies. Collectively, our data therefore shows that, despite very different presentation, and apparently distinct mechanisms, of parasite accumulation, there appear to be a number of comparable features of cerebral pathology in mice and in humans during ECM and HCM, respectively. Thus, when used appropriately, the ECM model may be useful for studying specific pathological features of HCM.

Correlation of histogram analysis of apparent diffusion coefficient with uterine cervical pathologic finding.

PubMed

Lin, Yuning; Li, Hui; Chen, Ziqian; Ni, Ping; Zhong, Qun; Huang, Huijuan; Sandrasegaran, Kumar

2015-05-01

The purpose of this study was to investigate the application of histogram analysis of apparent diffusion coefficient (ADC) in characterizing pathologic features of cervical cancer and benign cervical lesions. This prospective study was approved by the institutional review board, and written informed consent was obtained. Seventy-three patients with cervical cancer (33-69 years old; 35 patients with International Federation of Gynecology and Obstetrics stage IB cervical cancer) and 38 patients (38-61 years old) with normal cervix or cervical benign lesions (control group) were enrolled. All patients underwent 3-T diffusion-weighted imaging (DWI) with b values of 0 and 800 s/mm(2). ADC values of the entire tumor in the patient group and the whole cervix volume in the control group were assessed. Mean ADC, median ADC, 25th and 75th percentiles of ADC, skewness, and kurtosis were calculated. Histogram parameters were compared between different pathologic features, as well as between stage IB cervical cancer and control groups. Mean ADC, median ADC, and 25th percentile of ADC were significantly higher for adenocarcinoma (p = 0.021, 0.006, and 0.004, respectively), and skewness was significantly higher for squamous cell carcinoma (p = 0.011). Median ADC was statistically significantly higher for well or moderately differentiated tumors (p = 0.044), and skewness was statistically significantly higher for poorly differentiated tumors (p = 0.004). No statistically significant difference of ADC histogram was observed between lymphovascular space invasion subgroups. All histogram parameters differed significantly between stage IB cervical cancer and control groups (p < 0.05). Distribution of ADCs characterized by histogram analysis may help to distinguish early-stage cervical cancer from normal cervix or cervical benign lesions and may be useful for evaluating the different pathologic features of cervical cancer.

Long-term pathological and immunohistochemical features in the liver after intraoperative whole-liver irradiation in rats.

PubMed

Imaeda, Masumi; Ishikawa, Hitoshi; Yoshida, Yukari; Takahashi, Takeo; Ohkubo, Yu; Musha, Atsushi; Komachi, Mayumi; Nakazato, Yoichi; Nakano, Takashi

2014-07-01

Radiation therapy (RT) has become particularly important recently for treatment of liver tumors, but there are few experimental investigations pertaining to radiation-induced liver injuries over long-term follow-up periods. Thus, the present study examined pathological liver features over a 10-month period using an intraoperative whole-liver irradiation model. Liver function tests were performed in blood samples, whereas cell death, cell proliferation, and fibrotic changes were evaluated pathologically in liver tissues, which were collected from irradiated rats 24 h, 1, 2, 4 and 40 weeks following administration of single irradiation doses of 0 (control), 15 or 30 Gy. The impaired liver function, increased hepatocyte number, and decreased apoptotic cell proportion observed in the 15 Gy group, but not the 30 Gy group, returned to control group levels after 40 weeks; however, the Ki-67 indexes in the 15 Gy group were still higher than those in the control group after 40 weeks. Azan staining showed a fibrotic pattern in the irradiated liver in the 30 Gy group only, but the expression levels of alpha smooth muscle actin (α-SMA) and transforming growth factor-beta 1 (TGF-β1) in both the 15 and 30 Gy groups were significantly higher than those in the control group (P < 0.05). There were differences in the pathological features of the irradiated livers between the 15 Gy and 30 Gy groups, but TGF-β1 and α-SMA expression patterns supported the gradual progression of radiation-induced liver fibrosis in both groups. These findings will be useful in the future development of protective drugs for radiation-induced liver injury. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Intratumor partitioning and texture analysis of dynamic contrast-enhanced (DCE)-MRI identifies relevant tumor subregions to predict pathological response of breast cancer to neoadjuvant chemotherapy.

PubMed

Wu, Jia; Gong, Guanghua; Cui, Yi; Li, Ruijiang

2016-11-01

To predict pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multiregion analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). In this Institutional Review Board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using 3T DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with high temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitative Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast washout were statistically significant (P < 0.05) after correcting for multiple testing, with area under the receiver operating characteristic (ROC) curve (AUC) or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (P = 0.002) in leave-one-out cross-validation. This improved upon conventional imaging predictors such as tumor volume (AUC = 0.53) and texture features based on whole-tumor analysis (AUC = 0.65). The heterogeneity of the tumor subregion associated with fast washout on DCE-MRI predicted pathological response to NAC in breast cancer. J. Magn. Reson. Imaging 2016;44:1107-1115. © 2016 International Society for Magnetic Resonance in Medicine.

Simultaneous induction of Graves’ hyperthyroidism and Graves’ ophthalmopathy by TSHR genetic immunization in BALB/c mice

PubMed Central

Hu, Xiaohao; Song, Shiyu; Xu, Hui; Niu, Mengyuan; Wang, Hongwei; Wang, Jian

2017-01-01

Background Graves’ disease is the most common form of autoimmune thyroid disorder, characterized by hyperthyroidism due to circulating autoantibodies. To address the pathological features and establish a therapeutic approach of this disease, an animal model carrying the phenotype of Graves’ disease (GD) in concert with Graves’ Ophthalmopathy (GO) will be very important. However, there are no ideal animal models that are currently available. The aim of the present study is to establish an animal model of GD and GO disease, and its pathological features were further characterized. Methods A recombinant plasmid pcDNA3.1- T289 was constructed by inserting the TSHR A-subunit gene into the expression vector pcDNA3.1, and genetic immunization was successfully performed by intramuscular injection of the plasmid pcDNA3.1-T289 on female 8-week-old BALB/c mice. Each injection was immediately followed by in vivo electroporation using ECM830 square wave electroporator. Morphological changes of the eyes were examined using 7.0T MRI scanner. Levels of serum T4 and TSHR antibodies (TRAb) were assessed by ELISA. The pathological changes of the thyroid and orbital tissues were examined by histological staining such as H&E staining and Alcian blue staining. Results More than 90% of the immunized mice spontaneously developed goiter, and about 80% of the immunized mice manifested increased serum T4 and TRAb levels, combined with hypertrophy and hyperplasia of thyroid follicles. A significantly increased synthesis of hyaluronic acid was detected in in the immunized mice compared with the control groups. Conclusion We have successfully established an animal model manifesting Graves’ hyperthyroidism and ophthalmopathy, which provides a useful tool for future study of the pathological features and the development of novel therapies of the diseases. PMID:28319174

Preoperative easily misdiagnosed telangiectatic osteosarcoma: clinical-radiologic-pathologic correlations.

PubMed

Gao, Zhen-Hua; Yin, Jun-Qiang; Liu, Da-Wei; Meng, Quan-Fei; Li, Jia-Ping

2013-12-11

To describe the clinical, imaging, and pathologic characteristics and diagnostic methods of telangiectatic osteosarcoma (TOS) for improving the diagnostic level. The authors retrospectively reviewed patient demographics, serum alkaline phosphatase (AKP) levels, preoperative biopsy pathologic reports, pathologic materials, imaging findings, and treatment outcomes from 26 patients with TOS. Patient images from radiography (26 cases) and magnetic resonance (MR) imaging (22 cases) were evaluated by 3 authors in consensus for intrinsic characteristics. There were 15 male and 11 female patients in the study, with an age of 9-32 years (mean age 15.9 years). Eighteen of 26 patients died of lung metastases within 5 years of follow-up. The distal femur was affected more commonly (14 cases, 53.8%). Regarding serum AKP, normal (8 cases) or mildly elevated (18 cases) levels were found before preoperative chemotherapy. Radiographs showed geographic bone lysis without sclerotic margin (26 cases), cortical destruction (26 cases), periosteal new bone formation (24 cases), soft-tissue mass (23 cases), and matrix mineralization (4 cases). The aggressive radiographic features of TOS simulated the appearance of conventional high-grade intramedullary osteosarcoma, though different from aneurysmal bone cyst. MR images demonstrated multiple big (16 cases) or small (6 cases) cystic spaces, fluid-fluid levels (14 cases), soft-tissue mass (22 cases), and thick peripheral and septal enhancement (22 cases). Nine of 26 cases were misdiagnosed as aneurysmal bone cysts by preoperative core-needle biopsy, owing to the absence of viable high-grade sarcomatous cells in the small tissue samples. The aggressive growth pattern with occasional matrix mineralization, and multiple big or small fluid-filled cavities with thick peripheral, septal, and nodular tissue surrounding the fluid-filled cavities are characteristic imaging features of TOS, and these features are helpful in making the correct preoperative diagnosis of TOS.

A Tissue Systems Pathology Assay for High-Risk Barrett's Esophagus.

PubMed

Critchley-Thorne, Rebecca J; Duits, Lucas C; Prichard, Jeffrey W; Davison, Jon M; Jobe, Blair A; Campbell, Bruce B; Zhang, Yi; Repa, Kathleen A; Reese, Lia M; Li, Jinhong; Diehl, David L; Jhala, Nirag C; Ginsberg, Gregory; DeMarshall, Maureen; Foxwell, Tyler; Zaidi, Ali H; Lansing Taylor, D; Rustgi, Anil K; Bergman, Jacques J G H M; Falk, Gary W

2016-06-01

Better methods are needed to predict risk of progression for Barrett's esophagus. We aimed to determine whether a tissue systems pathology approach could predict progression in patients with nondysplastic Barrett's esophagus, indefinite for dysplasia, or low-grade dysplasia. We performed a nested case-control study to develop and validate a test that predicts progression of Barrett's esophagus to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), based upon quantification of epithelial and stromal variables in baseline biopsies. Data were collected from Barrett's esophagus patients at four institutions. Patients who progressed to HGD or EAC in ≥1 year (n = 79) were matched with patients who did not progress (n = 287). Biopsies were assigned randomly to training or validation sets. Immunofluorescence analyses were performed for 14 biomarkers and quantitative biomarker and morphometric features were analyzed. Prognostic features were selected in the training set and combined into classifiers. The top-performing classifier was assessed in the validation set. A 3-tier, 15-feature classifier was selected in the training set and tested in the validation set. The classifier stratified patients into low-, intermediate-, and high-risk classes [HR, 9.42; 95% confidence interval, 4.6-19.24 (high-risk vs. low-risk); P < 0.0001]. It also provided independent prognostic information that outperformed predictions based on pathology analysis, segment length, age, sex, or p53 overexpression. We developed a tissue systems pathology test that better predicts risk of progression in Barrett's esophagus than clinicopathologic variables. The test has the potential to improve upon histologic analysis as an objective method to risk stratify Barrett's esophagus patients. Cancer Epidemiol Biomarkers Prev; 25(6); 958-68. ©2016 AACR. ©2016 American Association for Cancer Research.

Fuzzy logic algorithm for quantitative tissue characterization of diffuse liver diseases from ultrasound images.

PubMed

Badawi, A M; Derbala, A S; Youssef, A M

1999-08-01

Computerized ultrasound tissue characterization has become an objective means for diagnosis of liver diseases. It is difficult to differentiate diffuse liver diseases, namely cirrhotic and fatty liver by visual inspection from the ultrasound images. The visual criteria for differentiating diffused diseases are rather confusing and highly dependent upon the sonographer's experience. This often causes a bias effects in the diagnostic procedure and limits its objectivity and reproducibility. Computerized tissue characterization to assist quantitatively the sonographer for the accurate differentiation and to minimize the degree of risk is thus justified. Fuzzy logic has emerged as one of the most active area in classification. In this paper, we present an approach that employs Fuzzy reasoning techniques to automatically differentiate diffuse liver diseases using numerical quantitative features measured from the ultrasound images. Fuzzy rules were generated from over 140 cases consisting of normal, fatty, and cirrhotic livers. The input to the fuzzy system is an eight dimensional vector of feature values: the mean gray level (MGL), the percentile 10%, the contrast (CON), the angular second moment (ASM), the entropy (ENT), the correlation (COR), the attenuation (ATTEN) and the speckle separation. The output of the fuzzy system is one of the three categories: cirrhosis, fatty or normal. The steps done for differentiating the pathologies are data acquisition and feature extraction, dividing the input spaces of the measured quantitative data into fuzzy sets. Based on the expert knowledge, the fuzzy rules are generated and applied using the fuzzy inference procedures to determine the pathology. Different membership functions are developed for the input spaces. This approach has resulted in very good sensitivities and specificity for classifying diffused liver pathologies. This classification technique can be used in the diagnostic process, together with the history information, laboratory, clinical and pathological examinations.

Intraocular osseous metaplasia. A clinico-pathological study.

PubMed

Vemuganti, Geeta K; Honavar, Santosh G; Jalali, Subhadra

2002-09-01

To evaluate the clinico-pathologic features of intraocular osseous metaplasia. Pathology specimens of enucleated eyes submitted to the ophthalmic pathology service at a tertiary eye-care referral center between January 1995 and June 1999 were studied for intraocular osseous metaplasia. Specific histopathologic features noted in specimens with osseous metaplasia were the presence of retinal detachment, gliosis, retinal pigment epithelial hyperplasia, drusen, epiretinal membrane, fibrovascular proliferation and inflammation. Immunohistochemistry using monoclonal antibody against glial fibrillary acidic protein was performed to assess the glial component within the membranes and the proliferative vitreoretinal mass. Clinical records were reviewed and correlated with histopathologic findings. Osseous metaplasiaS was noted in 8 of 151 (5.2%) eyes examined. Clinical diagnosis in these was phthisis bulbi, staphyloma, absolute glaucoma and microphthalmos. Enucleation was performed for relief of symptoms (in painful blind eyes) or for cosmesis, and in an eye inciting sympathetic ophthalmia. Retinal detachment, gliosis and retinal pigment epithelial hyperplasia were noted in all the cases. Drusen with calcification or ossification (5 of 8), fibrovascular proliferation in the vitreous (5 of 8) and active inflammation (4 of 8) were the other associated histologic features. Location of ossification was subretinal in 3 cases, preretinal (ora serrata) in 1 case and in both locations in 4 cases. The eyes with subretinal osseous metaplasia had associated calcified drusen, while preretinal ossification was seen within the fibrovascular membranes. Chronic retinal detachment, hyperplasia and transdifferentiation of retinal pigment epithelium appear to be a few of the prerequisites for intraocular osseous metaplasia. Ossification can occur at isolated subretinal and preretinal locations or can involve both. Though a larger study is required to postulate the chronology of events, in this small series, isolated subretinal ossification appears to be initiated by calcification and ossification of drusen, while in the pre-retinal region it is associated with vitreoretinal proliferation.

Clinical features and axis I comorbidity of Australian adolescent pathological Internet and video game users.

PubMed

King, Daniel L; Delfabbro, Paul H; Zwaans, Tara; Kaptsis, Dean

2013-11-01

Although there is growing international recognition of pathological technology use (PTU) in adolescence, there has been a paucity of empirical research conducted in Australia. This study was designed to assess the clinical features of pathological video gaming (PVG) and pathological Internet use (PIU) in a normative Australian adolescent population. A secondary objective was to investigate the axis I comorbidities associated with PIU and video gaming. A total of 1287 South Australian secondary school students aged 12-18 years were recruited. Participants were assessed using the PTU checklist, Revised Children's Anxiety and Depression Scale, Social Anxiety Scale for Adolescents, revised UCLA Loneliness Scale, and Teenage Inventory of Social Skills. Adolescents who met the criteria for PVG or PIU or both were compared to normal adolescents in terms of axis I comorbidity. The prevalence rates of PIU and PVG were 6.4% and 1.8%, respectively. A subgroup with co-occurring PIU and PVG was identified (3.3%). The most distinguishing clinical features of PTU were withdrawal, tolerance, lies and secrecy, and conflict. Symptoms of preoccupation, inability to self-limit, and using technology as an escape were commonly reported by adolescents without PTU, and therefore may be less useful as clinical indicators. Depression, panic disorder, and separation anxiety were most prevalent among adolescents with PIU. PTU among Australian adolescents remains an issue warranting clinical concern. These results suggest an emerging trend towards the greater uptake and use of the Internet among female adolescents, with associated PIU. Although there exists an overlap of PTU disorders, adolescents with PIU appear to be at greater risk of axis I comorbidity than adolescents with PVG alone. Further research with an emphasis on validation techniques, such as verified identification of harm, may enable an informed consensus on the definition and diagnosis of PTU.

A quantitative brain map of experimental cerebral malaria pathology

PubMed Central

Schwartz, Jean-Marc; Greig, Rachel; Mironov, Aleksandr; de Souza, J. Brian; Cruickshank, Sheena M.; Craig, Alister G.; Milner, Danny A.; Allan, Stuart M.

2017-01-01

The murine model of experimental cerebral malaria (ECM) has been utilised extensively in recent years to study the pathogenesis of human cerebral malaria (HCM). However, it has been proposed that the aetiologies of ECM and HCM are distinct, and, consequently, no useful mechanistic insights into the pathogenesis of HCM can be obtained from studying the ECM model. Therefore, in order to determine the similarities and differences in the pathology of ECM and HCM, we have performed the first spatial and quantitative histopathological assessment of the ECM syndrome. We demonstrate that the accumulation of parasitised red blood cells (pRBCs) in brain capillaries is a specific feature of ECM that is not observed during mild murine malaria infections. Critically, we show that individual pRBCs appear to occlude murine brain capillaries during ECM. As pRBC-mediated congestion of brain microvessels is a hallmark of HCM, this suggests that the impact of parasite accumulation on cerebral blood flow may ultimately be similar in mice and humans during ECM and HCM, respectively. Additionally, we demonstrate that cerebrovascular CD8+ T-cells appear to co-localise with accumulated pRBCs, an event that corresponds with development of widespread vascular leakage. As in HCM, we show that vascular leakage is not dependent on extensive vascular destruction. Instead, we show that vascular leakage is associated with alterations in transcellular and paracellular transport mechanisms. Finally, as in HCM, we observed axonal injury and demyelination in ECM adjacent to diverse vasculopathies. Collectively, our data therefore shows that, despite very different presentation, and apparently distinct mechanisms, of parasite accumulation, there appear to be a number of comparable features of cerebral pathology in mice and in humans during ECM and HCM, respectively. Thus, when used appropriately, the ECM model may be useful for studying specific pathological features of HCM. PMID:28273147

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.

Modern Pathologic Diagnosis of Renal Oncocytoma.

PubMed

Wobker, Sara E; Williamson, Sean R

2017-01-01

Oncocytoma is a well-defined benign renal tumor, with classic gross and histologic features, including a tan or mahogany-colored mass with central scar, microscopic nested architecture, bland cytology, and round, regular nuclei with prominent central nucleoli. As a result of variations in this classic appearance, difficulty in standardizing diagnostic criteria, and entities that mimic oncocytoma, such as eosinophilic variant chromophobe renal cell carcinoma and succinate dehydrogenase-deficient renal cell carcinoma, pathologic diagnosis remains a challenge. This review addresses the current state of pathologic diagnosis of oncocytoma, with emphasis on modern diagnostic markers, areas of controversy, and emerging techniques for less invasive diagnosis, including renal mass biopsy and advanced imaging.

Exploring the Association between Emotional Abuse and Childhood Borderline Personality Features: The Moderating Role of Personality Traits

ERIC Educational Resources Information Center

Gratz, Kim L.; Latzman, Robert D.; Tull, Matthew T.; Reynolds, Elizabeth K.; Lejuez, C. W.

2011-01-01

Most of the extant literature on borderline personality disorder has focused on the course, consequences, and correlates of this disorder among adults. However, little is known about childhood borderline personality (BP) features, or the factors associated with the emergence of BP pathology in childhood. A greater understanding of childhood BP…

Membrane lipid alterations in the metabolic syndrome and the role of dietary oils.

PubMed

Perona, Javier S

2017-09-01

The metabolic syndrome is a cluster of pathological conditions, including hypertension, hyperglycemia, hypertriglyceridemia, obesity and low HDL levels that is of great concern worldwide, as individuals with metabolic syndrome have an increased risk of type-2 diabetes and cardiovascular disease. Insulin resistance, the key feature of the metabolic syndrome, might be at the same time cause and consequence of impaired lipid composition in plasma membranes of insulin-sensitive tissues like liver, muscle and adipose tissue. Diet intervention has been proposed as a powerful tool to prevent the development of the metabolic syndrome, since healthy diets have been shown to have a protective role against the components of the metabolic syndrome. Particularly, dietary fatty acids are capable of modulating the deleterious effects of these conditions, among other mechanisms, by modifications of the lipid composition of the membranes in insulin-sensitive tissues. However, there is still scarce data based of high-level evidence on the effects of dietary oils on the effects of the metabolic syndrome and its components. This review summarizes the current knowledge on the effects of dietary oils on improving alterations of the components of the metabolic syndrome. It also examines their influence in the modulation of plasma membrane lipid composition and in the functionality of membrane proteins involved in insulin activity, like the insulin receptor, GLUT-4, CD36/FAT and ABCA-1, and their effect in the metabolism of glucose, fatty acids and cholesterol, and, in turn, the key features of the metabolic syndrome. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 Elsevier B.V. All rights reserved.

Forensic Pathology Education in Pathology Residency: A Survey of Current Practices, a Novel Curriculum, and Recommendations for the Future.

PubMed

Spencer, Amanda; Ross, Wayne K; Domen, Ronald E

2017-01-01

Forensic pathology is a fundamental part of anatomic pathology training during pathology residency. However, the lack of information on forensic teaching suggests the highly variable nature of forensic education. A survey of pathology residency program directors was performed to determine key aspects of their respective forensic rotations and curriculum. A total of 38.3% of programs from across the country responded, and the survey results show 5.6% don't require a forensic pathology rotation. In those that do, most forensic pathology rotations are 4 weeks long, are done at a medical examiner's office, and require set prerequisites. A total of 21.1% of responding programs have residents who are not receiving documented evaluations for this rotation. While 39.6% of programs have a defined forensics curriculum, as many as 15% do not. Furthermore, nearly 43% of programs place no limit on counting forensic autopsies when applying for pathology board examinations. Our survey confirmed the inconsistent nature of forensic pathology training in resident education. Additionally, our curriculum was reorganized to create a more robust educational experience. A pre- and post-forensic lecture quiz and Resident In-Service Examination scores were analyzed to determine our curriculum's impact and effectiveness. Analysis of our pre- and post-lecture quiz showed an improved overall average as well as an increase in Resident In-Service Examination scores, indicating improved general forensic pathology knowledge. Using this knowledge, along with changes in our curriculum, we generated a number of recommendations for improving forensic pathology education in pathology residency.

NCAM is hyposialylated in hereditary inclusion body myopathy due to GNE mutations.

PubMed

Ricci, E; Broccolini, A; Gidaro, T; Morosetti, R; Gliubizzi, C; Frusciante, R; Di Lella, G M; Tonali, P A; Mirabella, M

2006-03-14

The authors found that the neural cell adhesion molecule (NCAM) is hyposialylated in hereditary inclusion body myopathy (HIBM) muscle, as suggested by its decreased molecular weight by Western blot. This abnormality represented the only pathologic feature differentiating HIBM due to GNE mutations from other myopathies with similar clinical and pathologic characteristics. If further confirmed in larger series of patients, this may be a useful diagnostic marker of GNE-related HIBM.

Risk factors and clinical features of text message injuries.

PubMed

Sharan, Deepak; Ajeesh, P S

2012-01-01

Use of mobile phone and sending text message is a very common in today's life. While sending a text message the users need to use their thumb and other palm muscles extensively. The thumb most of the time adducted on the key pad of the mobile and use high force to type the letters. Studies in literature showed that text messaging has an adverse effect on musculoskeletal system of hand. But the extensive study on the type of disorders set in among the users who extensively use mobile phone for texting. This study aims at to evaluate risk factor and clinical feature of the MSD due to hand held devices. Twenty seven subjects participated in this study. Predefined protocols were used to evaluate type of MSD occurred among the subjects. The study revealed that development of tendinitis in extensor pollicis longus, myofascial pain syndrome (70.37%) of adductor pollicis, 1st interossei and extensor digitorum communis . Other associated problems diagnosed were thoracic outlet syndrome (51.85%), fibromyalgia syndrome (25.93%), hypothyroidism (7.41%), wrist tendinitis (14.81%) and De Quervain's syndrome (7.41%). It has been observed that the pathology were tendinitis of extensor pollicis longus, myofascial pain syndrome of thenar muscles and 1st interossei, extensor digitorum communis.

[Ocular cicatricial pemphigoid - state of the art in clinic and therapy for a problematic disease].

PubMed

Rübsam, A; Klein, J P; Pleyer, U

2013-08-01

The ocular cicatricial pemphigoid (OCP) belongs to a family of chronically progressive autoimmune disorders, predominantly affecting mucous membranes (mucous membrane pemphigoids). It is an immunopathologically heterogeneous group of disorders with variable phenotypes that share the unique feature of a subepidermal blistering, through disruption of the adhesion between epidermis and dermis. A key feature is the chronically active inflammation with consecutive fibrosis, leading to a partial or complete loss of function of the affected organ. The ocular disease as a chronic cicatrising conjunctivitis is a common manifestation of the mucous membrane pemphigoid. The identification of the subtle pathology and the prompt initiation of an appropriate therapy are of pivotal importance. One purpose is to prevent further vision loss due to extensive corneal scarring and life-threatening systemic complications, such as the formation of oesophageal or tracheal strictures. So far there are no prospective, randomised studies, regarding the therapy guidelines with an evidence level more than III. The autoimmune nature of the disease implies that systemic immunosuppression is the only effective treatment option, most notably in extended stages. The aim of our study is to give a guideline for a stage adjusted therapy with conventional immunosuppressants and to give a perspective for alternative therapies, especially for recalcitrant disease. Georg Thieme Verlag KG Stuttgart · New York.

Methuosis

PubMed Central

Maltese, William A.; Overmeyer, Jean H.

2015-01-01

Apoptosis is the most widely recognized form of physiological programmed cell death. During the past three decades, various nonapoptotic forms of cell death have gained increasing attention, largely because of their potential importance in pathological processes, toxicology, and cancer therapy. A recent addition to the panoply of cell death phenotypes is methuosis. The neologism is derived from the Greek methuo (to drink to intoxication) because the hallmark of this form of cell death is displacement of the cytoplasm by large fluid-filled vacuoles derived from macropinosomes. The demise of the cell resembles many forms of necrosis, insofar as there is a loss of metabolic capacity and plasma membrane integrity, without the cell shrinkage and nuclear fragmentation associated with apoptosis. Methuosis was initially defined in glioblastoma cells after ectopic expression of activated Ras, but recent reports have described small molecules that can induce the features of methuosis in a broad spectrum of cancer cells, including those that are resistant to conventional apoptosis-inducing drugs. This review summarizes the available information about the distinguishing morphological characteristics and underlying mechanisms of methuosis. We compare and contrast methuosis with other cytopathological conditions in which accumulation of clear cytoplasmic vacuoles is a prominent feature. Finally, we highlight key questions that need to be answered to determine whether methuosis truly represents a unique form of regulated cell death. PMID:24726643

Evolution and function of CAG/polyglutamine repeats in protein–protein interaction networks

PubMed Central

Schaefer, Martin H.; Wanker, Erich E.; Andrade-Navarro, Miguel A.

2012-01-01

Expanded runs of consecutive trinucleotide CAG repeats encoding polyglutamine (polyQ) stretches are observed in the genes of a large number of patients with different genetic diseases such as Huntington's and several Ataxias. Protein aggregation, which is a key feature of most of these diseases, is thought to be triggered by these expanded polyQ sequences in disease-related proteins. However, polyQ tracts are a normal feature of many human proteins, suggesting that they have an important cellular function. To clarify the potential function of polyQ repeats in biological systems, we systematically analyzed available information stored in sequence and protein interaction databases. By integrating genomic, phylogenetic, protein interaction network and functional information, we obtained evidence that polyQ tracts in proteins stabilize protein interactions. This happens most likely through structural changes whereby the polyQ sequence extends a neighboring coiled-coil region to facilitate its interaction with a coiled-coil region in another protein. Alteration of this important biological function due to polyQ expansion results in gain of abnormal interactions, leading to pathological effects like protein aggregation. Our analyses suggest that research on polyQ proteins should shift focus from expanded polyQ proteins into the characterization of the influence of the wild-type polyQ on protein interactions. PMID:22287626

Ensemble transcript interaction networks: a case study on Alzheimer's disease.

PubMed

Armañanzas, Rubén; Larrañaga, Pedro; Bielza, Concha

2012-10-01

Systems biology techniques are a topic of recent interest within the neurological field. Computational intelligence (CI) addresses this holistic perspective by means of consensus or ensemble techniques ultimately capable of uncovering new and relevant findings. In this paper, we propose the application of a CI approach based on ensemble Bayesian network classifiers and multivariate feature subset selection to induce probabilistic dependences that could match or unveil biological relationships. The research focuses on the analysis of high-throughput Alzheimer's disease (AD) transcript profiling. The analysis is conducted from two perspectives. First, we compare the expression profiles of hippocampus subregion entorhinal cortex (EC) samples of AD patients and controls. Second, we use the ensemble approach to study four types of samples: EC and dentate gyrus (DG) samples from both patients and controls. Results disclose transcript interaction networks with remarkable structures and genes not directly related to AD by previous studies. The ensemble is able to identify a variety of transcripts that play key roles in other neurological pathologies. Classical statistical assessment by means of non-parametric tests confirms the relevance of the majority of the transcripts. The ensemble approach pinpoints key metabolic mechanisms that could lead to new findings in the pathogenesis and development of AD. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Deregulation of Bone Forming Cells in Bone Diseases and Anabolic Effects of Strontium-Containing Agents and Biomaterials

PubMed Central

Tan, Shuang; Zhang, Binbin; Zhu, Xiaomei; Ao, Ping; Guo, Huajie; Yi, Weihong; Zhou, Guang-Qian

2014-01-01

Age-related bone loss and osteoporosis are associated with bone remodeling changes that are featured with decreased trabecular and periosteal bone formation relative to bone resorption. Current anticatabolic therapies focusing on the inhibition of bone resorption may not be sufficient in the prevention or reversal of age-related bone deterioration and there is a big need in promoting osteoblastogenesis and bone formation. Enhanced understanding of the network formed by key signaling pathways and molecules regulating bone forming cells in health and diseases has therefore become highly significant. The successful development of agonist/antagonist of the PTH and Wnt signaling pathways are profits of the understanding of these key pathways. As the core component of an approved antiosteoporosis agent, strontium takes its effect on osteoblasts at multilevel through multiple pathways, representing a good example in revealing and exploring anabolic mechanisms. The recognition of strontium effects on bone has led to its expected application in a variety of biomaterial scaffolds used in tissue engineering strategies aiming at bone repairing and regeneration. While summarizing the recent progress in these respects, this review also proposes the new approaches such as systems biology in order to reveal new insights in the pathology of osteoporosis as well as possible discovery of new therapies. PMID:24800251

[Myofibrillar myopaathy].

PubMed

Hayashi, Yukiko

2013-01-01

Myofibrillar myopathy (MFM) is a group of hereditary disorders pathologically characterized by focal disorganizations of myofibril structures with cytoplasmic inclusions. Most of the diseases so-called desmin-related or storage myopathy, cytoplasmic body myopathy, spheroid body myopathy, reducing body myopathy, and hyaline body myopathy are included in MFM. Several causative genes have been identified such as DES, CRYAB, MYOT, ZASP, BAG3, FLNC, DNAJB6, FHL1, TTN, and VCP. Most of these genes encode Z-line related proteins or proteins associated with protein quality control. Since MFM is the name from pathological characteristics, clinical features of the patients including the age at disease onset, affected muscles, disease course, and complications are quite variable. In this paper, characteristic clinical and pathological features of each causative gene are summarized. Unexpectedly, hereditary myopathy with early respiratory failure (HMERF) caused by mutation in the A-band region of TTN is the most common cause of MFM in our cohort. Despite of intensive mutation screening, the causative gene of more than 60% of MFM patients is still unknown. Further identification of novel causative genes and elucidate pathomechanisms of protein aggregation in necessary.

[Morphological pathology of vessels in granulomatosis with polyangiitis (Wegener's disease)].

PubMed

Zerbino, D D; Zimba, E A

2015-01-01

to investigate the incidence of injuries in different vascular beds and the morphopathological changes in vessels in granulomatosis with polyangiitis. The morphopathological features of vascular injuries were investigated in 11 dead patients aged 16--74 years with granulomatosis with polyangiitis. Proliferative and destructive angiitis with predominant involvement of microcirculatory vessels and with development of necrosis-prone granulomas in their walls and perivascularly was established to underlie the clinical manifestations of granulomatosis with polyangiitis. The most typical localization of the pathologic process is the vessels of the upper respiratory tract, lungs, and kidneys. Cardiopulmonary and renal failures are causes of death in the majority of cases. It should be noted that the vessels of the heart, liver, and gastrointestinal tract are frequently involved in the pathological process. Vascular changes in these organs determine the clinical features of granulomatosis with polyangiitis and lead to a number of fatal complications. Granulomatosis with polyangiitis is a systemic disease with polymorphism of clinical manifestations, which requires in-depth analysis based on current precision patient examination methods, including a histopathological study.

Diprosopia/dicephalia in calves in northern Italy: clinical and aetio-pathological features.

PubMed

Biasibetti, E; D'Angelo, A; Bellino, C; Gay, L; Gianella, P; Capucchio, M T

2011-12-01

Cephalic parapagia, a rare congenital anomaly caused by the fusion of two monozygotic embryos, is characterized by a single body and a spectrum of duplication of craniofacial structures. The authors describe the clinical and pathological aspects of the parapagus conjoined twin defect in nine calves referred to the Department of Animal Pathology, Turin, between 1999 and 2009. The majority of the calves (eight cases) presented two snouts that shared three or four eyes (diprosopia); one calf presented two separate skulls fused at the foramen magnum (dicephalia). Bilateral inferior brachygnathia was observed in four calves. Post-mortem examination of the skull revealed complete brain duplication with fusion at the caudal portion of the brainstem in all calves. Histological features of the cerebral hemispheres and brainstem were normal; moderate disorganization of the cerebellar cortex was noted in two cases. Cardiac malformations were observed in three calves. No aetiologic cause was determined. This article underscores the importance of diprosopia in cattle species and suggests the need for more detailed investigations to better understand its pathogenesis. © 2011 Blackwell Verlag GmbH.

[Gastritis and gastropathy].

PubMed

Mihály, Emese; Micsik, Tamás; Juhász, Márk; Herszényi, László; Tulassay, Zsolt

2014-01-12

Alterations of the stomach mucosa in response to different adverse effects result in various morphological and clinical symptoms. Gastric mucosa alterations can be classified on the bases of diverse viewpoints. It makes this overview difficult, that identical toxic effects may cause different mucosal changes and different toxic agents may produce similar mucosal appearance. The more accurate understanding of the pathological processes which develop in the stomach mucosa needs reconsideration. The authors make an attempt to define gastritis and gastropathy in order to classify and present their features. Gastritis is a histological definition indicating mucosal inflammation. Acute gastritis is caused by infections. The two most important forms of chronic gastritis are metaplastic atrophic gastritis with an autoimmune origin and Helicobacter pylori inflammation. Gastropathy is the name of different structural alterations of the mucosa. Its most important feature is the paucity of inflammatory signs. Gastropathies can be divided into 4 categories based on the nature of the underlying pathological effect, on its morphological appearance and the way of the development. Differential diagnosis is an important pathological and clinical task because different treatment methods and prognosis.

Leigh syndrome: neuropathology and pathogenesis.

PubMed

Lake, Nicole J; Bird, Matthew J; Isohanni, Pirjo; Paetau, Anders

2015-06-01

Leigh syndrome (LS) is the most common pediatric presentation of a defined mitochondrial disease. This progressive encephalopathy is characterized pathologically by the development of bilateral symmetrical lesions in the brainstem and basal ganglia that show gliosis, vacuolation, capillary proliferation, relative neuronal preservation, and by hyperlacticacidemia in the blood and/or cerebrospinal fluid. Understanding the molecular mechanisms underlying this unique pathology has been challenging, particularly in view of the heterogeneous and not yet fully determined genetic basis of LS. Moreover, animal models that mimic features of LS have only been created relatively recently. Here, we review the pathology of LS and consider what might be the molecular mechanisms underlying its pathogenesis. Data from a wide range of sources, including patient samples, animal models, and studies of hypoxic-ischemic encephalopathy (a condition that shares features with LS), were used to provide insight into the pathogenic mechanisms that may drive lesion development. Based on current data, we suggest that severe ATP depletion, gliosis, hyperlacticacidemia, reactive oxygen species, and potentially excitotoxicity cumulatively contribute to the neuropathogenesis of LS. An intimate understanding of the molecular mechanisms causing LS is required to accelerate the development of LS treatments.

Breast Histopathological Image Retrieval Based on Latent Dirichlet Allocation.

PubMed

Ma, Yibing; Jiang, Zhiguo; Zhang, Haopeng; Xie, Fengying; Zheng, Yushan; Shi, Huaqiang; Zhao, Yu

2017-07-01

In the field of pathology, whole slide image (WSI) has become the major carrier of visual and diagnostic information. Content-based image retrieval among WSIs can aid the diagnosis of an unknown pathological image by finding its similar regions in WSIs with diagnostic information. However, the huge size and complex content of WSI pose several challenges for retrieval. In this paper, we propose an unsupervised, accurate, and fast retrieval method for a breast histopathological image. Specifically, the method presents a local statistical feature of nuclei for morphology and distribution of nuclei, and employs the Gabor feature to describe the texture information. The latent Dirichlet allocation model is utilized for high-level semantic mining. Locality-sensitive hashing is used to speed up the search. Experiments on a WSI database with more than 8000 images from 15 types of breast histopathology demonstrate that our method achieves about 0.9 retrieval precision as well as promising efficiency. Based on the proposed framework, we are developing a search engine for an online digital slide browsing and retrieval platform, which can be applied in computer-aided diagnosis, pathology education, and WSI archiving and management.

Endemic chronic kidney disease of unknown etiology in Sri Lanka: Correlation of pathology with clinical stages.

PubMed

Wijetunge, S; Ratnatunga, N V I; Abeysekera, T D J; Wazil, A W M; Selvarajah, M

2015-01-01

Chronic kidney disease of unknown etiology (CKDU) is endemic among the rural farming communities in several localities in and around the North Central region of Sri Lanka. This is an interstitial type renal disease and typically has an insidious onset and slow progression. This study was conducted to identify the pathological features in the different clinical stages of CKDU. This is a retrospective study of 251 renal biopsies identified to have a primary interstitial disease from regions endemic for CKDU. Pathological features were assessed and graded in relation to the clinical stage. The mean age of those affected by endemic CKDU was 37.3 ± 12.5 years and the male to female ratio was 3.3:1. The predominant feature of stage I disease was mild and moderate interstitial fibrosis; most did not have interstitial inflammation. The typical stage II disease had moderate interstitial fibrosis with or without mild interstitial inflammation. Stage III disease had moderate and severe interstitial fibrosis, moderate interstitial inflammation, tubular atrophy and some glomerulosclerosis. Stage IV disease typically had severe interstitial fibrosis and inflammation, tubular atrophy and glomerulosclerosis. The mean age of patients with stage I disease (27 ± 10.8 years) was significantly lower than those of the other stages. About 79.2%, 55%, 49.1% and 50% in stage I, II, III and IV disease respectively were asymptomatic at the time of biopsy.

[Cerebral gliosarcoma: clinico-pathologic study of 8 cases].

PubMed

Ayadi, Lobna; Charfi, Slim; Khabir, Abdemajid; Kalle, Rim; Sellami, Ahmed; Makni, Saloua; Boudawara, Zaher; Sellami-Boudawara, Tahya

2010-03-01

Gliosarcomas are biphasic neoplasms composed of a glioblastoma admixed to a sarcomatous component with different lines of differentiation. Histogenesis of these tumors is still discussed. Our objective is to specify clinical and pathological characteristics of this rare neoplasm and to discuss its histogenesis. Retrospective study of eight cases of gliosarcomas diagnosed between January 1998 and December 2004. Clinical, radiological, therapeutic and follow-up data were reviewed. Histological features and immunohistochemical results were also included in this review. Five patients were male, three women with a median age of 50.7 (range 31-74 years). Symptoms were dominated by intracranial hypertension and paralysis. The most common location was parietal or temporo-parietal (5 cases: 62.5%). Pathological exam including histochemical and immunohistochemical study confirmed the diagnosis of gliosarcoma in all cases. Sarcomatous component had features of fibrosarcoma in 5 cases, osteosarcoma in 2 cases and malignant fibrous histiocytoma in 1 case. All patients were treated by surgical excision (complete in five cases and partial in three cases). Adjuvant radiotherapy was received in three cases. One patient was lost on follow-up. Two patients died from postoperative. complications and the five remaining patients died with a medium follow up of 9 months (extremes: 2-24 months). Clinical, radiological and follow-up features of gliosarcomas share great similarities with glioblastomas. Histopathological, histochemical and immunohistochemical studies are helpful in accuracy diagnosis. Recent cytogenetic and molecular data support a monoclonal origin for these tumors.

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.

mTOR-Dependent Cell Proliferation in the Brain.

PubMed

Ryskalin, Larisa; Lazzeri, Gloria; Flaibani, Marina; Biagioni, Francesca; Gambardella, Stefano; Frati, Alessandro; Fornai, Francesco

2017-01-01

The mammalian Target of Rapamycin (mTOR) is a molecular complex equipped with kinase activity which controls cell viability being key in the PI3K/PTEN/Akt pathway. mTOR acts by integrating a number of environmental stimuli to regulate cell growth, proliferation, autophagy, and protein synthesis. These effects are based on the modulation of different metabolic pathways. Upregulation of mTOR associates with various pathological conditions, such as obesity, neurodegeneration, and brain tumors. This is the case of high-grade gliomas with a high propensity to proliferation and tissue invasion. Glioblastoma Multiforme (GBM) is a WHO grade IV malignant, aggressive, and lethal glioma. To date, a few treatments are available although the outcome of GBM patients remains poor. Experimental and pathological findings suggest that mTOR upregulation plays a major role in determining an aggressive phenotype, thus determining relapse and chemoresistance. Among several activities, mTOR-induced autophagy suppression is key in GBM malignancy. In this article, we discuss recent evidence about mTOR signaling and its role in normal brain development and pathological conditions, with a special emphasis on its role in GBM.

mTOR-Dependent Cell Proliferation in the Brain

PubMed Central

Lazzeri, Gloria; Frati, Alessandro

2017-01-01

The mammalian Target of Rapamycin (mTOR) is a molecular complex equipped with kinase activity which controls cell viability being key in the PI3K/PTEN/Akt pathway. mTOR acts by integrating a number of environmental stimuli to regulate cell growth, proliferation, autophagy, and protein synthesis. These effects are based on the modulation of different metabolic pathways. Upregulation of mTOR associates with various pathological conditions, such as obesity, neurodegeneration, and brain tumors. This is the case of high-grade gliomas with a high propensity to proliferation and tissue invasion. Glioblastoma Multiforme (GBM) is a WHO grade IV malignant, aggressive, and lethal glioma. To date, a few treatments are available although the outcome of GBM patients remains poor. Experimental and pathological findings suggest that mTOR upregulation plays a major role in determining an aggressive phenotype, thus determining relapse and chemoresistance. Among several activities, mTOR-induced autophagy suppression is key in GBM malignancy. In this article, we discuss recent evidence about mTOR signaling and its role in normal brain development and pathological conditions, with a special emphasis on its role in GBM. PMID:29259984

Novel histopathologic feature identified through image analysis augments stage II colorectal cancer clinical reporting

PubMed Central

Caie, Peter D.; Zhou, Ying; Turnbull, Arran K.; Oniscu, Anca; Harrison, David J.

2016-01-01

A number of candidate histopathologic factors show promise in identifying stage II colorectal cancer (CRC) patients at a high risk of disease-specific death, however they can suffer from low reproducibility and none have replaced classical pathologic staging. We developed an image analysis algorithm which standardized the quantification of specific histopathologic features and exported a multi-parametric feature-set captured without bias. The image analysis algorithm was executed across a training set (n = 50) and the resultant big data was distilled through decision tree modelling to identify the most informative parameters to sub-categorize stage II CRC patients. The most significant, and novel, parameter identified was the ‘sum area of poorly differentiated clusters’ (AreaPDC). This feature was validated across a second cohort of stage II CRC patients (n = 134) (HR = 4; 95% CI, 1.5– 11). Finally, the AreaPDC was integrated with the significant features within the clinical pathology report, pT stage and differentiation, into a novel prognostic index (HR = 7.5; 95% CI, 3–18.5) which improved upon current clinical staging (HR = 4.26; 95% CI, 1.7– 10.3). The identification of poorly differentiated clusters as being highly significant in disease progression presents evidence to suggest that these features could be the source of novel targets to decrease the risk of disease specific death. PMID:27322148

General morphological and biological features of neoplasms: integration of molecular findings.

PubMed

Diaz-Cano, S J

2008-07-01

This review highlights the importance of morphology-molecular correlations for a proper implementation of new markers. It covers both general aspects of tumorigenesis (which are normally omitted in papers analysing molecular pathways) and the general mechanisms for the acquired capabilities of neoplasms. The mechanisms are also supported by appropriate diagrams for each acquired capability that include overlooked features such as mobilization of cellular resources and changes in chromatin, transcription and epigenetics; fully accepted oncogenes and tumour suppressor genes are highlighted, while the pathways are also presented as activating or inactivating with appropriate colour coding. Finally, the concepts and mechanisms presented enable us to understand the basic requirements for the appropriate implementation of molecular tests in clinical practice. In summary, the basic findings are presented to serve as a bridge to clinical applications. The current definition of neoplasm is descriptive and difficult to apply routinely. Biologically, neoplasms develop through acquisition of capabilities that involve tumour cell aspects and modified microenvironment interactions, resulting in unrestricted growth due to a stepwise accumulation of cooperative genetic alterations that affect key molecular pathways. The correlation of these molecular aspects with morphological changes is essential for better understanding of essential concepts as early neoplasms/precancerous lesions, progression/dedifferentiation, and intratumour heterogeneity. The acquired capabilities include self-maintained replication (cell cycle dysregulation), extended cell survival (cell cycle arrest, apoptosis dysregulation, and replicative lifespan), genetic instability (chromosomal and microsatellite), changes of chromatin, transcription and epigenetics, mobilization of cellular resources, and modified microenvironment interactions (tumour cells, stromal cells, extracellular, endothelium). The acquired capabilities defining neoplasms are the hallmarks of cancer, but they also comprise useful tools to improve diagnosis and prognosis, as well as potential therapeutic targets. The application of these concepts in oncological pathology leads to consideration of the molecular test requirements (Molecular Test Score System) for reliable implementation; these requirements should cover biological effects, molecular pathway, biological validation, and technical validation. Sensible application of molecular markers in tumour pathology always needs solid morphological support.

Hepatocellular Adenoma: Evaluation with Contrast-Enhanced Ultrasound and MRI and Correlation with Pathologic and Phenotypic Classification in 26 Lesions

PubMed Central

Manichon, Anne-Frédérique; Bancel, Brigitte; Durieux-Millon, Marion; Ducerf, Christian; Mabrut, Jean-Yves; Lepogam, Marie-Annick; Rode, Agnès

2012-01-01

Purpose. To review the contrast-enhanced ultrasonographic (CEUS) and magnetic resonance (MR) imaging findings in 25 patients with 26 hepatocellular adenomas (HCAs) and to compare imaging features with histopathologic results from resected specimen considering the new immunophenotypical classification. Material and Methods. Two abdominal radiologists reviewed retrospectively CEUS cineloops and MR images in 26 HCA. All pathological specimens were reviewed and classified into four subgroups (steatotic or HNF 1α mutated, inflammatory, atypical or β-catenin mutated, and unspecified). Inflammatory infiltrates were scored, steatosis, and telangiectasia semiquantitatively evaluated. Results. CEUS and MRI features are well correlated: among the 16 inflammatory HCA, 7/16 presented typical imaging features: hypersignal T2, strong arterial enhancement with a centripetal filling, persistent on delayed phase. 6 HCA were classified as steatotic with typical imaging features: a drop out signal, slight arterial enhancement, vanishing on late phase. Four HCA were classified as atypical with an HCC developed in one. Five lesions displayed important steatosis (>50%) without belonging to the HNF1α group. Conclusion. In half cases, inflammatory HCA have specific imaging features well correlated with the amount of telangiectasia and inflammatory infiltrates. An HCA with important amount of steatosis noticed on chemical shift images does not always belong to the HNF1α group. PMID:22811588

Why Synchrony Matters during Mother-Child Interactions: A Systematic Review

PubMed Central

Leclère, Chloë; Viaux, Sylvie; Avril, Marie; Achard, Catherine; Chetouani, Mohamed; Missonnier, Sylvain; Cohen, David

2014-01-01

Background Assessment of mother-child interactions is a core issue of early child development and psychopathology. This paper focuses on the concept of “synchrony” and examines (1) how synchrony in mother-child interaction is defined and operationalized; (2) the contribution that the concept of synchrony has brought to understanding the nature of mother-child interactions. Method Between 1977 and 2013, we searched several databases using the following key-words: « synchrony » « interaction » and « mother-child ». We focused on studies examining parent-child interactions among children aged 2 months to 5 years. From the 63 relevant studies, we extracted study description variables (authors, year, design, number of subjects, age); assessment conditions and modalities; and main findings. Results The most common terms referring to synchrony were mutuality, reciprocity, rhythmicity, harmonious interaction, turn-taking and shared affect; all terms were used to characterize the mother-child dyad. As a consequence, we propose defining synchrony as a dynamic and reciprocal adaptation of the temporal structure of behaviors and shared affect between interactive partners. Three main types of assessment methods for studying synchrony emerged: (1) global interaction scales with dyadic items; (2) specific synchrony scales; and (3) micro-coded time-series analyses. It appears that synchrony should be regarded as a social signal per se as it has been shown to be valid in both normal and pathological populations. Better mother-child synchrony is associated with familiarity (vs. unknown partner), a healthy mother (vs. pathological mother), typical development (vs. psychopathological development), and a more positive child outcomes. Discussion Synchrony is a key feature of mother-infant interactions. Adopting an objective approach in studying synchrony is not a simple task given available assessment tools and due to its temporality and multimodal expression. We propose an integrative approach combining clinical observation and engineering techniques to improve the quality of synchrony analysis. PMID:25469637

B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements are aggressive neoplasms with clinical and pathologic features distinct from Burkitt lymphoma and diffuse large B-cell lymphoma.

PubMed

Snuderl, Matija; Kolman, Olga K; Chen, Yi-Bin; Hsu, Jessie J; Ackerman, Adam M; Dal Cin, Paola; Ferry, Judith A; Harris, Nancy Lee; Hasserjian, Robert P; Zukerberg, Lawrence R; Abramson, Jeremy S; Hochberg, Ephraim P; Lee, Hang; Lee, Alfred I; Toomey, Christiana E; Sohani, Aliyah R

2010-03-01

B-cell lymphomas with concurrent IGH-BCL2 and MYC rearrangements, also known as "double-hit" lymphomas (DHL), are rare neoplasms characterized by highly aggressive clinical behavior, complex karyotypes, and a spectrum of pathologic features overlapping with Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) and B-lymphoblastic lymphoma/leukemia (B-LBL). The clinical and pathologic spectrum of this rare entity, including comparison to other high-grade B-cell neoplasms, has not been well defined. We conducted a retrospective analysis of clinical and pathologic features of 20 cases of DHL seen at our institution during a 5-year period. In addition, we carried out case-control comparisons of DHL with BL and International Prognostic Index (IPI)-matched DLBCL. The 11 men and 9 women had a median age of 63.5 years (range 32 to 91). Six patients had a history of grade 1 to 2 follicular lymphoma; review of the prior biopsy specimens in 2 of 5 cases revealed blastoid morphology. Eighteen patients had Ann Arbor stage 3 or 4 disease and all had elevated serum lactate dehydrogenase (LDH) levels at presentation. Extranodal disease was present in 17/20 (85%), bone marrow involvement in 10/17 (59%) and central nervous system (CNS) disease in 5/11 (45%). Nineteen patients were treated with combination chemotherapy, of whom 18 received rituximab and 14 received CNS-directed therapy. Fourteen patients (70%) died within 8 months of diagnosis. Median overall survival in the DHL group (4.5 mo) was inferior to both BL (P=0.002) and IPI-matched DLBCL (P=0.04) control patients. Twelve DHL cases (60%) were classified as B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL, 7 cases (35%) as DLBCL, not otherwise specified, and 1 case as B-LBL. Distinguishing features from BL included expression of Bcl2 (P<0.0001), Mum1/IRF4 (P=0.006), Ki-67 <95% (P<0.0001), and absence of EBV-EBER (P=0.006). DHL commonly contained the t(8;22) rather than the t(8;14) seen in most BL controls (P=0.001), and exhibited a higher number of chromosomal aberrations (P=0.0009). DHL is a high-grade B-cell neoplasm with a poor prognosis, resistance to multiagent chemotherapy, and clinical and pathologic features distinct from other high-grade B-cell neoplasms. Familiarity with the morphologic and immunophenotypic spectrum of DHL is important in directing testing to detect concurrent IGH-BCL2 and MYC rearrangements when a karyotype is unavailable. The aggressive clinical behavior and combination of genetic abnormalities seen in these cases may warrant categorization as a separate entity in future classifications and call for novel therapeutic approaches.

Detection of Pathological Voice Using Cepstrum Vectors: A Deep Learning Approach.

PubMed

Fang, Shih-Hau; Tsao, Yu; Hsiao, Min-Jing; Chen, Ji-Ying; Lai, Ying-Hui; Lin, Feng-Chuan; Wang, Chi-Te

2018-03-19

Computerized detection of voice disorders has attracted considerable academic and clinical interest in the hope of providing an effective screening method for voice diseases before endoscopic confirmation. This study proposes a deep-learning-based approach to detect pathological voice and examines its performance and utility compared with other automatic classification algorithms. This study retrospectively collected 60 normal voice samples and 402 pathological voice samples of 8 common clinical voice disorders in a voice clinic of a tertiary teaching hospital. We extracted Mel frequency cepstral coefficients from 3-second samples of a sustained vowel. The performances of three machine learning algorithms, namely, deep neural network (DNN), support vector machine, and Gaussian mixture model, were evaluated based on a fivefold cross-validation. Collective cases from the voice disorder database of MEEI (Massachusetts Eye and Ear Infirmary) were used to verify the performance of the classification mechanisms. The experimental results demonstrated that DNN outperforms Gaussian mixture model and support vector machine. Its accuracy in detecting voice pathologies reached 94.26% and 90.52% in male and female subjects, based on three representative Mel frequency cepstral coefficient features. When applied to the MEEI database for validation, the DNN also achieved a higher accuracy (99.32%) than the other two classification algorithms. By stacking several layers of neurons with optimized weights, the proposed DNN algorithm can fully utilize the acoustic features and efficiently differentiate between normal and pathological voice samples. Based on this pilot study, future research may proceed to explore more application of DNN from laboratory and clinical perspectives. Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Microstructural white matter alterations in preclinical Alzheimer’s disease detected using free water elimination diffusion tensor imaging

PubMed Central

Ly, Martina; Carlsson, Cynthia M.; Okonkwo, Ozioma C.; Zetterberg, Henrik; Blennow, Kaj; Sager, Mark A.; Asthana, Sanjay; Johnson, Sterling C.; Alexander, Andrew L.; Bendlin, Barbara B.

2017-01-01

Brain changes associated with Alzheimer’s disease (AD) begin decades before disease diagnosis. While β-amyloid plaques and neurofibrillary tangles are defining features of AD, neuronal loss and synaptic pathology are closely related to the cognitive dysfunction. Brain imaging methods that are tuned to assess degeneration of myelinated nerve fibers in the brain (collectively called white matter) include diffusion tensor imaging (DTI) and related techniques, and are expected to shed light on disease-related loss of structural connectivity. Participants (N = 70, ages 47–76 years) from the Wisconsin Registry for Alzheimer’s Prevention study underwent DTI and hybrid diffusion imaging to determine a free-water elimination (FWE-DTI) model. The study assessed the extent to which preclinical AD pathology affects brain white matter. Preclinical AD pathology was determined using cerebrospinal fluid (CSF) biomarkers. The sample was enriched for AD risk (APOE ε4 and parental history of AD). AD pathology assessed by CSF analyses was significantly associated with altered microstructure on both DTI and FWE-DTI. Affected regions included frontal, parietal, and especially temporal white matter. The f-value derived from the FWE-DTI model appeared to be the most sensitive to the relationship between the CSF AD biomarkers and microstructural alterations in white matter. These findings suggest that white matter degeneration is an early pathological feature of AD that may have utility both for early disease detection and as outcome measures for clinical trials. More complex models of microstructural diffusion properties including FWE-DTI may provide increased sensitivity to early brain changes associated with AD over standard DTI. PMID:28291839

Cross-species approaches to pathological gambling: a review targeting sex differences, adolescent vulnerability and ecological validity of research tools.

PubMed

van den Bos, Ruud; Davies, William; Dellu-Hagedorn, Francoise; Goudriaan, Anna E; Granon, Sylvie; Homberg, Judith; Rivalan, Marion; Swendsen, Joel; Adriani, Walter

2013-12-01

Decision-making plays a pivotal role in daily life as impairments in processes underlying decision-making often lead to an inability to make profitable long-term decisions. As a case in point, pathological gamblers continue gambling despite the fact that this disrupts their personal, professional or financial life. The prevalence of pathological gambling will likely increase in the coming years due to expanding possibilities of on-line gambling through the Internet and increasing liberal attitudes towards gambling. It therefore represents a growing concern for society. Both human and animal studies rapidly advance our knowledge on brain-behaviour processes relevant for understanding normal and pathological gambling behaviour. Here, we review in humans and animals three features of pathological gambling which hitherto have received relatively little attention: (1) sex differences in (the development of) pathological gambling, (2) adolescence as a (putative) sensitive period for (developing) pathological gambling and (3) avenues for improving ecological validity of research tools. Based on these issues we also discuss how research in humans and animals may be brought in line to maximize translational research opportunities. Copyright © 2013 Elsevier Ltd. All rights reserved.

Targeting GPCR-Gβγ-GRK2 signaling as a novel strategy for treating cardiorenal pathologies.

PubMed

Rudomanova, Valeria; Blaxall, Burns C

2017-08-01

The pathologic crosstalk between the heart and kidney is known as cardiorenal syndrome (CRS). While the specific mechanisms underlying this crosstalk remain poorly understood, CRS is associated with exacerbated dysfunction of either or both organs and reduced survival. Maladaptive fibrotic remodeling is a key component of both heart and kidney failure pathogenesis and progression. G-protein coupled receptor (GPCR) signaling is a crucial regulator of cardiovascular and renal function. Chronic/pathologic GPCR signaling elicits the interaction of the G-protein Gβγ subunit with GPCR kinase 2 (GRK2), targeting the receptor for internalization, scaffolding to pathologic signals, and receptor degradation. Targeting this pathologic Gβγ-GRK2 interaction has been suggested as a possible strategy for the treatment of HF. In the current review, we discuss recent updates in understanding the role of GPCR-Gβγ-GRK2 signaling as a crucial mediator of maladaptive organ remodeling detected in HF and kidney dysfunction, with specific attention to small molecule-mediated inhibition of pathologic Gβγ-GRK2 interactions. Further, we explore the potential of GPCR-Gβγ-GRK2 signaling as a possible therapeutic target for cardiorenal pathologies. Copyright © 2017 Elsevier B.V. All rights reserved.

Managing demand for laboratory tests: a laboratory toolkit.

PubMed

Fryer, Anthony A; Smellie, W Stuart A

2013-01-01

Healthcare budgets worldwide are facing increasing pressure to reduce costs and improve efficiency, while maintaining quality. Laboratory testing has not escaped this pressure, particularly since pathology investigations cost the National Health Service £2.5 billion per year. Indeed, the Carter Review, a UK Department of Health-commissioned review of pathology services in England, estimated that 20% of this could be saved by improving pathology services, despite an average annual increase of 8%-10% in workload. One area of increasing importance is managing the demands for pathology tests and reducing inappropriate requesting. The Carter Review estimated that 25% of pathology tests were unnecessary, representing a huge potential waste. Certainly, the large variability in levels of requesting between general practitioners suggests that inappropriate requesting is widespread. Unlocking the key to this variation and implementing measures to reduce inappropriate requesting would have major implications for patients and healthcare resources alike. This article reviews the approaches to demand management. Specifically, it aims to (a) define demand management and inappropriate requesting, (b) assess the drivers for demand management, (c) examine the various approaches used, illustrating the potential of electronic requesting and (d) provide a wider context. It will cover issues, such as educational approaches, information technology opportunities and challenges, vetting, duplicate request identification and management, the role of key performance indicators, profile composition and assessment of downstream impact of inappropriate requesting. Currently, many laboratories are exploring demand management using a plethora of disparate approaches. Hence, this review seeks to provide a 'toolkit' with the view to allowing laboratories to develop a standardised demand management strategy.

Granulomatous lobular mastitis.

PubMed Central

Going, J J; Anderson, T J; Wilkinson, S; Chetty, U

1987-01-01

The clinical and pathological features of nine cases of granulomatous mastitis were compared with those of 10 cases of duct ectasia/periductal mastitis (DE/PM), all of which were associated with active granulomatous inflammation. Granulomatous mastitis affects a younger age group, and although there is some overlap with DE/PM, it has distinctive pathological features, particularly a lobule centred distribution, for which the term "granulomatous lobular mastitis" is recommended. There is a strong tendency for persistence or recurrence. Our cases of granulomatous mastitis all occurred in parous women, five of them within three years of pregnancy. Awareness of this condition is important, because surgery does not offer the best treatment of recurrent disease, and trials of adequate drug treatment, including corticosteroids, are required. Images Fig 1 Fig 2 Fig 3 Fig 4 PMID:3584506

Child maltreatment, personality pathology, and stalking victimization among male and female college students.

PubMed

Ménard, Kim S; Pincus, Aaron L

2014-01-01

Self-report college student surveys on childhood maltreatment, and borderline and narcissistic personality features are examined to determine their influence on stalking victimization vulnerability. Stalking victimization was measured using Spitzberg and Cupach's (2008) Obsessive Relational Intrusion scale. Ordinary least squares (OLS) regression models were run separately for men (N = 677) and women (N = 1,017). Results indicated childhood sexual maltreatment and borderline traits were associated with stalking victimization among both men and women. These were the only significant relationships for men (R2 = .10). For women, stalking victimization was also associated with narcissistic grandiosity and vulnerability and with a child sexual abuse by borderline features interaction (R2 = .13), demonstrating women reporting prior sexual abuse and borderline personality pathology are especially vulnerable. Methodological and policy implications are discussed.

Multidisciplinary Care.

PubMed

Daly, Megan E; Riess, Jonathan W

Optimal multidisciplinary care of the lung cancer patient at all stages should encompass integration of the key relevant medical specialties, including not only medical, surgical, and radiation oncology, but also pulmonology, interventional and diagnostic radiology, pathology, palliative care, and supportive services such as physical therapy, case management, smoking cessation, and nutrition. Multidisciplinary management starts at staging and tissue diagnosis with pathologic and molecular phenotyping, extends through selection of a treatment modality or modalities, management of treatment and cancer-related symptoms, and to survivorship and end-of-life care. Well-integrated multidisciplinary care may reduce treatment delays, improve cancer-specific outcomes, and enhance quality of life. We address key topics and areas of ongoing investigation in multidisciplinary decision making at each stage of the lung cancer treatment course for early-stage, locally advanced, and metastatic lung cancer patients.

Sense and nonsense in the process of accreditation of a pathology laboratory.

PubMed

Long-Mira, Elodie; Washetine, Kevin; Hofman, Paul

2016-01-01

The aim of accreditation of a pathology laboratory is to control and optimize, in a permanent manner, good professional practice in clinical and molecular pathology, as defined by internationally established standards. Accreditation of a pathology laboratory is a key element in fine in increasing recognition of the quality of the analyses performed by a laboratory and in improving the care it provides to patients. One of the accreditation standards applied to clinical chemistry and pathology laboratories in the European Union is the ISO 15189 norm. Continued functioning of a pathology laboratory might in time be determined by whether or not it has succeeded the accreditation process. Necessary requirements for accreditation, according to the ISO 15189 norm, include an operational quality management system and continuous control of the methods used for diagnostic purposes. Given these goals, one would expect that all pathologists would agree on the positive effects of accreditation. Yet, some of the requirements stipulated in the accreditation standards, coming from the bodies that accredit pathology laboratories, and certain normative issues are perceived as arduous and sometimes not adapted to or even useless in daily pathology practice. The aim of this review is to elaborate why it is necessary to obtain accreditation but also why certain requirements for accreditation might be experienced as inappropriate.

Biomarker clusters are differentially associated with longitudinal cognitive decline in late midlife

PubMed Central

Racine, Annie M.; Koscik, Rebecca L.; Berman, Sara E.; Nicholas, Christopher R.; Clark, Lindsay R.; Okonkwo, Ozioma C.; Rowley, Howard A.; Asthana, Sanjay; Bendlin, Barbara B.; Blennow, Kaj; Zetterberg, Henrik; Gleason, Carey E.; Carlsson, Cynthia M.

2016-01-01

The ability to detect preclinical Alzheimer’s disease is of great importance, as this stage of the Alzheimer’s continuum is believed to provide a key window for intervention and prevention. As Alzheimer’s disease is characterized by multiple pathological changes, a biomarker panel reflecting co-occurring pathology will likely be most useful for early detection. Towards this end, 175 late middle-aged participants (mean age 55.9 ± 5.7 years at first cognitive assessment, 70% female) were recruited from two longitudinally followed cohorts to undergo magnetic resonance imaging and lumbar puncture. Cluster analysis was used to group individuals based on biomarkers of amyloid pathology (cerebrospinal fluid amyloid-β42/amyloid-β40 assay levels), magnetic resonance imaging-derived measures of neurodegeneration/atrophy (cerebrospinal fluid-to-brain volume ratio, and hippocampal volume), neurofibrillary tangles (cerebrospinal fluid phosphorylated tau181 assay levels), and a brain-based marker of vascular risk (total white matter hyperintensity lesion volume). Four biomarker clusters emerged consistent with preclinical features of (i) Alzheimer’s disease; (ii) mixed Alzheimer’s disease and vascular aetiology; (iii) suspected non-Alzheimer’s disease aetiology; and (iv) healthy ageing. Cognitive decline was then analysed between clusters using longitudinal assessments of episodic memory, semantic memory, executive function, and global cognitive function with linear mixed effects modelling. Cluster 1 exhibited a higher intercept and greater rates of decline on tests of episodic memory. Cluster 2 had a lower intercept on a test of semantic memory and both Cluster 2 and Cluster 3 had steeper rates of decline on a test of global cognition. Additional analyses on Cluster 3, which had the smallest hippocampal volume, suggest that its biomarker profile is more likely due to hippocampal vulnerability and not to detectable specific volume loss exceeding the rate of normal ageing. Our results demonstrate that pathology, as indicated by biomarkers, in a preclinical timeframe is related to patterns of longitudinal cognitive decline. Such biomarker patterns may be useful for identifying at-risk populations to recruit for clinical trials. PMID:27324877

Biomarker clusters are differentially associated with longitudinal cognitive decline in late midlife.

PubMed

Racine, Annie M; Koscik, Rebecca L; Berman, Sara E; Nicholas, Christopher R; Clark, Lindsay R; Okonkwo, Ozioma C; Rowley, Howard A; Asthana, Sanjay; Bendlin, Barbara B; Blennow, Kaj; Zetterberg, Henrik; Gleason, Carey E; Carlsson, Cynthia M; Johnson, Sterling C

2016-08-01

The ability to detect preclinical Alzheimer's disease is of great importance, as this stage of the Alzheimer's continuum is believed to provide a key window for intervention and prevention. As Alzheimer's disease is characterized by multiple pathological changes, a biomarker panel reflecting co-occurring pathology will likely be most useful for early detection. Towards this end, 175 late middle-aged participants (mean age 55.9 ± 5.7 years at first cognitive assessment, 70% female) were recruited from two longitudinally followed cohorts to undergo magnetic resonance imaging and lumbar puncture. Cluster analysis was used to group individuals based on biomarkers of amyloid pathology (cerebrospinal fluid amyloid-β42/amyloid-β40 assay levels), magnetic resonance imaging-derived measures of neurodegeneration/atrophy (cerebrospinal fluid-to-brain volume ratio, and hippocampal volume), neurofibrillary tangles (cerebrospinal fluid phosphorylated tau181 assay levels), and a brain-based marker of vascular risk (total white matter hyperintensity lesion volume). Four biomarker clusters emerged consistent with preclinical features of (i) Alzheimer's disease; (ii) mixed Alzheimer's disease and vascular aetiology; (iii) suspected non-Alzheimer's disease aetiology; and (iv) healthy ageing. Cognitive decline was then analysed between clusters using longitudinal assessments of episodic memory, semantic memory, executive function, and global cognitive function with linear mixed effects modelling. Cluster 1 exhibited a higher intercept and greater rates of decline on tests of episodic memory. Cluster 2 had a lower intercept on a test of semantic memory and both Cluster 2 and Cluster 3 had steeper rates of decline on a test of global cognition. Additional analyses on Cluster 3, which had the smallest hippocampal volume, suggest that its biomarker profile is more likely due to hippocampal vulnerability and not to detectable specific volume loss exceeding the rate of normal ageing. Our results demonstrate that pathology, as indicated by biomarkers, in a preclinical timeframe is related to patterns of longitudinal cognitive decline. Such biomarker patterns may be useful for identifying at-risk populations to recruit for clinical trials. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

PubMed

Jauregui, Paula; Estévez, Ana; Urbiola, Irache

2016-06-01

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

Three-dimensional spatiotemporal features for fast content-based retrieval of focal liver lesions.

PubMed

Roy, Sharmili; Chi, Yanling; Liu, Jimin; Venkatesh, Sudhakar K; Brown, Michael S

2014-11-01

Content-based image retrieval systems for 3-D medical datasets still largely rely on 2-D image-based features extracted from a few representative slices of the image stack. Most 2 -D features that are currently used in the literature not only model a 3-D tumor incompletely but are also highly expensive in terms of computation time, especially for high-resolution datasets. Radiologist-specified semantic labels are sometimes used along with image-based 2-D features to improve the retrieval performance. Since radiological labels show large interuser variability, are often unstructured, and require user interaction, their use as lesion characterizing features is highly subjective, tedious, and slow. In this paper, we propose a 3-D image-based spatiotemporal feature extraction framework for fast content-based retrieval of focal liver lesions. All the features are computer generated and are extracted from four-phase abdominal CT images. Retrieval performance and query processing times for the proposed framework is evaluated on a database of 44 hepatic lesions comprising of five pathological types. Bull's eye percentage score above 85% is achieved for three out of the five lesion pathologies and for 98% of query lesions, at least one same type of lesion is ranked among the top two retrieved results. Experiments show that the proposed system's query processing is more than 20 times faster than other already published systems that use 2-D features. With fast computation time and high retrieval accuracy, the proposed system has the potential to be used as an assistant to radiologists for routine hepatic tumor diagnosis.

Key features of an EU health information system: a concept mapping study.

PubMed

Rosenkötter, Nicole; Achterberg, Peter W; van Bon-Martens, Marja J H; Michelsen, Kai; van Oers, Hans A M; Brand, Helmut

2016-02-01

Despite the acknowledged value of an EU health information system (EU-HISys) and the many achievements in this field, the landscape is still heavily fragmented and incomplete. Through a systematic analysis of the opinions and valuations of public health stakeholders, this study aims to conceptualize key features of an EU-HISys. Public health professionals and policymakers were invited to participate in a concept mapping procedure. First, participants (N = 34) formulated statements that reflected their vision of an EU-HISys. Second, participants (N = 28) rated the relative importance of each statement and grouped conceptually similar ones. Principal Component and cluster analyses were used to condense these results to EU-HISys key features in a concept map. The number of key features and the labelling of the concept map were determined by expert consensus. The concept map contains 10 key features that summarize 93 statements. The map consists of a horizontal axis that represents the relevance of an 'organizational strategy', which deals with the 'efforts' to design and develop an EU-HISys and the 'achievements' gained by a functioning EU-HISys. The vertical axis represents the 'professional orientation' of the EU-HISys, ranging from the 'scientific' through to the 'policy' perspective. The top ranking statement expressed the need to establish a system that is permanent and sustainable. The top ranking key feature focuses on data and information quality. This study provides insights into key features of an EU-HISys. The results can be used to guide future planning and to support the development of a health information system for Europe. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Defining competency-based evaluation objectives in family medicine

PubMed Central

Lawrence, Kathrine; Allen, Tim; Brailovsky, Carlos; Crichton, Tom; Bethune, Cheri; Donoff, Michel; Laughlin, Tom; Wetmore, Stephen; Carpentier, Marie-Pierre; Visser, Shaun

2011-01-01

Abstract Objective To develop key features for priority topics previously identified by the College of Family Physicians of Canada that, together with skill dimensions and phases of the clinical encounter, broadly describe competence in family medicine. Design Modified nominal group methodology, which was used to develop key features for each priority topic through an iterative process. Setting The College of Family Physicians of Canada. Participants An expert group of 7 family physicians and 1 educational consultant, all of whom had experience in assessing competence in family medicine. Group members represented the Canadian family medicine context with respect to region, sex, language, community type, and experience. Methods The group used a modified Delphi process to derive a detailed operational definition of competence, using multiple iterations until consensus was achieved for the items under discussion. The group met 3 to 4 times a year from 2000 to 2007. Main findings The group analyzed 99 topics and generated 773 key features. There were 2 to 20 (average 7.8) key features per topic; 63% of the key features focused on the diagnostic phase of the clinical encounter. Conclusion This project expands previous descriptions of the process of generating key features for assessment, and removes this process from the context of written examinations. A key-features analysis of topics focuses on higher-order cognitive processes of clinical competence. The project did not define all the skill dimensions of competence to the same degree, but it clearly identified those requiring further definition. This work generates part of a discipline-specific, competency-based definition of family medicine for assessment purposes. It limits the domain for assessment purposes, which is an advantage for the teaching and assessment of learners. A validation study on the content of this work would ensure that it truly reflects competence in family medicine. PMID:21998245

The Prion Concept and Synthetic Prions.

PubMed

Legname, Giuseppe; Moda, Fabio

2017-01-01

Transmissible spongiform encephalopathies or prion diseases are a group of fatal neurodegenerative diseases caused by unconventional infectious agents, known as prions (PrP Sc ). Prions derive from a conformational conversion of the normally folded prion protein (PrP C ), which acquires pathological and infectious features. Moreover, PrP Sc is able to transmit the pathological conformation to PrP C through a mechanism that is still not well understood. The generation of synthetic prions, which behave like natural prions, is of fundamental importance to study the process of PrP C conversion and to assess the efficacy of therapeutic strategies to interfere with this process. Moreover, the ability of synthetic prions to induce pathology in animals confirms that the pathological properties of the prion strains are all enciphered in abnormal conformations, characterizing these infectious agents. © 2017 Elsevier Inc. 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.

Time-frequency analysis of pediatric murmurs

NASA Astrophysics Data System (ADS)

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

1998-05-01

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

Insulin regulates Presenilin 1 localization via PI3K/Akt signaling.

PubMed

Maesako, Masato; Uemura, Kengo; Kubota, Masakazu; Ando, Koichi; Kuzuya, Akira; Asada, Megumi; Kihara, Takeshi; Kinoshita, Ayae

2010-10-15

Recently, insulin signaling has been highlighted in the pathology of Alzheimer's disease (AD). Although the association between insulin signaling and Tau pathology has been investigated in several studies, the interaction between insulin signaling and Presenilin 1 (PS1), a key molecule of amyloid beta (Abeta) pathology, has not been elucidated so far. In this study, we demonstrated that insulin inhibited PS1 phosphorylation at serine residues (serine 353, 357) via phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway and strengthened the trimeric complex of PS1/N-cadherin/beta-catenin, consequently relocalizing PS1 to the cell surface. Since our recent report suggests that PS1/N-cadherin/beta-catenin complex regulates Abeta production, it is likely that insulin signaling affects Abeta pathology by regulating PS1 localization. 2010 Elsevier Ireland Ltd. All rights reserved.

Pathology as the enabler of human research.

PubMed

Crawford, James M; Tykocinski, Mark L

2005-09-01

Academic Pathology is a key player in human molecular science and in the powerful initiatives of the National Institutes of Health. Pathologists generate data crucial to virtually every molecular study of human tissue, and have the necessary skills and authority to oversee processing of human tissues for research analysis. We advocate that Academic Pathology is optimally positioned to drive the molecular revolution in study of human disease, through human tissue collection, analysis, and databasing. This can be achieved through playing a major role in human tissue procurement and management; establishing high-quality 'Pathology Resource Laboratories'; providing the scientific expertise for pathology data sharing; and recruiting and training physician scientists. Pathology should position itself to be the local institutional driver of technology implementation and development, by operating the resource laboratories, providing the expertise for technical and conceptual design of research projects, maintaining the databases that link molecular and morphological information on human tissues with the requisite clinical databases, providing education and mentorship of technology users, and nurturing new research through the development of preliminary data. We also consider that outstanding pathology journals are available for the publication of research emanating from such studies, to the benefit of the pathology profession as an academic enterprise. It is our earnest hope that Academic Pathology can play a leading role in the remarkable advances to be made as the 21st century unfolds.

Filopodia and Viruses: An Analysis of Membrane Processes in Entry Mechanisms

PubMed Central

Chang, Kenneth; Baginski, John; Hassan, Samer F.; Volin, Michael; Shukla, Deepak; Tiwari, Vaibhav

2016-01-01

Filopodia are thin, actin rich bundles protruding from cell plasma membranes, serving physiological purposes, such as probing the environment and facilitating cell-to-cell adhesion. Recent studies have highlighted that actively polymerized filopodial-protrusions are exploited during virus entry, trafficking, spread, and the development of clinical pathology of viral diseases. These observations have caused a surge in investigation of the key determinants of filopodial induction and their influence on cell topography including receptor expression for viral entry. It is now very clear that filopodia can provide unique opportunities for many viruses to invade host cells vertically during primary infection, or horizontally during virus spread from cell-to-cell. These emerging concepts can explain the unprecedented ability of viruses to invade both nearby and long-distant host cells, a feature that may directly contribute to viral tropism. In this review, we summarize the significance of filopodia in viral diseases and discuss future therapeutic possibilities to precisely target filopodial-flyovers to prevent or control infectious diseases. PMID:27014223

Acute Cutaneous Necrosis: A Guide to Early Diagnosis and Treatment.

PubMed

Karimi, Karen; Odhav, Ashika; Kollipara, Ramya; Fike, Jesse; Stanford, Carol; Hall, John C

Acute cutaneous necrosis is characterised by a wide range of aetiologies and is associated with significant morbidity and mortality, warranting complex considerations in management. Early recognition is imperative in diagnosis and management of sudden gangrenous changes in the skin. This review discusses major causes of cutaneous necrosis, examines the need for early assessment, and integrates techniques related to diagnosis and management. The literature, available via PubMed, on acute cutaneous necrotic syndromes was reviewed to summarise causes and synthesise appropriate treatment strategies to create a clinician's guide in the early diagnosis and management of acute cutaneous necrosis. Highlighted in this article are key features associated with common causes of acute cutaneous necrosis: warfarin-induced skin necrosis, heparin-induced skin necrosis, calciphylaxis, pyoderma gangrenosum, embolic phenomena, purpura fulminans, brown recluse spider bite, necrotising fasciitis, ecthyma gangrenosum, antiphospholipid syndrome, hypergammaglobulinemia, and cryoglobulinemia. This review serves to increase recognition of these serious pathologies and complications, allowing for prompt diagnosis and swift limb- or life-saving management.