Pathology Residency Programme of a Developing Country--Landscape of Last 25 Years

ERIC Educational Resources Information Center

Siddiqui, Imran; Ali, Natasha; Kayani, Naila

2016-01-01

We report the evolution of a residency programme in Pathology from a developing country. This article highlights the historical perspective of our application procedure, the number of inductions, the programme framework, acheivements and limitations.

The role of the pathologist in translational and personalized medicine.

PubMed

Perl, Daniel P

2007-04-01

Over the years, pathologists have served to make morphologic diagnoses for clinicians when provided with a biopsy or surgically resected tissue specimen. Traditionally, pathologists have used a series of morphologic techniques and relied on the microscopic appearance of resected tissues to determine a pathologic diagnosis and, with respect to neoplastic lesions, provide predictions of the potential growth pattern that might be anticipated. With the introduction of the techniques of molecular biology in medicine, the role of the pathologist has changed as have the tools available for characterizing pathologic specimens. With the pathologist's unique perspective on disease processes and access to tissue specimens from the operating room, he has become a key player in the area of translational and personalized medicine and the development of new approaches to diagnosis and translational research. Copyright (c) 2007 Mount Sinai School of Medicine.

Challenges in Transgender Healthcare: The Pathology Perspective.

PubMed

Gupta, Sarika; Imborek, Katherine L; Krasowski, Matthew D

2016-08-01

The transgender community is one of the most marginalized sections of our society. The literature is scarce regarding the pathology and laboratory medicine challenges associated with caring for transgender patients. To summarize the available gender-transitioning options and to discuss healthcare challenges, from a pathology/laboratory medicine perspective, in the care of transgender patients. We reviewed the current terminology and epidemiology relevant to the transgender population in preparing our analysis. The main transgender healthcare challenges in pathology/laboratory medicine practice include the inflexibility of electronic medical records in documenting affirmed gender, unfamiliarity among medical and laboratory professional with the needs of and terminology related to the transgender population, lack of reference ranges for laboratory tests, unclear guidelines regarding gender classification for blood donation eligibility criteria, and paucity of experience in handling and interpreting surgical and cytologic specimens from gender-transitioning individuals. Directed efforts to overcome these shortcomings, coupled with a more welcoming posture, are essential to achieving the highest standards of care for the transgender population. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Technology-Enhanced Pathology Education: Nigerian Medical Students Perspectives

ERIC Educational Resources Information Center

Vhriterhire, Raymond A.; Orkuma, Joseph A.; Jegede, Olushola O.; Omotosho, Ayodele J.; Adekwu, Amali

2016-01-01

The delivery of pathology education traditionally through instructor centred didactic lectures, small group tutorials, and practical demonstrations using microscope glass slides, gross pot specimens and autopsy sessions, is paving way for electronic learner-centred methods. Successful adoption and implementation of rapidly advancing educational…

Diagnosis of multiple sclerosis through the lens of ultra-high-field MRI

NASA Astrophysics Data System (ADS)

Sati, Pascal

2018-06-01

The long-standing relationship between ultra-high-field (7 T) MRI and multiple sclerosis (MS) has brought new insights to our understanding of lesion evolution and its associated pathology. With the recent FDA approval of a commercially available scanner, 7 T MRI is finally entering the clinic with great expectations about its potential added value. By looking through the prism of MS diagnosis, this perspective article discusses current limitations and prospects of 7 T MRI techniques relevant to helping clinicians diagnose patients encountered in daily practice.

The brain MRI classification problem from wavelets perspective

NASA Astrophysics Data System (ADS)

Bendib, Mohamed M.; Merouani, Hayet F.; Diaba, Fatma

2015-02-01

Haar and Daubechies 4 (DB4) are the most used wavelets for brain MRI (Magnetic Resonance Imaging) classification. The former is simple and fast to compute while the latter is more complex and offers a better resolution. This paper explores the potential of both of them in performing Normal versus Pathological discrimination on the one hand, and Multiclassification on the other hand. The Whole Brain Atlas is used as a validation database, and the Random Forest (RF) algorithm is employed as a learning approach. The achieved results are discussed and statistically compared.

The anthropology of dementia: a narrative perspective.

PubMed

Randall, William L

2009-03-01

This article draws on recent thinking in the field of narrative gerontology to lend support to Mahnaz Hashmi's "anthropological perspective" on dementia. From a narrative perspective, the relational component of human life--and thus of dementia--is underscored. Moreover, when the narrative dimensions of memory are considered, the line between "normal" and "pathological" is revealed as finer than commonly assumed.

Challenges in Transgender Healthcare: The Pathology Perspective

PubMed Central

Gupta, Sarika; Imborek, Katherine L.; Krasowski, Matthew D.

2016-01-01

Background: The transgender community is one of the most marginalized sections of our society. The literature is scarce regarding the pathology and laboratory medicine challenges associated with caring for transgender patients. Objective: To summarize the available gender-transitioning options and to discuss healthcare challenges, from a pathology/laboratory medicine perspective, in the care of transgender patients. Method: We reviewed the current terminology and epidemiology relevant to the transgender population in preparing our analysis. Conclusions: The main transgender healthcare challenges in pathology/laboratory medicine practice include the inflexibility of electronic medical records in documenting affirmed gender, unfamiliarity among medical and laboratory professional with the needs of and terminology related to the transgender population, lack of reference ranges for laboratory tests, unclear guidelines regarding gender classification for blood donation eligibility criteria, and paucity of experience in handling and interpreting surgical and cytologic specimens from gender-transitioning individuals. Directed efforts to overcome these shortcomings, coupled with a more welcoming posture, are essential to achieving the highest standards of care for the transgender population. PMID:27287942

In vitro pathological modelling using patient-specific induced pluripotent stem cells: the case of progeria.

PubMed

Nissan, Xavier; Blondel, Sophie; Peschanski, Marc

2011-12-01

Progeria, also known as HGPS (Hutchinson-Gilford progeria syndrome), is a rare fatal genetic disease characterized by an appearance of accelerated aging in children. This syndrome is typically caused by mutations in codon 608 (C1804T) of the gene encoding lamins A and C, LMNA, leading to the production of a truncated form of the protein called progerin. Owing to their unique potential to self-renew and to differentiate into any cell types of the organism, pluripotent stem cells offer a unique tool to study molecular and cellular mechanisms related to this global and systemic disease. Recent studies have exploited this potential by generating human induced pluripotent stem cells from HGPS patients' fibroblasts displaying several phenotypic defects characteristic of HGPS such as nuclear abnormalities, progerin expression, altered DNA-repair mechanisms and premature senescence. Altogether, these findings provide new insights on the use of pluripotent stem cells for pathological modelling and may open original therapeutic perspectives for diseases that lack pre-clinical in vitro human models, such as HGPS.

Surgical pathology and the patient: a systematic review evaluating the primary audience of pathology reports.

PubMed

Mossanen, Matthew; True, Lawrence D; Wright, Jonathan L; Vakar-Lopez, Funda; Lavallee, Danielle; Gore, John L

2014-11-01

The pathology report is a critical document that helps guide the management of patients with cancer. More and more patients read their reports, intending to participate in decisions about their care. However, a substantial subset of patients may lack the ability to comprehend this often technical and complex document. We hypothesized that most literature on pathology reports discusses reports from the perspective of other physicians and not from the perspective of patients. An expert panel of physicians developed a list of search criteria, which we used to identify articles on PubMed, MEDLINE, Cochrane Reviews, and Google Scholar databases. Two reviewers independently evaluated all articles to identify for detailed review those that met search criteria. We identified the primary audience of the selected articles and the degree to which these articles addressed clarity of communication of pathology reports with patients. Of 801 articles identified in our search, 25 involved the formatting of pathology reports for clarity of communication. Recurrent themes in proposed improvements in reports included content standardization, variation in terminology, clarity of communication, and quality improvement. No articles discussed patients as their target audience. No study evaluated the health literacy level required of patients to comprehend pathology reports. In summary, there is a scarcity of patient-centered approaches to improve pathology reports. The literature on pathology reports does not include patients as a target audience. Limited resources are available to help patients comprehend their reports. Efforts to improve patient-centered communication are desirable to address this overlooked aspect of patient care. Copyright © 2014 Elsevier Inc. All rights reserved.

Stem cells and bone diseases: new tools, new perspective

PubMed Central

Riminucci, Mara; Remoli, Cristina; Robey, Pamela G.; Bianco, Paolo

2017-01-01

Postnatal skeletal stem cells are a unique class of progenitors with biological properties that extend well beyond the limits of stemness as commonly defined. Skeletal stem cells sustain skeletal tissue homeostasis, organize and maintain the complex architectural structure of the bone marrow microenvironment and provide a niche for hematopoietic progenitor cells. The identification of stem cells in the human post-natal skeleton has profoundly changed our approach to the physiology and pathology of this system. Skeletal diseases have been long interpreted essentially in terms of defective function of differentiated cells and/or abnormal turnover of the matrix they produce. The notion of a skeletal stem cell has brought forth multiple, novel concepts in skeletal biology that provide potential alternative concepts. At the same time, the recognition of the complex functions played by skeletal progenitors, such as the structural and functional organization of the bone marrow, has provided an innovative, unifying perspective for understanding bone and bone marrow changes simultaneously occurring in many disorders. Finally, the possibility to isolate and highly enrich for skeletal progenitors, enables us to reproduce perfectly normal or pathological organ miniatures. These, in turn, provide suitable models to investigate and manipulate the pathogenetic mechanisms of many genetic and non-genetic skeletal diseases. PMID:25240458

Emerging Role of Spinal Cord TRPV1 in Pain Exacerbation

PubMed Central

Choi, Seung-In; Lim, Ji Yeon; Yoo, Sungjae; Kim, Hyun; Hwang, Sun Wook

2016-01-01

TRPV1 is well known as a sensor ion channel that transduces a potentially harmful environment into electrical depolarization of the peripheral terminal of the nociceptive primary afferents. Although TRPV1 is also expressed in central regions of the nervous system, its roles in the area remain unclear. A series of recent reports on the spinal cord synapses have provided evidence that TRPV1 plays an important role in synaptic transmission in the pain pathway. Particularly, in pathologic pain states, TRPV1 in the central terminal of sensory neurons and interneurons is suggested to commonly contribute to pain exacerbation. These observations may lead to insights regarding novel synaptic mechanisms revealing veiled roles of spinal cord TRPV1 and may offer another opportunity to modulate pathological pain by controlling TRPV1. In this review, we introduce historical perspectives of this view and details of the recent promising results. We also focus on extended issues and unsolved problems to fully understand the role of TRPV1 in pathological pain. Together with recent findings, further efforts for fine analysis of TRPV1's plastic roles in pain synapses at different levels in the central nervous system will promote a better understanding of pathologic pain mechanisms and assist in developing novel analgesic strategies. PMID:26885404

Ultrasonography in lung pathologies: new perspectives.

PubMed

Demi, Libertario; Demi, Marcello; Smargiassi, Andrea; Inchingolo, Riccardo; Faita, Francesco; Soldati, Gino

2014-01-01

Nowadays, ultrasound techniques have not gained importance in the diagnosis and monitoring of lung pathologies yet because of the high mismatch in acoustic impedance between air and intercostal tissues. However, it is evident that B-mode imaging provides important information on pulmonary tissue, although in the form of image artifacts. Notwithstanding medical evidences, there exists no ultrasound-based method dedicated to the lung, hampering de facto the full exploitation of ultrasound potentials. A chance is given by the experience acquired in other fields, where acoustic attenuation is used to estimate concentrations of suspended particles in liquids and of air-bubbles in aerated foods. Custom hardware must be developed since commercial echographic equipment has been optimized to work with low acoustic impedance mismatches, and, in general, does not provide the primitive radiofrequency (RF) signals nor the possibility to tune key acquisition parameters such as ultrasound carrier frequency and pulse bandwidth, which are surely needed for our application.

Ultrasonography in lung pathologies: new perspectives

PubMed Central

2014-01-01

Background Nowadays, ultrasound techniques have not gained importance in the diagnosis and monitoring of lung pathologies yet because of the high mismatch in acoustic impedance between air and intercostal tissues. However, it is evident that B-mode imaging provides important information on pulmonary tissue, although in the form of image artifacts. Findings Notwithstanding medical evidences, there exists no ultrasound-based method dedicated to the lung, hampering de facto the full exploitation of ultrasound potentials. A chance is given by the experience acquired in other fields, where acoustic attenuation is used to estimate concentrations of suspended particles in liquids and of air-bubbles in aerated foods. Conclusions Custom hardware must be developed since commercial echographic equipment has been optimized to work with low acoustic impedance mismatches, and, in general, does not provide the primitive radiofrequency (RF) signals nor the possibility to tune key acquisition parameters such as ultrasound carrier frequency and pulse bandwidth, which are surely needed for our application. PMID:24834347

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

Epigenetics in Alzheimer's Disease: Perspective of DNA Methylation.

PubMed

Qazi, Talal Jamil; Quan, Zhenzhen; Mir, Asif; Qing, Hong

2018-02-01

Research over the years has shown that causes of Alzheimer's disease are not well understood, but over the past years, the involvement of epigenetic mechanisms in the developing memory formation either under pathological or physiological conditions has become clear. The term epigenetics represents the heredity of changes in phenotype that are independent of altered DNA sequences. Different studies validated that cytosine methylation of genomic DNA decreases with age in different tissues of mammals, and therefore, the role of epigenetic factors in developing neurological disorders in aging has been under focus. In this review, we summarized and reviewed the involvement of different epigenetic mechanisms especially the DNA methylation in Alzheimer's disease (AD), late-onset Alzheimer's disease (LOAD), familial Alzheimer's disease (FAD), and autosomal dominant Alzheimer's disease (ADAD). Down to the minutest of details, we tried to discuss the methylation patterns like mitochondrial DNA methylation and ribosomal DNA (rDNA) methylation. Additionally, we mentioned some therapeutic approaches related to epigenetics, which could provide a potential cure for AD. Moreover, we reviewed some recent studies that validate DNA methylation as a potential biomarker and its role in AD. We hope that this review will provide new insights into the understanding of AD pathogenesis from the epigenetic perspective especially from the perspective of DNA methylation.

Diagnosis of inflammatory bowel disease: Potential role of molecular biometrics.

PubMed

M'Koma, Amosy E

2014-11-27

Accurate diagnosis of predominantly colonic inflammatory bowel disease (IBD) is not possible in 30% of patients. For decades, scientists have worked to find a solution to improve diagnostic accuracy for IBD, encompassing Crohn's colitis and ulcerative colitis. Evaluating protein patterns in surgical pathology colectomy specimens of colonic mucosal and submucosal compartments, individually, has potential for diagnostic medicine by identifying integrally independent, phenotype-specific cellular and molecular characteristics. Mass spectrometry (MS) and imaging (I) MS are analytical technologies that directly measure molecular species in clinical specimens, contributing to the in-depth understanding of biological molecules. The biometric-system complexity and functional diversity is well suited to proteomic and diagnostic studies. The direct analysis of cells and tissues by Matrix-Assisted-Laser Desorption/Ionization (MALDI) MS/IMS has relevant medical diagnostic potential. MALDI-MS/IMS detection generates molecular signatures obtained from specific cell types within tissue sections. Herein discussed is a perspective on the use of MALDI-MS/IMS and bioinformatics technologies for detection of molecular-biometric patterns and identification of differentiating proteins. I also discuss a perspective on the global challenge of transferring technologies to clinical laboratories dealing with IBD issues. The significance of serologic-immunometric advances is also discussed.

Diagnosis of inflammatory bowel disease: Potential role of molecular biometrics

PubMed Central

M’Koma, Amosy E

2014-01-01

Accurate diagnosis of predominantly colonic inflammatory bowel disease (IBD) is not possible in 30% of patients. For decades, scientists have worked to find a solution to improve diagnostic accuracy for IBD, encompassing Crohn’s colitis and ulcerative colitis. Evaluating protein patterns in surgical pathology colectomy specimens of colonic mucosal and submucosal compartments, individually, has potential for diagnostic medicine by identifying integrally independent, phenotype-specific cellular and molecular characteristics. Mass spectrometry (MS) and imaging (I) MS are analytical technologies that directly measure molecular species in clinical specimens, contributing to the in-depth understanding of biological molecules. The biometric-system complexity and functional diversity is well suited to proteomic and diagnostic studies. The direct analysis of cells and tissues by Matrix-Assisted-Laser Desorption/Ionization (MALDI) MS/IMS has relevant medical diagnostic potential. MALDI-MS/IMS detection generates molecular signatures obtained from specific cell types within tissue sections. Herein discussed is a perspective on the use of MALDI-MS/IMS and bioinformatics technologies for detection of molecular-biometric patterns and identification of differentiating proteins. I also discuss a perspective on the global challenge of transferring technologies to clinical laboratories dealing with IBD issues. The significance of serologic-immunometric advances is also discussed. PMID:25429322

Cyber addictions: toward a psychosocial perspective.

PubMed

Suissa, Amnon Jacob

2015-04-01

The concept of cyberaddiction is far from being unanimously accepted by scientists (Ko, Yen, Yen, Chen, & Chen 2012; Pezoa-Jares, Espinoza-Luna & Vasquez-Medina 2012; Nadeau et al., 2011; Perraton, Fusaro & Bonenfant 2011). The same is true of addiction to videogames (Hellman, Schoenmakers, Nordstrom, & Van Holst 2013; Coulombe 2010); or to Facebook (Andreassen et al., 2012; Levard & Soulas, 2010). While certain researchers wished to see this condition included in the DSM-5 (Block, 2008), others question the operational and practical bases for the diagnostic criteria. Some see cyberaddiction as a problem linked more to time management, to brain deficits, to an impulse-control disorder or to psychosocial conditions while others consider it to be a pre-existing comorbidity. Considering that most addiction problems are generally understood more as individual and pathological problems rather than the result of psychosocial conditions (poverty, unemployment, weak social ties, social exclusion, hyper individualism, etc), the aim of this article is to propose a psychosocial perspective for this emerging trend in cyberaddictions. To what extent social conditions and cyberaddiction behaviors constitute a potential pathology? Can we include a psychosocial approach to gain a more general picture of this contemporary issue? In response to these questions, a contextualization and an attempt to define cyberaddiction will be followed by an analysis of some major issues in the development of this type of addiction. A demonstration of the cycle of addiction on how people develop addictions, including cyberaddictions, will be done within a psychosocial perspective in order to seize the multifactorial aspects of this addiction. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

A Disease or Not a Disease? Aging As a Pathology.

PubMed

Gladyshev, Timothy V; Gladyshev, Vadim N

2016-12-01

The debate on the relationship between aging and disease is centered on whether aging is a normal/natural/physiological process or it represents a pathology. Considering this relationship from medical, molecular, social, and historical perspectives, we argue that aging is neither a disease, nor a non-disease. Instead, it combines all age-related diseases and their preclinical forms, in addition to other pathological changes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Problematic Online Pornography Use: A Media Attendance Perspective.

PubMed

Sirianni, Joseph M; Vishwanath, Arun

2016-01-01

Since the rise of the popularity of the Internet, the accessibility of pornography has been a growing concern. One particular concern is the potential risk for addictive behaviors to occur as a result of the ease of viewing online pornographic material. The research presented herein explored online pornography addiction using a media attendance perspective, which allows media critics to examine the needs that people seek to fulfill from engaging with various media. Past studies that have used a media attendance perspective to explore media addiction, rephrased here as problematic media use, have done so using social cognitive theory and the concept of deficient self-regulation. Deficient self-regulation may be experienced by all media consumers and can range from normally impulsive media choices to pathological media choices which may result in detrimental life consequences. Borrowing from this, the current study reevaluated online pornography addiction using deficient self-regulation within a sociocognitive framework of media attendance. Results of our model show deficient self-regulation influences habitual online pornography consumption. Moreover, online pornography use motivated by social needs is perpetuated by deficient self-regulation and may lead to negative life consequences in some individuals. These findings contribute a new perspective and framework for understanding problematic online pornography use.

Osteoarthritis-like pathologic changes in the knee joint induced by environmental disruption of circadian rhythms is potentiated by a high-fat diet.

PubMed

Kc, Ranjan; Li, Xin; Forsyth, Christopher B; Voigt, Robin M; Summa, Keith C; Vitaterna, Martha Hotz; Tryniszewska, Beata; Keshavarzian, Ali; Turek, Fred W; Meng, Qing-Jun; Im, Hee-Jeong

2015-11-20

A variety of environmental factors contribute to progressive development of osteoarthritis (OA). Environmental factors that upset circadian rhythms have been linked to various diseases. Our recent work establishes chronic environmental circadian disruption - analogous to rotating shiftwork-associated disruption of circadian rhythms in humans - as a novel risk factor for the development of OA. Evidence suggests shift workers are prone to obesity and also show altered eating habits (i.e., increased preference for high-fat containing food). In the present study, we investigated the impact of chronic circadian rhythm disruption in combination with a high-fat diet (HFD) on progression of OA in a mouse model. Our study demonstrates that when mice with chronically circadian rhythms were fed a HFD, there was a significant proteoglycan (PG) loss and fibrillation in knee joint as well as increased activation of the expression of the catabolic mediators involved in cartilage homeostasis. Our results, for the first time, provide the evidence that environmental disruption of circadian rhythms plus HFD potentiate OA-like pathological changes in the mouse joints. Thus, our findings may open new perspectives on the interactions of chronic circadian rhythms disruption with diet in the development of OA and may have potential clinical implications.

Renewing Our Cultural Borderlands: Equitable Population Innovations for Communication (EPIC)

ERIC Educational Resources Information Center

Pillay, Mershen; Kathard, Harsha

2018-01-01

The professions of speech-language pathology and audiology provide valuable services for persons with communication, hearing, and feeding/swallowing disabilities. However, from a global perspective, mainstream practice discourses represent values from colonial perspectives (called Northern here). As such, they remain largely inaccessible to most…

Black Families. Interdisciplinary Perspectives.

ERIC Educational Resources Information Center

Cheatham, Harold E., Ed.; Stewart, James B., Ed.

Since the early 1960s, the black family has been characterized as pathological. This six-part collection of 18 research studies presents alternative approaches to understanding the special characteristics of black families. Part I, "Theoretical and Methodological Perspectives," comprises a comparison of the pioneering work of W. E. B. Du…

[Search for potential gastric cancer biomarkers using low molecular weight blood plasma proteome profiling by mass spectrometry].

PubMed

Shevchenko, V E; Arnotskaia, N E; Ogorodnikova, E V; Davydov, M M; Ibraev, M A; Turkin, I N; Davydov, M I

2014-01-01

Gastric cancer, one of the most widespread malignant tumors, still lacks reliable serum/plasma biomarkers of its early detection. In this study we have developed, unified, and tested a new methodology for search of gastric cancer biomarkers based on profiling of low molecular weight proteome (LMWP) (1-17 kDa). This approach included three main components: sample pre-fractionation, matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS), data analysis by a bioinformatics software package. Applicability and perspectives of the developed approach for detection of potential gastric cancer markers during LMWP analysis have been demonstrated using 69 plasma samples from patients with gastric cancer (stages I-IV) and 238 control samples. The study revealed peptides/polypeptides, which may be potentially used for detection of this pathology.

Alzheimer’s in 3D culture: Challenges and perspectives

PubMed Central

D'Avanzo, Carla; Aronson, Jenna; Kim, Young Hye; Choi, Se Hoon; Tanzi, Rudolph E.; Kim, Doo Yeon

2015-01-01

Summary Alzheimer’s disease (AD) is the most common cause of dementia, and there is currently no cure. The “β-amyloid cascade hypothesis” of AD is the basis of current understanding of AD pathogenesis and drug discovery. However, no AD models have fully validated this hypothesis. We recently developed a human stem cell culture model of AD by cultivating genetically modified human neural stem cells in a three-dimensional (3D) cell culture system. These cells were able to recapitulate key events of AD pathology including β-amyloid plaques and neurofibrillary tangles. In this review, we will discuss the progress and current limitations of AD mouse models and human stem cell models as well as explore the breakthroughs of 3D cell culture systems. We will also share our perspective on the potential of dish models of neurodegenerative diseases for studying pathogenic cascades and therapeutic drug discovery. PMID:26252541

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

PubMed

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

2016-11-01

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

Pathological gambling and the loss of willpower: a neurocognitive perspective.

PubMed

Brevers, Damien; Noël, Xavier

2013-01-01

The purpose of this review is to gain more insight on the neurocognitive processes involved in the maintenance of pathological gambling. Firstly, we describe structural factors of gambling games that could promote the repetition of gambling experiences to such an extent that some individuals may become unable to control their gambling habits. Secondly, we review findings of neurocognitive studies on pathological gambling. As a whole, poor ability to resist gambling is a product of an imbalance between any one or a combination of three key neural systems: (1) an hyperactive 'impulsive' system, which is fast, automatic, and unconscious and promotes automatic and habitual actions; (2) a hypoactive 'reflective' system, which is slow and deliberative, forecasting the future consequences of a behavior, inhibitory control, and self-awareness; and (3) the interoceptive system, translating bottom-up somatic signals into a subjective state of craving, which in turn potentiates the activity of the impulsive system, and/or weakens or hijacks the goal-driven cognitive resources needed for the normal operation of the reflective system. Based on this theoretical background, we focus on certain clinical interventions that could reduce the risks of both gambling addiction and relapse.

Pathological gambling and the loss of willpower: a neurocognitive perspective

PubMed Central

Brevers, Damien; Noël, Xavier

2013-01-01

The purpose of this review is to gain more insight on the neurocognitive processes involved in the maintenance of pathological gambling. Firstly, we describe structural factors of gambling games that could promote the repetition of gambling experiences to such an extent that some individuals may become unable to control their gambling habits. Secondly, we review findings of neurocognitive studies on pathological gambling. As a whole, poor ability to resist gambling is a product of an imbalance between any one or a combination of three key neural systems: (1) an hyperactive ‘impulsive’ system, which is fast, automatic, and unconscious and promotes automatic and habitual actions; (2) a hypoactive ‘reflective’ system, which is slow and deliberative, forecasting the future consequences of a behavior, inhibitory control, and self-awareness; and (3) the interoceptive system, translating bottom-up somatic signals into a subjective state of craving, which in turn potentiates the activity of the impulsive system, and/or weakens or hijacks the goal-driven cognitive resources needed for the normal operation of the reflective system. Based on this theoretical background, we focus on certain clinical interventions that could reduce the risks of both gambling addiction and relapse. PMID:24693357

Conceptions of narcissism and the DSM-5 pathological personality traits.

PubMed

Wright, Aidan G C; Pincus, Aaron L; Thomas, Katherine M; Hopwood, Christopher J; Markon, Kristian E; Krueger, Robert F

2013-06-01

The Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) features two conceptions of Narcissistic Personality Disorder (NPD), one based on the retained DSM-IV's categorical diagnosis and the other based on a model that blends impairments in personality functioning with a specific trait profile intended to recapture DSM-IV NPD. Nevertheless, the broader literature contains a richer array of potential conceptualizations of narcissism, including distinguishable perspectives from psychiatric nosology, clinical observation and theory, and social/personality psychology. This raises questions about the most advantageous pattern of traits to use to reflect various conceptions of narcissistic pathology via the Personality Inventory for the DSM-5 (PID-5). In this study, we examine the associations of the Personality Disorder Questionnaire-Narcissistic Personality Disorder scale, Narcissistic Personality Inventory-16, and the Pathological Narcissism Inventory and the PID-5 dimensions and facets in a large sample (N = 1,653) of undergraduate student participants. Results point to strong associations with PID-5 Antagonism scales across narcissism measures, consistent with the DSM-5's proposed representation of NPD. However, additional notable associations emerged with PID-5 Negative Affectivity and Psychoticism scales when considering more clinically relevant narcissism measures.

Deaf: A Concept Analysis From a Cultural Perspective Using the Wilson Method of Concept Analysis Development.

PubMed

Pendergrass, Kathy M; Newman, Susan D; Jones, Elaine; Jenkins, Carolyn H

2017-07-01

The purpose of this article is to provide an analysis of the concept Deaf to increase health care provider (HCP) understanding from a cultural perspective. Deaf signers, people with hearing loss who communicate primarily in American Sign Language (ASL), generally define the term Deaf as a cultural heritage. In the health care setting, the term deaf is most often defined as a pathological condition requiring medical intervention. When HCPs are unaware that there are both cultural and pathological views of hearing loss, significant barriers may exist between the HCP and the Deaf individual. The concept of Deaf is analyzed using the Wilsonian method. Essential elements of the concept "Deaf" from a cultural perspective include a personal choice to communicate primarily in ASL and identify with the Deaf community. Resources for HCPs are needed to quickly identify Deaf signers and provide appropriate communication.

An Aphasia Mentoring Program: Perspectives of Speech-Language Pathology Students and of Mentors with Aphasia

ERIC Educational Resources Information Center

Purves, Barbara A.; Petersen, Jill; Puurveen, Gloria

2013-01-01

Purpose: In contrast to clinician-as-expert models, social models of clinical practice typically acknowledge people with aphasia as equal partners in intervention. Given this, there may be a place within speech-language pathology education for programs situating people with aphasia as experts. This paper describes an aphasia mentoring program that…

Experiences of Student Speech-Language Pathology Clinicians in the Initial Clinical Practicum: A Phenomenological Study

ERIC Educational Resources Information Center

Nelson, Lori A.

2011-01-01

Speech-language pathology literature is limited in describing the clinical practicum process from the student perspective. Much of the supervision literature in this field focuses on quantitative research and/or the point of view of the supervisor. Understanding the student experience serves to enhance the quality of clinical supervision. Of…

Speech and Language Therapy/Pathology: Perspectives on a Gendered Profession

ERIC Educational Resources Information Center

Litosseliti, Lia; Leadbeater, Claire

2013-01-01

Background: The speech and language therapy/pathology (SLT/SLP) profession is characterized by extreme "occupational sex segregation", a term used to refer to persistently male- or female-dominated professions. Men make up only 2.5% of all SLTs in the UK, and a similar imbalance is found in other countries. Despite calls to increase…

Individual vulnerabilities relative for potential pathological conditions.

PubMed

Moal, Michel Le

2016-08-15

It is not a usual venture to review experiments conducted decades ago in the context of interests of that time and replace them in a long-term historical perspective. These investigations were the product of a long-standing interest for individual differences in vulnerabilities relative to coping with stressful situations and for potential pathological conditions such as drug abuse. The rationale was, and still is, to decipher the psychobiological characteristics of these complex traits. STRESS- AND PHARMACOLOGICALLY-INDUCED BEHAVIORAL SENSITIZATION INCREASES VULNERABILITY TO ACQUISITION OF AMPHETAMINE SELF-ADMINISTRATION: Individual vulnerability to drug addiction may be an important factor in the prognosis of pathological behavior in man. However, experimental investigations have largely neglected the psychobiological substrate of predisposition to addiction. In this study, we use a self-administration (SA) acquisition paradigm showing that previous repeated exposure to a stressful experience (tail-pinch) or to amphetamine increases the locomotor response to this drug (behavioral sensitization) and enhances vulnerability to amphetamine SA. These results show that vulnerability to developing amphetamine SA may be influenced by stressful experiences, and that previous contact with the drug may also enhance a predisposition to amphetamine-taking behavior. As tail-pinch and amphetamine sensitization affect both the dopamine (DA) neural system and the propensity to self-administer amphetamine (a behavior also modulated by DA activity), stress may influence SA via an action on the DA system. © 1990. This article is part of a Special Issue entitled SI:50th Anniversary Issue. Copyright © 2016 Elsevier B.V. All rights reserved.

Stem cells and bone diseases: new tools, new perspective.

PubMed

Riminucci, Mara; Remoli, Cristina; Robey, Pamela G; Bianco, Paolo

2015-01-01

Postnatal skeletal stem cells are a unique class of progenitors with biological properties that extend well beyond the limits of stemness as commonly defined. Skeletal stem cells sustain skeletal tissue homeostasis, organize and maintain the complex architectural structure of the bone marrow microenvironment and provide a niche for hematopoietic progenitor cells. The identification of stem cells in the human post-natal skeleton has profoundly changed our approach to the physiology and pathology of this system. Skeletal diseases have been long interpreted essentially in terms of defective function of differentiated cells and/or abnormal turnover of the matrix that they produce. The notion of a skeletal stem cell has brought forth multiple, novel concepts in skeletal biology that provide potential alternative concepts. At the same time, the recognition of the complex functions played by skeletal progenitors, such as the structural and functional organization of the bone marrow, has provided an innovative, unifying perspective for understanding bone and bone marrow changes simultaneously occurring in many disorders. Finally, the possibility to isolate and highly enrich for skeletal progenitors, enables us to reproduce perfectly normal or pathological organ miniatures. These, in turn, provide suitable models to investigate and manipulate the pathogenetic mechanisms of many genetic and non-genetic skeletal diseases. This article is part of a Special Issue entitled Stem cells and Bone. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Survey of Spouse Abuse Shelters: A Family Systems Perspective.

ERIC Educational Resources Information Center

Lindegren, Tina M.

Traditional psychological theories which focus on the pathological tendencies of the individual account for little of the reported widespread spouse abuse. Social exchange and general systems theories focus on problems in the relationship rather than problems in the person. Given that a family perspective may be helpful in long-term treatment of…

Mirror, Mirror on the Wall: Reflections on Speech-Language Pathologists' Image as Advocates, Activists, and Aides

ERIC Educational Resources Information Center

Donaldson, Amy L.; Chabon, Shelly; Lee-Wilkerson, Dorian; Kapantzoglou, Maria

2017-01-01

Traditionally speech-language pathology, along with other educational and rehabilitation-based professions, has approached disability from a deficits-based or medical-model perspective with an aim toward normalizing or ameliorating a child's atypical behaviors or performance. However, an alternative perspective rooted in a social model of…

The behavioral economics of substance use disorders: reinforcement pathologies and their repair.

PubMed

Bickel, Warren K; Johnson, Matthew W; Koffarnus, Mikhail N; MacKillop, James; Murphy, James G

2014-01-01

The field of behavioral economics has made important inroads into the understanding of substance use disorders through the concept of reinforcer pathology. Reinforcer pathology refers to the joint effects of (a) the persistently high valuation of a reinforcer, broadly defined to include tangible commodities and experiences, and/or (b) the excessive preference for the immediate acquisition or consumption of a commodity despite long-term negative outcomes. From this perspective, reinforcer pathology results from the recursive interactions of endogenous person-level variables and exogenous environment-level factors. The current review describes the basic principles of behavioral economics that are central to reinforcer pathology, the processes that engender reinforcer pathology, and the approaches and procedures that can repair reinforcement pathologies. The overall goal of this review is to present a new understanding of substance use disorders as viewed by recent advances in behavioral economics.

The Behavioral Economics of Substance Use Disorders: reinforcement pathologies and their repair

PubMed Central

Bickel, Warren K.; Johnson, Matthew W.; Koffarnus, Mikhail N.; MacKillop, James; Murphy, James G.

2015-01-01

The field of behavioral economics has made important inroads into the understanding of substance use disorders through the concept of reinforcer pathology. Reinforcer pathology refers to the joint effects of (a) the persistently high valuation of a reinforcer, broadly defined to include tangible commodities and experiences, and/or (b) the excessive preference for the immediate acquisition or consumption of a commodity despite long-term negative outcomes. From this perspective, reinforcer pathology results from the recursive interactions of endogenous person-level variables and exogenous environment-level factors. The current review describes the basic principles of behavioral economics that are central to reinforcer pathology, the processes that engender reinforcer pathology, and the approaches and procedures that can repair reinforcement pathologies. The overall goal of this review is to present a new understanding of substance use disorders as viewed by recent advances in behavioral economics. PMID:24679180

Mitochondrial Disease: Clinical Aspects, Molecular Mechanisms, Translational Science, and Clinical Frontiers

PubMed Central

Thornton, Ben; Cohen, Bruce; Copeland, William; Maria, Bernard L.

2015-01-01

Mitochondrial medicine provides a metabolic perspective on the pathology of conditions linked with inadequate oxidative phosphorylation. Dysfunction in the mitochondrial machinery can result in improper energy production, leading to cellular injury or even apoptosis. Clinical presentations are often subtle, so clinicians must have a high index of suspicion to make early diagnoses. Symptoms could include muscle weakness and pain, seizures, loss of motor control, decreased visual and auditory functions, metabolic acidosis, acute developmental regression, and immune system dysfunction. The 2013 Neurobiology of Disease in Children Symposium, held in conjunction with the 42nd Annual Meeting of the Child Neurology Society, aimed to (1) describe accepted clinical phenotypes of mitochondrial disease produced from various mitochondrial mutations, (2) discuss contemporary understanding of molecular mechanisms that contribute to disease pathology, (3) highlight the systemic effects produced by dysfunction within the mitochondrial machinery, and (4) introduce current strategies that are being translated from bench to bedside as potential therapeutics. PMID:24916430

Linking Gambling and Trauma: A Phenomenological Hermeneutic Case Study Using Almaas' Transformation of Narcissism Approach

ERIC Educational Resources Information Center

Nixon, Gary; Solowoniuk, Jason; Boni, Lauren Julia; Kalischuk, Ruth Grant

2013-01-01

The purpose of this article is to examine the phenomenon of pathological gambling and addiction from the perspective of writer and teacher A.H Almaas. By drawing on his Diamond Mind approach we trace the origin of addictive behaviors and pathological gambling to narcissistic wounding, which constitutes the loss of connection with the Essential…

African American Therapists Working with African American Families: An Exploration of the Strengths Perspective in Treatment

ERIC Educational Resources Information Center

Bell-Tolliver, Laverne; Burgess, Ruby; Brock, Linda J.

2009-01-01

With the exception of Hill's (1971, 1999) work, historically much of the literature on African American families has focused more on pathology than strengths. This study used interviews with 30 African American psychotherapists, self-identified as employing a strengths perspective with African American families, to investigate which strengths they…

The Estrogen Receptors: An Overview from Different Perspectives.

PubMed

Eyster, Kathleen M

2016-01-01

The estrogen receptors, ERα, ERβ, and GPER, mediate the effects of estrogenic compounds on their target tissues. Estrogen receptors are located in the tissues of the female reproductive tract and breast as one would expect, but also in tissues as diverse as bone, brain, liver, colon, skin, and salivary gland. The purpose of this discussion of the estrogen receptors is to provide a brief overview of the estrogen receptors and estrogen action from perspectives such as the historical, physiological, pharmacological, pathological, structural, and ligand perspectives.

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

PubMed

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

2014-08-01

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

Multiplex biomarker approach to cardiovascular diseases.

PubMed

Adamcova, Michaela; Šimko, Fedor

2018-04-12

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

La Ferrassie 1: New perspectives on a "classic" Neandertal.

PubMed

Gómez-Olivencia, Asier; Quam, Rolf; Sala, Nohemi; Bardey, Morgane; Ohman, James C; Balzeau, Antoine

2018-04-01

The La Ferrassie 1 (LF1) skeleton, discovered over a century ago, is one of the most important Neandertal individuals both for its completeness and due to the role it has played historically in the interpretation of Neandertal anatomy and lifeways. Here we present new skeletal remains from this individual, which include a complete right middle ear ossicular chain (malleus, incus, and stapes), three vertebral fragments, and two costal remains. Additionally, the study of the skeleton has allowed us to identify new pathological lesions, including a congenital variant in the atlas, a greenstick fracture of the left clavicle, and a lesion in a mid-thoracic rib of unknown etiology. In addition, we have quantified the amount of vertebral pathology, which is greater than previously appreciated. We have complemented the paleopathological analysis with a taphonomic analysis to identify any potential perimortem fractures. The taphonomic analysis indicates that no surface alteration is present in the LF1 skeleton and that the breakage pattern is that of bone that has lost collagen, which would be consistent with the intentional burial of this individual proposed by previous researchers. In this study, we used CT and microCT scans in order to discover new skeletal elements to better characterize the pathological lesions and to quantify the fracture orientation of those bones in which the current plaster reconstruction did not allow its direct visualization, which underlines the broad potential of imaging technologies in paleoanthropological research. A century after its discovery, LF1 is still providing new insights into Neandertal anatomy and behavior. Copyright © 2018 Elsevier Ltd. All rights reserved.

Post-translational quantitation by SRM/MRM: applications in cardiology.

PubMed

Gianazza, Erica; Banfi, Cristina

2018-06-04

Post-translational modifications (PTMs) have an important role in the regulation of protein function, localization and interaction with other molecules. PTMs apply a dynamic control of proteins both in physiological and pathological conditions. The study of disease-specific PTMs allows identifying potential biomarkers and developing effective drugs. Enrichment techniques combined with high-resolution MS/MS analysis provide attractive results on PTMs characterization. Selected reaction monitoring/multiple reaction monitoring (SRM/MRM) is a powerful targeted assay for the quantitation and validation of PTMs in complex biological samples. Areas covered: The most frequent PTMs are described in terms of biological role and analytical methods commonly used to detect them. The applications of SRM/MRM for the absolute quantitation of PTMs are reported and a specific section is focused on PTMs detection in proteins that are involved in cardiovascular system and heart diseases. Expert commentary: PTMs characterization in relation to disease pathology is still in progress, but targeted proteomics by LC-MS/MS has significantly upgraded the knowledge in the last years. Advances in enrichment strategies and software tools will facilitate the interpretation of high PTMs complexity. Promising studies confirm the great potentiality of SRM/MRM to study PTMs in cardiovascular field and PTMomics could be very useful in a clinical perspective.

Executive functions in mono- and bilingual children with language impairment - issues for speech-language pathology.

PubMed

Sandgren, Olof; Holmström, Ketty

2015-01-01

The clinical assessment of language impairment (LI) in bilingual children imposes challenges for speech-language pathology services. Assessment tools standardized for monolingual populations increase the risk of misinterpreting bilingualism as LI. This Perspective article summarizes recent studies on the assessment of bilingual LI and presents new results on including non-linguistic measures of executive functions in the diagnostic assessment. Executive functions shows clinical utility as less subjected to language use and exposure than linguistic measures. A possible bilingual advantage, and consequences for speech-language pathology practices and future research are discussed.

Mental Health and Inclusion Seen from the Children's and Teachers' Perspectives: A Case Study in Spain

ERIC Educational Resources Information Center

Pérez-Parreño, Miriam; Padilla-Petry, Paulo

2018-01-01

Inclusive school requires the coexistence of what is perceived as normal and what is seen as pathologically different. Considering the growing pathologization of childhood, attempt is made to know the view of the students that do not have any diagnosed mental disorder on the ones that do have and the teachers' view on the inclusion of these…

Gambling and the Health of the Public: Adopting a Public Health Perspective.

PubMed

Korn, David A.; Shaffer, Howard J.

1999-01-01

During the last decade there has been an unprecedented expansion of legalized gambling throughout North America. Three primary forces appear to be motivating this growth: (1) the desire of governments to identify new sources of revenue without invoking new or higher taxes; (2) tourism entrepreneurs developing new destinations for entertainment and leisure; and (3) the rise of new technologies and forms of gambling (e.g., video lottery terminals, powerball mega-lotteries, and computer offshore gambling). Associated with this phenomenon, there has been an increase in the prevalence of problem and pathological gambling among the general adult population, as well as a sustained high level of gambling-related problems among youth. To date there has been little dialogue within the public health sector in particular, or among health care practitioners in general, about the potential health impact of gambling or gambling-related problems. This article encourages the adoption of a public health perspective towards gambling. More specifically, this discussion has four primary objectives:1. Create awareness among health professionals about gambling, its rapid expansion and its relationship with the health care system;2. Place gambling within a public health framework by examining it from several perspectives, including population health, human ecology and addictive behaviors;3. Outline the major public health issues about how gambling can affect individuals, families and communities;4. Propose an agenda for strengthening policy, prevention and treatment practices through greater public health involvement, using the framework of The Ottawa Charter for Health Promotion as a guide.By understanding gambling and its potential impacts on the public's health, policy makers and health practitioners can minimize gambling's negative impacts and appreciate its potential benefits.

Circuit and synaptic mechanisms of repeated stress: Perspectives from differing contexts, duration, and development.

PubMed

Bath, Kevin G; Russo, Scott J; Pleil, Kristen E; Wohleb, Eric S; Duman, Ronald S; Radley, Jason J

2017-12-01

The current review is meant to synthesize research presented as part of a symposium at the 2016 Neurobiology of Stress workshop in Irvine California. The focus of the symposium was "Stress and the Synapse: New Concepts and Methods" and featured the work of several junior investigators. The presentations focused on the impact of various forms of stress (altered maternal care, binge alcohol drinking, chronic social defeat, and chronic unpredictable stress) on synaptic function, neurodevelopment, and behavioral outcomes. One of the goals of the symposium was to highlight the mechanisms accounting for how the nervous system responds to stress and their impact on outcome measures with converging effects on the development of pathological behavior. Dr. Kevin Bath's presentation focused on the impact of disruptions in early maternal care and its impact on the timing of hippocampus maturation in mice, finding that this form of stress drove accelerated synaptic and behavioral maturation, and contributed to the later emergence of risk for cognitive and emotional disturbance. Dr. Scott Russo highlighted the impact of chronic social defeat stress in adolescent mice on the development and plasticity of reward circuity, with a focus on glutamatergic development in the nucleus accumbens and mesolimbic dopamine system, and the implications of these changes for disruptions in social and hedonic response, key processes disturbed in depressive pathology. Dr. Kristen Pleil described synaptic changes in the bed nuclei of the stria terminalis that underlie the behavioral consequences of allostatic load produced by repeated cycles of alcohol binge drinking and withdrawal. Dr. Eric Wohleb and Dr. Ron Duman provided new data associating decreased mammalian target of rapamycin (mTOR) signaling and neurobiological changes in the synapses in response to chronic unpredictable stress, and highlighted the potential for the novel antidepressant ketamine to rescue synaptic and behavioral effects. In aggregate, these presentations showcased how divergent perspectives provide new insights into the ways in which stress impacts circuit development and function, with implications for understanding emergence of affective pathology.

Compartmentalized and systemic control of tissue immunity by commensals

PubMed Central

Belkaid, Yasmine; Naik, Shruti

2013-01-01

The body is composed of various tissue microenvironments with finely tuned local immunosurveillance systems, many of which are in close apposition with distinct commensal niches. Mammals have formed an evolutionary partnership with the microbiota that is critical for metabolism, tissue development and host defense. Despite our growing understanding of the impact of this host-microbe alliance on immunity in the gastrointestinal tract, the extent to which individual microenvironments are controlled by resident microbiota remains unclear. In this Perspective we discuss how resident commensals outside the gastrointestinal tract can control unique physiological niches and the potential implications of the dialog between these commensals and the host for the establishment of immune homeostasis, protective responses and tissue pathology. PMID:23778791

Evaluation of margins in head and neck squamous cell carcinoma from the surgeon's perspective.

PubMed

Baumeister, Philipp; Baumüller, Konstantin; Harréus, Ulrich; Reiter, Maximilian; Welz, Christian

2018-05-01

The surgeon's evaluation of resection status based on frozen section analysis during operation and pathological examination of resected specimens often differ. For this study, we recapitulated the surgeon's perspective during an operation, accordingly classified the evaluation of margins by the surgeon, and analyzed its impact on the outcome compared with the pathological results. This was a retrospective analysis. As data sources, paper-based and digital patient files, as well as the Munich Cancer Registry database were used. Three hundred ninety-six cases were included in this analysis. Only the evaluation of margins by the surgeon influenced local control, and the pathological results influenced disease-free survival (DFS). Surprisingly, margins of >5 mm of normal tissue to cancer growth led to local control and overall survival (OS) significantly worse than 1 to 5-mm resections. The evaluation of margins by the surgeon is of significant importance for local control and OS. It is largely based on frozen section analysis, which, therefore, should be used whenever possible. © 2018 Wiley Periodicals, Inc.

A unifying perspective on personality pathology across the life span: Developmental considerations for the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders

PubMed Central

TACKETT, JENNIFER L.; BALSIS, STEVE; OLTMANNS, THOMAS F.; KRUEGER, ROBERT F.

2010-01-01

Proposed changes in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) include replacing current personality disorder (PD) categories on Axis II with a taxonomy of dimensional maladaptive personality traits. Most of the work on dimensional models of personality pathology, and on personality disorders per se, has been conducted on young and middle-aged adult populations. Numerous questions remain regarding the applicability and limitations of applying various PD models to early and later life. In the present paper, we provide an overview of such dimensional models and review current proposals for conceptualizing PDs in DSM-V. Next, we extensively review existing evidence on the development, measurement, and manifestation of personality pathology in early and later life focusing on those issues deemed most relevant for informing DSM-V. Finally, we present overall conclusions regarding the need to incorporate developmental issues in conceptualizing PDs in DSM-V and highlight the advantages of a dimensional model in unifying PD perspectives across the life span. PMID:19583880

Bmi-1: At the crossroads of physiological and pathological biology

PubMed Central

Bhattacharya, Resham; Mustafi, Soumyajit Banerjee; Street, Mark; Dey, Anindya; Dwivedi, Shailendra Kumar Dhar

2015-01-01

Bmi-1 is a member of the Polycomb Repressor Complex1 that mediates gene silencing by regulating chromatin structure and is indispensable for self-renewal of both normal and cancer stem cells. Despite three decades of research that have elucidated the transcriptional regulation, post-translational modifications and functions of Bmi-1 in regulating the DNA damage response, cellular bioenergetics, and pathologies, the entire potential of a protein with such varied function remains to be realized. This review attempts to synthesize the current knowledge on Bmi-1 with an emphasis on its role in both normal physiology and cancer. Additionally, since cancer stem cells are emerging as a new paradigm for therapy resistance, the role of Bmi-1 in this perspective is also highlighted. The wide spectrum of malignancies that implicate Bmi-1 as a signature for stemness and oncogenesis also make it a suitable candidate for therapy. Nonetheless new approaches are vitally needed to further characterize physiological roles of Bmi-1 with the long-term goal of using Bmi-1 as a prognostic marker and a therapeutic target. PMID:26448339

Pathological gambling in Montreal's Chinese community: an anthropological perspective.

PubMed

Papineau, Elisabeth

2005-01-01

Pathological gambling has been identified as a major issue in Montreal's Chinese community. A variety of sources attest to the fact that, though we live in an increasingly heterogeneous society, the services provided to minority communities for preventing and treating pathological gambling are inadequate. An anthropological approach that takes into account cultural characteristics of one's community could lead to better strategies for acknowledgement, definition, diagnosis and treatment of pathological gambling among culturally different communities. Research paths that could help to provide effective treatment and services to specific populations are suggested. An overview of the way the Chinese view gambling, pathological gambling and treatment is presented. The concepts of fate, destiny and luck in Chinese thought, as well as Montreal's Chinese community social norms related to gambling are then described. The incorporation of those cultural understandings in future studies and treatment attempts is suggested.

Complementary roles for toxicologic pathology and mathematics in toxicogenomics, with special reference to data interpretation and oscillatory dynamics.

PubMed

Morgan, Kevin T; Pino, Michael; Crosby, Lynn M; Wang, Min; Elston, Timothy C; Jayyosi, Zaid; Bonnefoi, Marc; Boorman, Gary

2004-01-01

Toxicogenomics is an emerging multidisciplinary science that will profoundly impact the practice of toxicology. New generations of biologists, using evolving toxicogenomics tools, will generate massive data sets in need of interpretation. Mathematical tools are necessary to cluster and otherwise find meaningful structure in such data. The linking of this structure to gene functions and disease processes, and finally the generation of useful data interpretation remains a significant challenge. The training and background of pathologists make them ideally suited to contribute to the field of toxicogenomics, from experimental design to data interpretation. Toxicologic pathology, a discipline based on pattern recognition, requires familiarity with the dynamics of disease processes and interactions between organs, tissues, and cell populations. Optimal involvement of toxicologic pathologists in toxicogenomics requires that they communicate effectively with the many other scientists critical for the effective application of this complex discipline to societal problems. As noted by Petricoin III et al (Nature Genetics 32, 474-479, 2002), cooperation among regulators, sponsors and experts will be essential for realizing the potential of microarrays for public health. Following a brief introduction to the role of mathematics in toxicogenomics, "data interpretation" from the perspective of a pathologist is briefly discussed. Based on oscillatory behavior in the liver, the importance of an understanding of mathematics is addressed, and an approach to learning mathematics "later in life" is provided. An understanding of pathology by mathematicians involved in toxicogenomics is equally critical, as both mathematics and pathology are essential for transforming toxicogenomics data sets into useful knowledge.

Human Colors-The Rainbow Garden of Pathology: What Gives Normal and Pathologic Tissues Their Color?

PubMed

Piña-Oviedo, Sergio; Ortiz-Hidalgo, Carlos; Ayala, Alberto G

2017-03-01

- Colors are important to all living organisms because they are crucial for camouflage and protection, metabolism, sexual behavior, and communication. Human organs obviously have color, but the underlying biologic processes that dictate the specific colors of organs and tissues are not completely understood. A literature search on the determinants of color in human organs yielded scant information. - To address 2 specific questions: (1) why do human organs have color, and (2) what gives normal and pathologic tissues their distinctive colors? - Endogenous colors are the result of complex biochemical reactions that produce biologic pigments: red-brown cytochromes and porphyrins (blood, liver, spleen, kidneys, striated muscle), brown-black melanins (skin, appendages, brain nuclei), dark-brown lipochromes (aging organs), and colors that result from tissue structure (tendons, aponeurosis, muscles). Yellow-orange carotenes that deposit in lipid-rich tissues are only produced by plants and are acquired from the diet. However, there is lack of information about the cause of color in other organs, such as the gray and white matter, neuroendocrine organs, and white tissues (epithelia, soft tissues). Neoplastic tissues usually retain the color of their nonneoplastic counterpart. - Most available information on the function of pigments comes from studies in plants, microorganisms, cephalopods, and vertebrates, not humans. Biologic pigments have antioxidant and cytoprotective properties and should be considered as potential future therapies for disease and cancer. We discuss the bioproducts that may be responsible for organ coloration and invite pathologists and pathology residents to look at a "routine grossing day" with a different perspective.

Personality assessment of substance-dependent patients in a therapeutic community.

PubMed

Moffett, L A; Steinberg, S L; Rohde, P

1996-01-01

The design and implementation of a personality assessment system for severely substance-dependent men in a therapeutic community (TC) are described. The system was designed from a treatment utility perspective (Hayes, Nelson, & Jarrett, 1987) and uses the Personality Research Form E (Jackson, 1984) to provide each patient with feedback (a) describing his normal personality traits, (b) predicting his probable pattern of adjustment to the treatment setting, and (c) prescribing specific actions he can take to address potentially problematic behaviors. Discussing the the results with the patient helps him cope with the TC. Reviewing the assessment results with the staff promotes their empathy for the patient as a person whose behavior can be understood as an interaction of his personality with the specific demands of the TC rather than seeing the patient in exclusively pathological terms. Specific suggestions for behavior change guide both the patient and the staff and are potentially useful in various treatment settings.

Fentanyl novel derivative-related deaths.

PubMed

Giorgetti, Arianna; Centola, Carmela; Giorgetti, Raffaele

2017-05-01

Fentanyl (FEN) is a potent, synthetic narcotic used as an anaesthetic and a pain reliever, but also illegally manufactured. For diversion purpose, it is being steadily modified to produce new analogous compounds and derivatives (FENS), categorised as novel psychoactive substances. While potential FEN abuse is already known, even in the absence of a clear lethal dosage, there is still a shortage of data on its derivatives. A literature review of FENS-related deaths was performed, to better understand potential damage and future perspectives of FEN congeners. Epidemiological data, pathological findings, administration routes, average concentrations and lethal doses, toxicological issues, trends in misuses, comparison among FENS, and possible explanation for FENS abuse are reviewed and discussed in depth. This study provides a medical-legal and toxicological assessment of this phenomenon in order to understand the role of illegal fentanyl and its congeners in deaths from FENS overdose. Copyright © 2017 John Wiley & Sons, Ltd.

Striated Muscle Function, Regeneration, and Repair

PubMed Central

Shadrin, I.Y.; Khodabukus, A.; Bursac, N.

2016-01-01

As the only striated muscle tissues in the body, skeletal and cardiac muscle share numerous structural and functional characteristics, while exhibiting vastly different size and regenerative potential. Healthy skeletal muscle harbors a robust regenerative response that becomes inadequate after large muscle loss or in degenerative pathologies and aging. In contrast, the mammalian heart loses its regenerative capacity shortly after birth, leaving it susceptible to permanent damage by acute injury or chronic disease. In this review, we compare and contrast the physiology and regenerative potential of native skeletal and cardiac muscles, mechanisms underlying striated muscle dysfunction, and bioengineering strategies to treat muscle disorders. We focus on different sources for cellular therapy, biomaterials to augment the endogenous regenerative response, and progress in engineering and application of mature striated muscle tissues in vitro and in vivo. Finally, we discuss the challenges and perspectives in translating muscle bioengineering strategies to clinical practice. PMID:27271751

Renal dopaminergic system: Pathophysiological implications and clinical perspectives

PubMed Central

Choi, Marcelo Roberto; Kouyoumdzian, Nicolás Martín; Rukavina Mikusic, Natalia Lucía; Kravetz, María Cecilia; Rosón, María Inés; Rodríguez Fermepin, Martín; Fernández, Belisario Enrique

2015-01-01

Fluid homeostasis, blood pressure and redox balance in the kidney are regulated by an intricate interaction between local and systemic anti-natriuretic and natriuretic systems. Intrarenal dopamine plays a central role on this interactive network. By activating specific receptors, dopamine promotes sodium excretion and stimulates anti-oxidant and anti-inflammatory pathways. Different pathological scenarios where renal sodium excretion is dysregulated, as in nephrotic syndrome, hypertension and renal inflammation, can be associated with impaired action of renal dopamine including alteration in biosynthesis, dopamine receptor expression and signal transduction. Given its properties on the regulation of renal blood flow and sodium excretion, exogenous dopamine has been postulated as a potential therapeutic strategy to prevent renal failure in critically ill patients. The aim of this review is to update and discuss on the most recent findings about renal dopaminergic system and its role in several diseases involving the kidneys and the potential use of dopamine as a nephroprotective agent. PMID:25949933

Subduing the green-eyed monster: bridging the psychopharmacological and psychosocial treatment perspective in understanding pathological jealousy.

PubMed

Samad, Farah Deena Abdul; Sidi, Hatta; Kumar, Jaya; Das, Srijit; Midin, Marhani; Hatta, Nurul Hazwani

2017-07-04

Human being is not spared from a broad-ranged emotional state, including being jealous. Jealousy has both affective-cognitive and behavioural-evaluative dimension where the person perceives, or experiences a real threat on a valued relationship. As this complex emotion becomes irrational and not amenable to reason, it later transforms into a dangerously 'green-eyed monster'. This perilous situation which is viewed as pathological jealousy is a form of delusion, which is maintained by a fixed and false reasoning in an originally entrusted intimate relationship. Pathological jealousy is equally prevailing among both gender, and with a greater ubiquitous among the geriatric population. The role of dopamine hyperactivity in the fronto-parietal-temporal region was implicated, with the anatomical mapping of the ventromedial prefrontal cortex (vmPFC), cingulate gyrus (CG), and amygdala involvement in the context of the disease's neurobiology. The etiology of pathological jealousy includes major psychiatric disorders, i.e. delusional disorder, schizophrenia, mood disorder, organic brain syndrome, and among others, the drug-induced psychosis. The role of relationship issues and psychodynamic perspective, i.e. psychological conflicts with dependence on a romantic partner, and low self-esteem are involved. Pathological jealousy inherits high-risk forensic psychiatry entanglement, which may warrant intensive intervention, including hospital admission and antipsychotic treatment. Treatment options include an early recognition, managing underlying neuropsychiatric disorders, psycho education, cognitive psychotherapy, and choosing an effective psychopharmacological agent. The management strategy may also resort to a geographical intervention, i.e. separation between both persons to complement the biological treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Telemedicine in Cardiology - Perspectives in Bosnia and Herzegovina

PubMed Central

Naser, Nabil; Tandir, Salih; Begic, Edin

2017-01-01

Introduction: Aim of article was to present perspectives of telemedicine in the field of cardiology in Bosnia and Herzegovina. Material and methods: Article has descriptive character and present review of literature. Results: Information technology can have the application in the education of students, starting from basic medical sciences up to clinical subjects. Information technologies are used for ECG analysis, 24h ECG Holter monitoring, which detects different rhythm disorders. By developing software packages for electrocardiogram analysis, which can be divided and interpreted by mobile phones, and complete the whole of the patient in the ambulance, specialist, experienced specialists, or even consultations in various illnesses and cities. Image segmentation algorithms have significance in the quantization and diagnostics of anatomic and pathological structures, and 3D representation has an important role in education, topography and clinical anatomy, radiology, pathology, as well as in clinical cardiology itself, especially in the sphere of coronary arteries identification in the multislice computerized angiography of coronary arteries. Interactive video consultations with subspecialists from the state and the region in adult cardiology, adult interventional cardiology, cardiovascular surgery, pediatric invasive and non-invasive cardiology enable better access to heart specialists and subspecialist, accurate diagnosis, better treatment, reduction of mortality, and a significant reduction in costs. Conclusion: Telemedicine by slow steps in entering the soil of Bosnia and Herzegovina, but the potential exists. It is necessary to educate the medical staff, as well as to provide a tempting environment for software engineers. Investing in infrastructure and equipment is imperative, as well as a positive climate for the its implementation. PMID:29284918

Treatment of Hepatitis C Infections with Interferon: A Historical Perspective

DTIC Science & Technology

2010-01-01

infected AKR cells: a novel effect of interferon,” Proceedings of the National Academy of Sciences of the United States of America, vol. 71, no. 9, pp...Treatment of Hepatitis C Infections with Interferon: A Historical Perspective Robert M. Friedman and Sara Contente Department of Pathology, Uniformed...involve new anti-HCV agents that are currently under development. The antiviral activity of interferon (IFN), first described in 1957, was in a chick cell

Cyberaddictions: toward a psychosocial perspective.

PubMed

Suissa, Amnon Jacob

2014-12-01

The concept of cyberaddiction is far from being unanimously accepted by scientists (Ko, Yen, Yen, Chen, & Chen, 2012; Pezoa-Jares, Espinoza-Luna & Vasquez-Medina, 2012; Nadeau & et al. 2011; Perraton, Fusaro & Bonenfant, 2011. The same is true of addiction to videogames (Hellman, Schoenmakers, Nordstrom, & Van Holst 2013); Coulombe (2010); or to Facebook (Andreassen et al. 2012; Levard & Soulas, 2010). While certain researchers wished to see this condition included in the DSM-5, others question the operational and practical basis for the diagnostic criteria (Block, 2008). Through a review of litterature and results from research findings; the aim of this article is to propose a psychosocial perspective for the cyberaddiction phenomenon. By a psychosocial perspective, we mean the inclusion of social determinants (weak social ties, social exclusion, hyper individualism, poverty, unemployment, etc) and not only the individual characteristics associated with the disease model in the addiction field. To what extent social conditions and cyberaddiction behaviors constitute a potential pathology ? Can we include a psychosocial approach to gain a more general picture of this contemporary issue? In response to these questions, a contextualization and an attempt to define cyberaddiction will be followed by an analysis of some major issues in the development of this type of addiction. As a conclusion, a demonstration of the cycle of addiction on how people develop addictions, including cyberaddictions, will be done within a psychosocial perspective in order to seize the multifactorial aspects of this addiction. Copyright © 2014 Elsevier Ltd. All rights reserved.

Small-cell carcinoma of the urinary bladder: where do we stand?

PubMed

Ghervan, Liviu; Zaharie, Andreea; Ene, Bogdan; Elec, Florin I

2017-01-01

Small-cell carcinoma of the urinary bladder is a very rare pathology, but with a very aggressive behavior and disappointing prognosis. The literature concerning this type of cancer is scarce and physicians may encounter difficulty trying to manage it. Most articles involve the study of case series, without definite results due to the small number of patients. The present article aims at gathering the most significant articles and results in order to offer a broad perspective on the existing literature concerning this pathology.

Identifying associations between pig pathologies using a multi-dimensional machine learning methodology.

PubMed

Sanchez-Vazquez, Manuel J; Nielen, Mirjam; Edwards, Sandra A; Gunn, George J; Lewis, Fraser I

2012-08-31

Abattoir detected pathologies are of crucial importance to both pig production and food safety. Usually, more than one pathology coexist in a pig herd although it often remains unknown how these different pathologies interrelate to each other. Identification of the associations between different pathologies may facilitate an improved understanding of their underlying biological linkage, and support the veterinarians in encouraging control strategies aimed at reducing the prevalence of not just one, but two or more conditions simultaneously. Multi-dimensional machine learning methodology was used to identify associations between ten typical pathologies in 6485 batches of slaughtered finishing pigs, assisting the comprehension of their biological association. Pathologies potentially associated with septicaemia (e.g. pericarditis, peritonitis) appear interrelated, suggesting on-going bacterial challenges by pathogens such as Haemophilus parasuis and Streptococcus suis. Furthermore, hepatic scarring appears interrelated with both milk spot livers (Ascaris suum) and bacteria-related pathologies, suggesting a potential multi-pathogen nature for this pathology. The application of novel multi-dimensional machine learning methodology provided new insights into how typical pig pathologies are potentially interrelated at batch level. The methodology presented is a powerful exploratory tool to generate hypotheses, applicable to a wide range of studies in veterinary research.

Going fully digital: Perspective of a Dutch academic pathology lab

PubMed Central

Stathonikos, Nikolas; Veta, Mitko; Huisman, André; van Diest, Paul J.

2013-01-01

During the last years, whole slide imaging has become more affordable and widely accepted in pathology labs. Digital slides are increasingly being used for digital archiving of routinely produced clinical slides, remote consultation and tumor boards, and quantitative image analysis for research purposes and in education. However, the implementation of a fully digital Pathology Department requires an in depth look into the suitability of digital slides for routine clinical use (the image quality of the produced digital slides and the factors that affect it) and the required infrastructure to support such use (the storage requirements and integration with lab management and hospital information systems). Optimization of digital pathology workflow requires communication between several systems, which can be facilitated by the use of open standards for digital slide storage and scanner management. Consideration of these aspects along with appropriate validation of the use of digital slides for routine pathology can pave the way for pathology departments to go “fully digital.” In this paper, we summarize our experiences so far in the process of implementing a fully digital workflow at our Pathology Department and the steps that are needed to complete this process. PMID:23858390

Quality and patient safety in the diagnosis of breast cancer.

PubMed

Raab, Stephen S; Swain, Justin; Smith, Natasha; Grzybicki, Dana M

2013-09-01

The media, medical legal, and safety science perspectives of a laboratory medical error differ and assign variable levels of responsibility on individuals and systems. We examine how the media identifies, communicates, and interprets information related to anatomic pathology breast diagnostic errors compared to groups using a safety science Lean-based quality improvement perspective. The media approach focuses on the outcome of error from the patient perspective and some errors have catastrophic consequences. The medical safety science perspective does not ignore the importance of patient outcome, but focuses on causes including the active events and latent factors that contribute to the error. Lean improvement methods deconstruct work into individual steps consisting of tasks, communications, and flow in order to understand the affect of system design on current state levels of quality. In the Lean model, system redesign to reduce errors depends on front-line staff knowledge and engagement to change the components of active work to develop best practices. In addition, Lean improvement methods require organizational and environmental alignment with the front-line change in order to improve the latent conditions affecting components such as regulation, education, and safety culture. Although we examine instances of laboratory error for a specific test in surgical pathology, the same model of change applies to all areas of the laboratory. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Residency choices by graduating medical students: why not pathology?

PubMed

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

2011-06-01

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

Communication rights: Fundamental human rights for all.

PubMed

McLeod, Sharynne

2018-02-01

The right to communicate includes the right to "freedom of opinion and expression" and rights and freedoms "without distinction of … language". The 70th anniversary of the Universal Declaration of Human Rights is a time to celebrate and reflect on communication as a human right, particularly with respect to Article 19 and its relationship to national and international conventions, declarations, policies and practices. This review profiles articles from the special issue of International Journal of Speech-Language Pathology (volume 20, issue 1) addressing communication rights from four perspectives: (1) communication rights of all people; (2) communication rights of people with communication disabilities; (3) communication rights of children and (4) communication rights relating to language. Divergent perspectives from across the globe are considered. First-hand accounts of people whose right to communicate is compromised/upheld are included and perspectives are provided from people with expertise and advocacy roles in speech-language pathology, audiology, linguistics, education, media, literature and law, including members of the International Communication Project. Three steps are outlined to support communication rights: acknowledge people - adjust the communication style - take time to listen. Future advocacy for communication rights could be informed by replicating processes used to generate the Yogyakarta Principles.

Comparing alternate learning pathways within a problem-based learning speech-language pathology curriculum.

PubMed

Erickson, Shane; Serry, Tanya Anne

2016-02-01

This qualitative study investigated the learning process for speech-language pathology (SLP) students engaging in a problem-based learning (PBL) curriculum and compared the perspectives of students from two pathways. Sixteen final-year SLP students participated in one of four focus groups. Half the participants entered the course directly via an undergraduate pathway and the other half entered via a graduate entry pathway. Each focus group comprised two students from each pathway. Data were generated via a semi-structured interview and analysed thematically. Regardless of participants' pathway, many similar themes about factors that influenced their expectations prior to PBL commencing as well as their actual PBL experiences were raised. Participants believed that PBL was a productive way to learn and to develop clinical competencies. Many were critical of variations in PBL facilitation styles and were sensitive to changes in facilitators. The majority of participants viewed experiential opportunities to engage in PBL prior to commencement of semester as advantageous. Combining students with different backgrounds has many advantages to the PBL learning process. Regardless of prior experiences, all students must be sufficiently prepared. Furthermore, the facilitator has a crucial role with the potential to optimise or detract from the learning experience.

Attacking the Multi-tiered Proteolytic Pathology of COPD: New Insights from Basic and Translational Studies

PubMed Central

Djekic, Uros V; Gaggar, Amit; Weathington, Nathaniel M

2015-01-01

Protease activity in inflammation is complex. Proteases released by cells in response to infection, cytokines, or environmental triggers like cigarette smoking cause breakdown of the extracellular matrix (ECM). In chronic inflammatory diseases like chronic obstructive pulmonary disease (COPD), current findings indicate that pathology and morbidity are driven by dysregulation of protease activity, either through hyperactivity of proteases or deficiency or dysfunction their antiprotease regulators. Animal studies demonstrate the accuracy of this hypothesis through genetic and pharmacologic tools. New work shows that ECM destruction generates peptide fragments active on leukocytes via neutrophil or macrophage chemotaxis towards collagen and elastin derived peptides respectively. Such fragments now have been isolated and characterized in vivo in each case. Collectively, this describes a biochemical circuit in which protease activity leads to activation of local immunocytes, which in turn release cytokines and more proteases, leading to further leukocyte infiltration and cyclical disease progression that is chronic. This circuit concept is well known, and is intrinsic to the protease-antiprotease hypothesis; recently analytic techniques have become sensitive enough to establish fundamental mechanisms of this hypothesis, and basic and clinical data now implicate protease activity and peptide signaling as pathologically significant pharmacologic targets. This review discusses targeting protease activity for chronic inflammatory disease with special attention to COPD, covering important basic and clinical findings in the field; novel therapeutic strategies in animal or human studies; and a perspective on the successes and failures of agents with a focus on clinical potential in human disease. PMID:19026684

[Diagnostic categories and gender: two examples in contemporary Spanish medicine, chlorosis and neurasthenia (1877-1936)].

PubMed

Bernabeu-Mestre, Josep; Santos, Ana Paula Cid; Pellicer, Josep Xavier Esplugues; Galiana-Sánchez, María Eugenia

2008-01-01

Chlorosis and Neurasthenia are two classical examples of pathological dissociations and the difficulties involved in approaching their diagnosis using scientific-naturalistic criteria. In the realm of those difficulties, the study examines the androcentric viewpoint and the ideological perspective of Contemporary Spanish Medicine when addressing the feminine nature and women's pathologies. Moreover, based on the similarities with present-day pain and fatigue syndromes, the study underlines the need to review the clinical approach to these illnesses by attempting to overcome the existing biomedical limitations.

Small-cell carcinoma of the urinary bladder: where do we stand?

PubMed Central

GHERVAN, LIVIU; ZAHARIE, ANDREEA; ENE, BOGDAN; ELEC, FLORIN I.

2017-01-01

Small-cell carcinoma of the urinary bladder is a very rare pathology, but with a very aggressive behavior and disappointing prognosis. The literature concerning this type of cancer is scarce and physicians may encounter difficulty trying to manage it. Most articles involve the study of case series, without definite results due to the small number of patients. The present article aims at gathering the most significant articles and results in order to offer a broad perspective on the existing literature concerning this pathology. PMID:28246491

The stress response and immune system share, borrow, and reconfigure their physiological network elements: Evidence from the insects.

PubMed

Adamo, Shelley A

2017-02-01

The classic biomedical view is that stress hormone effects on the immune system are largely pathological, especially if the stress is chronic. However, more recent interpretations have focused on the potential adaptive function of these effects. This paper examines stress response-immune system interactions from a physiological network perspective, using insects because of their simpler physiology. For example, stress hormones can reduce disease resistance, yet activating an immune response results in the release of stress hormones in both vertebrates and invertebrates. From a network perspective, this phenomenon is consistent with the 'sharing' of the energy-releasing ability of stress hormones by both the stress response and the immune system. Stress-induced immunosuppression is consistent with the stress response 'borrowing' molecular components from the immune system to increase the capacity of stress-relevant physiological processes (i.e. a trade off). The insect stress hormones octopamine and adipokinetic hormone can also 'reconfigure' the immune system to help compensate for the loss of some of the immune system's molecular resources (e.g. apolipophorin III). This view helps explain seemingly maladaptive interactions between the stress response and immune system. The adaptiveness of stress hormone effects on individual immune components may be apparent only from the perspective of the whole organism. These broad principles will apply to both vertebrates and invertebrates. Copyright © 2016 Elsevier Inc. All rights reserved.

Applications of mass spectrometry for quantitative protein analysis in formalin-fixed paraffin-embedded tissues

PubMed Central

Steiner, Carine; Ducret, Axel; Tille, Jean-Christophe; Thomas, Marlene; McKee, Thomas A; Rubbia-Brandt, Laura A; Scherl, Alexander; Lescuyer, Pierre; Cutler, Paul

2014-01-01

Proteomic analysis of tissues has advanced in recent years as instruments and methodologies have evolved. The ability to retrieve peptides from formalin-fixed paraffin-embedded tissues followed by shotgun or targeted proteomic analysis is offering new opportunities in biomedical research. In particular, access to large collections of clinically annotated samples should enable the detailed analysis of pathologically relevant tissues in a manner previously considered unfeasible. In this paper, we review the current status of proteomic analysis of formalin-fixed paraffin-embedded tissues with a particular focus on targeted approaches and the potential for this technique to be used in clinical research and clinical diagnosis. We also discuss the limitations and perspectives of the technique, particularly with regard to application in clinical diagnosis and drug discovery. PMID:24339433

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

Chronic traumatic encephalopathy: historical origins and current perspective.

PubMed

Montenigro, Philip H; Corp, Daniel T; Stein, Thor D; Cantu, Robert C; Stern, Robert A

2015-01-01

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that is most often identified in postmortem autopsies of individuals exposed to repetitive head impacts, such as boxers and football players. The neuropathology of CTE is characterized by the accumulation of hyperphosphorylated tau protein in a pattern that is unique from that of other neurodegenerative diseases, including Alzheimer's disease. The clinical features of CTE are often progressive, leading to dramatic changes in mood, behavior, and cognition, frequently resulting in debilitating dementia. In some cases, motor features, including parkinsonism, can also be present. In this review, the historical origins of CTE are revealed and an overview of the current state of knowledge of CTE is provided, including the neuropathology, clinical features, proposed clinical and pathological diagnostic criteria, potential in vivo biomarkers, known risk factors, and treatment options.

Decreased activity and accelerated apoptosis of neutrophils in the presence of natural polyphenols

PubMed Central

Perečko, Tomáš; Harmatha, Juraj; Nosáľ, Radomír; Drábiková, Katarína

2012-01-01

Prolonged or excessive formation and liberation of cytotoxic substances from neutrophils intensifies inflammation and the risk of tissue damage. From this perspective, administration of substances which are able to reduce activity of neutrophils and to enhance apoptosis of these cells may improve the therapy of pathological states connected with persistent inflammation. In this short review, neutrophil oxidative burst and apoptosis are presented as potential targets for pharmacological intervention. Effects of natural polyphenols (resveratrol, pterostilbene, pinosylvin, piceatannol, curcumin, N-feruloylserotonin) are summarised, considering the ability of these compounds to affect inflammation and particularly neutrophil activity. The intended neutrophil inhibition is introduced as a part of a new strategy for pharmacological modulation of chronic inflammatory processes, focused on supporting innate anti-inflammatory mechanisms and enhancing resolution of inflammation. PMID:23118588

The science of animal behavior and welfare: challenges, opportunities and global perspective

USDA-ARS?s Scientific Manuscript database

Animal welfare science is a relatively new scientific discipline. Originally heavily focused on animal behavior, it has emerged into a truly multi- and inter-disciplinary science, encompassing such sciences as behavior, physiology, pathology, immunology, endocrinology and neuroscience, and influence...

Placenta-derived exosomes: potential biomarkers of preeclampsia.

PubMed

Pillay, Preenan; Moodley, Kogi; Moodley, Jagidesa; Mackraj, Irene

2017-01-01

Preeclampsia remains a leading cause of maternal and fetal mortality, due to ineffective treatment and diagnostic strategies, compounded by the lack of clarity on the etiology of the disorder. Although several clinical and biological markers of preeclampsia have been evaluated, they have proven to be ineffective in providing a definitive diagnosis during the various stages of the disorder. Exosomes have emerged as ideal biomarkers of pathological states, such as cancer, and have more recently gained interest in pregnancy-related complications, due to their role in cellular communication in normal and complicated pregnancies. This occurs as a result of the specific placenta-derived exosomal molecular cargo, which may be involved in normal pregnancy-associated immunological events, such as the maintenance of maternal-fetal tolerance. This review provides perspectives on placenta-derived exosomes as possible biomarkers for the diagnosis/prognosis of preeclampsia. Using keywords, online databases were searched to identify relevant publications to review the potential use of placenta-derived exosomes as biomarkers of preeclampsia.

The impact of rehabilitative interventions on quality of life: a qualitative evidence synthesis of personal experiences of individuals with amyotrophic lateral sclerosis.

PubMed

Soofi, Ammarah Y; Bello-Haas, Vanina Dal; Kho, Michelle E; Letts, Lori

2018-04-01

The nature of amyotrophic lateral sclerosis (ALS) is progressive and degenerative, thus influencing individuals physically, emotionally, and socially. A broad review of qualitative studies that describe the personal experiences of people with ALS with physiotherapy, occupational therapy and speech and language pathology interventions, and how those affect QoL is warranted. This study synthesizes qualitative research regarding the potential that rehabilitation interventions have to maintain and/or improve QoL from the perspective of people with ALS. The SPIDER search strategy was applied and five articles met inclusion criteria addressing the perceived impact of rehabilitation on QoL for individuals with ALS. Four themes emerged: the concept of control; adapting interventions to disease stage; struggles with interventions; and barriers between healthcare providers and patients. Rehabilitation interventions were perceived to have potential to support QoL by people with ALS. Advantages and limitations of rehabilitation services within this population were identified.

[Gambling and internet addiction: review and research agenda].

PubMed

Wölfling, K; Bühler, M; Leménager, T; Mörsen, C; Mann, K

2009-09-01

Behavioral addictions, especially pathological gambling and internet addiction, have become a growing concern in research and health policy. Similarities between behavioral addictions and substance dependency are currently being discussed in the scientific community. Unfortunately the number of scientific studies on pathological gambling and internet addiction is still very low. The estimated prevalence of pathological gambling among the German population is 0.2-0.5%. These numbers are comparable to prevalence rates reported for illegal drug dependency. About 1.5 million people, i.e. 3% of the German population, are believed to be at risk of internet addiction. Therefore, it is important to investigate in more detail the clinical and neuroscientific basis of pathological gambling and internet addiction. In this review we summarize the current status of research regarding pathological gambling and internet addiction and outline possible future research perspectives in the field of neuroimaging and genetics. The aim is to develop a multifactorial and explanatory model which helps to improve the quality of existing therapeutic approaches and prevention strategies. At present, parts of the research are funded by the federal states. The authors of this article, supported by scientific associations, have established a research platform called 'pathological gambling' in which research methods and strategies will be discussed which facilitate the implementation of different studies on pathological gambling.

Effects of time perspective and self-control on procrastination and Internet addiction.

PubMed

Kim, Jinha; Hong, Hyeongi; Lee, Jungeun; Hyun, Myoung-Ho

2017-06-01

Background and aims College students experiencing stress show tendencies to procrastinate and can develop Internet addiction problems. This study investigated the structural relationship between time perspective and self-control on procrastination and Internet addiction. Methods College students (N = 377) residing in South Korea completed the following questionnaires: the Pathological Internet Use Behavior Symptom Scale for Adults, the Zimbardo Time Perspective Inventory, the Self-Control Rating Scale, and the Aitken Procrastination Inventory. The sample variance-covariance matrix was analyzed using AMOS 20.0. Results Time perspective had a direct effect on self-control and an indirect effect on Internet use and procrastination. In addition, self-control affected procrastination and Internet use. Conclusions Individuals with a present-oriented time perspective tend to evidence poorer self-control, increasing the likelihood of procrastination and Internet addiction. Individuals with a future-oriented time perspective, on the other hand, tend to have stronger self-control, decreasing their risk of procrastination and Internet addiction.

Effects of time perspective and self-control on procrastination and Internet addiction

PubMed Central

Kim, Jinha; Hong, Hyeongi; Lee, Jungeun; Hyun, Myoung-Ho

2017-01-01

Background and aims College students experiencing stress show tendencies to procrastinate and can develop Internet addiction problems. This study investigated the structural relationship between time perspective and self-control on procrastination and Internet addiction. Methods College students (N = 377) residing in South Korea completed the following questionnaires: the Pathological Internet Use Behavior Symptom Scale for Adults, the Zimbardo Time Perspective Inventory, the Self-Control Rating Scale, and the Aitken Procrastination Inventory. The sample variance–covariance matrix was analyzed using AMOS 20.0. Results Time perspective had a direct effect on self-control and an indirect effect on Internet use and procrastination. In addition, self-control affected procrastination and Internet use. Conclusions Individuals with a present-oriented time perspective tend to evidence poorer self-control, increasing the likelihood of procrastination and Internet addiction. Individuals with a future-oriented time perspective, on the other hand, tend to have stronger self-control, decreasing their risk of procrastination and Internet addiction. PMID:28494615

Satisfaction with ophthalmology residency training from the perspective of recent graduates: a cross-sectional study

PubMed Central

2013-01-01

Background Few studies have evaluated satisfaction with medical residency programs from the perspective of residents or recent graduates. Knowledge of current conditions of teaching might help to identify deficiencies and to provide adequate training. So, the aim of this study was to assess the satisfaction with residency training and to identify deficiencies in this training from the perspective of recent graduates in ophthalmology residency. Methods For this purpose, we developed a questionnaire and gaved it to recent graduates in ophthalmology residency in São Paulo, Brazil, from January to December 2010. The questions contained demographic information (age, sex and time of practice in ophthalmology), a Likert scale to evaluate the level of satisfaction with medical residency concerning clinical knowledge, surgical skills and doctor-patient relationship and questions about deficiency in clinical and surgical areas. Results The areas in which recent residency graduates were very or extremely satisfied were: acquisition of clinical knowledge (89.1%), acquisition of surgical skills (93.4%) and the development of doctor-patient relationship (74.9%). Specific areas of clinical knowledge in which they perceived more deficiency were orbit (48.3%) and ophthalmic pathology (47.9%), and in surgical skills were refractive surgery (65.9%) and orbit (59.2%) Conclusions The assessment of the satisfaction with residency training in ophthalmology from the perspective of recent graduates showed high level of satisfaction and identified specific deficiencies in ophthalmic pathology, refractive surgery and orbit. PMID:23706136

Practical Applications of Digital Pathology.

PubMed

Saeed-Vafa, Daryoush; Magliocco, Anthony M

2015-04-01

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

Gambling

PubMed Central

Potenza, Marc N; Fiellin, David A; Heninger, George R; Rounsaville, Bruce J; Mazure, Carolyn M

2002-01-01

Over the past several decades, and particularly during the last 10 to 15 years, there has been a rapid increase in the accessibility of legalized gambling in the United States and other parts of the world. Few studies have systematically explored the relationships between patterns of gambling and health status. Existing data support the notion that some gambling behaviors, particularly problem and pathological gambling, are associated with nongambling health problems. The purpose of this article is to provide a perspective on the relationship between gambling behaviors and substance use disorders, review the data regarding health associations and screening and treatment options for problem and pathological gambling, and suggest a role for generalist physicians in assessing problem and pathological gambling. A rationale for conceptualization of pathological gambling as an addictive disorder and a model proposing stress as a possible mediating factor in the relationship between gambling and health status are presented. More research is needed to investigate directly the biological and health correlates associated with specific types of gambling behaviors and to define the role for generalist physicians in the prevention and treatment of problem and pathological gambling. PMID:12220370

Dissociation in Children and Adolescents: A Developmental Perspective.

ERIC Educational Resources Information Center

Putnam, Frank W.

From amnesia to auditory hallucinations, the symptoms of pathological dissociation are among the most devastating effects of childhood maltreatment. Ways in which therapists can provide a comprehensive developmental approach to understanding, diagnosing, and treating this challenging clinical population are presented in this text. After reviewing…

Childhood-Onset Schizophrenia: Insights from Neuroimaging Studies

ERIC Educational Resources Information Center

Gogtay, Nitin; Rapoport, Judith L.

2008-01-01

The use of longitudinal neuroimaging to study the developmental perspectives of brain pathology in children with childhood-onset schizophrenia (COS) is described. Structural neuroimaging is capable of providing evidence of neurobiological specificity of COS to distinguish it from other brain abnormalities seen in neuropsychiatric illnesses like…

Parkinson’s disease dementia: a neural networks perspective

PubMed Central

Jahanshahi, Marjan; Foltynie, Thomas

2015-01-01

In the long-term, with progression of the illness, Parkinson’s disease dementia affects up to 90% of patients with Parkinson’s disease. With increasing life expectancy in western countries, Parkinson’s disease dementia is set to become even more prevalent in the future. However, current treatments only give modest symptomatic benefit at best. New treatments are slow in development because unlike the pathological processes underlying the motor deficits of Parkinson’s disease, the neural mechanisms underlying the dementing process and its associated cognitive deficits are still poorly understood. Recent insights from neuroscience research have begun to unravel the heterogeneous involvement of several distinct neural networks underlying the cognitive deficits in Parkinson’s disease dementia, and their modulation by both dopaminergic and non-dopaminergic transmitter systems in the brain. In this review we collate emerging evidence regarding these distinct brain networks to give a novel perspective on the pathological mechanisms underlying Parkinson’s disease dementia, and discuss how this may offer new therapeutic opportunities. PMID:25888551

Parkinson's disease dementia: a neural networks perspective.

PubMed

Gratwicke, James; Jahanshahi, Marjan; Foltynie, Thomas

2015-06-01

In the long-term, with progression of the illness, Parkinson's disease dementia affects up to 90% of patients with Parkinson's disease. With increasing life expectancy in western countries, Parkinson's disease dementia is set to become even more prevalent in the future. However, current treatments only give modest symptomatic benefit at best. New treatments are slow in development because unlike the pathological processes underlying the motor deficits of Parkinson's disease, the neural mechanisms underlying the dementing process and its associated cognitive deficits are still poorly understood. Recent insights from neuroscience research have begun to unravel the heterogeneous involvement of several distinct neural networks underlying the cognitive deficits in Parkinson's disease dementia, and their modulation by both dopaminergic and non-dopaminergic transmitter systems in the brain. In this review we collate emerging evidence regarding these distinct brain networks to give a novel perspective on the pathological mechanisms underlying Parkinson's disease dementia, and discuss how this may offer new therapeutic opportunities. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

A methodological approach to studying resilience mechanisms: demonstration of utility in age and Alzheimer's disease-related brain pathology.

PubMed

Wolf, Dominik; Fischer, Florian Udo; Fellgiebel, Andreas

2018-05-01

The present work aims at providing a methodological approach for the investigation of resilience factors and mechanisms in normal aging, Alzheimer's disease (AD) and other neurodegenerative disorders. By expanding and re-conceptualizing traditional regression approaches, we propose an approach that not only aims at identifying potential resilience factors but also allows for a differentiation between general and dynamic resilience factors in terms of their association with pathology. Dynamic resilience factors are characterized by an increasing relevance with increasing levels of pathology, while the relevance of general resilience factors is independent of the amount of pathology. Utility of the approach is demonstrated in age and AD-related brain pathology by investigating widely accepted resilience factors, including education and brain volume. Moreover, the approach is used to test hippocampal volume as potential resilience factor. Education and brain volume could be identified as general resilience factors against age and AD-related pathology. Beyond that, analyses highlighted that hippocampal volume may not only be disease target but also serve as a potential resilience factor in age and AD-related pathology, particularly at higher levels of tau-pathology (i.e. dynamic resilience factor). Given its unspecific and superordinate nature the approach is suitable for the investigation of a wide range of potential resilience factors in normal aging, AD and other neurodegenerative disorders. Consequently, it may find a wide application and thereby promote the comparability between studies.

Pathological Buying Online as a Specific Form of Internet Addiction: A Model-Based Experimental Investigation

PubMed Central

Trotzke, Patrick; Starcke, Katrin; Müller, Astrid; Brand, Matthias

2015-01-01

The study aimed to investigate different factors of vulnerability for pathological buying in the online context and to determine whether online pathological buying has parallels to a specific Internet addiction. According to a model of specific Internet addiction by Brand and colleagues, potential vulnerability factors may consist of a predisposing excitability from shopping and as mediating variable, specific Internet use expectancies. Additionally, in line with models on addiction behavior, cue-induced craving should also constitute an important factor for online pathological buying. The theoretical model was tested in this study by investigating 240 female participants with a cue-reactivity paradigm, which was composed of online shopping pictures, to assess excitability from shopping. Craving (before and after the cue-reactivity paradigm) and online shopping expectancies were measured. The tendency for pathological buying and online pathological buying were screened with the Compulsive Buying Scale (CBS) and the Short Internet Addiction Test modified for shopping (s-IATshopping). The results demonstrated that the relationship between individual’s excitability from shopping and online pathological buying tendency was partially mediated by specific Internet use expectancies for online shopping (model’s R² = .742, p < .001). Furthermore, craving and online pathological buying tendencies were correlated (r = .556, p < .001), and an increase in craving after the cue presentation was observed solely in individuals scoring high for online pathological buying (t(28) = 2.98, p < .01, d = 0.44). Both screening instruments were correlated (r = .517, p < .001), and diagnostic concordances as well as divergences were indicated by applying the proposed cut-off criteria. In line with the model for specific Internet addiction, the study identified potential vulnerability factors for online pathological buying and suggests potential parallels. The presence of craving in individuals with a propensity for online pathological buying emphasizes that this behavior merits potential consideration within the non-substance/behavioral addictions. PMID:26465593

Pathological Buying Online as a Specific Form of Internet Addiction: A Model-Based Experimental Investigation.

PubMed

Trotzke, Patrick; Starcke, Katrin; Müller, Astrid; Brand, Matthias

2015-01-01

The study aimed to investigate different factors of vulnerability for pathological buying in the online context and to determine whether online pathological buying has parallels to a specific Internet addiction. According to a model of specific Internet addiction by Brand and colleagues, potential vulnerability factors may consist of a predisposing excitability from shopping and as mediating variable, specific Internet use expectancies. Additionally, in line with models on addiction behavior, cue-induced craving should also constitute an important factor for online pathological buying. The theoretical model was tested in this study by investigating 240 female participants with a cue-reactivity paradigm, which was composed of online shopping pictures, to assess excitability from shopping. Craving (before and after the cue-reactivity paradigm) and online shopping expectancies were measured. The tendency for pathological buying and online pathological buying were screened with the Compulsive Buying Scale (CBS) and the Short Internet Addiction Test modified for shopping (s-IATshopping). The results demonstrated that the relationship between individual's excitability from shopping and online pathological buying tendency was partially mediated by specific Internet use expectancies for online shopping (model's R² = .742, p < .001). Furthermore, craving and online pathological buying tendencies were correlated (r = .556, p < .001), and an increase in craving after the cue presentation was observed solely in individuals scoring high for online pathological buying (t(28) = 2.98, p < .01, d = 0.44). Both screening instruments were correlated (r = .517, p < .001), and diagnostic concordances as well as divergences were indicated by applying the proposed cut-off criteria. In line with the model for specific Internet addiction, the study identified potential vulnerability factors for online pathological buying and suggests potential parallels. The presence of craving in individuals with a propensity for online pathological buying emphasizes that this behavior merits potential consideration within the non-substance/behavioral addictions.

Age-related differences in associative memory: Empirical evidence and theoretical perspectives.

PubMed

Naveh-Benjamin, Moshe; Mayr, Ulrich

2018-02-01

Systematic research and anecdotal evidence both indicate declines in episodic memory in older adults in good health without dementia-related disorders. Several hypotheses have been proposed to explain these age-related changes in episodic memory, some of which attribute such declines to a deterioration in associative memory. The current special issue of Psychology and Aging on Age-Related Differences in Associative Memory includes 16 articles by top researchers in the area of memory and aging. Their contributions provide a wealth of empirical work that addresses different aspects of aging and associative memory, including different mediators and predictors of age-related declines in binding and associative memory, cognitive, noncognitive, genetic, and neuro-related ones. The contributions also address the processing phases where these declines manifest themselves and look at ways to ameliorate these age-related declines. Furthermore, the contributions in this issue draw on different theoretical perspectives to explain age-related changes in associative memory and provide a wealth of varying methodologies to assess older and younger adults' performance. Finally, although most of the studies focus on normative/healthy aging, some of them contain insights that are potentially applicable to disorders and pathologies. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Threat-detection in child development: an evolutionary perspective.

PubMed

Boyer, Pascal; Bergstrom, Brian

2011-03-01

Evidence for developmental aspects of fear-targets and anxiety suggests a complex but stable pattern whereby specific kinds of fears emerge at different periods of development. This developmental schedule seems appropriate to dangers encountered repeatedly during human evolution. Also consistent with evolutionary perspective, the threat-detection systems are domain-specific, comprising different kinds of cues to do with predation, intraspecific violence, contamination-contagion and status loss. Proper evolutionary models may also be relevant to outstanding issues in the domain, notably the connections between typical development and pathology. Copyright © 2010 Elsevier Ltd. All rights reserved.

The aging-disease false dichotomy: understanding senescence as pathology

PubMed Central

Gems, David

2015-01-01

From a biological perspective aging (senescence) appears to be a form of complex disease syndrome, though this is not the traditional view. This essay aims to foster a realistic understanding of aging by scrutinizing ideas old and new. The conceptual division between aging-related diseases and an underlying, non-pathological aging process underpins various erroneous traditional ideas about aging. Among biogerontologists, another likely error involves the aspiration to treat the entire aging process, which recent advances suggest is somewhat utopian. It also risks neglecting a more modest but realizable goal: to develop preventative treatments that partially protect against aging. PMID:26136770

Diagnostic histochemistry and clinical-pathological testings as molecular pathways to pathogenesis and treatment of the ageing neuromuscular system: a personal view.

PubMed

Engel, W King

2015-04-01

Ageing of the neuromuscular system in elderhood ingravescently contributes to slowness, weakness, falling and death, often accompanied by numbness and pain. This article is to put in perspective examples from a half-century of personal and team neuromuscular histochemical-pathological and clinical-pathological research, including a number of lucky and instructive accomplishments identifying new treatments and new diseases. A major focus currently is on some important, still enigmatic, aspects of the ageing neuromuscular system. It is also includes some of the newest references of others on various closely-related aspects of this ageing system. The article may help guide others in their molecular-based endeavors to identify paths leading to discovering new treatments and new pathogenic aspects. These are certainly needed - our ageing and unsteady constituents are steadily increasing. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. Copyright © 2014. Published by Elsevier B.V.

Prostatic cancers: understanding their molecular pathology and the 2016 WHO classification

PubMed Central

Inamura, Kentaro

2018-01-01

Accumulating evidence suggests that prostatic cancers represent a group of histologically and molecularly heterogeneous diseases with variable clinical courses. In accordance with the increased knowledge of their clinicopathologies and genetics, the World Health Organization (WHO) classification of prostatic cancers has been revised. Additionally, recent data on their comprehensive molecular characterization have increased our understanding of the genomic basis of prostatic cancers and enabled us to classify them into subtypes with distinct molecular pathologies and clinical features. Our increased understanding of the molecular pathologies of prostatic cancers has permitted their evolution from a poorly understood, heterogeneous group of diseases with variable clinical courses to characteristic molecular subtypes that allow the implementation of personalized therapies and better patient management. This review provides perspectives on the new 2016 WHO classification of prostatic cancers as well as recent knowledge of their molecular pathologies. The WHO classification of prostatic cancers will require additional revisions to allow for reliable and clinically meaningful cancer diagnoses as a better understanding of their molecular characteristics is obtained. PMID:29581876

Discovery of pathologies by orthodontists on lateral cephalograms.

PubMed

Moffitt, Allen Hall

2011-01-01

To determine the frequency of significant pathologies on lateral cephalograms discovered by orthodontists during their careers. A five-statement survey was sent to the 417 active and affiliate members of the Edward H. Angle Society of Orthodontists. The survey asked orthodontists to identify any significant radiographic pathology that they had discovered on lateral cephalograms during their careers to date. The data were analyzed statistically. Of the 417 surveys, 201 were returned for a 48% response rate. Ninety-nine respondents or 49.3% of the sample had discovered at least one significant pathology. Of the 1.3 million patients observed by the orthodontists in the sample, 268 patients (0.02%) with significant pathologies had been identified. Younger orthodontists had a statistically greater potential to discover pathologies than older orthodontists. The general types of pathologies discovered were musculoskeletal (38%), glandular (28%), and dental groups (12%). About 50% of orthodontists will likely discover a significant, potentially life-affecting pathology on a lateral cephalogram.

Automated Decision-Support Technologies for Prehospital Care of Trauma Casualties

DTIC Science & Technology

2010-04-01

insensitive to prehospital major traumatic pathology . Second, there are numerous potential sources of decision-support failure, and it is not possible...been speculated to be insensitive to prehospital major traumatic pathology . Second, there are numerous potential sources of decision-support failure...the soldiers, and the diagnostic value of prehospital vital signs for major traumatic pathologies has often been questioned [4-8]. Indeed, our

Simulated learning environments in speech-language pathology: an Australian response.

PubMed

MacBean, Naomi; Theodoros, Deborah; Davidson, Bronwyn; Hill, Anne E

2013-06-01

The rising demand for health professionals to service the Australian population is placing pressure on traditional approaches to clinical education in the allied health professions. Existing research suggests that simulated learning environments (SLEs) have the potential to increase student placement capacity while providing quality learning experiences with comparable or superior outcomes to traditional methods. This project investigated the current use of SLEs in Australian speech-language pathology curricula, and the potential future applications of SLEs to the clinical education curricula through an extensive consultative process with stakeholders (all 10 Australian universities offering speech-language pathology programs in 2010, Speech Pathology Australia, members of the speech-language pathology profession, and current student body). Current use of SLEs in speech-language pathology education was found to be limited, with additional resources required to further develop SLEs and maintain their use within the curriculum. Perceived benefits included: students' increased clinical skills prior to workforce placement, additional exposure to specialized areas of speech-language pathology practice, inter-professional learning, and richer observational experiences for novice students. Stakeholders perceived SLEs to have considerable potential for clinical learning. A nationally endorsed recommendation for SLE development and curricula integration was prepared.

Sole Dependence on Urine Testing Strips and the Ability to Identify Clinically Significant Disease: Challenging the Current Paradigm for Heme Detection in General Clinical Situations.

PubMed

Rothschild, Bruce

2016-05-01

The ability of health care professionals to provide patient care is potentially compromised when predicated on untested, although longstanding, perspectives. One such example is urinalysis testing, which has been currently simplified to use only urine testing strips for detection of microscopic hematuria. To determine whether urine testing strips are sufficient for identification of clinically significant findings in urinalysis. To determine the presence of microscopic hematuria, I examined a collection of urine specimens that had tested heme negative during the 3-month study period. Of the 342 patients from whom urine specimens were examined during this interval, 50 had microscopic hematuria, despite having tested negative for heme via urine testing strip. Also, 30% were not receiving any medication known to produce microscopic hematuria, and 18% had clinically significant pathology. Diagnosis of significant clinical pathologic manifestations would have been compromised had microscopic examination not been performed on the urine specimens from the cohort individuals. Examination of the novel approach of including microscopic examination of specimens in a specific clinical situation challenges the dominant paradigm of reliance on assaying using urine testing strips only, revealing that the current method is not only unreliable for determining microscopic hematuria but also is less than optimal in general clinical practice. The findings of this study provide evidence of the importance of microscopic evaluation as a routine component of urinalysis. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pornography addiction - a supranormal stimulus considered in the context of neuroplasticity.

PubMed

Hilton, Donald L

2013-01-01

Addiction has been a divisive term when applied to various compulsive sexual behaviors (CSBs), including obsessive use of pornography. Despite a growing acceptance of the existence of natural or process addictions based on an increased understanding of the function of the mesolimbic dopaminergic reward systems, there has been a reticence to label CSBs as potentially addictive. While pathological gambling (PG) and obesity have received greater attention in functional and behavioral studies, evidence increasingly supports the description of CSBs as an addiction. This evidence is multifaceted and is based on an evolving understanding of the role of the neuronal receptor in addiction-related neuroplasticity, supported by the historical behavioral perspective. This addictive effect may be amplified by the accelerated novelty and the 'supranormal stimulus' (a phrase coined by Nikolaas Tinbergen) factor afforded by Internet pornography.

Allostatic load: single parents, stress-related health issues, and social care.

PubMed

Johner, Randy L

2007-05-01

This article explores the possible relationships between allostatic load (AL) and stress-related health issues in the low-income single-parent population, using both a population health perspective (PHP) and a biological framework. A PHP identifies associations among such factors as gender, income, employment, and social support and their potential effect on health outcomes. A PHP also recognizes physiological and pathological manifestations of the body such as stress (mental or somatic) and individual biological parameters (for example, glucose levels) as health determinants. AL uses an aggregate score of individual biological parameters as a health measure that is exacerbated through repetitive movement of physiologic systems under stress. The social work profession should incorporate knowledge of both PHP and AL into its theory and practice domains for effective care of vulnerable populations such as single-parent families.

Platelet proteomics: from discovery to diagnosis.

PubMed

Looße, Christina; Swieringa, Frauke; Heemskerk, Johan W M; Sickmann, Albert; Lorenz, Christin

2018-05-22

Platelets are the smallest cells within the circulating blood with key roles in physiological haemostasis and pathological thrombosis regulated by the onset of activating/inhibiting processes via receptor responses and signalling cascades. Areas covered: Proteomics as well as genomic approaches have been fundamental in identifying and quantifying potential targets for future diagnostic strategies in the prevention of bleeding and thrombosis, and uncovering the complexity of platelet functions in health and disease. In this article, we provide a critical overview on current functional tests used in diagnostics and the future perspectives for platelet proteomics in clinical applications. Expert commentary: Proteomics represents a valuable tool for the identification of patients with diverse platelet associated defects. In-depth validation of identified biomarkers, e.g. receptors, signalling proteins, post-translational modifications, in large cohorts is decisive for translation into routine clinical diagnostics.

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.

Pornography addiction – a supranormal stimulus considered in the context of neuroplasticity

PubMed Central

Hilton, Donald L.

2013-01-01

Addiction has been a divisive term when applied to various compulsive sexual behaviors (CSBs), including obsessive use of pornography. Despite a growing acceptance of the existence of natural or process addictions based on an increased understanding of the function of the mesolimbic dopaminergic reward systems, there has been a reticence to label CSBs as potentially addictive. While pathological gambling (PG) and obesity have received greater attention in functional and behavioral studies, evidence increasingly supports the description of CSBs as an addiction. This evidence is multifaceted and is based on an evolving understanding of the role of the neuronal receptor in addiction-related neuroplasticity, supported by the historical behavioral perspective. This addictive effect may be amplified by the accelerated novelty and the ‘supranormal stimulus’ (a phrase coined by Nikolaas Tinbergen) factor afforded by Internet pornography. PMID:24693354

Self-and Peer Perspectives on Pathological Personality Traits and Interpersonal Problems

ERIC Educational Resources Information Center

Clifton, Allan; Turkheimer, Eric; Oltmanns, Thomas F.

2005-01-01

This study compares the relationship between personality disorders and interpersonal problems as obtained by self-report and peer-report measures. Participants (N=393) were administered self-and peer-report versions of the Peer Inventory for Personality Disorder and the Inventory of Interpersonal Problems-64. Canonical analyses demonstrated…

Industry-contract research organization pathology interactions: a perspective of contract research organizations in producing the best quality pathology report.

PubMed

Gosselin, Sylvie J; Palate, Bernard; Parker, George A; Engelhardt, Jeffery A; Hardisty, Jerry F; McDorman, Kevin S; Tellier, Pierre A; Silverman, Lee R

2011-02-01

This article provides observations on the features of sponsor-contract research organization communication that will achieve the best quality pathology report based on our collective experience. Information on the test article and any anticipated findings should be provided, and initial slide examination should be done with knowledge of treatment group (but may be followed by blinded review of target tissues to determine no-effect levels). Only a pathologist should write or revise the pathology report or the pathology section of the overall study report. To address concerns related to undue sponsor influence, comments by sponsors should be presented as suggestions rather than directives. Adversity should be defined for each finding by the study pathologist, but the no-observed adverse effect level should not be discussed in the pathology report. Board-certified pathologists are recommended, but are not essential. Sponsors that have a particular format or report preferences should make them known well in advance. Histologic processing "to glass" of protocol-specified tissues from all dosage groups is recommended for rapid evaluation of target tissues. Telepathology is beneficial in certain situations, but it is usually more efficient for the study pathologist and reviewing pathologist to be in the same physical location to review differences of opinion and reach a consensus.

[The auto-addictive hypothesis of pathological eating disorders].

PubMed

Lienard, Yasmine; Vamecq, Joseph

2004-10-23

The pathogenic role of self-addiction. Addiction to an endogenous chemical is a new paradigm termed 'self-addiction'. It may contribute to the development of certain habits, the pathological nature of which may set-in on the basis of this "self-addictive"dimension. Pathological eating habits could be inscribed in this perspective. Two extreme situations. In well-fed populations, the ingestion of food does not represent a limiting phase in the global feeding process. Its pathological management may, however, lead to two extreme situations: the absence of ingestion (anorexia) and excessive ingestion (bulimia). In favour of the self-addictive hypothesis. Eating disorders are associated with abnormal levels of endorphins and share clinical similarities with psychoactive drug abuse. The key role of endorphins has recently been demonstrated in animals with regard to certain aspects of normal, pathological and experimental eating habits (food restriction combined with stress, locomotor hyperactivity). The factors leading to pathological eating habits. Neurobiological bases for eating disorders and their durability have recently come to light in the recent implication of abnormalities in the recompense system in the onset of addiction. The endorphin self-addictive model in fact appears the most pertinent with regard to the clinical profile of eating habits and integrates the role of stress.

Should Psychiatrists Resurrect the Body?

PubMed

Benning, Tony B

2016-01-01

The current article interrogates the mind-body dualism that characterizes modern psychiatry and contends that the dualism is manifested by the relative neglect by psychiatrists of the body, or soma. The article argues that the state of affairs has several consequences, including psychiatrists' underappreciation of the somatic manifestations of mental disorders and of the therapeutic potential of somatic or body-based therapies. Empirical data attest to the association of a range of mental illnesses with somatic pathologies, as does the fact that a range of somatic therapies, including yoga and t'ai chi, are increasingly being shown to be efficacious in the treatment of a range of mental illnesses. The current article contextualizes contemporary Western psychiatry's relative neglect of the body by drawing on some historical as well as cross-cultural perspectives. Although their overall effect has been minimal, various theoretical perspectives in Western psychiatry, including Jungian thought, psychoanalytical psychosomatics, Reichian and related schools, and the phenomenological tradition, have sought to overcome psychiatry's mind-body dualism. Neither has psychiatry incorporated the values of various non-Western schools of medicine that maintain a far more integrated conceptualization of the relationship between mind and body than is seen in modern Western psychiatry. The field of psychosomatics could potentially influence general psychiatry to reverse its bifurcated mind-body relationship, but that field's increasingly narrow mandate and organizational separation from general psychiatry conspire to militate against the latter's incorporation of psychosomatic medicine's conceptual advances or pragmatic insights in any convincing or enduring manner.

Three-dimensional analysis of the early development of the dentition

PubMed Central

Peterkova, R; Hovorakova, M; Peterka, M; Lesot, H

2014-01-01

Tooth development has attracted the attention of researchers since the 19th century. It became obvious even then that morphogenesis could not fully be appreciated from two-dimensional histological sections. Therefore, methods of three-dimensional (3D) reconstructions were employed to visualize the surface morphology of developing structures and to help appreciate the complexity of early tooth morphogenesis. The present review surveys the data provided by computer-aided 3D analyses to update classical knowledge of early odontogenesis in the laboratory mouse and in humans. 3D reconstructions have demonstrated that odontogenesis in the early stages is a complex process which also includes the development of rudimentary odontogenic structures with different fates. Their developmental, evolutionary, and pathological aspects are discussed. The combination of in situ hybridization and 3D reconstruction have demonstrated the temporo-spatial dynamics of the signalling centres that reflect transient existence of rudimentary tooth primordia at loci where teeth were present in ancestors. The rudiments can rescue their suppressed development and revitalize, and then their subsequent autonomous development can give rise to oral pathologies. This shows that tooth-forming potential in mammals can be greater than that observed from their functional dentitions. From this perspective, the mouse rudimentary tooth primordia represent a natural model to test possibilities of tooth regeneration. PMID:24495023

Lung and Heart Sounds Analysis: State-of-the-Art and Future Trends.

PubMed

Padilla-Ortiz, Ana L; Ibarra, David

2018-01-01

Lung sounds, which include all sounds that are produced during the mechanism of respiration, may be classified into normal breath sounds and adventitious sounds. Normal breath sounds occur when no respiratory problems exist, whereas adventitious lung sounds (wheeze, rhonchi, crackle, etc.) are usually associated with certain pulmonary pathologies. Heart and lung sounds that are heard using a stethoscope are the result of mechanical interactions that indicate operation of cardiac and respiratory systems, respectively. In this article, we review the research conducted during the last six years on lung and heart sounds, instrumentation and data sources (sensors and databases), technological advances, and perspectives in processing and data analysis. Our review suggests that chronic obstructive pulmonary disease (COPD) and asthma are the most common respiratory diseases reported on in the literature; related diseases that are less analyzed include chronic bronchitis, idiopathic pulmonary fibrosis, congestive heart failure, and parenchymal pathology. Some new findings regarding the methodologies associated with advances in the electronic stethoscope have been presented for the auscultatory heart sound signaling process, including analysis and clarification of resulting sounds to create a diagnosis based on a quantifiable medical assessment. The availability of automatic interpretation of high precision of heart and lung sounds opens interesting possibilities for cardiovascular diagnosis as well as potential for intelligent diagnosis of heart and lung diseases.

[Mourning and depression, from the attachment theory perspective].

PubMed

Wolfberg, Elsa; Ekboir, Alberto; Faiman, Graciela; Finzi, Josefina; Freedman, Margarita; Heath, Adela; Martínez de Cipolatti, María C

2011-01-01

Since depression, according to OMS, is such a worldwide condition, it is necessary to be able to distinguish a normal mourning from a pathological mourning and a depression, so as to qualify patients and health professionals to be able to support a normal mourning without medicating it nor hurrying (hasting) it, as well as being able to treat a depression adequately when it appears as a complication. Attachment theory focuses on mourning after loss with notions such as 1- acceptance of search for the lost person as a normal fact; 2- that mourning in children may have non-pathological outcomes; 3- that a non-processed mourning may be transmitted in an intergenerational way, and 4- also defines which elements may determine a pathological mourning or a depression. A clinical case is presented with an analysis of these notions.

Frontiers in the bioarchaeology of stress and disease: cross-disciplinary perspectives from pathophysiology, human biology, and epidemiology.

PubMed

Klaus, Haagen D

2014-10-01

Over the last four decades, bioarchaeology has experienced significant technical growth and theoretical maturation. Early 21st century bioarchaeology may also be enhanced from a renewed engagement with the concept of biological stress. New insights on biological stress and disease can be gained from cross-disciplinary perspectives regarding human skeletal variation and disease. First, pathophysiologic and molecular signaling mechanisms can provide more precise understandings regarding formation of pathological phenotypes in bone. Using periosteal new bone formation as an example, various mechanisms and pathways are explored in which new bone can be formed under conditions of biological stress, particularly in bone microenvironments that involve inflammatory changes. Second, insights from human biology are examined regarding some epigenetic factors and disease etiology. While epigenetic effects on stress and disease outcomes appear profoundly influential, they are mostly invisible in skeletal tissue. However, some indirect and downstream effects, such as the developmental origins of adult health outcomes, may be partially observable in bioarchaeological data. Emerging perspectives from the human microbiome are also considered. Microbiomics involves a remarkable potential to understand ancient biology, disease, and stress. Third, tools from epidemiology are examined that may aid bioarchaeologists to better cope with some of the inherent limitations of skeletal samples to better measure and quantify the expressions of skeletal stress markers. Such cross-disciplinary synergisms hopefully will promote more complete understandings of health and stress in bioarchaeological science. Copyright © 2014 Wiley Periodicals, Inc.

Placental Pathology Associated with Household Air Pollution in a Cohort of Pregnant Women from Dar es Salaam, Tanzania.

PubMed

Wylie, Blair J; Matechi, Emmanuel; Kishashu, Yahya; Fawzi, Wafaie; Premji, Zul; Coull, Brent A; Hauser, Russ; Ezzati, Majid; Roberts, Drucilla J

2017-01-01

Smoke from the burning of biomass fuels has been linked with adverse pregnancy outcomes such as low birth weight, stillbirth, and prematurity. To identify potential underlying mechanisms of adverse perinatal outcomes, we explored the association of placental pathology with household air pollution in pregnant women from urban/periurban Tanzania who cook predominantly with charcoal. Between 2011 and 2013, we measured personal exposures to fine particulate matter (PM2.5) and carbon monoxide (CO) over 72 hr among a cohort of Tanzanian pregnant women. Placentas were collected after delivery for examination. Placental pathologies of inflammatory, hypoxic, ischemic/hypertensive, infectious and thrombotic etiologies were diagnosed, blinded to exposure levels. Using multiple logistic regression, we explored the association of PM2.5 and CO exposure with placental pathology. One hundred sixteen women had personal air exposure measurements and placental histopathology available for analysis. PM2.5 and CO exposures were moderate [geometric means (GSD) were 40.5 μg/m3 (17.3) and 2.21 ppm (1.47) respectively]; 88.6% of PM2.5 measurements exceeded World Health Organization air quality guidelines. We observed an increase in the odds (per 1-unit increase in exposure on the ln-scale) of fetal thrombotic vasculopathy (FTV) both with increasing PM2.5 [adjusted odds ratio (aOR) = 5.5; 95% CI: 1.1, 26.8] and CO measurements (aOR = 2.5; 95% CI: 1.0, 6.4) in adjusted models only. FTV also was more common among pregnancies complicated by stillbirth or low birth weight. Fetal thrombosis may contribute to the adverse outcomes associated with household air pollution from cook stoves during pregnancy. Larger studies are necessary for confirmation. Citation: Wylie BJ, Matechi E, Kishashu Y, Fawzi W, Premji Z, Coull BA, Hauser R, Ezzati M, Roberts D. 2017. Placental pathology associated with household air pollution in a cohort of pregnant women from Dar es Salaam, Tanzania. Environ Health Perspect 125:134-140; http://dx.doi.org/10.1289/EHP256.

Hitchhiker's guide to multi-dimensional plant pathology.

PubMed

Saunders, Diane G O

2015-02-01

Filamentous pathogens pose a substantial threat to global food security. One central question in plant pathology is how pathogens cause infection and manage to evade or suppress plant immunity to promote disease. With many technological advances over the past decade, including DNA sequencing technology, an array of new tools has become embedded within the toolbox of next-generation plant pathologists. By employing a multidisciplinary approach plant pathologists can fully leverage these technical advances to answer key questions in plant pathology, aimed at achieving global food security. This review discusses the impact of: cell biology and genetics on progressing our understanding of infection structure formation on the leaf surface; biochemical and molecular analysis to study how pathogens subdue plant immunity and manipulate plant processes through effectors; genomics and DNA sequencing technologies on all areas of plant pathology; and new forms of collaboration on accelerating exploitation of big data. As we embark on the next phase in plant pathology, the integration of systems biology promises to provide a holistic perspective of plant–pathogen interactions from big data and only once we fully appreciate these complexities can we design truly sustainable solutions to preserve our resources.

Considerations for standardizing predictive molecular pathology for cancer prognosis.

PubMed

Fiorentino, Michelangelo; Scarpelli, Marina; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo

2017-01-01

Molecular tests that were once ancillary to the core business of cyto-histopathology are becoming the most relevant workload in pathology departments after histopathology/cytopathology and before autopsies. This has resulted from innovations in molecular biology techniques, which have developed at an incredibly fast pace. Areas covered: Most of the current widely used techniques in molecular pathology such as FISH, direct sequencing, pyrosequencing, and allele-specific PCR will be replaced by massive parallel sequencing that will not be considered next generation, but rather, will be considered to be current generation sequencing. The pre-analytical steps of molecular techniques such as DNA extraction or sample preparation will be largely automated. Moreover, all the molecular pathology instruments will be part of an integrated workflow that traces the sample from extraction to the analytical steps until the results are reported; these steps will be guided by expert laboratory information systems. In situ hybridization and immunohistochemistry for quantification will be largely digitalized as much as histology will be mostly digitalized rather than viewed using microscopy. Expert commentary: This review summarizes the technical and regulatory issues concerning the standardization of molecular tests in pathology. A vision of the future perspectives of technological changes is also provided.

Drugs of abuse that mediate advanced glycation end product formation: a chemical link to disease pathology.

PubMed

Treweek, Jennifer B; Dickerson, Tobin J; Janda, Kim D

2009-05-19

Nicotine and methamphetamine are frequently abused in modern society, despite the increasing evidence of their addictive, neuropharmacological, and toxic effects. Tobacco, the most widely abused substance, is the leading cause of preventable death in the United States, killing nearly half a million Americans annually. A methamphetamine epidemic has also spread during the past decade; severe neurotoxicity and addictiveness contribute to the drug's notoriety. Although the majority of research on these two drugs is of pharmacological and neurobiological motivation, further study of these molecules from a chemical perspective may provide novel mechanistic insight into either their addictive potential or their pathological effects. For example, nicotine and methamphetamine share a common structural feature, a secondary amine, suggesting that these molecules could possess similar (or analogous) in vivo reactivity. Discoveries concerning the synthetic requirements for aqueous aldol catalysis and the feasibility of the enamine mechanism under physiological conditions have given rise to the hypothesis that ingested molecules, such as abused drugs, could participate in reactions utilizing an enamine intermediate in vivo. The chemical reactivity of exogenous drugs with amine functionalities was initially examined in the context of the Maillard reaction, or nonenzymatic browning. The heating of reducing sugars with amino acids yields a brown solution; studies of this reaction were originally applied to food chemistry for the production of distinct flavors and aromas. Further research has since revealed numerous instances in which the in vivo production of advanced glycation end products (AGEs) through the Maillard reaction contribute to the pathology of disease states. Specifically, the modification of long-lived proteins by glycation and glycoxidation and the accumulation of these AGEs compromise the original function of such proteins and change the mechanical properties of affected tissue. In this Account, we summarize our investigations into the capacity for exogenous compounds to initiate the Maillard reaction and the corresponding physiological and immunological impact of the drug-conjugated AGEs that form. Many of the pathological components of diabetes, atherosclerosis, cancer, macular degeneration, Alzheimer's disease, and even the normal aging process are attributable to AGEs and their potential for aggregate formation in the vasculature. A deeper understanding of AGEs, and particularly glycated proteins, will provide fundamental mechanistic insight into disease origins.

Blood biomarkers for brain injury: What are we measuring?

PubMed Central

Kawata, Keisuke; Liu, Charles Y.; Merkel, Steven F.; Ramirez, Servio H.; Tierney, Ryan T.; Langford, Dianne

2016-01-01

Accurate diagnosis for mild traumatic brain injury (mTBI) remains challenging, as prognosis and return-to-play/work decisions are based largely on patient reports. Numerous investigations have identified and characterized cellular factors in the blood as potential biomarkers for TBI, in the hope that these factors may be used to gauge the severity of brain injury. None of these potential biomarkers have advanced to use in the clinical setting. Some of the most extensively studied blood biomarkers for TBI include S100β, neuron-specific enolase, glial fibrillary acidic protein, and Tau. Understanding the biological function of each of these factors may be imperative to achieve progress in the field. We address the basic question: what are we measuring? This review will discuss blood biomarkers in terms of cellular origin, normal and pathological function, and possible reasons for increased blood levels. Considerations in the selection, evaluation, and validation of potential biomarkers will also be addressed, along with mechanisms that allow brain-derived proteins to enter the bloodstream after TBI. Lastly, we will highlight perspectives and implications for repetitive neurotrauma in the field of blood biomarkers for brain injury. PMID:27181909

Digital slides and ACGME resident competencies in anatomic pathology: An altered paradigm for acquisition and assessment

PubMed Central

Hassell, Lewis A.; Fung, Kar-Ming; Chaser, Brad

2011-01-01

Whole slide digital imaging technology has matured considerably over the past decade. Applications in pathology education are widespread and are rapidly transforming the manner in which medical students learn pathology and histology, and they have a novel and significant impact on postgraduate continuing medical education. Whole slide digital images for use in pathology graduate education have been slower in adoption and remain much less widespread. Emphasis on professional competency by the Accreditation Council on Graduate Medical Education (ACGME) and credentialing organizations, however, appear poised to significantly increase. The convergence of these two forces is propitious for pathology training. This article examines the opportunities for the use of whole slide images (WSI) in pathology residency training along with the developing potential uses in each of the areas of competency, as categorized by the ACGME. Barriers to WSI adoption in the pathology community are identified along with potentially significant promoters for adoption in training and practice. Current literature and recent presentations are reviewed. Digital pathology coupled with emphasis on competency is a shift of tremendous magnitude that can dramatically improve our abilities to help trainees acquire, demonstrate, and maintain the skills to practice pathology in the generation ahead. PMID:21773058

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.

An industry perspective: An update on the adoption of whole slide imaging.

PubMed

Montalto, Michael C

2016-01-01

This manuscript is an adaptation of the closing keynote presentation of the Digital Pathology Association Pathology Visions Conference 2015 in Boston, MA, USA. In this presentation, analogies are drawn between the adoption of whole slide imaging (WSI) and other mainstream digital technologies, including digital music and books. In doing so, it is revealed that the adoption of seemingly similar digital technologies does not follow the same adoption profiles and that understanding the unique aspects of value for each customer segment is critical. Finally, a call to action is given to academia and industry to study the value that WSI brings to the global healthcare community.

Trigeminal Neuralgia and Multiple Sclerosis: A Historical Perspective.

PubMed

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

2017-09-01

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

Modulating Cell Fate as a Therapeutic Strategy.

PubMed

Lin, Brian; Srikanth, Priya; Castle, Alison C; Nigwekar, Sagar; Malhotra, Rajeev; Galloway, Jenna L; Sykes, David B; Rajagopal, Jayaraj

2018-05-23

In injured tissues, regeneration is often associated with cell fate plasticity, in that cells deviate from their normal lineage paths. It is becoming increasingly clear that this plasticity often creates alternative strategies to restore damaged or lost cells. Alternatively, cell fate plasticity is also part and parcel of pathologic tissue transformations that accompany disease. In this Perspective, we summarize a few illustrative examples of physiologic and aberrant cellular plasticity. Then, we speculate on how one could enhance endogenous plasticity to promote regeneration and reverse pathologic plasticity, perhaps inspiring interest in a new class of therapies targeting cell fate modulation. Copyright © 2018 Elsevier Inc. All rights reserved.

Do endothelial cells dream of eclectic shape?

PubMed

Bentley, Katie; Philippides, Andrew; Ravasz Regan, Erzsébet

2014-04-28

Endothelial cells (ECs) exhibit dramatic plasticity of form at the single- and collective-cell level during new vessel growth, adult vascular homeostasis, and pathology. Understanding how, when, and why individual ECs coordinate decisions to change shape, in relation to the myriad of dynamic environmental signals, is key to understanding normal and pathological blood vessel behavior. However, this is a complex spatial and temporal problem. In this review we show that the multidisciplinary field of Adaptive Systems offers a refreshing perspective, common biological language, and straightforward toolkit that cell biologists can use to untangle the complexity of dynamic, morphogenetic systems. Copyright © 2014 Elsevier Inc. All rights reserved.

[New insights into the neuroscience of human altruism].

PubMed

Hurlemann, R; Marsh, N

2016-11-01

Numerous honorary initiatives for humanitarian aid towards refugees illustrate the high prevalence of altruistic behavior in the population. In medicine, an exquisite example of a human propensity for altruism is organ donation. Current perspectives on the neurobiology of altruism suggest that it is deeply rooted in the motivational architecture of the social brain. This is reflected by the social evolution of cooperation and parochialism, both of which are modulated by the evolutionarily conserved peptide hormone oxytocin. From a psychiatric perspective, altruism varies along a dimensional spectrum, with pathological hyperaltruism resulting in unexpected harm for oneself and others.

Long-term potentiation and long-term depression: a clinical perspective

PubMed Central

Bliss, Timothy V.P.; Cooke, Sam F

2011-01-01

Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke. PMID:21779718

Exploring International Perspectives in Hearing Health Care

ERIC Educational Resources Information Center

Montgomery, Judy K.

2007-01-01

This article presents an interview with Dr. Dolores E. Battle, a professor of speech-language pathology and senior advisor to the president for equity and campus diversity at Buffalo State College. She is a former president of the American Speech-Language-Hearing Association (in 2005) and a very active member of international organizations of both…

Bad Kids and Bad Feelings: What Children's Literature Teaches about ADHD, Creativity, and Openness

ERIC Educational Resources Information Center

Stearns, Clio

2015-01-01

This paper uses data from children's literature and classroom narratives to consider hyperactivity, inattention, and other non-normative behaviors in children. It encourages educational thinkers and childhood mental health professionals to take a historical perspective on children's badness rather than consigning it to the realm of pathology.…

Some Questions about "The History of Community Psychology"

ERIC Educational Resources Information Center

Fryer, David

2008-01-01

Most histories of the discipline of community psychology attribute its beginning to the Swampscott Conference that occurred in the mid-20th century. The author argues that recognition of the community perspective on human behavior and on its positive as well as pathological characteristics arose far earlier and is reflected in the work of European…

Deconstructing Barriers: Perceptions of Students Labeled with Learning Disabilities in Higher Education

ERIC Educational Resources Information Center

Denhart, Hazel

2008-01-01

This phenomenological study investigated barriers to higher education faced by 11 college students labeled with learning disabilities (LD) using their voice as the primary data. Data were analyzed and interpreted through a disability theory perspective revealing barriers stemmed largely from external social causes rather than individual pathology.…

Accountability and the Affective Labour of Teachers: A Marxist-Vygotskian Perspective

ERIC Educational Resources Information Center

Kostogriz, Alex

2012-01-01

This article addresses the issue of affective labour in education in the context of standards-based reforms and accountability. In particular, it focuses on neoliberal strategies of rationalization and control that produce a number of social pathologies, such as alienated teaching and learning and reified social relations between teachers and…

Expertise in Clinical Pathology: Combining the Visual and Cognitive Perspective

ERIC Educational Resources Information Center

Jaarsma, Thomas; Jarodzka, Halszka; Nap, Marius; van Merriënboer, Jeroen J. G.; Boshuizen, Henny P. A.

2015-01-01

Expertise studies in the medical domain often focus on either visual or cognitive aspects of expertise. As a result, characteristics of expert behaviour are often described as either cognitive or visual abilities. This study focuses on both aspects of expertise and analyses them along three overarching constructs: (1) encapsulations, (2)…

Molecular identification, genetic diversity, population genetics and genomics of Rhizoctonia solani. In:perspective of plant pathology in genomic era

USDA-ARS?s Scientific Manuscript database

The basidiomycetous soilborne fungus Rhizoctonia (sensu lato) is an economically important pathogen of worldwide distribution and it is known to attack at least 188 species of higher plants, including agronomic crops, vegetables, ornamentals, forest trees and turfgrasses. The pathogenic isolates may...

Eurocentrism and the Postcolonial Implications of Skin Color among Latinos

ERIC Educational Resources Information Center

Hall, Ronald E.

2011-01-01

Eurocentrism is a worldview of the academic mainstream. It is grounded in a European perspective that manifests as a tendency to interpret and prioritize the world in Western terms, Western values, and Western experiences. Eurocentric frames of reference are pathological as pertains to the psychological well-being of Latinos. Evidence of said…

The Regulatory Roles of MicroRNAs in Bone Remodeling and Perspectives as Biomarkers in Osteoporosis

PubMed Central

Sun, Mengge; Zhou, Xiaoya; Chen, Lili; Huang, Shishu; Leung, Victor; Wu, Nan; Pan, Haobo; Zhen, Wanxin; Lu, William; Peng, Songlin

2016-01-01

MicroRNAs are involved in many cellular and molecular activities and played important roles in many biological and pathological processes, such as tissue formation, cancer development, diabetes, neurodegenerative diseases, and cardiovascular diseases. Recently, it has been reported that microRNAs can modulate the differentiation and activities of osteoblasts and osteoclasts, the key cells that are involved in bone remodeling process. Meanwhile, the results from our and other research groups showed that the expression profiles of microRNAs in the serum and bone tissues are significantly different in postmenopausal women with or without fractures compared to the control. Therefore, it can be postulated that microRNAs might play important roles in bone remodeling and that they are very likely to be involved in the pathological process of postmenopausal osteoporosis. In this review, we will present the updated research on the regulatory roles of microRNAs in osteoblasts and osteoclasts and the expression profiles of microRNAs in osteoporosis and osteoporotic fracture patients. The perspective of serum microRNAs as novel biomarkers in bone loss disorders such as osteoporosis has also been discussed. PMID:27073801

The Fragile X Mental Retardation 1 Gene (FMR1): Historical Perspective, Phenotypes, Mechanism, Pathology, and Epidemiology

PubMed Central

Grigsby, Jim

2016-01-01

Objectives To provide an historical perspective and overview of the phenotypes, mechanism, pathology, and epidemiology of the fragile X-associated tremor/ataxia syndrome (FXTAS) for neuropsychologists. Methods Selective review of the literature on FXTAS. Results FXTAS is an X-linked neurodegenerative disorder of late onset. One of several phenotypes associated with different mutations of the fragile X mental retardation 1 gene (FMR1), FXTAS involves progressive action tremor, gait ataxia, and impaired executive functioning, among other features. It affects carriers of the FMR1 premutation, which may expand when passed from a mother to her children, in which case it is likely to cause fragile X syndrome (FXS), the most common inherited developmental disability. Conclusion This review briefly summarizes current knowledge of the mechanisms, epidemiology, and mode of transmission of FXTAS and FXS, as well as the neuropsychological, neurologic, neuropsychiatric, neuropathologic, and neuroradiologic phenotypes of FXTAS. Because it was only recently identified, FXTAS is not well known to most practitioners, and it remains largely misdiagnosed, despite the fact that its prevalence may be relatively high. PMID:27356167

The fragile X mental retardation 1 gene (FMR1): historical perspective, phenotypes, mechanism, pathology, and epidemiology.

PubMed

Grigsby, Jim

2016-08-01

To provide an historical perspective and overview of the phenotypes, mechanism, pathology, and epidemiology of the fragile X-associated tremor/ataxia syndrome (FXTAS) for neuropsychologists. Selective review of the literature on FXTAS. FXTAS is an X-linked neurodegenerative disorder of late onset. One of several phenotypes associated with different mutations of the fragile X mental retardation 1 gene (FMR1), FXTAS involves progressive action tremor, gait ataxia, and impaired executive functioning, among other features. It affects carriers of the FMR1 premutation, which may expand when passed from a mother to her children, in which case it is likely to cause fragile X syndrome (FXS), the most common inherited developmental disability. This review briefly summarizes current knowledge of the mechanisms, epidemiology, and mode of transmission of FXTAS and FXS, as well as the neuropsychological, neurologic, neuropsychiatric, neuropathologic, and neuroradiologic phenotypes of FXTAS. Because it was only recently identified, FXTAS is not well known to most practitioners, and it remains largely misdiagnosed, despite the fact that its prevalence may be relatively high.

The emergence of psychiatric semiology during the Age of Revolution: evolving concepts of 'normal' and 'pathological'.

PubMed

Londoño, Diego Enrique; Dening, Tom

2016-06-01

This article addresses some important questions in psychiatric semiology. The concept of a sign is crucial in psychiatry. How do signs emerge, and what gives them validity and legitimacy? What are the boundaries of 'normal' and 'pathological' behaviour and mental experiences? To address these issues, we analyse the characteristics and rules that govern semiological signs and clinical elements. We examine 'normality' from the perspective of Georges Canguilehm and compare the differences of 'normal' in physiology and psychiatry. We then examine the history and the philosophical, linguistic and medical-psychiatric origins of semiology during the eighteenth and nineteenth centuries (the Age of Revolution). The field of rhetoric and oratory has emphasized the importance of passions, emotions and language as applied to signs of madness. Another perspective on semiology, provided by Michel Foucault, lays stress on the concept of 'instinct' and the axis of voluntary-involuntary behaviour. Finally, we analyse how statistics and eugenics have played an important role in our current conceptualization of the norm and therefore the scientific discourse behind the established clinical signs. © The Author(s) 2016.

The neurocognitive consequences of the wandering mind: a mechanistic account of sensory-motor decoupling

PubMed Central

Kam, Julia W. Y.; Handy, Todd C.

2013-01-01

A unique human characteristic is our ability to mind wander – a state in which we are free to engage in thoughts that are not directly tied to sensations and perceptions from our immediate physical environment. From a neurocognitive perspective, it has been proposed that during mind wandering, our executive resources are decoupled from the external environment and directed to these internal thoughts. In this review, we examine an underappreciated aspect of this phenomenon – attenuation of sensory-motor processing – from two perspectives. First, we describe the range of widespread sensory, cognitive and motor processes attenuated during mind wandering states, and how this impacts our neurocognitive processing of external events. We then consider sensory-motor attenuation in a class of clinical neurocognitive disorders that have ties to pathological patterns of decoupling, reviews suggesting that mind wandering and these clinical states may share a common mechanism of sensory-motor attenuation. Taken together, these observations suggest the sensory-motor consequences of decoupled thinking are integral to normal and pathological neurocognitive states. PMID:24133472

Conventional Microscopy vs. Computer Imagery in Chiropractic Education.

PubMed

Cunningham, Christine M; Larzelere, Elizabeth D; Arar, Ilija

2008-01-01

As human tissue pathology slides become increasingly difficult to obtain, other methods of teaching microscopy in educational laboratories must be considered. The purpose of this study was to evaluate our students' satisfaction with newly implemented computer imagery based laboratory instruction and to obtain input from their perspective on the advantages and disadvantages of computerized vs. traditional microscope laboratories. This undertaking involved the creation of a new computer laboratory. Robbins and Cotran Pathologic Basis of Disease, 7(th)ed, was chosen as the required text which gave students access to the Robbins Pathology website, including complete content of text, Interactive Case Study Companion, and Virtual Microscope. Students had experience with traditional microscopes in their histology and microbiology laboratory courses. Student satisfaction with computer based learning was assessed using a 28 question survey which was administered to three successive trimesters of pathology students (n=193) using the computer survey website Zoomerang. Answers were given on a scale of 1-5 and statistically analyzed using weighted averages. The survey data indicated that students were satisfied with computer based learning activities during pathology laboratory instruction. The most favorable aspect to computer imagery was 24-7 availability (weighted avg. 4.16), followed by clarification offered by accompanying text and captions (weighted avg. 4.08). Although advantages and disadvantages exist in using conventional microscopy and computer imagery, current pathology teaching environments warrant investigation of replacing traditional microscope exercises with computer applications. Chiropractic students supported the adoption of computer-assisted instruction in pathology laboratories.

The history of pathology informatics: A global perspective

PubMed Central

Park, Seung; Parwani, Anil V.; Aller, Raymond D.; Banach, Lech; Becich, Michael J.; Borkenfeld, Stephan; Carter, Alexis B.; Friedman, Bruce A.; Rojo, Marcial Garcia; Georgiou, Andrew; Kayser, Gian; Kayser, Klaus; Legg, Michael; Naugler, Christopher; Sawai, Takashi; Weiner, Hal; Winsten, Dennis; Pantanowitz, Liron

2013-01-01

Pathology informatics has evolved to varying levels around the world. The history of pathology informatics in different countries is a tale with many dimensions. At first glance, it is the familiar story of individuals solving problems that arise in their clinical practice to enhance efficiency, better manage (e.g., digitize) laboratory information, as well as exploit emerging information technologies. Under the surface, however, lie powerful resource, regulatory, and societal forces that helped shape our discipline into what it is today. In this monograph, for the first time in the history of our discipline, we collectively perform a global review of the field of pathology informatics. In doing so, we illustrate how general far-reaching trends such as the advent of computers, the Internet and digital imaging have affected pathology informatics in the world at large. Major drivers in the field included the need for pathologists to comply with national standards for health information technology and telepathology applications to meet the scarcity of pathology services and trained people in certain countries. Following trials by a multitude of investigators, not all of them successful, it is apparent that innovation alone did not assure the success of many informatics tools and solutions. Common, ongoing barriers to the widespread adoption of informatics devices include poor information technology infrastructure in undeveloped areas, the cost of technology, and regulatory issues. This review offers a deeper understanding of how pathology informatics historically developed and provides insights into what the promising future might hold. PMID:23869286

Comparison of mathematical models of fibrosis. Comment on "Towards a unified approach in the modeling of fibrosis: A review with research perspectives" by M. Ben Amar and C. Bianca

NASA Astrophysics Data System (ADS)

Kachapova, Farida

2016-07-01

Mathematical and computational models in biology and medicine help to improve diagnostics and medical treatments. Modeling of pathological fibrosis is reviewed by M. Ben Amar and C. Bianca in [4]. Pathological fibrosis is the process when excessive fibrous tissue is deposited on an organ or tissue during a wound healing and can obliterate their normal function. In [4] the phenomena of fibrosis are briefly explained including the causes, mechanism and management; research models of pathological fibrosis are described, compared and critically analyzed. Different models are suitable at different levels: molecular, cellular and tissue. The main goal of mathematical modeling of fibrosis is to predict long term behavior of the system depending on bifurcation parameters; there are two main trends: inhibition of fibrosis due to an active immune system and swelling of fibrosis because of a weak immune system.

A warning to the Brazilian Speech-Language Pathology and Audiology community about the importance of scientific and clinical activities in primary progressive aphasia.

PubMed

Beber, Bárbara Costa; Brandão, Lenisa; Chaves, Márcia Lorena Fagundes

2015-01-01

This article aims to warn the Brazilian Speech-Language Pathology and Audiology scientific community about the importance and necessity of scientific and clinical activities regarding Primary Progressive Aphasia. This warning is based on a systematic literature review of the scientific production on Primary Progressive Aphasia, from which nine Brazilian articles were selected. It was observed that there is an obvious lack of studies on the subject, as all the retrieved articles were published in medical journals and much of it consisted of small samples; only two articles described the effectiveness of speech-language therapy in patients with Primary Progressive Aphasia. A perspective for the future in the area and characteristics of Speech-Language Therapy for Primary Progressive Aphasia are discussed. As a conclusion, it is evident the need for greater action by Speech-Language Pathology and Audiology on Primary Progressive Aphasia.

Ego Defense Mechanisms and Types of Object Relations in Adults With ADHD.

PubMed

de Almeida Silva, Vanessa; Louzã, Mario Rodrigues; da Silva, Maria Aparecida; Nakano, Eduardo Yoshio

2016-11-01

This research evaluates the personality structure of adults with ADHD from a psychodynamic perspective. The hypothesis was that possible structural characteristics in personality could be correlated with this syndrome. Assessment tools for ego functions (Bell Object Relations and Reality Testing Inventory [BORRTI-Form O], Defense Style Questionnaire ( DSQ-40)) were applied to a sample of 90 adults with ADHD, recruited in a specialized clinic. Among the ADHD sample, 84.4% of the participants were identified as having object relations pathologies. Pathological elevations were observed mainly in the Alienation, Egocentricity, and Insecure Attachment subscales. Statistically, significant differences were found especially in the use of immature and neurotic defense mechanisms, compared with normative data. The findings indicate that adults with ADHD make more use of immature and neurotic defense mechanisms, and presented pathological internalized object relations that are typical of an archaic and poorly structured egoic structure. © The Author(s) 2012.

Zika Fetal Neuropathogenesis: Etiology of a Viral Syndrome

PubMed Central

Klase, Zachary A.; Khakhina, Svetlana; Schneider, Adriano De Bernardi; Callahan, Michael V.; Glasspool-Malone, Jill

2016-01-01

The ongoing Zika virus epidemic in the Americas and the observed association with both fetal abnormalities (primary microcephaly) and adult autoimmune pathology (Guillain–Barré syndrome) has brought attention to this neglected pathogen. While initial case studies generated significant interest in the Zika virus outbreak, larger prospective epidemiology and basic virology studies examining the mechanisms of Zika viral infection and associated pathophysiology are only now starting to be published. In this review, we analyze Zika fetal neuropathogenesis from a comparative pathology perspective, using the historic metaphor of “TORCH” viral pathogenesis to provide context. By drawing parallels to other viral infections of the fetus, we identify common themes and mechanisms that may illuminate the observed pathology. The existing data on the susceptibility of various cells to both Zika and other flavivirus infections are summarized. Finally, we highlight relevant aspects of the known molecular mechanisms of flavivirus replication. PMID:27560129

Pathological and Molecular Evaluation of Pancreatic Neoplasms

PubMed Central

Rishi, Arvind; Goggins, Michael; Wood, Laura D.; Hruban, Ralph H.

2015-01-01

Pancreatic neoplasms are morphologically and genetically heterogeneous and include wide variety of neoplasms ranging from benign to malignant with an extremely poor clinical outcome. Our understanding of these pancreatic neoplasms has improved significantly with recent advances in cancer sequencing. Awareness of molecular pathogenesis brings in new opportunities for early detection, improved prognostication, and personalized gene-specific therapies. Here we review the pathological classification of pancreatic neoplasms from their molecular and genetic perspective. All of the major tumor types that arise in the pancreas have been sequenced, and a new classification that incorporates molecular findings together with pathological findings is now possible (Table 1). This classification has significant implications for our understanding of why tumors aggregate in some families, for the development of early detection tests, and for the development of personalized therapies for patients with established cancers. Here we describe this new classification using the framework of the standard histological classification. PMID:25726050

The mirror has two faces: dissociative identity disorder and the defence of pathological criminal incapacity--a South African criminal law perspective.

PubMed

Stevens, Philip

2013-03-01

Dissociative identity disorder poses numerous medico legal issues whenever the insanity defence emerges. Within the context of the South African criminal law, the impact of dissociative identity disorder on criminal responsibility has only been addressed very briefly in one decided case. Various questions arise as to the impact that the distinctive diagnostic features of dissociative identity disorder could possibly have on the defence of pathological criminal incapacity, or better known as the insanity defence, within the ambit of the South African criminal law. In this contribution the author reflects on the mental disorder known as dissociative identity disorder or multiple personality disorder, against the backdrop of the defence of pathological criminal incapacity. Reflections are also provided pertaining to the various medico legal issues at stake whenever this defence has to be adjudicated upon.

The oral cavity microbiota: between health, oral disease, and cancers of the aerodigestive tract.

PubMed

Le Bars, Pierre; Matamoros, Sébastien; Montassier, Emmanuel; Le Vacon, Françoise; Potel, Gilles; Soueidan, Assem; Jordana, Fabienne; de La Cochetière, Marie-France

2017-06-01

Many studies show that the human microbiome plays a critical role in the chronic pathologies of obesity, inflammatory bowel diseases, and diabetes. More recently, the interaction between cancer and the microbiome has been highlighted. Most studies have focused on the gut microbiota because it represents the most extensive bacterial community, and the body of evidence correlating it with gut syndromes is increasing. However, in the strict sense, the gastrointestinal (GI) tract begins in the oral cavity, and special attention should be paid to the specific flora of this cavity. This study reviewed the current knowledge about the various microbial ecosystems of the upper part of the GI tract and discussed their potential link to carcinogenesis. The overall composition of the microbial communities, as well as the presence or absence of "key species", in relation to carcinogenesis is addressed. Alterations in the oral microbiota can potentially be used to predict the risk of cancer. Molecular advances and the further monitoring of the microbiota will increase our understanding of the role of the microbiota in carcinogenesis and open new perspectives for future therapeutic and prophylactic modalities.

Multiple Stakeholder Perspectives on Teletherapy Delivery of Speech Pathology Services in Rural Schools: A Preliminary, Qualitative Investigation

PubMed Central

LINCOLN, MICHELLE; HINES, MONIQUE; FAIRWEATHER, CRAIG; RAMSDEN, ROBYN; MARTINOVICH, JULIA

2015-01-01

The objective of this study was to investigate stakeholders’ views on the feasibility and acceptability of a pilot speech pathology teletherapy program for children attending schools in rural New South Wales, Australia. Nine children received speech pathology sessions delivered via Adobe Connect® web-conferencing software. During semi-structured interviews, school principals (n = 3), therapy facilitators (n = 7), and parents (n = 6) described factors that promoted or threatened the program’s feasibility and acceptability. Themes were categorized according to whether they related to (a) the use of technology; (b) the school-based nature of the program; or (c) the combination of using technology with a school-based program. Despite frequent reports of difficulties with technology, teletherapy delivery of speech pathology services in schools was highly acceptable to stakeholders. However, the use of technology within a school environment increased the complexities of service delivery. Service providers should pay careful attention to planning processes and lines of communication in order to promote efficiency and acceptability of teletherapy programs. PMID:25945230

[The Base of the Skull. Rudolf Virchow between Pathology and Anthropology].

PubMed

Seemann, Sophie

2016-01-01

Throughout his scientific career, the pathologist and anthropologist Rudolf Virchow (1821-1902) examined countless skulls, gradually changing his perspective on this object of research. Initially, he was mainly concerned with pathologically deformed skulls. From the 1850s onwards, he gradually developed a more anthropological approach, and anthropology increasingly came to dominate his scientific interest. This article shows how different influences became central for the establishment of his specific and dynamic model of the human skull development and its successful application in anthropology. Crucial for this process were Virchow's collaboration with his teacher Robert Froriep (1804-1861) in the department of pathology of the Charité, his research on cretinism and rickets, as well as his description of the base of the skull as the center of skull development. His research work was attended by and showed a reciprocal interaction with the buildup of large skull collections. This article uses Virchow's original publications on skull pathology as well as his still preserved skull specimens from the collection of the Berlin Museum of Medical History at the Charité for an integrated text and object based analysis.

Plenoptic Ophthalmoscopy: A Novel Imaging Technique.

PubMed

Adam, Murtaza K; Aenchbacher, Weston; Kurzweg, Timothy; Hsu, Jason

2016-11-01

This prospective retinal imaging case series was designed to establish feasibility of plenoptic ophthalmoscopy (PO), a novel mydriatic fundus imaging technique. A custom variable intensity LED array light source adapter was created for the Lytro Gen1 light-field camera (Lytro, Mountain View, CA). Initial PO testing was performed on a model eye and rabbit fundi. PO image acquisition was then performed on dilated human subjects with a variety of retinal pathology and images were subjected to computational enhancement. The Lytro Gen1 light-field camera with custom LED array captured fundus images of eyes with diabetic retinopathy, age-related macular degeneration, retinal detachment, and other diagnoses. Post-acquisition computational processing allowed for refocusing and perspective shifting of retinal PO images, resulting in improved image quality. The application of PO to image the ocular fundus is feasible. Additional studies are needed to determine its potential clinical utility. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:1038-1043.]. Copyright 2016, SLACK Incorporated.

Role of Adipokines in Atherosclerosis: Interferences with Cardiovascular Complications in Rheumatic Diseases

PubMed Central

Scotece, Morena; Conde, Javier; Gómez, Rodolfo; López, Verónica; Pino, Jesús; González, Antonio; Lago, Francisca; Gómez-Reino, Juan J.; Gualillo, Oreste

2012-01-01

Patients with rheumatic diseases have an increased risk of mortality by cardiovascular events. In fact, several rheumatic diseases such as rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis are associated with a higher prevalence of cardiovascular diseases (CVDs). Although traditional cardiovascular risk factors have been involved in the pathogenesis of cardiovascular diseases in rheumatic patients, these alterations do not completely explain the enhanced cardiovascular risk in this population. Obesity and its pathologic alteration of fat mass and dysfunction, due to an altered pattern of secretion of proinflammatory adipokines, could be one of the links between cardiovascular and rheumatic diseases. Indeed, the incidence of CVDs is augmented in obese individuals with rheumatic disorders. Thus, in this paper we explore in detail the relationships among adipokines, rheumatic diseases, and cardiovascular complications by giving to the reader a holistic vision and several suggestions for future perspectives and potential clinical implications. PMID:22910888

Selective pathologies of the head and neck in children: a developmental perspective.

PubMed

Ozolek, John A

2009-09-01

The range of pathology seen in the head and neck region is truly amazing and to a large extent probably mirrors the complex signaling pathways and careful orchestration of events that occurs between the primordial germ layers during the development of this region. As is true in general for the entire discipline of pediatric pathology, the head and neck pathology within this age group is as diverse and different as its adult counterpart. Cases that come across the pediatric head and neck surgical pathology bench are more heavily weighted toward developmental and congenital lesions such as branchial cleft anomalies, thyroglossal duct cysts, ectopias, heterotopias, choristomas, and primitive tumors. Many congenital "benign" lesions can cause significant morbidity and even mortality if they compress the airway or other vital structures. Exciting investigations into the molecular embryology of craniofacial development have begun to shed light on the pathogenesis of craniofacial developmental lesions and syndromes. Much more investigation is needed, however, to intertwine aberrations in the molecular ontogeny and development of the head and neck regions to the represented pathology. This review will integrate traditional morphologic embryology with some of the recent advances in the molecular pathways of head and neck development followed by a discussion of a variety of developmental lesions finishing with tumors presumed to be derived from pluripotent/progenitor cells and tumors that show anomalous or aborted development.

[Stem Cells in the Brain of Mammals and Human: Fundamental and Applied Aspects].

PubMed

Aleksandrova, M A; Marey, M V

2015-01-01

Brain stem cells represent an extremely intriguing phenomenon. The aim of our review is to present an integrity vision of their role in the brain of mammals and humans, and their clinical perspectives. Over last two decades, investigations of biology of the neural stem cells produced significant changes in general knowledge about the processes of development and functioning of the brain. Researches on the cellular and molecular mechanisms of NSC differentiation and behavior led to new understanding of their involvement in learning and memory. In the regenerative medicine, original therapeutic approaches to neurodegenerative brain diseases have been elaborated due to fundamental achievements in this field. They are based on specific regenerative potential of neural stem cells and progenitor cells, which possess the ability to replace dead cells and express crucially significant biologically active factors that are missing in the pathological brain. For the needs of cell substitution therapy in the neural diseases, adequate methods of maintaining stem cells in culture and their differentiation into different types of neurons and glial cells, have been developed currently. The success of modern cellular technologies has significantly expanded the range of cells used for cell therapy. The near future may bring new perspective and distinct progress in brain cell therapy due to optimizing the cells types most promising for medical needs.

In vitro blood-brain barrier models: current and perspective technologies.

PubMed

Naik, Pooja; Cucullo, Luca

2012-04-01

Even in the 21st century, studies aimed at characterizing the pathological paradigms associated with the development and progression of central nervous system diseases are primarily performed in laboratory animals. However, limited translational significance, high cost, and labor to develop the appropriate model (e.g., transgenic or inbred strains) have favored parallel in vitro approaches. In vitro models are of particular interest for cerebrovascular studies of the blood-brain barrier (BBB), which plays a critical role in maintaining the brain homeostasis and neuronal functions. Because the BBB dynamically responds to many events associated with rheological and systemic impairments (e.g., hypoperfusion), including the exposure of potentially harmful xenobiotics, the development of more sophisticated artificial systems capable of replicating the vascular properties of the brain microcapillaries are becoming a major focus in basic, translational, and pharmaceutical research. In vitro BBB models are valuable and easy to use supporting tools that can precede and complement animal and human studies. In this article, we provide a detailed review and analysis of currently available in vitro BBB models ranging from static culture systems to the most advanced flow-based and three-dimensional coculture apparatus. We also discuss recent and perspective developments in this ever expanding research field. Copyright © 2011 Wiley Periodicals, Inc.

In this issue: Nef, a lingering problem; are there better immunoglobulins for human use; and Takayasu arteritis, still a mystery.

PubMed

Bot, Adrian

2012-12-01

The current issue of the International Reviews of Immunology brings the latest in three different areas of basic and clinical immunology. First, there is the lingering question of residual HIV-related pathology in patients on chronic antiretroviral therapy. The specific role of Nef in the macrophage-mediated disease manifested through lymphoma, metabolic disease and neurological disorder, is extensively discussed. A second topic is a clinical immunology one, a critical perspective on the efficacy and safety profile of various preparations of immunoglobulin products currently prescribed for a range of immunodeficiencies. Surprisingly, the authors showed that while the available preparations are equivalent from efficacy standpoint, they differ from the standpoint of toxicity. The third subject is again, in the arena of clinical immunology and deals with a relatively rare yet extremely puzzling disease -Takayasu arteritis -with a pathogenesis that needs elucidation and a dire need for better treatments. The authors provide a state of the art in terms of genetic association, other factors possibly involved in the onset and progression of this unusual inflammatory disease of large arteries, and provide a perspective on current standard of care and potential usefulness of TNF-α blockade as therapy for Takayasu arteritis.

Computer-aided auscultation of murmurs in children: evaluation of commercially available software.

PubMed

Lee, Cecilia; Rankin, Kathryn N; Zuo, Kevin J; Mackie, Andrew S

2016-10-01

Heart murmurs are common in children and may represent congenital or acquired cardiac pathology. Auscultation is challenging and many primary-care physicians lack the skill to differentiate innocent from pathologic murmurs. We sought to determine whether computer-aided auscultation (CardioscanTM) identifies which children require referral to a cardiologist. We consecutively enrolled children aged between 0 and 17 years with a murmur, innocent or pathologic, being evaluated in a tertiary-care cardiology clinic. Children being evaluated for the first time and patients with known cardiac pathology were eligible. We excluded children who had undergone cardiac surgery previously or were unable to sit still for auscultation. CardioscanTM auscultation was performed in a quiet room with the subject in the supine position. The sensitivity and specificity of a potentially pathologic murmur designation by CardioscanTM - that is, requiring referral - was determined using echocardiography as the reference standard. We enrolled 126 subjects (44% female) with a median age of 1.7 years, with 93 (74%) having cardiac pathology. The sensitivity and specificity of a potentially pathologic murmur determination by CardioscanTM for identification of cardiac pathology were 83.9 and 30.3%, respectively, versus 75.0 and 71.4%, respectively, when limited to subjects with a heart rate of 50-120 beats per minute. The combination of a CardioscanTM potentially pathologic murmur designation or an abnormal electrocardiogram improved sensitivity to 93.5%, with no haemodynamically significant lesions missed. Sensitivity of CardioscanTM when interpreted in conjunction with an abnormal electrocardiogram was high, although specificity was poor. Re-evaluation of computer-aided auscultation will remain necessary as advances in this technology become available.

Autism and anorexia nervosa: Two facets of the same disease?

PubMed

Odent, Michel

2010-07-01

We compiled data included in the Primal Health Research Database (www.primalhealthresearch.com) to test the hypothesis that when two pathological conditions or personality traits share the same critical period for gene-environment interaction, we should expect further similarities, particularly from clinical and pathophysiological perspectives. The keywords 'autism' and 'anorexia nervosa' (but not bulimia nervosa) lead to studies suggesting that for both conditions the perinatal period is critical. We take this example to look at other possible links between these pathological entities. From a clinical perspective, several teams have independently emphasized the importance of autistic traits in anorexia nervosa. Deficits in the processing of oxytocin have been demonstrated in both cases. Autistic groups have significantly lower blood oxytocin levels than normal groups, and oxytocin levels increase with age in the normal group only. In autistic groups there is a high ratio of intermediates of oxytocin synthesis (OX-T) to the nonapeptide oxytocin (OT). On the other hand, it has been reported that the level of oxytocin in the cerebrospinal fluid of anorexic women is significantly lower than the level of oxytocin in bulimic and control subjects. Scanning data reveal similar asymmetric functions with left hemisphere preponderance in autistic spectrum disorders and anorexia. A comparative study of the mirror neurons systems is another promising avenue for research. Such an accumulation of similarities from a great diversity of perspectives suggests that anorexia nervosa might be considered a female variant of the autistic spectrum. A plausible interpretation is that prenatal exposure to male hormones might protect against the expression of this disease: girls who have a twin brother are at low risk for anorexia nervosa, compared with girls who have a twin sister, and with controls; furthermore genetic linkage analyses do not detect change on the X chromosome. From an overview of the database, the perinatal period appears to be critical for all disorders related to the capacity to love (including love of oneself), to the potential for aggression (including self-destructive behaviours), or to sociability. Is the perinatal period critical for the organisation of the oxytocin system? This is an important question at a time when we learn that the widely used synthetic oxytocin can probably diffuse across the placenta. On the other hand, where the genesis of metabolic types is concerned, it is prenatal life that appears to be critical. Copyright 2010 Elsevier Ltd. All rights reserved.

Concepts and implications of altruism bias and pathological altruism

PubMed Central

Oakley, Barbara A.

2013-01-01

The profound benefits of altruism in modern society are self-evident. However, the potential hurtful aspects of altruism have gone largely unrecognized in scientific inquiry. This is despite the fact that virtually all forms of altruism are associated with tradeoffs—some of enormous importance and sensitivity—and notwithstanding that examples of pathologies of altruism abound. Presented here are the mechanistic bases and potential ramifications of pathological altruism, that is, altruism in which attempts to promote the welfare of others instead result in unanticipated harm. A basic conceptual approach toward the quantification of altruism bias is presented. Guardian systems and their over arching importance in the evolution of cooperation are also discussed. Concepts of pathological altruism, altruism bias, and guardian systems may help open many new, potentially useful lines of inquiry and provide a framework to begin moving toward a more mature, scientifically informed understanding of altruism and cooperative behavior. PMID:23754434

So Perfect It's Positively Harmful?: Reflections on the Adaptiveness and Maladaptiveness of Positive and Negative Perfectionism

ERIC Educational Resources Information Center

Owens, R. Glynn; Slade, Peter D.

2008-01-01

The article by Flatt and Hewitt (2006) highlights a number of important issues in the study of perfectionism and rightly urges caution against simplistic conceptualizations. Their view that the term "perfectionism" should be reserved for pathological forms of behavior is questionable, though understandable given the perspective from which they…

The Psychological Armor of Urban Adolescents: Exploring the Influence of Critical Consciousness and Racial Identity on Career Adaptability

ERIC Educational Resources Information Center

Phan, Olivia M.

2010-01-01

Deficit-oriented research has ignored the strengths of urban adolescents of color, perpetuating interpretations that they are deviant and pathological (Spencer et al., 2006). Generally unacknowledged by problem-focused perspectives is how youths of color grapple with vulnerability to negative socialization messages, prejudice and discrimination,…

Subjectivity in Education and Health: Research Notes on School Learning Area and Physical Education in Mental Health

ERIC Educational Resources Information Center

Bezerra, Marilia; da Costa, Jonatas Maia

2016-01-01

This paper presents the results of two studies researching the theory of subjectivity from a cultural-historical perspective. The studies are situated in the fields of education and health and are conducted using Qualitative Epistemology. The first study discusses the pathological movement problems of learning disabilities in Brazilian schools and…

A Masculine Perspective of Gendered Topics in the Research Literature on Males and Females with Intellectual Disability

ERIC Educational Resources Information Center

Wilson, Nathan J.; Parmenter, Trevor R.; Stancliffe, Roger J.; Shuttleworth, Russell P.; Parker, Desrae

2010-01-01

Background: A focus on male social pathologies may have evolved within parts of the intellectual disability research literature. This article explores this notion and makes some connections between mainstream gender theory about hegemonic masculinity and the current gendered discourse in intellectual disability research. Method: We conducted a…

Broadening the "Ports of Entry" for Speech-Language Pathologists: A Relational and Reflective Model for Clinical Supervision

ERIC Educational Resources Information Center

Geller, Elaine; Foley, Gilbert M.

2009-01-01

Purpose: To offer a framework for clinical supervision in speech-language pathology that embeds a mental health perspective within the study of communication sciences and disorders. Method: Key mental health constructs are examined as to how they are applied in traditional versus relational and reflective supervision models. Comparisons between…

[Spongiform encephalitis].

PubMed

Domínguez Carmona, M; Domínguez de la Calle, M

2001-01-01

The authors present a personal interpretation of the pathogeny of prionic processes, showing the role played by heredity. They also present the very surprising fact that a protein codified by a mutant gene can act as transmissible agent in a serious illness opening new chapters to the pathology of a series of important diseases. This is a completely new perspective in the biology.

Dialectical Behavioral Therapy and EMDR for Adolescents in Residential Treatment: A Practical and Theoretical Perspective

ERIC Educational Resources Information Center

Lovelle, Carole

2005-01-01

DBT and EMDR as primary treatment methods provide effective treatment for adolescents in the setting of group residential facilities. Regardless of the intensity of the pathology or the length of stay, these compatible treatment methods provide adolescents with significant decreases in the impact of traumatic memories and increased emotional…

Neural correlates of the impact of control on decision making in pathological gambling.

PubMed

Hudgens-Haney, Matthew E; Hamm, Jordan P; Goodie, Adam S; Krusemark, Elizabeth A; McDowell, Jennifer E; Clementz, Brett A

2013-02-01

Perceived control over a gambling outcome leads individuals to accept more and larger bets, increased risk-taking. Pathological gamblers, however, do not diminish risk-taking when control is absent, suggesting an illusion of control. To evaluate neural correlates of perceived control in gamblers, this study compared magnetoencephalography responses of 36 pathological (PG) and 36 non-pathological gamblers (NPG) during the Georgia Gambling Task. PGs exhibited greater activity in bilateral primary sensory regions. An interaction between pathology and control over the gambling task was observed bilaterally throughout dorsal and ventral visual processing streams, and lateral PFC. NPGs showed decreased activity when control was absent. Groups did not differ in response to potential bet cost. These findings provide neurophysiological evidence that PGs suffer from the pattern of risk-taking associated with perceived control, even when no control exists. They suggest that gambling pathology contributes to differential processing of gambling stimuli other than potential costs or rewards. Copyright © 2012 Elsevier B.V. All rights reserved.

The role of exercise dependence for the relationship between exercise behavior and eating pathology: mediator or moderator?

PubMed

Cook, Brian J; Hausenblas, Heather A

2008-05-01

Our study examined the potential mediating or moderating effect of exercise dependence on the exercise-eating pathology relationship. Female university students (N = 330) completed Internet-based self-report measures of exercise behavior, exercise dependence, and eating pathology. Exercise dependence served as a mediator for the relationship between exercise and eating pathology. This unidirectional causal model suggests that an individual's pathological motivation or compulsion to exercise is the critical mediating component in the exercise-eating pathology relationship. The best target for removing the link between exercise behavior and eating pathology may be reformulating exercise dependence symptoms.

Emotion intensity modulates perspective taking in men and women: an event-related potential study.

PubMed

Luo, Pinchao; Xu, Danna; Huang, Fengjuan; Wei, Fang

2018-06-13

When empathizing with another individual, one can imagine the individual's emotional states and how he or she perceives a situation. However, it is not known to what extent imagining the other differs from imagining oneself under different emotional intensity situations in both sexes. The present study investigated the regulatory effect of emotional intensity on perspective taking in men and women by event-related potentials. The participants were shown pictures of individuals in highly negative (HN), moderately negative, and neutral situations, and instructed to imagine the degree of pain perceived from either a self-perspective or an other-perspective. The results showed that there was no N2 differentiation between the self-perspective and other-perspective under all conditions. Nor was there late positive potential differentiation under moderately negative and neutral conditions in either sex. In contrast, late positive potential induced by HN pictures under the self-perspective was significantly larger than that under the other-perspective only in women. These results suggested that women tended to overestimate the pain of HN stimuli from a self-perspective than from an other-perspective.

Benefits of applying low-temperature plasma treatment to wound care and hemostasis from the viewpoints of physics and pathology

NASA Astrophysics Data System (ADS)

Shimizu, Tetsuji; Ikehara, Yuzuru

2017-12-01

Over the last decade, low-temperature plasma (LTP) technology has reached the life sciences and introduced the benefits of using such technology at atmospheric pressure for medical applications. The active elements from LTP, such as reactive molecular species, charged particles and photons, appear to react with biomolecules on wounds and at bleeding points. This action by LTP might be analogous with semiconductor fabrication techniques such as etching and surface modification. From this perspective, we discuss the general aspects and principles of LTP devices used at atmospheric pressure in wound care and hemostasis as an interdisciplinary fusion of applied physics and pathology.

Guillain-Barré syndrome: What have we learnt during one century? A personal historical perspective.

PubMed

Uncini, A

2016-10-01

We are approaching the centenary of the first description of Guillain-Barré syndrome. The past 30 years had witnessed an amazing progress in the understanding of the immunological and pathological mechanisms of this disorder. We now recognize that Guillain-Barré syndrome is remarkably heterogeneous and under this umbrella term are several variants and subtypes with distinct clinical, electrophysiological and immunopathological features. This review is a historical journey, through a personal perspective, following the milestones that led to the current substantial knowledge of Guillain-Barré syndrome. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Barriers and facilitators to adoption of soft copy interpretation from the user perspective: Lessons learned from filmless radiology for slideless pathology

PubMed Central

Patterson, Emily S.; Rayo, Mike; Gill, Carolina; Gurcan, Metin N.

2011-01-01

Background: Adoption of digital images for pathological specimens has been slower than adoption of digital images in radiology, despite a number of anticipated advantages for digital images in pathology. In this paper, we explore the factors that might explain this slower rate of adoption. Materials and Method: Semi-structured interviews on barriers and facilitators to the adoption of digital images were conducted with two radiologists, three pathologists, and one pathologist's assistant. Results: Barriers and facilitators to adoption of digital images were reported in the areas of performance, workflow-efficiency, infrastructure, integration with other software, and exposure to digital images. The primary difference between the settings was that performance with the use of digital images as compared to the traditional method was perceived to be higher in radiology and lower in pathology. Additionally, exposure to digital images was higher in radiology than pathology, with some radiologists exclusively having been trained and/or practicing with digital images. The integration of digital images both improved and reduced efficiency in routine and non-routine workflow patterns in both settings, and was variable across the different organizations. A comparison of these findings with prior research on adoption of other health information technologies suggests that the barriers to adoption of digital images in pathology are relatively tractable. Conclusions: Improving performance using digital images in pathology would likely accelerate adoption of innovative technologies that are facilitated by the use of digital images, such as electronic imaging databases, electronic health records, double reading for challenging cases, and computer-aided diagnostic systems. PMID:21383925

Studies of the transmissibility of the agent of bovine spongiform encephalopathy to the domestic chicken

PubMed Central

2011-01-01

Background Transmission of the prion disease bovine spongiform encephalopathy (BSE) occurred accidentally to cattle and several other mammalian species via feed supplemented with meat and bone meal contaminated with infected bovine tissue. Prior to United Kingdom controls in 1996 on the feeding of mammalian meat and bone meal to farmed animals, the domestic chicken was potentially exposed to feed contaminated with the causal agent of BSE. Although confirmed prion diseases are unrecorded in avian species a study was undertaken to transmit BSE to the domestic chicken by parenteral and oral inoculations. Transmissibility was assessed by clinical monitoring, histopathological examinations, detection of a putative disease form of an avian prion protein (PrP) in recipient tissues and by mouse bioassay of tissues. Occurrence of a progressive neurological syndrome in the primary transmission study was investigated by sub-passage experiments. Results No clinical, pathological or bioassay evidence of transmission of BSE to the chicken was obtained in the primary or sub-passage experiments. Survival data showed no significant differences between control and treatment groups. Neurological signs observed, not previously described in the domestic chicken, were not associated with significant pathology. The diagnostic techniques applied failed to detect a disease associated form of PrP. Conclusion Important from a risk assessment perspective, the present study has established that the domestic chicken does not develop a prion disease after large parenteral exposures to the BSE agent or after oral exposures equivalent to previous exposures via commercial diets. Future investigations into the potential susceptibility of avian species to mammalian prion diseases require species-specific immunochemical techniques and more refined experimental models. PMID:22093239

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

DTIC Science & Technology

2012-07-16

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

Oral pathology patterns in late farmers of the Central Andes: A comparative perspective between coastal and highland populations.

PubMed

Pezo-Lanfranco, Luis; Peralta, Arturo; Guillén, Sonia; Eggers, Sabine

2017-10-01

Aiming at future comparisons with earlier hunter-gatherers or transitional populations, this paper intends to characterize and describe the oral pathology pattern of late agriculturalists from Central Andes dating to the Late Intermediate Period (LIP) and Inca periods (1000-1532 CE), and identify differences and/or similarities between coastal and highland populations. Although the botanical inventories of the LIP suggest carbohydrate-rich diets and similar components, it has been hypothesized that coastal and highland populations had, nevertheless, substantially different oral pathology patterns. We evaluated 14 indicators of oral pathology from Los Pinos (n=200) and Armatambo (n=25) sites in the Central Coast and two chronological phases from Laguna de los Cóndores site (LC-Inca, n=23; and LC-LIP, n=55), in the Peruvian northern highlands. The results showed a recurrent pattern of oral pathologies characterized by cervical caries (above 30%), extra-occlusal caries (above 60%), high rates of gross-gross caries, high frequency of ante mortem tooth loss, and signals of periodontal disease among these four populations. The diets of the coast were slightly more abrasive than those of the highlands. Oral pathology patterns were compatible with a slightly more cariogenic diet in the coast than in the highlands. In all four populations, those patterns were modulated by other common factors such as consumption of fermented drinks (maize beer - chicha) and the coca leaf chewing habit. Copyright © 2017 Elsevier GmbH. All rights reserved.

Opening Spaces for Dialogue and Re-Envisioning Children's Bathroom in a Preschool: Practitioner Research with Children on a Sensitive and Neglected Area of Concern

ERIC Educational Resources Information Center

Millei, Zsuzsa; Gallagher, Jannelle

2012-01-01

Early years environments play a significant role in children's sense of belonging, wellbeing, and learning. Yet, bathroom spaces have received minimal considerations as part of early years environments. Bathroom practices in early childhood settings are usually examined from medical and developmental perspectives, such as pathologies related to…

Development and Validation of the Pride in Eating Pathology Scale (PEP-S).

PubMed

Faija, Cintia L; Fox, John R E; Tierney, Stephanie; Peters, Sarah; Gooding, Patricia A

2017-01-01

There is a growing body of theoretical and clinical literature highlighting the role of pride in maintaining eating disordered behaviours. Despite its clinical importance, there are no measures to assess feelings of pride associated with eating psychopathology. This study describes the development and validation of the Pride in Eating Pathology Scale (PEP-S), a self-report questionnaire that examines feelings of pride towards eating disordered symptoms (e.g., pride in food restriction, thinness and weight loss). Participants were 390 females, recruited from university and community populations, whose mean age was 26.99 years. Respondents rated pride in eating pathology on a 7-point Likert-scale. Principal Component Analysis indicated that the 60-item scale comprised a four component structure: (1) pride in weight loss, food control and thinness, (2) pride in healthy weight and healthy eating, (3) pride in outperforming others and social recognition and (4) pride in capturing other people's attention due to extreme thinness. These four components explained a total of 65.31% of the variance. The PEP-S demonstrated very good internal reliability (α ranging from 0.88 to 0.98) and very good test-retest reliability over a 3-week time-span (r ranging from 0.81 to 0.93). The PEP-S also showed excellent convergent and discriminant validity. Furthermore, the scale discriminated between women with high and low levels of eating psychopathology. The PEP-S is a psychometrically robust measure of pride in eating pathology. It has the potential to advance theoretical understanding and may also be clinically useful. Copyright © 2015 John Wiley & Sons, Ltd. The PEP-S is a valid, reliable, quick and easy to administer self-report questionnaire that measures pride related to eating pathology. The PEP-S assesses four clinically relevant dimensions: (1) pride in weight loss, food control and thinness, (2) pride in healthy weight and healthy eating, (3) pride in outperforming others and social recognition and (4) pride in capturing other people's attention due to extreme thinness. The PEP-S has very good internal and test-retest reliability, and very good convergent and discriminant validity. The PEP-S distinguishes between women with higher and lower levels of eating psychopathology. The PEP-S makes an important contribution to understanding pride in eating psychopathology, which is essential from both clinical and theoretical perspectives. Copyright © 2015 John Wiley & Sons, Ltd.

An eye witness perspective of the changing patterns of food allergy.

PubMed

Walker-Smith, John

2005-12-01

Food allergy may affect the gastrointestinal tract of children and adults too, albeit less commonly. The changing clinico-pathological expression of such food allergy in children over a 30 year period is related, from the eye witness perspective of a paediatric gastroenterologist in London. Tissue diagnosis by biopsy, related to dietary elimination and challenge has been the basis for the first clinico-pathological descriptions and accurate clinical diagnosis of these syndromes as they affect the gastrointestinal tract. In the 1970s cow's milk sensitive enteropathy presenting as chronic diarrhoea and failure to thrive in infancy often after infective gastroenteritis, especially with enteropathogenic Escherichia coli, was an important problem. By the late 1990s such presentations had become most uncommon in developed communities but they continue to occur in developing communities. By contrast in more recent times, multiple food allergy associated with minor small intestinal enteropathy and gastro-oesophageal reflux in older children has become an important clinical problem in children seen in developed communities. Accompanying these changes has been a dramatic fall in the number of children with clinically severe gastroenteritis with severe dehydration requiring hospital admission. Furthermore, the widespread diagnostic use of endoscopy of the upper and lower gastrointestinal tract in children with multiple biopsies has expanded gastroenterological diagnosis in children. This approach gives information about the oesophagus and ileo-colon not available in the earlier studies, which largely concentrated upon small intestinal biopsies, obtained by Crosby capsule biopsy. So, over this 30 year period clinico-pathological expression has altered but also the diagnostic approach has technically changed.

Management of Acute Upper Gastrointestinal Disease While at Sea.

PubMed

Carr, Matthew J; Oxner, Christopher; Elster, Eric A; Ritter, Eric M; Vicente, Diego

2018-02-06

Management of complex acute surgical pathology in austere environments necessitates rapid evaluation and resource appropriate management to avoid time-associated morbidity and potentially mortality. Obstructive upper gastrointestinal (UGI) pathologies can be particularly challenging and associated with significant morbidity. Herein, we present six patients with UGI obstructions encountered over the course of an 8-mo deployment onboard a US Navy Aircraft Carrier. Each patient presented to our medical department with signs and symptoms of obstructive UGI pathology including one gastric volvulus requiring operative management at sea, one with a new diagnosis of achalasia requiring transportation and continental United States outpatient evaluation, and four patients with food impaction requiring urgent endoscopic management. Although UGI pathology is seldom encountered at sea, definitive surgical interventions, including prompt evaluation and management of these acute pathologies, can be performed in an austere environment. We wish to call attention to these potential encounters in order that underway deployed medical units and supporting resources ashore are prepared and equipped to intervene on acute UGI obstructive pathology. © Association of Military Surgeons of the United States 2018. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Pathological Jealousy: An Interactive Condition.

PubMed

Seeman, Mary V

2016-01-01

The aim of this review is to describe the psychopathology, antecedents, and current management of pathological jealousy from an interpersonal perspective. The Google Scholar database was searched with the following terms: delusional jealousy; morbid jealousy; paranoid jealousy; pathological jealousy; Othello syndrome; delusional disorder-jealous type; conjugal paranoia. From a total of 600 articles, 40 were selected based on their currency and pertinence to the interpersonal aspects of jealousy. Findings were that delusional jealousy is equally prevalent among men and women, with a greater prevalence in the elderly. Antecedents to this condition can be neurologic, drug related, and/or psychological, most often preceded by low self-esteem and excessive dependence on a romantic partner. Pathological jealousy can be triggered by the behavior of the partner and maintained by reasoning biases and by the psychological benefits that it initially bestows on the relationship. In the long run, however, it poses dangerous risks to the patient, the partner, and the imagined rival so that involuntary hospitalization is sometimes required. Treatment recommendations include couple therapy, a strong cognitive focus, antipsychotic medication, and interventions which enhance self-esteem of both partners and which address the solidarity of the existing relationship. Treatment effectiveness does not yet have a firm evidence base.

Rural and remote speech-language pathology service inequities: An Australian human rights dilemma.

PubMed

Jones, Debra M; McAllister, Lindy; Lyle, David M

2018-02-01

Access to healthcare is a fundamental human right for all Australians. Article 19 of the Universal Declaration of Human Rights acknowledges the right to freedom of opinion and to seek, receive and impart information and ideas. Capacities for self-expression and effective communication underpin the realisation of these fundamental human rights. For rural and remote Australian children this realisation is compromised by complex disadvantages and inequities that contribute to communication delays, inequity of access to essential speech-language pathology services and poorer later life outcomes. Localised solutions to the provision of civically engaged, accessible, acceptable and sustainable speech-language pathology services within rural and remote Australian contexts are required if we are to make substantive human rights gains. However, civically engaged and sustained healthcare can significantly challenge traditional professionalised perspectives on how best to design and implement speech-language pathology services that seek to address rural and remote communication needs and access inequities. A failure to engage these communities in the identification of childhood communication delays and solutions to address these delays, ultimately denies children, families and communities of their human rights for healthcare access, self-expression, self-dignity and meaningful inclusion within Australian society.

[Peculiarities of mitosis and nucleolar characteristics of the birch plantlets under antropogenous pollution].

PubMed

Butorina, A K; Kalaev, V N; Karpova, S S

2002-01-01

A study was made of some cytogenetic characteristics (mitotic activity, the level and spectrum of pathological mitosis, nucleolar features in root tip cells) in birch plantlets. The seeds were collected in four districts of Voronezh and in the ecologically clean territory. The index of mitotic activity has a considerable resistance to anthropogenous pollution. In the experimental areas, the level and spectrum of pathological mitosis increase. In contaminated areas we observed changes of nucleolar characteristics (the increased surface area of nucleoli and their higher number in cells, the increased number of cells with highly active types of nucleoli, the appearance of residual nucleoli). These changes can be considered as possible mechanisms of adaptation to stress due to antropogenous pollution. It is suggested that the use of such indices as single nucleolar surface area or the level of pathological mitosis may be perspective for cytogenetic monitoring of the environment, and for prognostification of environmental conditions suitable or unsuitable for the human health.

Perspectives on Games, Computers, and Mental Health: Questions about Paradoxes, Evidences, and Challenges.

PubMed

Desseilles, Martin

2016-01-01

In the field of mental health, games and computerized games present questions about paradoxes, evidences, and challenges. This perspective article offers perspectives and personal opinion about these questions, evidences, and challenges with an objective of presenting several ideas and issues in this rapidly developing field. First, games raise some questions in the sense of the paradox between a game and an issue, as well as the paradox of using an amusing game to treat a serious pathology. Second, games also present evidence in the sense that they involve relationships with others, as well as learning, communication, language, emotional regulation, and hedonism. Third, games present challenges, such as the risk of abuse, the critical temporal period that may be limited to childhood, their important influence on sociocognitive learning and the establishment of social norms, and the risk of misuse of games.

Perspectives on Games, Computers, and Mental Health: Questions about Paradoxes, Evidences, and Challenges

PubMed Central

Desseilles, Martin

2016-01-01

In the field of mental health, games and computerized games present questions about paradoxes, evidences, and challenges. This perspective article offers perspectives and personal opinion about these questions, evidences, and challenges with an objective of presenting several ideas and issues in this rapidly developing field. First, games raise some questions in the sense of the paradox between a game and an issue, as well as the paradox of using an amusing game to treat a serious pathology. Second, games also present evidence in the sense that they involve relationships with others, as well as learning, communication, language, emotional regulation, and hedonism. Third, games present challenges, such as the risk of abuse, the critical temporal period that may be limited to childhood, their important influence on sociocognitive learning and the establishment of social norms, and the risk of misuse of games. PMID:27458390

Prevalence of alcohol-related pathologies at autopsy: Estonian Forensic Study of Alcohol and Premature Death

PubMed Central

Tuusov, Jana; Lang, Katrin; Väli, Marika; Pärna, Kersti; Tõnisson, Mailis; Ringmets, Inge; McKee, Martin; Helander, Anders; Leon, David A

2014-01-01

Aims Alcohol can induce diverse serious pathologies, yet this complexity may be obscured when alcohol-related deaths are classified according to a single underlying cause. We sought to quantify this issue and its implications for analysing mortality data. Design, Setting and Participants Cross-sectional study included 554 men aged 25–54 in Estonia undergoing forensic autopsy in 2008–09. Measurements Potentially alcohol-related pathologies were identified following macroscopic and histological examination. Alcohol biomarkers levels were determined. For a subset (26%), drinking behaviour was provided by next-of-kin. The Estonian Statistics Office provided underlying cause of death. Findings Most deaths (75%) showed evidence of potentially alcohol-related pathologies, and 32% had pathologies in two or more organs. The liver was most commonly affected [60.5%, 95% confidence interval (CI) = 56.3–64.6] followed by the lungs (18.6%, 95% CI = 15.4–22.1), stomach (17.5%, 95% CI = 14.4–20.9), pancreas (14.1%, 95% CI = 11.3–17.3), heart (4.9%, 95% CI = 3.2–7.0) and oesophagus (1.4%, 95% CI = 0.6–2.8). Only a minority with liver pathology had a second pathology. The number of pathologies correlated with alcohol biomarkers (phosphatidylethanol, gamma-glytamyl transpeptidase in blood, ethylglucuronide, ethylsulphate in urine). Despite the high prevalence of liver pathology, few deaths had alcoholic liver disease specified as the underlying cause. Conclusion The majority of 554 men aged 25–54 undergoing forensic autopsy in Estonia in 2008–09 showed evidence of alcohol-related pathology. However, the recording of deaths by underlying cause failed to capture the scale and nature of alcohol-induced pathologies found. PMID:25066373

Principles and management of adrenal cancer

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

Javadpour, N.

1987-01-01

This book provides information on adrenal diseases of latest developments and guides the clinicians in the care of their patients. The book is divided into two parts. The first section gives an overview of the embryology, anatomy, physiology, markers, pathology, imaging and the current progress in the field. The second edition covers specific diseases of the adrenal cortex and medulla. The increasingly significant roles played by steroids, catecholamines, blockers, computed tomography and magnetic resonance are elucidated and discussed. The contents include: Overview of progress; current problems, and perspectives - embryology anatomy, physiology, and biologic markers; pathology; advances in diagnosis; imagingmore » techniques; adrenal disorders in childhood; primary aldosteronism; Cushing's syndrome; carcinoma; pheochromocytoma; neuroblastoma; metastatic disease; surgical management; and subject index.« less

Speech-language pathology students' self-reports on voice training: easier to understand or to do?

PubMed

Lindhe, Christina; Hartelius, Lena

2009-01-01

The aim of the study was to describe the subjective ratings of the course 'Training of the student's own voice and speech', from a student-centred perspective. A questionnaire was completed after each of the six individual sessions. Six speech and language pathology (SLP) students rated how they perceived the practical exercises in terms of doing and understanding. The results showed that five of the six participants rated the exercises as significantly easier to understand than to do. The exercises were also rated as easier to do over time. Results are interpreted within in a theoretical framework of approaches to learning. The findings support the importance of both the physical and reflective aspects of the voice training process.

A biopsychological review of gambling disorder

PubMed Central

Quintero, Gabriel C

2017-01-01

The present review is an overview of previous experimental work on biopsychological aspects of gambling disorder. It includes the topics 1) gambling disorder from the neuroimaging and electroencephalography (EEG) perspective, 2) cognitive, executive functioning, and neuropsychological aspects of gambling disorder, and 3) rodent models of gambling disorder. Penalties and losses in gambling can differ in terms of brain activity. Also, specific patterns of brain activity, brain anatomical traits, EEG responses, and cognitive and executive performance can discriminate pathological gamblers from nonpathological gamblers. Also, pathological gamblers can display dysfunction in such brain areas as the insula, frontal lobe, and orbitofrontal cortex. Pathological gambling is a heterogeneous disorder that can vary depending on the severity of cognition, the style of gambling (strategic or not), the prospect of recovery, proneness to relapse, and proneness to treatment withdrawal. Finally, based on rodent models of gambling, the appropriateness of gambling decision is influenced by the presence of cues, the activity of dopamine receptors, and the activity of some brain areas (infralimbic, prelimbic, or rostral agranular insular cortex). Pathological gamblers differed in terms of frontoparietal brain activation compared to nonpathological gamblers (if winning or losing a game). Pathological gamblers had dysfunctional EEG activity. The severity of gambling was linked to the magnification and content of cognitive distortions. The insula was fundamental in the distortion of cognitions linked to result analysis during gambling activity. PMID:28096672

The Need for Careful Data Collection for Pattern Recognition in Digital Pathology.

PubMed

Marée, Raphaël

2017-01-01

Effective pattern recognition requires carefully designed ground-truth datasets. In this technical note, we first summarize potential data collection issues in digital pathology and then propose guidelines to build more realistic ground-truth datasets and to control their quality. We hope our comments will foster the effective application of pattern recognition approaches in digital pathology.

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

PubMed

Goulet, Carol; Henrie, James; Szymanski, Lynda

2017-04-01

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

Comparative Study of the Pathological Effects of Western Equine Encephalomyelitis Virus in Four Strains of Culex tarsalis Coquillett (Diptera: Culicidae)

PubMed Central

Neira, Marco V.; Mahmood, Farida; Reisen, William K.; James, Calvin B. L.; Romoser, William S.

2014-01-01

Early reports suggested that mosquito cells infected with arboviruses remain viable and undamaged. However, more recent experimental evidence suggests that arboviral infection of mosquito tissues might indeed result in pathological changes, with potential implications for vector survival and virus transmission. Here, we compare the pathological effects of western equine encephalomyelitis virus (WEEV) infection in four strains of Culex tarsalis previously reported to differ in their competence as WEEV vectors. Pathological effects were observed in cells of the midgut epithelium, salivary glands, and eggs. Cell rounding and sloughing of midgut epithelial cells was associated with those strains reported to be the least susceptible to WEEV infection, whereas midgut necrosis and vacuolation upon infection were associated with strains showing higher susceptibility. Although pathological effects were sporadically observed in infected salivary glands, further studies are required to evaluate their impact on vector competence. Additionally, the potential implications of observed C. tarsalis egg infection with WEEV are discussed. PMID:25346928

Anti-inflammatory functions of Houttuynia cordata Thunb. and its compounds: A perspective on its potential role in rheumatoid arthritis.

PubMed

Li, Jun; Zhao, Futao

2015-07-01

The aim of this review was to take a look at the anti-inflammatory functions of Houttuynia cordata Thunb. (HCT) that have been illustrated in the literature and to explore new fields in which HCT could be used in the future. The use of HCT has been described in broad inflammatory domains, where it has exhibited a variety of activities, including antiviral, antibacterial, antiparasitic and immunostimulant activity, with high efficiency, mild features and definite therapeutic effects. The numerous anti-inflammatory functions of HCT have demonstrated that HCT has wide application prospects. New uses of HCT and the full extent of its utilization await further investigation. The basic pathological change of rheumatoid arthritis (RA) is synovial proliferation which leads to joint destruction in the long-term. There are types of drugs that have been used clinically for patients with RA, however, due to their side-effects or high prices their broad usage is limited. A safe and low-cost drug is urgently required to be developed for the clinical usage of patients with RA. Thus, HCT has the potential to be a good candidate in the treatment of rheumatoid arthritis.

Anti-inflammatory functions of Houttuynia cordata Thunb. and its compounds: A perspective on its potential role in rheumatoid arthritis

PubMed Central

LI, JUN; ZHAO, FUTAO

2015-01-01

The aim of this review was to take a look at the anti-inflammatory functions of Houttuynia cordata Thunb. (HCT) that have been illustrated in the literature and to explore new fields in which HCT could be used in the future. The use of HCT has been described in broad inflammatory domains, where it has exhibited a variety of activities, including antiviral, antibacterial, antiparasitic and immunostimulant activity, with high efficiency, mild features and definite therapeutic effects. The numerous anti-inflammatory functions of HCT have demonstrated that HCT has wide application prospects. New uses of HCT and the full extent of its utilization await further investigation. The basic pathological change of rheumatoid arthritis (RA) is synovial proliferation which leads to joint destruction in the long-term. There are types of drugs that have been used clinically for patients with RA, however, due to their side-effects or high prices their broad usage is limited. A safe and low-cost drug is urgently required to be developed for the clinical usage of patients with RA. Thus, HCT has the potential to be a good candidate in the treatment of rheumatoid arthritis. PMID:26170903

Koumine exhibits anxiolytic properties without inducing adverse neurological effects on functional observation battery, open-field and Vogel conflict tests in rodents.

PubMed

Chen, Chao-Jie; Zhong, Zhi-Feng; Xin, Zhi-Ming; Hong, Long-Hui; Su, Yan-Ping; Yu, Chang-Xi

2017-04-01

Koumine, an active alkaloid of neurotoxic plant Gelsemium, has been focused on its therapeutic uses, especially in central nervous system. Nevertheless, less is known about the neurological effects of koumine, which hampers its potential therapeutic exploitation. Moreover, as the anxiolytic potential of Gelsemium has raised many critical issues, its active principles on the anxiolytic and other neurological effects need to be further investigated. Here, we used functional observation battery (FOB) of mice to systematically measure the neurological effects of koumine at the effective doses, and then further confirmed its anxiolytic properties in open-field test (OFT) of mice and Vogel conflict test (VCT) of rats. Koumine exhibited anxiolytic-like activities but did not affect other autonomic, neurological and physical functions in FOB. Furthermore, koumine released anxiolytic responses and anti-punishment action in a manner similar to diazepam in OFT and VCT, respectively. The results constitutes solid set of fundamental data further demonstrating anxiolytic properties of koumine at the therapeutic doses without inducing adverse neurological effects, which supports the perspectives for the development of safe and effective koumine medicine against pathological anxiety.

Understanding Caries From the Oral Microbiome Perspective.

PubMed

Tanner, Anne C R; Kressirer, Christine A; Faller, Lina L

2016-07-01

Dental caries is a major disease of the oral cavity with profound clinical significance. Caries results from a transition of a healthy oral microbiome into an acidogenic community of decreased microbial diversity in response to excessive dietary sugar intake. Microbiological cultivation, molecular identification, gene expression and metabolomic analyses show the importance of the entire microbial community in understanding the role of the microbiome in the pathology of caries.

Interleukin-6 from subchondral bone mesenchymal stem cells contributes to the pathological phenotypes of experimental osteoarthritis

PubMed Central

Wu, Xiaofeng; Cao, Lei; Li, Fan; Ma, Chao; Liu, Guangwang; Wang, Qiugen

2018-01-01

As a main cause of morbidity in the aged population, osteoarthritis (OA) is characterized by cartilage destruction, synovium inflammation, osteophytes, and subchondral bone sclerosis. To date its etiology remains elusive. Recent data highlight an important role of subchondral bone in the onset and progression of OA. Therefore, elucidating the mechanisms underlying abnormal subchondral bone could be of importance in the treatment of OA. Interleukin-6 is a proinflammatory cytokine involved in many physiological and pathological processes. Although in vitro and in vivo studies have indicated that IL-6 is an important cytokine in the physiopathogenesis of OA, its effects on subchondral bone have not been studied in OA animal models. In this study, we aimed to i) investigate the role of IL-6 in the pathological phenotypes of OA subchondral bone MSCs including increase in cell numbers, mineralization disorder and abnormal type I collagen production; ii) explore whether the systemic blockade of IL-6 signaling could alleviate the pathological phenotypes of experimental OA. We found that IL-6 was over-secreted by OA subchondral bone MSCs compared with normal MSCs and IL-6/STAT3 signaling was over-activated in subchondral bone MSCs, which contributed to the pathological phenotypes of OA subchondral bone MSCs. More importantly, systemic inhibition of IL-6/STAT3 signaling with IL-6 antibody or STAT3 inhibitor AG490 decreased the severity of pathological phenotypes of OA subchondral bone MSCs and cartilage lesions in OA. Our findings provide strong evidence for a pivotal role for IL-6 signaling in OA and open up new therapeutic perspectives. PMID:29736207

Quantitative label-free proteomic analysis of human urine to identify novel candidate protein biomarkers for schistosomiasis.

PubMed

Onile, Olugbenga Samson; Calder, Bridget; Soares, Nelson C; Anumudu, Chiaka I; Blackburn, Jonathan M

2017-11-01

Schistosomiasis is a chronic neglected tropical disease that is characterized by continued inflammatory challenges to the exposed population and it has been established as a possible risk factor in the aetiology of bladder cancer. Improved diagnosis of schistosomiasis and its associated pathology is possible through mass spectrometry to identify biomarkers among the infected population, which will influence early detection of the disease and its subtle morbidity. A high-throughput proteomic approach was used to analyse human urine samples for 49 volunteers from Eggua, a schistosomiasis endemic community in South-West, Nigeria. The individuals were previously screened for Schistosoma haematobium and structural bladder pathologies via microscopy and ultrasonography respectively. Samples were categorised into schistosomiasis, schistosomiasis with bladder pathology, bladder pathology, and a normal healthy control group. These samples were analysed to identify potential protein biomarkers. A total of 1306 proteins and 9701 unique peptides were observed in this study (FDR = 0.01). Fifty-four human proteins were found to be potential biomarkers for schistosomiasis and bladder pathologies due to schistosomiasis by label-free quantitative comparison between groups. Thirty-six (36) parasite-derived potential biomarkers were also identified, which include some existing putative schistosomiasis biomarkers that have been previously reported. Some of these proteins include Elongation factor 1 alpha, phosphopyruvate hydratase, histone H4 and heat shock proteins (HSP 60, HSP 70). These findings provide an in-depth analysis of potential schistosoma and human host protein biomarkers for diagnosis of chronic schistosomiasis caused by Schistosoma haematobium and its pathogenesis.

A review of breast cancer survivorship issues from survivors' perspectives.

PubMed

Cho, Jihyoung; Jung, So-Youn; Lee, Jung Eun; Shim, Eun-Jung; Kim, Nam Hyoung; Kim, Zisun; Sohn, Guiyun; Youn, Hyun Jo; Kim, Ku Sang; Kim, Hanna; Lee, Jong Won; Lee, Min Hyuk

2014-09-01

Despite the fact that more breast cancer survivors are currently enjoying longer lifespans, there remains limited knowledge about the factors and issues that are of greatest significance for these survivors, particularly from their perspectives. This review was based on the concept that the topics addressed should focus on the perspectives of current survivors and should be extended to future modalities, which physicians will be able to use to gain a better understanding of the hidden needs of these patients. We intended to choose and review dimensions other than the pathology and the disease process that could have been overlooked during treatment. The eight topics upon which we focused included: delay of treatment and survival outcome; sexual well-being; concerns about childbearing; tailored follow-up; presence of a family history of breast cancer; diet and physical activity for survivors and their families; qualitative approach toward understanding of breast cancer survivorship, and; mobile health care for breast cancer survivors. Through this review, we aimed to examine the present clinical basis of the central issues noted from the survivors' perspectives and suggest a direction for future survivorship-related research.

Improving the pathologic evaluation of lung cancer resection specimens.

PubMed

Osarogiagbon, Raymond U; Hilsenbeck, Holly L; Sales, Elizabeth W; Berry, Allen; Jarrett, Robert W; Giampapa, Christopher S; Finch-Cruz, Clara N; Spencer, David

2015-08-01

Accurate post-operative prognostication and management heavily depend on pathologic nodal stage. Patients with nodal metastasis benefit from post-operative adjuvant chemotherapy, those with mediastinal nodal involvement may also benefit from adjuvant radiation therapy. However, the quality of pathologic nodal staging varies significantly, with major survival implications in large populations of patients. We describe the quality gap in pathologic nodal staging, and provide evidence of its potential reversibility by targeted corrective interventions. One intervention, designed to improve the surgical lymphadenectomy, specimen labeling, and secure transfer between the operating theatre and the pathology laboratory, involves use of pre-labeled specimen collection kits. Another intervention involves application of an improved method of gross dissection of lung resection specimens, to reduce the inadvertent loss of intrapulmonary lymph nodes to histologic examination for metastasis. These corrective interventions are the subject of a regional dissemination and implementation project in diverse healthcare systems in a tri-state region of the United States with some of the highest lung cancer incidence and mortality rates. We discuss the potential of these interventions to significantly improve the accuracy of pathologic nodal staging, risk stratification, and the quality of specimens available for development of stage-independent prognostic markers in lung cancer.

PathEdEx – Uncovering High-explanatory Visual Diagnostics Heuristics Using Digital Pathology and Multiscale Gaze Data

PubMed Central

Shin, Dmitriy; Kovalenko, Mikhail; Ersoy, Ilker; Li, Yu; Doll, Donald; Shyu, Chi-Ren; Hammer, Richard

2017-01-01

Background: Visual heuristics of pathology diagnosis is a largely unexplored area where reported studies only provided a qualitative insight into the subject. Uncovering and quantifying pathology visual and nonvisual diagnostic patterns have great potential to improve clinical outcomes and avoid diagnostic pitfalls. Methods: Here, we present PathEdEx, an informatics computational framework that incorporates whole-slide digital pathology imaging with multiscale gaze-tracking technology to create web-based interactive pathology educational atlases and to datamine visual and nonvisual diagnostic heuristics. Results: We demonstrate the capabilities of PathEdEx for mining visual and nonvisual diagnostic heuristics using the first PathEdEx volume of a hematopathology atlas. We conducted a quantitative study on the time dynamics of zooming and panning operations utilized by experts and novices to come to the correct diagnosis. We then performed association rule mining to determine sets of diagnostic factors that consistently result in a correct diagnosis, and studied differences in diagnostic strategies across different levels of pathology expertise using Markov chain (MC) modeling and MC Monte Carlo simulations. To perform these studies, we translated raw gaze points to high-explanatory semantic labels that represent pathology diagnostic clues. Therefore, the outcome of these studies is readily transformed into narrative descriptors for direct use in pathology education and practice. Conclusion: PathEdEx framework can be used to capture best practices of pathology visual and nonvisual diagnostic heuristics that can be passed over to the next generation of pathologists and have potential to streamline implementation of precision diagnostics in precision medicine settings. PMID:28828200

PathEdEx - Uncovering High-explanatory Visual Diagnostics Heuristics Using Digital Pathology and Multiscale Gaze Data.

PubMed

Shin, Dmitriy; Kovalenko, Mikhail; Ersoy, Ilker; Li, Yu; Doll, Donald; Shyu, Chi-Ren; Hammer, Richard

2017-01-01

Visual heuristics of pathology diagnosis is a largely unexplored area where reported studies only provided a qualitative insight into the subject. Uncovering and quantifying pathology visual and nonvisual diagnostic patterns have great potential to improve clinical outcomes and avoid diagnostic pitfalls. Here, we present PathEdEx, an informatics computational framework that incorporates whole-slide digital pathology imaging with multiscale gaze-tracking technology to create web-based interactive pathology educational atlases and to datamine visual and nonvisual diagnostic heuristics. We demonstrate the capabilities of PathEdEx for mining visual and nonvisual diagnostic heuristics using the first PathEdEx volume of a hematopathology atlas. We conducted a quantitative study on the time dynamics of zooming and panning operations utilized by experts and novices to come to the correct diagnosis. We then performed association rule mining to determine sets of diagnostic factors that consistently result in a correct diagnosis, and studied differences in diagnostic strategies across different levels of pathology expertise using Markov chain (MC) modeling and MC Monte Carlo simulations. To perform these studies, we translated raw gaze points to high-explanatory semantic labels that represent pathology diagnostic clues. Therefore, the outcome of these studies is readily transformed into narrative descriptors for direct use in pathology education and practice. PathEdEx framework can be used to capture best practices of pathology visual and nonvisual diagnostic heuristics that can be passed over to the next generation of pathologists and have potential to streamline implementation of precision diagnostics in precision medicine settings.

Non-coding RNAs and exercise: pathophysiological role and clinical application in the cardiovascular system.

PubMed

Gomes, Clarissa P C; de Gonzalo-Calvo, David; Toro, Rocio; Fernandes, Tiago; Theisen, Daniel; Wang, Da-Zhi; Devaux, Yvan

2018-05-23

There is overwhelming evidence that regular exercise training is protective against cardiovascular disease (CVD), the main cause of death worldwide. Despite the benefits of exercise, the intricacies of their underlying molecular mechanisms remain largely unknown. Non-coding RNAs (ncRNAs) have been recognized as a major regulatory network governing gene expression in several physiological processes and appeared as pivotal modulators in a myriad of cardiovascular processes under physiological and pathological conditions. However, little is known about ncRNA expression and role in response to exercise. Revealing the molecular components and mechanisms of the link between exercise and health outcomes will catalyse discoveries of new biomarkers and therapeutic targets. Here we review the current understanding of the ncRNA role in exercise-induced adaptations focused on the cardiovascular system and address their potential role in clinical applications for CVD. Finally, considerations and perspectives for future studies will be proposed. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Metabonomics Indicates Inhibition of Fatty Acid Synthesis, β-Oxidation, and Tricarboxylic Acid Cycle in Triclocarban-Induced Cardiac Metabolic Alterations in Male Mice.

PubMed

Xie, Wenping; Zhang, Wenpeng; Ren, Juan; Li, Wentao; Zhou, Lili; Cui, Yuan; Chen, Huiming; Yu, Wenlian; Zhuang, Xiaomei; Zhang, Zhenqing; Shen, Guolin; Li, Haishan

2018-02-14

Triclocarban (TCC) has been identified as a new environmental pollutant that is potentially hazardous to human health; however, the effects of short-term TCC exposure on cardiac function are not known. The aim of this study was to use metabonomics and molecular biology techniques to systematically elucidate the molecular mechanisms of TCC-induced effects on cardiac function in mice. Our results show that TCC inhibited the uptake, synthesis, and oxidation of fatty acids, suppressed the tricarboxylic acid (TCA) cycle, and increased aerobic glycolysis levels in heart tissue after short-term TCC exposure. TCC also inhibited the nuclear peroxisome proliferator-activated receptor α (PPARα), confirming its inhibitory effects on fatty acid uptake and oxidation. Histopathology and other analyses further confirm that TCC altered mouse cardiac physiology and pathology, ultimately affecting normal cardiac metabolic function. We elucidate the molecular mechanisms of TCC-induced harmful effects on mouse cardiac metabolism and function from a new perspective, using metabonomics and bioinformatics analysis data.

Natural products, an important resource for discovery of multitarget drugs and functional food for regulation of hepatic glucose metabolism.

PubMed

Li, Jian; Yu, Haiyang; Wang, Sijian; Wang, Wei; Chen, Qian; Ma, Yanmin; Zhang, Yi; Wang, Tao

2018-01-01

Imbalanced hepatic glucose homeostasis is one of the critical pathologic events in the development of metabolic syndromes (MSs). Therefore, regulation of imbalanced hepatic glucose homeostasis is important in drug development for MS treatment. In this review, we discuss the major targets that regulate hepatic glucose homeostasis in human physiologic and pathophysiologic processes, involving hepatic glucose uptake, glycolysis and glycogen synthesis, and summarize their changes in MSs. Recent literature suggests the necessity of multitarget drugs in the management of MS disorder for regulation of imbalanced glucose homeostasis in both experimental models and MS patients. Here, we highlight the potential bioactive compounds from natural products with medicinal or health care values, and focus on polypharmacologic and multitarget natural products with effects on various signaling pathways in hepatic glucose metabolism. This review shows the advantage and feasibility of discovering multicompound-multitarget drugs from natural products, and providing a new perspective of ways on drug and functional food development for MSs.

A high definition Mueller polarimetric endoscope for tissue characterisation

NASA Astrophysics Data System (ADS)

Qi, Ji; Elson, Daniel S.

2016-05-01

The contrast mechanism of medical endoscopy is mainly based on metrics of optical intensity and wavelength. As another fundamental property of light, polarization can not only reveal tissue scattering and absorption information from a different perspective, but can also provide insight into directional tissue birefringence properties to monitor pathological changes in collagen and elastin. Here we demonstrate a low cost wide field high definition Mueller polarimetric endoscope with minimal alterations to a rigid endoscope. We show that this novel endoscopic imaging modality is able to provide a number of image contrast mechanisms besides traditional unpolarized radiation intensity, including linear depolarization, circular depolarization, cross-polarization, directional birefringence and dichroism. This enhances tissue features of interest, and additionally reveals tissue micro-structure and composition, which is of central importance for tissue diagnosis and image guidance for surgery. The potential applications of the Mueller polarimetric endoscope include wide field early epithelial cancer diagnosis, surgical margin detection and energy-based tissue fusion monitoring, and could further benefit a wide range of endoscopic investigations through intra-operative guidance.

Fighting against acquired immunodeficiency syndrome with Chinese medicine: a perspective from China.

PubMed

Tang, Yan-li; Wang, Jie

2011-05-01

Continuing expansion of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) pandemic has been recognized as an exceptional challenge to global health. Taking highly active antiretroviral treatment (HAART), a confirmed effective treatment, has its limitations. While a much cheaper and potential treatment-the Chinese medicine (CM) has not been paid enough attention from the worldwide. We explained the CM viewpoints about pathology and etiology to answer some questions about whether and how CM can treat AIDS. Some herbal formulae and their targeted patterns and common symptoms were also introduced. Chinese government has realized the important role of CM as an independent therapy for early management, bolstering immune-system functions depressed by HIV, and has funded large randomized double-blind controlled clinical trials to more accurately assess the benefits, and valued the fundamental research to establish a quantitative standardization of pattern diagnosis. Researchers of CM are looking for cooperation with all the world's top experts in the areas of AIDS and immunity to strive for victories in the fight against AIDS.

The interferon-dependent orchestration of innate and adaptive immunity after transplantation.

PubMed

Robb, Renee J; Hill, Geoffrey R

2012-06-07

The therapeutic GVL effect after allogeneic stem cell transplantation is limited by the development of GVHD. The ultimate aim of current research is to separate the 2 processes in a meaningful fashion. The IFNs are a pleiotropic group of cytokines that were originally recognized because of their ability to interfere with viral replication. However, it is now established that these cytokines play an important role in orchestrating both innate and adaptive immunity. Multiple studies have investigated the effects of both types I and II IFN on GVHD and GVL in preclinical transplant models. The results indicate variable effects that are dependent on the period of activity within the developing immune response, the presence and type of pretransplant conditioning and the differential mechanisms, and IFN sensitivity of immune pathology within individual target organs during GVHD. This Perspective discusses the current literature on the IFNs and their potential modulation within clinical transplantation, focusing particularly on enhancing the therapeutic GVL effects.

The Emerging Roles of Microparticles in Diabetic Nephropathy.

PubMed

Lu, Chen Chen; Ma, Kun Ling; Ruan, Xiong Zhong; Liu, Bi Cheng

2017-01-01

Microparticles (MPs) are a type of extracellular vesicles (EVs) shed from the outward budding of plasma membranes during cell apoptosis and/or activation. These microsized particles then release specific contents (e.g., lipids, proteins, microRNAs) which are active participants in a wide range of both physiological and pathological processes at the molecular level, e.g., coagulation and angiogenesis, inflammation, immune responses. Research limitations, such as confusing nomenclature and overlapping classification, have impeded our comprehension of these tiny molecules. Diabetic nephropathy (DN) is currently the greatest contributor to end-stage renal diseases (ESRD) worldwide, and its public health impact will continue to grow due to the persistent increase in the prevalence of diabetes mellitus (DM). MPs have recently been considered as potentially involved in DN onset and progression, and this review juxtaposes some of the research updates about the possible mechanisms from several relevant aspects and insights into the therapeutic perspectives of MPs in clinical management and pharmacological treatment of DN patients.

Natural products, an important resource for discovery of multitarget drugs and functional food for regulation of hepatic glucose metabolism

PubMed Central

Wang, Sijian; Wang, Wei; Chen, Qian; Ma, Yanmin; Zhang, Yi; Wang, Tao

2018-01-01

Imbalanced hepatic glucose homeostasis is one of the critical pathologic events in the development of metabolic syndromes (MSs). Therefore, regulation of imbalanced hepatic glucose homeostasis is important in drug development for MS treatment. In this review, we discuss the major targets that regulate hepatic glucose homeostasis in human physiologic and pathophysiologic processes, involving hepatic glucose uptake, glycolysis and glycogen synthesis, and summarize their changes in MSs. Recent literature suggests the necessity of multitarget drugs in the management of MS disorder for regulation of imbalanced glucose homeostasis in both experimental models and MS patients. Here, we highlight the potential bioactive compounds from natural products with medicinal or health care values, and focus on polypharmacologic and multitarget natural products with effects on various signaling pathways in hepatic glucose metabolism. This review shows the advantage and feasibility of discovering multicompound–multitarget drugs from natural products, and providing a new perspective of ways on drug and functional food development for MSs. PMID:29391777

Current perspectives of CASA applications in diverse mammalian spermatozoa.

PubMed

van der Horst, Gerhard; Maree, Liana; du Plessis, Stefan S

2018-03-26

Since the advent of computer-aided sperm analysis (CASA) some four decades ago, advances in computer technology and software algorithms have helped establish it as a research and diagnostic instrument for the analysis of spermatozoa. Despite mammalian spermatozoa being the most diverse cell type known, CASA is a great tool that has the capacity to provide rapid, reliable and objective quantitative assessment of sperm quality. This paper provides contemporary research findings illustrating the scientific and commercial applications of CASA and its ability to evaluate diverse mammalian spermatozoa (human, primates, rodents, domestic mammals, wildlife species) at both structural and functional levels. The potential of CASA to quantitatively measure essential aspects related to sperm subpopulations, hyperactivation, morphology and morphometry is also demonstrated. Furthermore, applications of CASA are provided for improved mammalian sperm quality assessment, evaluation of sperm functionality and the effect of different chemical substances or pathologies on sperm fertilising ability. It is clear that CASA has evolved significantly and is currently superior to many manual techniques in the research and clinical setting.

Consumerism in prenatal diagnosis: a challenge for ethical guidelines

PubMed Central

Henn, W.

2000-01-01

The ethical guidelines for prenatal diagnosis proposed by the World Health Organisation (WHO), as well as by national regulations, only refer to paternity and gender of the fetus as unacceptable, disease-unrelated criteria for prenatal selection, as no other such parameters are at hand so far. This perspective is too narrow because research on complex genetic systems such as cognition and ageing is about to provide clinically applicable tests for genetic constituents of potentially desirable properties such as intelligence or longevity which could be misused as parameters for prenatal diagnosis. Moreover, there is an increasing number of prenatally testable genetic traits, such as heritable deafness, which are generally regarded as pathological but desired by some prospective parents and taken into account as parameters for pro-disability selection. To protect prenatal diagnosis from ethically unacceptable genetic consumerism, guidelines must be clarified as soon as possible and updated towards a worldwide restriction of prenatal genetic testing to immediately disease-determining traits. Key Words: Genetics • prenatal diagnosis • ethics • consumerism PMID:11129845

New Perspectives in Amblyopia Therapy on Adults: A Critical Role for the Excitatory/Inhibitory Balance

PubMed Central

Baroncelli, Laura; Maffei, Lamberto; Sale, Alessandro

2011-01-01

Amblyopia is the most common form of impairment of visual function affecting one eye, with a prevalence of about 1–5% of the total world population. This pathology is caused by early abnormal visual experience with a functional imbalance between the two eyes owing to anisometropia, strabismus, or congenital cataract, resulting in a dramatic loss of visual acuity in an apparently healthy eye and various other perceptual abnormalities, including deficits in contrast sensitivity and in stereopsis. It is currently accepted that, due to a lack of sufficient plasticity within the brain, amblyopia is untreatable in adulthood. However, recent results obtained both in clinical trials and in animal models have challenged this traditional view, unmasking a previously unsuspected potential for promoting recovery after the end of the critical period for visual cortex plasticity. These studies point toward the intracortical inhibitory transmission as a crucial brake for therapeutic rehabilitation and recovery from amblyopia in the adult brain. PMID:22144947

The promise of translational and personalised approaches for paediatric obstructive sleep apnoea: an 'Omics' perspective.

PubMed

Tan, Hui-Leng; Kheirandish-Gozal, Leila; Gozal, David

2014-05-01

Obstructive sleep apnoea (OSA) can result in significant morbidities including the cardiovascular, metabolic and neurocognitive systems. These effects are purportedly mediated via activation of inflammatory cascades and the induction of oxidative stress, ultimately resulting in cellular injury and dysfunction. While great advances have been made in sleep medicine research in the past decades, there are still wide gaps in our knowledge concerning the exact underlying pathophysiological mechanisms of OSA and consequences. Without resolving these issues, the reasons why patients with a similar severity of OSA can have markedly different clinical presentation and end-organ morbidity, that is, phenotype, will continue to remain elusive. This review aims to highlight the recent exciting discoveries in genotype-phenotype interactions, epigenetics, genomics and proteomics related to OSA. Just as PCR revolutionised the field of genetics, the potential power of 'Omics' promises to transform the field of sleep medicine, and provide critical insights into the downstream pathological cascades inherent to OSA, thereby enabling personalised diagnosis and management for this highly prevalent sleep disorder.

Mammalian pre-implantation chromosomal instability: species comparison, evolutionary considerations, and pathological correlations.

PubMed

Carbone, Lucia; Chavez, Shawn L

2015-01-01

Pre-implantation embryo development in mammals begins at fertilization with the migration and fusion of the maternal and paternal pro-nuclei, followed by the degradation of inherited factors involved in germ cell specification and the activation of embryonic genes required for subsequent cell divisions, compaction, and blastulation. The majority of studies on early embryogenesis have been conducted in the mouse or non-mammalian species, often requiring extrapolation of the findings to human development. Given both conserved similarities and species-specific differences, however, even comparison between closely related mammalian species may be challenging as certain aspects, including susceptibility to chromosomal aberrations, varies considerably across mammals. Moreover, most human embryo studies are limited to patient samples obtained from in vitro fertilization (IVF) clinics and donated for research, which are generally of poorer quality and produced with germ cells that may be sub-optimal. Recent technical advances in genetic, epigenetic, chromosomal, and time-lapse imaging analyses of high quality whole human embryos have greatly improved our understanding of early human embryogenesis, particularly at the single embryo and cell level. This review summarizes the major characteristics of mammalian pre-implantation development from a chromosomal perspective, in addition to discussing the technological achievements that have recently been developed to obtain this data. We also discuss potential translation to clinical applications in reproductive medicine and conclude by examining the broader implications of these findings for the evolution of mammalian species and cancer pathology in somatic cells.

Gray matter alterations in chronic pain: A network-oriented meta-analytic approach

PubMed Central

Cauda, Franco; Palermo, Sara; Costa, Tommaso; Torta, Riccardo; Duca, Sergio; Vercelli, Ugo; Geminiani, Giuliano; Torta, Diana M.E.

2014-01-01

Several studies have attempted to characterize morphological brain changes due to chronic pain. Although it has repeatedly been suggested that longstanding pain induces gray matter modifications, there is still some controversy surrounding the direction of the change (increase or decrease in gray matter) and the role of psychological and psychiatric comorbidities. In this study, we propose a novel, network-oriented, meta-analytic approach to characterize morphological changes in chronic pain. We used network decomposition to investigate whether different kinds of chronic pain are associated with a common or specific set of altered networks. Representational similarity techniques, network decomposition and model-based clustering were employed: i) to verify the presence of a core set of brain areas commonly modified by chronic pain; ii) to investigate the involvement of these areas in a large-scale network perspective; iii) to study the relationship between altered networks and; iv) to find out whether chronic pain targets clusters of areas. Our results showed that chronic pain causes both core and pathology-specific gray matter alterations in large-scale networks. Common alterations were observed in the prefrontal regions, in the anterior insula, cingulate cortex, basal ganglia, thalamus, periaqueductal gray, post- and pre-central gyri and inferior parietal lobule. We observed that the salience and attentional networks were targeted in a very similar way by different chronic pain pathologies. Conversely, alterations in the sensorimotor and attention circuits were differentially targeted by chronic pain pathologies. Moreover, model-based clustering revealed that chronic pain, in line with some neurodegenerative diseases, selectively targets some large-scale brain networks. Altogether these findings indicate that chronic pain can be better conceived and studied in a network perspective. PMID:24936419

New paradigms in clonal evolution: punctuated equilibrium in cancer.

PubMed

Cross, William Ch; Graham, Trevor A; Wright, Nicholas A

2016-10-01

Evolutionary theories are themselves subject to evolution. Clonal evolution - the model that describes the initiation and progression of cancer - is entering a period of profound change, brought about largely by technological developments in genome analysis. A flurry of recent publications, using modern mathematical and bioinformatics techniques, have revealed both punctuated and neutral evolution phenomena that are poorly explained by the conventional graduated perspectives. In this review, we propose that a hybrid model, inspired by the evolutionary model of punctuated equilibrium, could better explain these recent observations. We also discuss the conceptual changes and clinical implications of variable evolutionary tempos. 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.

A Review on Ubiquitination of Neurotrophin Receptors: Facts and Perspectives

PubMed Central

Sánchez-Sánchez, Julia; Arévalo, Juan Carlos

2017-01-01

Ubiquitination is a reversible post-translational modification involved in a plethora of different physiological functions. Among the substrates that are ubiquitinated, neurotrophin receptors (TrkA, TrkB, TrkC, and p75NTR) have been studied recently. TrkA is the most studied receptor in terms of its ubiquitination, and different E3 ubiquitin ligases and deubiquitinases have been implicated in its ubiquitination, whereas not much is known about the other neurotrophin receptors aside from their ubiquitination. Additional studies are needed that focus on the ubiquitination of TrkB, TrkC, and p75NTR in order to further understand the role of ubiquitination in their physiological and pathological functions. Here we review what is currently known regarding the ubiquitination of neurotrophin receptors and its physiological and pathological relevance. PMID:28335430

The Neuropsychopharmacology of Pathological Gambling.

PubMed

Zakeri, Kourosh; Potenza, Marc N

2012-02-01

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

Rejoinder: A Construct Validity Approach to the Assessment of Narcissism.

PubMed

Miller, Joshua D; Lynam, Donald R; Campbell, W Keith

2016-02-01

In this rejoinder, we comment on Wright's response to our reanalysis and reinterpretation of the data presented by Wright and colleagues. Two primary differences characterize these perspectives. First, the conceptualization of grandiose narcissism differs such that emotional and ego vulnerability, dysregulation, and pervasive impairments are more characteristic of Wright's conception, likely due to the degree to which it is tied to clinical observations. Our conceptualization is closer to psychopathy and describes an extraverted, dominant, and antagonistic individual who is relatively less likely to be found in clinical settings. Second, our approach to construct validation differs in that we take an empirical perspective that focuses on the degree to which inventories yield scores consistent with a priori predictions. The grandiose dimension of the Pathological Narcissism Inventory (PNI-G) yields data that fail to align with expert ratings of narcissistic personality disorder and grandiose narcissism. We suggest that caution should be taken in treating the PNI-G as a gold standard measure of pathological narcissism, that revision of the PNI-G is required before it can serve as a stand-alone measure of grandiose narcissism, and that the PNI-G should be buttressed by other scales when being used as a measure of grandiose narcissism. © The Author(s) 2015.

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.

Photomatrix LED therapy of extensive cutaneous pathology

NASA Astrophysics Data System (ADS)

Zharov, Vladimir P.; Menyaev, Yulian A.; Zharova, I. Z.; Leviev, Dmitry O.; Tsarev, V. N.; Sarantsev, V. P.; Krusic, Joze

2000-05-01

Standard sources of radiation have not sufficient efficiency at treating spatially extended pathology, especially when pathologic areas involve opposite sides of the human being's body or when they are uneven in shape. The typical examples of such pathology are extensive burns, oedema, inflammatory processes, infectious wounds, actinic keratosis, psoriasis, arthritis and neurological diseases. Superbright LEDs gathered in a matrix and grasping the area of irradiation are the most suitable sources of radiation. This article presents the result of investigation of the effectiveness of various types of the blue-to-infrared spectrum range LED array that allow irradiating a surface with an area from several cm2 to several thousand cm2 including the whole human being's body with the intensity varying from 1 to 100 mW/cm2. Besides the matrixes, composed of separate light diodes, modular systems with separate monolithic hybrid chips with a high density of positioning the sources of radiation are considered. The peculiarities and results of applying such systems to treat oedema, cancer, weight regulation, neurological diseases, different infections diseases in combination with PDT, stomatitis and paradontosis are analyzed. The parameters of the photomatrix LED for different spectral regions and different geometry from flat shape to semispherical and cylindrical are presented. The perspective combination photomatrix LED with another therapeutical devices including photovacuum and photomagnetic therapy are considered.

Correlation between expressions of ERCC1/TS mRNA and effects of gastric cancer to chemotherapy in the short term.

PubMed

Chen, Liqi; Li, Guoli; Li, Jieshou; Fan, Chaogang; Xu, Jian; Wu, Bo; Liu, Kun; Zhang, Caihua

2013-04-01

To study the correlation between expression levels of ERCC1/TS mRNA and the susceptibility of preoperative chemotherapy for patients with gastric cancer. A total of forty cases with advanced gastric cancer of T3-4N1-2M0 were treated with preoperative chemotherapy according to FLEEOX regimen based on endarterial-intravenous coadministration. Sufficient, fresh gastric tissue specimens were obtained with the help of gastroscope, and the expression levels of ERCC1/TS mRNA were detected by qRT-PCR before chemotherapy. The chemotherapeutic response was evaluated with Choi Criteria after chemotherapy, and pathologic remission extent was observed after surgery. The correlation between the expression levels of ERCC1/TS mRNA before chemotherapy and the chemotherapeutic effect based on imageology and pathology was analyzed. The response rate of Chemotherapy in this cohort was 80.0 % based on imageology and 51.43 % based on pathology. The expression levels of ERCC1/TS mRNA were significantly associated with imageology remission extent (P = 0.033, P = 0.025) and pathologic remission extent (P = 0.044, P = 0.016), respectively. The chemotherapeutic effect on patients with low-expression levels of ERCC1/TS mRNA was better. From the perspective of pathology and imageology evaluating the preoperative chemotherapeutic response for patients with gastric cancer, ERCC1 and TS were used as the molecular predictors and provided prognostic information in this study.

Understanding Transgender and Medically Assisted Gender Transition: Feminism as a Critical Resource.

PubMed

Nelson, Jamie Lindemann

2016-11-01

Feminism has fought the trivialization of women's experiences, championed women's security, and insisted on respect for women's choices. In so doing, feminism has developed important perspectives on the complicated connections between what gender means as it plays itself in people's lives, and the inequalities of power and authority that structure much of human experience. Here, I put a few of these perspectives into contact with an issue where the interactions of gender and power are squarely in play: medicine's role in assisting gender transitioning generally and, specifically, the enduring controversy between medicine and many transgender people about the pathologization of transgender and the role of clinicians as gatekeepers to gender-transition interventions. © 2016 American Medical Association. All Rights Reserved.

African American therapists working with African American families: an exploration of the strengths perspective in treatment.

PubMed

Bell-Tolliver, LaVerne; Burgess, Ruby; Brock, Linda J

2009-07-01

With the exception of Hill's (1971, 1999) work, historically much of the literature on African American families has focused more on pathology than strengths. This study used interviews with 30 African American psychotherapists, self-identified as employing a strengths perspective with African American families, to investigate which strengths they identified in the families and how they use those strengths in therapy. Themes emerging from data analysis confirmed the continued importance of the five strengths Hill noted. In addition, two new strengths were identified by the participants: a willingness of a greater number of families to seek therapy, and the importance of family structure. Strategies used in engaging the families in therapy and practice implications for family therapists are discussed.

Aversive Startle Potentiation and Fear Pathology: Mediating Role of Threat Sensitivity and Moderating Impact of Depression

PubMed Central

Yancey, James R.; Vaidyanathan, Uma; Patrick, Christopher J.

2015-01-01

Enhanced startle during exposure to unpleasant cues (aversive startle potentiation; ASP) appears in the RDoC matrix as a physiological index of acute threat response. Increased ASP has been linked to focal fear disorders and to scale measures of dispositional fearfulness (i.e., threat sensitivity; THT+). However, some studies have reported reduced ASP for fear pathology accompanied by major depressive disorder (MDD) or pervasive distress. The current study evaluated whether (a) THT+ as indexed by reported dispositional fearfulness mediates the relationship between fear disorders (when unaccompanied by depression) and ASP, and (b) depression moderates relations of THT+ and fear disorders with ASP. Fear disorder participants without MDD showed enhanced ASP whereas those with MDD (or other distress conditions) showed evidence of reduced ASP. Continuous THT+ scores also predicted ASP, and this association: (a) was likewise moderated by depression/distress, and (b) accounted for the relationship between ASP and fear pathology without MDD. These findings point to a role for the RDoC construct of acute threat, operationalized dispositionally, in enhanced ASP shown by individuals with fear pathology unaccompanied by distress pathology. PMID:25448265

Urine metabolic profiling for the pathogenesis research of erosive oral lichen planus.

PubMed

Li, Xu-Zhao; Yang, Xu-Yan; Wang, Yu; Zhang, Shuai-Nan; Zou, Wei; Wang, Yan; Li, Xiao-Nan; Wang, Ling-Shu; Zhang, Zhi-Gang; Xie, Liang-Zhen

2017-01-01

Oral lichen planus (OLP) is a relatively common chronic immune-pathological and inflammatory disease and potentially oral precancerous lesion. Erosive OLP patients show the higher rate of malignant transformation than patients with non-erosive OLP. Identifying the potential biomarkers related to erosive OLP may help to understand the pathogenesis of the diseases. Metabolic profiles were compared in control and patient subjects with erosive OLP by using ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-QTOF-MS) coupled with pattern recognition methods An integrative analysis was used to identify the perturbed metabolic pathways and pathological processes that may be associated with the disease. In total, 12 modulated metabolites were identified and considered as the potential biomarkers of erosive OLP. Multiple metabolic pathways and pathological processes were involved in erosive OLP. The dysregulations of these metabolites could be used to explain the pathogenesis of the disease, which could also be the potential therapeutic targets for the disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of Ambient Air Pollution Exposure on Olfaction: A Review.

PubMed

Ajmani, Gaurav S; Suh, Helen H; Pinto, Jayant M

2016-11-01

Olfactory dysfunction affects millions of people worldwide. This sensory impairment is associated with neurodegenerative disease and significantly decreased quality of life. Exposure to airborne pollutants has been implicated in olfactory decline, likely due to the anatomic susceptibility of the olfactory nerve to the environment. Historically, studies have focused on occupational exposures, but more recent studies have considered effects from exposure to ambient air pollutants. To examine all relevant human data evaluating a link between ambient pollution exposure and olfaction and to review supporting animal data in order to examine potential mechanisms for pollution-associated olfactory loss. We identified and reviewed relevant articles from 1950 to 2015 using PubMed and Web of Science and focusing on human epidemiologic and pathophysiologic studies. Animal studies were included only to support pertinent data on humans. We reviewed findings from these studies evaluating a relationship between environmental pollutant exposure and olfactory function. We identified and reviewed 17 articles, with 1 additional article added from a bibliography search, for a total of 18 human studies. There is evidence in human epidemiologic and pathologic studies that increased exposure to ambient air pollutants is associated with olfactory dysfunction. However, most studies have used proxies for pollution exposure in small samples of convenience. Human pathologic studies, with supporting animal work, have also shown that air pollution can contact the olfactory epithelium, translocate to the olfactory bulb, and migrate to the olfactory cortex. Pollutants can deposit at each location, causing direct damage and disruption of tissue morphology or inducing local inflammation and cellular stress responses. Ambient air pollution may impact human olfactory function. Additional studies are needed to examine air pollution-related olfactory impacts on the general population using measured pollution exposures and to link pollution exposure with olfactory dysfunction and related pathology. Citation: Ajmani GS, Suh HH, Pinto JM. 2016. Effects of ambient air pollution exposure on olfaction: a review. Environ Health Perspect 124:1683-1693; http://dx.doi.org/10.1289/EHP136.

Speech and language therapy/pathology: perspectives on a gendered profession.

PubMed

Litosseliti, Lia; Leadbeater, Claire

2013-01-01

The speech and language therapy/pathology (SLT/SLP) profession is characterized by extreme 'occupational sex segregation', a term used to refer to persistently male- or female-dominated professions. Men make up only 2.5% of all SLTs in the UK, and a similar imbalance is found in other countries. Despite calls to increase diversity in the allied health professions more generally, research into the reasons for occupational sex segregation and gender as a potential key factor remains scarce. This study aims to explore the potential role of gender/gendered discourses in people's decision to pursue a career in SLT/SLP. It seeks to illustrate how gendered assumptions/expectations/discourses continue to construct SLT as a 'gendered' profession, and to make some recommendations in this area for SLT recruitment and practice. The study adopted a qualitative design which elicited research participants' views, knowledge and experiences (in their own words) in relation to the research questions. Data collection involved two iterative phases: a preliminary data phase--which involved semi-structured interviews with newly qualified SLT graduates and practising SLTs, and the completion of questionnaires by undergraduate SLTs--and a main/focus group phase. In the focus group phase reported in this paper, six focus groups in total were held with SLTs, teachers of SLT, and careers advisors in London, UK. The data were analysed qualitatively using grounded theory principles, thematic analysis and discourse analysis. The findings extend our knowledge and understanding of gender as a parameter of people's motivations and perceptions, which can influence their choice of career (e.g. as regards pay and flexibility). The findings also show that discourses around women as carers, nurturers and communicators constitute key ways through which the SLT profession continues to be constructed as 'women's work'. The topic of structural gender inequalities in the profession was also discussed in the data. Some recommendations for change, with implications for SLT recruitment and practice, were made by the participants themselves. Gender imbalance in SLT needs to be researched further in order to help address inequalities, re-evaluate professional practices and develop service delivery in the profession. This area also needs to be researched via analysis that goes beyond gender distribution in numerical terms to consider the complex perceptions or discourses around gender and work. Cross-disciplinary and comparative perspectives in future research would also be fruitful. © 2012 Royal College of Speech and Language Therapists.

Toxicologic Pathology: The Basic Building Block of Risk Assessment

EPA Science Inventory

Human health risk assessment is a critical factor in many risk management decisions. Evaluation of human health risk requires research the provides information that appropriately characterizes potential hazards from exposure. Pathology endpoints are the central response around ...

Endothelial TWIST1 Promotes Pathological Ocular Angiogenesis

PubMed Central

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

2014-01-01

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

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.

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.

The Challenges of Dysphagia Management and Rehabilitation in Two Complex Cases Post Chemical Ingestion Injury.

PubMed

Rumbach, Anna F; Cremer, Rebecca; Chatwood, Astra; Fink, Sari; Haider, Sadaf; Yee, Michelle

2016-11-01

Dysphagia is common sequelae of chemical ingestion injury, resulting from damage to critical swallowing structures. From a speech-language pathology perspective, this study outlines the physiological deficits in 2 individuals with severe injury (1 woman, acid; 1 man, alkali) and the pattern of dysphagia rehabilitation and recovery. A retrospective chart review of clinical and instrumental assessments was conducted to examine swallow characteristics and speech-language pathology management (compensatory and rehabilitation strategies) at multiple time points. Chemical ingestion injury resulted in severe pharyngeal dysphagia for both participants, warranting speech-language pathology management. Dysphagia was characterized by poor base of tongue mobility and reduced laryngeal excursion. Decreased airway patency and protection, secondary to mucosal sloughing, widespread edema, and structural deficits necessitated tracheostomy. Recovery was complicated by physical alterations of pharyngeal and laryngeal structures (e.g., interarytenoid adhesions) and esophageal strictures. Participant 1 was discharged (Day 135) consuming a texture-modified diet; Participant 2 remained nil by mouth (Day 329). Dysphagia recovery subsequent to chemical ingestion is protracted and complex. Clinical outcomes may be improved through individualized and intensive rehabilitation by speech-language pathologists.

Tinnitus: pathology of synaptic plasticity at the cellular and system levels

PubMed Central

Guitton, Matthieu J.

2012-01-01

Despite being more and more common, and having a high impact on the quality of life of sufferers, tinnitus does not yet have a cure. This has been mostly the result of limited knowledge of the biological mechanisms underlying this adverse pathology. However, the last decade has witnessed tremendous progress in our understanding on the pathophysiology of tinnitus. Animal models have demonstrated that tinnitus is a pathology of neural plasticity, and has two main components: a molecular, peripheral component related to the initiation phase of tinnitus; and a system-level, central component-related to the long-term maintenance of tinnitus. Using the most recent experimental data and the molecular/system dichotomy as a framework, we describe here the biological basis of tinnitus. We then discuss these mechanisms from an evolutionary perspective, highlighting similarities with memory. Finally, we consider how these discoveries can translate into therapies, and we suggest operative strategies to design new and effective combined therapeutic solutions using both pharmacological (local and systemic) and behavioral tools (e.g., using tele-medicine and virtual reality settings). PMID:22408611

Glenohumeral internal rotation deficit in throwing athletes: current perspectives

PubMed Central

Rose, Michael B; Noonan, Thomas

2018-01-01

Glenohumeral internal rotation deficit (GIRD) is an adaptive process in which the throwing shoulder experiences a loss of internal rotation (IR). GIRD has most commonly been defined by a loss of >20° of IR compared to the contralateral shoulder. Total rotational motion of the shoulder is the sum of internal and external rotation and may be more important than the absolute value of IR loss. Pathologic GIRD has been defined as a loss of IR combined with a loss of total rotational motion. The leading pathologic process in GIRD is posterior capsular and rotator-cuff tightness, due to the repetitive cocking that occurs with the overhead throwing motion. GIRD has been associated with numerous pathologic conditions, including posterior superior labral tears, partial articular-sided rotator-cuff tears, and superior labral anterior-to-posterior tears. The mainstay of treatment for patients with GIRD is posterior capsular stretching and strengthening to improve scapular mechanics. In patients who fail nonoperative therapy, shoulder arthroscopy can be performed. Arthroscopic surgery in the high-level throwing athlete should be to restore them to their functional baseline with the minimum amount of intervention possible. PMID:29593438

Quality of life and time perspective in inflammatory bowel disease patients.

PubMed

Laguette, Vanessa; Apostolidis, Themis; Dany, Lionel; Bellon, Nelly; Grimaud, Jean-Charles; Lagouanelle-Simeoni, Marie-Claude

2013-12-01

Numerous studies have shown the impact of inflammatory bowel disease (IBD) on patient quality of life (QoL), but no research has yet examined the impact of time's experience in the assessment of QoL in IBD. Our goal is to explore the links between QoL and time perspective (TP) and the role of TP as a determinant of QoL. Data were collected from 156 patients who completed a questionnaire comprising a generic measure (SF-12) and a specific measure (Inflammatory Bowel Disease Questionnaire) of QoL, a measure of TP (ZTPI) and a collection of socio-demographic and medical data. Correlational analyses illustrated the links between TP and QoL. Regression analyses revealed that records of Past-negative and Present-hedonistic perspectives predicted QoL. Past-negative time perspective seemed to have a deleterious impact, while a Present-hedonistic time perspective predicted a better QoL, and this was irrespective of the level of severity of the disease. These results suggest the importance of considering TP as a determinant of psychological QoL. They corroborate earlier findings on the relationship between TP and QoL associated with other pathologies. The past-negative register, which indicates rumination, tells us about the importance of considering the psychological experience of time in order to improve the QoL of patients.

Overview of the "epigenetic end points in toxicologic pathology and relevance to human health" session of the 2014 Society Of Toxicologic Pathology Annual Symposium.

PubMed

Hoenerhoff, Mark J; Hartke, James

2015-01-01

The theme of the Society of Toxicologic Pathology 2014 Annual Symposium was "Translational Pathology: Relevance of Toxicologic Pathology to Human Health." The 5th session focused on epigenetic end points in biology, toxicity, and carcinogenicity, and how those end points are relevant to human exposures. This overview highlights the various presentations in this session, discussing integration of epigenetics end points in toxicologic pathology studies, investigating the role of epigenetics in product safety assessment, epigenetic changes in cancers, methodologies to detect them, and potential therapies, chromatin remodeling in development and disease, and epigenomics and the microbiome. The purpose of this overview is to discuss the application of epigenetics to toxicologic pathology and its utility in preclinical or mechanistic based safety, efficacy, and carcinogenicity studies. © 2014 by The Author(s).

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

PubMed

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

2016-07-21

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

Nondestructive, epi-illumination surface microscopic characterization of surface discontinuity in bone: a new approach offers a descriptive vocabulary and new insights.

PubMed

Rothschild, Bruce M

2013-04-01

Perspectives are in the eye of the beholder and are expanded with increased scrutiny (e.g., magnification). The term "porosity' for macroscopically or radiologically identifiable discontinuity in bone is so variably applied as to be incomprehensible in its meanings. A closer examination of surface discontinuity seems appropriate. Histological and atomic level analysis of bone alterations misses the forest for the trees and the former destroys the very subject it attempts to characterize. Surface discontinuity was therefore evaluated at the three-dimensional submacroscopic level. An epifluorescent/illumination microscope was used to characterize surface discontinuity in intact specimens of known pathophysiology and/or derivation. The derived perspectives were then utilized to characterize other surface discontinuity. The smooth boundaries of vascular foramen and internal bifurcation, continuity of the expanded base of nerve structures and surrounding elevated rings of Sharpey fibers are all clearly distinguishable from fronts of resorption in erosive arthritis, serpentine discontinuity associated with infectious processes, specific zones of resorption noted in tuberculosis, and structural bone exposure by taphonomic abrasion. These perspectives allow the bone pathology associated with hematoma to be characterized as accentuated Sharpey fiber insertions; maxillary and sphenoid surface discontinuity, as vascular in origin; and periosteal reaction, as manifest by superficial bifurcating channels and in-growth, similar to healing trephanation. Epi-illumination microscopy bridges macroscopic and histological examination, providing greater understanding of the pathology, at no cost to the integrity of the material studied. It explains a number of observed results, while providing discriminatory descriptions of phenomena for which pathophysiology has not yet been clarified. Copyright © 2013 Wiley Periodicals, Inc.

Recommendations for Clinical Pathology Data Generation, Interpretation, and Reporting in Target Animal Safety Studies for Veterinary Drug Development.

PubMed

Siska, William; Gupta, Aradhana; Tomlinson, Lindsay; Tripathi, Niraj; von Beust, Barbara

Clinical pathology testing is routinely performed in target animal safety studies in order to identify potential toxicity associated with administration of an investigational veterinary pharmaceutical product. Regulatory and other testing guidelines that address such studies provide recommendations for clinical pathology testing but occasionally contain outdated analytes and do not take into account interspecies physiologic differences that affect the practical selection of appropriate clinical pathology tests. Additionally, strong emphasis is often placed on statistical analysis and use of reference intervals for interpretation of test article-related clinical pathology changes, with limited attention given to the critical scientific review of clinically, toxicologically, or biologically relevant changes. The purpose of this communication from the Regulatory Affairs Committee of the American Society for Veterinary Clinical Pathology is to provide current recommendations for clinical pathology testing and data interpretation in target animal safety studies and thereby enhance the value of clinical pathology testing in these studies.

Can digital pathology result in cost savings? A financial projection for digital pathology implementation at a large integrated health care organization.

PubMed

Ho, Jonhan; Ahlers, Stefan M; Stratman, Curtis; Aridor, Orly; Pantanowitz, Liron; Fine, Jeffrey L; Kuzmishin, John A; Montalto, Michael C; Parwani, Anil V

2014-01-01

Digital pathology offers potential improvements in workflow and interpretive accuracy. Although currently digital pathology is commonly used for research and education, its clinical use has been limited to niche applications such as frozen sections and remote second opinion consultations. This is mainly due to regulatory hurdles, but also to a dearth of data supporting a positive economic cost-benefit. Large scale adoption of digital pathology and the integration of digital slides into the routine anatomic/surgical pathology "slide less" clinical workflow will occur only if digital pathology will offer a quantifiable benefit, which could come in the form of more efficient and/or higher quality care. As a large academic-based health care organization expecting to adopt digital pathology for primary diagnosis upon its regulatory approval, our institution estimated potential operational cost savings offered by the implementation of an enterprise-wide digital pathology system (DPS). Projected cost savings were calculated for the first 5 years following implementation of a DPS based on operational data collected from the pathology department. Projected savings were based on two factors: (1) Productivity and lab consolidation savings; and (2) avoided treatment costs due to improvements in the accuracy of cancer diagnoses among nonsubspecialty pathologists. Detailed analyses of incremental treatment costs due to interpretive errors, resulting in either a false positive or false negative diagnosis, was performed for melanoma and breast cancer and extrapolated to 10 other common cancers. When phased in over 5-years, total cost savings based on anticipated improvements in pathology productivity and histology lab consolidation were estimated at $12.4 million for an institution with 219,000 annual accessions. The main contributing factors to these savings were gains in pathologist clinical full-time equivalent capacity impacted by improved pathologist productivity and workload distribution. Expanding the current localized specialty sign-out model to an enterprise-wide shared general/subspecialist sign-out model could potentially reduce costs of incorrect treatment by $5.4 million. These calculations were based on annual over and under treatment costs for breast cancer and melanoma estimated to be approximately $26,000 and $11,000/case, respectively, and extrapolated to $21,500/case for other cancer types. The projected 5-year total cost savings for our large academic-based health care organization upon fully implementing a DPS was approximately $18 million. If the costs of digital pathology acquisition and implementation do not exceed this value, the return on investment becomes attractive to hospital administrators. Furthermore, improved patient outcome enabled by this technology strengthens the argument supporting adoption of an enterprise-wide DPS.

Can Digital Pathology Result In Cost Savings? A Financial Projection For Digital Pathology Implementation At A Large Integrated Health Care Organization

PubMed Central

Ho, Jonhan; Ahlers, Stefan M.; Stratman, Curtis; Aridor, Orly; Pantanowitz, Liron; Fine, Jeffrey L.; Kuzmishin, John A.; Montalto, Michael C.; Parwani, Anil V.

2014-01-01

Background: Digital pathology offers potential improvements in workflow and interpretive accuracy. Although currently digital pathology is commonly used for research and education, its clinical use has been limited to niche applications such as frozen sections and remote second opinion consultations. This is mainly due to regulatory hurdles, but also to a dearth of data supporting a positive economic cost-benefit. Large scale adoption of digital pathology and the integration of digital slides into the routine anatomic/surgical pathology “slide less” clinical workflow will occur only if digital pathology will offer a quantifiable benefit, which could come in the form of more efficient and/or higher quality care. Aim: As a large academic-based health care organization expecting to adopt digital pathology for primary diagnosis upon its regulatory approval, our institution estimated potential operational cost savings offered by the implementation of an enterprise-wide digital pathology system (DPS). Methods: Projected cost savings were calculated for the first 5 years following implementation of a DPS based on operational data collected from the pathology department. Projected savings were based on two factors: (1) Productivity and lab consolidation savings; and (2) avoided treatment costs due to improvements in the accuracy of cancer diagnoses among nonsubspecialty pathologists. Detailed analyses of incremental treatment costs due to interpretive errors, resulting in either a false positive or false negative diagnosis, was performed for melanoma and breast cancer and extrapolated to 10 other common cancers. Results: When phased in over 5-years, total cost savings based on anticipated improvements in pathology productivity and histology lab consolidation were estimated at $12.4 million for an institution with 219,000 annual accessions. The main contributing factors to these savings were gains in pathologist clinical full-time equivalent capacity impacted by improved pathologist productivity and workload distribution. Expanding the current localized specialty sign-out model to an enterprise-wide shared general/subspecialist sign-out model could potentially reduce costs of incorrect treatment by $5.4 million. These calculations were based on annual over and under treatment costs for breast cancer and melanoma estimated to be approximately $26,000 and $11,000/case, respectively, and extrapolated to $21,500/case for other cancer types. Conclusions: The projected 5-year total cost savings for our large academic-based health care organization upon fully implementing a DPS was approximately $18 million. If the costs of digital pathology acquisition and implementation do not exceed this value, the return on investment becomes attractive to hospital administrators. Furthermore, improved patient outcome enabled by this technology strengthens the argument supporting adoption of an enterprise-wide DPS. PMID:25250191

Roles of PDE1 in Pathological Cardiac Remodeling and Dysfunction.

PubMed

Chen, Si; Knight, Walter E; Yan, Chen

2018-04-23

Pathological cardiac hypertrophy and dysfunction is a response to various stress stimuli and can result in reduced cardiac output and heart failure. Cyclic nucleotide signaling regulates several cardiac functions including contractility, remodeling, and fibrosis. Cyclic nucleotide phosphodiesterases (PDEs), by catalyzing the hydrolysis of cyclic nucleotides, are critical in the homeostasis of intracellular cyclic nucleotide signaling and hold great therapeutic potential as drug targets. Recent studies have revealed that the inhibition of the PDE family member PDE1 plays a protective role in pathological cardiac remodeling and dysfunction by the modulation of distinct cyclic nucleotide signaling pathways. This review summarizes recent key findings regarding the roles of PDE1 in the cardiac system that can lead to a better understanding of its therapeutic potential.

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

NASA Astrophysics Data System (ADS)

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

2018-03-01

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

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

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

Liu, Xianglin; Wang, Yang; Eisenbach, Markus

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

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

DOE PAGES

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

2017-10-28

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

Identification of novel biomarker and therapeutic target candidates for acute intracerebral hemorrhage by quantitative plasma proteomics.

PubMed

Li, Guo-Chun; Zhang, Lina; Yu, Ming; Jia, Haiyu; Tian, Ting; Wang, Junqin; Wang, Fuqiang; Zhou, Ling

2017-01-01

The systematic mechanisms of acute intracerebral hemorrhage are still unknown and unverified, although many recent researches have indicated the secondary insults. This study was aimed to disclose the pathological mechanism and identify novel biomarker and therapeutic target candidates by plasma proteome. Patients with AICH (n = 8) who demographically matched healthy controls (n = 4) were prospectively enrolled, and their plasma samples were obtained. The TMT-LC-MS/MS-based proteomics approach was used to quantify the differential proteome across plasma samples, and the results were analyzed by Ingenuity Pathway Analysis to explore canonical pathways and the relationship involved in the uploaded data. Compared with healthy controls, there were 31 differentially expressed proteins in the ICH group ( P  < 0.05), of which 21 proteins increased while 10 proteins decreased in abundance. These proteins are involved in 21 canonical pathways. One network with high confidence level was selected by the function network analysis, in which 23 proteins, P38MAPK and NFκB signaling pathways participated. Upstream regulator analysis found two regulators, IL6 and TNF, with an activation z -score. Seven biomarker candidates: APCS, FGB, LBP, MGMT, IGFBP2, LYZ, and APOA4 were found. Six candidate proteins were selected to assess the validity of the results by subsequent Western blotting analysis. Our analysis provided several intriguing pathways involved in ICH, like LXR/RXR activation, acute phase response signaling, and production of NO and ROS in macrophages pathways. The three upstream regulators: IL-6, TNF, LPS, and seven biomarker candidates: APCS, APOA4, FGB, IGFBP2, LBP, LYZ, and MGMT were uncovered. LPS, APOA4, IGFBP2, LBP, LYZ, and MGMT are novel potential biomarkers in ICH development. The identified proteins and pathways provide new perspectives to the potential pathological mechanism and therapeutic targets underlying ICH.

How to grow a kidney: patient-specific kidney organoids come of age.

PubMed

Schmidt-Ott, Kai M

2017-01-01

The notion of regrowing a patient's kidney in a dish has fascinated researchers for decades and has spurred visions of revolutionary clinical applications. Recently, this option has come closer to reality. Key technologies have been developed to generate patient-specific pluripotent stem cells and to edit their genome. Several laboratories have devised protocols to differentiate patient-specific pluripotent stem cells into kidney cells or into in vitro organoids that resemble the kidney with respect to cell types, tissue architecture and disease pathology. This was possible because of rapidly expanding knowledge regarding the cellular and molecular basis of embryonic kidney development. Generating kidney cells or organoids from patient-specific stem cells may prove to be clinically useful in several ways. First, patient-specific kidney cells or organoids could be used to predict an individual's response to stressors, toxins or medications and thereby develop personalized treatment decisions. Second, patient-specific stem cells harbour the individual's genetic defects. This may potentially enable genetic rescue attempts to establish the significance of a genetic defect in a stem cell-derived organoid or it may allow testing of patient-specific targeted therapies for kidney disease in vitro. From a tissue engineering perspective, patient-specific kidney organoids might provide a key advance towards engineering immunocompatible transplantable kidneys. This review article summarizes recent developments in the field and discusses its current limitations and future perspectives. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Emerging Role of Probiotics in the Management of Helicobacter pylori Infection: Histopathologic Perspectives.

PubMed

Emara, Mohamed H; Elhawari, Soha A; Yousef, Salem; Radwan, Mohamed I; Abdel-Aziz, Hesham R

2016-02-01

There is growing evidence from preclinical and clinical studies that emphasizes the efficacy of probiotics in the management of Helicobacter (H) pylori infection; it increased the eradication rate, improved patient clinical manifestations and lowered treatment associated side effects. In this review we documented the potential ability of probiotics to ameliorate H. pylori induced histological features. We searched the available literature for full length articles focusing the role of probiotics on H. pylori induced gastritis from histologic perspectives. Probiotics lowered H. pylori density at the luminal side of epithelium, improved histological inflammatory and activity scores both in the gastric corpus and antrum. This effect persists for long period of time after discontinuation of probiotic supplementation and this is probably through an immune mechanism. The current evidence support the promising role of probiotics in improving H. pylori induced histopathological features both in gastric antrum and corpus and for long periods of time. Because increased density of H. pylori on the gastric mucosa is linked to more severe gastritis and increased incidence of peptic ulcers, we can infer that a reduction of the density might help to decrease the risk of developing pathologies, probably the progression toward atrophic gastritis and gastric adenocarcinoma. These effects together with improving the H. pylori eradication rates and amelioration of treatment related side effects might open the door for probiotics to be added to H. pylori eradication regimens. © 2015 John Wiley & Sons Ltd.

Through Their Lens: The Potential of Photovoice for Documentation of Environmental Perspectives among Kenyan Teachers

ERIC Educational Resources Information Center

Quigley, Cassie F.; Dogbey, James; Che, S. Megan; Hallo, Jeffrey; Womac, Patrick

2014-01-01

This study explores the potential of photovoice for understanding environmental perspectives of teachers in the Narok District of Kenya. The objective of this paper is to share this photo-methodology with environmental educators so they may use it as an innovative methodological tool to understand the construction of environmental perspectives.…

Toxicity, toxicokinetics and biodistribution of dextran stabilized Iron oxide Nanoparticles for biomedical applications.

PubMed

Remya, N S; Syama, S; Sabareeswaran, A; Mohanan, P V

2016-09-10

Advancement in the field of nanoscience and technology has alarmingly raised the call for comprehending the potential health effects caused by deliberate or unintentional exposure to nanoparticles. Iron oxide magnetic nanoparticles have an increasing number of biomedical applications and hence a complete toxicological profile of the nanomaterial is therefore a mandatory requirement prior to its intended usage to ensure safety and to minimize potential health hazards upon its exposure. The present study elucidates the toxicity of in house synthesized Dextran stabilized iron oxide nanoparticles (DINP) in a regulatory perspective through various routes of exposure, its associated molecular, immune, genotoxic, carcinogenic effects and bio distribution profile. Synthesized ferrite nanomaterials were successfully coated with dextran (<25nm) and were physicochemically characterized and subjected to in vitro and in vivo toxicity evaluations. The results suggest that surface coating of ferrite nanoparticles with dextran helps in improvising particle stability in biological environments. The nanoparticles do not seem to induce oxidative stress mediated toxicological effects, nor altered physiological process or behavior changes or visible pathological lesions. Furthermore no anticipated health hazards are likely to be associated with the use of DINP and could be concluded that the synthesized DINP is nontoxic/safe to be used for biomedical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

The hippocampal longitudinal axis-relevance for underlying tau and TDP-43 pathology.

PubMed

Lladó, Albert; Tort-Merino, Adrià; Sánchez-Valle, Raquel; Falgàs, Neus; Balasa, Mircea; Bosch, Beatriz; Castellví, Magda; Olives, Jaume; Antonell, Anna; Hornberger, Michael

2018-06-01

Recent studies suggest that hippocampus has different cortical connectivity and functionality along its longitudinal axis. We sought to elucidate the possible different pattern of atrophy in longitudinal axis of hippocampus between Amyloid/Tau pathology and TDP-43-pathies. Seventy-three presenile subjects were included: Amyloid/Tau group (33 Alzheimer's disease with confirmed cerebrospinal fluid [CSF] biomarkers), probable TDP-43 group (7 semantic variant progressive primary aphasia, 5 GRN and 2 C9orf72 mutation carriers) and 26 healthy controls. We conducted a region-of-interest voxel-based morphometry analysis on the hippocampal longitudinal axis, by contrasting the groups, covarying with CSF biomarkers (Aβ 42 , total tau, p-tau) and covarying with episodic memory scores. Amyloid/Tau pathology affected mainly posterior hippocampus while anterior left hippocampus was more atrophied in probable TDP-43-pathies. We also observed a significant correlation of posterior hippocampal atrophy with Alzheimer's disease CSF biomarkers and visual memory scores. Taken together, these data suggest that there is a potential differentiation along the hippocampal longitudinal axis based on the underlying pathology, which could be used as a potential biomarker to identify the underlying pathology in different neurodegenerative diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

Negative events and their potential risk of precipitating pathological forms of dental anxiety.

PubMed

Oosterink, F M D; de Jongh, A; Aartman, I H A

2009-05-01

The purpose of the present study was to assess which types of experiences are most closely associated with pathological forms of dental anxiety. Data came from a sample of dental patients (n=1462). Pathological dental anxiety was operationalized in two ways: (1) a score of > or =36 on the Short form of the Dental Anxiety Inventory (S-DAI; high dental anxiety, HDA), or (2) fulfilling the screening criteria of specific phobia (DSM-IV-TR; dental phobia, DP). A wide variety of dental experiences appeared to be significantly related with both HDA and DP, while general traumatic experiences were not. No differences were found between women and men. Retrospective accounts of dental experiences involving helplessness were most strongly associated with having HDA [OR=8.2] and positive screens of DP [OR=16.2]. The results suggest that disruptive emotional and interoceptive reactions during dental treatment (particularly helplessness) have the greatest potential risk of precipitating pathological forms of dental anxiety.

Fractal lacunarity of trabecular bone and magnetic resonance imaging: New perspectives for osteoporotic fracture risk assessment

PubMed Central

Zaia, Annamaria

2015-01-01

Osteoporosis represents one major health condition for our growing elderly population. It accounts for severe morbidity and increased mortality in postmenopausal women and it is becoming an emerging health concern even in aging men. Screening of the population at risk for bone degeneration and treatment assessment of osteoporotic patients to prevent bone fragility fractures represent useful tools to improve quality of life in the elderly and to lighten the related socio-economic impact. Bone mineral density (BMD) estimate by means of dual-energy X-ray absorptiometry is normally used in clinical practice for osteoporosis diagnosis. Nevertheless, BMD alone does not represent a good predictor of fracture risk. From a clinical point of view, bone microarchitecture seems to be an intriguing aspect to characterize bone alteration patterns in aging and pathology. The widening into clinical practice of medical imaging techniques and the impressive advances in information technologies together with enhanced capacity of power calculation have promoted proliferation of new methods to assess changes of trabecular bone architecture (TBA) during aging and osteoporosis. Magnetic resonance imaging (MRI) has recently arisen as a useful tool to measure bone structure in vivo. In particular, high-resolution MRI techniques have introduced new perspectives for TBA characterization by non-invasive non-ionizing methods. However, texture analysis methods have not found favor with clinicians as they produce quite a few parameters whose interpretation is difficult. The introduction in biomedical field of paradigms, such as theory of complexity, chaos, and fractals, suggests new approaches and provides innovative tools to develop computerized methods that, by producing a limited number of parameters sensitive to pathology onset and progression, would speed up their application into clinical practice. Complexity of living beings and fractality of several physio-anatomic structures suggest fractal analysis as a promising approach to quantify morpho-functional changes in both aging and pathology. In this particular context, fractal lacunarity seems to be the proper tool to characterize TBA texture as it is able to describe both discontinuity of bone network and sizes of bone marrow spaces, whose changes are an index of bone fracture risk. In this paper, an original method of MRI texture analysis, based on TBA fractal lacunarity is described and discussed in the light of new perspectives for early diagnosis of osteoporotic fractures. PMID:25793162

Correlation of Insurance, Race, and Ethnicity with Pathologic Risk in a Controlled Retinoblastoma Cohort: A Children's Oncology Group Study.

PubMed

Green, Adam L; Chintagumpala, Murali; Krailo, Mark; Langholz, Bryan; Albert, Daniel; Eagle, Ralph; Cockburn, Myles; Chevez-Barrios, Patricia; Rodriguez-Galindo, Carlos

2016-08-01

To determine whether insurance status, race, and ethnicity correlate with increased retinoblastoma invasiveness as a marker of both risk and time to diagnosis. Retrospective case-control study. All 203 patients from the United States enrolled in the Children's Oncology Group (COG) trial ARET0332, a study of patients with unilateral retinoblastoma requiring enucleation. All surgical specimens underwent pathologic review to determine the presence of well-defined histopathologic features correlating with a higher risk of disease progression. Insurance status, race, and ethnicity were compiled from the study record for each patient. On institutional pathologic review, nonprivate insurance, nonwhite race, and Hispanic ethnicity all correlated significantly with a greater rate of high-risk pathologic findings. Hispanic ethnicity remained a significant predictor on multivariate analysis. On central pathologic review, these correlations remained but did not reach statistical significance. The differences in results from institutional versus central pathologic reviews appeared to be due to a higher likelihood of patients in minority groups of being misclassified as high risk by institutional pathologists. In this controlled study population of patients with retinoblastoma who had central pathologic review, our findings suggest a higher rate of more advanced disease associated with nonprivate insurance, nonwhite race, and Hispanic ethnicity; these findings may be due to delays in diagnosis for these groups. Future work should use direct methods to study the impact of other variables, including English-language proficiency and socioeconomic status. Further effort also should focus on where in the diagnostic process potential delays exist, so that interventions can be designed to overcome barriers to care for these groups. In addition, potential systematic differences in pathologic reads based on demographic variables deserve further study. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Histochemical stains as promising means for the laser histochemical surgery of a number of pathologies

NASA Astrophysics Data System (ADS)

Piruzyan, L. A.; Mikhailovskiy, Ye. M.; Piruzyan, A. L.

1999-12-01

The directions of laboratory and clinical studies oriented to experimental confirmation of the priority concept of `laser histochemical surgery' are presented. The goal of the studies is reproduction on experimental model of a number of pathologies (in vivo and in vitro) of the `sensitization to laser radiation by staining' effect. Testing of the histochemical stains as sensitizers to laser irradiation of their `address substrates', i.e. vitally stained intracellular structures which participate in the pathologic processes evolution is under planning. The processes include: (a) metabolic disorders in the brain cells, i.e. disseminated sclerosis; (b) generalized metabolic disorders- -mucopolysaccharidosis and collagenosises (periarteritis nodosa, rheumatism, rheumatoid arthritis, sclerodermia); (3) metabolic disorders in individual organs--vessel atherosclerosis, hypercholesterolemia, myocardial infarction, cardiosclerosis, caries and parodontosis. The conditions of the studies are detailed in the recommendations along the positions: (1) disease name; (2) disease characteristics: (a) pathomorphologic, (b) biochemical; (3) stains revealing the disease signs and recommended for testing; (4) `address substrates' of the stains that are targets for laser radiation; (5) lasers recommended for the testing after the cells staining in vivo in the corresponding pathology; (6) experimental models of the pathologies suggested for the testing; (7) criteria of the stain efficiency as target sensitizer to the laser light (criteria of the `laser sensitization by staining' efficiency). Possible perspectives for the experimental clinical medicine are indicated of common histochemical stains and lasers use and of practice introduction of the `laser histochemical surgery' in the case the described concept is confirmed in experiments and clinically.

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.

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

PubMed

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

2008-11-01

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

Is the Internet gaming-addicted brain close to be in a pathological state?

PubMed

Park, Chang-Hyun; Chun, Ji-Won; Cho, Huyn; Jung, Young-Chul; Choi, Jihye; Kim, Dai Jin

2017-01-01

Internet gaming addiction (IGA) is becoming a common and widespread mental health concern. Although IGA induces a variety of negative psychosocial consequences, it is yet ambiguous whether the brain addicted to Internet gaming is considered to be in a pathological state. We investigated IGA-induced abnormalities of the brain specifically from the network perspective and qualitatively assessed whether the Internet gaming-addicted brain is in a state similar to the pathological brain. Topological properties of brain functional networks were examined by applying a graph-theoretical approach to analyzing functional magnetic resonance imaging data acquired during a resting state in 19 IGA adolescents and 20 age-matched healthy controls. We compared functional distance-based measures, global and local efficiency of resting state brain functional networks between the two groups to assess how the IGA subjects' brain was topologically altered from the controls' brain. The IGA subjects had severer impulsiveness and their brain functional networks showed higher global efficiency and lower local efficiency relative to the controls. These topological differences suggest that IGA induced brain functional networks to shift toward the random topological architecture, as exhibited in other pathological states. Furthermore, for the IGA subjects, the topological alterations were specifically attributable to interregional connections incident on the frontal region, and the degree of impulsiveness was associated with the topological alterations over the frontolimbic connections. The current findings lend support to the proposition that the Internet gaming-addicted brain could be in the state similar to pathological states in terms of topological characteristics of brain functional networks. © 2015 Society for the Study of Addiction.

Developing Disease-Modifying Treatments in Alzheimer's Disease - A Perspective from Roche and Genentech.

PubMed

Doody, R

2017-01-01

Alzheimer's disease (AD) is a chronic neurodegenerative disease for which no preventative or disease-modifying treatments currently exist. Pathological hallmarks include amyloid plaques and neurofibrillary tangles composed of hyper-phosphorylated tau protein. Evidence suggests that both pathologies are self-propagating once established. However, the lag time between neuropathological changes in the brain and the onset of even subtle clinical symptomatology means that patients are often diagnosed late when pathology, and neurodegeneration secondary to these changes, may have been established for several years. Complex pathological pathways associated with susceptibility to AD and changes that occur downstream of the neuropathologic process further contribute to the challenging endeavour of developing novel disease-modifying therapy. Recognising this complexity, effective management of AD must include reliable screening and early diagnosis in combination with effective therapeutic management of the pathological processes. Roche and Genentech are committed to addressing these unmet needs through developing a comprehensive portfolio of diagnostics and novel therapies. Beginning with the most scientifically supported targets, this approach includes two targeted amyloid-β monoclonal antibody therapies, crenezumab and gantenerumab, and an anti-tau monoclonal antibody, RO7105705, as well as a robust biomarker platform to aid in the early identification of people at risk or in the early stages of AD. Identification and implementation of diagnostic tools will support the enrolment of patients into clinical trials; furthermore, these tools should also support evaluation of the clinical efficacy and safety profile of the novel therapeutic agents tested in these trials. This review discusses the therapeutic agents currently under clinical development.

A theoretical study on predicted protein targets of apple polyphenols and possible mechanisms of chemoprevention in colorectal cancer

PubMed Central

Scafuri, Bernardina; Marabotti, Anna; Carbone, Virginia; Minasi, Paola; Dotolo, Serena; Facchiano, Angelo

2016-01-01

We investigated the potential role of apple phenolic compounds in human pathologies by integrating chemical characterization of phenolic compounds in three apple varieties, computational approaches to identify potential protein targets of the compounds, bioinformatics analyses on data from public archive of gene expression data, and functional analyses to hypothesize the effects of the selected compounds in molecular pathways. Starting by the analytic characterization of phenolic compounds in three apple varieties, i.e. Annurca, Red Delicious, and Golden Delicious, we used computational approaches to verify by reverse docking the potential protein targets of the identified compounds. Direct docking validation of the potential protein-ligand interactions has generated a short list of human proteins potentially bound by the apple phenolic compounds. By considering the known chemo-preventive role of apple antioxidants’ extracts against some human pathologies, we performed a functional analysis by comparison with experimental gene expression data and interaction networks, obtained from public repositories. The results suggest the hypothesis that chemo-preventive effects of apple extracts in human pathologies, in particular for colorectal cancer, may be the interference with the activity of nucleotide metabolism and methylation enzymes, similarly to some classes of anticancer drugs. PMID:27587238

[The inter-university learning website: a national university network for online teaching of pathology].

PubMed

Gauchotte, Guillaume; Ameisen, David; Boutonnat, Jean; Battistella, Maxime; Copie, Christiane; Garcia, Stéphane; Rigau, Valérie; Galateau-Sallé, Françoise; Terris, Benoit; Vergier, Béatrice; Wendum, Dominique; Bertheau, Philippe

2013-06-01

Building online teaching materials is a highly time and energy consuming task for teachers of a single university. With the help of the Collège des pathologistes, we initiated a French national university network for building mutualized online teaching pathology cases, tests and other pedagogic resources. Nineteen French universities are associated to this project, initially funded by UNF3S (http://www.unf3s.org/). One national e-learning Moodle platform (http://virtual-slides.univ-paris7.fr/moodle/) contains texts, medias and URL pointing toward decentralized virtual slides. The Moodle interface has been explained to the teachers since september 2011 using web-based conferences with screen-sharing. The following contents have been created: 20 clinical cases, several tests with multiple choices and short answer questions, and gross examination videos. A survey with 16 teachers and students showed a 94 % satisfaction rate, most of the 16 participants being favorable to the development of e-learning, in parallel with other courses in classroom. These tools will be further developed for the different study levels of pathology. In conclusion, these tools offer very interesting perspectives for pathology teaching. The organization of a national inter-university network is a useful way to create and share numerous and good-quality pedagogic resources. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Virtual slides in peer reviewed, open access medical publication

PubMed Central

2011-01-01

Background Application of virtual slides (VS), the digitalization of complete glass slides, is in its infancy to be implemented in routine diagnostic surgical pathology and to issues that are related to tissue-based diagnosis, such as education and scientific publication. Approach Electronic publication in Pathology offers new features of scientific communication in pathology that cannot be obtained by conventional paper based journals. Most of these features are based upon completely open or partly directed interaction between the reader and the system that distributes the article. One of these interactions can be applied to microscopic images allowing the reader to navigate and magnify the presented images. VS and interactive Virtual Microscopy (VM) are a tool to increase the scientific value of microscopic images. Technology and Performance The open access journal Diagnostic Pathology http://www.diagnosticpathology.org has existed for about five years. It is a peer reviewed journal that publishes all types of scientific contributions, including original scientific work, case reports and review articles. In addition to digitized still images the authors of appropriate articles are requested to submit the underlying glass slides to an institution (DiagnomX.eu, and Leica.com) for digitalization and documentation. The images are stored in a separate image data bank which is adequately linked to the article. The normal review process is not involved. Both processes (peer review and VS acquisition) are performed contemporaneously in order to minimize a potential publication delay. VS are not provided with a DOI index (digital object identifier). The first articles that include VS were published in March 2011. Results and Perspectives Several logistic constraints had to be overcome until the first articles including VS could be published. Step by step an automated acquisition and distribution system had to be implemented to the corresponding article. The acceptance of VS by the reader is high as well as by the authors. Of specific value are the increased confidence to and reputation of authors as well as the presented information to the reader. Additional associated functions such as access to author-owned related image collections, reader-controlled automated image measurements and image transformations are in preparation. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1232133347629819. PMID:22182763

Spatial variability in T-tubule and electrical remodeling of left ventricular epicardium in mouse hearts with transgenic Gαq overexpression-induced pathological hypertrophy

PubMed Central

Tao, Wen; Shi, Jianjian; Dorn, Gerald W.; Wei, Lei; Rubart, Michael

2012-01-01

Pathological left ventricular hypertrophy (LVH) is consistently associated with prolongation of the ventricular action potentials. A number of previous studies, employing various experimental models of hypertrophy, have revealed marked differences in the effects of hypertrophy on action potential duration (APD) between myocytes from endocardial and epicardial layers of the LV free wall. It is not known, however, whether pathological LVH is also accompanied by redistribution of APD among myocytes from the same layer in the LV free wall. In the experiments here, LV epicardial action potential remodeling was examined in a mouse model of decompensated LVH, produced by cardiac-restricted transgenic Gαq overexpression. Confocal linescanning-based optical recordings of propagated action potentials from individual in situ cardiomyocytes across the outer layer of the anterior LV epicardium demonstrated spatially non-uniform action potential prolongation in transgenic hearts, giving rise to alterations in spatial dispersion of epicardial repolarization. Local density and distribution of anti-Cx43 mmune reactivity in Gαq hearts were unchanged compared to wild-type hearts, suggesting preservation of intercellular coupling. Confocal microscopy also revealed heterogeneous disorganization of T-tubules in epicardial cardiomyocytes in situ. These data provide evidence of the existence of significant electrical and structural heterogeneity within the LV epicardial layer of hearts with transgenic Gαq overexpression-induced hypertrophy, and further support the notion that a small portion of electrically well connected LV tissue can maintain dispersion of action potential duration through heterogeneity in the activities of sarcolemmal ionic currents that control repolarization. It remains to be examined whether other experimental models of pathological LVH, including pressure overload LVH, similarly exhibit alterations in T-tubule organization and/or dispersion of repolarization within distinct layers of LV myocardium. PMID:22728217

Probing Compulsive and Impulsive Behaviors, from Animal Models to Endophenotypes: A Narrative Review

PubMed Central

Fineberg, Naomi A; Potenza, Marc N; Chamberlain, Samuel R; Berlin, Heather A; Menzies, Lara; Bechara, Antoine; Sahakian, Barbara J; Robbins, Trevor W; Bullmore, Edward T; Hollander, Eric

2010-01-01

Failures in cortical control of fronto-striatal neural circuits may underpin impulsive and compulsive acts. In this narrative review, we explore these behaviors from the perspective of neural processes and consider how these behaviors and neural processes contribute to mental disorders such as obsessive–compulsive disorder (OCD), obsessive–compulsive personality disorder, and impulse-control disorders such as trichotillomania and pathological gambling. We present findings from a broad range of data, comprising translational and human endophenotypes research and clinical treatment trials, focussing on the parallel, functionally segregated, cortico-striatal neural projections, from orbitofrontal cortex (OFC) to medial striatum (caudate nucleus), proposed to drive compulsive activity, and from the anterior cingulate/ventromedial prefrontal cortex to the ventral striatum (nucleus accumbens shell), proposed to drive impulsive activity, and the interaction between them. We suggest that impulsivity and compulsivity each seem to be multidimensional. Impulsive or compulsive behaviors are mediated by overlapping as well as distinct neural substrates. Trichotillomania may stand apart as a disorder of motor-impulse control, whereas pathological gambling involves abnormal ventral reward circuitry that identifies it more closely with substance addiction. OCD shows motor impulsivity and compulsivity, probably mediated through disruption of OFC-caudate circuitry, as well as other frontal, cingulate, and parietal connections. Serotonin and dopamine interact across these circuits to modulate aspects of both impulsive and compulsive responding and as yet unidentified brain-based systems may also have important functions. Targeted application of neurocognitive tasks, receptor-specific neurochemical probes, and brain systems neuroimaging techniques have potential for future research in this field. PMID:19940844

Is the ADHD brain wired differently? A review on structural and functional connectivity in attention deficit hyperactivity disorder.

PubMed

Konrad, Kerstin; Eickhoff, Simon B

2010-06-01

In recent years, a change in perspective in etiological models of attention deficit hyperactivity disorder (ADHD) has occurred in concordance with emerging concepts in other neuropsychiatric disorders such as schizophrenia and autism. These models shift the focus of the assumed pathology from regional brain abnormalities to dysfunction in distributed network organization. In the current contribution, we report findings from functional connectivity studies during resting and task states, as well as from studies on structural connectivity using diffusion tensor imaging, in subjects with ADHD. Although major methodological limitations in analyzing connectivity measures derived from noninvasive in vivo neuroimaging still exist, there is convergent evidence for white matter pathology and disrupted anatomical connectivity in ADHD. In addition, dysfunctional connectivity during rest and during cognitive tasks has been demonstrated. However, the causality between disturbed white matter architecture and cortical dysfunction remains to be evaluated. Both genetic and environmental factors might contribute to disruptions in interactions between different brain regions. Stimulant medication not only modulates regionally specific activation strength but also normalizes dysfunctional connectivity, pointing to a predominant network dysfunction in ADHD. By combining a longitudinal approach with a systems perspective in ADHD in the future, it might be possible to identify at which stage during development disruptions in neural networks emerge and to delineate possible new endophenotypes of ADHD. (c) 2010 Wiley-Liss, Inc.

Gene therapy in liver diseases: state-of-the-art and future perspectives.

PubMed

Domvri, Kalliopi; Zarogoulidis, Paul; Porpodis, Konstantinos; Koffa, Maria; Lambropoulou, Maria; Kakolyris, Stylianos; Kolios, George; Zarogoulidis, Konstantinos; Chatzaki, Ekaterini

2012-12-01

Gene therapy is a fundamentally novel therapeutic approach that involves introducing genetic material into target cells in order to fight or prevent disease. A number of different strategies of gene therapy are tested at experimental and clinical levels, including: a) replacing a mutated gene that causes disease with a healthy copy of the gene, b) inactivating a mutated gene that its improper function causes pathogenesis, c) introducing a new gene coding a therapeutic compound to fight a disease, d) introducing to the target organ an enzyme converting an inactive pro-drug to its cytotoxic metabolite. In gene therapy, the transcriptional machinery of the patient is used to produce the active factor that exerts the intended therapeutic effect, ideally in a permanent, tissue-specific and manageable way. The liver is a major target for gene therapy, presenting inherited metabolic defects of single-gene etiology, but also severe multifactorial pathologies with limited therapeutic options such as hepatocellular carcinoma. The initial promising results from gene therapy strategies in liver diseases were followed by skepticism on the actual clinical value due to specificity, efficacy, toxicity and immune limitations, but are recently re-evaluated due to progress in vector technology and monitoring techniques. The significant amount of experimental data along with the available information from clinical trials are systematically reviewed here and presented per pathological entity. Finally, future perspectives of gene therapy protocols in hepatology are summarized.

Emerging Themes in Image Informatics and Molecular Analysis for Digital Pathology.

PubMed

Bhargava, Rohit; Madabhushi, Anant

2016-07-11

Pathology is essential for research in disease and development, as well as for clinical decision making. For more than 100 years, pathology practice has involved analyzing images of stained, thin tissue sections by a trained human using an optical microscope. Technological advances are now driving major changes in this paradigm toward digital pathology (DP). The digital transformation of pathology goes beyond recording, archiving, and retrieving images, providing new computational tools to inform better decision making for precision medicine. First, we discuss some emerging innovations in both computational image analytics and imaging instrumentation in DP. Second, we discuss molecular contrast in pathology. Molecular DP has traditionally been an extension of pathology with molecularly specific dyes. Label-free, spectroscopic images are rapidly emerging as another important information source, and we describe the benefits and potential of this evolution. Third, we describe multimodal DP, which is enabled by computational algorithms and combines the best characteristics of structural and molecular pathology. Finally, we provide examples of application areas in telepathology, education, and precision medicine. We conclude by discussing challenges and emerging opportunities in this area.

Emerging Themes in Image Informatics and Molecular Analysis for Digital Pathology

PubMed Central

Bhargava, Rohit; Madabhushi, Anant

2017-01-01

Pathology is essential for research in disease and development, as well as for clinical decision making. For more than 100 years, pathology practice has involved analyzing images of stained, thin tissue sections by a trained human using an optical microscope. Technological advances are now driving major changes in this paradigm toward digital pathology (DP). The digital transformation of pathology goes beyond recording, archiving, and retrieving images, providing new computational tools to inform better decision making for precision medicine. First, we discuss some emerging innovations in both computational image analytics and imaging instrumentation in DP. Second, we discuss molecular contrast in pathology. Molecular DP has traditionally been an extension of pathology with molecularly specific dyes. Label-free, spectroscopic images are rapidly emerging as another important information source, and we describe the benefits and potential of this evolution. Third, we describe multimodal DP, which is enabled by computational algorithms and combines the best characteristics of structural and molecular pathology. Finally, we provide examples of application areas in telepathology, education, and precision medicine. We conclude by discussing challenges and emerging opportunities in this area. PMID:27420575

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.

Pathology resident and fellow education in a time of disruptive technologies.

PubMed

Ziai, James M; Smith, Brian R

2012-12-01

The development of disruptive technologies is changing the practice of pathology. Their implementation challenges traditional educational paradigms. Training programs must adapt to these heuristic needs. The dual explosion of new medical knowledge and innovative methodologies adds new practice aspects to the pathologist's areas of expertise. This transformation potentially challenges the traditional core model of training. It raises questions as to how pathology should incorporate future expanding subspecialty needs into educational and practice models. This article examines the impact of these disruptive technologies on resident and fellow education and explores alternative educational and practice models that may better accommodate pathology's future. Copyright © 2012 Elsevier Inc. All rights reserved.

BIOSENSORS FOR ENVIRONMENTAL MONITORING: A REGULATORY PERSPECTIVE

EPA Science Inventory

Biosensors show the potential to complement laboratory-based analytical methods for environmental applications. Although biosensors for potential environmental-monitoring applications have been reported for a wide range of environmental pollutants, from a regulatory perspective, ...

Effect of pathological use of the internet on adolescent mental health: a prospective study.

PubMed

Lam, Lawrence T; Peng, Zi-Wen

2010-10-01

To examine the effect of pathological use of the Internet on the mental health, including anxiety and depression, of adolescents in China. It is hypothesized that pathological use of the Internet is detrimental to adolescents’ mental health. A prospective study with a randomly generated cohort from the population. High schools in Guangzhou, China. Adolescents aged between 13 and 18 years. Pathological use of the Internet was assessed using the Pathological Use of the Internet Test. Depression and anxiety were assessed by the Zung Depression and Anxiety Scales. After adjusting for potential confounding factors, the relative risk of depression for those who used the Internet pathologically was about 21⁄2 times (incidence rate ratio,2.5;95%confidence interval,1.3-4.3) that of those who did not exhibit the targeted pathological internet use behaviors. No significant relationship between pathological use of the Internet and anxiety at follow-up was observed. Results suggested that young people who are initially free of mental health problems but use the Internet pathologically could develop depression as a consequence. These results have direct implications for the prevention of mental illness in young people, particularly in developing countries.

Challenging previous conceptions of vegetarianism and eating disorders.

PubMed

Fisak, B; Peterson, R D; Tantleff-Dunn, S; Molnar, J M

2006-12-01

The purpose of this study was to replicate and expand upon previous research that has examined the potential association between vegetarianism and disordered eating. Limitations of previous research studies are addressed, including possible low reliability of measures of eating pathology within vegetarian samples, use of only a few dietary restraint measures, and a paucity of research examining potential differences in body image and food choice motives of vegetarians versus nonvegetarians. Two hundred and fifty-six college students completed a number of measures of eating pathology and body image, and a food choice motives questionnaire. Interestingly, no significant differences were found between vegetarians and nonvegetarians in measures of eating pathology or body image. However, significant differences in food choice motives were found. Implications for both researchers and clinicians are discussed.

Pathological prolongation of action potential duration as a cause of the reduced alpha-adrenoceptor-mediated negative inotropy in streptozotocin-induced diabetic mice myocardium.

PubMed

Kanae, Haruna; Hamaguchi, Shogo; Wakasugi, Yumi; Kusakabe, Taichi; Kato, Keisuke; Namekata, Iyuki; Tanaka, Hikaru

2017-11-01

Effect of pathological prolongation of action potential duration on the α-adrenoceptor-mediated negative inotropy was studied in streptozotocin-induced diabetic mice myocardium. In streptozotocin-treated mouse ventricular myocardium, which had longer duration of action potential than that in control mice, the negative inotropic response induced by phenylephrine was smaller than that in control mice. 4-Aminopyridine prolonged the action potential duration and decreased the negative inotropy in control mice. Cromakalim shortened the action potential duration and increased the negative inotropy in streptozotocin-treated mice. These results suggest that the reduced α-adrenoceptor-mediated inotropy in the diabetic mouse myocardium is partly due to its prolonged action potential. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

A developmental perspective on early-life exposure to neurotoxicants.

PubMed

Bellinger, David C; Matthews-Bellinger, Julia A; Kordas, Katarzyna

2016-09-01

Studies of early-life neurotoxicant exposure have not been designed, analyzed, or interpreted in the context of a fully developmental perspective. The goal of this paper is to describe the key principles of a developmental perspective and to use examples from the literature to illustrate the relevance of these principles to early-life neurotoxicant exposures. Four principles are discussed: 1) the effects of early-life neurotoxicant exposure depend on a child's developmental context; 2) deficits caused by early-life exposure initiate developmental cascades that can lead to pathologies that differ from those observed initially; 3) early-life neurotoxicant exposure has intra-familial and intergenerational impacts; 4) the impacts of early-life neurotoxicant exposure influence a child's ability to respond to future insults. The first principle is supported by considerable evidence, but the other three have received much less attention. Incorporating a developmental perspective in studies of early-life neurotoxicant exposures requires prospective collection of data on a larger array of covariates than usually considered, using analytical approaches that acknowledge the transactional processes between a child and the environment and the phenomenon of developmental cascades. Consideration of early-life neurotoxicant exposure within a developmental perspective reveals that many issues remain to be explicated if we are to achieve a deep understanding of the societal health burden associated with early-life neurotoxicant exposures. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Adaptogenic potentialities of dynamic magnetotherapy in the treatment and prevention of ENT pathology in ailing children].

PubMed

Bolotova, N V; Grinkevich, A V; Grishchenko, T P; Raĭgorodskiĭ, Iu M; Tupkin, V D

2007-01-01

Efficacy of dynamic magnetotherapy (in transcranial and adrenal variants) for treatment of ENT pathology and prevention of its exacerbations is demonstrated in 126 ailing children. Mechanism of action of this magnetotherapy is due to formation of adequate adaptation reactions raising resistance to pathogens.

Social Motor Coordination in Unaffected Relatives of Schizophrenia Patients: A Potential Intermediate Phenotype

PubMed Central

Del-Monte, Jonathan; Capdevielle, Delphine; Varlet, Manuel; Marin, Ludovic; Schmidt, Richard C.; Salesse, Robin N.; Bardy, Benoît G.; Boulenger, Jean Philippe; Gély-Nargeot, Marie Christine; Attal, Jérôme; Raffard, Stéphane

2013-01-01

Intermediate endophenotypes emerge as an important concept in the study of schizophrenia. Although research on phenotypes mainly investigated cognitive, metabolic or neurophysiological markers so far, some authors also examined the motor behavior anomalies as a potential trait-marker of the disease. However, no research has investigated social motor coordination despite the possible importance of its anomalies in schizophrenia. The aim of this study was thus to determine whether coordination modifications previously demonstrated in schizophrenia are trait-markers that might be associated with the risk for this pathology. Interpersonal motor coordination in 27 unaffected first-degree relatives of schizophrenia patients and 27 healthy controls was assessed using a hand-held pendulum task to examine the presence of interpersonal coordination impairments in individuals at risk for the disorder. Measures of neurologic soft signs, clinical variables and neurocognitive functions were collected to assess the cognitive and clinical correlates of social coordination impairments in at-risk relatives. After controlling for potential confounding variables, unaffected relatives of schizophrenia patients had impaired intentional interpersonal coordination compared to healthy controls while unintentional interpersonal coordination was preserved. More specifically, in intentional coordination, the unaffected relatives of schizophrenia patients exhibited coordination patterns that had greater variability and in which relatives did not lead the coordination. These results show that unaffected relatives of schizophrenia patients, like the patients themselves, also present deficits in intentional interpersonal coordination. For the first time, these results suggest that intentional interpersonal coordination impairments might be a potential motor intermediate endophenotype of schizophrenia opening new perspectives for early diagnosis. PMID:24106467

Alzheimer's disease in the omics era.

PubMed

Sancesario, Giulia M; Bernardini, Sergio

2018-06-18

Recent progresses in high-throughput technologies have led to a new scenario in investigating pathologies, named the "Omics era", which integrate the opportunity to collect large amounts of data and information at the molecular and protein levels together with the development of novel computational and statistical tools that are able to analyze and filter such data. Subsequently, advances in genotyping arrays, next generation sequencing, mass spectrometry technology, and bioinformatics allowed for the simultaneous large-scale study of thousands of genes (genomics), epigenetics factors (epigenomics), RNA (transcriptomics), metabolites (metabolomics) and proteins(proteomics), with the possibility of integrating multiple types of omics data ("multi -omics"). All of these technological innovations have modified the approach to the study of complex diseases, such as Alzheimer's Disease (AD), thus representing a promising tool to investigate the relationship between several molecular pathways in AD as well as other pathologies. This review focuses on the current knowledge on the pathology of AD, the recent findings from Omics sciences, and the challenge of the use of Big Data. We then focus on future perspectives for Omics sciences, such as the discovery of novel diagnostic biomarkers or drugs. Copyright © 2018. Published by Elsevier Inc.

Collective consciousness and its pathologies: Understanding the failure of AIDS control and treatment in the United States

PubMed Central

Wallace, Rodrick M; Fullilove, Mindy T; Fullilove, Robert E; Wallace, Deborah N

2007-01-01

We address themes of distributed cognition by extending recent formal developments in the theory of individual consciousness. While single minds appear biologically limited to one dynamic structure of linked cognitive submodules instantiating consciousness, organizations, by contrast, can support several, sometimes many, such constructs simultaneously, although these usually operate relatively slowly. System behavior remains, however, constrained not only by culture, but by a developmental path dependence generated by organizational history, in the context of market selection pressures. Such highly parallel multitasking – essentially an institutional collective consciousness – while capable of reducing inattentional blindness and the consequences of failures within individual workspaces, does not eliminate them, and introduces new characteristic malfunctions involving the distortion of information sent between workspaces and the possibility of pathological resilience – dysfunctional institutional lock-in. Consequently, organizations remain subject to canonical and idiosyncratic failures analogous to, but more complicated than, those afflicting individuals. Remediation is made difficult by the manner in which pathological externalities can write images of themselves onto both institutional function and corrective intervention. The perspective is applied to the failure of AIDS control and treatment in the United States. PMID:17324268

Image processing and 3D visualization in the interpretation of patterned injury of the skin

NASA Astrophysics Data System (ADS)

Oliver, William R.; Altschuler, Bruce R.

1995-09-01

The use of image processing is becoming increasingly important in the evaluation of violent crime. While much work has been done in the use of these techniques for forensic purposes outside of forensic pathology, its use in the pathologic examination of wounding has been limited. We are investigating the use of image processing in the analysis of patterned injuries and tissue damage. Our interests are currently concentrated on 1) the use of image processing techniques to aid the investigator in observing and evaluating patterned injuries in photographs, 2) measurement of the 3D shape characteristics of surface lesions, and 3) correlation of patterned injuries with deep tissue injury as a problem in 3D visualization. We are beginning investigations in data-acquisition problems for performing 3D scene reconstructions from the pathology perspective of correlating tissue injury to scene features and trace evidence localization. Our primary tool for correlation of surface injuries with deep tissue injuries has been the comparison of processed surface injury photographs with 3D reconstructions from antemortem CT and MRI data. We have developed a prototype robot for the acquisition of 3D wound and scene data.

Renin-angiotensin-aldosterone (RAAS): The ubiquitous system for homeostasis and pathologies.

PubMed

Patel, Seema; Rauf, Abdur; Khan, Haroon; Abu-Izneid, Tareq

2017-10-01

Renin-angiotensin-aldosterone system (RAAS) is a vital system of human body, as it maintains plasma sodium concentration, arterial blood pressure and extracellular volume. Kidney-secreted renin enzyme acts on its substrate to form angiotensin II, a versatile effector peptide hormone. Every organ is affected by RAAS activation and the resultant hypertension, cell proliferation, inflammation, and fibrosis. The imbalance of renin and angiotensin II can result in an overwhelming number of chronic and acute diseases. RAAS is influenced by other enzymes, hormones, pumps and signaling pathways, hence, this review discusses important facets of this system, its crosstalk with other crucial factors like estrogen, thyroid, cortisol, kallikrein-kinin system, Wnt/β-catenin signaling, and sodium-potassium pump. The nexus of RAAS with the above-discussed systems was scantily explored before. So, this review furnishes a new perspective in comprehension of inflammation diseases. It is followed by the formulation of hypotheses, which can contribute to better management of an array of pathologies plaguing mankind. Manipulation of RAAS, by bending it towards ACE2 expression can regulate endocrine functions, which can be critical for a number of pathological management. Dietary intervention can restore RAAS to normalcy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

A Study on the Perceptions About Potential Advantages of FMS (Foreign Military Sales) and Commercial Sales: Seller and Buyer Perspectives

DTIC Science & Technology

1987-09-01

SFl WILE coP DTIC ELECTEI DEC0 419871 OFD IIN A STUDY ON THE PERCEPTIONS ABOUT COMMERCIAL SALES: SELLER ANDI • BUYER PERSPECTIVES THESIS Yong Sang Kim...PERCEPTIONS ABOUT H𔃾 POTENTIAL ADVANTAGES OF FMS AND COMMERCIAL SALES: SELLER AND BUYER PERSPECTIVES THESIS Accession For Yong Sang Kim NTIS ,RA&I Major...AND COMMERCIAL SALES: SELLER AND BUYER PERSPECTIVES THESIS Presented to the Faculty of the School of Systems and Logistics of the Air Force Institute

Introducing 3-Dimensional Printing of a Human Anatomic Pathology Specimen: Potential Benefits for Undergraduate and Postgraduate Education and Anatomic Pathology Practice.

PubMed

Mahmoud, Amr; Bennett, Michael

2015-08-01

Three-dimensional (3D) printing, a rapidly advancing technology, is widely applied in fields such as mechanical engineering and architecture. Three-dimensional printing has been introduced recently into medical practice in areas such as reconstructive surgery, as well as in clinical research. Three-dimensionally printed models of anatomic and autopsy pathology specimens can be used for demonstrating pathology entities to undergraduate medical, dental, and biomedical students, as well as for postgraduate training in examination of gross specimens for anatomic pathology residents and pathology assistants, aiding clinicopathological correlation at multidisciplinary team meetings, and guiding reconstructive surgical procedures. To apply 3D printing in anatomic pathology for teaching, training, and clinical correlation purposes. Multicolored 3D printing of human anatomic pathology specimens was achieved using a ZCorp 510 3D printer (3D Systems, Rock Hill, South Carolina) following creation of a 3D model using Autodesk 123D Catch software (Autodesk, Inc, San Francisco, California). Three-dimensionally printed models of anatomic pathology specimens created included pancreatoduodenectomy (Whipple operation) and radical nephrectomy specimens. The models accurately depicted the topographic anatomy of selected specimens and illustrated the anatomic relation of excised lesions to adjacent normal tissues. Three-dimensional printing of human anatomic pathology specimens is achievable. Advances in 3D printing technology may further improve the quality of 3D printable anatomic pathology specimens.

Multimodal assessment of emotional reactivity in borderline personality pathology: The moderating role of posttraumatic stress disorder symptoms

PubMed Central

Dixon-Gordon, Katherine L.; Gratz, Kim L.; Tull, Matthew T.

2013-01-01

Emotional reactivity has been theorized to play a central role in borderline personality (BP) pathology. Although growing research provides evidence for subjective emotional reactivity in BP pathology, research on physiological or biological reactivity among people with BP pathology is less conclusive. With regard to biological reactivity in particular, research on cortisol reactivity (a neurobiological marker of emotional reactivity) in response to stressors among individuals with BP pathology has produced contradictory results and highlighted the potential moderating role of PTSD-related pathology. Thus, this study sought to examine the moderating role of PTSD symptoms in the relation between BP pathology and both subjective (self-report) and biological (cortisol) emotional reactivity to a laboratory stressor. Participants were 171 patients in a residential substance use disorder treatment center. Consistent with hypotheses, results revealed a significant main effect of BP pathology on subjective emotional reactivity to the laboratory stressor. Furthermore, results revealed a significant interaction between BP pathology and PTSD symptoms in the prediction of cortisol reactivity, such that BP pathology was associated with heightened cortisol reactivity only among participants with low levels of PTSD symptoms. Similar findings were obtained when examining the interaction between BP pathology and the reexperiencing and avoidance/numbing symptoms of PTSD specifically. Results highlight the moderating role of PTSD symptoms in the BP-reactivity relation. PMID:23375184

A framework for treating DSM-5 alternative model for personality disorder features.

PubMed

Hopwood, Christopher J

2018-04-15

Despite its demonstrated empirical superiority over the DSM-5 Section 2 categorical model of personality disorders for organizing the features of personality pathology, limitations remain with regard to the translation of the DSM-5 Section 3 alternative model of personality disorders (AMPD) to clinical practice. The goal of this paper is to outline a general and preliminary framework for approaching treatment from the perspective of the AMPD. Specific techniques are discussed for the assessment and treatment of both Criterion A personality dysfunction and Criterion B maladaptive traits. A concise and step-by-step model is presented for clinical decision making with the AMPD, in the hopes of offering clinicians a framework for treating personality pathology and promoting further research on the clinical utility of the AMPD. Copyright © 2018 John Wiley & Sons, Ltd. Copyright © 2018 John Wiley & Sons, Ltd.

A Looking-Glass of Non-Coding RNAs in Oral Cancer

PubMed Central

Irimie, Alexandra Iulia; Braicu, Cornelia; Sonea, Laura; Zimta, Alina Andreea; Diudea, Diana; Buduru, Smaranda; Berindan-Neagoe, Ioana

2017-01-01

Oral cancer is a multifactorial pathology and is characterized by the lack of efficient treatment and accurate diagnostic tools. This is mainly due the late diagnosis; therefore, reliable biomarkers for the timely detection of the disease and patient stratification are required. Non-coding RNAs (ncRNAs) are key elements in the physiological and pathological processes of various cancers, which is also reflected in oral cancer development and progression. A better understanding of their role could give a more thorough perspective on the future treatment options for this cancer type. This review offers a glimpse into the ncRNA involvement in oral cancer, which can help the medical community tap into the world of ncRNAs and lay the ground for more powerful diagnostic, prognostic and treatment tools for oral cancer that will ultimately help build a brighter future for these patients. PMID:29206174

[Personal genome research and neurological diseases: overview].

PubMed

Toda, Tatsushi

2013-03-01

Neurological diseases include those caused by a single defective gene,e.g., Huntington's disease, other polyglutamine diseases, and muscular dystrophies, and those that are mostly sporadic but rarely show Mendelian inheritance in some families, e.g., Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and epilepsy. The latter diseases are considered polygenic disorders. Both sporadic and Mendelian cases of these diseases are believed to share some common pathological mechanisms. Since the detection of causal genes for the Mendelian cases, studies have been initiated on disease pathology. SNPs and rare gene variants play important roles in common neurological diseases. From a technological perspective, next-generation sequencers have become widely available and have contributed to the advancement of research based on individual genome sequences (personal genome). This paper presents an overview, as well as a historical context, of the contribution of personal genome research to neurological disease studies.

Chronic ankle instability: Current perspectives

PubMed Central

Al-Mohrej, Omar A.; Al-Kenani, Nader S.

2016-01-01

Ankle sprain is reported to be among the most common recurrent injuries. About 20% of acute ankle sprain patients develop chronic ankle instability. The failure of functional rehabilitation after acute ankle sprain leads to the development of chronic ankle instability. Differentiation between functional and anatomical ankle instability is very essential to guide the proper treatment. Stability testing by varus stress test and anterior drawer test should be carried out. Subtalar instability is an important pathology that is commonly by passed during the assessment of chronic ankle instability. Unlike acute ankle sprain, chronic ankle instability might require surgical intervention. The surgical and conservative management options can be very much developed by in-depth knowledge of the ankle anatomy, biomechanics, and pathology. Anatomical repair, augmentation by tendon, or both are the basic methods of surgical intervention. Arthroscopy is becoming more popular in the management of chronic ankle instability. PMID:27843798

Sasang Constitutional Medicine and Traditional Chinese Medicine: A Comparative Overview

PubMed Central

Yoo, Junghee; Lee, Euiju; Kim, Chungmi; Lee, Junhee; Lixing, Lao

2012-01-01

Sasang constitutional medicine (SCM) is a holistic typological constitution medicine which balances psychological, social, and physical aspects of an individual to achieve wellness and increase longevity. SCM has the qualities of preventative medicine, as it emphasizes daily health management based on constitutionally differentiated regimens and self-cultivation of the mind and body. This review's goal is to establish a fundamental understanding of SCM and to provide a foundation for further study. It compares the similarities and differences of philosophical origins, perspectives on the mind (heart), typological systems, pathology, and therapeutics between SCM and traditional Chinese medicine (TCM). TCM is based on the Taoist view of the universe and humanity. The health and longevity of an individual depends on a harmonious relationship with the universe. On the other hand, SCM is based on the Confucian view of the universe and humanity. SCM focuses on the influence of human affairs on the psyche, physiology, and pathology. PMID:21941592

ADHD and Present Hedonism: time perspective as a potential diagnostic and therapeutic tool.

PubMed

Weissenberger, S; Klicperova-Baker, M; Zimbardo, P; Schonova, K; Akotia, D; Kostal, J; Goetz, M; Raboch, J; Ptacek, R

2016-01-01

The article draws primarily from the behavioral findings (mainly psychiatric and psychological observations) and points out the important relationships between attention-deficit/hyperactivity disorder (ADHD) symptoms and time orientation. Specifically, the authors argue that there is a significant overlap between the symptoms of ADHD and Present Hedonism. Present Hedonism is defined by Zimbardo's time perspective theory and assessed by Zimbardo Time Perspective Inventory. Developmental data on Present Hedonism of males and females in the Czech population sample (N=2201) are also presented. The hypothesis of relationship between ADHD and Present Hedonism is mainly derived from the prevalence of addictive behavior (mainly excessive Internet use, alcohol abuse, craving for sweets, fatty foods, and fast foods), deficits in social learning, and increased aggressiveness both in ADHD and in the population scoring high on Present Hedonism in the Zimbardo Time Perspective Inventory. We conclude that Zimbardo's time perspective offers both: 1) a potential diagnostic tool - the Zimbardo Time Perspective Inventory, particularly its Present Hedonism scale, and 2) a promising preventive and/or therapeutic approach by the Time Perspective Therapy. Time Perspective Therapy has so far been used mainly to treat past negative trauma (most notably, posttraumatic stress disorder); however, it also has value as a potential therapeutic tool for possible behavioral compensation of ADHD.

ADHD and Present Hedonism: time perspective as a potential diagnostic and therapeutic tool

PubMed Central

Weissenberger, S; Klicperova-Baker, M; Zimbardo, P; Schonova, K; Akotia, D; Kostal, J; Goetz, M; Raboch, J; Ptacek, R

2016-01-01

The article draws primarily from the behavioral findings (mainly psychiatric and psychological observations) and points out the important relationships between attention-deficit/hyperactivity disorder (ADHD) symptoms and time orientation. Specifically, the authors argue that there is a significant overlap between the symptoms of ADHD and Present Hedonism. Present Hedonism is defined by Zimbardo’s time perspective theory and assessed by Zimbardo Time Perspective Inventory. Developmental data on Present Hedonism of males and females in the Czech population sample (N=2201) are also presented. The hypothesis of relationship between ADHD and Present Hedonism is mainly derived from the prevalence of addictive behavior (mainly excessive Internet use, alcohol abuse, craving for sweets, fatty foods, and fast foods), deficits in social learning, and increased aggressiveness both in ADHD and in the population scoring high on Present Hedonism in the Zimbardo Time Perspective Inventory. We conclude that Zimbardo’s time perspective offers both: 1) a potential diagnostic tool – the Zimbardo Time Perspective Inventory, particularly its Present Hedonism scale, and 2) a promising preventive and/or therapeutic approach by the Time Perspective Therapy. Time Perspective Therapy has so far been used mainly to treat past negative trauma (most notably, posttraumatic stress disorder); however, it also has value as a potential therapeutic tool for possible behavioral compensation of ADHD. PMID:27895485

Dermatophyte-host relationship of a murine model of experimental invasive dermatophytosis.

PubMed

Venturini, James; Alvares, Anuska Marcelino; Camargo, Marcela Rodrigues de; Marchetti, Camila Martins; Fraga-Silva, Thais Fernanda de Campos; Luchini, Ana Carolina; Arruda, Maria Sueli Parreira de

2012-11-01

Recognizing the invasive potential of the dermatophytes and understanding the mechanisms involved in this process will help with disease diagnosis and with developing an appropriate treatment plan. In this report, we present the histopathological, microbiological and immunological features of a model of invasive dermatophytosis that is induced by subcutaneous infection of Trichophyton mentagrophytes in healthy adult Swiss mice. Using this model, we observed that the fungus rapidly spreads to the popliteal lymph nodes, spleen, liver and kidneys. Similar to the human disease, the lymph nodes were the most severely affected sites. The fungal infection evoked acute inflammation followed by a granulomatous reaction in the mice, which is similar to what is observed in patients. The mice were able to mount a Th1-polarized immune response and displayed IL-10-mediated immune regulation. We believe that the model described here will provide valuable information regarding the dermatophyte-host relationship and will yield new perspective for a better understanding of the immunological and pathological aspects of invasive dermatophytosis. Copyright © 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Highly Disordered Proteins in Prostate Cancer.

PubMed

Uversky, Vladimir N; Na, Insung; Landau, Kevin S; Schenck, Ryan O

2017-01-01

Prostate cancer is one of the major threats to the man's health. There are several mechanisms of the prostate cancer development characterized by the involvement of various androgen-related and androgen-unrelated factors in prostate cancer pathogenesis and in the metastatic carcinogenesis of prostate. In all these processes, proteins play various important roles, and the KEGG database has information on 88 human proteins experimentally shown to be involved in prostate cancer. It is known that many proteins associated with different human maladies are intrinsically disordered (i.e., they do not have stable secondary and/or tertiary structure in their unbound states). The goal of this review is to consider several highly disordered proteins known to be associated with the prostate cancer pathogenesis in order to better understand the roles of disordered proteins in this disease. We also hope that consideration of the pathology-related proteins from the perspective of intrinsic disorder can potentially lead to future experimental studies of these proteins to find novel pathways associated with prostate cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Alzheimer’s disease: biological aspects, therapeutic perspectives and diagnostic tools

NASA Astrophysics Data System (ADS)

Di Carlo, M.; Giacomazza, D.; San Biagio, P. L.

2012-06-01

Alzheimer’s disease (AD) is the most common form of dementia among older people. Dementia is an irreversible brain disorder that seriously affects a person’s ability to carry out daily activities. It is characterized by loss of cognitive functioning and behavioral abilities, to such an extent that it interferes with the daily life and activities of the affected patients. Although it is still unknown how the disease process begins, it seems that brain damage starts a decade or more before problems become evident. Scientific data seem to indicate that changes in the generation or the degradation of the amyloid-b peptide (Aβ) lead to the formation of aggregated structures that are the triggering molecular events in the pathogenic cascade of AD. This review summarizes some characteristic features of Aβ misfolding and aggregation and how cell damage and death mechanisms are induced by these supramolecular and toxic structures. Further, some interventions for the early diagnosis of AD are described and in the last part the potential therapeutic strategies adoptable to slow down, or better block, the progression of the pathology are reported.

Perinatal asphyxia: a review from a metabolomics perspective.

PubMed

Fattuoni, Claudia; Palmas, Francesco; Noto, Antonio; Fanos, Vassilios; Barberini, Luigi

2015-04-17

Perinatal asphyxia is defined as an oxygen deprivation that occurs around the time of birth, and may be caused by several perinatal events. This medical condition affects some four million neonates worldwide per year, causing the death of one million subjects. In most cases, infants successfully recover from hypoxia episodes; however, some patients may develop HIE, leading to permanent neurological conditions or impairment of different organs and systems. Given its multifactor dependency, the timing, severity and outcome of this disease, mainly assessed through Sarnat staging, are of difficult evaluation. Moreover, although the latest newborn resuscitation guideline suggests the use of a 21% oxygen concentration or room air, such an approach is still under debate. Therefore, the pathological mechanism is still not clear and a golden standard treatment has yet to be defined. In this context, metabolomics, a new discipline that has described important perinatal issues over the last years, proved to be a useful tool for the monitoring, the assessment, and the identification of potential biomarkers associated with asphyxia events. This review covers metabolomics research on perinatal asphyxia condition, examining in detail the studies reported both on animal and human models.

Future perspectives toward the early definition of a multivariate decision-support scheme employed in clinical decision making for senior citizens.

PubMed

Frantzidis, Christos A; Gilou, Sotiria; Billis, Antonis; Karagianni, Maria; Bratsas, Charalampos D; Bamidis, Panagiotis

2016-03-01

Recent neuroscientific studies focused on the identification of pathological neurophysiological patterns (emotions, geriatric depression, memory impairment and sleep disturbances) through computerised clinical decision-support systems. Almost all these research attempts employed either resting-state condition (e.g. eyes-closed) or event-related potentials extracted during a cognitive task known to be affected by the disease under consideration. This Letter reviews existing data mining techniques and aims to enhance their robustness by proposing a holistic decision framework dealing with comorbidities and early symptoms' identification, while it could be applied in realistic occasions. Multivariate features are elicited and fused in order to be compared with average activities characteristic of each neuropathology group. A proposed model of the specific cognitive function which may be based on previous findings (a priori information) and/or validated by current experimental data should be then formed. So, the proposed scheme facilitates the early identification and prevention of neurodegenerative phenomena. Neurophysiological semantic annotation is hypothesised to enhance the importance of the proposed framework in facilitating the personalised healthcare of the information society and medical informatics research community.

Marfan Syndrome: Clinical, Surgical, and Anesthetic Considerations.

PubMed

Castellano, José M; Silvay, George; Castillo, Javier G

2014-09-01

Marfan syndrome is a multisystem connective tissue disorder, with primary involvement of the cardiovascular, ocular, and skeletal systems. This autosomal heritable disease is mainly attributable to a defect in the FBN1 gene. Clinical diagnosis of Marfan syndrome has been based on the Ghent criteria since 1996. In 2010, these criteria were updated, and the revised guidelines place more emphasis on aortic root dilation, ectopia lentis, and FBN1 mutation testing in the diagnostic assessment of Marfan syndrome. Among its many different clinical manifestations, cardiovascular involvement deserves special consideration, owing to its impact on prognosis. Recent molecular, surgical, and clinical research has yielded profound new insights into the pathological mechanisms that ultimately lead to tissue degradation and weakening of the aortic wall, which has led to exciting new treatment strategies. Furthermore, with the increasing life expectancy of patients with Marfan syndrome, there has been a subtle shift in the spectrum of medical problems. Consequently, this article focuses on recent advances to highlight their potential impact on future concepts of patient care from a clinical, surgical, and anesthetic perspective. © The Author(s) 2013.

[Severe asymptomatic carotid stenosis: a neurological perspective].

PubMed

de la Cruz-Cosme, Carlos; Segura, Tomás

2012-09-01

Asymptomatic carotid stenosis is a relatively frequent pathology, although when considering the possibility of managing it surgically, there is still an important amount of disagreement concerning the criteria to be taken into account. This study conducts a broad examination of the condition, from its concept and epidemiology to the studies that triggered the boom in its surgical treatment during the nineties. The research also reviews the tools available for a better selection of cases that could potentially benefit most from surgery, the presence of silent brain lesions, the severity of the stenosis, its progression, the characteristics of the plaque, colaterality and vasoreactivity studies, the detection of micro-emboli, the presence of risk factors independently associated to the symptomatic conversion of the stenosis, and other elements that have recently been reported either clinically or experimentally. Finally, the article outlines the current state of the surgical technique and the advances being made in its pharmacological treatment. This review is not intended to be a set of clinical practice guidelines, but to offer a global integrating overview of the management of high-grade asymptomatic carotid stenosis.

A Review of Mid-Infrared and Near-Infrared Imaging: Principles, Concepts and Applications in Plant Tissue Analysis.

PubMed

Türker-Kaya, Sevgi; Huck, Christian W

2017-01-20

Plant cells, tissues and organs are composed of various biomolecules arranged as structurally diverse units, which represent heterogeneity at microscopic levels. Molecular knowledge about those constituents with their localization in such complexity is very crucial for both basic and applied plant sciences. In this context, infrared imaging techniques have advantages over conventional methods to investigate heterogeneous plant structures in providing quantitative and qualitative analyses with spatial distribution of the components. Thus, particularly, with the use of proper analytical approaches and sampling methods, these technologies offer significant information for the studies on plant classification, physiology, ecology, genetics, pathology and other related disciplines. This review aims to present a general perspective about near-infrared and mid-infrared imaging/microspectroscopy in plant research. It is addressed to compare potentialities of these methodologies with their advantages and limitations. With regard to the organization of the document, the first section will introduce the respective underlying principles followed by instrumentation, sampling techniques, sample preparations, measurement, and an overview of spectral pre-processing and multivariate analysis. The last section will review selected applications in the literature.

Modulation of Food Reward by Endocrine and Environmental Factors: Update and Perspective.

PubMed

Figlewicz, Dianne P

2015-01-01

Palatable foods are frequently high in energy density. Chronic consumption of high-energy density foods can contribute to the development of cardiometabolic pathology including obesity, diabetes, and cardiovascular disease. This article reviews the contributions of extrinsic and intrinsic factors that influence the reward components of food intake. A narrative review was conducted to determine the behavioral and central nervous system (CNS) related processes involved in the reward components of high-energy density food intake. The rewarding aspects of food, particularly palatable and preferred foods, are regulated by CNS circuitry. Overlaying this regulation is modulation by intrinsic endocrine systems and metabolic hormones relating to energy homeostasis, developmental stage, or gender. It is now recognized that extrinsic or environmental factors, including ambient diet composition and the provocation of stress or anxiety, also contribute substantially to the expression of food reward behaviors such as motivation for, and seeking of, preferred foods. High-energy density food intake is influenced by both physiological and pathophysiological processes. Contextual, behavioral, and psychological factors and CNS-related processes represent potential targets for multiple types of therapeutic intervention.

MicroRNA-7: A miRNA with expanding roles in development and disease.

PubMed

Horsham, Jessica L; Ganda, Clarissa; Kalinowski, Felicity C; Brown, Rikki A M; Epis, Michael R; Leedman, Peter J

2015-12-01

MicroRNAs (miRNAs) are a family of short, non-coding RNA molecules (∼22nt) involved in post-transcriptional control of gene expression. They act via base-pairing with mRNA transcripts that harbour target sequences, resulting in accelerated mRNA decay and/or translational attenuation. Given miRNAs mediate the expression of molecules involved in many aspects of normal cell development and functioning, it is not surprising that aberrant miRNA expression is closely associated with many human diseases. Their pivotal role in driving a range of normal cellular physiology as well as pathological processes has established miRNAs as potential therapeutics, as well as potential diagnostic and prognostic tools in human health. MicroRNA-7 (miR-7) is a highly conserved miRNA which displays restricted spatiotemporal expression during development and in maturity. In humans and mice, mature miR-7 is generated from three different genes, illustrating unexpected redundancy and also the importance of this miRNA in regulating key cellular processes. In this review we examine the expanding role of miR-7 in the context of health, with emphasis on organ differentiation and development, as well as in various mammalian diseases, particularly of the brain, heart, endocrine pancreas and skin, as well as in cancer. The more we learn about miR-7, the more we realise the complexity of its regulation and potential functional application both from a biomarker and therapeutic perspective. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pathological video-gaming among Singaporean youth.

PubMed

Choo, Hyekyung; Gentile, Douglas A; Sim, Timothy; Li, Dongdong; Khoo, Angeline; Liau, Albert K

2010-11-01

Increase in internet use and video-gaming contributes to public concern on pathological or obsessive play of video games among children and adolescents worldwide. Nevertheless, little is known about the prevalence of pathological symptoms in video-gaming among Singaporean youth and the psychometric properties of instruments measuring pathological symptoms in video-gaming. A total of 2998 children and adolescents from 6 primary and 6 secondary schools in Singapore responded to a comprehensive survey questionnaire on sociodemographic characteristics, video-gaming habits, school performance, somatic symptoms, various psychological traits, social functioning and pathological symptoms of video-gaming. After weighting, the survey data were analysed to determine the prevalence of pathological video-gaming among Singaporean youth and gender differences in the prevalence. The construct validity of instrument used to measure pathological symptoms of video-gaming was tested. Of all the study participants, 8.7% were classified as pathological players with more boys reporting more pathological symptoms than girls. All variables, including impulse control problem, social competence, hostility, academic performance, and damages to social functioning, tested for construct validity, were significantly associated with pathological status, providing good evidence for the construct validity of the instrument used. The prevalence rate of pathological video-gaming among Singaporean youth is comparable with that from other countries studied thus far, and gender differences are also consistent with the findings of prior research. The positive evidence of construct validity supports the potential use of the instrument for future research and clinical screening on Singapore children and adolescents' pathological video-gaming.

Contrasting Pathology of the Stress Granule Proteins TIA-1 and G3BP in Tauopathies

PubMed Central

Vanderweyde, Tara; Yu, Haung; Varnum, Megan; Liu-Yesucevitz, Liqun; Citro, Allison; Ikezu, Tsuneya; Duff, Karen; Wolozin, Benjamin

2012-01-01

Stress induces aggregation of RNA-binding proteins to form inclusions, termed stress granules (SGs). Recent evidence suggests that SG proteins also colocalize with neuropathological structures, but whether this occurs in Alzheimer’s disease is unknown. We examined the relationship between SG proteins and neuropathology in brain tissue from P301L Tau transgenic mice, as well as in cases of Alzheimer’s disease and FTDP-17. The pattern of SG pathology differs dramatically based on the RNA-binding protein examined. SGs positive for T-cell intracellular antigen-1 (TIA-1) or tristetraprolin (TTP) initially do not colocalize with tau pathology, but then merge with tau inclusions as disease severity increases. In contrast, G3BP (ras GAP-binding protein) identifies a novel type of molecular pathology that shows increasing accumulation in neurons with increasing disease severity, but often is not associated with classic markers of tau pathology. TIA-1 and TTP both bind phospho-tau, and TIA-1 overexpression induces formation of inclusions containing phospho-tau. These data suggest that SG formation might stimulate tau pathophysiology. Thus, study of RNA-binding proteins and SG biology highlights novel pathways interacting with the pathophysiology of AD, providing potentially new avenues for identifying diseased neurons and potentially novel mechanisms regulating tau biology. PMID:22699908

Could Better Phenotyping Small Vessel Disease Provide New Insights into Alzheimer Disease and Improve Clinical Trial Outcomes?

PubMed

Marnane, Michael; Hsiung, Ging-Yuek R

2016-01-01

Alzheimer Disease (AD) is the most common primary cause of dementia with a burgeoning epidemic as life expectancy and general medical care improve worldwide. Recent data from pathologic studies has shown that the cooccurrence of other neurodegenerative and vascular pathologies is in fact the rule rather than the exception. In late onset AD, cerebral small vessel disease (SVD) is almost invariably co-existent to a greater or lesser extent and is known to promote cognitive deterioration. Previous observational studies and clinical trials have largely sought to divide dementia based on predominant neurodegenerative or vascular mechanisms. Given the high degree of overlap, findings from such studies may be difficult to interpret and apply to population cohorts. Additionally opportunities may be lost for uncovering novel interventions that target interactions between co-existent vascular and neurodegenerative pathologies. In the current review, we consider potential pathophysiologic mechanisms through which SVD may be associated with and promote AD pathology. In particular we explore shared environmental and genetic associations and how these may converge via neuroinflammatory pathways potentially providing novel therapeutic targets. SVD has heterogenous manifestations on cerebral imaging and at pathology. We discuss how studying SVD topography may enable us to better identify those at risk for more rapid cognitive decline and improve future clinical trial design.

Rhinoceros Feet Step Out of a Rule-of-Thumb: A Wildlife Imaging Pioneering Approach of Synchronized Computed Tomography-Digital Radiography

PubMed Central

Saragusty, Joseph; Göritz, Frank; Potier, Romain; Mulot, Baptiste; Maillot, Alexis; Etienne, Pascal; Bernardino, Rui; Fernandes, Teresa; Mews, Jurgen; Hildebrandt, Thomas Bernd

2014-01-01

Currently, radiography is the only imaging technique used to diagnose bone pathology in wild animals situated under “field conditions”. Nevertheless, while chronic foot disease in captive mega-herbivores is widely reported, foot radiographic imaging is confronted with scarcity of studies. Numerous hindrances lead to such limited numbers and it became very clear that the traditional perspective on bone imaging in domestic animals based on extensive studies and elaborated statistical evaluations cannot be extrapolated to their non-domestic relatives. For these reasons, the authors initiated a multi-modality imaging study and established a pioneering approach of synchronized computed tomography (CT) and digital radiography (DR), based on X-ray projections derived from three-dimensional CT reconstructed images. Whereas this approach can be applied in any clinical field, as a case of outstanding importance and great concern for zoological institutions, we selected foot bone pathologies in captive rhinoceroses to demonstrate the manifold applications of the method. Several advances were achieved, endowing the wildlife clinician with all-important tools: prototype DR exposure protocols and a modus operandi for foot positioning, advancing both traditional projections and, for the first-time, species-related radiographic views; assessment of radiographic diagnostic value for the whole foot and, in premiere, for each autopodial bone; together with additional insights into radiographic appearance of bone anatomy and pathology with a unique, simultaneous CT-DR correlation. Based on its main advantages in availing a wide range of keystone data in wildlife imaging from a limited number of examined subjects and combining advantages of CT as the golden standard method for bone diseases' diagnostic with DR's clinical feasibility under field conditions, synchronized CT-DR presents a new perspective on wildlife's health management. With this we hope to provide veterinary clinicians with concrete imaging techniques and substantial diagnostic tools, which facilitate straightforward attainment and interpretation of field radiography images taken worldwide. PMID:24963807

Rhinoceros feet step out of a rule-of-thumb: a wildlife imaging pioneering approach of synchronized computed tomography-digital radiography.

PubMed

Galateanu, Gabriela; Hermes, Robert; Saragusty, Joseph; Göritz, Frank; Potier, Romain; Mulot, Baptiste; Maillot, Alexis; Etienne, Pascal; Bernardino, Rui; Fernandes, Teresa; Mews, Jurgen; Hildebrandt, Thomas Bernd

2014-01-01

Currently, radiography is the only imaging technique used to diagnose bone pathology in wild animals situated under "field conditions". Nevertheless, while chronic foot disease in captive mega-herbivores is widely reported, foot radiographic imaging is confronted with scarcity of studies. Numerous hindrances lead to such limited numbers and it became very clear that the traditional perspective on bone imaging in domestic animals based on extensive studies and elaborated statistical evaluations cannot be extrapolated to their non-domestic relatives. For these reasons, the authors initiated a multi-modality imaging study and established a pioneering approach of synchronized computed tomography (CT) and digital radiography (DR), based on X-ray projections derived from three-dimensional CT reconstructed images. Whereas this approach can be applied in any clinical field, as a case of outstanding importance and great concern for zoological institutions, we selected foot bone pathologies in captive rhinoceroses to demonstrate the manifold applications of the method. Several advances were achieved, endowing the wildlife clinician with all-important tools: prototype DR exposure protocols and a modus operandi for foot positioning, advancing both traditional projections and, for the first-time, species-related radiographic views; assessment of radiographic diagnostic value for the whole foot and, in premiere, for each autopodial bone; together with additional insights into radiographic appearance of bone anatomy and pathology with a unique, simultaneous CT-DR correlation. Based on its main advantages in availing a wide range of keystone data in wildlife imaging from a limited number of examined subjects and combining advantages of CT as the golden standard method for bone diseases' diagnostic with DR's clinical feasibility under field conditions, synchronized CT-DR presents a new perspective on wildlife's health management. With this we hope to provide veterinary clinicians with concrete imaging techniques and substantial diagnostic tools, which facilitate straightforward attainment and interpretation of field radiography images taken worldwide.

Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

DOE PAGES

Zivcec, Marko; Scholte, Florine; Spiropoulou, Christina; ...

2016-04-21

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen that causes high morbidity and mortality. Efficacy of vaccines and antivirals to treat human CCHFV infections remains limited and controversial. Research into pathology and underlying molecular mechanisms of CCHFV and other nairoviruses is limited. Significant progress has been made in our understanding of CCHFV replication and pathogenesis in the past decade. Here we review the most recent molecular advances in CCHFV-related research, and provide perspectives on future research.

Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus.

PubMed

Zivcec, Marko; Scholte, Florine E M; Spiropoulou, Christina F; Spengler, Jessica R; Bergeron, Éric

2016-04-21

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen that causes high morbidity and mortality. Efficacy of vaccines and antivirals to treat human CCHFV infections remains limited and controversial. Research into pathology and underlying molecular mechanisms of CCHFV and other nairoviruses is limited. Significant progress has been made in our understanding of CCHFV replication and pathogenesis in the past decade. Here we review the most recent molecular advances in CCHFV-related research, and provide perspectives on future research.

Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

PubMed Central

Zivcec, Marko; Scholte, Florine E. M.; Spiropoulou, Christina F.; Spengler, Jessica R.; Bergeron, Éric

2016-01-01

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen that causes high morbidity and mortality. Efficacy of vaccines and antivirals to treat human CCHFV infections remains limited and controversial. Research into pathology and underlying molecular mechanisms of CCHFV and other nairoviruses is limited. Significant progress has been made in our understanding of CCHFV replication and pathogenesis in the past decade. Here we review the most recent molecular advances in CCHFV-related research, and provide perspectives on future research. PMID:27110812

Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

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

Zivcec, Marko; Scholte, Florine; Spiropoulou, Christina

Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen that causes high morbidity and mortality. Efficacy of vaccines and antivirals to treat human CCHFV infections remains limited and controversial. Research into pathology and underlying molecular mechanisms of CCHFV and other nairoviruses is limited. Significant progress has been made in our understanding of CCHFV replication and pathogenesis in the past decade. Here we review the most recent molecular advances in CCHFV-related research, and provide perspectives on future research.

Sex Offending and Situational Motivation: Findings From a Qualitative Analysis of Desistance From Sexual Offending.

PubMed

Farmer, Mark; McAlinden, Anne-Marie; Maruna, Shadd

2016-09-25

Sex offending is typically understood from a pathology perspective with the origin of the behavior thought to be within the offending individual. Such a perspective may not be beneficial for those seeking to desist from sexual offending and reintegrate into mainstream society. A thematic analysis of 32 self-narratives of men convicted of sexual offences against children suggests that such individuals typically explain their pasts utilizing a script consistent with routine activity theory, emphasizing the role of circumstantial changes in both the onset of and desistance from sexual offending. It is argued that the self-framing of serious offending in this way might be understood as a form of "shame management," a protective cognition that enables desistance by shielding individuals from internalizing stigma for past violence. © The Author(s) 2016.

Biomedical photoacoustics: fundamentals, instrumentation and perspectives on nanomedicine

PubMed Central

Zou, Chunpeng; Wu, Beibei; Dong, Yanyan; Song, Zhangwei; Zhao, Yaping; Ni, Xianwei; Yang, Yan; Liu, Zhe

2017-01-01

Photoacoustic imaging (PAI) is an integrated biomedical imaging modality which combines the advantages of acoustic deep penetration and optical high sensitivity. It can provide functional and structural images with satisfactory resolution and contrast which could provide abundant pathological information for disease-oriented diagnosis. Therefore, it has found vast applications so far and become a powerful tool of precision nanomedicine. However, the investigation of PAI-based imaging nanomaterials is still in its infancy. This perspective article aims to summarize the developments in photoacoustic technologies and instrumentations in the past years, and more importantly, present a bright outlook for advanced PAI-based imaging nanomaterials as well as their emerging biomedical applications in nanomedicine. Current challenges and bottleneck issues have also been discussed and elucidated in this article to bring them to the attention of the readership. PMID:28053532

Accuracy of vision technicians in screening ocular pathology at rural vision centres of southern India.

PubMed

Suram, Vasantha; Addepalli, Uday Kumar; Krishnaiah, Sannapaneni; Kovai, Vilas; Khanna, Rohit C

2016-03-01

There is paucity of data on the inter-observer agreement and diagnostic accuracy between a primary-care technician (vision technician) and an ophthalmologist. Hence, the current study was conducted to assess the accuracy of vision technicians, to screen potentially sight-threatening ocular conditions at rural vision centres of southern India and their agreement with an ophthalmologist. In July to August 2010, patients presenting to seven vision centres in Adilabad district (Andhra Pradesh) were selected and screened in a masked manner by seven vision technicians followed by an examination by a consultant ophthalmologist. Agreement was assessed between vision technicians and the ophthalmologist for screening of potential sight-threatening ocular conditions and decisions for referral. The ophthalmologist's findings were considered as the reference standard. Two hundred and seventy-nine patients were enrolled at seven vision centres with a mean age of 32.9 ± 21.8 years. Agreement for screening of ocular pathology was 0.82 (95 per cent CI, 0.8-0.83). There was excellent agreement for cataract (0.97; 95 per cent CI, 0.93-1), refractive error (0.98; 95 per cent CI, 0.96-1), corneal pathology (1.0; 95 per cent CI, 1.0-1.0) and other anterior segment pathology (0.95; 95 per cent CI, 0.9-1); the agreement was moderate to fair for detection of glaucoma suspects (0.43; 95 per cent CI, 0.28-0.60) and retinal pathology (0.39; 95 per cent CI, 0.14-0.63). Sensitivity for screening of anterior segment pathology was 94.6-100 per cent. There was a fair to moderate sensitivity for glaucoma suspect; 35.6 per cent (95 per cent CI, 21.9-51.2) and retinal pathology 26.3 per cent (95 per cent CI, 9.2-51.2). Specificity for screening of ocular pathology was 98.2 to 100 per cent. The kappa (κ) agreement for referral for any pathology was 0.82 (0.8-0.83) CONCLUSION: As there is good agreement between the vision technicians and the ophthalmologist for screening and referral of anterior segment pathology but moderate to fair for glaucoma suspects and retinal pathology, vision technicians would be a good resource at the primary level to screen for anterior segment pathology; however, they may need further training to detect posterior segment pathology. © 2016 Optometry Australia.

A proof of concept study to assess the potential of PCR testing to detect natural Mycobacterium bovis infection in South American camelids.

PubMed

Crawshaw, Timothy R; Chanter, Jeremy I; McGoldrick, Adrian; Line, Kirsty

2014-02-07

Cases of Mycobacterium bovis infection South American camelids have been increasing in Great Britain. Current antemortem immunological tests have some limitations. Cases at post mortem examination frequently show extensive pathology. The feasibility of detecting Mycobacterium bovis DNA in clinical samples was investigated. A sensitive extraction methodology was developed and used on nasal swabs and faeces taken post-mortem to assess the potential for a PCR test to detect Mycobacterium bovis in clinical samples. The gross pathology of the studied South American camelids was scored and a significantly greater proportion of South American camelids with more severe pathology were positive in both the nasal swab and faecal PCR tests. A combination of the nasal swab and faecal PCR tests detected 63.9% of all the South American camelids with pathology that were tested. The results suggest that antemortem diagnosis of Mycobacterium bovis in South American camelids may be possible using a PCR test on clinical samples, however more work is required to determine sensitivity and specificity, and the practicalities of applying the test in the field.

A Systems Level, Functional Genomics Analysis of Chronic Epilepsy

PubMed Central

Bragin, Anatol; Kudo, Lili C.; Gehman, Lauren; Ruidera, Josephine; Geschwind, Daniel H.; Engel, Jerome

2011-01-01

Neither the molecular basis of the pathologic tendency of neuronal circuits to generate spontaneous seizures (epileptogenicity) nor anti-epileptogenic mechanisms that maintain a seizure-free state are well understood. Here, we performed transcriptomic analysis in the intrahippocampal kainate model of temporal lobe epilepsy in rats using both Agilent and Codelink microarray platforms to characterize the epileptic processes. The experimental design allowed subtraction of the confounding effects of the lesion, identification of expression changes associated with epileptogenicity, and genes upregulated by seizures with potential homeostatic anti-epileptogenic effects. Using differential expression analysis, we identified several hundred expression changes in chronic epilepsy, including candidate genes associated with epileptogenicity such as Bdnf and Kcnj13. To analyze these data from a systems perspective, we applied weighted gene co-expression network analysis (WGCNA) to identify groups of co-expressed genes (modules) and their central (hub) genes. One such module contained genes upregulated in the epileptogenic region, including multiple epileptogenicity candidate genes, and was found to be involved the protection of glial cells against oxidative stress, implicating glial oxidative stress in epileptogenicity. Another distinct module corresponded to the effects of chronic seizures and represented changes in neuronal synaptic vesicle trafficking. We found that the network structure and connectivity of one hub gene, Sv2a, showed significant changes between normal and epileptogenic tissue, becoming more highly connected in epileptic brain. Since Sv2a is a target of the antiepileptic levetiracetam, this module may be important in controlling seizure activity. Bioinformatic analysis of this module also revealed a potential mechanism for the observed transcriptional changes via generation of longer alternatively polyadenlyated transcripts through the upregulation of the RNA binding protein HuD. In summary, combining conventional statistical methods and network analysis allowed us to interpret the differentially regulated genes from a systems perspective, yielding new insight into several biological pathways underlying homeostatic anti-epileptogenic effects and epileptogenicity. PMID:21695113

Effects of Tributyltin Chloride on Cybrids with or without an ATP Synthase Pathologic Mutation

PubMed Central

López-Gallardo, Ester; Llobet, Laura; Emperador, Sonia; Montoya, Julio; Ruiz-Pesini, Eduardo

2016-01-01

Background: The oxidative phosphorylation system (OXPHOS) includes nuclear chromosome (nDNA)– and mitochondrial DNA (mtDNA)–encoded polypeptides. Many rare OXPHOS disorders, such as striatal necrosis syndromes, are caused by genetic mutations. Despite important advances in sequencing procedures, causative mutations remain undetected in some patients. It is possible that etiologic factors, such as environmental toxins, are the cause of these cases. Indeed, the inhibition of a particular enzyme by a poison could imitate the biochemical effects of pathological mutations in that enzyme. Moreover, environmental factors can modify the penetrance or expressivity of pathological mutations. Objectives: We studied the interaction between mitochondrially encoded ATP synthase 6 (p.MT-ATP6) subunit and an environmental exposure that may contribute phenotypic differences between healthy individuals and patients suffering from striatal necrosis syndromes or other mitochondriopathies. Methods: We analyzed the effects of the ATP synthase inhibitor tributyltin chloride (TBTC), a widely distributed environmental factor that contaminates human food and water, on transmitochondrial cell lines with or without an ATP synthase mutation that causes striatal necrosis syndrome. Doses were selected based on TBTC concentrations previously reported in human whole blood samples. Results: TBTC modified the phenotypic effects caused by a pathological mtDNA mutation. Interestingly, wild-type cells treated with this xenobiotic showed similar bioenergetics when compared with the untreated mutated cells. Conclusions: In addition to the known genetic causes, our findings suggest that environmental exposure to TBTC might contribute to the etiology of striatal necrosis syndromes. Citation: López-Gallardo E, Llobet L, Emperador S, Montoya J, Ruiz-Pesini E. 2016. Effects of tributyltin chloride on cybrids with or without an ATP synthase pathologic mutation. Environ Health Perspect 124:1399–1405; http://dx.doi.org/10.1289/EHP182 PMID:27129022

Effects of Tributyltin Chloride on Cybrids with or without an ATP Synthase Pathologic Mutation.

PubMed

López-Gallardo, Ester; Llobet, Laura; Emperador, Sonia; Montoya, Julio; Ruiz-Pesini, Eduardo

2016-09-01

The oxidative phosphorylation system (OXPHOS) includes nuclear chromosome (nDNA)- and mitochondrial DNA (mtDNA)-encoded polypeptides. Many rare OXPHOS disorders, such as striatal necrosis syndromes, are caused by genetic mutations. Despite important advances in sequencing procedures, causative mutations remain undetected in some patients. It is possible that etiologic factors, such as environmental toxins, are the cause of these cases. Indeed, the inhibition of a particular enzyme by a poison could imitate the biochemical effects of pathological mutations in that enzyme. Moreover, environmental factors can modify the penetrance or expressivity of pathological mutations. We studied the interaction between mitochondrially encoded ATP synthase 6 (p.MT-ATP6) subunit and an environmental exposure that may contribute phenotypic differences between healthy individuals and patients suffering from striatal necrosis syndromes or other mitochondriopathies. We analyzed the effects of the ATP synthase inhibitor tributyltin chloride (TBTC), a widely distributed environmental factor that contaminates human food and water, on transmitochondrial cell lines with or without an ATP synthase mutation that causes striatal necrosis syndrome. Doses were selected based on TBTC concentrations previously reported in human whole blood samples. TBTC modified the phenotypic effects caused by a pathological mtDNA mutation. Interestingly, wild-type cells treated with this xenobiotic showed similar bioenergetics when compared with the untreated mutated cells. In addition to the known genetic causes, our findings suggest that environmental exposure to TBTC might contribute to the etiology of striatal necrosis syndromes. López-Gallardo E, Llobet L, Emperador S, Montoya J, Ruiz-Pesini E. 2016. Effects of tributyltin chloride on cybrids with or without an ATP synthase pathologic mutation. Environ Health Perspect 124:1399-1405; http://dx.doi.org/10.1289/EHP182.

Adjudicating pathological criminal incapacity within a climate of ultimate issue barriers: a comparative perspective.

PubMed

Stevens, Geert Philip

2015-01-01

Mental health experts are increasingly being utilised by the criminal justice system to provide assistance to courts during the assessment of issues falling beyond the knowledge and/or experience of the courts. A particular domain where the assistance of qualified psychiatrists and psychologists is becoming essential is where the defence of pathological criminal incapacity falls to be assessed. Mental health professionals testifying during trials where the defence of pathological criminal incapacity is raised will present opinion evidence which is one of the exceptions to the rule of inadmissibility of opinion evidence. Mental health professionals providing their opinion evidence are, however, prohibited from expressing opinions on so-called "ultimate issues" upon which only the court may ultimately rule upon. The latter rule is also commonly known in practice as the "ultimate issue" rule which presents multifaceted challenges in respect of the application of the defence of pathological criminal incapacity. In this article, the author assesses the application of the ultimate issue rule with reference to the defence of pathological criminal incapacity as it operates within the South African criminal law context. A comparative analysis is also provided with reference to the rule as it operates in the United States of America and more specifically Federal Rule 704. It is concluded that the ultimate issue rule unnecessarily restricts testimony provided by mental health professionals as such placing a barrier on such evidence. As such, it is argued that the rule is superfluous as it remains within the discretion of the trier of fact to decide as to what weight to attach to such evidence. Copyright © 2015. Published by Elsevier Ltd.

A historical perspective on crush syndrome: the clinical application of its pathogenesis, established by the study of wartime crush injuries.

PubMed

Peiris, Dilini

2017-04-01

Crush syndrome is a fine example of how pathology can play a direct role in revealing the best treatment and management for diseases. It can occur when crush injuries are sustained. Skeletal muscle becomes damaged under the weight of a heavy object, and victims experience severe shock and renal failure. The discovery of the pathology of crush syndrome belongs to two individuals: Seigo Minami and Eric Bywaters. They separately helped to define the pathogenesis of crush syndrome during World Wars I and II. Seigo Minami is believed to have been the first to record the pathogenesis of crush syndrome. In 1923, he described the cases of three soldiers who died of renal failure caused by crush injury during World War I. Using microscopic studies to investigate the pathology of their kidneys, he found the soldiers had died due to 'autointoxication' caused by rhabdomyolysis. This discovery was not known to Eric Bywaters, who described crush syndrome in 1941, having studied victims of the London Blitz during World War II. He defined the 'autointoxication' as the release of rhabdomyolysis products via reperfusion. He therefore established the need for emergency fluid replacement to treat crush syndrome. The findings made by Minami and Bywaters highlight a remarkable achievement in clinical pathology, despite the adversity of war. It is these findings on which current guidelines are based. By reviewing their work, it is hoped that the role of pathology can be better appreciated as a valuable resource for delineating the treatment and management of diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Opportunities and challenges associated with clinical diagnostic genome sequencing: a report of the Association for Molecular Pathology.

PubMed

Schrijver, Iris; Aziz, Nazneen; Farkas, Daniel H; Furtado, Manohar; Gonzalez, Andrea Ferreira; Greiner, Timothy C; Grody, Wayne W; Hambuch, Tina; Kalman, Lisa; Kant, Jeffrey A; Klein, Roger D; Leonard, Debra G B; Lubin, Ira M; Mao, Rong; Nagan, Narasimhan; Pratt, Victoria M; Sobel, Mark E; Voelkerding, Karl V; Gibson, Jane S

2012-11-01

This report of the Whole Genome Analysis group of the Association for Molecular Pathology illuminates the opportunities and challenges associated with clinical diagnostic genome sequencing. With the reality of clinical application of next-generation sequencing, technical aspects of molecular testing can be accomplished at greater speed and with higher volume, while much information is obtained. Although this testing is a next logical step for molecular pathology laboratories, the potential impact on the diagnostic process and clinical correlations is extraordinary and clinical interpretation will be challenging. We review the rapidly evolving technologies; provide application examples; discuss aspects of clinical utility, ethics, and consent; and address the analytic, postanalytic, and professional implications. Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Confounders in interpreting pathology for safety and risk assessment

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

Wolf, Douglas C.; Mann, Peter C.

2005-02-01

The contribution of pathology to toxicity assessment is invaluable but often not clearly understood. Pathology endpoints are the central response around which human health risk assessment is frequently determined; therefore, it is important that the general toxicology community understand current concepts and nomenclature of toxicologic pathology. Toxicologic pathology encompasses the study of changes in tissue morphology that help define the risk of exposure to xenobiotics. Toxicologic pathology is a discipline that has changed and adapted over time including methods of analysis and nomenclature of lesions. As risk assessments are updated for chemicals in commerce, frequently the older literature must bemore » reviewed and reevaluated. When interpreting pathology data from animal studies, it is important to consider the biological significance of a lesion as well as its relationship to the ultimate adverse health effect. Assessing the potential for a chemical to cause harm to humans must include the examination of the entire pathology database in context of the study design, the mode of action of the chemical of concern, and using the most current interpretation of a lesion to determine the significance for human health effects of a particular tissue response.« less

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

PubMed

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

2017-03-01

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

Recent developments in emerging therapeutic targets of osteoarthritis.

PubMed

Sun, Margaret Man-Ger; Beier, Frank; Pest, Michael A

2017-01-01

Despite the tremendous individual suffering and socioeconomic burden caused by osteoarthritis, there are currently no effective disease-modifying treatment options. This is in part because of our incomplete understanding of osteoarthritis disease mechanism. This review summarizes recent developments in therapeutic targets identified from surgical animal models of osteoarthritis that provide novel insight into osteoarthritis pathology and possess potential for progression into preclinical studies. Several candidate pathways and processes that have been identified include chondrocyte autophagy, growth factor signaling, inflammation, and nociceptive signaling. Major strategies that possess therapeutic potential at the cellular level include inhibiting autophagy suppression and decreasing reactive oxygen species (ROS) production. Cartilage anabolism and prevention of cartilage degradation has been shown to result from growth factor signaling modulation, such as TGF-β, TGF-α, and FGF; however, the results are context-dependent and require further investigation. Pain assessment studies in rodent surgical models have demonstrated potential in employing anti-NGF strategies for minimizing osteoarthritis-associated pain. Studies of potential therapeutic targets in osteoarthritis using animal surgical models are helping to elucidate osteoarthritis pathology and propel therapeutics development. Further studies should continue to elucidate pathological mechanisms and therapeutic targets in various joint tissues to improve overall joint health.

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

PubMed

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

2017-01-01

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

The overall pathological status of the left hippocampus determines preoperative verbal memory performance in left mesial temporal lobe epilepsy.

PubMed

Witt, Juri-Alexander; Coras, Roland; Schramm, Johannes; Becker, Albert J; Elger, Christian E; Blümcke, Ingmar; Helmstaedter, Christoph

2014-04-01

Studies on hippocampal cell loss in epilepsy have produced diverging evidence as to which subfields are specifically related to memory. This may be due to rather small and often heterogeneous samples, or to different memory measures. Therefore, the current study examined hippocampal cell densities and memory in a large sample of patients with solely mesial temporal lobe epilepsy (mTLE), employing measures with proven sensitivity to mesiotemporal pathology. In 104 patients who had undergone epilepsy surgery for mTLE, we evaluated the role of segmental hippocampal cell loss and its underlying factor structure with regard to presurgical verbal and figural memory while controlling for side-of-surgery and hemispheric dominance. First of all, patients showed material-specific memory impairment concordant with the lateralization of epilepsy. Factor analysis of segmental cell loss revealed a single factor reflecting the overall integrity of the hippocampus. The overall pathological status of the left hippocampus correlated with verbal memory parameters (r = 0.33-0.34, P < 0.05), especially when controlling for atypical hemispheric dominance (r = 0.50-0.57, P < 0.01), and explained up to 33% of the observed variance. Further analyses revealed no superior role of a single subfield or cell loss pattern for memory performance. No systematic relations between neuronal cell densities of the right hippocampus and memory function were found, nor did left or right hippocampal pathology explain figural memory parameters. The results suggest that the overall pathological status of the left hippocampus - rather than a specific subfield pathology - is predictive for verbal memory in mTLE. The finding that figural memory parameters, although sensitive to right mTLE, were not related to neuronal cell densities of the right hippocampus, puts the left/right hippocampus verbal/nonverbal memory dichotomy into perspective. Copyright © 2013 Wiley Periodicals, Inc.

Gender differences in both the pathology and surgical outcome of patients with esophageal achalasia.

PubMed

Tsuboi, Kazuto; Omura, Nobuo; Yano, Fumiaki; Hoshino, Masato; Yamamoto, Se-Ryung; Akimoto, Shusuke; Masuda, Takahiro; Kashiwagi, Hideyuki; Yanaga, Katsuhiko

2016-12-01

Esophageal achalasia is a relatively rare disease that occurs usually in middle-aged patients. The laparoscopic Heller-Dor (LHD) procedure is the gold-standard surgical treatment for esophageal achalasia. There are many studies on the pathology and surgical outcome of esophageal achalasia from various perspectives, but there are no studies on gender differences in both the pathology and surgical outcome. This study aimed to evaluate gender differences in the surgical outcome with the LHD procedure and in the pathology of esophageal achalasia patients. The study included 474 LHD-treated patients who were postoperatively followed up for 6 months or more. The patients were divided into 2 groups by gender, to compare the preoperative pathology, surgical outcome, symptom scores before and after LHD, symptom score improvement frequency, and patient satisfaction with the surgery. The study population consisted of 248 male and 226 female, having a mean age of 45.1 years. There were no gender differences in the preoperative pathology, but a significantly lower BMI (p < 0.0001) and a smaller esophageal dilation (p = 0.0061) were observed in the female group. The frequency and severity of chest pain before the surgery were significantly higher in the female group (p = 0.0117 and p = 0.0103, respectively), and the improvement in both the frequency and severity of chest pain was significantly higher in the female group (p = 0.0005 and p = 0.003, respectively). No differences were identified in the surgical outcomes and postoperative course. The patient satisfaction with the surgery was high in both groups and comparable (p = 0.6863). The female patients with esophageal achalasia were characterized by low BMI, less esophageal dilation, and increased frequency and severity of chest pain. LHD improved the chest pain in the female patients, whereas the surgical outcome and satisfaction with the surgery were excellent regardless of gender.

Deciphering Sources of Variability in Clinical Pathology.

PubMed

Tripathi, Niraj K; Everds, Nancy E; Schultze, A Eric; Irizarry, Armando R; Hall, Robert L; Provencher, Anne; Aulbach, Adam

2017-01-01

The objectives of this session were to explore causes of variability in clinical pathology data due to preanalytical and analytical variables as well as study design and other procedures that occur in toxicity testing studies. The presenters highlighted challenges associated with such variability in differentiating test article-related effects from the effects of experimental procedures and its impact on overall data interpretation. These presentations focused on preanalytical and analytical variables and study design-related factors and their influence on clinical pathology data, and the importance of various factors that influence data interpretation including statistical analysis and reference intervals. Overall, these presentations touched upon potential effect of many variables on clinical pathology parameters, including animal physiology, sample collection process, specimen handling and analysis, study design, and some discussion points on how to manage those variables to ensure accurate interpretation of clinical pathology data in toxicity studies. This article is a brief synopsis of presentations given in a session entitled "Deciphering Sources of Variability in Clinical Pathology-It's Not Just about the Numbers" that occurred at the 35th Annual Symposium of the Society of Toxicologic Pathology in San Diego, California.

Do schema processes mediate links between parenting and eating pathology?

PubMed

Sheffield, Alex; Waller, Glenn; Emanuelli, Francesca; Murray, James; Meyer, Caroline

2009-07-01

Adverse parenting experiences are commonly linked to eating pathology. A schema-based model of the development and maintenance of eating pathology proposes that one of the potential mediators of the link between parenting and eating pathology might be the development of schema maintenance processes--mechanisms that operate to help the individual avoid intolerable emotions. To test this hypothesis, 353 female students and 124 female eating-disordered clients were recruited. They completed a measure of perceived parenting experiences as related to schema development (Young Parenting Inventory-Revised (YPI-R)), two measures of schema processes (Young Compensatory Inventory; Young-Rygh Avoidance Inventory (YRAI)) and a measure of eating pathology (Eating Disorders Inventory (EDI)). In support of the hypothesis, certain schema processes did mediate the relationship between specific perceptions of parenting and particular forms of eating pathology, although these were different for the clinical and non-clinical samples. In those patients where parenting is implicated in the development of eating pathology, treatment might need to target the cognitive processes that can explain this link. 2009 John Wiley & Sons, Ltd and Eating Disorders Association

The role of potential agents in making spatial perspective taking social

PubMed Central

Clements-Stephens, Amy M.; Vasiljevic, Katarina; Murray, Alexandra J.; Shelton, Amy L.

2013-01-01

A striking relationship between visual spatial perspective taking (VSPT) and social skills has been demonstrated for perspective-taking tasks in which the target of the imagined or inferred perspective is a potential agent, suggesting that the presence of a potential agent may create a social context for the seemingly spatial task of imagining a novel visual perspective. In a series of studies, we set out to investigate how and when a target might be viewed as sufficiently agent-like to incur a social influence on VSPT performance. By varying the perceptual and conceptual features that defined the targets as potential agents, we find that even something as simple as suggesting animacy for a simple wooden block may be sufficient. More critically, we found that experience with one potential agent influenced the performance with subsequent targets, either by inducing or eliminating the influence of social skills on VSPT performance. These carryover effects suggest that the relationship between social skills and VSPT performance is mediated by a complex relationship that includes the task, the target, and the context in which that target is perceived. These findings highlight potential problems that arise when identifying a task as belonging exclusively to a single cognitive domain and stress instead the highly interactive nature of cognitive domains and their susceptibility to cross-domain individual differences. PMID:24046735

[The experimental research of inner ear metabolism and electrical physiology of autoimmune sensorineural hearing loss].

PubMed

Tan, C; Cao, Y; Hu, P

1998-09-01

Inquire into the mechanism of inner ear pathological physiology in autoimmune sensorineural hearing loss (ASHL). With the auditory electric-physiological techniques and enzyme-histochemical method, the change of inner ear hearing function and enzyme activity were observed. These animals, which threshold of auditory nerve compound active potential (CAP) and cochlear microphonic potential(CM) heightening evidently, showed that the amplitude of endolymphatic potential(EP) (include-EP) bring down in various degrees, which was related to the change of the active of Na(+)-K(+)-ATPase and SDH in vascularis stria and endolymphatic sac. The abnormality of enzymes metabolism in inner ear tissues, which following autoimmune inflammation damage, is the pathological foundation of hearing dysfunction.

Impulsivity, self-regulation,and pathological video gaming among youth: testing a mediation model.

PubMed

Liau, Albert K; Neo, Eng Chuan; Gentile, Douglas A; Choo, Hyekyung; Sim, Timothy; Li, Dongdong; Khoo, Angeline

2015-03-01

Given the potential negative mental health consequences of pathological video gaming, understanding its etiology may lead to useful treatment developments. The purpose of the study was to examine the influence of impulsive and regulatory processes on pathological video gaming. Study 1 involved 2154 students from 6 primary and 4 secondary schools in Singapore. Study 2 involved 191 students from 2 secondary schools. The results of study 1 and study 2 supported the hypothesis that self-regulation is a mediator between impulsivity and pathological video gaming. Specifically, higher levels of impulsivity was related to lower levels of self-regulation, which in turn was related to higher levels of pathological video gaming. The use of impulsivity and self-regulation in predicting pathological video gaming supports the dual-system model of incorporating both impulsive and reflective systems in the prediction of self-control outcomes. The study highlights the development of self-regulatory resources as a possible avenue for future prevention and treatment research. © 2011 APJPH.

Digital pathology in nephrology clinical trials, research, and pathology practice.

PubMed

Barisoni, Laura; Hodgin, Jeffrey B

2017-11-01

In this review, we will discuss (i) how the recent advancements in digital technology and computational engineering are currently applied to nephropathology in the setting of clinical research, trials, and practice; (ii) the benefits of the new digital environment; (iii) how recognizing its challenges provides opportunities for transformation; and (iv) nephropathology in the upcoming era of kidney precision and predictive medicine. Recent studies highlighted how new standardized protocols facilitate the harmonization of digital pathology database infrastructure and morphologic, morphometric, and computer-aided quantitative analyses. Digital pathology enables robust protocols for clinical trials and research, with the potential to identify previously underused or unrecognized clinically useful parameters. The integration of digital pathology with molecular signatures is leading the way to establishing clinically relevant morpho-omic taxonomies of renal diseases. The introduction of digital pathology in clinical research and trials, and the progressive implementation of the modern software ecosystem, opens opportunities for the development of new predictive diagnostic paradigms and computer-aided algorithms, transforming the practice of renal disease into a modern computational science.

Elevated C-reactive protein and posttraumatic stress pathology among survivors of the 9/11 World Trade Center attacks.

PubMed

Rosen, Rebecca L; Levy-Carrick, Nomi; Reibman, Joan; Xu, Ning; Shao, Yongzhao; Liu, Mengling; Ferri, Lucia; Kazeros, Angeliki; Caplan-Shaw, Caralee E; Pradhan, Deepak R; Marmor, Michael; Galatzer-Levy, Isaac R

2017-06-01

Systemic inflammation has emerged as a promising marker and potential mechanism underlying post-traumatic stress disorder (PTSD). The relationship between posttraumatic stress pathology and systemic inflammation has not, however, been consistently replicated and is potentially confounded by comorbid illness or injury, common complications of trauma exposure. We analyzed a large naturalistic cohort sharing a discrete physical and mental health trauma from the destruction of the World Trade Center (WTC) towers on September 11, 2001 (n = 641). We evaluated the relationship between multiple physical and mental health related indices collected through routine evaluations at the WTC Environmental Health Center (WTC EHC), a treatment program for community members exposed to the disaster. C-Reactive Protein (CRP), a marker of systemic inflammation, was examined in relation to scores for PTSD, PTSD symptom clusters (re-experiencing, avoidance, negative cognitions/mood, arousal), depression and anxiety, while controlling for WTC exposures, lower respiratory symptoms, age, sex, BMI and smoking as potential risks or confounders. CRP was positively associated with PTSD severity (p < 0.001), trending toward association with depression (p = 0.06), but not with anxiety (p = 0.27). CRP was positively associated with re-experiencing (p < 0.001) and avoidance (p < 0.05) symptom clusters, and trended toward associations with negative cognitions/mood (p = 0.06) and arousal (p = 0.08). In this large study of the relationship between CRP and posttraumatic stress pathology, we demonstrated an association between systemic inflammation and stress pathology (PTSD; trending with depression), which remained after adjusting for potentially confounding variables. These results contribute to research findings suggesting a salient relationship between inflammation and posttraumatic stress pathology. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Schistosoma egg-induced liver pathology resolution by Sm-p80-based schistosomiasis vaccine in baboons.

PubMed

Le, Loc; Molehin, Adebayo J; Nash, Stewart; Sennoune, Souad R; Ahmad, Gul; Torben, Workineh; Zhang, Weidong; Siddiqui, Afzal A

2018-05-05

Schistosomiasis remains a serious chronic debilitating hepato-intestinal disease. Current control measures based on mass drug administration are inadequate due to sustained re-infection rates, low treatment coverage and emergence of drug resistance. Hence, there is an urgent need for a schistosomiasis vaccine for disease control. In this study, we assessed the anti-pathology efficacy of Schistosoma mansoni large subunit of calpain (Sm-p80)-based vaccine against schistosomiasis caused by infections with Schistosoma mansoni in baboons. We also evaluated the disease transmission-blocking potential of Sm-p80 vaccine. Immunisations with Sm-p80-based vaccine resulted in significant reduction of hepatic egg load in vaccinated baboons (67.7% reduction, p = 0.0032) when compared to the control animals, indicative of reduction in pathology. There was also a significant reduction in sizes of egg-induced granulomas in baboons immunised with Sm-p80 vaccine compared to their control counterparts. Egg hatching rate analysis revealed an overall 85.6% reduction (p = 0.0018) in vaccinated animals compared to the controls, highlighting the potential role of Sm-p80 vaccine in disease transmission. The findings on anti-pathology efficacy and transmission-blocking potential presented in this study have formed the basis for a large-scale double-blinded baboon experiment that is currently underway. Copyright © 2018 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Nootropic potential of Ashwagandha leaves: Beyond traditional root extracts.

PubMed

Wadhwa, Renu; Konar, Arpita; Kaul, Sunil C

2016-05-01

Rapidly increasing aging population and environmental stressors are the two main global concerns of the modern society. These have brought in light rapidly increasing incidence of a variety of pathological conditions including brain tumors, neurodegenerative & neuropsychiatric disorders, and new challenges for their treatment. The overlapping symptoms, complex etiology and lack of full understanding of the brain structure and function to-date further complicate these tasks. On the other hand, several herbal reagents with a long history of their use have been asserted to possess neurodifferentiation, neuroregenerative and neuroprotective potentials, and hence been recommended as supplement to enhance and maintain brain health and function. Although they have been claimed to function by holistic approach resulting in maintaining body homeostasis and brain health, there are not enough laboratory studies in support to these and mechanism(s) of such beneficial activities remain largely undefined. One such herb is Ashwagandha, also called "Queen of Ayurveda" for its popular use in Indian traditional home medicine because of its extensive benefits including anticancer, anti-stress and remedial potential for aging and neurodegenerative pathologies. However, active principles and underlying mechanism(s) of action remain largely unknown. Here we provide a review on the effects of Ashwagandha extracts and active principles, and underlying molecular mechanism(s) for brain pathologies. We highlight our findings on the nootropic potential of Ashwagandha leaves. The effects of Ashwagandha leaf extracts are multidimensional ranging from differentiation of neuroblastoma and glioma cells, reversal of Alzheimer and Parkinson's pathologies, protection against environmental neurotoxins and enhancement of memory. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pathological evaluation of postmortem human eyes implanted with a new single-piece hydrophobic acrylic lens.

PubMed

Izak, Andrea M; Werner, Liliana; Pandey, Suresh K; Apple, David J

2004-07-01

To report the pathological findings in 14 human cadaver eyes implanted with a single-piece AcrySof(Alcon Laboratories) posterior chamber intraocular lens (IOL). David J. Apple, MD Laboratories for Ophthalmic Devices Research, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. Fourteen human autopsy eyes implanted with a single-piece AcrySof (SA30AL) IOL were evaluated. The eyes were sectioned at the equatorial plane, and the anterior segment containing the IOL in the capsular bag was evaluated from a posterior perspective (Miyake-Apple view) and from an anterior perspective (surgeon's view) after removal of cornea and iris. They were then processed through paraffin, sectioned, and stained with hematoxylin-eosin, periodic acid-Schiff, and Masson's trichrome and examined under light microscopy. All IOLs had symmetric in-the-bag fixation. Slight decentration was measured in 1 eye, which also had an anterior capsule tear. Grade 1 anterior capsule opacification was present in 9 eyes. No central posterior capsule opacification or posterior capsule folds were observed in any eye. Soemmering's ring formation was observed in 5 eyes. Zonular stretch caused by different degrees of capsular bag contraction was present in 4 eyes without decentration of the IOL. Analyses of pseudophakic cadaver eyes from the posterior (Miyake-Apple) view, complemented by microscopic analyses, proved useful in the evaluation of IOL-capsular bag interaction. These studies are more important in cases of newly introduced lens designs.

The Rho-ROCK pathway as a new pathological mechanism of innate immune subversion in chronic myeloid leukaemia.

PubMed

Basbous, Sara; Levescot, Anaïs; Piccirilli, Nathalie; Brizard, Françoise; Guilhot, François; Roy, Lydia; Bourmeyster, Nicolas; Gombert, Jean-Marc; Herbelin, André

2016-11-01

CD1d-restricted invariant natural killer T (iNKT) cells are believed to play a key role in cancer immune surveillance, and are functionally deficient in patients with chronic myeloid leukaemia (CML). Herein, we have hypothesized that this defect might originate from BCR-ABL-dependent dysfunctions in myeloid dendritic cells (mDCs). Indeed, flow cytometry and confocal microscopy revealed that cell surface expression of CD1d was downregulated in CML mDCs, relative to healthy donor (HD) controls. The decreased cell surface display of CD1d could not be ascribed to defective mDC differentiation, as attested by normal expression of HLA-DR and the CD86 maturation marker. On the other hand, reduced membrane expression was not associated with decreased intracytoplasmic levels of CD1d or its mRNA transcripts, consistent with intracellular retention. In vitro treatment of CML mDCs with the Rho-associated protein kinase (ROCK) inhibitor Y-27632 partially restored both cell surface CD1d expression and CD1d-mediated antigen presentation, whereas it had no effect on HD mDCs. An inhibitor of BCR-ABL tyrosine kinase (TK), imatinib mesylate (IM), had no such activity. Similar recovery of CD1d expression occurred with fasudil, another ROCK inhibitor that is commonly used in clinical trials. Our data support the conclusion that BCR-ABL-dependent ROCK, but not TK, is involved in CD1d downregulation. We propose that ROCK, which is most likely activated by the DH/PH domain of BCR-ABL, mediates iNKT-cell immune subversion in CML patients by downregulating CD1d expression on CML mDCs. Our study reveals the ROCK-mDC axis as a new potential target to restore immune surveillance in patients with CML, offering new therapeutic perspectives for CML treatment. 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 P2X7 Receptor in Inflammatory Diseases: Angel or Demon?

PubMed Central

Savio, Luiz E. B.; de Andrade Mello, Paola; da Silva, Cleide Gonçalves; Coutinho-Silva, Robson

2018-01-01

Under physiological conditions, adenosine triphosphate (ATP) is present at low levels in the extracellular milieu, being massively released by stressed or dying cells. Once outside the cells, ATP and related nucleotides/nucleoside generated by ectonucleotidases mediate a high evolutionary conserved signaling system: the purinergic signaling, which is involved in a variety of pathological conditions, including inflammatory diseases. Extracellular ATP has been considered an endogenous adjuvant that can initiate inflammation by acting as a danger signal through the activation of purinergic type 2 receptors—P2 receptors (P2Y G-protein coupled receptors and P2X ligand-gated ion channels). Among the P2 receptors, the P2X7 receptor is the most extensively studied from an immunological perspective, being involved in both innate and adaptive immune responses. P2X7 receptor activation induces large-scale ATP release via its intrinsic ability to form a membrane pore or in association with pannexin hemichannels, boosting purinergic signaling. ATP acting via P2X7 receptor is the second signal to the inflammasome activation, inducing both maturation and release of pro-inflammatory cytokines, such as IL-1β and IL-18, and the production of reactive nitrogen and oxygen species. Furthermore, the P2X7 receptor is involved in caspases activation, as well as in apoptosis induction. During adaptive immune response, P2X7 receptor modulates the balance between the generation of T helper type 17 (Th17) and T regulatory (Treg) lymphocytes. Therefore, this receptor is involved in several inflammatory pathological conditions. In infectious diseases and cancer, P2X7 receptor can have different and contrasting effects, being an angel or a demon depending on its level of activation, cell studied, type of pathogen, and severity of infection. In neuroinflammatory and neurodegenerative diseases, P2X7 upregulation and function appears to contribute to disease progression. In this review, we deeply discuss P2X7 receptor dual function and its pharmacological modulation in the context of different pathologies, and we also highlight the P2X7 receptor as a potential target to treat inflammatory related diseases. PMID:29467654

Effects of Ambient Air Pollution Exposure on Olfaction: A Review

PubMed Central

Ajmani, Gaurav S.; Suh, Helen H.; Pinto, Jayant M.

2016-01-01

Background: Olfactory dysfunction affects millions of people worldwide. This sensory impairment is associated with neurodegenerative disease and significantly decreased quality of life. Exposure to airborne pollutants has been implicated in olfactory decline, likely due to the anatomic susceptibility of the olfactory nerve to the environment. Historically, studies have focused on occupational exposures, but more recent studies have considered effects from exposure to ambient air pollutants. Objectives: To examine all relevant human data evaluating a link between ambient pollution exposure and olfaction and to review supporting animal data in order to examine potential mechanisms for pollution-associated olfactory loss. Methods: We identified and reviewed relevant articles from 1950 to 2015 using PubMed and Web of Science and focusing on human epidemiologic and pathophysiologic studies. Animal studies were included only to support pertinent data on humans. We reviewed findings from these studies evaluating a relationship between environmental pollutant exposure and olfactory function. Results: We identified and reviewed 17 articles, with 1 additional article added from a bibliography search, for a total of 18 human studies. There is evidence in human epidemiologic and pathologic studies that increased exposure to ambient air pollutants is associated with olfactory dysfunction. However, most studies have used proxies for pollution exposure in small samples of convenience. Human pathologic studies, with supporting animal work, have also shown that air pollution can contact the olfactory epithelium, translocate to the olfactory bulb, and migrate to the olfactory cortex. Pollutants can deposit at each location, causing direct damage and disruption of tissue morphology or inducing local inflammation and cellular stress responses. Conclusions: Ambient air pollution may impact human olfactory function. Additional studies are needed to examine air pollution–related olfactory impacts on the general population using measured pollution exposures and to link pollution exposure with olfactory dysfunction and related pathology. Citation: Ajmani GS, Suh HH, Pinto JM. 2016. Effects of ambient air pollution exposure on olfaction: a review. Environ Health Perspect 124:1683–1693; http://dx.doi.org/10.1289/EHP136 PMID:27285588

Risk for exercise dependence, eating disorder pathology, alcohol use disorder and addictive behaviors among clients of fitness centers.

PubMed

Müller, Astrid; Loeber, Sabine; Söchtig, Johanna; Te Wildt, Bert; De Zwaan, Martina

2015-12-01

Exercise dependence (EXD) is considered a behavioral addiction that is often associated with eating disorders. To date, only few studies examined the potential overlap between EXD and other addictive behaviors. Therefore, the present study aimed at investigating the relationship of EXD with pathological buying, pathological video gaming (offline and online), hypersexual behavior, and alcohol use disorder in a sample of clients of fitness centers. The following questionnaires were answered by 128 individuals (age M = 26.5, SD = 6.7 years; 71.7% men, 74.2% university students): Exercise Dependence Scale, Eating Disorder Examination-Questionnaire, Compulsive Buying Scale, Pathological Computer-Gaming Scale, Hypersexual Behavior Inventory, and Alcohol Use Disorders Identification Test (AUDIT). 7.8% of the sample were at-risk for EXD, 10.9% reported eating disorder pathology, 2.3% pathological buying, 3.1% hypersexual behavior, and none of the participants suffered from pathological video gaming. The criteria for severe alcohol disorder pathology (AUDIT ≥ 16) were fulfilled by 10.2%. With regard to continuous symptom scores, EXD symptoms were positively correlated with both eating disorder pathology and pathological buying but not with pathological video gaming, hypersexuality or alcohol use disorder. It is noteworthy that more symptoms of pathological buying corresponded with more symptoms of hypersexual behavior. The correlation pattern did not differ by gender. The co-occurrence of EXD, pathological buying and hypersexual behavior on a subclinical level or in the early stage of the disorders should be taken into account when assessing and treating patients. More research is warranted in order to investigate possible interactions between these conditions.

Risk for exercise dependence, eating disorder pathology, alcohol use disorder and addictive behaviors among clients of fitness centers

PubMed Central

Müller, Astrid; Loeber, Sabine; Söchtig, Johanna; Te Wildt, Bert; De Zwaan, Martina

2015-01-01

Background and Aims Exercise dependence (EXD) is considered a behavioral addiction that is often associated with eating disorders. To date, only few studies examined the potential overlap between EXD and other addictive behaviors. Therefore, the present study aimed at investigating the relationship of EXD with pathological buying, pathological video gaming (offline and online), hypersexual behavior, and alcohol use disorder in a sample of clients of fitness centers. Methods The following questionnaires were answered by 128 individuals (age M = 26.5, SD = 6.7 years; 71.7% men, 74.2% university students): Exercise Dependence Scale, Eating Disorder Examination-Questionnaire, Compulsive Buying Scale, Pathological Computer-Gaming Scale, Hypersexual Behavior Inventory, and Alcohol Use Disorders Identification Test (AUDIT). Results 7.8% of the sample were at-risk for EXD, 10.9% reported eating disorder pathology, 2.3% pathological buying, 3.1% hypersexual behavior, and none of the participants suffered from pathological video gaming. The criteria for severe alcohol disorder pathology (AUDIT ≥ 16) were fulfilled by 10.2%. With regard to continuous symptom scores, EXD symptoms were positively correlated with both eating disorder pathology and pathological buying but not with pathological video gaming, hypersexuality or alcohol use disorder. It is noteworthy that more symptoms of pathological buying corresponded with more symptoms of hypersexual behavior. The correlation pattern did not differ by gender. Discussion The co-occurrence of EXD, pathological buying and hypersexual behavior on a subclinical level or in the early stage of the disorders should be taken into account when assessing and treating patients. More research is warranted in order to investigate possible interactions between these conditions. PMID:26690622

A Design Study Investigating Augmented Reality and Photograph Annotation in a Digitalized Grossing Workstation

PubMed Central

Chow, Joyce A.; Törnros, Martin E.; Waltersson, Marie; Richard, Helen; Kusoffsky, Madeleine; Lundström, Claes F.; Kurti, Arianit

2017-01-01

Context: Within digital pathology, digitalization of the grossing procedure has been relatively underexplored in comparison to digitalization of pathology slides. Aims: Our investigation focuses on the interaction design of an augmented reality gross pathology workstation and refining the interface so that information and visualizations are easily recorded and displayed in a thoughtful view. Settings and Design: The work in this project occurred in two phases: the first phase focused on implementation of an augmented reality grossing workstation prototype while the second phase focused on the implementation of an incremental prototype in parallel with a deeper design study. Subjects and Methods: Our research institute focused on an experimental and “designerly” approach to create a digital gross pathology prototype as opposed to focusing on developing a system for immediate clinical deployment. Statistical Analysis Used: Evaluation has not been limited to user tests and interviews, but rather key insights were uncovered through design methods such as “rapid ethnography” and “conversation with materials”. Results: We developed an augmented reality enhanced digital grossing station prototype to assist pathology technicians in capturing data during examination. The prototype uses a magnetically tracked scalpel to annotate planned cuts and dimensions onto photographs taken of the work surface. This article focuses on the use of qualitative design methods to evaluate and refine the prototype. Our aims were to build on the strengths of the prototype's technology, improve the ergonomics of the digital/physical workstation by considering numerous alternative design directions, and to consider the effects of digitalization on personnel and the pathology diagnostics information flow from a wider perspective. A proposed interface design allows the pathology technician to place images in relation to its orientation, annotate directly on the image, and create linked information. Conclusions: The augmented reality magnetically tracked scalpel reduces tool switching though limitations in today's augmented reality technology fall short of creating an ideal immersive workflow by requiring the use of a monitor. While this technology catches up, we recommend focusing efforts on enabling the easy creation of layered, complex reports, linking, and viewing information across systems. Reflecting upon our results, we argue for digitalization to focus not only on how to record increasing amounts of data but also how these data can be accessed in a more thoughtful way that draws upon the expertise and creativity of pathology professionals using the systems. PMID:28966831

A Design Study Investigating Augmented Reality and Photograph Annotation in a Digitalized Grossing Workstation.

PubMed

Chow, Joyce A; Törnros, Martin E; Waltersson, Marie; Richard, Helen; Kusoffsky, Madeleine; Lundström, Claes F; Kurti, Arianit

2017-01-01

Within digital pathology, digitalization of the grossing procedure has been relatively underexplored in comparison to digitalization of pathology slides. Our investigation focuses on the interaction design of an augmented reality gross pathology workstation and refining the interface so that information and visualizations are easily recorded and displayed in a thoughtful view. The work in this project occurred in two phases: the first phase focused on implementation of an augmented reality grossing workstation prototype while the second phase focused on the implementation of an incremental prototype in parallel with a deeper design study. Our research institute focused on an experimental and "designerly" approach to create a digital gross pathology prototype as opposed to focusing on developing a system for immediate clinical deployment. Evaluation has not been limited to user tests and interviews, but rather key insights were uncovered through design methods such as " rapid ethnography " and " conversation with materials ". We developed an augmented reality enhanced digital grossing station prototype to assist pathology technicians in capturing data during examination. The prototype uses a magnetically tracked scalpel to annotate planned cuts and dimensions onto photographs taken of the work surface. This article focuses on the use of qualitative design methods to evaluate and refine the prototype. Our aims were to build on the strengths of the prototype's technology, improve the ergonomics of the digital/physical workstation by considering numerous alternative design directions, and to consider the effects of digitalization on personnel and the pathology diagnostics information flow from a wider perspective. A proposed interface design allows the pathology technician to place images in relation to its orientation, annotate directly on the image, and create linked information. The augmented reality magnetically tracked scalpel reduces tool switching though limitations in today's augmented reality technology fall short of creating an ideal immersive workflow by requiring the use of a monitor. While this technology catches up, we recommend focusing efforts on enabling the easy creation of layered, complex reports, linking, and viewing information across systems. Reflecting upon our results, we argue for digitalization to focus not only on how to record increasing amounts of data but also how these data can be accessed in a more thoughtful way that draws upon the expertise and creativity of pathology professionals using the systems.

Pathological anxiety in animals.

PubMed

Ohl, Frauke; Arndt, Saskia S; van der Staay, F Josef

2008-01-01

Selective breeding programmes in domestic and laboratory animals generally focus on physiological and/or anatomical characteristics. However, selection may have an (unintended) impact on other characteristics and may lead to dysfunctional behaviour that can affect biological functioning and, as a consequence, compromise welfare and quality of life. In this review it is proposed that various behavioural dysfunctions in animals are due to pathological anxiety. Although several approaches have been undertaken to specify the diagnostic criteria of pathological anxiety as a behavioural disorder in animals, the causal aetiology largely remains unknown. This is mainly due to the fact that integrated concepts, combining the behavioural syndrome and (neuro-) physiological processes, are widely lacking. Moreover, even the term anxiety itself represents a poorly defined concept or category. A definition is suggested and the potential causes of pathological anxiety are explored with a plea for developing adequate diagnostic tools and therapies to fight pathological anxiety in animals based on insight from scientific research.

The incidence of pathological gambling among Native Americans treated for alcohol dependence.

PubMed

Elia, C; Jacobs, D F

1993-05-01

The prevalence rate of potential and pathological gambling was examined among Native American and Caucasian patients (n = 85) being treated for alcohol dependence. Previous studies with alcohol-dependent (mainly Caucasian) populations revealed 10-15% to have gambling problems. This study, the first to measure pathological gambling among a Native American population, utilized the South Oaks Gambling Screen and was administered in a group setting, between 1/91 and 4/91 on the alcohol treatment ward of the Ft. Meade Veterans Administration Hospital. Results showed that 22% of the Native Americans studied (compared to 7.3% Caucasian), scored in a range indicating a probable pathological gambling addiction. Furthermore, 41% of the Native Americans studied (compared to 21.3% Caucasian) admitted to some difficulty with gambling. Education and treatment is encouraged to help stem projected radical increases in pathological gambling and related problems among this cultural group as Native American gambling becomes widespread.

Pathological Narcissism and Interpersonal Behavior in Daily Life

PubMed Central

Roche, Michael J.; Pincus, Aaron L.; Conroy, David E.; Hyde, Amanda L.; Ram, Nilam

2014-01-01

The Cognitive-Affective Processing System (CAPS) has been proposed as a useful meta-framework for integrating contextual differences in situations with individual differences in personality pathology. In this article, we evaluated the potential of combining the CAPS meta-framework and contemporary interpersonal theory to investigate how individual differences in pathological narcissism influenced interpersonal functioning in daily life. University students (N = 184) completed event-contingent reports about interpersonal interactions across a 7-day diary study. Using multilevel regression models, we found that combinations of narcissistic expression (grandiosity, vulnerability) were associated with different interpersonal behavior patterns reflective of interpersonal dysfunction. These results are among the first to empirically demonstrate the usefulness of the CAPS model to conceptualize personality pathology through the patterning of if-then interpersonal processes. PMID:23205698

Pathologic Criteria to Estimate the State of the Liver in Potential Donors.

PubMed

Shaimardanova, Caliya; Fedotovskikh, Galina; Savchuk, Aleksandr; Doszhan, Ainura; Smagulova, Aigerim; Gaipov, Abduzhappar

2015-11-01

The pathologic evaluation of the liver is one of the most important issues in liver transplants. We evaluated the histopathological condition of livers in potential donors. After liver biopsy, 37 potential donor livers were histologically studied. Liver tissue was stained by hematoxylin and eosin as well as Masson Trichrome. The results of the study showed the morphologic criteria used to estimate the state of the liver in potential donors is not only steatosis and fibrosis, but other important histologic criteria, such as proteinosis, necrosis of hepatocytes, endotheliitis of central veins, inflammatory infiltration, endarteritis in portal tracts and phlebitis in portal tracts, proliferation of the bile ducts, and cholestasis. Results of the study showed that the morphologic criteria to estimate the state of the liver in potential donors includes not only steatosis and fibrosis, but other important histologic criteria as well.

The physiological determinants of Sudden Infant Death Syndrome☆,☆☆

PubMed Central

Garcia, Alfredo J.; Koschnitzky, Jenna E.; Ramirez, Jan-Marino

2013-01-01

It is well-established that environmental and biological risk factors contribute to Sudden Infant Death Syndrome (SIDS). There is also growing consensus that SIDS requires the intersection of multiple risk factors that result in the failure of an infant to overcome cardio-respiratory challenges. Thus, the critical next steps in understanding SIDS are to unravel the physiological determinants that actually cause the sudden death, to synthesize how these determinants are affected by the known risk factors, and to develop novel ideas for SIDS prevention. In this review, we will examine current and emerging perspectives related to cardio-respiratory dysfunctions in SIDS. Specifically, we will review: (1) the role of the preBötzinger complex (preBötC) as a multi-functional network that is critically involved in the failure to adequately respond to hypoxic and hypercapnic challenges; (2) the potential involvement of the pre-BötC in the gender and age distributions that are characteristic for SIDS; (3) the link between SIDS and prematurity; and (4) the potential relationship between SIDS, auditory function, and central chemosensitivity. Each section underscores the importance of marrying the epidemiological and pathological data to experimental data in order to understand the physiological determinants of this syndrome. We hope that a better understanding will lead to novel ways to reduce the risk to succumb to SIDS. PMID:23735486

Three Dimensional Optical Coherence Tomography Imaging: Advantages and Advances

PubMed Central

Gabriele, Michelle L; Wollstein, Gadi; Ishikawa, Hiroshi; Xu, Juan; Kim, Jongsick; Kagemann, Larry; Folio, Lindsey S; Schuman, Joel S.

2010-01-01

Three dimensional (3D) ophthalmic imaging using optical coherence tomography (OCT) has revolutionized assessment of the eye, the retina in particular. Recent technological improvements have made the acquisition of 3D-OCT datasets feasible. However, while volumetric data can improve disease diagnosis and follow-up, novel image analysis techniques are now necessary in order to process the dense 3D-OCT dataset. Fundamental software improvements include methods for correcting subject eye motion, segmenting structures or volumes of interest, extracting relevant data post hoc and signal averaging to improve delineation of retinal layers. In addition, innovative methods for image display, such as C-mode sectioning, provide a unique viewing perspective and may improve interpretation of OCT images of pathologic structures. While all of these methods are being developed, most remain in an immature state. This review describes the current status of 3D-OCT scanning and interpretation, and discusses the need for standardization of clinical protocols as well as the potential benefits of 3D-OCT scanning that could come when software methods for fully exploiting these rich data sets are available clinically. The implications of new image analysis approaches include improved reproducibility of measurements garnered from 3D-OCT, which may then help improve disease discrimination and progression detection. In addition, 3D-OCT offers the potential for preoperative surgical planning and intraoperative surgical guidance. PMID:20542136

Patient-Derived iPSCs and iNs-Shedding New Light on the Cellular Etiology of Neurodegenerative Diseases.

PubMed

Tang, Bor Luen

2018-05-08

Induced pluripotent stem cells (iPSCs) and induced neuronal (iN) cells are very much touted in terms of their potential promises in therapeutics. However, from a more fundamental perspective, iPSCs and iNs are invaluable tools for the postnatal generation of specific diseased cell types from patients, which may offer insights into disease etiology that are otherwise unobtainable with available animal or human proxies. There are two good recent examples of such important insights with diseased neurons derived via either the iPSC or iN approaches. In one, induced motor neurons (iMNs) derived from iPSCs of Amyotrophic lateral sclerosis/Frontotemporal dementia (ALS/FTD) patients with a C9orf72 repeat expansion revealed a haploinsufficiency of protein function resulting from the intronic expansion and deficiencies in motor neuron vesicular trafficking and lysosomal biogenesis that were not previously obvious in knockout mouse models. In another, striatal medium spinal neurons (MSNs) derived directly from fibroblasts of Huntington’s disease (HD) patients recapitulated age-associated disease signatures of mutant Huntingtin (mHTT) aggregation and neurodegeneration that were not prominent in neurons differentiated indirectly via iPSCs from HD patients. These results attest to the tremendous potential for pathologically accurate and mechanistically revealing disease modelling with advances in the derivation of iPSCs and iNs.

Magical flight and monstrous stress: technologies of absorption and mental wellness in Azeroth.

PubMed

Snodgrass, Jeffrey G; Lacy, Michael G; Francois Dengah, H J; Fagan, Jesse; Most, David E

2011-03-01

Videogame players commonly report reaching deeply "immersive" states of consciousness, in some cases growing to feel like they actually are their characters and really in the game, with such fantastic characters and places potentially only loosely connected to offline selves and realities. In the current investigation, we use interview and survey data to examine the effects of such "dissociative" experiences on players of the popular online videogame, World of Warcraft (WoW). Of particular interest are ways in which WoW players' emotional identification with in-game second selves can lead either to better mental well-being, through relaxation and satisfying positive stress, or, alternatively, to risky addiction-like experiences. Combining universalizing and context-dependent perspectives, we suggest that WoW and similar games can be thought of as new "technologies of absorption"--contemporary practices that can induce dissociative states in which players attribute dimensions of self and experience to in-game characters, with potential psychological benefit or harm. We present our research as an empirically grounded exploration of the mental health benefits and risks associated with dissociation in common everyday contexts. We believe that studies such as ours may enrich existing theories of the health dynamics of dissociation, relying, as they often do, on data drawn either from Western clinical contexts involving pathological disintegrated personality disorders or from non-Western ethnographic contexts involving spiritual trance.

A scoping review of anorexia of aging correlates and their relevance to population health interventions.

PubMed

Roy, Mathieu; Gaudreau, Pierrette; Payette, Hélène

2016-10-01

Anorexia of aging (AA, i.e., loss of appetite and/or reduction of food intake with aging) is an important public health issue. It leads to unintentional weight loss, which is an independent risk factor for morbidity and mortality among seniors. AA has mainly been studied from a biological perspective and regarded as a normal physiological consequence of aging, rather than a negative health outcome with underlying determinants. Some potentially modifiable correlates have however been found to be associated with this geriatric condition. Here, we conducted a scoping review of the literature to: 1) identify AA correlates, and 2) discuss their relevance to population health interventions. Our results indicate two main categories of AA correlates, namely, physiopathological and non-physiopathological. The first category relates to physiological dysfunctions, pathologies involving (or culminating in) biomarker dysregulation, and polypharmacy. These correlates are difficult to modify, especially through population health interventions. The second category, which contains fewer correlates, includes potentially modifiable public health targets, such as food-related properties, psychological, sociocultural, and environmental issues. We conclude that there are several AA correlates. Some of them are modifiable and could be targeted for development and implementation as appropriate population health interventions to prevent appetite loss and promote maintenance of adequate food intake in aging. Copyright © 2016 Elsevier Ltd. All rights reserved.

Localization of Epileptogenic Zone With the Correction of Pathological Networks.

PubMed

Yang, Chuanzuo; Luan, Guoming; Wang, Qian; Liu, Zhao; Zhai, Feng; Wang, Qingyun

2018-01-01

Patients with focal drug-resistant epilepsy are potential candidates for surgery. Stereo-electroencephalograph (SEEG) is often considered as the "gold standard" to identify the epileptogenic zone (EZ) that accounts for the onset and propagation of epileptiform discharges. However, visual analysis of SEEG still prevails in clinical practice. In addition, epilepsy is increasingly understood to be the result of network disorder, but the specific organization of the epileptic network is still unclear. Therefore, it is necessary to quantitatively localize the EZ and investigate the nature of epileptogenic networks. In this study, intracranial recordings from 10 patients were analyzed through adaptive directed transfer function, and the out-degree of effective network was selected as the principal indicator to localize the epileptogenic area. Furthermore, a coupled neuronal population model was used to qualitatively simulate electrical activity in the brain. By removing individual populations, virtual surgery adjusting the network organization could be performed. Results suggested that the accuracy and detection rate of the EZ localization were 82.86 and 85.29%, respectively. In addition, the same stage shared a relatively stable connectivity pattern, while the patterns changed with transition to different processes. Meanwhile, eight cases of simulations indicated that networks in the ictal stage were more likely to generate rhythmic spikes. This indicated the existence of epileptogenic networks, which could enhance local excitability and facilitate synchronization. The removal of the EZ could correct these pathological networks and reduce the amount of spikes by at least 75%. This might be one reason why accurate resection could reduce or even suppress seizures. This study provides novel insights into epilepsy and surgical treatments from the network perspective.

Quantitative pathology in virtual microscopy: history, applications, perspectives.

PubMed

Kayser, Gian; Kayser, Klaus

2013-07-01

With the emerging success of commercially available personal computers and the rapid progress in the development of information technologies, morphometric analyses of static histological images have been introduced to improve our understanding of the biology of diseases such as cancer. First applications have been quantifications of immunohistochemical expression patterns. In addition to object counting and feature extraction, laws of thermodynamics have been applied in morphometric calculations termed syntactic structure analysis. Here, one has to consider that the information of an image can be calculated for separate hierarchical layers such as single pixels, cluster of pixels, segmented small objects, clusters of small objects, objects of higher order composed of several small objects. Using syntactic structure analysis in histological images, functional states can be extracted and efficiency of labor in tissues can be quantified. Image standardization procedures, such as shading correction and color normalization, can overcome artifacts blurring clear thresholds. Morphometric techniques are not only useful to learn more about biological features of growth patterns, they can also be helpful in routine diagnostic pathology. In such cases, entropy calculations are applied in analogy to theoretical considerations concerning information content. Thus, regions with high information content can automatically be highlighted. Analysis of the "regions of high diagnostic value" can deliver in the context of clinical information, site of involvement and patient data (e.g. age, sex), support in histopathological differential diagnoses. It can be expected that quantitative virtual microscopy will open new possibilities for automated histological support. Automated integrated quantification of histological slides also serves for quality assurance. The development and theoretical background of morphometric analyses in histopathology are reviewed, as well as their application and potential future implementation in virtual microscopy. Copyright © 2012 Elsevier GmbH. All rights reserved.

Dissociating electrophysiological correlates of subjective, objective, and correct memory in investigating the emotion-induced recognition bias.

PubMed

Windmann, Sabine; Hill, Holger

2014-10-01

Performance on tasks requiring discrimination of at least two stimuli can be viewed either from an objective perspective (referring to actual stimulus differences), or from a subjective perspective (corresponding to participant's responses). Using event-related potentials recorded during an old/new recognition memory test involving emotionally laden and neutral words studied either blockwise or randomly intermixed, we show here how the objective perspective (old versus new items) yields late effects of blockwise emotional item presentation at parietal sites that the subjective perspective fails to find, whereas the subjective perspective ("old" versus "new" responses) is more sensitive to early effects of emotion at anterior sites than the objective perspective. Our results demonstrate the potential advantage of dissociating the subjective and the objective perspective onto task performance (in addition to analyzing trials with correct responses), especially for investigations of illusions and information processing biases, in behavioral and cognitive neuroscience studies. Copyright © 2014 Elsevier Inc. All rights reserved.

Competing neurobehavioral decision systems theory of cocaine addiction: From mechanisms to therapeutic opportunities.

PubMed

Bickel, Warren K; Snider, Sarah E; Quisenberry, Amanda J; Stein, Jeffrey S; Hanlon, Colleen A

2016-01-01

Cocaine dependence is a difficult-to-treat, chronically relapsing disorder. Multiple scientific disciplines provide distinct perspectives on this disorder; however, connections between disciplines are rare. The competing neurobehavioral decision systems (CNDS) theory posits that choice results from the interaction between two decision systems (impulsive and executive) and that regulatory imbalance between systems can induce pathology, including addiction. Using this view, we integrate a diverse set of observations on cocaine dependence, including bias for immediacy, neural activity and structure, developmental time course, behavioral comorbidities, and the relationship between cocaine dependence and socioeconomic status. From the CNDS perspective, we discuss established and emerging behavioral, pharmacological, and neurological treatments and identify possible targets for future treatments. The ability of the CNDS theory to integrate diverse findings highlights its utility for understanding cocaine dependence and supports that dysregulation between the decision systems contributes to addiction. © 2016 Elsevier B.V. All rights reserved.

Introduction and historical perspective.

PubMed

Gunning, Peter

2008-01-01

Tropomyosin is a coiled coil dimer which forms a polymer along the major groove of the majority of actin filaments. It is therefore one of the two primary components of the actin filament. Our understanding of the biological function of tropomyosin has been driven almost entirely by its role in striated muscle. This reflects both its original discovery as part of the thin filament in skeletal muscle and its pivotal role in regulating muscle contraction. In contrast, its role in the function of the cytoskeleton of all cells has been poorly understood due, at least in part, to the technical challenge of deciphering the function of a large number of isoforms. This book has brought together many of the leading researchers who have defined the function of tropomyosin in both normal and pathological conditions. Each author brings their own perspective in a series of stand alone reviews of the areas of tropomyosin research they have played a major role in defining.

Competing neurobehavioral decision systems theory of cocaine addiction: From mechanisms to therapeutic opportunities

PubMed Central

Bickel, Warren K.; Snider, Sarah E.; Quisenberry, Amanda J.; Stein, Jeffrey S.; Hanlon, Colleen A.

2017-01-01

Cocaine dependence is a difficult-to-treat, chronically relapsing disorder. Multiple scientific disciplines provide distinct perspectives on this disorder; however, connections between disciplines are rare. The competing neurobehavioral decision systems (CNDS) theory posits that choice results from the interaction between two decision systems (impulsive and executive) and that regulatory imbalance between systems can induce pathology, including addiction. Using this view, we integrate a diverse set of observations on cocaine dependence, including bias for immediacy, neural activity and structure, developmental time course, behavioral comorbidities, and the relationship between cocaine dependence and socioeconomic status. From the CNDS perspective, we discuss established and emerging behavioral, pharmacological, and neurological treatments and identify possible targets for future treatments. The ability of the CNDS theory to integrate diverse findings highlights its utility for understanding cocaine dependence and supports that dysregulation between the decision systems contributes to addiction. PMID:26806781

Learning in the tutorial group: a balance between individual freedom and institutional control.

PubMed

McAllister, Anita; Aanstoot, Janna; Hammarström, Inger Lundeborg; Samuelsson, Christina; Johannesson, Eva; Sandström, Karin; Berglind, Ulrika

2014-01-01

The study investigates factors in problem-based learning tutorial groups which promote or inhibit learning. The informants were tutors and students from speech-language pathology and physiotherapy programmes. Semi-structured focus-group interviews and individual interviews were used. Results revealed three themes: Responsibility. Time and Support. Under responsibility, the delicate balance between individual and institutional responsibility and control was shown. Time included short and long-term perspectives on learning. Under support, supporting documents, activities and personnel resources were mentioned. In summary, an increased control by the program and tutors decreases student's motivation to assume responsibility for learning. Support in tutorial groups needs to adapt to student progression and to be well aligned to tutorial work to have the intended effect. A lifelong learning perspective may help students develop a meta-awareness regarding learning that could make tutorial work more meaningful.

Pathological game use in adults with and without Autism Spectrum Disorder

PubMed Central

Engelhardt, Christopher R.

2017-01-01

This study tested whether adults with autism spectrum disorder (ASD) are at higher risk for pathological game use than typically developing (TD) adults. Participants included 119 adults with and without ASD. Participants completed measures assessing daily hours of video game use, percent of free time spent playing video games, and symptoms of pathological game use. The results indicated that adults with ASD endorsed more symptoms of video game pathology than did TD adults. This relationship was strong, enjoying 300,000-to-1 odds in Bayesian model comparison. Results also showed that adults with ASD spent more daily hours playing video games and spent a higher percent of their free time playing video games than did TD adults. Even after adjustment for these differences in daily video game hours and proportion of free time spent on games, model comparisons found evidence for a difference in game pathology scores associated with ASD status. Additionally, escapism motives for playing video games was associated with game pathology scores in both ASD and TD adults, replicating and extending a previous report. In conclusion, the risk for pathological game use appears larger in adults with ASD compared with TD adults. These findings point to pathological game use as a potentially important focus of clinical attention in adults with ASD. PMID:28663933

Pathological game use in adults with and without Autism Spectrum Disorder.

PubMed

Engelhardt, Christopher R; Mazurek, Micah O; Hilgard, Joseph

2017-01-01

This study tested whether adults with autism spectrum disorder (ASD) are at higher risk for pathological game use than typically developing (TD) adults. Participants included 119 adults with and without ASD. Participants completed measures assessing daily hours of video game use, percent of free time spent playing video games, and symptoms of pathological game use. The results indicated that adults with ASD endorsed more symptoms of video game pathology than did TD adults. This relationship was strong, enjoying 300,000-to-1 odds in Bayesian model comparison. Results also showed that adults with ASD spent more daily hours playing video games and spent a higher percent of their free time playing video games than did TD adults. Even after adjustment for these differences in daily video game hours and proportion of free time spent on games, model comparisons found evidence for a difference in game pathology scores associated with ASD status. Additionally, escapism motives for playing video games was associated with game pathology scores in both ASD and TD adults, replicating and extending a previous report. In conclusion, the risk for pathological game use appears larger in adults with ASD compared with TD adults. These findings point to pathological game use as a potentially important focus of clinical attention in adults with ASD.

Cue reactivity towards shopping cues in female participants.

PubMed

Starcke, Katrin; Schlereth, Berenike; Domass, Debora; Schöler, Tobias; Brand, Matthias

2013-03-01

Background and aims It is currently under debate whether pathological buying can be considered as a behavioural addiction. Addictions have often been investigated with cue-reactivity paradigms to assess subjective, physiological and neural craving reactions. The current study aims at testing whether cue reactivity towards shopping cues is related to pathological buying tendencies. Methods A sample of 66 non-clinical female participants rated shopping related pictures concerning valence, arousal, and subjective craving. In a subgroup of 26 participants, electrodermal reactions towards those pictures were additionally assessed. Furthermore, all participants were screened concerning pathological buying tendencies and baseline craving for shopping. Results Results indicate a relationship between the subjective ratings of the shopping cues and pathological buying tendencies, even if baseline craving for shopping was controlled for. Electrodermal reactions were partly related to the subjective ratings of the cues. Conclusions Cue reactivity may be a potential correlate of pathological buying tendencies. Thus, pathological buying may be accompanied by craving reactions towards shopping cues. Results support the assumption that pathological buying can be considered as a behavioural addiction. From a methodological point of view, results support the view that the cue-reactivity paradigm is suited for the investigation of craving reactions in pathological buying and future studies should implement this paradigm in clinical samples.

Innovating undergraduate pathology education through public engagement.

PubMed

Mukundu Nagesh, Navin; Chiva Giurca, Bogdan; Lishman, Suzy

2018-05-01

The trends in modern undergraduate medical education focus on a patient-centred approach through problem-based learning over the traditional modular curriculum. Integrating pathology into this style of learning has resulted in the dilution of core scientific principles which may have contributed to reduced understanding and interest in the subject. We aim to innovate pathology education by utilising National Pathology Week which is organised by the Royal College of Pathologists to develop the public engagement model which empowers students to learn pathology by teaching the public. Through this model, we hope to generate a greater interest in pathology at both undergraduate and postgraduate stages of education. We obtained funding from the Royal College of Pathologists to organise National Pathology Week at Exeter Medical School and the Royal Devon & Exeter Hospital. We involved 125 undergraduate student volunteers from health-related courses. We designed a curriculum aiming to educate both students and public on current topics such as cancer screening programmes, antibiotic resistance, diagnosis of inflammatory bowel disease and the role of pathologists. We hosted 15 pathologists, biomedical scientists and microbiologists to engage with students, share experiences and offer an insight into their careers. Through this project, we interacted with over 500 members of the public and 150 school students. The medical student volunteers developed a range of skills including competent use of microscopes to visualise pathology slides, effective communication with lay audiences to teach pathology and understanding of the clinical application of pathology. We believe the public engagement model of teaching undergraduate students has the potential to develop a greater interest in pathology whilst benefitting the wider community.

Disrupted sensory gating in pathological gambling.

PubMed

Stojanov, Wendy; Karayanidis, Frini; Johnston, Patrick; Bailey, Andrew; Carr, Vaughan; Schall, Ulrich

2003-08-15

Some neurochemical evidence as well as recent studies on molecular genetics suggest that pathologic gambling may be related to dysregulated dopamine neurotransmission. The current study examined sensory (motor) gating in pathologic gamblers as a putative measure of endogenous brain dopamine activity with prepulse inhibition of the acoustic startle eye-blink response and the auditory P300 event-related potential. Seventeen pathologic gamblers and 21 age- and gender-matched healthy control subjects were assessed. Both prepulse inhibition measures were recorded under passive listening and two-tone prepulse discrimination conditions. Compared to the control group, pathologic gamblers exhibited disrupted sensory (motor) gating on all measures of prepulse inhibition. Sensory motor gating deficits of eye-blink responses were most profound at 120-millisecond prepulse lead intervals in the passive listening task and at 240-millisecond prepulse lead intervals in the two-tone prepulse discrimination task. Sensory gating of P300 was also impaired in pathologic gamblers, particularly at 500-millisecond lead intervals, when performing the discrimination task on the prepulse. In the context of preclinical studies on the disruptive effects of dopamine agonists on prepulse inhibition, our findings suggest increased endogenous brain dopamine activity in pathologic gambling in line with previous neurobiological findings.

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.

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

PubMed Central

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

2012-01-01

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

The Pathologist 2.0: An Update on Digital Pathology in Veterinary Medicine.

PubMed

Bertram, Christof A; Klopfleisch, Robert

2017-09-01

Using light microscopy to describe the microarchitecture of normal and diseased tissues has changed very little since the middle of the 19th century. While the premise of histologic analysis remains intact, our relationship with the microscope is changing dramatically. Digital pathology offers new forms of visualization, and delivery of images is facilitated in unprecedented ways. This new technology can untether us entirely from our light microscopes, with many pathologists already performing their jobs using virtual microscopy. Several veterinary colleges have integrated virtual microscopy in their curriculum, and some diagnostic histopathology labs are switching to virtual microscopy as their main tool for the assessment of histologic specimens. Considering recent technical advancements of slide scanner and viewing software, digital pathology should now be considered a serious alternative to traditional light microscopy. This review therefore intends to give an overview of the current digital pathology technologies and their potential in all fields of veterinary pathology (ie, research, diagnostic service, and education). A future integration of digital pathology in the veterinary pathologist's workflow seems to be inevitable, and therefore it is proposed that trainees should be taught in digital pathology to keep up with the unavoidable digitization of the profession.

A Future with Hybrid Electric Propulsion Systems: A NASA Perspective

NASA Technical Reports Server (NTRS)

DelRosario, Ruben

2014-01-01

The presentation highlights a NASA perspective on Hybrid Electric Propulsion Systems for aeronautical applications. Discussed are results from NASA Advance Concepts Study for Aircraft Entering service in 2030 and beyond and the potential use of hybrid electric propulsion systems as a potential solution to the requirements for energy efficiency and environmental compatibility. Current progress and notional potential NASA research plans are presented.

Enhancing preclinical year pathology exposure: the Angevine approach.

PubMed

Brooks, Erin G; Paus, Amanda M; Corliss, Robert F; Ranheim, Erik A

2016-07-01

Less than 2% of graduating US medical seniors select pathology residencies. One major obstacle to attracting prospective residents is the relative "invisibility" of pathology; medical students lacking positive preclinical exposure to pathology are unlikely to later select pathology clerkships or residencies. The Angevine Fellowship is a 10-week competitive pathology internship medical students may apply for the summer following their first year of preclinical training at our institution. We sought to determine whether it was an effective pathology recruitment tool and how it compared with the postsophomore pathology fellowship (PSF). Angevine fellow and PSF data from 2000 to 2014 were retrospectively analyzed. Specialty choices of former fellows already matched into residency programs were tabulated. Data regarding annual percentage of graduating seniors at our institution who matched into pathology during the years former fellow cohorts matched were also examined. Our results showed that of the former Angevine fellow cohorts already matched into residency programs, 40% (8/20) matched in pathology and 20% (4/20) at our own institution. Angevine fellows comprised a disproportionately high number of the graduating seniors matching in pathology at our medical school (26.7%). PSFs comprised 6.67%. Although we have endowment funding for 2 Angevine fellows annually, the level of interest among applicants has increased to the point that our department has consistently contributed funding for 1-2 additional fellowship spots since 2011. We conclude that the Angevine Fellowship offers an effective alternative to the postsophomore fellowship. It has proven successful at our institution and could be implemented at others to potentially improve pathology recruitment trends nationwide. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Pathological anxiety and function/dysfunction in the brain's fear/defense circuitry.

PubMed

Lang, Peter J; McTeague, Lisa M; Bradley, Margaret M

2014-01-01

Research from the University of Florida Center for the Study of Emotion and Attention aims to develop neurobiological measures that objectively discriminate among symptom patterns in patients with anxiety disorders. From this perspective, anxiety and mood pathologies are considered to be brain disorders, resulting from dysfunction and maladaptive plasticity in the neural circuits that determine fearful/defensive and appetitive/reward behavior (Insel et al., 2010). We review recent studies indicating that an enhanced probe startle reflex during the processing of fear memory cues (mediated by cortico-limbic circuitry and thus indicative of plastic brain changes), varies systematically in strength over a spectrum-wide dimension of anxiety pathology-across and within diagnoses-extending from strong focal fear reactions to a consistently blunted reaction in patients with more generalized anxiety and comorbid mood disorders. Preliminary studies with functional magnetic resonance imaging (fMRI) encourage the hypothesis that fear/defense circuit dysfunction covaries with this same dimension of psychopathology. Plans are described for an extended study of the brain's motivation circuitry in anxiety spectrum patients, with the aim of defining the specifics of circuit dysfunction in severe disorders. A sub-project explores the use of real-time fMRI feedback in circuit analysis and as a modality to up-regulate circuit function in the context of blunted affect.

Clinicians' perspectives of therapeutic alliance in face-to-face and telepractice speech-language pathology sessions.

PubMed

Freckmann, Anneka; Hines, Monique; Lincoln, Michelle

2017-06-01

To investigate the face validity of a measure of therapeutic alliance for paediatric speech-language pathology and to determine whether a difference exists in therapeutic alliance reported by speech-language pathologists (SLPs) conducting face-to-face sessions, compared with telepractice SLPs or in their ratings of confidence with technology. SLPs conducting telepractice (n = 14) or face-to-face therapy (n = 18) completed an online survey which included the Therapeutic Alliance Scales for Children - Revised (TASC-r) (Therapist Form) to rate clinicians' perceptions of rapport with up to three clients. Participants also reported their overall perception of rapport with each client and their comfort with technology. There was a strong correlation between TASC-r total scores and overall ratings of rapport, providing preliminary evidence of TASC-r face validity. There was no significant difference between TASC-r scores for telepractice and face-to-face therapy (p = 0.961), nor face-to-face and telepractice SLPs' confidence with familiar (p = 0.414) or unfamiliar technology (p = 0.780). The TASC-r may be a promising tool for measuring therapeutic alliance in speech-language pathology. Telepractice does not appear to have a negative effect on rapport between SLPs and paediatric clients. Future research is required to identify how SLPs develop rapport in telepractice.

Automatic Cone Photoreceptor Localisation in Healthy and Stargardt Afflicted Retinas Using Deep Learning.

PubMed

Davidson, Benjamin; Kalitzeos, Angelos; Carroll, Joseph; Dubra, Alfredo; Ourselin, Sebastien; Michaelides, Michel; Bergeles, Christos

2018-05-21

We present a robust deep learning framework for the automatic localisation of cone photoreceptor cells in Adaptive Optics Scanning Light Ophthalmoscope (AOSLO) split-detection images. Monitoring cone photoreceptors with AOSLO imaging grants an excellent view into retinal structure and health, provides new perspectives into well known pathologies, and allows clinicians to monitor the effectiveness of experimental treatments. The MultiDimensional Recurrent Neural Network (MDRNN) approach developed in this paper is the first method capable of reliably and automatically identifying cones in both healthy retinas and retinas afflicted with Stargardt disease. Therefore, it represents a leap forward in the computational image processing of AOSLO images, and can provide clinical support in on-going longitudinal studies of disease progression and therapy. We validate our method using images from healthy subjects and subjects with the inherited retinal pathology Stargardt disease, which significantly alters image quality and cone density. We conduct a thorough comparison of our method with current state-of-the-art methods, and demonstrate that the proposed approach is both more accurate and appreciably faster in localizing cones. As further validation to the method's robustness, we demonstrate it can be successfully applied to images of retinas with pathologies not present in the training data: achromatopsia, and retinitis pigmentosa.

Microparticles: A New Perspective in Central Nervous System Disorders

PubMed Central

Schindler, Stephanie M.; Little, Jonathan P.

2014-01-01

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

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

A proof of concept study to assess the potential of PCR testing to detect natural Mycobacterium bovis infection in South American camelids

PubMed Central

2014-01-01

Background Cases of Mycobacterium bovis infection South American camelids have been increasing in Great Britain. Current antemortem immunological tests have some limitations. Cases at post mortem examination frequently show extensive pathology. The feasibility of detecting Mycobacterium bovis DNA in clinical samples was investigated. Findings A sensitive extraction methodology was developed and used on nasal swabs and faeces taken post-mortem to assess the potential for a PCR test to detect Mycobacterium bovis in clinical samples. The gross pathology of the studied South American camelids was scored and a significantly greater proportion of South American camelids with more severe pathology were positive in both the nasal swab and faecal PCR tests. A combination of the nasal swab and faecal PCR tests detected 63.9% of all the South American camelids with pathology that were tested. Conclusions The results suggest that antemortem diagnosis of Mycobacterium bovis in South American camelids may be possible using a PCR test on clinical samples, however more work is required to determine sensitivity and specificity, and the practicalities of applying the test in the field. PMID:24507471

Imaging of normal and pathologic joint synovium using nonlinear optical microscopy as a potential diagnostic tool

NASA Astrophysics Data System (ADS)

Tiwari, Nivedan; Chabra, Sanjay; Mehdi, Sheherbano; Sweet, Paula; Krasieva, Tatiana B.; Pool, Roy; Andrews, Brian; Peavy, George M.

2010-09-01

An estimated 1.3 million people in the United States suffer from rheumatoid arthritis (RA). RA causes profound changes in the synovial membrane of joints, and without early diagnosis and intervention, progresses to permanent alterations in joint structure and function. The purpose of this study is to determine if nonlinear optical microscopy (NLOM) can utilize the natural intrinsic fluorescence properties of tissue to generate images that would allow visualization of the structural and cellular composition of fresh, unfixed normal and pathologic synovial tissue. NLOM is performed on rabbit knee joint synovial samples using 730- and 800-nm excitation wavelengths. Less than 30 mW of excitation power delivered with a 40×, 0.8-NA water immersion objective is sufficient for the visualization of synovial structures to a maximum depth of 70 μm without tissue damage. NLOM imaging of normal and pathologic synovial tissue reveals the cellular structure, synoviocytes, adipocytes, collagen, vascular structures, and differential characteristics of inflammatory infiltrates without requiring tissue processing or staining. Further study to evaluate the ability of NLOM to assess the characteristics of pathologic synovial tissue and its potential role for the management of disease is warranted.

Specific Immunotherapy of Experimental Myasthenia Gravis by A Novel Mechanism

PubMed Central

Luo, Jie; Kuryatov, Alexander; Lindstrom, Jon

2009-01-01

Objective Myasthenia gravis (MG) and its animal model, experimental autoimmune myasthenia gravis (EAMG), are antibody-mediated autoimmune diseases, in which autoantibodies bind to and cause loss of muscle nicotinic acetylcholine receptors (AChRs) at the neuromuscular junction. To develop a specific immunotherapy of MG, we treated rats with ongoing EAMG by intraperitoneal injection of bacterially-expressed human muscle AChR constructs. Methods Rats with ongoing EAMG received intraperitoneal treatment with the constructs weekly for 5 weeks beginning after the acute phase. Autoantibody concentration, subclassification, and specificity were analyzed to address underlying therapeutic mechanism. Results EAMG was specifically suppressed by diverting autoantibody production away from pathologically relevant specificities directed at epitopes on the extracellular surface of muscle AChRs toward pathologically irrelevant epitopes on the cytoplasmic domain. A mixture of subunit cytoplasmic domains was more effective than a mixture containing both extracellular and cytoplasmic domains or than only the extracellular domain of α1 subunits. Interpretation Therapy using only cytoplasmic domains, which lack pathologically relevant epitopes, avoids the potential liability of boosting the pathological response. Use of a mixture of bacterially-expressed human muscle AChR cytoplasmic domains for antigen-specific immunosuppression of myasthenia gravis has the potential to be specific, robust, and safe. PMID:20437579

Mangiferin: A xanthonoid with multipotent anti-inflammatory potential.

PubMed

Saha, Sukanya; Sadhukhan, Pritam; Sil, Parames C

2016-09-10

Over the last era, small molecules sourced from different plants have gained attention for their varied and long-term medicinal benefits. Their advantageous therapeutic effects in diverse pathological complications lead researchers to give an ever-increasing emphasis on them and discover their novel therapeutic potentials. Among these, the heat stable, xanthonoid group of organic molecules has gained special importance with distinctive regards to the bioactive molecule mangiferin due to its solubility in water. Mangiferin, a yellow polyphenol having C-glycosyl xanthone structure, is widely present in different edible sources like mango, and possesses numerous biological activities. Extensive research with this molecule shows its antioxidant, anti-inflammatory, antidiabetic, anticancer, antimicrobial, analgesic, and immunomodulatory properties. Thus, it provides protection against a wide range of physiological disorders. The C-glucosyl linkage and polyhydroxy groups in mangiferin's structure contribute essentially to its free radical-scavenging activity. Moreover, its ability in regulating various transcription factors like NF-κB, Nrf-2, etc. and modulating the expression of different proinflammatory signaling intermediates like tumor necrosis factor-α, COX-2, etc. contribute to its anti-inflammatory, anticancer, and antidiabetic potentials. In this comprehensive article, information has been provided about the sources, chemical structure, metabolism, and different biological activities of mangiferin with special emphasis on the underlying cellular signal transduction pathways. Insights into an in-depth assessment of mangiferin's anti-inflammatory therapeutic potential have also been discussed in detail. On an overall perspective, this review aims to stage mangiferin's diversified therapeutic applications and its emerging possibility as a promising drug in future based on its anti-inflammatory property. © 2016 BioFactors, 42(5):459-474, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

PERSPECTIVES ON LARGE-SCALE NATURAL RESOURCES SURVEYS WHEN CAUSE-EFFECT IS A POTENTIAL ISSUE

EPA Science Inventory

Our objective is to present a perspective on large-scale natural resource monitoring when cause-effect is a potential issue. We believe that the approach of designing a survey to meet traditional commodity production and resource state descriptive objectives is too restrictive an...

Latin American traditions and perspectives

NASA Astrophysics Data System (ADS)

Garcia, Celina

1983-09-01

Educational and related non-pedagogical issues are generally described and discussed. Implicitly or explicitly, the theology of liberation, educación popular and traditional education tend to perpetuate male/female roles and very often incite violence. Peace education in Latin America should concentrate more on the pathology of the violent man. The so-called `weaknesses' associated with women and their `powerlessness' in Western civilization are precisely those which are absolutely essential to our survival. It is important for women to reject Western patterns of violence and participate actively in finding a viable alternative.

Endoscopic medial maxillectomy breaking new frontiers.

PubMed

Mohanty, Sanjeev; Gopinath, M

2013-07-01

Endoscopy has changed the perspective of rhinologist towards the nose. It has revolutionised the surgical management of sinonasal disorders. Sinus surgeries were the first to get the benefit of endoscope. Gradually the domain of endoscopic surgery extended to the management of sino nasal tumours. Traditionally medial maxillectomy was performed through lateral rhinotomy or mid facial degloving approach. Endoscopic medial maxillectomy has been advocated by a number of authors in the management of benign sino-nasal tumours. We present our experience of endoscopic medial maxillectomy in the management of sinonasal pathologies.

Intravital imaging of dendritic spine plasticity

PubMed Central

Sau Wan Lai, Cora

2014-01-01

Abstract Dendritic spines are the postsynaptic part of most excitatory synapses in the mammalian brain. Recent works have suggested that the structural and functional plasticity of dendritic spines have been associated with information coding and memories. Advances in imaging and labeling techniques enable the study of dendritic spine dynamics in vivo. This perspective focuses on intravital imaging studies of dendritic spine plasticity in the neocortex. I will introduce imaging tools for studying spine dynamics and will further review current findings on spine structure and function under various physiological and pathological conditions. PMID:28243511

The right to health care for transsexual people in Cuba.

PubMed

Roque, Alberto; Rodríguez, R Mayra

2012-04-01

Gender identity is a sociocultural construct based (in nearly every society) on a binary norm: female and male. Transsexual individuals suffer from intense family and social discrimination because they express a dissident sexuality incongruent with this norm. They assert they feel trapped in a body that does not belong to them, so they seek help from health professionals to modify their bodies, to "adapt their bodies to their minds." This essay discusses health care for transsexual persons in Cuba from a human rights perspective that does not pathologize their gender identification.

Can you treat the cheat in sports?

PubMed

Glick, Ira D; Begel, Dan

2015-07-01

This editorial examines the issue of "cheating" (broadly defined) in sports from youth through professional sports. We describe possible underlying causes focusing on the development of a "personality disorder" and psychiatric/psychodynamic needs (e.g. a pathological need to be the best). We detail treatment and management from a medical-psychiatric perspective as well as implications for coaches, teams, leagues and professional organizations (e.g. soccer, bicycling, etc). Cheating behavior exists in other fields, for example, politics, law among others and some of the management principles mentioned here may apply there.

Two Different Cell Populations Is an Important Clue for Diagnosis of Primary Cutaneous Adenoid Cystic Carcinoma: Immunohistochemical Study

PubMed Central

Alkan, Banu Ince; Karadeniz, Müjde; Bozdoğan, Nazan

2017-01-01

Primary cutaneous adenoid cystic carcinoma (PCACC) is a very rare malignancy. The differential diagnosis of PCACCs in pathology practice can be difficult and a group of primary and metastatic lesions, including adenoid basal cell carcinoma of the skin, should be considered in the differential diagnosis. Besides histomorphological clues, immunohistochemistry studies are very helpful in the differential diagnosis of PCACC. We report herein a case of PCACC with extensive immunohistochemical studies and review the literature from an immunohistochemistry perspective. PMID:28243477

The future of laboratory medicine - a 2014 perspective.

PubMed

Kricka, Larry J; Polsky, Tracey G; Park, Jason Y; Fortina, Paolo

2015-01-01

Predicting the future is a difficult task. Not surprisingly, there are many examples and assumptions that have proved to be wrong. This review surveys the many predictions, beginning in 1887, about the future of laboratory medicine and its sub-specialties such as clinical chemistry and molecular pathology. It provides a commentary on the accuracy of the predictions and offers opinions on emerging technologies, economic factors and social developments that may play a role in shaping the future of laboratory medicine. Copyright © 2014 Elsevier B.V. All rights reserved.

PML nuclear bodies: regulation, function and therapeutic perspectives.

PubMed

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

2014-11-01

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

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

A Review on the Applications of Crowdsourcing in Human Pathology.

PubMed

Alialy, Roshanak; Tavakkol, Sasan; Tavakkol, Elham; Ghorbani-Aghbologhi, Amir; Ghaffarieh, Alireza; Kim, Seon Ho; Shahabi, Cyrus

2018-01-01

The advent of the digital pathology has introduced new avenues of diagnostic medicine. Among them, crowdsourcing has attracted researchers' attention in the recent years, allowing them to engage thousands of untrained individuals in research and diagnosis. While there exist several articles in this regard, prior works have not collectively documented them. We, therefore, aim to review the applications of crowdsourcing in human pathology in a semi-systematic manner. We first, introduce a novel method to do a systematic search of the literature. Utilizing this method, we, then, collect hundreds of articles and screen them against a predefined set of criteria. Furthermore, we crowdsource part of the screening process, to examine another potential application of crowdsourcing. Finally, we review the selected articles and characterize the prior uses of crowdsourcing in pathology.

Transient receptor potential (TRP) channels as drug targets for diseases of the digestive system

PubMed Central

Holzer, Peter

2011-01-01

Approximately 20 of the 30 mammalian transient receptor potential (TRP) channel subunits are expressed by specific neurons and cells within the alimentary canal. They subserve important roles in taste, chemesthesis, mechanosensation, pain and hyperalgesia and contribute to the regulation of gastrointestinal motility, absorptive and secretory processes, blood flow, and mucosal homeostasis. In a cellular perspective, TRP channels operate either as primary detectors of chemical and physical stimuli, as secondary transducers of ionotropic or metabotropic receptors, or as ion transport channels. The polymodal sensory function of TRPA1, TRPM5, TRPM8, TRPP2, TRPV1, TRPV3 and TRPV4 enables the digestive system to survey its physical and chemical environment, which is relevant to all processes of digestion. TRPV5 and TRPV6 as well as TRPM6 and TRPM7 contribute to the absorption of Ca2+ and Mg2+, respectively. TRPM7 participates in intestinal pacemaker activity, and TRPC4 transduces muscarinic acetylcholine receptor activation to smooth muscle contraction. Changes in TRP channel expression or function are associated with a variety of diseases/disorders of the digestive system, notably gastro-esophageal reflux disease, inflammatory bowel disease, pain and hyperalgesia in heartburn, functional dyspepsia and irritable bowel syndrome, cholera, hypomagnesemia with secondary hypocalcemia, infantile hypertrophic pyloric stenosis, esophageal, gastrointestinal and pancreatic cancer, and polycystic liver disease. These implications identify TRP channels as promising drug targets for the management of a number of gastrointestinal pathologies. As a result, major efforts are put into the development of selective TRP channel agonists and antagonists and the assessment of their therapeutic potential. PMID:21420431

From distress to disease: a critique of the medicalisation of possession in DSM-5.

PubMed

Padmanabhan, Divya

2017-12-01

This paper critiques the category of possession-form dissociative identity disorder as defined in the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) published in 2013 by the American Psychiatric Association (APA). The DSM as an index of psychiatry pathologises possession by categorising it as a form of dissociative identity disorder. Drawing upon ethnographic fieldwork, this paper argues that such a pathologisation medicalises possession, which is understood as a non-pathological condition in other contexts such as by those individuals who manifest possession at a temple in Kerala, South India. Through medicalising and further by creating distinctions between acceptable and pathological possession, the DSM converts a form of distress into a disease. This has both conceptual and pragmatic implications. The temple therefore becomes reduced to a culturally acceptable site for the manifestation of a mental illness in a form that is culturally available and possession is explained solely through a biomedical framework, denying alternative conceptualisations and theories which inform possession. By focussing on the DSM-5 classification of possession and the limitations of such a classification, this paper seeks to posit an alternative conceptualisation of possession by engaging with three primary areas which are significant in the DSM categorisation of possession: the DSM's conceptualisation of self in the singular, the distinction between pathological and non-pathological forms of possession, and the limitations of the DSM's equation of the condition of possession with the manifestation of possession. Finally, the paper briefly highlights alternative conceptualisations of possession, which emerged from the perspective of those seeking to heal possession at the Chottanikkara temple.

Animal models of non-alcoholic fatty liver disease: current perspectives and recent advances.

PubMed

Lau, Jennie Ka Ching; Zhang, Xiang; Yu, Jun

2017-01-01

Non-alcoholic fatty liver disease (NAFLD) is a continuous spectrum of diseases characterized by excessive lipid accumulation in hepatocytes. NAFLD progresses from simple liver steatosis to non-alcoholic steatohepatitis and, in more severe cases, to liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Because of its growing worldwide prevalence, various animal models that mirror both the histopathology and the pathophysiology of each stage of human NAFLD have been developed. The selection of appropriate animal models continues to be one of the key questions faced in this field. This review presents a critical analysis of the histopathology and pathogenesis of NAFLD, the most frequently used and recently developed animal models for each stage of NAFLD and NAFLD-induced HCC, the main mechanisms involved in the experimental pathogenesis of NAFLD in different animal models, and a brief summary of recent therapeutic targets found by the use of animal models. Integrating the data from human disease with those from animal studies indicates that, although current animal models provide critical guidance in understanding specific stages of NAFLD pathogenesis and progression, further research is necessary to develop more accurate models that better mimic the disease spectrum, in order to provide both increased mechanistic understanding and identification/testing of novel therapeutic approaches. © 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.

Human induced pluripotent stem cells can reach complete terminal maturation: in vivo and in vitro evidence in the erythropoietic differentiation model

PubMed Central

Kobari, Ladan; Yates, Frank; Oudrhiri, Noufissa; Francina, Alain; Kiger, Laurent; Mazurier, Christelle; Rouzbeh, Shaghayegh; El-Nemer, Wassim; Hebert, Nicolas; Giarratana, Marie-Catherine; François, Sabine; Chapel, Alain; Lapillonne, Hélène; Luton, Dominique; Bennaceur-Griscelli, Annelise; Douay, Luc

2012-01-01

Background Human induced pluripotent stem cells offer perspectives for cell therapy and research models for diseases. We applied this approach to the normal and pathological erythroid differentiation model by establishing induced pluripotent stem cells from normal and homozygous sickle cell disease donors. Design and Methods We addressed the question as to whether these cells can reach complete erythroid terminal maturation notably with a complete switch from fetal to adult hemoglobin. Sickle cell disease induced pluripotent stem cells were differentiated in vitro into red blood cells and characterized for their terminal maturation in terms of hemoglobin content, oxygen transport capacity, deformability, sickling and adherence. Nucleated erythroblast populations generated from normal and pathological induced pluripotent stem cells were then injected into non-obese diabetic severe combined immunodeficiency mice to follow the in vivo hemoglobin maturation. Results We observed that in vitro erythroid differentiation results in predominance of fetal hemoglobin which rescues the functionality of red blood cells in the pathological model of sickle cell disease. We observed, in vivo, the switch from fetal to adult hemoglobin after infusion of nucleated erythroid precursors derived from either normal or pathological induced pluripotent stem cells into mice. Conclusions These results demonstrate that human induced pluripotent stem cells: i) can achieve complete terminal erythroid maturation, in vitro in terms of nucleus expulsion and in vivo in terms of hemoglobin maturation; and ii) open the way to generation of functionally corrected red blood cells from sickle cell disease induced pluripotent stem cells, without any genetic modification or drug treatment. PMID:22733021

Review at a multidisciplinary tumor board impacts critical management decisions of pediatric patients with cancer.

PubMed

Thenappan, Arun; Halaweish, Ihab; Mody, Rajen J; Smith, Ethan A; Geiger, James D; Ehrlich, Peter F; Jasty Rao, Rama; Hutchinson, Raymond; Yanik, Gregory; Rabah, Raja M; Heider, Amer; Stoll, Tammy; Newman, Erika A

2017-02-01

Optimal cancer care requires a multidisciplinary approach. The purpose of the current study was to evaluate the impact of a multidisciplinary tumor board on the treatment plans of children with solid tumors. The records of 158 consecutive patients discussed at a formal multidisciplinary pediatric tumor board between July 2012 and April 2014 were reviewed. Treatment plans were based on clinical practice guidelines and on current Children's Oncology Group protocols. Alterations in radiologic, pathologic, surgical, and medical interpretations were analyzed to determine the impact on changes in recommendations for clinical management. Overall, 55 of 158 children (35%) had alterations in radiologic, pathologic, medical, or surgical interpretation of clinical data following multidisciplinary discussion. Of these, 64% had changes to the initial recommendation for clinical management. Review of imaging studies resulted in interpretation changes in 30 of 158 patients studied (19%), with 12 clinical management changes. Six of 158 patients (3.9%) had changes in pathologic interpretation, with four patients (2.5%) requiring treatment changes. In eight patients (5%), a change in medical management was recommended, while in 11 patients (7%) there were changes in surgical management that were based solely on discussion and not on interpretation of imaging or pathology. Formal multidisciplinary review led to alterations in interpretation of clinical data in 35% of patients, and the majority led to changes in recommendations for treatment. Comprehensive multidisciplinary tumor board incorporated into the care of children with cancer provides additional perspectives for families and care providers when delineating optimal treatment plans. © 2016 Wiley Periodicals, Inc.

Regulatory Forum Opinion Piece: Review of FDA Draft Guidance Testicular Toxicity-Evaluation during Drug Development Guidance for Industry.

PubMed

Hukkanen, Renee R; Halpern, Wendy G; Vidal, Justin D

2016-10-01

In July 2015, the U.S. Food and Drug Administration (FDA) posted a new draft guidance entitled "Testicular Toxicity: Evaluation during Drug Development Guidance for Industry," with a 90-day public comment period. As the nonclinical assessment of testicular toxicity often relies on the expert interpretation of pathology affecting the male reproductive tract, this draft guidance is considered directly relevant to the toxicologic pathology community. Therefore, a working group was formed through the Scientific and Regulatory Policy Committee of the Society of Toxicologic Pathologists (STPs) to provide a detailed review of the draft guidance. Specific comments on the guidance were submitted to the FDA by the STP. The draft guidance and all comments received are currently under review with the FDA. This commentary provides a summary of the components of the draft guidance and the comments submitted by the STP with acknowledgment of different perspectives reflected in comments from other respondents. © The Author(s) 2016.

Perspectives on the rapid eye movement sleep switch in rapid eye movement sleep behavior disorder.

PubMed

Ramaligam, Vetrivelan; Chen, Michael C; Saper, Clifford B; Lu, Jun

2013-08-01

Rapid eye movement (REM) sleep in mammals is associated with wakelike cortical and hippocampal activation and concurrent postural muscle atonia. Research during the past 5 decades has revealed the details of the neural circuitry regulating REM sleep and muscle atonia during this state. REM-active glutamatergic neurons in the sublaterodorsal nucleus (SLD) of the dorsal pons are critical for generation for REM sleep atonia. Descending projections from SLD glutamatergic neurons activate inhibitory premotor neurons in the ventromedial medulla (VMM) and in the spinal cord to antagonize the glutamatergic supraspinal inputs on the motor neurons during REM sleep. REM sleep behavior disorder (RBD) consists of simple behaviors (i.e., twitching, jerking) and complex behaviors (i.e., defensive behavior, talking). Animal research has lead to the hypothesis that complex behaviors in RBD are due to SLD pathology, while simple behaviors of RBD may be due to less severe SLD pathology or dysfunction of the VMM, ventral pons, or spinal cord. Copyright © 2013 Elsevier B.V. All rights reserved.

Parkinson's disease--the debate on the clinical phenomenology, aetiology, pathology and pathogenesis.

PubMed

Jenner, Peter; Morris, Huw R; Robbins, Trevor W; Goedert, Michel; Hardy, John; Ben-Shlomo, Yoav; Bolam, Paul; Burn, David; Hindle, John V; Brooks, David

2013-01-01

The definition of Parkinson's disease (PD) is changing with the expansion of clinical phenomenology and improved understanding of environmental and genetic influences that impact on the pathogenesis of the disease at the cellular and molecular level. This had led to debate and discussion with as yet, no general acceptance of the direction that change should take either at the level of diagnosis or of what should and should not be sheltered under an umbrella of PD. This article is one contribution to this on-going discussion. There are two different themes running through the article--widening the definition of PD/LBD/synucleinopathies and the heterogeneity that exists within PD itself from a clinical, pathological and genetic perspective. The conclusion reached is that in the future, further diagnostic categories will need to be recognized. These are likely to include--Parkinson's syndrome, Parkinson's syndrome likely to be Lewy body PD, clinical PD (defined by QSBB criteria), Lewy body disease (PD, LBD, REM SBD) and synucleinopathies (including LBD, MSA).

Turning Microscopy in the Medical Curriculum Digital: Experiences from The Faculty of Health and Medical Sciences at University of Copenhagen

PubMed Central

Vainer, Ben; Mortensen, Niels Werner; Poulsen, Steen Seier; Sørensen, Allan Have; Olsen, Jørgen; Saxild, Hans Henrik; Johansen, Flemming Fryd

2017-01-01

Familiarity with the structure and composition of normal tissue and an understanding of the changes that occur during disease is pivotal to the study of the human body. For decades, microscope slides have been central to teaching pathology in medical courses and related subjects at the University of Copenhagen. Students had to learn how to use a microscope and envisage three-dimensional processes that occur in the body from two-dimensional glass slides. Here, we describe how a PathXL virtual microscopy system for teaching pathology and histology at the Faculty has recently been implemented, from an administrative, an economic, and a teaching perspective. This fully automatic digital microscopy system has been received positively by both teachers and students, and a decision was made to convert all courses involving microscopy to the virtual microscopy format. As a result, conventional analog microscopy will be phased out from the fall of 2016. PMID:28382225

Perspectives on the Role and Relevance of Copper in Cardiac Disease.

PubMed

Medeiros, Denis M

2017-03-01

Cardiac hypertrophy as a result of dietary copper deficiency has been studied for 40 plus years and is the subject of this review. While connective tissue anomalies occur, a hallmark pathology is cardiac hypertrophy, increased mitochondrial biogenesis, with disruptive cristae, vacuolization of mitochondria, and deposition of lipid droplets. Electrocardiogram abnormalities have been demonstrated along with biochemical changes especially as it relates to the copper-containing enzyme cytochrome c oxidase. The master controller of mitochondrial biogenesis, PGC1-α expression and protein, along with other proteins and transcriptional factors that play a role are upregulated. Nitric oxide, vascular endothelial growth factor, and cytochrome c oxidase all may enhance the upregulation of mitochondrial biogenesis. Marginal copper intakes reveal similar pathologies in the absence of cardiac hypertrophy. Reversibility of the copper-deficient rat heart with a copper-replete diet has resulted in mixed results, depending on both the animal model used and temporal relationships. New information has revealed that copper supplementation may rescue cardiac hypertrophy induced by pressure overload.

Fungal biology and agriculture: revisiting the field

USGS Publications Warehouse

Yarden, O.; Ebbole, D.J.; Freeman, S.; Rodriguez, R.J.; Dickman, M. B.

2003-01-01

Plant pathology has made significant progress over the years, a process that involved overcoming a variety of conceptual and technological hurdles. Descriptive mycology and the advent of chemical plant-disease management have been followed by biochemical and physiological studies of fungi and their hosts. The later establishment of biochemical genetics along with the introduction of DNA-mediated transformation have set the stage for dissection of gene function and advances in our understanding of fungal cell biology and plant-fungus interactions. Currently, with the advent of high-throughput technologies, we have the capacity to acquire vast data sets that have direct relevance to the numerous subdisciplines within fungal biology and pathology. These data provide unique opportunities for basic research and for engineering solutions to important agricultural problems. However, we also are faced with the challenge of data organization and mining to analyze the relationships between fungal and plant genomes and to elucidate the physiological function of pertinent DNA sequences. We present our perspective of fungal biology and agriculture, including administrative and political challenges to plant protection research.

Wound repair and regeneration: mechanisms, signaling, and translation.

PubMed

Eming, Sabine A; Martin, Paul; Tomic-Canic, Marjana

2014-12-03

The cellular and molecular mechanisms underpinning tissue repair and its failure to heal are still poorly understood, and current therapies are limited. Poor wound healing after trauma, surgery, acute illness, or chronic disease conditions affects millions of people worldwide each year and is the consequence of poorly regulated elements of the healthy tissue repair response, including inflammation, angiogenesis, matrix deposition, and cell recruitment. Failure of one or several of these cellular processes is generally linked to an underlying clinical condition, such as vascular disease, diabetes, or aging, which are all frequently associated with healing pathologies. The search for clinical strategies that might improve the body's natural repair mechanisms will need to be based on a thorough understanding of the basic biology of repair and regeneration. In this review, we highlight emerging concepts in tissue regeneration and repair, and provide some perspectives on how to translate current knowledge into viable clinical approaches for treating patients with wound-healing pathologies. Copyright © 2014, American Association for the Advancement of Science.

Specific personality traits and general personality dysfunction as predictors of the presence and severity of personality disorders in a clinical sample.

PubMed

Berghuis, Han; Kamphuis, Jan H; Verheul, Roel

2014-01-01

This study examined the associations of specific personality traits and general personality dysfunction in relation to the presence and severity of Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994) personality disorders in a Dutch clinical sample. Two widely used measures of specific personality traits were selected, the Revised NEO Personality Inventory as a measure of normal personality traits, and the Dimensional Assessment of Personality Pathology-Basic Questionnaire as a measure of pathological traits. In addition, 2 promising measures of personality dysfunction were selected, the General Assessment of Personality Disorder and the Severity Indices of Personality Problems. Theoretically predicted associations were found between the measures, and all measures predicted the presence and severity of DSM-IV personality disorders. The combination of general personality dysfunction models and personality traits models provided incremental information about the presence and severity of personality disorders, suggesting that an integrative approach of multiple perspectives might serve comprehensive assessment of personality disorders.

[Prostate cancer. Part 2: Review of the various tumor grading systems over the years 1966-2015 and future perspectives of the new grading of the International Society of Urological Pathology (ISUP)].

PubMed

Helpap, B; Bubendorf, L; Kristiansen, G

2016-02-01

The continued development of methods in needle biopsies and radical prostatectomy for treatment of prostate cancer has given special emphasis to the question of the prognostic relevance of the various systems of grading. The classical purely histological grading system of Gleason has been modified several times in the past decades and cleared the way for a new grading system by the prognostic grading of Epstein. Assessment of the old and also modified combined histological and cytological grading of Mostofi, the World health Organization (WHO) and the urologic-pathological working group of prostate cancer in connection with the Gleason grading (combined Gleason-Helpap grading), has led to considerably improved rates of concordance between biopsy and radical prostatectomy and to improved estimations of prognosis beside its contribution to the development of a more practicable grading system for clinical use.

Wound repair and regeneration: Mechanisms, signaling, and translation

PubMed Central

Eming, Sabine A.; Martin, Paul; Tomic-Canic, Marjana

2015-01-01

The cellular and molecular mechanisms underpinning tissue repair and its failure to heal are still poorly understood, and current therapies are limited. Poor wound healing after trauma, surgery, acute illness, or chronic disease conditions affects millions of people worldwide each year and is the consequence of poorly regulated elements of the healthy tissue repair response, including inflammation, angiogenesis, matrix deposition, and cell recruitment. Failure of one or several of these cellular processes is generally linked to an underlying clinical condition, such as vascular disease, diabetes, or aging, which are all frequently associated with healing pathologies. The search for clinical strategies that might improve the body’s natural repair mechanisms will need to be based on a thorough understanding of the basic biology of repair and regeneration. In this review, we highlight emerging concepts in tissue regeneration and repair, and provide some perspectives on how to translate current knowledge into viable clinical approaches for treating patients with wound-healing pathologies. PMID:25473038

Changing course in ageing research: The healthy ageing phenotype.

PubMed

Franco, Oscar H; Karnik, Kavita; Osborne, Gabrielle; Ordovas, Jose M; Catt, Michael; van der Ouderaa, Frans

2009-05-20

Ageing is often associated with the aged and the diseased, nevertheless ageing is a process that starts in-uterus and is characterised by a progressive functional loss but not necessarily by the presence of disease and poor quality of life. How to meander through life without crossing the confines of major chronic disease and cognitive and physical impairment remains one of the most relevant challenges for science and humankind. Delimiting that 'immaculate' trajectory - that we dub as the 'Healthy Ageing Phenotype' - and exploring solutions to help the population to stay or return to this trajectory should constitute the core focus of scientific research. Nevertheless, current efforts on ageing research are mainly focused on developing animal models to disentangle the human ageing process, and on age-related disorders often providing merely palliative solutions. Therefore, to identify alternative perspectives in ageing research, Unilever and the Medical Research Council (MRC) UK convened a Spark workshop entitled 'The Healthy Ageing Phenotype'. In this meeting, international specialists from complementary areas related to ageing research, gathered to find clear attributes and definitions of the 'Healthy Ageing Phenotype', to identify potential mechanisms and interventions to improve healthy life expectancy of the population; and to highlight areas within ageing research that should be prioritised in the future. General agreement was reached in recognising ageing research as a disaggregated field with little communication between basic, epidemiological and clinical areas of research and limited translation to society. A more holistic, multi-disciplinary approach emanating from a better understanding of healthy ageing trajectories and centred along human biological resilience, its maintenance and the reversibility from early deviations into pathological trajectories, is urgently required. Future research should concentrate on understanding the mechanisms that permit individuals to maintain optimal health when facing pathological hazards and on developing and assessing potential interventions that could aid to re-establish resilience when lost or guarantee its integrity if present. Furthermore it is fundamental that scientific findings are translated incessantly into clear messages delivered to governmental institutions, the industry and society in general.

The contribution of alpha synuclein to neuronal survival and function - Implications for Parkinson's disease.

PubMed

Benskey, Matthew J; Perez, Ruth G; Manfredsson, Fredric P

2016-05-01

The aggregation of alpha synuclein (α-syn) is a neuropathological feature that defines a spectrum of disorders collectively termed synucleinopathies, and of these, Parkinson's disease (PD) is arguably the best characterized. Aggregated α-syn is the primary component of Lewy bodies, the defining pathological feature of PD, while mutations or multiplications in the α-syn gene result in familial PD. The high correlation between α-syn burden and PD has led to the hypothesis that α-syn aggregation produces toxicity through a gain-of-function mechanism. However, α-syn has been implicated to function in a diverse range of essential cellular processes such as the regulation of neurotransmission and response to cellular stress. As such, an alternative hypothesis with equal explanatory power is that the aggregation of α-syn results in toxicity because of a toxic loss of necessary α-syn function, following sequestration of functional forms α-syn into insoluble protein aggregates. Within this review, we will provide an overview of the literature linking α-syn to PD and the knowledge gained from current α-syn-based animal models of PD. We will then interpret these data from the viewpoint of the α-syn loss-of-function hypothesis and provide a potential mechanistic model by which loss of α-syn function could result in at least some of the neurodegeneration observed in PD. By providing an alternative perspective on the etiopathogenesis of PD and synucleinopathies, this may reveal alternative avenues of research in order to identify potential novel therapeutic targets for disease modifying strategies. The correlation between α-synuclein burden and Parkinson's disease pathology has led to the hypothesis that α-synuclein aggregation produces toxicity through a gain-of-function mechanism. However, in this review, we discuss data supporting the alternative hypothesis that the aggregation of α-synuclein results in toxicity because of loss of necessary α-synuclein function at the presynaptic terminal, following sequestration of functional forms of α-synuclein into aggregates. © 2016 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

The other self: psychopathology and literature.

PubMed

Macías, Javier Saavedra; Núñez, Rafael Velez

2011-12-01

The figure of the "double" or the other self is an important topic in the history of literature. Many centuries before Jean Paul Richter coined the term, "doppelgänger," at the beginning of the Romantic Movement in the year 1796, it is possible to find the figure of the double in myths and legends. The issue of the double emphaszses the contradictory character of the human being and invokes a sinister dimension of the psychological world, what has been called in German as "umheimlich." However, does multiciplicity always involve pathology? Related to this figure in literary history, a new perspective from clinical psychology called "dialogical self" defines the self as a multi-voice reality. Along the same line, postmodernist psychology considers the self a discursive construction. From these perspectives, the "self" is situated a long way away from the classical essential conception of the self. In this paper, we review briefly some important landmarks of the figure of the double in the literature, and we compare the coincidences of the "double" experiencies described in literature with the experiences of our patients. Finally, we discuss how this literary tradition can help us to understand new psychological perspectives.

Exploring the relationship between client perspectives, clinical expertise and research evidence.

PubMed

Roulstone, Sue

2015-06-01

This paper examines the relationship between components of evidence-based practice (clinical expertise, patient perspective and research evidence). Findings are examined from two research programs: the Better Communication Research Program and Child Talk, including exploratory studies of the views of parents and children regarding speech-language pathology and studies of current practice by SLPs in England. Systematic reviews of the research literature were also undertaken. The paper analyses relationships between outcomes valued by children and parents and those reported in the literature and in practice, parents' perspectives regarding intervention in comparison with clinicians' reports of practice and the extent to which research evidence underpins current practice is examined. Parents and children value functional outcomes and positive experiences; these are not routinely measured in research or practice. Therapy is perceived positively by most parents; however, some are ambivalent and less clear about the rationale. Commonly used interventions are supported by evidence, but there are gaps regarding some critical therapy components. The paper discusses four challenges to evidence-based practice: the consistency and clarity of descriptions of interventions; consensus based models of practice; understanding of the mechanisms of change; and, finally, the operationalization of client preferences within an evidence-based practice framework.

Cue-induced craving in pathological buying: empirical evidence and clinical implications.

PubMed

Trotzke, Patrick; Starcke, Katrin; Pedersen, Anya; Brand, Matthias

2014-01-01

Pathological buying is associated with marked distress and impaired functioning in important life domains. It is currently under debate whether pathological buying can be considered a behavioral addiction. In analogy to results reported in addicted individuals, craving reactions elicited by addiction-related cues might be an underlying mechanism for the etiology and pathogenesis of pathological buying. In the present study, 30 pathological buyers and 30 matched control participants were examined with a cue-reactivity paradigm consisting of shopping and control cues. Skin conductance responses, as well as subjective ratings for arousal, valence, and urge to buy, were assessed. Subjective craving reactions were measured before and after the cue-reactivity paradigm. On a physiological level, skin conductance responses toward shopping cues were higher in pathological buyers (mean [M; standard deviation {SD}] = 0.26 [0.13]) compared with control participants (M [SD] = 0.19 [0.09]; t(58) = 2.29, p = .025, d = 0.60). On a behavioral level, the individuals with pathological buying rated the shopping cues as more arousing and more positive, and reported a greater urge to buy compared with control participants and with control cues. An increase in subjective craving after completing the cue-reactivity paradigm was observed only in the pathological buyers (Mpre [SD] = 1.95 [1.47], Mpost [SD] = 2.87 [1.79]; t(29) = 5.07, p < .001, d = 0.97). Cue-reactivity and craving might be potential correlates for the development and maintenance of pathological buying. The results demonstrate similarities between pathological buying and substance or behavioral addictions and provide implications for clinical treatment.

Using Pupil Perspective in the Primary Classroom: An Exploration of Some of the Potential Issues

ERIC Educational Resources Information Center

Fisher, Helen

2014-01-01

This article uses the author's original study of over hundred Year six children's perspectives of literacy and the wider curriculum, in English schools, to explore the potential challenges of exploring "pupil voice". Using collective case studies, with descriptive and time-sampled observations, and semi-structured interviews, across an…

Physiological and structural differences in spatially distinct subpopulations of cardiac mitochondria: influence of cardiac pathologies

PubMed Central

Thapa, Dharendra; Shepherd, Danielle L.

2014-01-01

Cardiac tissue contains discrete pools of mitochondria that are characterized by their subcellular spatial arrangement. Subsarcolemmal mitochondria (SSM) exist below the cell membrane, interfibrillar mitochondria (IFM) reside in rows between the myofibrils, and perinuclear mitochondria are situated at the nuclear poles. Microstructural imaging of heart tissue coupled with the development of differential isolation techniques designed to sequentially separate spatially distinct mitochondrial subpopulations have revealed differences in morphological features including shape, absolute size, and internal cristae arrangement. These findings have been complemented by functional studies indicating differences in biochemical parameters and, potentially, functional roles for the ATP generated, based upon subcellular location. Consequently, mitochondrial subpopulations appear to be influenced differently during cardiac pathologies including ischemia/reperfusion, heart failure, aging, exercise, and diabetes mellitus. These influences may be the result of specific structural and functional disparities between mitochondrial subpopulations such that the stress elicited by a given cardiac insult differentially impacts subcellular locales and the mitochondria contained within. The goal of this review is to highlight some of the inherent structural and functional differences that exist between spatially distinct cardiac mitochondrial subpopulations as well as provide an overview of the differential impact of various cardiac pathologies on spatially distinct mitochondrial subpopulations. As an outcome, we will instill a basis for incorporating subcellular spatial location when evaluating the impact of cardiac pathologies on the mitochondrion. Incorporation of subcellular spatial location may offer the greatest potential for delineating the influence of cardiac pathology on this critical organelle. PMID:24778166

The δ isoform of CaM kinase II is required for pathological cardiac hypertrophy and remodeling after pressure overload

PubMed Central

Backs, Johannes; Backs, Thea; Neef, Stefan; Kreusser, Michael M.; Lehmann, Lorenz H.; Patrick, David M.; Grueter, Chad E.; Qi, Xiaoxia; Richardson, James A.; Hill, Joseph A.; Katus, Hugo A.; Bassel-Duby, Rhonda; Maier, Lars S.; Olson, Eric N.

2009-01-01

Acute and chronic injuries to the heart result in perturbation of intracellular calcium signaling, which leads to pathological cardiac hypertrophy and remodeling. Calcium/calmodulin-dependent protein kinase II (CaMKII) has been implicated in the transduction of calcium signals in the heart, but the specific isoforms of CaMKII that mediate pathological cardiac signaling have not been fully defined. To investigate the potential involvement in heart disease of CaMKIIδ, the major CaMKII isoform expressed in the heart, we generated CaMKIIδ-null mice. These mice are viable and display no overt abnormalities in cardiac structure or function in the absence of stress. However, pathological cardiac hypertrophy and remodeling are attenuated in response to pressure overload in these animals. Cardiac extracts from CaMKIIδ-null mice showed diminished kinase activity toward histone deacetylase 4 (HDAC4), a substrate of stress-responsive protein kinases and suppressor of stress-dependent cardiac remodeling. In contrast, phosphorylation of the closely related HDAC5 was unaffected in hearts of CaMKIIδ-null mice, underscoring the specificity of the CaMKIIδ signaling pathway for HDAC4 phosphorylation. We conclude that CaMKIIδ functions as an important transducer of stress stimuli involved in pathological cardiac remodeling in vivo, which is mediated, at least in part, by the phosphorylation of HDAC4. These findings point to CaMKIIδ as a potential therapeutic target for the maintenance of cardiac function in the setting of pressure overload. PMID:19179290

Impaired Decisional Impulsivity in Pathological Videogamers

PubMed Central

Irvine, Michael A.; Worbe, Yulia; Bolton, Sorcha; Harrison, Neil A.; Bullmore, Edward T.; Voon, Valerie

2013-01-01

Background Pathological gaming is an emerging and poorly understood problem. Impulsivity is commonly impaired in disorders of behavioural and substance addiction, hence we sought to systematically investigate the different subtypes of decisional and motor impulsivity in a well-defined pathological gaming cohort. Methods Fifty-two pathological gaming subjects and age-, gender- and IQ-matched healthy volunteers were tested on decisional impulsivity (Information Sampling Task testing reflection impulsivity and delay discounting questionnaire testing impulsive choice), and motor impulsivity (Stop Signal Task testing motor response inhibition, and the premature responding task). We used stringent diagnostic criteria highlighting functional impairment. Results In the Information Sampling Task, pathological gaming participants sampled less evidence prior to making a decision and scored fewer points compared with healthy volunteers. Gaming severity was also negatively correlated with evidence gathered and positively correlated with sampling error and points acquired. In the delay discounting task, pathological gamers made more impulsive choices, preferring smaller immediate over larger delayed rewards. Pathological gamers made more premature responses related to comorbid nicotine use. Greater number of hours played also correlated with a Motivational Index. Greater frequency of role playing games was associated with impaired motor response inhibition and strategy games with faster Go reaction time. Conclusions We show that pathological gaming is associated with impaired decisional impulsivity with negative consequences in task performance. Decisional impulsivity may be a potential target in therapeutic management. PMID:24146789

Pathology Dynamics Predict Spinal Cord Injury Therapeutic Success

PubMed Central

Mitchell, Cassie S.

2008-01-01

Abstract Secondary injury, the complex cascade of cellular events following spinal cord injury (SCI), is a major source of post-insult neuron death. Experimental work has focused on the details of individual factors or mechanisms that contribute to secondary injury, but little is known about the interactions among factors leading to the overall pathology dynamics that underlie its propagation. Prior hypotheses suggest that the pathology is dominated by interactions, with therapeutic success lying in combinations of neuroprotective treatments. In this study, we provide the first comprehensive, system-level characterization of the entire secondary injury process using a novel relational model methodology that aggregates the findings of ~250 experimental studies. Our quantitative examination of the overall pathology dynamics suggests that, while the pathology is initially dominated by “fire-like,” rate-dependent interactions, it quickly switches to a “flood-like,” accumulation-dependent process with contributing factors being largely independent. Our evaluation of ~20,000 potential single and combinatorial treatments indicates this flood-like pathology results in few highly influential factors at clinically realistic treatment time frames, with multi-factor treatments being merely additive rather than synergistic in reducing neuron death. Our findings give new fundamental insight into the understanding of the secondary injury pathology as a whole, provide direction for alternative therapeutic strategies, and suggest that ultimate success in treating SCI lies in the pursuit of pathology dynamics in addition to individually involved factors. PMID:19125684

Regression of Pathological Cardiac Hypertrophy: Signaling Pathways and Therapeutic Targets

PubMed Central

Hou, Jianglong; Kang, Y. James

2012-01-01

Pathological cardiac hypertrophy is a key risk factor for heart failure. It is associated with increased interstitial fibrosis, cell death and cardiac dysfunction. The progression of pathological cardiac hypertrophy has long been considered as irreversible. However, recent clinical observations and experimental studies have produced evidence showing the reversal of pathological cardiac hypertrophy. Left ventricle assist devices used in heart failure patients for bridging to transplantation not only improve peripheral circulation but also often cause reverse remodeling of the geometry and recovery of the function of the heart. Dietary supplementation with physiologically relevant levels of copper can reverse pathological cardiac hypertrophy in mice. Angiogenesis is essential and vascular endothelial growth factor (VEGF) is a constitutive factor for the regression. The action of VEGF is mediated by VEGF receptor-1, whose activation is linked to cyclic GMP-dependent protein kinase-1 (PKG-1) signaling pathways, and inhibition of cyclic GMP degradation leads to regression of pathological cardiac hypertrophy. Most of these pathways are regulated by hypoxia-inducible factor. Potential therapeutic targets for promoting the regression include: promotion of angiogenesis, selective enhancement of VEGF receptor-1 signaling pathways, stimulation of PKG-1 pathways, and sustention of hypoxia-inducible factor transcriptional activity. More exciting insights into the regression of pathological cardiac hypertrophy are emerging. The time of translating the concept of regression of pathological cardiac hypertrophy to clinical practice is coming. PMID:22750195

Applications of QCL mid-IR imaging to the advancement of pathology

NASA Astrophysics Data System (ADS)

Sreedhar, Hari; Varma, Vishal K.; Bird, Benjamin; Guzman, Grace; Walsh, Michael J.

2017-03-01

Quantum Cascade Laser (QCL) spectroscopic imaging is a novel technique with many potential applications to histopathology. Like traditional Fourier Transform Infrared (FT-IR) imaging, QCL spectroscopic imaging derives biochemical data coupled to the spatial information of a tissue sample, and can be used to improve the diagnostic and prognostic value of assessment of a tissue biopsy. This technique also offers advantages over traditional FT-IR imaging, specifically the capacity for discrete frequency and real-time imaging. In this work we present applications of QCL spectroscopic imaging to tissue samples, including discrete frequency imaging, to compare with FT-IR and its potential value to pathology.

Fishing for causes and cures of motor neuron disorders

PubMed Central

Patten, Shunmoogum A.; Armstrong, Gary A. B.; Lissouba, Alexandra; Kabashi, Edor; Parker, J. Alex; Drapeau, Pierre

2014-01-01

Motor neuron disorders (MNDs) are a clinically heterogeneous group of neurological diseases characterized by progressive degeneration of motor neurons, and share some common pathological pathways. Despite remarkable advances in our understanding of these diseases, no curative treatment for MNDs exists. To better understand the pathogenesis of MNDs and to help develop new treatments, the establishment of animal models that can be studied efficiently and thoroughly is paramount. The zebrafish (Danio rerio) is increasingly becoming a valuable model for studying human diseases and in screening for potential therapeutics. In this Review, we highlight recent progress in using zebrafish to study the pathology of the most common MNDs: spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and hereditary spastic paraplegia (HSP). These studies indicate the power of zebrafish as a model to study the consequences of disease-related genes, because zebrafish homologues of human genes have conserved functions with respect to the aetiology of MNDs. Zebrafish also complement other animal models for the study of pathological mechanisms of MNDs and are particularly advantageous for the screening of compounds with therapeutic potential. We present an overview of their potential usefulness in MND drug discovery, which is just beginning and holds much promise for future therapeutic development. PMID:24973750

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

PubMed

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

2006-11-14

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

Examination of changes in pathology tests ordered by Diagnosis-Related Group (DRGs) following CPOE introduction.

PubMed

Vecellio, Elia; Georgiou, Andrew; Toouli, George; Eigenstetter, Alex; Li, Ling; Wilson, Roger; Westbrook, Johanna I

2013-01-01

Electronic test ordering, via the Electronic Medical Record (EMR), which incorporates computerised provider order entry (CPOE), is widely considered as a useful tool to support appropriate pathology test ordering. Diagnosis-related groups (DRGs) are clinically meaningful categories that allow comparisons in pathology utilisation by patient groups by controlling for many potentially confounding variables. This study used DRG data linked to pathology test data to examine changes in rates of test ordering across four years coinciding with the introduction of an EMR in six hospitals in New South Wales, Australia. This method generated a list of high pathology utilisation DRGs. We investigated patients with a Chest pain DRG to examine whether tests rates changed for specific test groups by hospital emergency department (ED) pre- and post-EMR. There was little change in testing rates between EDs or between time periods pre- and post-EMR. This is a valuable method for monitoring the impact of EMR and clinical decision support on test order rates.

Review of advanced imaging techniques

PubMed Central

Chen, Yu; Liang, Chia-Pin; Liu, Yang; Fischer, Andrew H.; Parwani, Anil V.; Pantanowitz, Liron

2012-01-01

Pathology informatics encompasses digital imaging and related applications. Several specialized microscopy techniques have emerged which permit the acquisition of digital images (“optical biopsies”) at high resolution. Coupled with fiber-optic and micro-optic components, some of these imaging techniques (e.g., optical coherence tomography) are now integrated with a wide range of imaging devices such as endoscopes, laparoscopes, catheters, and needles that enable imaging inside the body. These advanced imaging modalities have exciting diagnostic potential and introduce new opportunities in pathology. Therefore, it is important that pathology informaticists understand these advanced imaging techniques and the impact they have on pathology. This paper reviews several recently developed microscopic techniques, including diffraction-limited methods (e.g., confocal microscopy, 2-photon microscopy, 4Pi microscopy, and spatially modulated illumination microscopy) and subdiffraction techniques (e.g., photoactivated localization microscopy, stochastic optical reconstruction microscopy, and stimulated emission depletion microscopy). This article serves as a primer for pathology informaticists, highlighting the fundamentals and applications of advanced optical imaging techniques. PMID:22754737

Who Seeks Treatment When Medicine Opens the Door to Pathological Gambling Patients-Psychiatric Comorbidity and Heavy Predominance of Online Gambling.

PubMed

Håkansson, Anders; Mårdhed, Emma; Zaar, Mats

2017-01-01

Few studies have assessed treatment-seeking behavior and patient characteristics in pathological gambling focusing on psychiatric comorbidity, particularly in a setting of heavy exposure to online gambling. This study aimed to address patient characteristics in a novel health care-based treatment modality for pathological gambling, including potential associations between gambling types, psychiatric comorbidity, and gender. All patients undergoing structured assessment between January 2016 and April 2017 were included ( N  = 106), and patient records were reviewed for cooccurring psychiatric disorders and types of problem games. Eighty percent were men, and 58% received a psychiatric disorder apart from pathological gambling. Problematic gambling on online casino and online sports betting represented 84% of patients. Non-substance-related psychiatric comorbidity was significantly associated with female gender. Online gambling is more clearly predominating in this setting than in studies from other countries. High rates of comorbidity call for structured psychiatric assessment in problem gambling, with a particular focus on female patients with pathological gambling.

[Pathology websites in the World Wide Web. A guide for a specific research of pathology information on the Internet].

PubMed

Böhm, J

2008-05-01

Being a global information network, the internet has becoming increasingly important for pathologists as a medium for professional communication and information. Although a large number of pathology-specific websites (PSWs) are accessible on the internet, the potentials of PSWs are still barely known. Since there is no global catalog for all the pathology websites, certain PSWs are difficult to find on the internet. PSWs offer lavishly illustrated education material for undergraduates and postgraduates in pathology, but may also be very useful as reference books or as an instrument of continuing medical education (CME) for experienced pathologists. The spectrum of PSW media comprises electronic training manuals, journals, case collections, photo-archives, and even complete section series of virtual microscopy. PSWs are available at any time, can be updated permanently and linked to further online sources of information. We demonstrate how to find PSWs and present an annotated list of some 100 of the best PSWs.

Biomarkers for Cognitive Impairment in Parkinson Disease

PubMed Central

Shi, Min; Huber, Bertrand R.; Zhang, Jing

2010-01-01

Cognitive impairment, including dementia, is commonly seen in those afflicted with Parkinson disease (PD), particularly at advanced disease stages. Pathologically, PD with dementia (PD-D) is most often associated with the presence of cortical Lewy bodies, as is the closely related dementia with Lewy bodies (DLB). Both PD-D and DLB are also frequently complicated by the presence of neurofibrillary tangles and amyloid plaques, features most often attributed to Alzheimer disease. Biomarkers are urgently needed to differentiate among these disease processes and predict dementia in PD as well as monitor responses of patients to new therapies. A few clinical assessments, along with structural and functional neuroimaging, have been utilized in the last few years with some success in this area. Additionally, a number of other strategies have been employed to identify biochemical/molecular biomarkers associated with cognitive impairment and dementia in PD, e.g., targeted analysis of candidate proteins known to be important to PD pathogenesis and progression in cerebrospinal fluid or blood. Finally, interesting results are emerging from preliminary studies with unbiased and high throughput genomic, proteomic and metabolomic techniques. The current findings and perspectives of applying these strategies and techniques are reviewed in this article, together with potential areas of advancement. PMID:20522092

Micro-optical coherence tomography of the mammalian cochlea

PubMed Central

Iyer, Janani S.; Batts, Shelley A.; Chu, Kengyeh K.; Sahin, Mehmet I.; Leung, Hui Min; Tearney, Guillermo J.; Stankovic, Konstantina M.

2016-01-01

The mammalian cochlea has historically resisted attempts at high-resolution, non-invasive imaging due to its small size, complex three-dimensional structure, and embedded location within the temporal bone. As a result, little is known about the relationship between an individual’s cochlear pathology and hearing function, and otologists must rely on physiological testing and imaging methods that offer limited resolution to obtain information about the inner ear prior to performing surgery. Micro-optical coherence tomography (μOCT) is a non-invasive, low-coherence interferometric imaging technique capable of resolving cellular-level anatomic structures. To determine whether μOCT is capable of resolving mammalian intracochlear anatomy, fixed guinea pig inner ears were imaged as whole temporal bones with cochlea in situ. Anatomical structures such as the tunnel of Corti, space of Nuel, modiolus, scalae, and cell groupings were visualized, in addition to individual cell types such as neuronal fibers, hair cells, and supporting cells. Visualization of these structures, via volumetrically-reconstructed image stacks and endoscopic perspective videos, represents an improvement over previous efforts using conventional OCT. These are the first μOCT images of mammalian cochlear anatomy, and they demonstrate μOCT’s potential utility as an imaging tool in otology research. PMID:27633610

The chronobiology, etiology and pathophysiology of obesity

PubMed Central

Garaulet, M; Ordovás, JM; Madrid, JA

2015-01-01

The effect of CD on human health is an emerging issue. Many records link CD with diseases such as cancer, cardiovascular, cognitive impairment and obesity, all of them conducive to premature aging. The amount of sleep has declined by 1.5 h over the past century, accompanied by an important increase in obesity. Shift work, sleep deprivation and exposure to bright light at night increase the prevalence of adiposity. Animal models have shown that mice with Clock gene disruption are prone to developing obesity and MetS. This review summarizes the latest developments with regard to chronobiology and obesity, considering (1) how molecular clocks coordinate metabolism and the specific role of the adipocyte; (2) CD and its causes and pathological consequences; (3) the epidemiological evidence of obesity as a chronobiological illness; and (4) theories of circadian disruption and obesity. Energy intake and expenditure, relevance of sleep, fat intake from a circadian perspective and psychological and genetic aspects of obesity are examined. Finally, ideas about the use of chronobiology in the treatment of obesity are discussed. Such knowledge has the potential to become a valuable tool in the understanding of the relationship between the chronobiology, etiology and pathophysiology of obesity. PMID:20567242

Inorganic Nitrite Therapy: Historical perspective and future directions

PubMed Central

Kevil, Christopher G.; Kolluru, Gopi K.; Pattillo, Christopher B.; Giordano, Tony

2015-01-01

Over the past several years, investigators studying nitric oxide (NO) biology and metabolism have come to learn that the one electron oxidation product of NO, nitrite anion, serves as a unique player in modulating tissue NO bioavailability. Numerous studies have examined how this oxidized metabolite of NO can act as a salvage pathway for maintaining NO equivalents through multiple reduction mechanisms in permissive tissue environments. Moreover, it is now clear that nitrite anion production and distribution throughout the body can act in an endocrine manner to augment NO bioavailability that is important for physiological and pathological processes. These discoveries have led to renewed hope and efforts for an effective NO based therapeutic agent through the unique action of sodium nitrite as an NO pro-drug. More recent studies also indicate that sodium nitrate may also increase plasma nitrite levels via the enterosalivary circulatory system resulting in nitrate reduction to nitrite by microorganisms found within the oral cavity. In this review, we discuss the importance of nitrite anion in several disease models along with an appraisal of sodium nitrite therapy in the clinic, potential caveats of such clinical uses, and future possibilities of nitrite based therapies. PMID:21619929

Medico-legal perspectives on sudden cardiac death in young athletes.

PubMed

Oliva, Antonio; Grassi, Vincenzo M; Campuzano, Oscar; Brion, Maria; Arena, Vincenzo; Partemi, Sara; Coll, Monica; Pascali, Vincenzo L; Brugada, Josep; Carracedo, Angel; Brugada, Ramon

2017-03-01

Sudden cardiac death (SCD) in a young athlete represents a dramatic event, and an increasing number of medico-legal cases have addressed this topic. In addition to representing an ethical and medico-legal responsibility, prevention of SCD is directly correlated with accurate eligibility/disqualification decisions, with an inappropriate pronouncement in either direction potentially leading to legal controversy. This review summarizes the common causes of SCD in young athletes, divided into structural (hypertrophic cardiomyopathy, arrhythmogenic cardiomyopathy, congenital coronary artery anomalies, etc.), electrical (Brugada, congenital LQT, Wolf-Parkinson-White syndrome, etc.), and acquired cardiac abnormalities (myocarditis, etc.). In addition, the roles of hereditary cardiac anomalies in SCD in athletes and the effects of a positive result on them and their families are discussed. The medico-legal relevance of pre-participation screening is analyzed, and recommendations from the American Heart Association and European Society of Cardiology are compared. Finally, the main issues concerning the differentiation between physiologic cardiac adaptation in athletes and pathologic findings and, thereby, definition of the so-called gray zone, which is based on exact knowledge of the mechanism of cardiac remodeling including structural or functional adaptions, will be addressed.

Diagnosis and treatment of chronic constipation – a European perspective

PubMed Central

Tack, J; Müller-Lissner, S; Stanghellini, V; Boeckxstaens, G; Kamm, M A; Simren, M; Galmiche, J-P; Fried, M

2011-01-01

Background Although constipation can be a chronic and severe problem, it is largely treated empirically. Evidence for the efficacy of some of the older laxatives from well-designed trials is limited. Patients often report high levels of dissatisfaction with their treatment, which is attributed to a lack of efficacy or unpleasant side-effects. Management guidelines and recommendations are limited and are not sufficiently current to include treatments that became available more recently, such as prokinetic agents in Europe. Purpose We present an overview of the pathophysiology, diagnosis, current management and available guidelines for the treatment of chronic constipation, and include recent data on the efficacy and potential clinical use of the more newly available therapeutic agents. Based on published algorithms and guidelines on the management of chronic constipation, secondary pathologies and causes are first excluded and then diet, lifestyle, and, if available, behavioral measures adopted. If these fail, bulk-forming, osmotic, and stimulant laxatives can be used. If symptoms are not satisfactorily resolved, a prokinetic agent such as prucalopride can be prescribed. Biofeedback is recommended as a treatment for chronic constipation in patients with disordered defecation. Surgery should only be considered once all other treatment options have been exhausted. PMID:21605282

Liquid Biopsy in Lung Cancer: A Perspective From Members of the Pulmonary Pathology Society.

PubMed

Sholl, Lynette M; Aisner, Dara L; Allen, Timothy Craig; Beasley, Mary Beth; Cagle, Philip T; Capelozzi, Vera L; Dacic, Sanja; Hariri, Lida P; Kerr, Keith M; Lantuejoul, Sylvie; Mino-Kenudson, Mari; Raparia, Kirtee; Rekhtman, Natasha; Roy-Chowdhuri, Sinchita; Thunnissen, Eric; Tsao, Ming; Vivero, Marina; Yatabe, Yasushi

2016-08-01

Liquid biopsy has received extensive media coverage and has been called the holy grail of cancer detection. Attempts at circulating tumor cell and genetic material capture have been progressing for several years, and recent financially and technically feasible improvements of cell capture devices, plasma isolation techniques, and highly sensitive polymerase chain reaction- and sequencing-based methods have advanced the possibility of liquid biopsy of solid tumors. Although practical use of circulating RNA-based testing has been hindered by the need to fractionate blood to enrich for RNAs, the detection of circulating tumor cells has profited from advances in cell capture technology. In fact, the US Food and Drug Administration has approved one circulating tumor cell selection platform, the CellSearch System. Although the use of liquid biopsy in a patient population with a genomically defined solid tumor may potentially be clinically useful, it currently does not supersede conventional pretreatment tissue diagnosis of lung cancer. Liquid biopsy has not been validated for lung cancer diagnosis, and its lower sensitivity could lead to significant diagnostic delay if liquid biopsy were to be used in lieu of tissue biopsy. Ultimately, notwithstanding the enthusiasm encompassing liquid biopsy, its clinical utility remains unproven.

Innate lymphoid cells: the role in respiratory infections and lung tissue damage.

PubMed

Głobińska, Anna; Kowalski, Marek L

2017-10-01

Innate lymphoid cells (ILCs) represent a diverse family of cells of the innate immune system, which play an important role in regulation of tissue homeostasis, immunity and inflammation. Emerging evidence has highlighted the importance of ILCs in both protective immunity to respiratory infections and their pathological roles in the lungs. Therefore, the aim of this review is to summarize the current knowledge, interpret and integrate it into broader perspective, enabling greater insight into the role of ILCs in respiratory diseases. Areas covered: In this review we highlighted the role of ILCs in the lungs, citing the most recent studies in this area. PubMed searches (2004- July 2017) were conducted using the term 'innate lymphoid cells respiratory viral infections' in combination with other relevant terms including various respiratory viruses. Expert commentary: Since studies of ILCs have opened new areas of investigation, understanding the role of ILCs in respiratory infections may help to clarify the mechanisms underlying viral-induced exacerbations of lung diseases, providing the basis for novel therapeutic strategies. Potential therapeutic targets have already been identified. So far, the most promising strategy is cytokine-targeting, although further clinical trials are needed to verify its effectiveness.

miRNA assays in the clinical laboratory: workflow, detection technologies and automation aspects.

PubMed

Kappel, Andreas; Keller, Andreas

2017-05-01

microRNAs (miRNAs) are short non-coding RNA molecules that regulate gene expression in eukaryotes. Their differential abundance is indicative or even causative for a variety of pathological processes including cancer or cardiovascular disorders. Due to their important biological function, miRNAs represent a promising class of novel biomarkers that may be used to diagnose life-threatening diseases, and to monitor disease progression. Further, they may guide treatment selection or dosage of drugs. miRNAs from blood or derived fractions are particularly interesting candidates for routine laboratory applications, as they can be measured in most clinical laboratories already today. This assures a good accessibility of respective tests. Albeit their great potential, miRNA-based diagnostic tests have not made their way yet into the clinical routine, and hence no standardized workflows have been established to measure miRNAs for patients' benefit. In this review we summarize the detection technologies and workflow options that exist to measure miRNAs, and we describe the advantages and disadvantages of each of these options. Moreover, we also provide a perspective on data analysis aspects that are vital for translation of raw data into actionable diagnostic test results.

Alpha-7 Nicotinic Receptors in Nervous System Disorders: From Function to Therapeutic Perspectives.

PubMed

De Jaco, Antonella; Bernardini, Laura; Rosati, Jessica; Tata, Ada Maria

2017-01-01

The α7 nicotinic receptor consists of identical subunits and is one of the most abundant acetylcholine receptors in the mammalian central nervous system. However its expression is also found in the peripheral nervous system as well as in the immune system and various peripheral tissues. Nicotinic Receptors: They are involved in the regulation of several activities ranging from excitatory neurotransmission, the modulation of the release of several neurotransmitters, regulation of neurite outgrowth, and even neuronal survival/death. Its expression is found in brain areas that underlie learning and memory, suggesting their involvement in regulating cognitive functions. The α7-nicotinic receptor has a strategic role during development in regulating molecular pathways activated during neurogenesis. Because of its pleiotropic effects, receptor dysfunction or dysregulated expression is found in pathophysiological conditions of the nervous system including neurodegenerative diseases and neurodevelopmental disorders. Here we review the physiological and pathological roles of alpha-7 nicotinic receptor in different nervous system disorders and the current therapeutic strategies developed to target selectively this receptor for potentiating or reducing its functions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

hERG trafficking inhibition in drug-induced lethal cardiac arrhythmia.

PubMed

Nogawa, Hisashi; Kawai, Tomoyuki

2014-10-15

Acquired long QT syndrome induced by non-cardiovascular drugs can cause lethal cardiac arrhythmia called torsades de points and is a significant problem in drug development. The prolongation of QT interval and cardiac action potential duration are mainly due to reduced physiological function of the rapidly activating voltage-dependent potassium channels encoded by human ether-a-go-go-related gene (hERG). Structurally diverse groups of drugs are known to directly inhibit hERG channel conductance. Therefore, the ability of acute hERG inhibition is routinely assessed at the preclinical stages in pharmaceutical testing. Recent findings indicated that chronic treatment with various drugs not only inhibits hERG channels but also decreases hERG channel expression in the plasma membrane of cardiomyocytes, which has become another concern in safety pharmacology. The mechanisms involve the disruption of hERG trafficking to the surface membrane or the acceleration of hERG protein degradation. From this perspective, we present a brief overview of mechanisms of drug-induced trafficking inhibition and pathological regulation. Understanding of drug-induced hERG trafficking inhibition may provide new strategies for predicting drug-induced QT prolongation and lethal cardiac arrhythmia in pharmaceutical drug development. Copyright © 2014 Elsevier B.V. All rights reserved.

Social networks and future direction for obesity research: A scoping review

PubMed Central

Nam, Soohyun; Redeker, Nancy; Whittemore, Robin

2014-01-01

Despite significant efforts to decrease obesity rates, the prevalence of obesity continues to increase in the United States. Obesity-risk behaviors—physical inactivity, unhealthy eating, and sleep deprivation—are intertwined during daily life and are difficult to improve in the current social environment. Studies show that social networks—the thick webs of social relations and interactions—influence various health outcomes, such as HIV risk behaviors, alcohol consumption, smoking, depression, and cardiovascular mortality; however, there is limited information on the influences of social networks on obesity and obesity-risk behaviors. Given the complexities of the bio-behavioral pathology of obesity, and the lack of clear evidence of effectiveness and sustainability of existing interventions that are usually focused on an individual approach, targeting change in an individual’s health behaviors or attitude may not take socio-contextual factors into account; there is a pressing need for a new perspective on this problem. In this review we evaluate the literature on social networks as a potential approach for obesity prevention and treatment: how social networks affect various health outcomes and present two major social network data analyses (i.e. egocentric and sociometric analysis); and discuss implications and future direction for obesity research using social networks. PMID:25982770

Stem Cells in Skin Regeneration, Wound Healing, and Their Clinical Applications

PubMed Central

Ojeh, Nkemcho; Pastar, Irena; Tomic-Canic, Marjana; Stojadinovic, Olivera

2015-01-01

The skin is the largest organ of the body and has an array of functions. Skin compartments, epidermis, and hair follicles house stem cells that are indispensable for skin homeostasis and regeneration. These stem cells also contribute to wound repair, resulting in restoration of tissue integrity and function of damaged tissue. Unsuccessful wound healing processes often lead to non-healing wounds. Chronic wounds are caused by depletion of stem cells and a variety of other cellular and molecular mechanisms, many of which are still poorly understood. Current chronic wound therapies are limited, so the search to develop better therapeutic strategies is ongoing. Adult stem cells are gaining recognition as potential candidates for numerous skin pathologies. In this review, we will discuss epidermal and other stem cells present in the skin, and highlight some of the therapeutic applications of epidermal stem cells and other adult stem cells as tools for cell/scaffold-based therapies for non-healing wounds and other skin disorders. We will also discuss emerging concepts and offer some perspectives on how skin tissue-engineered products can be optimized to provide efficacious therapy in cutaneous repair and regeneration. PMID:26512657

Pathological Left Ventricular Hypertrophy and Stem Cells: Current Evidence and New Perspectives.

PubMed

Marketou, Maria E; Parthenakis, Fragiskos; Vardas, Panos E

2016-01-01

Left ventricular hypertrophy (LVH) is a strong predictor of adverse cardiovascular outcomes. It is the result of complex mechanisms that include not only an increase in protein synthesis and cell size but also proliferating cardiac progenitor cells and the influx of bone marrow-derived cells developing into cardiomyocytes. Stem and progenitor cells are known to contribute to the renewal of adult mammalian cardiomyocytes in case of myocardial injury or pressure and volume overload. They are activated in LVH and play a regulatory role in myocardial repair. They have high proliferative potential and secrete numerous cytokines, growth factors, and microRNAs that play important roles in cell differentiation, cardiac remodeling, and neovascularization. They are mobilized in response to either mechanical or chemical stimuli, hormones, or pharmacologic agents. Another important source of progenitor cells is the epicardial layer. It appears that precursor cells migrate from the epicardium to the myocardium in order to interact with myocardial cells. In addition, migratory cells participate in the formation of almost all cardiac structures in myocardial hypertrophy. Although the pathophysiological mechanisms are still obscure and further studies are required, their properties may open the door to regenerative cell therapy for the prevention of adverse remodeling.

The chronobiology, etiology and pathophysiology of obesity.

PubMed

Garaulet, M; Ordovás, J M; Madrid, J A

2010-12-01

The effect of CD on human health is an emerging issue. Many records link CD with diseases such as cancer, cardiovascular, cognitive impairment and obesity, all of them conducive to premature aging. The amount of sleep has declined by 1.5 h over the past century, accompanied by an important increase in obesity. Shift work, sleep deprivation and exposure to bright light at night increase the prevalence of adiposity. Animal models have shown that mice with Clock gene disruption are prone to developing obesity and MetS. This review summarizes the latest developments with regard to chronobiology and obesity, considering (1) how molecular clocks coordinate metabolism and the specific role of the adipocyte; (2) CD and its causes and pathological consequences; (3) the epidemiological evidence of obesity as a chronobiological illness; and (4) theories of circadian disruption and obesity. Energy intake and expenditure, relevance of sleep, fat intake from a circadian perspective and psychological and genetic aspects of obesity are examined. Finally, ideas about the use of chronobiology in the treatment of obesity are discussed. Such knowledge has the potential to become a valuable tool in the understanding of the relationship between the chronobiology, etiology and pathophysiology of obesity.

Advances and Prospects in Tissue-Engineered Meniscal Scaffolds for Meniscus Regeneration

PubMed Central

Guo, Weimin; Liu, Shuyun; Zhu, Yun; Yu, Changlong; Lu, Shibi; Yuan, Mei; Huang, Jingxiang; Yuan, Zhiguo; Peng, Jiang; Wang, Aiyuan; Wang, Yu; Chen, Jifeng; Zhang, Li; Sui, Xiang; Xu, Wenjing; Guo, Quanyi

2015-01-01

The meniscus plays a crucial role in maintaining knee joint homoeostasis. Meniscal lesions are relatively common in the knee joint and are typically categorized into various types. However, it is difficult for inner avascular meniscal lesions to self-heal. Untreated meniscal lesions lead to meniscal extrusions in the long-term and gradually trigger the development of knee osteoarthritis (OA). The relationship between meniscal lesions and knee OA is complex. Partial meniscectomy, which is the primary method to treat a meniscal injury, only relieves short-term pain; however, it does not prevent the development of knee OA. Similarly, other current therapeutic strategies have intrinsic limitations in clinical practice. Tissue engineering technology will probably address this challenge by reconstructing a meniscus possessing an integrated configuration with competent biomechanical capacity. This review describes normal structure and biomechanical characteristics of the meniscus, discusses the relationship between meniscal lesions and knee OA, and summarizes the classifications and corresponding treatment strategies for meniscal lesions to understand meniscal regeneration from physiological and pathological perspectives. Last, we present current advances in meniscal scaffolds and provide a number of prospects that will potentially benefit the development of meniscal regeneration methods. PMID:26199629

Stem Cells in Skin Regeneration, Wound Healing, and Their Clinical Applications.

PubMed

Ojeh, Nkemcho; Pastar, Irena; Tomic-Canic, Marjana; Stojadinovic, Olivera

2015-10-23

The skin is the largest organ of the body and has an array of functions. Skin compartments, epidermis, and hair follicles house stem cells that are indispensable for skin homeostasis and regeneration. These stem cells also contribute to wound repair, resulting in restoration of tissue integrity and function of damaged tissue. Unsuccessful wound healing processes often lead to non-healing wounds. Chronic wounds are caused by depletion of stem cells and a variety of other cellular and molecular mechanisms, many of which are still poorly understood. Current chronic wound therapies are limited, so the search to develop better therapeutic strategies is ongoing. Adult stem cells are gaining recognition as potential candidates for numerous skin pathologies. In this review, we will discuss epidermal and other stem cells present in the skin, and highlight some of the therapeutic applications of epidermal stem cells and other adult stem cells as tools for cell/scaffold-based therapies for non-healing wounds and other skin disorders. We will also discuss emerging concepts and offer some perspectives on how skin tissue-engineered products can be optimized to provide efficacious therapy in cutaneous repair and regeneration.

Computed tomography in hypersensitivity pneumonitis: main findings, differential diagnosis and pitfalls.

PubMed

Dias, Olívia Meira; Baldi, Bruno Guedes; Pennati, Francesca; Aliverti, Andrea; Chate, Rodrigo Caruso; Sawamura, Márcio Valente Yamada; Carvalho, Carlos Roberto Ribeiro de; Albuquerque, André Luis Pereira de

2018-01-01

Hypersensitivity pneumonitis (HP) is a disease with variable clinical presentation in which inflammation in the lung parenchyma is caused by the inhalation of specific organic antigens or low molecular weight substances in genetically susceptible individuals. Alterations of the acute, subacute and chronic forms may eventually overlap, and the diagnosis based on temporality and presence of fibrosis (acute/inflammatory HP vs. chronic HP) seems to be more feasible and useful in clinical practice. Differential diagnosis of chronic HP with other interstitial fibrotic diseases is challenging due to the overlap of the clinical history, and the functional and imaging findings of these pathologies in the terminal stages. Areas covered: This article reviews the essential features of HP with emphasis on imaging features. Moreover, the main methodological limitations of high-resolution computed tomography (HRCT) interpretation are discussed, as well as new perspectives with volumetric quantitative CT analysis as a useful tool for retrieving detailed and accurate information from the lung parenchyma. Expert commentary: Mosaic attenuation is a prominent feature of this disease, but air trapping in chronic HP seems overestimated. Quantitative analysis has the potential to estimate the involvement of the pulmonary parenchyma more accurately and could correlate better with pulmonary function results.

Potassium Channels in Peripheral Pain Pathways: Expression, Function and Therapeutic Potential

PubMed Central

Du, Xiaona; Gamper, Nikita

2013-01-01

Electrical excitation of peripheral somatosensory nerves is a first step in generation of most pain signals in mammalian nervous system. Such excitation is controlled by an intricate set of ion channels that are coordinated to produce a degree of excitation that is proportional to the strength of the external stimulation. However, in many disease states this coordination is disrupted resulting in deregulated peripheral excitability which, in turn, may underpin pathological pain states (i.e. migraine, neuralgia, neuropathic and inflammatory pains). One of the major groups of ion channels that are essential for controlling neuronal excitability is potassium channel family and, hereby, the focus of this review is on the K+ channels in peripheral pain pathways. The aim of the review is threefold. First, we will discuss current evidence for the expression and functional role of various K+ channels in peripheral nociceptive fibres. Second, we will consider a hypothesis suggesting that reduced functional activity of K+ channels within peripheral nociceptive pathways is a general feature of many types of pain. Third, we will evaluate the perspectives of pharmacological enhancement of K+ channels in nociceptive pathways as a strategy for new analgesic drug design. PMID:24396338

Audiology and speech-language pathology practice in Saudi Arabia.

PubMed

Alanazi, Ahmad A

2017-01-01

Audiology and speech-language pathology (SLP) are relatively new professions in Saudi Arabia. The idea of establishing new audiology and SLP programs in some education facilities has become popular across Saudi Arabia; yet, only four undergraduate and graduate programs are currently available. This study aimed to explore the fields of audiology and SLP in Saudi Arabia, obtain demography of audiologists and Speech-language pathologists (SLPs), understand their current practices, and identify their perspective on what both professions need to improve. A cross-sectional mixed methods study design was used to address the aim of this study. Two online surveys were prepared and distributed to reach a large number of audiologists and SLPs. Both surveys consisted of close- and open-ended questions and primarily focused on three categories demography, audiology or SLP practices, and audiologists' or SLPs' perspective on their professions in Saudi Arabia. A total of 23 audiologists and 37 SLPs completed the surveys (age range = 21-50 years). The majority of respondents were from Riyadh with different academic qualifications and working experiences. Various practices were noticed among audiologists and SLPs who mainly worked in hospitals. Several suggestions regarding the development of audiology and SLP education and practice in Saudi Arabia are discussed. This study provides useful information about audiology and SLP education and practices in Saudi Arabia. Collaborative work between stakeholders to achieve high-quality educational and practical standards is critical. National database, clinical guidelines and policies should be developed, employed, and supervised. Further research is needed to improve education and practice of both professions in Saudi Arabia.

Robotic Telecytology for Remote Cytologic Evaluation without an On-site Cytotechnologist or Cytopathologist: A Tale of Implementation and Review of Constraints

PubMed Central

Sirintrapun, Sahussapont Joseph; Rudomina, Dorota; Mazzella, Allix; Feratovic, Rusmir; Alago, William; Siegelbaum, Robert; Lin, Oscar

2017-01-01

Background: The first satellite center to offer interventional radiology procedures at Memorial Sloan Kettering Cancer Center opened in October 2014. Two of the procedures offered, fine needle aspirations and core biopsies, required rapid on-site cytologic evaluation of smears and biopsy touch imprints for cellular content and adequacy. The volume and frequency of such evaluations did not justify hiring on-site cytotechnologists, and therefore, a dynamic robotic telecytology (TC) solution was created. In this technical article, we present a detailed description of our implementation of robotic TC. Methods: Pathology devised the remote robotic TC solution after acknowledging that it would not be cost effective to staff cytotechnologists on-site at the satellite location. Sakura VisionTek was selected as our robotic TC solution. In addition to configuration of the dynamic robotic TC solution, pathology realized integrating the technology solution into operations would require a multidisciplinary effort and reevaluation of existing staffing and workflows. Results: Extensively described are the architectural framework and multidisciplinary process re-design, created to navigate the constraints of our technical, cultural, and organizational environment. Also reviewed are the benefits and challenges associated with available desktop sharing solutions, particularly accounting for information security concerns. Conclusions: Dynamic robotic TC is effective for immediate evaluations performed without on-site cytotechnology staff. Our goal is providing an extensive perspective of the implementation process, particularly technical, cultural, and operational constraints. Through this perspective, our template can serve as an extensible blueprint for other centers interested in implementing robotic TC without on-site cytotechnologists. PMID:28966832

Robotic Telecytology for Remote Cytologic Evaluation without an On-site Cytotechnologist or Cytopathologist: A Tale of Implementation and Review of Constraints.

PubMed

Sirintrapun, Sahussapont Joseph; Rudomina, Dorota; Mazzella, Allix; Feratovic, Rusmir; Alago, William; Siegelbaum, Robert; Lin, Oscar

2017-01-01

The first satellite center to offer interventional radiology procedures at Memorial Sloan Kettering Cancer Center opened in October 2014. Two of the procedures offered, fine needle aspirations and core biopsies, required rapid on-site cytologic evaluation of smears and biopsy touch imprints for cellular content and adequacy. The volume and frequency of such evaluations did not justify hiring on-site cytotechnologists, and therefore, a dynamic robotic telecytology (TC) solution was created. In this technical article, we present a detailed description of our implementation of robotic TC. Pathology devised the remote robotic TC solution after acknowledging that it would not be cost effective to staff cytotechnologists on-site at the satellite location. Sakura VisionTek was selected as our robotic TC solution. In addition to configuration of the dynamic robotic TC solution, pathology realized integrating the technology solution into operations would require a multidisciplinary effort and reevaluation of existing staffing and workflows. Extensively described are the architectural framework and multidisciplinary process re-design, created to navigate the constraints of our technical, cultural, and organizational environment. Also reviewed are the benefits and challenges associated with available desktop sharing solutions, particularly accounting for information security concerns. Dynamic robotic TC is effective for immediate evaluations performed without on-site cytotechnology staff. Our goal is providing an extensive perspective of the implementation process, particularly technical, cultural, and operational constraints. Through this perspective, our template can serve as an extensible blueprint for other centers interested in implementing robotic TC without on-site cytotechnologists.

Information Engineering and Workflow Design in a Clinical Decision Support System for Colorectal Cancer Screening in Iran.

PubMed

Maserat, Elham; Seied Farajollah, Seiede Sedigheh; Safdari, Reza; Ghazisaeedi, Marjan; Aghdaei, Hamid Asadzadeh; Zali, Mohammad Reza

2015-01-01

Colorectal cancer is a major cause of morbidity and mortality throughout the world. Colorectal cancer screening is an optimal way for reducing of morbidity and mortality and a clinical decision support system (CDSS) plays an important role in predicting success of screening processes. DSS is a computer-based information system that improves the delivery of preventive care services. The aim of this article was to detail engineering of information requirements and work flow design of CDSS for a colorectal cancer screening program. In the first stage a screening minimum data set was determined. Developed and developing countries were analyzed for identifying this data set. Then information deficiencies and gaps were determined by check list. The second stage was a qualitative survey with a semi-structured interview as the study tool. A total of 15 users and stakeholders' perspectives about workflow of CDSS were studied. Finally workflow of DSS of control program was designed by standard clinical practice guidelines and perspectives. Screening minimum data set of national colorectal cancer screening program was defined in five sections, including colonoscopy data set, surgery, pathology, genetics and pedigree data set. Deficiencies and information gaps were analyzed. Then we designed a work process standard of screening. Finally workflow of DSS and entry stage were determined. A CDSS facilitates complex decision making for screening and has key roles in designing optimal interactions between colonoscopy, pathology and laboratory departments. Also workflow analysis is useful to identify data reconciliation strategies to address documentation gaps. Following recommendations of CDSS should improve quality of colorectal cancer screening.

Biomarker-driven phenotyping in Parkinson disease: a translational missing link in disease-modifying clinical trials

PubMed Central

Espay, Alberto J.; Schwarzschild, Michael A.; Tanner, Caroline M.; Fernandez, Hubert H; Simon, David K.; Leverenz, James B.; Merola, Aristide; Chen-Plotkin, Alice; Brundin, Patrik; Kauffman, Marcelo A.; Erro, Roberto; Kieburtz, Karl; Woo, Daniel; Macklin, Eric A.; Standaert, David G.; Lang, Anthony E.

2016-01-01

Past clinical trials of putative neuroprotective therapies have targeted Parkinson disease (PD) as a single pathogenic disease entity. From an Oslerian clinico-pathologic perspective, the wide complexity of PD converges into Lewy bodies and justifies a reductionist approach to PD: a single-mechanism therapy can affect most of those sharing the classic pathologic hallmark. From a systems-biology perspective, PD is a group of disorders that, while related by sharing the feature of nigral dopamine-neuron degeneration, exhibit unique genetic, biological and molecular abnormalities, which probably respond differentially to a given therapeutic approach, particularly for strategies aimed at neuroprotection. Under this model, only biomarker-defined, homogenous subtypes of PD are likely to respond optimally to therapies proven to affect the biological processes within each subtype. Therefore, we suggest that precision medicine applied to PD requires a reevaluation of the biomarker-discovery effort. This effort is currently centered on correlating biological measures to clinical features of PD and on identifying factors that predict whether various prodromal states will convert into the classical movement disorder. We suggest, instead, that subtyping of PD requires the reverse view, where abnormal biological signals (i.e., biomarkers) rather than clinical definitions are used to define disease phenotypes. Successful development of disease-modifying strategies will depend on how relevant the specific biological processes addressed by an intervention are to the pathogenetic mechanisms in the subgroup of targeted patients. This precision-medicine approach will likely yield smaller but well-defined subsets of PD amenable to successful neuroprotection. PMID:28233927

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.

Functional TASK-3-Like Channels in Mitochondria of Aldosterone-Producing Zona Glomerulosa Cells.

PubMed

Yao, Junlan; McHedlishvili, David; McIntire, William E; Guagliardo, Nick A; Erisir, Alev; Coburn, Craig A; Santarelli, Vincent P; Bayliss, Douglas A; Barrett, Paula Q

2017-08-01

Ca 2+ drives aldosterone synthesis in the cytosolic and mitochondrial compartments of the adrenal zona glomerulosa cell. Membrane potential across each of these compartments regulates the amplitude of the Ca 2+ signal; yet, only plasma membrane ion channels and their role in regulating cell membrane potential have garnered investigative attention as pathological causes of human hyperaldosteronism. Previously, we reported that genetic deletion of TASK-3 channels (tandem pore domain acid-sensitive K + channels) from mice produces aldosterone excess in the absence of a change in the cell membrane potential of zona glomerulosa cells. Here, we report using yeast 2-hybrid, immunoprecipitation, and electron microscopic analyses that TASK-3 channels are resident in mitochondria, where they regulate mitochondrial morphology, mitochondrial membrane potential, and aldosterone production. This study provides proof of principle that mitochondrial K + channels, by modulating inner mitochondrial membrane morphology and mitochondrial membrane potential, have the ability to play a pathological role in aldosterone dysregulation in steroidogenic cells. © 2017 American Heart Association, Inc.

Assessing Individuals' Global Perspective

ERIC Educational Resources Information Center

Merrill, Kelly Carter; Braskamp, David C.; Braskamp, Larry A.

2012-01-01

This article introduces the Global Perspective Inventory (GPI), a survey instrument that measures participants' global perspective in terms of cognitive, intrapersonal, and interpersonal domains--each in terms of both development and acquisition. A summary of the recent research on the GPI is provided along with a discussion of potential uses.

Distance Education: Pros, Cons, and the Future.

ERIC Educational Resources Information Center

Li, Hongmei

This paper reviews recent publications on distance education and explores its promise and potential from the student's perspective, the faculty's perspective and the administrator's perspective. Findings indicate that only the self-motivated and self-disciplined students are most likely to succeed in distance education. Although the majority of…

Microglial internalization and degradation of pathological tau is enhanced by an anti-tau monoclonal antibody

PubMed Central

Luo, Wenjie; Liu, Wencheng; Hu, Xiaoyan; Hanna, Mary; Caravaca, April; Paul, Steven M.

2015-01-01

Microglia have been shown to contribute to the clearance of brain amyloid β peptides (Aβ), the major component of amyloid plaques, in Alzheimer’s disease (AD). However, it is not known whether microglia play a similar role in the clearance of tau, the major component of neurofibrillary tangles (NFTs). We now report that murine microglia rapidly internalize and degrade hyperphosphorylated pathological tau isolated from AD brain tissue in a time-dependent manner in vitro. We further demonstrate that microglia readily degrade human tau species released from AD brain sections and eliminate NFTs from brain sections of P301S tauopathy mice. The anti-tau monoclonal antibody MC1 enhances microglia-mediated tau degradation in an Fc-dependent manner. Our data identify a potential role for microglia in the degradation and clearance of pathological tau species in brain and provide a mechanism explaining the potential therapeutic actions of passively administered anti-tau monoclonal antibodies. PMID:26057852

[Forms of pathological gambling: empirical research on consumers behaviour of sport betting and lottery participants].

PubMed

Plöntzke, Babett; Albrecht, Ulrike; Thalemann, Carolin; Grüsser, Sabine Miriam

2004-08-01

Gambling is one of the favourite leisure activities. 70-90 % of the grown-up population have gambled at least once in their life. Over the last few years, however, the variety of opportunities to gamble has changed. Decreasing numbers of casino visitors can be seen against an ever-increasing number of people using slot machines, and taking part in national lotteries and sport betting. Comprehensive empirical research regarding consumer behaviour and addiction potential involved in sport betting has been non-existent and only a few studies have dealt with lottery. In the present study, 108 subjects were questioned in Austrian betting offices. 33.3 % of the sample fulfilled the diagnostic criteria for pathological sport betting. Of the sport betting subjects who additionally play lottery, 22.92 % were diagnosed as being pathological lottery gamblers. Based on the criteria of substance addiction, the data demonstrate that sport betting and lottery have addiction potential and can therefore be seen as non-substance-related addiction.

Semantic Integrative Digital Pathology: Insights into Microsemiological Semantics and Image Analysis Scalability.

PubMed

Racoceanu, Daniel; Capron, Frédérique

2016-01-01

Being able to provide a traceable and dynamic second opinion has become an ethical priority for patients and health care professionals in modern computer-aided medicine. In this perspective, a semantic cognitive virtual microscopy approach has been recently initiated, the MICO project, by focusing on cognitive digital pathology. This approach supports the elaboration of pathology-compliant daily protocols dedicated to breast cancer grading, in particular mitotic counts and nuclear atypia. A proof of concept has thus been elaborated, and an extension of these approaches is now underway in a collaborative digital pathology framework, the FlexMIm project. As important milestones on the way to routine digital pathology, a series of pioneer international benchmarking initiatives have been launched for mitosis detection (MITOS), nuclear atypia grading (MITOS-ATYPIA) and glandular structure detection (GlaS), some of the fundamental grading components in diagnosis and prognosis. These initiatives allow envisaging a consolidated validation referential database for digital pathology in the very near future. This reference database will need coordinated efforts from all major teams working in this area worldwide, and it will certainly represent a critical bottleneck for the acceptance of all future imaging modules in clinical practice. In line with recent advances in molecular imaging and genetics, keeping the microscopic modality at the core of future digital systems in pathology is fundamental to insure the acceptance of these new technologies, as well as for a deeper systemic, structured comprehension of the pathologies. After all, at the scale of routine whole-slide imaging (WSI; ∼0.22 µm/pixel), the microscopic image represents a structured 'genomic cluster', enabling a naturally structured support for integrative digital pathology approaches. In order to accelerate and structure the integration of this heterogeneous information, a major effort is and will continue to be devoted to morphological microsemiology (microscopic morphology semantics). Besides insuring the traceability of the results (second opinion) and supporting the orchestration of high-content image analysis modules, the role of semantics will be crucial for the correlation between digital pathology and noninvasive medical imaging modalities. In addition, semantics has an important role in modelling the links between traditional microscopy and recent label-free technologies. The massive amount of visual data is challenging and represents a characteristic intrinsic to digital pathology. The design of an operational integrative microscopy framework needs to focus on scalable multiscale imaging formalism. In this sense, we prospectively consider some of the most recent scalable methodologies adapted to digital pathology as marked point processes for nuclear atypia and point-set mathematical morphology for architecture grading. To orchestrate this scalable framework, semantics-based WSI management (analysis, exploration, indexing, retrieval and report generation support) represents an important means towards approaches to integrating big data into biomedicine. This insight reflects our vision through an instantiation of essential bricks of this type of architecture. The generic approach introduced here is applicable to a number of challenges related to molecular imaging, high-content image management and, more generally, bioinformatics. © 2016 S. Karger AG, Basel.

Stakeholders' Perspectives on Preclinical Testing for Alzheimer's Disease.

PubMed

Arias, Jalayne J; Cummings, Jeffrey; Grant, Alexander Rae; Ford, Paul J

2015-01-01

Progress towards validating amyloid beta as an early indicator of Alzheimer's disease (AD) heightens the need for evaluation of stakeholders' perspectives of the benefits and harms of preclinical testing in asymptomatic individuals. Investigators conducted and analyzed 14 semi-structured interviews with family members of patients diagnosed with AD. Participants reported benefits, including the potential to seek treatment, make lifestyle changes, and prepare for cognitive impairment. Participants identified harms, including social harms, adverse life decisions, and psychological harms. Nine participants reported either a "positive global perspective" or a "positive global perspective (qualified)." Results from this study characterized stakeholders' perspectives on the potential benefits and harms of clinical use of preclinical testing for AD. Investigators used data from this study to develop a framework that contributes to ongoing discussions that will evaluate widespread adoption of preclinical testing and will inform future research. Copyright 2015 The Journal of Clinical Ethics. All rights reserved.

Perspectives of academic faculty and clinical instructors on entry-level DPT preparation for pediatric physical therapist practice.

PubMed

Kenyon, Lisa K; Dole, Robin L; Kelly, Stephanie P

2013-12-01

To prepare students for pediatric practice, the professional (entry-level) curriculum must reflect the essential knowledge, skills, and abilities (KSA) required for pediatric physical therapist practice. The aim of this study was to develop consensus concerning the pediatric-specific KSA that should be expected of doctor of physical therapy (DPT) students at various points in the curriculum: prior to a pediatric clinical education experience, after a pediatric clinical education experience, and at the end of a DPT program. The study was conducted using the Delphi method. Purposive and snowball sampling were used to recruit pediatric academic faculty and pediatric clinical instructors. Three Web-based survey rounds were used to achieve consensus, defined as agreement among ≥70% of informants. The first round identified pediatric-specific KSA that were essential for DPT students to demonstrate at the identified points in the curriculum. In the second round, informants indicated their level of agreement with each item identified in the first round. Items that achieved consensus were included in the third round, in which informants rated the level of proficiency that DPT students should demonstrate related to pediatric-specific KSA. Consensus revealed the informants' perspectives concerning pediatric-specific KSA that a DPT student should be able to demonstrate at the identified curricular points. Consensus was reached on items in the curricular categories of basic science and foundations for practice; common pediatric diagnoses/pathologies, examination, interventions/plan of care/documentation; and general skills and abilities. Limitations included the small sample size and the potential for informants to feel uncomfortable prioritizing KSA. This study is an initial step toward identifying pediatric-specific KSA that should be demonstrated by DPT students.

CURRENT CONCEPTS ON THE GENETIC FACTORS IN ROTATOR CUFF PATHOLOGY AND FUTURE IMPLICATIONS FOR SPORTS PHYSICAL THERAPISTS

PubMed Central

Paré, Jessica; Froehlich, John E

2017-01-01

Context Recent advances within the field of genetics are currently changing many of the methodologies in which medicine is practiced. These advances are also beginning to influence the manner in which physical therapy services are rendered. Rotator cuff pathology is one of the most common diagnoses treated by the sports physical therapist. The purpose of this commentary is to educate sports physical therapists on the recent advances regarding how genetics influences rotator cuff pathology, including rotator cuff tears, and provide a perspective on how this information will likely influence post-operative shoulder rehabilitation in the near future. Evidence Acquisition A comprehensive review of the literature was completed using the Medline database along with individual searches of relevant physical therapy, surgical, cell biology, and sports medicine journals. Search terms included: shoulder, rotator cuff pathology, genetics, apoptosis, and physical therapy. Search results were compiled and evaluated; relevant primary studies and review articles were gathered; the results from this comprehensive review are summarized here. Study Design Clinical Commentary, Review of the Literature Results Recent advances within the understanding of rotator cuff pathology have further elucidated the cellular and molecular mechanisms associated with rotator cuff tears. There appears to be a hypoxic-induced apoptotic cellular pathway that contributes to rotator cuff tears. Activation of specific proteins termed matrix metalloproteinases appear to be involved in not only primary rotator cuff tears, but also may influence the re-tear rate after surgical intervention. Further advancements in the understanding of the cellular mechanisms contributing to rotator cuff tears and postoperative techniques to help prevent re-tears, may soon influence the methodology in which physical therapy services are provided to patients sustaining a rotator cuff injury. Conclusions At this time continued research is required to more fully develop a comprehensive understanding of the role of genetic variables both within primary rotator cuff tears and their influences on post-operative rehabilitation from rotator cuff repair surgery. Level of Evidence Level 5 PMID:28515982

Online teaching of inflammatory skin pathology by a French-speaking International University Network

PubMed Central

2014-01-01

Introduction Developments in technology, web-based teaching and whole slide imaging have broadened the teaching horizon in anatomic pathology. Creating online learning material including many types of media such as radiologic images, whole slides, videos, clinical and macroscopic photographs, is now accessible to most universities. Unfortunately, a major limiting factor to maintain and update the learning material is the amount of resources needed. In this perspective, a French-national university network was initiated in 2011 to build joint online teaching modules consisting of clinical cases and tests. The network has since expanded internationally to Québec, Switzerland and Ivory Coast. Method One of the first steps of the project was to build a learning module on inflammatory skin pathology for interns and residents in pathology and dermatology. A pathology resident from Québec spent 6 weeks in France and Switzerland to develop the contents and build the module on an e-learning Moodle platform under the supervision of two dermatopathologists. The learning module contains text, interactive clinical cases, tests with feedback, virtual slides, images and clinical photographs. For that module, the virtual slides are decentralized in 2 universities (Bordeaux and Paris 7). Each university is responsible of its own slide scanning, image storage and online display with virtual slide viewers. Results The module on inflammatory skin pathology includes more than 50 web pages with French original content, tests and clinical cases, links to over 45 virtual images and more than 50 microscopic and clinical photographs. The whole learning module is being revised by four dermatopathologists and two senior pathologists. It will be accessible to interns and residents in the spring of 2014. The experience and knowledge gained from that work will be transferred to the next international resident whose work will be aimed at creating lung and breast pathology learning modules. Conclusion The challenges of sustaining a project of this scope are numerous. The technical aspect of whole-slide imaging and storage needs to be developed by each university or group. The content needs to be regularly updated and its accuracy reviewed by experts in each individual domain. The learning modules also need to be promoted within the academic community to ensure maximal benefit for trainees. A collateral benefit of the project was the establishment of international partnerships between French-speaking universities and pathologists with the common goal of promoting pathology education through the use of multi-media technology including whole slide imaging. PMID:25564778

Online teaching of inflammatory skin pathology by a French-speaking International University Network.

PubMed

Perron, Emilie; Battistella, Maxime; Vergier, Béatrice; Fiche, Maryse; Bertheau, Philippe; Têtu, Bernard

2014-01-01

Developments in technology, web-based teaching and whole slide imaging have broadened the teaching horizon in anatomic pathology. Creating online learning material including many types of media such as radiologic images, whole slides, videos, clinical and macroscopic photographs, is now accessible to most universities. Unfortunately, a major limiting factor to maintain and update the learning material is the amount of resources needed. In this perspective, a French-national university network was initiated in 2011 to build joint online teaching modules consisting of clinical cases and tests. The network has since expanded internationally to Québec, Switzerland and Ivory Coast. One of the first steps of the project was to build a learning module on inflammatory skin pathology for interns and residents in pathology and dermatology. A pathology resident from Québec spent 6 weeks in France and Switzerland to develop the contents and build the module on an e-learning Moodle platform under the supervision of two dermatopathologists. The learning module contains text, interactive clinical cases, tests with feedback, virtual slides, images and clinical photographs. For that module, the virtual slides are decentralized in 2 universities (Bordeaux and Paris 7). Each university is responsible of its own slide scanning, image storage and online display with virtual slide viewers. The module on inflammatory skin pathology includes more than 50 web pages with French original content, tests and clinical cases, links to over 45 virtual images and more than 50 microscopic and clinical photographs. The whole learning module is being revised by four dermatopathologists and two senior pathologists. It will be accessible to interns and residents in the spring of 2014. The experience and knowledge gained from that work will be transferred to the next international resident whose work will be aimed at creating lung and breast pathology learning modules. The challenges of sustaining a project of this scope are numerous. The technical aspect of whole-slide imaging and storage needs to be developed by each university or group. The content needs to be regularly updated and its accuracy reviewed by experts in each individual domain. The learning modules also need to be promoted within the academic community to ensure maximal benefit for trainees. A collateral benefit of the project was the establishment of international partnerships between French-speaking universities and pathologists with the common goal of promoting pathology education through the use of multi-media technology including whole slide imaging.

Iranian EFL Teachers and Learners Perspective on Potentiality of Top Notch Series for Intercultural Competence Development

ERIC Educational Resources Information Center

Ahmadi Safa, Mohammad; Moradi, Mohammad; Hamzavi, Raouf

2015-01-01

The current study aimed at investigating the nature of EFL teachers and learners' perspectives on the intercultural competence potentiality of an EFL textbook, i.e. "Top Notch Series," which is used extensively in Iranian institutional EFL context. To this end, forty EFL teachers and eighty-eight advanced EFL learners from private…

The Evoked Potential. An Experimental Method for Biomechanical Analysis of Brain and Spinal Injury

DTIC Science & Technology

1980-01-01

Newtons produced marked changes in blood pressure, heart rate and distraction of the cervical spinal column with minimal ligamentous disruption...pathologic distraction and pathologic flexion of the thoracic ver- tebral column (8). Cerebral responses were lost within two minutes aftex complete...However, the immediate flexion and distraction responses were not altered. These findings suggest that mechanical trauma alters the spinal cord evoked

Mapping auditory nerve firing density using high-level compound action potentials and high-pass noise masking a

PubMed Central

Earl, Brian R.; Chertoff, Mark E.

2012-01-01

Future implementation of regenerative treatments for sensorineural hearing loss may be hindered by the lack of diagnostic tools that specify the target(s) within the cochlea and auditory nerve for delivery of therapeutic agents. Recent research has indicated that the amplitude of high-level compound action potentials (CAPs) is a good predictor of overall auditory nerve survival, but does not pinpoint the location of neural damage. A location-specific estimate of nerve pathology may be possible by using a masking paradigm and high-level CAPs to map auditory nerve firing density throughout the cochlea. This initial study in gerbil utilized a high-pass masking paradigm to determine normative ranges for CAP-derived neural firing density functions using broadband chirp stimuli and low-frequency tonebursts, and to determine if cochlear outer hair cell (OHC) pathology alters the distribution of neural firing in the cochlea. Neural firing distributions for moderate-intensity (60 dB pSPL) chirps were affected by OHC pathology whereas those derived with high-level (90 dB pSPL) chirps were not. These results suggest that CAP-derived neural firing distributions for high-level chirps may provide an estimate of auditory nerve survival that is independent of OHC pathology. PMID:22280596

Hypoxia and Redox Signaling on Extracellular Matrix Remodeling: From Mechanisms to Pathological Implications.

PubMed

Labrousse-Arias, David; Martínez-Ruiz, Antonio; Calzada, María J

2017-10-20

The extracellular matrix (ECM) is an essential modulator of cell behavior that influences tissue organization. It has a strong relevance in homeostasis and translational implications for human disease. In addition to ECM structural proteins, matricellular proteins are important regulators of the ECM that are involved in a myriad of different pathologies. Recent Advances: Biochemical studies, animal models, and study of human diseases have contributed to the knowledge of molecular mechanisms involved in remodeling of the ECM, both in homeostasis and disease. Some of them might help in the development of new therapeutic strategies. This review aims to review what is known about some of the most studied matricellular proteins and their regulation by hypoxia and redox signaling, as well as the pathological implications of such regulation. Matricellular proteins have complex regulatory functions and are modulated by hypoxia and redox signaling through diverse mechanisms, in some cases with controversial effects that can be cell or tissue specific and context dependent. Therefore, a better understanding of these regulatory processes would be of great benefit and will open new avenues of considerable therapeutic potential. Characterizing the specific molecular mechanisms that modulate matricellular proteins in pathological processes that involve hypoxia and redox signaling warrants additional consideration to harness the potential therapeutic value of these regulatory proteins. Antioxid. Redox Signal. 27, 802-822.

Chemical chaperone ameliorates pathological protein aggregation in plectin-deficient muscle

PubMed Central

Winter, Lilli; Staszewska, Ilona; Mihailovska, Eva; Fischer, Irmgard; Goldmann, Wolfgang H.; Schröder, Rolf; Wiche, Gerhard

2014-01-01

The ubiquitously expressed multifunctional cytolinker protein plectin is essential for muscle fiber integrity and myofiber cytoarchitecture. Patients suffering from plectinopathy-associated epidermolysis bullosa simplex with muscular dystrophy (EBS-MD) and mice lacking plectin in skeletal muscle display pathological desmin-positive protein aggregation and misalignment of Z-disks, which are hallmarks of myofibrillar myopathies (MFMs). Here, we developed immortalized murine myoblast cell lines to examine the pathogenesis of plectinopathies at the molecular and single cell level. Plectin-deficient myotubes, derived from myoblasts, were fully functional and mirrored the pathological features of EBS-MD myofibers, including the presence of desmin-positive protein aggregates and a concurrent disarrangement of the myofibrillar apparatus. Using this cell model, we demonstrated that plectin deficiency leads to increased intermediate filament network and sarcomere dynamics, marked upregulation of HSPs, and reduced myotube resilience following mechanical stretch. Currently, no specific therapy or treatment is available to improve plectin-related or other forms of MFMs; therefore, we assessed the therapeutic potential of chemical chaperones to relieve plectinopathies. Treatment with 4-phenylbutyrate resulted in remarkable amelioration of the pathological phenotypes in plectin-deficient myotubes as well as in plectin-deficient mice. Together, these data demonstrate the biological relevance of the MFM cell model and suggest that this model has potential use for the development of therapeutic approaches for EBS-MD. PMID:24487589

Online Education: A Science and Technology Studies Perspective

ERIC Educational Resources Information Center

Hamilton, Edward C.; Friesen, Norm

2013-01-01

This paper argues that research into the pedagogical value and potential of new technologies is limited by the implicit philosophical perspectives on technology that such research adopts. These perspectives either imbue technologies with inalienable qualities (essentialism) or posit technology as a neutral means for realizing goals defined by…

System-based identification of toxicity pathways associated with multi-walled carbon nanotube-induced pathological responses

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

Snyder-Talkington, Brandi N.; Dymacek, Julian; Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV 26506-9300

2013-10-15

The fibrous shape and biopersistence of multi-walled carbon nanotubes (MWCNT) have raised concern over their potential toxicity after pulmonary exposure. As in vivo exposure to MWCNT produced a transient inflammatory and progressive fibrotic response, this study sought to identify significant biological processes associated with lung inflammation and fibrosis pathology data, based upon whole genome mRNA expression, bronchoaveolar lavage scores, and morphometric analysis from C57BL/6J mice exposed by pharyngeal aspiration to 0, 10, 20, 40, or 80 μg MWCNT at 1, 7, 28, or 56 days post-exposure. Using a novel computational model employing non-negative matrix factorization and Monte Carlo Markov Chainmore » simulation, significant biological processes with expression similar to MWCNT-induced lung inflammation and fibrosis pathology data in mice were identified. A subset of genes in these processes was determined to be functionally related to either fibrosis or inflammation by Ingenuity Pathway Analysis and was used to determine potential significant signaling cascades. Two genes determined to be functionally related to inflammation and fibrosis, vascular endothelial growth factor A (vegfa) and C-C motif chemokine 2 (ccl2), were confirmed by in vitro studies of mRNA and protein expression in small airway epithelial cells exposed to MWCNT as concordant with in vivo expression. This study identified that the novel computational model was sufficient to determine biological processes strongly associated with the pathology of lung inflammation and fibrosis and could identify potential toxicity signaling pathways and mechanisms of MWCNT exposure which could be used for future animal studies to support human risk assessment and intervention efforts. - Highlights: • A novel computational model identified toxicity pathways matching in vivo pathology. • Systematic identification of MWCNT-induced biological processes in mouse lungs • MWCNT-induced functional networks of lung inflammation and fibrosis were revealed. • Two functional, representative genes, ccl2 and vegfa, were validated in vitro.« less

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

PubMed

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

2017-03-14

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

Induction of CNS α-synuclein pathology by fibrillar and non-amyloidogenic recombinant α-synuclein

PubMed Central

2013-01-01

Background α-Synuclein (αS) is the major component of several types of brain inclusions including Lewy bodies, a hallmark of Parkinson’s disease. Aberrant aggregation of αS also is associated with cellular demise in multiple neurologic disorders collectively referred to as synucleinopathies. Recent studies demonstrate the induction of αS pathology by a single intracerebral injection of exogenous amyloidogenic αS in adult non-transgenic and transgenic mice expressing human αS. To further investigate the mechanism of pathology induction and evaluate an experimental paradigm with potential for higher throughput, we performed similar studies in neonatal mice injected with αS. Results In non-transgenic mice, we observed limited induction of neuronal αS inclusions predominantly 8 months after brain injection of aggregated, amyloidogenic human αS. More robust inclusion pathology was induced in transgenic mice expressing wild-type human αS (line M20), and inclusion pathology was observed at earlier time points. Injection of a non-amyloidogenic (Δ71-82) deletion protein of αS was also able to induce similar pathology in a subset of M20 transgenic mice. M20 transgenic mice injected with amyloidogenic or non-amyloidogenic αS demonstrated a delayed and robust induction of brain neuroinflammation that occurs in mice with or without αS pathological inclusions implicating this mechanism in aggregate formation. Conclusions The finding that a non-amyloidogenic Δ71-82 αS can induce pathology calls into question the simple interpretation that exogenous αS catalyzes aggregation and spread of intracellular αS pathology solely through a nucleation dependent conformational templating mechanism. These results indicate that several mechanisms may act synergistically or independently to promote the spread of αS pathology. PMID:24252149

System-based Identification of Toxicity Pathways Associated With Multi-Walled Carbon Nanotube-Induced Pathological Responses

PubMed Central

Snyder-Talkington, Brandi N.; Dymacek, Julian; Porter, Dale W.; Wolfarth, Michael G.; Mercer, Robert R.; Pacurari, Maricica; Denvir, James; Castranova, Vincent; Qian, Yong; Guo, Nancy L.

2014-01-01

The fibrous shape and biopersistence of multi-walled carbon nanotubes (MWCNT) have raised concern over their potential toxicity after pulmonary exposure. As in vivo exposure to MWCNT produced a transient inflammatory and progressive fibrotic response, this study sought to identify significant biological processes associated with lung inflammation and fibrosis pathology data, based upon whole genome mRNA expression, bronchoaveolar lavage scores, and morphometric analysis from C57BL/6J mice exposed by pharyngeal aspiration to 0, 10, 20, 40, or 80 µg MWCNT at 1, 7, 28, or 56 days post-exposure. Using a novel computational model employing non-negative matrix factorization and Monte Carlo Markov Chain simulation, significant biological processes with expression similar to MWCNT-induced lung inflammation and fibrosis pathology data in mice were identified. A subset of genes in these processes was determined to be functionally related to either fibrosis or inflammation by Ingenuity Pathway Analysis and were used to determine potential significant signaling cascades. Two genes determined to be functionally related to inflammation and fibrosis, vascular endothelial growth factor A (vegfa) and C-C motif chemokine 2 (ccl2), were confirmed by in vitro studies of mRNA and protein expression in small airway epithelial cells exposed to MWCNT as concordant with in vivo expression. This study identified that the novel computational model was sufficient to determine biological processes strongly associated with the pathology of lung inflammation and fibrosis and could identify potential toxicity signaling pathways and mechanisms of MWCNT exposure which could be used for future animal studies to support human risk assessment and intervention efforts. PMID:23845593

The validity of the Personality Diagnostic Questionnaire-4 Narcissistic Personality Disorder scale for assessing pathological grandiosity.

PubMed

Hopwood, Christopher J; Donnellan, M Brent; Ackerman, Robert A; Thomas, Katherine M; Morey, Leslie C; Skodol, Andrew E

2013-01-01

Although controversy surrounds the definition and measurement of narcissism, the claim that pathological grandiosity is central to the construct generates little disagreement. Yet representations of pathological grandiosity vary across measures of narcissism, leading to conceptual confusion in the literature. The validity of a DSM-based measure of pathological narcissism, the Personality Diagnostic Questionnaire-4 Narcissistic Personality Disorder scale (PDQ-4 NPD), was evaluated in 1 clinical and 3 nonclinical samples (total N=2,391) for its ability to measure pathological grandiosity. Findings were generally supportive: average scores were higher in the clinical than nonclinical samples and the PDQ-4 NPD scale correlated most strongly with (a) other measures of NPD; (b) other DSM Cluster B personality disorders; (c) traits involving antagonism, hostility, and assertiveness; and (d) interpersonal distress and disaffiliative dominance. However, the low internal consistency of the PDQ-4 NPD scale and unexpected associations with Cluster A and obsessive-compulsive features point to potential psychometric weaknesses with this instrument. These findings are useful for evaluating the PDQ-4 NPD scale and for informing ongoing debates regarding how to define and assess pathological narcissism.

Pathology informatics questions and answers from the University of Pittsburgh pathology residency informatics rotation.

PubMed

Harrison, James H

2004-01-01

Effective pathology practice increasingly requires familiarity with concepts in medical informatics that may cover a broad range of topics, for example, traditional clinical information systems, desktop and Internet computer applications, and effective protocols for computer security. To address this need, the University of Pittsburgh (Pittsburgh, Pa) includes a full-time, 3-week rotation in pathology informatics as a required component of pathology residency training. To teach pathology residents general informatics concepts important in pathology practice. We assess the efficacy of the rotation in communicating these concepts using a short-answer examination administered at the end of the rotation. Because the increasing use of computers and the Internet in education and general communications prior to residency training has the potential to communicate key concepts that might not need additional coverage in the rotation, we have also evaluated incoming residents' informatics knowledge using a similar pretest. This article lists 128 questions that cover a range of topics in pathology informatics at a level appropriate for residency training. These questions were used for pretests and posttests in the pathology informatics rotation in the Pathology Residency Program at the University of Pittsburgh for the years 2000 through 2002. With slight modification, the questions are organized here into 15 topic categories within pathology informatics. The answers provided are brief and are meant to orient the reader to the question and suggest the level of detail appropriate in an answer from a pathology resident. A previously published evaluation of the test results revealed that pretest scores did not increase during the 3-year evaluation period, and self-assessed computer skill level correlated with pretest scores, but all pretest scores were low. Posttest scores increased substantially, and posttest scores did not correlate with the self-assessed computer skill level recorded at pretest time. Even residents who rated themselves high in computer skills lacked many concepts important in pathology informatics, and posttest scores showed that residents with both high and low self-assessed skill levels learned pathology informatics concepts effectively.

Physical frailty in older persons is associated with Alzheimer disease pathology.

PubMed

Buchman, Aron S; Schneider, Julie A; Leurgans, Sue; Bennett, David A

2008-08-12

We examined the extent to which physical frailty in older persons is associated with common age-related brain pathology, including cerebral infarcts, Lewy body pathology, and Alzheimer disease (AD) pathology. We studied brain autopsies from 165 deceased participants from the Rush Memory and Aging Project, a longitudinal clinical-pathologic study of aging. Physical frailty, based on four components, including grip strength, time to walk 8 feet, body composition, and fatigue, was assessed at annual clinical evaluations. Multiple regression analyses were used to examine the relation of postmortem neuropathologic findings to frailty proximate to death, controlling for age, sex, and education. The mean age at death was 88.1 years (SD = 5.7 years). The level of AD pathology was associated with frailty proximate to death ( = 0.252, SE = 0.077, p = 0.001), accounting for 4% of the variance of physical frailty. Neither cerebral infarcts ( = -0.121, SE = 0.115, p = 0.294) nor Lewy body disease pathology ( = 0.07, SE = 0.156, p = 0.678) was associated with frailty. These associations were unchanged after controlling for the time interval from last clinical evaluation to autopsy. The association of AD pathology with frailty did not differ by the presence of dementia, and this association was unchanged even after considering potential confounders, including physical activity; parkinsonian signs; pulmonary function; or history of chronic diseases, including vascular risk factors, vascular disease burden, falls, joint pain, or use of antipsychotic or antihypertensive medications. Physical frailty in old age is associated with Alzheimer disease pathology in older persons with and without dementia.

Adapting another person's affective state modulates brain potentials to unpleasant pictures.

PubMed

Paul, Sandra; Endrass, Tanja; Kathmann, Norbert; Simon, Daniela

2016-10-01

Emotional processing is influenced by top-down processes such as reappraisal of emotion-inducing events. Besides one's own stimulus appraisal, information from the social environment can be used to modify the stimulus' meaning. This study investigated whether perspective taking changes participants' brain potentials to unpleasant pictures. Event-related potentials (ERPs) were measured while twenty-nine participants evaluated arousal of neutral or negative pictures. Subsequently, they received bogus feedback about another person's picture evaluation. Then, the same picture was presented again and participants were instructed to view the picture from the other person's perspective. Higher bogus- versus self-ratings of picture arousal increased P300 and late positive potential (LPP) amplitudes to unpleasant stimuli, whereas lower bogus- versus self-ratings did not influence ERPs. Thus, perspective taking only modulated ERPs when bogus ratings signaled potential underestimation of arousal. Resulting increases in responsiveness might constitute an adaptive mechanism preparing the organism against harm. Copyright © 2016 Elsevier B.V. All rights reserved.