Are obsessive-compulsive symptoms impulsive, compulsive or both?

PubMed Central

Chamberlain, Samuel R; Leppink, Eric W.; Redden, Sarah A.; Grant, Jon E.

2017-01-01

Background The relationships between obsessive-compulsive symptoms and distinct forms of impulsivity and compulsivity are unclear. Such examination would be relevant in terms of how best to classify psychiatric disorders and in understanding candidate ‘latent traits’ that extend across a continuum between normalcy and clinical disorders. Method 515 young adults (aged 18-29 years) completed the Padua Inventory and undertook detailed clinical and neurocognitive assessments. Relationships between obsessive-compulsive symptoms and distinct types of impulsivity and compulsivity were evaluated using linear regression modelling. Results Obsessive-compulsive symptoms were significantly predicted by female gender, lower quality of life, psychiatric disorders in general (but not impulse control disorders), and worse extra-dimensional set-shifting. Obsessive-compulsive symptoms were not significantly predicted by alcohol/nicotine consumption, stop-signal reaction times, or decision-making abilities. Conclusion These data indicate that obsessive-compulsive symptoms are more related to certain forms of compulsivity than to impulsivity. These findings have important implications for diagnostic conceptualizations and neurobiological models. PMID:27234191

The Role of Biofilms in Drinking Water Exposure to Potentially Pathogenic Legionella spp.

EPA Science Inventory

Legionellosis is a bacterial infection caused by species of the genera Legionella and is the most common waterborne disease reported in the United States. This type of infection has two clinically distinct forms: Legionnaire's disease, a severe type of infection, which include...

[A specific etiology of radiologic cannon balls: sarcoidosis. Apropos of a case].

PubMed

Blanc-Jouvan, F; Andre-Poyaud, P; Perrin, C; Brambilla, E; Brambilla, C

1988-01-01

A distinctive form of sarcoidosis is reported. A young woman, without any past medical history, presented with a cannon-ball radiographic appearance and a fever, suggesting an infection or underlying neoplasm. A lung biopsy gave the diagnosis of sarcoidosis after negative fibreoptic bronchoscopy, bronchial lavage and needle biopsy. This macronodular form of sarcoidosis is known but rarely described. There was a favourable clinical and radiological outcome, which occurred spontaneously.

Cognition, Language, and Clinical Pathological Features of Non-Alzheimer's Dementias: An Overview

ERIC Educational Resources Information Center

Reilly, Jamie; Rodriguez, Amy D.; Lamy, Martine; Neils-Strunjas, Jean

2010-01-01

There are many distinct forms of dementia whose pharmacological and behavioral management differ. Differential diagnosis among the dementia variants currently relies upon a weighted combination of genetic and protein biomarkers, neuroanatomical integrity, and behavior. Diagnostic specificity is complicated by a high degree of overlap in the…

Validity of Sensory Systems as Distinct Constructs

PubMed Central

Su, Chia-Ting

2014-01-01

This study investigated the validity of sensory systems as distinct measurable constructs as part of a larger project examining Ayres’s theory of sensory integration. Confirmatory factor analysis (CFA) was conducted to test whether sensory questionnaire items represent distinct sensory system constructs. Data were obtained from clinical records of two age groups, 2- to 5-yr-olds (n = 231) and 6- to 10-yr-olds (n = 223). With each group, we tested several CFA models for goodness of fit with the data. The accepted model was identical for each group and indicated that tactile, vestibular–proprioceptive, visual, and auditory systems form distinct, valid factors that are not age dependent. In contrast, alternative models that grouped items according to sensory processing problems (e.g., over- or underresponsiveness within or across sensory systems) did not yield valid factors. Results indicate that distinct sensory system constructs can be measured validly using questionnaire data. PMID:25184467

Rett Syndrome: Revised Diagnostic Criteria and Nomenclature

PubMed Central

Neul, Jeffrey L.; Kaufmann, Walter E.; Glaze, Daniel G.; Christodoulou, John; Clarke, Angus J.; Bahi-Buisson, Nadia; Leonard, Helen; Bailey, Mark E. S.; Schanen, N. Carolyn; Zappella, Michele; Renieri, Alessandra; Huppke, Peter; Percy, Alan K.

2010-01-01

Objective Rett syndrome (RTT) is a severe neurodevelopmental disease that affects approximately 1 in 10,000 live female births and is often caused by mutations in Methyl-CpG-binding protein 2 (MECP2). Despite distinct clinical features, the accumulation of clinical and molecular information in recent years has generated considerable confusion regarding the diagnosis of RTT. The purpose of this work was revise and clarify 2002 consensus criteria for the diagnosis of RTT in anticipation of treatment trials. Method RettSearch members, representing the majority of the international clinical RTT specialists, participated in an iterative process to come to a consensus on a revised and simplified clinical diagnostic criteria for RTT. Results The clinical criteria required for the diagnosis of classic and atypical RTT were clarified and simplified. Guidelines for the diagnosis and molecular evaluation of specific variant forms of RTT were developed. Interpretation These revised criteria provide clarity regarding the key features required for the diagnosis of RTT and reinforce the concept that RTT is a clinical diagnosis based on distinct clinical criteria, independent of molecular findings. We recommend that these criteria and guidelines be utilized in any proposed clinical research. PMID:21154482

Perry syndrome due to the DCTN1 G71R mutation – a distinctive L-DOPA responsive disorder with behavioural syndrome, vertical gaze palsy and respiratory failure

PubMed Central

Newsway, Victoria; Fish, Mark; Rohrer, Jonathan D.; Majounie, Elisa; Williams, Nigel; Hack, Melissa; Warren, Jason; Morris, Huw R

2015-01-01

Perry syndrome is a rare form of autosomal dominant parkinsonism with respiratory failiure recently defined as being due to mutations in the DCTN1 gene. We describe a new family carrying a G71R mutation in the DCTN1 gene. The proband displayed a series of distinctive features not previously described in Perry syndrome: a disorder of vertical downward saccades accompanied by progressive midbrain atrophy, predominant non-motor symptoms responsive to L-DOPA, distinctive cranio-cervical L-DOPA induced dyskinesias, and a good response to high dose L-DOPA therapy and respiratory support. The family was initially thought to have autosomal dominant behavioural variant frontotemporal dementia with parkinsonism. This report expands the clinical definition of this distinctive syndrome. PMID:20437543

Medical Teachers Conceptualize a Distinctive Form of Clinical Knowledge

ERIC Educational Resources Information Center

Barrett, J.; Yates, L.; McColl, G.

2015-01-01

For over four decades, there have been efforts to specify the types of knowledge that medical students need, how that knowledge is acquired and how its constituent parts are related. It is one of the areas of continuing concern underlying medical education reform. Despite their importance to medical students' learning and development, the…

Fear of knowledge: Clinical hypotheses in diagnostic and prognostic reasoning.

PubMed

Chiffi, Daniele; Zanotti, Renzo

2017-10-01

Patients are interested in receiving accurate diagnostic and prognostic information. Models and reasoning about diagnoses have been extensively investigated from a foundational perspective; however, for all its importance, prognosis has yet to receive a comparable degree of philosophical and methodological attention, and this may be due to the difficulties inherent in accurate prognostics. In the light of these considerations, we discuss a considerable body of critical thinking on the topic of prognostication and its strict relations with diagnostic reasoning, pointing out the distinction between nosographic and pathophysiological types of diagnosis and prognosis, underlying the importance of the explication and explanation processes. We then distinguish between various forms of hypothetical reasoning applied to reach diagnostic and prognostic judgments, comparing them with specific forms of abductive reasoning. The main thesis is that creative abduction regarding clinical hypotheses in diagnostic process is very unlikely to occur, whereas this seems to be often the case for prognostic judgments. The reasons behind this distinction are due to the different types of uncertainty involved in diagnostic and prognostic judgments. © 2016 John Wiley & Sons, Ltd.

Burnout-depression overlap: a review.

PubMed

Bianchi, Renzo; Schonfeld, Irvin Sam; Laurent, Eric

2015-03-01

Whether burnout is a form of depression or a distinct phenomenon is an object of controversy. The aim of the present article was to provide an up-to-date review of the literature dedicated to the question of burnout-depression overlap. A systematic literature search was carried out in PubMed, PsycINFO, and IngentaConnect. A total of 92 studies were identified as informing the issue of burnout-depression overlap. The current state of the art suggests that the distinction between burnout and depression is conceptually fragile. It is notably unclear how the state of burnout (i.e., the end stage of the burnout process) is conceived to differ from clinical depression. Empirically, evidence for the distinctiveness of the burnout phenomenon has been inconsistent, with the most recent studies casting doubt on that distinctiveness. The absence of consensual diagnostic criteria for burnout and burnout research's insufficient consideration of the heterogeneity of depressive disorders constitute major obstacles to the resolution of the raised issue. In conclusion, the epistemic status of the seminal, field-dominating definition of burnout is questioned. It is suggested that systematic clinical observation should be given a central place in future research on burnout-depression overlap. Copyright © 2015 Elsevier Ltd. All rights reserved.

Early clinics of the cardiac forms of Chagas' disease: Discovery and study of original medical files (1909-1915).

PubMed

Gachelin, Gabriel; Bestetti, Reinaldo B

2017-10-01

We have uncovered 80 medical files corresponding to original cases of Chagas' disease used for the classical description of the acute and cardiac forms of the disease. Sixty of them were diagnosed cardiac forms of the disease. The detailed clinical description of these 60 files is in excellent agreement with the nosography of progressive heart disease given by Chagas in his original 1922 paper. The reports we had access to, characterize a novel form of cardiac disease, dominated by progressive AV block, enlargement and displacement of the heart and sudden death, in relatively young adults including juveniles. In contrast to that remarkable clinical description, the assertion made by Chagas that this set of clinical signs was the consequence of an earlier infection by Trypanosoma cruzi rests on weak evidence, due to the difficulty to identify the parasite in most patients. Moreover, the association of thyroid dysfunction with cardiac disease emphasized by Chagas cannot be deduced from the files we have examined. Finally, the main reason why the disease had not been recognized for long as a defined clinical entity, is likely the absence of markedly distinctive clinical signs compared to most other parasitic diseases, poor sanitary conditions and the probable lack of clinical skills of the rare doctors working in the area where the disease was described. Copyright © 2017 Elsevier B.V. All rights reserved.

Three forms of somatization presenting in primary care settings in Spain.

PubMed

García-Campayo, J; Lobo, A; Pérez-Echeverría, M J; Campos, R

1998-09-01

The objective of this paper is to study the prevalence and clinical characteristics of functional, hypochondriacal, and presenting somatization (FSTS, HSTS, and PSTS, respectively) defined by standardized criteria, as well as the validity of their distinction in primary care in Spain. A two-stage epidemiological study of a representative sample (N = 1559) of primary care patients was carried out. In the first phase, the validated Spanish versions of General Health Questionnaire, Mini-Mental State Examination, and CAGE were used. In the second phase, the Standardized Polyvalent Psychiatric Interview, an interview for the multiaxial assessment of medical patients, was employed. The prevalence of any form of somatization in Spain was 21.3% (FSTS: 16.2%, PSTS: 9.4%, HSTS: 6.7%). Overlap of any of the three clinical forms was very frequent (42.7%). FSTS patients tended to be more chronic and showed higher scores in fatigue but lower scores in both depression and anxiety. Chronicity was frequent among somatizers, particularly in those who fulfilled more than one kind of somatization. Differences in diagnostic distribution among the three groups were also observed. In conclusion, this is the first study giving support to the validity of the distinction among three types of somatization in Spain, but overlap was more frequent than reported in North American studies.

Female genital tuberculosis cases with distinct clinical symptoms: Four case reports

PubMed Central

Aslan, Gonul; Ulger, Mahmut; Ulger, Seda Tezcan; Durukan, Huseyin; Yazici, Faik Gurkan; Emekdas, Gurol

2018-01-01

Background: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. Genital TB (GTB) is a form of extrapulmonary TB that occurs more frequently in women, in whom it classically presents in association with menstrual irregularity, pregnancy loss and short and long-term sequelae especially infertility in infected women. Patients with GTB are usually young women diagnosed during workup for infertility. GTB is rare in postmenopausal women and responsible for only approximately 1% of postmenopausal bleeding. In this study, we aimed to evaluate the laboratory, clinical and demographic characteristics of female GTB cases. Case: We presented four female GTB cases with distinct clinical symptoms. All patients have no history of TB, and no acid-fast bacilli were seen in smears prepared from the clinical materials of the patients. Histopathological examinations revealed granulomatous inflammation in all patients. Conclusion: In the light of the clinical features of these cases we aimed to emphasize that, female GTB must be taken into account in the patients with different clinical symptoms like postmenopausal bleeding, menometrorrhagia, infertility, and menstrual irregularities. We believe that these symptoms will be helpful for the diagnosis and treatment of female GTB. PMID:29675489

Clinical approach to Parkinson's disease: features, diagnosis, and principles of management.

PubMed

Massano, João; Bhatia, Kailash P

2012-06-01

Parkinson's disease (PD) is one of the most common neurodegenerative disorders. The condition causes a heavy burden both on those affected, as well as their families. Accurate diagnosis is critical and remains founded on clinical grounds as no specific diagnostic test is available so far. The clinical picture of PD is typical in many instances; however, features distinguishing it from other disorders should be thoroughly sought. Monogenic forms of PD also have some distinctive characteristics in many cases. This text is a roadmap to accurate diagnosis in PD, as it approaches clinical features, diagnostic methodology, and leading differential diagnoses. Therapeutic issues are also briefly discussed.

Somatic POLE mutations cause an ultramutated giant cell high-grade glioma subtype with better prognosis

PubMed Central

Erson-Omay, E. Zeynep; Çağlayan, Ahmet Okay; Schultz, Nikolaus; Weinhold, Nils; Omay, S. Bülent; Özduman, Koray; Köksal, Yavuz; Li, Jie; Serin Harmancı, Akdes; Clark, Victoria; Carrión-Grant, Geneive; Baranoski, Jacob; Çağlar, Caner; Barak, Tanyeri; Coşkun, Süleyman; Baran, Burçin; Köse, Doğan; Sun, Jia; Bakırcıoğlu, Mehmet; Moliterno Günel, Jennifer; Pamir, M. Necmettin; Mishra-Gorur, Ketu; Bilguvar, Kaya; Yasuno, Katsuhito; Vortmeyer, Alexander; Huttner, Anita J.; Sander, Chris; Günel, Murat

2015-01-01

Background Malignant high-grade gliomas (HGGs), including the most aggressive form, glioblastoma multiforme, show significant clinical and genomic heterogeneity. Despite recent advances, the overall survival of HGGs and their response to treatment remain poor. In order to gain further insight into disease pathophysiology by correlating genomic landscape with clinical behavior, thereby identifying distinct HGG molecular subgroups associated with improved prognosis, we performed a comprehensive genomic analysis. Methods We analyzed and compared 720 exome-sequenced gliomas (136 from Yale, 584 from The Cancer Genome Atlas) based on their genomic, histological, and clinical features. Results We identified a subgroup of HGGs (6 total, 4 adults and 2 children) that harbored a statistically significantly increased number of somatic mutations (mean = 9257.3 vs 76.2, P = .002). All of these “ultramutated” tumors harbored somatic mutations in the exonuclease domain of the polymerase epsilon gene (POLE), displaying a distinctive genetic profile, characterized by genomic stability and increased C-to-A transversions. Histologically, they all harbored multinucleated giant or bizarre cells, some with predominant infiltrating immune cells. One adult and both pediatric patients carried homozygous germline mutations in the mutS homolog 6 (MSH6) gene. In adults, POLE mutations were observed in patients younger than 40 years and were associated with a longer progression-free survival. Conclusions We identified a genomically, histologically, and clinically distinct subgroup of HGGs that harbored somatic POLE mutations and carried an improved prognosis. Identification of distinctive molecular and pathological HGG phenotypes has implications not only for improved classification but also for potential targeted treatments. PMID:25740784

Does Sluggish Cognitive Tempo Fit within a Bi-factor Model of Attention-Deficit/Hyperactivity Disorder?

PubMed Central

Garner, Annie A.; Peugh, James; Becker, Stephen P.; Kingery, Kathleen M.; Tamm, Leanne; Vaughn, Aaron J.; Ciesielski, Heather; Simon, John O.; Loren, Richard E. A.; Epstein, Jeffery N.

2014-01-01

Objective Studies demonstrate sluggish cognitive tempo (SCT) symptoms to be distinct from inattentive and hyperactive-impulsive dimensions of Attention-Deficit/Hyperactivity Disorder (ADHD). No study has examined SCT within a bi-factor model of ADHD whereby SCT may form a specific factor distinct from inattention and hyperactivity/impulsivity while still fitting within a general ADHD factor, which was the purpose of the current study. Method 168 children were recruited from an ADHD clinic. Most (92%) met diagnostic criteria for ADHD. Parents and teachers completed measures of ADHD and SCT. Results Although SCT symptoms were strongly associated with inattention they loaded onto a factor independent of ADHD ‘g’. Results were consistent across parent and teacher ratings. Conclusions SCT is structurally distinct from inattention as well as from the general ADHD latent symptom structure. Findings support a growing body of research suggesting SCT to be distinct and separate from ADHD. PMID:25005039

Balancing power: A grounded theory study on partnership of academic service institutes.

PubMed

Heshmati Nabavi, Fatemeh; Vanaki, Zohreh; Mohammadi, Eesa; Yazdani, Shahram

2017-07-01

Governments and professional organizations have called for new partnerships between health care providers and academics to improve clinical education for the benefit of both students and patients. To develop a substantive grounded theory on the process of forming academic-service partnerships in implementing clinical education, from the perspective of academic and clinical nursing staff members and managers working in Iranian settings. The participants included 15 hospital nurses, nurse managers, nurse educators, and educational managers from two central universities and clinical settings from 2009 to 2012. Data were collected through 30 in-depth, semi-structure interviews with the individual participants and then analyzed using the methodology of Strauss and Corbin's grounded theory. Utilizing "balancing power" as the core variable enabled us to integrate the concepts concerning the partnership processes between clinical and educational institutes. Three distinct and significant categories emerged to explain the process of partnership: 1) divergence, 2) conflict between educational and caring functions, and 3) creation of balance between educational and caring functions. In implementing clinical education, partnerships have been formed within a challenging context in Iran. Conflict between clinical and educational functions was the main concern of both sides of the partnership in forming a collaborative relationship, with our findings emphasizing the importance of nursing educators' role in the establishment of partnership programs.

Comorbid obsessive-compulsive disorder with bipolar disorder: A distinct form?

PubMed

Ozdemiroglu, Filiz; Sevincok, Levent; Sen, Gulnur; Mersin, Sanem; Kocabas, Oktay; Karakus, Kadir; Vahapoglu, Fatih

2015-12-30

We examined whether the patients with Bipolar Disorder (BD) and Obsessive-Compulsive Disorder (OCD) comorbidity may represent a distinct form of BD. The subjects diagnosed with BD (n=48), OCD (n=61), and BD with OCD (n=32) were compared in terms of several socio-demographic and clinical characteristics. Previous history of suicidal attempts was more likely to be higher in BD-OCD group compared to the other two groups. A more episodic course of OCD, higher rates of rapid cycling, and the seasonality were found in BD-OCD patients. The frequency of bipolar II and NOS subtypes was more prevalent in patients with BD-OCD than in OCD patients. The first diagnosed illness was BD in the majority of BD-OCD cases. It was found that first affective episode was major depression in half of BD-OCD patients. Age at onset of BD was found to be earlier in BD-OCD group compared to pure BD patients. Bipolarity may not have a specific effect on the phenomenology of OC symptoms. The episodic course of OCD, seasonality, rapid cycling, earlier onset of BD, and impulsivity in BD-OCD patients may be indicative for a distinct form of BD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Neural imaginaries and clinical epistemology: Rhetorically mapping the adolescent brain in the clinical encounter.

PubMed

Buchbinder, Mara

2015-10-01

The social work of brain images has taken center stage in recent theorizing of the intersections between neuroscience and society. However, neuroimaging is only one of the discursive modes through which public representations of neurobiology travel. This article adopts an expanded view toward the social implications of neuroscientific thinking to examine how neural imaginaries are constructed in the absence of visual evidence. Drawing on ethnographic fieldwork conducted over 18 months (2008-2009) in a United States multidisciplinary pediatric pain clinic, I examine the pragmatic clinical work undertaken to represent ambiguous symptoms in neurobiological form. Focusing on one physician, I illustrate how, by rhetorically mapping the brain as a therapeutic tool, she engaged in a distinctive form of representation that I call neural imagining. In shifting my focus away from the purely material dimensions of brain images, I juxtapose the cultural work of brain scanning technologies with clinical neural imaginaries in which the teenage brain becomes a space of possibility, not to map things as they are, but rather, things as we hope they might be. These neural imaginaries rely upon a distinctive clinical epistemology that privileges the creative work of the imagination over visualization technologies in revealing the truths of the body. By creating a therapeutic space for adolescents to exercise their imaginative faculties and a discursive template for doing so, neural imagining relocates adolescents' agency with respect to epistemologies of bodily knowledge and the role of visualization practices therein. In doing so, it provides a more hopeful alternative to the dominant popular and scientific representations of the teenage brain that view it primarily through the lens of pathology. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neural Imaginaries and Clinical Epistemology: Rhetorically Mapping the Adolescent Brain in the Clinical Encounter

PubMed Central

Buchbinder, Mara

2014-01-01

The social work of brain images has taken center stage in recent theorizing of the intersections between neuroscience and society. However, neuroimaging is only one of the discursive modes through which public representations of neurobiology travel. This article adopts an expanded view toward the social implications of neuroscientific thinking to examine how neural imaginaries are constructed in the absence of visual evidence. Drawing on ethnographic fieldwork conducted over 18 months (2008–2009) in a United States multidisciplinary pediatric pain clinic, I examine the pragmatic clinical work undertaken to represent ambiguous symptoms in neurobiological form. Focusing on one physician, I illustrate how, by rhetorically mapping the brain as a therapeutic tool, she engaged in a distinctive form of representation that I call neural imagining. In shifting my focus away from the purely material dimensions of brain images, I juxtapose the cultural work of brain scanning technologies with clinical neural imaginaries in which the teenage brain becomes a space of possibility, not to map things as they are, but rather, things as we hope they might be. These neural imaginaries rely upon a distinctive clinical epistemology that privileges the creative work of the imagination over visualization technologies in revealing the truths of the body. By creating a therapeutic space for adolescents to exercise their imaginative faculties and a discursive template for doing so, neural imagining relocates adolescents’ agency with respect to epistemologies of bodily knowledge and the role of visualization practices therein. In doing so, it provides a more hopeful alternative to the dominant popular and scientific representations of the teenage brain that view it primarily through the lens of pathology. PMID:24780561

Disease-mongering through clinical trials.

PubMed

González-Moreno, María; Saborido, Cristian; Teira, David

2015-06-01

Our goal in this paper is to articulate a precise concept of at least a certain kind of disease-mongering, showing how pharmaceutical marketing can commercially exploit certain diseases when their best definition is given through the success of a treatment in a clinical trial. We distinguish two types of disease-mongering according to the way they exploit the definition of the trial population for marketing purposes. We argue that behind these two forms of disease-mongering there are two well-known problems in the statistical methodology of clinical trials (the reference class problem and the distinction between statistical and clinical significance). Overcoming them is far from simple. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ferroptosis and Cell Death Analysis by Flow Cytometry.

PubMed

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

2017-01-01

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

[Channels: a new way to revisit pathology].

PubMed

Fournier, Emmanuel

2014-02-01

Many "essential" diseases that manifest themselves in the form of crises or fits (epilepsies, episodic ataxia, periodic paralyses, myotonia, heart rhythm disorders, etc.) are due to ionic channel dysfunction and are thus referred to as "channelopathies". Some of these disorders are congenital, due to mutations of genes encoding channel subunits, while others result from toxic, immune or hormonal disturbances affecting channelfunction. Channelopathies take on a wide variety of clinical forms, depending on the type of channel (sodium, potassium, calcium, chloride...) and the type of dysfunction (loss or gain of function). Some apparently unrelated diseases affecting distinct organs are due to a similar dysfunction of the same channel, revealing unsuspected relationships between organs and between medical specialties. In addition, a given syndrome can be caused by distinct channel dysfunctions. This provides new opportunities for diferential diagnosis and specific correction of the causal defects, although some treatments find applications across multiple medical specialties.

Histologic characterization of canine dilated cardiomyopathy.

PubMed

Tidholm, A; Jönsson, L

2005-01-01

Dilated cardiomyopathy (DCM), characterized by chamber dilatation and myocardial systolic and diastolic dysfunction, is one of the most common heart diseases in dogs. The clinical diagnosis is based on findings on echocardiographic and Doppler examinations, with the active exclusion of other acquired or congenital heart diseases. However, the echocardiographic criteria for the diagnosis of DCM are not wholly specific for the disease, and histologic examination may be necessary for final diagnosis. Review of reports on histologic findings in dogs with clinically diagnosed DCM reveals two histologically distinct forms of DCM: 1) cardiomyopathy of Boxers and Doberman Pinschers, corresponding to the "fatty infiltration-degenerative" type and 2) the form seen in many giant, large-, and medium-sized breeds, including some Boxers and Doberman Pinschers, classified as the "attenuated wavy fiber" type of DCM. The histologic changes of the attenuated wavy fiber type of DCM may precede clinical and echocardiographic signs of heart disease, thus indicating an early stage of DCM.

Politics, culture, and the legitimacy of disease: the case of Buerger's disease.

PubMed

Lockwood, Stephen J; Bresler, Scott C; Granter, Scott R

2016-09-01

Thromboangiitis obliterans (TAO) or Buerger's disease is a rare form of vasculitis with distinctive clinical and pathological features that carries significant morbidity, often leading to amputation, and is strongly associated with tobacco smoking. Despite its distinctive clinicopathological characteristics, the existence of TAO as an entity sui generis was challenged for many years as it languished in relative obscurity. Then, as societal attitudes towards smoking changed, TAO not only became accepted as a disease entity, it quite literally became a poster child to illustrate the ills of smoking. Herein, we examine the history of TAO to illustrate the power of societal attitudes and politics in shaping medicine.

Inherited dystonias: clinical features and molecular pathways.

PubMed

Weisheit, Corinne E; Pappas, Samuel S; Dauer, William T

2018-01-01

Recent decades have witnessed dramatic increases in understanding of the genetics of dystonia - a movement disorder characterized by involuntary twisting and abnormal posture. Hampered by a lack of overt neuropathology, researchers are investigating isolated monogenic causes to pinpoint common molecular mechanisms in this heterogeneous disease. Evidence from imaging, cellular, and murine work implicates deficiencies in dopamine neurotransmission, transcriptional dysregulation, and selective vulnerability of distinct neuronal populations to disease mutations. Studies of genetic forms of dystonia are also illuminating the developmental dependence of disease symptoms that is typical of many forms of the disease. As understanding of monogenic forms of dystonia grows, a clearer picture will develop of the abnormal motor circuitry behind this relatively common phenomenology. This chapter focuses on the current data covering the etiology and epidemiology, clinical presentation, and pathogenesis of four monogenic forms of isolated dystonia: DYT-TOR1A, DYT-THAP1, DYT-GCH1, and DYT-GNAL. Copyright © 2018 Elsevier B.V. All rights reserved.

Clinical signs of pancreatitis.

PubMed

Penny, Steven M

2012-01-01

The pancreas consists of complex structures that perform vital functions. Radiologic technologists must comprehend its normal structure and function to perform functional imaging procedures in their daily practice, as well as to know how any deviation from normalcy can disrupt homeostasis. Because pancreatitis is a potentially life-threatening disease, a thorough understanding of the clinical manifestation and imaging characteristics of the various forms of the disease is crucial. This article reviews distinctive pancreatic function and discusses basic pancreas imaging. In addition, acute and chronic pancreatitis is explored, including the role of medical imaging in its diagnosis, complications, and prognosis.

Balancing power: A grounded theory study on partnership of academic service institutes

PubMed Central

HESHMATI NABAVI, FATEMEH; VANAKI, ZOHREH; MOHAMMADI, EESA; YAZDANI, SHAHRAM

2017-01-01

Introduction: Governments and professional organizations have called for new partnerships between health care providers and academics to improve clinical education for the benefit of both students and patients. To develop a substantive grounded theory on the process of forming academic-service partnerships in implementing clinical education, from the perspective of academic and clinical nursing staff members and managers working in Iranian settings. Methods: The participants included 15 hospital nurses, nurse managers, nurse educators, and educational managers from two central universities and clinical settings from 2009 to 2012. Data were collected through 30 in-depth, semi-structure interviews with the individual participants and then analyzed using the methodology of Strauss and Corbin's grounded theory. Results: Utilizing “balancing power” as the core variable enabled us to integrate the concepts concerning the partnership processes between clinical and educational institutes. Three distinct and significant categories emerged to explain the process of partnership: 1) divergence, 2) conflict between educational and caring functions, and 3) creation of balance between educational and caring functions. Conclusions: In implementing clinical education, partnerships have been formed within a challenging context in Iran. Conflict between clinical and educational functions was the main concern of both sides of the partnership in forming a collaborative relationship, with our findings emphasizing the importance of nursing educators' role in the establishment of partnership programs. PMID:28761886

Targeting the colony stimulating factor 1 receptor alleviates two forms of Charcot-Marie-Tooth disease in mice.

PubMed

Klein, Dennis; Patzkó, Ágnes; Schreiber, David; van Hauwermeiren, Anemoon; Baier, Michaela; Groh, Janos; West, Brian L; Martini, Rudolf

2015-11-01

See Scherer (doi:10.1093/awv279) for a scientific commentary on this article.Charcot-Marie-Tooth type 1 neuropathies are inherited disorders of the peripheral nervous system caused by mutations in Schwann cell-related genes. Typically, no causative cure is presently available. Previous preclinical data of our group highlight the low grade, secondary inflammation common to distinct Charcot-Marie-Tooth type 1 neuropathies as a disease amplifier. In the current study, we have tested one of several available clinical agents targeting macrophages through its inhibition of the colony stimulating factor 1 receptor (CSF1R). We here show that in two distinct mouse models of Charcot-Marie-Tooth type 1 neuropathies, the systemic short- and long-term inhibition of CSF1R by oral administration leads to a robust decline in nerve macrophage numbers by ∼70% and substantial reduction of the typical histopathological and functional alterations. Interestingly, in a model for the dominant X-linked form of Charcot-Marie-Tooth type 1 neuropathy, the second most common form of the inherited neuropathies, macrophage ablation favours maintenance of axonal integrity and axonal resprouting, leading to preserved muscle innervation, increased muscle action potential amplitudes and muscle strengths in the range of wild-type mice. In another model mimicking a mild, demyelination-related Charcot-Marie-Tooth type 1 neuropathy caused by reduced P0 (MPZ) gene dosage, macrophage blockade causes an improved preservation of myelin, increased muscle action potential amplitudes, improved nerve conduction velocities and ameliorated muscle strength. These observations suggest that disease-amplifying macrophages can produce multiple adverse effects in the affected nerves which likely funnel down to common clinical features. Surprisingly, treatment of mouse models mimicking Charcot-Marie-Tooth type 1A neuropathy also caused macrophage blockade, but did not result in neuropathic or clinical improvements, most likely due to the late start of treatment of this early onset disease model. In summary, our study shows that targeting peripheral nerve macrophages by an orally administered inhibitor of CSF1R may offer a highly efficacious and safe treatment option for at least two distinct forms of the presently non-treatable Charcot-Marie-Tooth type 1 neuropathies. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Three forms of somatization in primary care: prevalence, co-occurrence, and sociodemographic characteristics.

PubMed

Kirmayer, L J; Robbins, J M

1991-11-01

Three definitions of somatization were operationalized: (a) high levels of functional somatic distress, measured by the Somatic Symptom Index (SSI) of the Diagnostic Interview Schedule; (b) hypochondriasis measured by high scores on a measure of illness worry in the absence of evidence for serious illness; and (c) exclusively somatic clinical presentations among patients with current major depression or anxiety. Of 685 patients attending two family medicine clinics, 26.3% met criteria for one or more forms of somatization. While DSM-III somatization disorder had a prevalence of only 1% in this population, 16.6% of the patients met abridged criteria for subsyndromal somatization disorder (SSI 4,6). Hypochondriacal worry had a prevalence of 7.7% in the clinic sample. Somatized presentations of current major depression or anxiety disorder had a prevalence of 8%. The three forms of somatization were associated with different sociodemographic and illness behavior characteristics. A majority of patients met criteria for only one type of somatization, suggesting that distinct pathogenic processes may be involved in each of the three types.

Differential diagnosis of common tremor syndromes

PubMed Central

Bhidayasiri, R

2005-01-01

Tremor is one of the most common involuntary movement disorders seen in clinical practice. In addition to the detailed history, the differential diagnosis is mainly clinical based on the distinction at rest, postural and intention, activation condition, frequency, and topographical distribution. The causes of tremor are heterogeneous and it can present alone (for example, essential tremor) or as a part of a neurological syndrome (for example, multiple sclerosis). Essential tremor and the tremor of Parkinson's disease are the most common tremors encountered in clinical practice. This article focuses on a practical approach to these different forms of tremor and how to distinguish them clinically. Evidence supporting various strategies used in the differentiation is then presented, followed by a review of formal guidelines or recommendations when they exist. PMID:16344298

Middle lobe syndrome in children today.

PubMed

Romagnoli, Vittorio; Priftis, Kostas N; de Benedictis, Fernando M

2014-06-01

Middle lobe syndrome in children is a distinct clinical and radiographic entity that has been well described in the pediatric literature. However, issues regarding its etiology, clinical presentation, and management continue to puzzle the clinical practitioner. Pathophysiologically, there are two forms of middle lobe syndrome, namely obstructive and nonobstructive. Middle lobe syndrome may present as symptomatic or asymptomatic, as persistent or recurrent atelectasis, or as pneumonitis or bronchiectasis of the middle lobe and/or lingula. A lower threshold of performing a chest radiograph is warranted in children with persistent or recurrent nonspecific respiratory symptoms, particularly if there is clinical deterioration, in order to detect middle lobe syndrome and to initiate a further diagnostic and therapeutic workup. Copyright © 2014 Elsevier Ltd. All rights reserved.

Clinical implications of recent breakthroughs in amyotrophic lateral sclerosis.

PubMed

Van Damme, Philip; Robberecht, Wim

2013-10-01

This review examines the clinical implications of recent breakthroughs in amyotrophic lateral sclerosis (ALS). ALS has been found to be a highly variable condition at the clinical, genetic and mechanistic level. The study of newly discovered genetic causes for ALS has demonstrated that in addition to the effect of toxic mutant proteins, abnormalities of RNA householding contribute to motor neuron degeneration. Furthermore, the classic distinction between gain of function and loss of function may be an oversimplification of the biological reality. The most important clinical breakthrough was the finding of intronic hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) as a common cause of ALS, frontotemporal lobar degeneration (FTLD) and ALS with concomitant FTLD. This provides unambiguous evidence that ALS and FTLD represent the ends of one spectrum of neurodegenerative diseases. The high prevalence of C9orf72 mutations in patients without family history further blurs the distinction between sporadic and familial forms of ALS and FTLD. It also opens opportunities for stratified clinical trials in ALS and for the development of targeted therapies. ALS is a heterogeneous disorder that overlaps with FTLD. C9orf72 mutations are the most common cause of ALS, and add to the evidence that disturbances in RNA householding contribute to ALS.

Kahlbaum, Hecker, and Kraepelin and the Transition From Psychiatric Symptom Complexes to Empirical Disease Forms.

PubMed

Kendler, Kenneth S; Engstrom, Eric J

2017-02-01

The nosology for major psychiatric disorders developed by Emil Kraepelin in the 1890s has substantially shaped psychiatry. His theories, however, did not arise de novo, being strongly influenced by Karl Kahlbaum and Ewald Hecker. From the 1860-1880s, they articulated a paradigm shift in the conceptualization of psychiatric diagnosis, from symptom-based syndromes, popular since the late 18th century, to proto-disease entities. This effort was influenced by parallel developments in general medicine, especially the rise of bacterial theories of disease where different syndromes had distinctive symptoms, courses, and etiologies. Their thinking was particularly shaped by the increasing understanding of general paresis of the insane. Indeed, this disorder, with its distinct course and characteristic symptoms, was paradigmatic for them. Their hope was that a similar progression of medical understanding would evolve for the other major psychiatric syndromes. Their thinking and its connection with Kraepelin's nosology are illustrated through a close reading of their essays on hebephrenia, catatonia, and cyclic insanity. Kahlbaum, Hecker, and Kraepelin shared both a commitment to a clinical research agenda for psychiatry (to utilize methods of clinical assessment and follow-up to help define disease forms) and a skepticism for the brain-based neuropathological paradigm of psychiatric research then dominant in most European centers. Understanding the historical origins of our key diagnostic concepts can help us to evaluate their strengths and limitations. It remains to be determined whether this "Kahlbaum-Hecker-Kraepelin paradigm"-defining disorders based on distinctive symptoms and course-will produce psychiatric syndromes of sufficient homogeneity to yield their etiologic secrets.

Epidemiological characteristics of patients with cutaneous lupus erythematosus.

PubMed

Avilés Izquierdo, J A; Cano Martínez, N; Lázaro Ochaita, P

2014-01-01

Lupus erythematosus is a chronic autoimmune inflammatory disease with a wide clinical spectrum and variable clinical course. Few studies have analyzed the characteristics of patients with only cutaneous lupus erythematosus (CLE). The aim of this study was to describe the epidemiological, clinical, and immunological characteristics of a series of patients diagnosed with CLE. An analysis was performed of the data from all patients over 18 years of age with a diagnosis of CLE and seen between January 1, 2007 and December 31, 2011 in a tertiary hospital. One hundred- one patients were included in the study. The mean age at diagnosis was 40 years and 84% were women. Subacute forms of presentation were observed in 94% of patients. The chronic discoid forms were localized to the head and neck in 79% of cases, whereas the subacute forms were on the trunk in 97% of cases. Patients with acute forms were positive for antinuclear, anti-DNA, anti-smooth muscle, and anti-RNP (ribonucleoprotein) antibodies, whereas anti-Ro and anti-La antibodies predominated in patients with subacute forms. Seventeen patients presented more than 1 subtype of CLE. Fifteen (88%) of these patients received immunosuppressor treatment versus 44 (52%) of the other 84 patients with only 1 subtype of CLE. Patients with distinct subtypes of CLE present different clinical and immunological characteristics. Oral immunosuppressants are often needed to control the disease in a large proportion of patients with different subtypes of CLE. Copyright © 2013 Elsevier España, S.L. and AEDV. All rights reserved.

Electret Acoustic Transducer Array For Computerized Ultrasound Risk Evaluation System

DOEpatents

Moore, Thomas L.; Fisher, Karl A.

2005-08-09

An electret-based acoustic transducer array is provided and may be used in a system for examining tissue. The acoustic transducer array is formed with a substrate that has a multiple distinct cells formed therein. Within each of the distinct cells is positioned an acoustic transducing element formed of an electret material. A conductive membrane is formed over the distinct cells and may be flexible.

Genetic heterogeneity in familial exudative vitreoretinopathy; exclusion of the EVR1 locus on chromosome 11q in a large autosomal dominant pedigree.

PubMed

Bamashmus, M A; Downey, L M; Inglehearn, C F; Gupta, S R; Mansfield, D C

2000-04-01

Familial exudative vitreoretinopathy (FEVR) is associated with mutations in the Norrie disease gene in X linked pedigrees and with linkage to the EVR1 locus at 11q13 in autosomal dominant cases. A large autosomal dominant FEVR family was studied, both clinically and by linkage analysis, to determine whether it differed from the known forms of FEVR. Affected members and obligate gene carriers from this family were examined by slit lamp biomicroscopy, indirect ophthalmoscopy, and in some cases fluorescein angiography. Patient DNAs were genotyped for markers at the EVR1 locus on chromosome 11q13. The clinical evaluation in this family is consistent with previous descriptions of FEVR pedigrees, but linkage analysis proves that it has a form of FEVR genetically distinct from the EVR1 locus on 11q. This proves that there are at least three different loci associated with comparable FEVR phenotypes, a situation similar to that existing for many forms of retinal degeneration.

Ehlers–Danlos syndrome type VIII is clinically heterogeneous disorder associated primarily with periodontal disease, and variable connective tissue features

PubMed Central

Reinstein, Eyal; DeLozier, Celia Dawn; Simon, Ziv; Bannykh, Serguei; Rimoin, David L; Curry, Cynthia J

2013-01-01

Ehlers–Danlos syndrome (EDS) type VIII (periodontitis type) is a distinct form of EDS characterized by periodontal disease leading to precocious dental loss and a spectrum of joint and skin manifestations. EDS type VIII is transmitted in an autosomal dominant pattern; however, the mutated gene has not been identified. There are insufficient data on the spectrum of clinical manifestations and natural history of the disorder, and only a limited number of patients and pedigrees with this condition have been reported. We present a four-generation EDS type VIII kindred and show that EDS VIII is clinically variable and although some cases lack the associated skin and joint manifestations, microscopic evidence of collagen disorganization is detectable. We further propose that the diagnosis of EDS type VIII should be considered in familial forms of periodontitis, even when the associated skin and joint manifestations are unconvincing for the diagnosis of a connective tissue disorder. This novel observation highlights the uncertainty of using connective tissue signs in clinical practice to diagnose EDS type VIII. PMID:22739343

Lymphoid papillary hyperplasia of the palatine tonsil: a Chinese case report

PubMed Central

Zhao, Ming; Yu, Jingjing; Li, Changshui

2013-01-01

Lymphoid papillary hyperplasia is a rare abnormality of the tonsils with a predilection for affecting young Asian girls. Herein, we report a 31-year-old Chinese woman presented as right lateral recurrent tonsillar hypertrophy with odynophagia and dysphagia over the past 5 years, worsening over a period of for half a year. Clinically, this lesion was similar to papillomatosis or lymphoid polyposis. However, histopathologic study showed a distinctive form of lymphoid hyperplasia with considerable distinct finger-like projections composed of many phyllodes which contained remarkable follicular lymphoid hyperplasia. This is the only Chinese case of lymphoid papillary hyperplasia of the palatine tonsils that has been reported in the most recent English literature so far. The importance of recognizing this disorder rests in the fact that in spite of the clinical features suggestive of both a benign and a malignant tumor, however, the process is a benign tumor-like proliferation, probably non-neoplastic, could easily be cured by tonsillectomy. PMID:24040465

Distinctiveness of Encoding and Word Learning: Forms of "Distinctiveness" and Retention of Vocabulary Words.

ERIC Educational Resources Information Center

Shaughnessy, Michael F.; Cockrell, Kelly

Two experiments examining the "distinctiveness of encoding" hypothesis are reported. The hypothesis suggests that specific forms of processing of events may result in the formation of more exact perceptual descriptions and thus more distinctive records in memory. The two experiments reported address shortcomings in previous research on…

[Clinical view of toxoplasmosis in children--personal observations].

PubMed

Czarnecka-Rudnik, D; Stanek-Bazylko, F

1997-05-01

In this work we presented our own experience with recognized and treated toxoplasmosis among children. Treated cases were observed over several years afterwards. We analyzed the frequency and character of clinical changes, evaluated the validity of serological screening and the effectiveness of treatment. The largest age group treated were children 13 months to 5 years old. 13 children had the congenital and 12 the acquired form. The most cases occurred in the nodal, ocular and ocular-cranial forms. Thus, the most common symptoms were enlarged lymphatic nodes, strabismus, febrile seizures, intracranial calcifications. In the acquired forms of the illness a distinct correlation between treatment and the decrease antibody levels, the clinical pictures showed stagnation. The fall in antibody levels occurred earlier with intermediate immunofluorescence than with ELISA method. Among 20 children associated 30-day treatment was implemented (Daraprim, Rovamycine, Biseptol), among 4 with Fansidar and Rovamycine for 2-3 weeks. Few complications occurred at the end of or after treatment and did not require treatment/intervention. Usually it was leukopenia and thrombocytopenia. Long time observation allows to state that both therapeutic models prevent renewal of illness and can be recommended for further use.

Structuring of Hydrogels across Multiple Length Scales for Biomedical Applications.

PubMed

Cooke, Megan E; Jones, Simon W; Ter Horst, Britt; Moiemen, Naiem; Snow, Martyn; Chouhan, Gurpreet; Hill, Lisa J; Esmaeli, Maryam; Moakes, Richard J A; Holton, James; Nandra, Rajpal; Williams, Richard L; Smith, Alan M; Grover, Liam M

2018-04-01

The development of new materials for clinical use is limited by an onerous regulatory framework, which means that taking a completely new material into the clinic can make translation economically unfeasible. One way to get around this issue is to structure materials that are already approved by the regulator, such that they exhibit very distinct physical properties and can be used in a broader range of clinical applications. Here, the focus is on the structuring of soft materials at multiple length scales by modifying processing conditions. By applying shear to newly forming materials, it is possible to trigger molecular reorganization of polymer chains, such that they aggregate to form particles and ribbon-like structures. These structures then weakly interact at zero shear forming a solid-like material. The resulting self-healing network is of particular use for a range of different biomedical applications. How these materials are used to allow the delivery of therapeutic entities (cells and proteins) and as a support for additive layer manufacturing of larger-scale tissue constructs is discussed. This technology enables the development of a range of novel materials and structures for tissue augmentation and regeneration. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Genetic diversity of Leishmania donovani that causes cutaneous leishmaniasis in Sri Lanka: a cross sectional study with regional comparisons.

PubMed

Kariyawasam, Udeshika Lakmini; Selvapandiyan, Angamuthu; Rai, Keshav; Wani, Tasaduq Hussain; Ahuja, Kavita; Beg, Mizra Adil; Premathilake, Hasitha Upendra; Bhattarai, Narayan Raj; Siriwardena, Yamuna Deepani; Zhong, Daibin; Zhou, Guofa; Rijal, Suman; Nakhasi, Hira; Karunaweera, Nadira D

2017-12-22

Leishmania donovani is the etiological agent of visceral leishmaniasis (VL) in the Indian subcontinent. However, it is also known to cause cutaneous leishmaniasis (CL) in Sri Lanka. Sri Lankan L. donovani differs from other L. donovani strains, both at the molecular and biochemical level. To investigate the different species or strain-specific differences of L. donovani in Sri Lanka we evaluated sequence variation of the kinetoplastid DNA (kDNA). Parasites isolated from skin lesions of 34 CL patients and bone marrow aspirates from 4 VL patients were genotyped using the kDNA minicircle PCR analysis. A total of 301 minicircle sequences that included sequences from Sri Lanka, India, Nepal and six reference species of Leishmania were analyzed. Haplotype diversity of Sri Lankan isolates were high (H d  = 0.757) with strong inter-geographical genetic differentiation (F ST  > 0.25). In this study, L. donovani isolates clustered according to their geographic origin, while Sri Lankan isolates formed a separate cluster and were clearly distinct from other Leishmania species. Within the Sri Lankan group, there were three distinct sub-clusters formed, from CL patients who responded to standard antimony therapy, CL patients who responded poorly to antimony therapy and from VL patients. There was no specific clustering of sequences based on geographical origin within Sri Lanka. This study reveals high levels of haplotype diversity of L. donovani in Sri Lanka with a distinct genetic association with clinically relevant phenotypic characteristics. The use of genetic tools to identify clinically relevant features of Leishmania parasites has important therapeutic implications for leishmaniasis.

MORPHOLOGICAL AND PATHOGENIC VARIATIONS IN TREPONEMA PALLIDUM

PubMed Central

Noguchi, Hideyo

1912-01-01

When many cultures of Treponema pallidum, whether obtained from the testicular lesions produced in rabbits or directly from human cases of syphilis, are compared, certain definite differences in morphological character become apparent. The different specimens can be divided into thicker and thinner forms or types, and an average or normal form or type. The last is the common or most frequent variety, but the other two occur with sufficient frequency and retain their characters with such constancy as to constitute distinct varieties. Indeed, two of the varieties—the average and the thinner—occurred in association in a chancre and were separated afterwards in cultures. The gross cultural properties of the three varieties present no points of distinction. The lesions caused in the testicle of the rabbit differ according to the variety inoculated, and consist either of a diffuse or of a nodular orchitis. This is a highly important distinction, and if, in the study of a still larger number of specimens of pallida, it is maintained, it is capable of throwing light on certain important clinical features of the human syphilitic disease. The thinner variety of Treponema pallidum resembles in morphology Treponema microdentium, from which it is unmistakably distinguished by cultural characters. The morphological and pathogenic variations in cultures of the pallidum may constitute racial differences within the species. PMID:19867516

Neutrophilic inflammation in asthma: mechanisms and therapeutic considerations.

PubMed

Chang, Hun Soo; Lee, Tae-Hyeong; Jun, Ji Ae; Baek, Ae Rin; Park, Jong-Sook; Koo, So-My; Kim, Yang-Ki; Lee, Ho Sung; Park, Choon-Sik

2017-01-01

Neutrophilic airway inflammation represents a pathologically distinct form of asthma and frequently appears in symptomatic adulthood asthmatics. However, clinical impacts and mechanisms of the neutrophilic inflammation have not been thoroughly evaluated up to date. Areas covered: Currently, distinct clinical manifestations, triggers, and molecular mechanisms of the neutrophilic inflammation (namely Toll-like receptor, Th1, Th17, inflammasome) are under investigation in asthma. Furthermore, possible role of the neutrophilic inflammation is being investigated in respect to the airway remodeling. We searched the related literatures published during the past 10 years on the website of Pub Med under the title of asthma and neutrophilic inflammation in human. Expert commentary: Epidemiologic and experimental studies have revealed that the neutrophilic airway inflammation is induced by a wide variety of stimuli including ozone, particulate matters, cigarette smoke, occupational irritants, endotoxins, microbial infection and colonization, and aeroallergens. These triggers provoke diverse immune and inflammatory responses leading to progressive and sometimes irreversible airway obstruction. Clinically, neutrophilic airway inflammation is frequently associated with severe asthma and poor response to glucocorticoid therapy, indicating the need for other treatment strategies. Accordingly, therapeutics will be targeted against the main mediators behind the underlying molecular mechanisms of the neutrophilic inflammation.

Losing the music: aging affects the perception and subcortical neural representation of musical harmony.

PubMed

Bones, Oliver; Plack, Christopher J

2015-03-04

When two musical notes with simple frequency ratios are played simultaneously, the resulting musical chord is pleasing and evokes a sense of resolution or "consonance". Complex frequency ratios, on the other hand, evoke feelings of tension or "dissonance". Consonance and dissonance form the basis of harmony, a central component of Western music. In earlier work, we provided evidence that consonance perception is based on neural temporal coding in the brainstem (Bones et al., 2014). Here, we show that for listeners with clinically normal hearing, aging is associated with a decline in both the perceptual distinction and the distinctiveness of the neural representations of different categories of two-note chords. Compared with younger listeners, older listeners rated consonant chords as less pleasant and dissonant chords as more pleasant. Older listeners also had less distinct neural representations of consonant and dissonant chords as measured using a Neural Consonance Index derived from the electrophysiological "frequency-following response." The results withstood a control for the effect of age on general affect, suggesting that different mechanisms are responsible for the perceived pleasantness of musical chords and affective voices and that, for listeners with clinically normal hearing, age-related differences in consonance perception are likely to be related to differences in neural temporal coding. Copyright © 2015 Bones and Plack.

Losing the Music: Aging Affects the Perception and Subcortical Neural Representation of Musical Harmony

PubMed Central

Plack, Christopher J.

2015-01-01

When two musical notes with simple frequency ratios are played simultaneously, the resulting musical chord is pleasing and evokes a sense of resolution or “consonance”. Complex frequency ratios, on the other hand, evoke feelings of tension or “dissonance”. Consonance and dissonance form the basis of harmony, a central component of Western music. In earlier work, we provided evidence that consonance perception is based on neural temporal coding in the brainstem (Bones et al., 2014). Here, we show that for listeners with clinically normal hearing, aging is associated with a decline in both the perceptual distinction and the distinctiveness of the neural representations of different categories of two-note chords. Compared with younger listeners, older listeners rated consonant chords as less pleasant and dissonant chords as more pleasant. Older listeners also had less distinct neural representations of consonant and dissonant chords as measured using a Neural Consonance Index derived from the electrophysiological “frequency-following response.” The results withstood a control for the effect of age on general affect, suggesting that different mechanisms are responsible for the perceived pleasantness of musical chords and affective voices and that, for listeners with clinically normal hearing, age-related differences in consonance perception are likely to be related to differences in neural temporal coding. PMID:25740534

Autophagy as a Therapeutic Target in Cardiovascular Disease

PubMed Central

Nemchenko, Andriy; Chiong, Mario; Turer, Aslan; Lavandero, Sergio; Hill, Joseph A.

2011-01-01

The epidemic of heart failure continues apace, and development of novel therapies with clinical efficacy has lagged. Now, important insights into the molecular circuitry of cardiovascular autophagy have raised the prospect that this cellular pathway of protein quality control may be a target of clinical relevance. Whereas basal levels of autophagy are required for cell survival, excessive levels – or perhaps distinct forms of autophagic flux – contribute to disease pathogenesis. Our challenge will be to distinguish mechanisms that drive adaptive versus maladaptive autophagy and to manipulate those pathways for therapeutic gain. Recent evidence suggests this may be possible. Here, we review the fundamental biology of autophagy and its role in a variety of forms of cardiovascular disease. We discuss ways in which this evolutionarily conserved catabolic mechanism can be manipulated, discuss studies presently underway in heart disease, and provide our perspective on where this exciting field may lead in the future. PMID:21723289

Common and rare forms of diabetes mellitus: towards a continuum of diabetes subtypes.

PubMed

Flannick, Jason; Johansson, Stefan; Njølstad, Pål R

2016-07-01

Insights into the genetic basis of type 2 diabetes mellitus (T2DM) have been difficult to discern, despite substantial research. More is known about rare forms of diabetes mellitus, several of which share clinical and genetic features with the common form of T2DM. In this Review, we discuss the extent to which the study of rare and low-frequency mutations in large populations has begun to bridge the gap between rare and common forms of diabetes mellitus. We hypothesize that the perceived division between these diseases might be due, in part, to the historical ascertainment bias of genetic studies, rather than a clear distinction between disease pathophysiologies. We also discuss possible implications of a new model for the genetic basis of diabetes mellitus subtypes, where the boundary between subtypes becomes blurred.

Redescription of Hepatozoon felis (Apicomplexa: Hepatozoidae) based on phylogenetic analysis, tissue and blood form morphology, and possible transplacental transmission.

PubMed

Baneth, Gad; Sheiner, Alina; Eyal, Osnat; Hahn, Shelley; Beaufils, Jean-Pierre; Anug, Yigal; Talmi-Frank, Dalit

2013-04-15

A Hepatozoon parasite was initially reported from a cat in India in 1908 and named Leucocytozoon felis domestici. Although domestic feline hepatozoonosis has since been recorded from Europe, Africa, Asia and America, its description, classification and pathogenesis have remained vague and the distinction between different species of Hepatozoon infecting domestic and wild carnivores has been unclear. The aim of this study was to carry out a survey on domestic feline hepatozoonosis and characterize it morphologically and genetically. Hepatozoon sp. DNA was amplified by PCR from the blood of 55 of 152 (36%) surveyed cats in Israel and from all blood samples of an additional 19 cats detected as parasitemic by microscopy during routine hematologic examinations. Hepatozoon sp. forms were also characterized from tissues of naturally infected cats. DNA sequencing determined that all cats were infected with Hepatozoon felis except for two infected by Hepatozoon canis. A significant association (p = 0.00001) was found between outdoor access and H. felis infection. H. felis meronts containing merozoites were characterized morphologically from skeletal muscles, myocardium and lungs of H. felis PCR-positive cat tissues and development from early to mature meront was described. Distinctly-shaped gamonts were observed and measured from the blood of these H. felis infected cats. Two fetuses from H. felis PCR-positive queens were positive by PCR from fetal tissue including the lung and amniotic fluid, suggesting possible transplacental transmission. Genetic analysis indicated that H. felis DNA sequences from Israeli cats clustered together with the H. felis Spain 1 and Spain 2 sequences. These cat H. felis sequences clustered separately from the feline H. canis sequences, which grouped with Israeli and foreign dog H. canis sequences. H. felis clustered distinctly from Hepatozoon spp. of other mammals. Feline hepatozoonosis caused by H. felis is mostly sub-clinical as a high proportion of the population is infected with no apparent overt clinical manifestations. This study aimed to integrate new histopathologic, hematologic, clinical, epidemiological and genetic findings on feline hepatozoonosis and promote the understanding of this infection. The results indicate that feline infection is primarily caused by a morphologically and genetically distinct species, H. felis, which has predilection to infecting muscular tissues, and is highly prevalent in the cat population studied. The lack of previous comprehensively integrated data merits the redescription of this parasite elucidating its parasitological characteristics.

Categorization of compensatory motions in transradial myoelectric prosthesis users.

PubMed

Hussaini, Ali; Zinck, Arthur; Kyberd, Peter

2017-06-01

Prosthesis users perform various compensatory motions to accommodate for the loss of the hand and wrist as well as the reduced functionality of a prosthetic hand. Investigate different compensation strategies that are performed by prosthesis users. Comparative analysis. A total of 20 able-bodied subjects and 4 prosthesis users performed a set of bimanual activities. Movements of the trunk and head were recorded using a motion capture system and a digital video recorder. Clinical motion angles were calculated to assess the compensatory motions made by the prosthesis users. The video recording also assisted in visually identifying the compensations. Compensatory motions by the prosthesis users were evident in the tasks performed (slicing and stirring activities) as compared to the benchmark of able-bodied subjects. Compensations took the form of a measured increase in range of motion, an observed adoption of a new posture during task execution, and prepositioning of items in the workspace prior to initiating a given task. Compensatory motions were performed by prosthesis users during the selected tasks. These can be categorized into three different types of compensations. Clinical relevance Proper identification and classification of compensatory motions performed by prosthesis users into three distinct forms allows clinicians and researchers to accurately identify and quantify movement. It will assist in evaluating new prosthetic interventions by providing distinct terminology that is easily understood and can be shared between research institutions.

Molecular characterization of circulating Foot and mouth disease virus (FMDV) serotype O topotype EA-3 and serotype A (African topotype) genotype IV in Egypt, 2016.

PubMed

Soltan, Mohamed A; Negmaldin, Ali H; El-Diasty, Mohamed M; Mansour, Shimaa M G; Elbadry, Maha A; Wilkes, Rebecca P

2017-09-01

In January-April 2016, cattle and buffalo farm owners and veterinarians reported clinical signs suggestive of foot and mouth disease virus (FMDV) outbreaks among non-vaccinated cattle and buffalo herds in Egypt. The clinical disease observed was either mild (small oral lesions and speedy recovery) or severe (extensive oral lesions and/or mortalities), and the form of the disease (either mild or severe) segregated by farm. This study aimed to confirm the presence of FMDV and to characterize the circulating strains associated with the outbreaks. Vesicular epithelia were collected from 41 animals representing 15 affected cattle and buffalo farms in five governorates (Behira, Cairo, Daqahlia, Giza and Ismailia), and tested by real time (rt) RT-PCR. Consequently, 92% (38/41) of examined samples were positive. Furthermore, the VP1 coding region of 60% (23/38) of positive specimens were amplified by RT-PCR and sequenced. The phylogenetic analysis identified two distinct strains characterized as serotype O topotype EA-3 and serotype A (African topotype) of genotype IV in the severe and mild disease forms, respectively. The newly identified strains clustered in distinct clades in the phylogenetic trees, indicating the likelihood of new incursions into Egypt. Those strains were most closely related to previously described Sudanese strains. Copyright © 2017 Elsevier B.V. All rights reserved.

Up to Four Distinct Polypeptides Are Produced from the γ34.5 Open Reading Frame of Herpes Simplex Virus 2

PubMed Central

Korom, Maria; Davis, Katie L.

2014-01-01

ABSTRACT The herpes simplex virus 1 (HSV-1) ICP34.5 protein strongly influences neurovirulence and regulates several cellular antiviral responses. Despite the clinical importance of HSV-2, relatively little is known about its ICP34.5 ortholog. We found that HSV-2 produces up to four distinct forms of ICP34.5 in infected cells: a full-length protein, one shorter form sharing the N terminus, and two shorter forms sharing the C terminus. These forms appeared with similar kinetics and accumulated in cells over much of the replication cycle. We confirmed that the N-terminal form is translated from the primary unspliced transcript to a stop codon within the intron unique to HSV-2 γ34.5. We found that the N-terminal form was produced in a variety of cell types and by 9 of 10 clinical isolates. ICP27 influenced but was not required for expression of the N-terminal form. Western blotting and reverse transcription-PCR indicated the C-terminal forms did not contain the N terminus and were not products of alternative splicing or internal transcript initiation. Expression plasmids encoding methionine at amino acids 56 and 70 generated products that comigrated in SDS-PAGE with the C1 and C2 forms, respectively, and mutation of these sites abolished C1 and C2. Using a recombinant HSV-2 encoding hemagglutinin (HA)-tagged ICP34.5, we demonstrated that the C-terminal forms were also produced during infection of many human and mouse cell types but were not detectable in mouse primary neurons. The protein diversity generated from the HSV-2 γ34.5 open reading frame implies additional layers of cellular regulation through potential independent activities associated with the various forms of ICP34.5. IMPORTANCE The herpes simplex virus 1 (HSV-1) protein ICP34.5, encoded by the γ34.5 gene, interferes with several host defense mechanisms by binding cellular proteins that would otherwise stimulate the cell's autophagic, translational-arrest, and type I interferon responses to virus infection. ICP34.5 also plays a crucial role in determining the severity of nervous system infections with HSV-1 and HSV-2. The HSV-2 γ34.5 gene contains an intron not present in HSV-1 γ34.5. A shorter N-terminal form of HSV-2 ICP34.5 can be translated from the unspliced γ34.5 mRNA. Here, we show that two additional forms consisting of the C-terminal portion of ICP34.5 are generated in infected cells. Production of these N- and C-terminal forms is highly conserved among HSV-2 strains, including many clinical isolates, and they are broadly expressed in several cell types, but not mouse primary neurons. Multiple ICP34.5 polypeptides add additional complexity to potential functional interactions influencing HSV-2 neurovirulence. PMID:25031346

Higher Impulsivity As a Distinctive Trait of Severe Cocaine Addiction among Individuals Treated for Cocaine or Alcohol Use Disorders.

PubMed

García-Marchena, Nuria; Ladrón de Guevara-Miranda, David; Pedraz, María; Araos, Pedro Fernando; Rubio, Gabriel; Ruiz, Juan Jesús; Pavón, Francisco Javier; Serrano, Antonia; Castilla-Ortega, Estela; Santín, Luis J; Rodríguez de Fonseca, Fernando

2018-01-01

Despite alcohol being the most often used addictive substance among addicted patients, use of other substances such as cocaine has increased over recent years, and the combination of both drugs aggravates health impairment and complicates clinical assessment. The aim of this study is to identify and characterize heterogeneous subgroups of cocaine- and alcohol-addicted patients with common characteristics based on substance use disorders, psychiatric comorbidity and impulsivity. A total of 214 subjects with cocaine and/or alcohol use disorders were recruited from outpatient treatment programs and clinically assessed. A latent class analysis was used to establish phenotypic categories according to diagnosis of cocaine and alcohol use disorders, mental disorders, and impulsivity scores. Relevant variables were examined in the latent classes (LCs) using correlation and analyses of variance and covariance. Four LCs of addicted patients were identified: Class 1 (45.3%) formed by alcohol-dependent patients exhibiting lifetime mood disorder diagnosis and mild impulsivity; Class 2 (14%) formed mainly by lifetime cocaine use disorder patients with low probability of comorbid mental disorders and mild impulsivity; Class 3 (10.7%) formed by cocaine use disorder patients with elevated probability to course with lifetime anxiety, early and personality disorders, and greater impulsivity scores; and Class 4 (29.9%) formed mainly by patients with alcohol and cocaine use disorders, with elevated probability in early and personality disorders and elevated impulsivity. Furthermore, there were significant differences among classes in terms of Diagnostic and Statistical Manual of Mental Disorders-4th Edition-Text Revision criteria for abuse and dependence: Class 3 showed more criteria for cocaine use disorders than other classes, while Class 1 and Class 4 showed more criteria for alcohol use disorders. Cocaine- and alcohol-addicted patients who were grouped according to diagnosis of substance use disorders, psychiatric comorbidity, and impulsivity show different clinical and sociodemographic variables. Whereas mood and anxiety disorders are more prevalent in alcohol-addicted patients, personality disorders are associated with cocaine use disorders and diagnosis of comorbid substance use disorders. Notably, increased impulsivity is a distinctive characteristic of patients with severe cocaine use disorder and comorbid personality disorders. Psychiatric disorders and impulsivity should be considered for improving the stratification of addicted patients with shared clinical and sociodemographic characteristics to select more appropriate treatments.

Exclusion of chromosome 1q21-q31 from linkage to three pedigrees affected by the pigment-dispersion syndrome

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

Paglinauan, C.; Haines, J.L.; Del Bono, E.A.

1995-05-01

The pigment-dispersion syndrome is a form of open-angle glaucoma that usually affects individuals in the first 3 decades of life. In addition to the typical optic-nerve degeneration seen in all types of glaucoma, the pigment-dispersion syndrome is characterized by distinctive clinical features including the deposition of pigment granules from the iris epithelium on a variety of ocular structures including the trabecular meshwork. Frequently this disorder affects young myopic individuals. In the early stages of the disease, affected individuals may have clinical evidence of dispersed pigment without an associated elevation of intraocular pressure and optic-nerve degeneration. However, as the disease processmore » progresses, many affected individuals ({approximately}50%) will develop elevated intraocular pressure and degeneration of the optic nerve, causing a permanent loss of sight. The pigment-dispersion syndrome shares several clinical features with the form of autosomal dominant juvenile open-angle glaucoma that recently has been mapped to the 1q21-q31 region of chromosome 1. Our results indicate that the pigment-dispersion syndrome, a form of glaucoma that may also affect the juvenile population, is genetically unrelated to the autosomal dominant form of juvenile glaucoma caused by a defect in a gene located in the 1q21-q31 region of chromosome 1. 15 refs., 2 figs., 1 tab.« less

Pseudoephedrine may cause "pigmenting" fixed drug eruption.

PubMed

Ozkaya, Esen; Elinç-Aslan, Meryem Sevinç

2011-05-01

Fixed drug eruption (FDE) is a distinctive drug eruption characterized by recurrent well-defined lesions in the same location each time the responsible drug is taken. Two different clinical forms have been described: the common classic pigmenting form and the rare nonpigmenting form. Nonpigmenting FDE is mainly characterized by symmetrical large erythematous plaques and the dermal histopathologic reaction pattern. Pseudoephedrine is known as the major inducer of nonpigmenting FDE. Pigmenting FDE from pseudoephedrine has not been reported previously. Here, the first case of pseudoephedrine-induced pigmenting FDE is reported, showing the characteristic features of classic pigmenting FDE such as asymmetry, normal-sized lesions, and the epidermodermal histopathologic reaction pattern. Moreover, a positive occlusive patch-test reaction to pseudoephedrine could be demonstrated on postlesional FDE skin for the first time.

Clinical appearances, healing patterns, risk factors, and outcomes of horses with fungal keratitis: 53 cases (1978-1996)

PubMed

Gaarder, J E; Rebhun, W C; Ball, M A; Patten, V; Shin, S; Erb, H

1998-07-01

To compare initial clinical appearances, healing mechanisms, risk factors, and outcomes of horses with fungal keratitis. Retrospective analysis. 52 horses (53 eyes) with fungal keratitis. Medical records and clinical photographs of eyes were reviewed. Keratomycoses were categorized on the basis of clinical appearance at initial examination and pattern of healing. Five distinct forms of mycotic keratitis were recognized. Of 53 affected eyes, 34 (64%) retained sight and had varying degrees of corneal scarring after treatment, 6 (11%) had a cosmetic appearance but were blind, and 13 (25%) were enucleated. Bacterial-like ulcers were the most frequent type and the most difficult for predicting outcome. Eyes affected by superficial fungal keratitis were likely to be chronically infected and to require debridement and extended treatment but usually healed with minimal scarring. Keratomycosis with a surrounding furrow resulted in a grave prognosis. Aspergillus organisms were isolated from 9 of 10 such eyes. Cake-frosting material was a positive prognostic sign. Fungal corneal stromal abscesses tended to be caused by yeast. This information will aid practitioners in recognizing various forms of fungal keratitis and guide them when making therapeutic decisions and prognoses for affected horses.

Novel RSPO1 mutation causing 46,XX testicular disorder of sex development with palmoplantar keratoderma: A review of literature and expansion of clinical phenotype.

PubMed

Tallapaka, Karthik; Venugopal, Vineeth; Dalal, Ashwin; Aggarwal, Shagun

2018-04-01

Palmoplantar hyperkeratosis with squamous cell carcinoma of skin and sex reversal (MIM # 610644) is a clinically distinctive form of SRY-negative 46,XX disorder of sex development. It is a rare autosomal recessive disorder caused due to biallelic loss of function mutations in RSPO1 gene. RSPO1 acts by activating the canonical β-catenin pathway and is one of the most important genes controlling female gonadal differentiation. RSPO1-associated disorders of sex development have been described only in three instances in the past. We report fourth such case with additional findings and perform a comparative review of previous phenotypic descriptions, thereby expanding the clinical phenotype of this syndrome. © 2018 Wiley Periodicals, Inc.

[A comparison of characteristics of pathologic hobbies in schizophrenic patients of different age].

PubMed

Sergeev, I I; Deych, R V; Malinochka, S A

2016-01-01

To analyze age-related pathologic hobbies in patients with schizophrenia spectrum disorders. Forty-three inpatients, aged from 4 to 16 years, and 31 patients, aged from 18 to 65 years, were studied. Clinical/psychopathological analysis, psychological experiment and clinical statistics were used. Pathological hobbies substantially differed depending on the age (3-6, 7-15 and 18-65 years). In preschool age, hobbies were immature and infantile, arose autochthonously, their course was relatively stable and they had limited maladaptive effects. In junior school/teenager age, hobbies were more distinct and were associated with more diverse and mature realization patterns. Their origin was more depended on environmental factors, the course was persistent or attack-like with more pronounced and steady maladaptive effects. In some cases, there was a trend to pathological hobby progression. Abnormal hobbies in patients of mature age were the most diverse in their subjects and forms of realization as well as in their clinical variants and dynamic types. In the group of mature patients with schizophrenic spectrum disorders, there was a significantly higher percentage of psychotic forms of pathological hobbies.

Chemical and microbiologic aspects of penems, a distinct class of beta-lactams: focus on faropenem.

PubMed

Hamilton-Miller, Jeremy M T

2003-11-01

Many beta-lactam antimicrobials were developed between the 1960s and 1980s, with continuing development driven by the emergence of microbial resistance. Penems form a discrete class of beta-lactams that comprises structural hybrids of penicillins (penams) and cephalosporins (cephems). The chemistry and microbiology of the representative penems MEN 10700, ritipenem, CGP 31608, sulopenem, BRL 42715, and faropenem are reviewed. Particular emphasis is placed on faropenem, which is in late clinical development.

Granulomatous mastitis: a report of seven cases

PubMed Central

Fletcher, A; Magrath, IM; Riddell, RH; Talbot, IC

1982-01-01

The clinical history and histological features of seven cases of granulomatous mastitis are presented. The lesion occurs in young parous women as a tender extra-areolar breast lump. Histologically, non-caseating discrete granulomas are present, confined to breast lobules with, in three cases, coalescence of the granulomas and microabscess formation. Pathogenesis of the changes is discussed. It is thought that granulomatous mastitis is an entity morphologically distinct from duct ectasia/plasma cell mastitis and the commoner forms of granulomatous breast diseases. Images PMID:6889612

Transgastric Local Pancreatic Hypothermia: A Novel, Rapid Multimodal Therapy for Acute Pancreatitis

DTIC Science & Technology

2016-02-01

PRINCIPAL INVESTIGATOR: Dr. Vijay P. Singh CONTRACTING ORGANIZATION: Mayo Clinic Arizona Scottsdale, AZ 85259. REPORT DATE : Feb 2016 TYPE OF REPORT...PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE Feb 2016 2. REPORT TYPE Annual Report 3. DATES COVERED 8Jan2015 - 7Jan2016 4...increased metabolic demand during severe (GTL) but not mild AP. Thus this concept/technology/ method may be used to make an early distinction between mild

Assessing the distinctiveness of psychotherapies and examining change over treatment for anorexia nervosa with cognitive-behavior therapy, interpersonal psychotherapy, and specialist supportive clinical management.

PubMed

McIntosh, Virginia V W; Jordan, Jennifer; Carter, Janet D; Luty, Suzanne E; Carter, Frances A; McKenzie, Janice M; Frampton, Christopher M A; Joyce, Peter R

2016-10-01

Therapist adherence to cognitive-behavior therapy (CBT), interpersonal psychotherapy (IPT), and specialist supportive clinical management (SSCM) for anorexia nervosa (AN), was examined across three phases of therapy in a randomized clinical trial. Adherence in early, middle, and late phase therapy sessions from 53 of 56 participants in the trial was assessed using the CSPRS-AN by independent raters after listening to complete therapy sessions. The three forms of psychotherapy were distinguishable by blind raters. Subscale scores were higher for the corresponding therapy than the other therapy modalities. In CBT and SSCM, a phase-by-therapy effect was found, with the CBT subscale highest for CBT, intermediate for SSCM, lowest for IPT, and elevated in the middle phase of CBT and SSCM. The SSCM subscale was highest for SSCM, intermediate for CBT, lowest for IPT, and elevated in the middle phase of SSCM. Adherence to activities around normalizing eating, weight gain, and education about anorexia nervosa was higher in SSCM than in either CBT or IPT. Ensuring the distinctiveness of therapies in existing clinical trials with differential treatment outcome is essential. Research on adherence to therapy modalities has the potential to help understanding of the effective components of new and existing treatments for AN. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:958-962). © 2016 Wiley Periodicals, Inc.

Contemporary Patterns of Multiple Organ Dysfunction in Trauma.

PubMed

Shepherd, Joanna M; Cole, Elaine; Brohi, Karim

2017-04-01

Multiple organ dysfunction syndrome (MODS) is associated with poor outcomes for trauma patients. Different forms of MODS may exist and have different consequences. The ability to distinguish them clinically may have implications for prognosis and treatment. We wished to study whether prolonged MODS (PRMODS) could be observed as a distinct clinical entity to early resolving MODS (ERMODS) in critically injured patients. Adult major trauma patients recruited to a prospective observational study at a single major trauma center were eligible for inclusion. MODS was defined as Sequential Organ Failure Assessment (SOFA) score >5; and PRMODS as lasting >7 days. Time to recovery (TTR) was calculated as the number of days before the SOFA fell below the MODS threshold (≤5). Five hundred ninety-five patients were enrolled of whom 285 developed ERMODS (48%) and 184 (31%) PRMODS. Organ dysfunction was more severe and protracted in PRMODS, especially in patients without brain injury (mean SOFA 11 vs. 6, Day 2, P < 0.001; TTR 17 vs. 3 days, P < 0.001). PRMODS exhibited higher rates of hepatic and renal dysfunction (84% vs. 56%; and 78% vs. 47%, P≤0.001). Patterns of recovery were distinct in hepatic, renal, and neurological systems (TTR 15 vs. 4; 20 vs. 3; and 28 vs. 7 days, P < 0.01). PRMODS was associated with higher infection and mortality rates (91% vs. 41%; and 22% vs. 7%, P < 0.001). PRMODS appears common, a distinct clinical entity, and associated with worse patient outcomes. PRMODS may represent an important endpoint for studies evaluating outcomes following trauma.

The changing face of Usher syndrome: clinical implications.

PubMed

Cohen, Mazal; Bitner-Glindzicz, Maria; Luxon, Linda

2007-02-01

Usher syndrome is both genetically and phenotypically heterogeneous. Traditionally, the condition has been classified into three clinical types, differentiated by the severity and progression of the hearing impairment and by the presence or absence of vestibular symptoms. Recent advances in molecular genetics have enabled researchers to study the phenotypic expression in confirmed molecular groups of Usher. In response to the expansion of clinical and genetic information on Usher, we report an up to date review of the different clinical forms of Usher in known molecular groups and use the emerging evidence to appraise the diagnostic utility of the traditional classification of Usher. Our findings undermine the traditional view that the clinical types of Usher have distinct genetic causes. The pleiotropic effects of some of the major causes of Usher lead to considerable overlap between the different clinical types, with very little evidence for phenotypic-genotypic correlations. The novel synthesis emerging from this review suggests more productive approaches to the diagnosis of Usher in hearing-impaired children which would provide more accurate prognostic information to families.

Using Patient-Reported Information to Improve Clinical Practice.

PubMed

Schlesinger, Mark; Grob, Rachel; Shaller, Dale

2015-12-01

To assess what is known about the relationship between patient experience measures and incentives designed to improve care, and to identify how public policy and medical practices can promote patient-valued outcomes in health systems with strong financial incentives. Existing literature (gray and peer-reviewed) on measuring patient experience and patient-reported outcomes, identified from Medline and Cochrane databases; evaluations of pay-for-performance programs in the United States, Europe, and the Commonwealth countries. We analyzed (1) studies of pay-for-performance, to identify those including metrics for patient experience, and (2) studies of patient experience and of patient-reported outcomes to identify evidence of influence on clinical practice, whether through public reporting or private reporting to clinicians. First, we identify four forms of "patient-reported information" (PRI), each with distinctive roles shaping clinical practice: (1) patient-reported outcomes measuring self-assessed physical and mental well-being, (2) surveys of patient experience with clinicians and staff, (3) narrative accounts describing encounters with clinicians in patients' own words, and (4) complaints/grievances signaling patients' distress when treatment or outcomes fall short of expectations. Because these forms vary in crucial ways, each must be distinctively measured, deployed, and linked with financial incentives. Second, although the literature linking incentives to patients experience is limited, implementing pay-for-performance systems appears to threaten certain patient-valued aspects of health care. But incentives can be made compatible with the outcomes patients value if: (a) a sufficient portion of incentives is tied to patient-reported outcomes and experiences, (b) incentivized forms of PRI are complemented by other forms of patient feedback, and (c) health care organizations assist clinicians to interpret and respond to PRI. Finally, we identify roles for the public and private sectors in financing PRI and orchestrating an appropriate balance among its four forms. Unless public policies are attentive to patients' perspectives, stronger financial incentives for clinicians can threaten aspects of care that patients most value. Certain policy parameters are already clear, but additional research is required to clarify how best to collect patient narratives in varied settings, how to report narratives to consumers in conjunction with quantified metrics, and how to promote a "culture of learning" at the practice level that incorporates patient feedback. © Health Research and Educational Trust.

Frontal lobe dementia and motor neuron disease.

PubMed Central

Neary, D; Snowden, J S; Mann, D M; Northen, B; Goulding, P J; Macdermott, N

1990-01-01

Four patients are described, in whom a profound and rapidly progressive dementia occurred in association with clinical features of motor neuron disease. The pattern of dementia indicated impaired frontal lobe function, confirmed by reduced tracer uptake in the frontal lobes on single photon emission computed tomography (SPECT). Pathological examination of the brains of two patients revealed frontal-lobe atrophy, with mild gliosis and spongiform change. The spinal cord changes were consistent with motor neuron disease. The clinical picture and pathological findings resembled those of dementia of frontal-lobe type and were distinct from those of Alzheimer's disease. The findings have implications for the understanding of the spectrum of non-Alzheimer forms of primary degenerative dementia. Images PMID:2303828

New clinical practice guidelines on the classification, evaluation and management of childhood interstitial lung disease in infants: what do they mean?

PubMed

Wambach, Jennifer A; Young, Lisa R

2014-12-01

The American Thoracic Society (ATS) recently published a clinical practice guideline regarding the classification, evaluation, and management of childhood interstitial lung disease in infancy (chILD). As disease entities among infants with ILD are often distinct from forms seen in older children and adults, the guideline encourages an age-based classification system and focuses on the diagnostic approach to neonates and infants <2 years of age. The guideline reviews current evidence and recommendations for the evaluation, relevant genetic studies, and management of symptomatic infants. Here, we summarize the ATS guideline, highlight the major concepts, and discuss future strategies aimed at addressing current gaps in knowledge.

Clinical Epidemiology of Buruli Ulcer from Benin (2005-2013): Effect of Time-Delay to Diagnosis on Clinical Forms and Severe Phenotypes.

PubMed

Capela, Carlos; Sopoh, Ghislain E; Houezo, Jean G; Fiodessihoué, René; Dossou, Ange D; Costa, Patrício; Fraga, Alexandra G; Menino, João F; Silva-Gomes, Rita; Ouendo, Edgard M; Rodrigues, Fernando; Pedrosa, Jorge

2015-01-01

Buruli Ulcer (BU) is a neglected infectious disease caused by Mycobacterium ulcerans that is responsible for severe necrotizing cutaneous lesions that may be associated with bone involvement. Clinical presentations of BU lesions are classically classified as papules, nodules, plaques and edematous infiltration, ulcer or osteomyelitis. Within these different clinical forms, lesions can be further classified as severe forms based on focality (multiple lesions), lesions' size (>15 cm diameter) or WHO Category (WHO Category 3 lesions). There are studies reporting an association between delay in seeking medical care and the development of ulcerative forms of BU or osteomyelitis, but the effect of time-delay on the emergence of lesions classified as severe has not been addressed. To address both issues, and in a cohort of laboratory-confirmed BU cases, 476 patients from a medical center in Allada, Benin, were studied. In this laboratory-confirmed cohort, we validated previous observations, demonstrating that time-delay is statistically related to the clinical form of BU. Indeed, for non-ulcerated forms (nodule, edema, and plaque) the median time-delay was 32.5 days (IQR 30.0-67.5), while for ulcerated forms it was 60 days (IQR 20.0-120.0) (p = 0.009), and for bone lesions, 365 days (IQR 228.0-548.0). On the other hand, we show here that time-delay is not associated with the more severe phenotypes of BU, such as multi-focal lesions (median 90 days; IQR 56-217.5; p = 0.09), larger lesions (diameter >15 cm) (median 60 days; IQR 30-120; p = 0.92) or category 3 WHO classification (median 60 days; IQR 30-150; p = 0.20), when compared with unifocal (median 60 days; IQR 30-90), small lesions (diameter ≤15 cm) (median 60 days; IQR 30-90), or WHO category 1+2 lesions (median 60 days; IQR 30-90), respectively. Our results demonstrate that after an initial period of progression towards ulceration or bone involvement, BU lesions become stable regarding size and focal/multi-focal progression. Therefore, in future studies on BU epidemiology, severe clinical forms should be systematically considered as distinct phenotypes of the same disease and thus subjected to specific risk factor investigation.

Selective Erasure of Distinct Forms of Long-Term Synaptic Plasticity Underlying Different Forms of Memory in the Same Postsynaptic Neuron.

PubMed

Hu, Jiangyuan; Ferguson, Larissa; Adler, Kerry; Farah, Carole A; Hastings, Margaret H; Sossin, Wayne S; Schacher, Samuel

2017-07-10

Generalization of fear responses to non-threatening stimuli is a feature of anxiety disorders. It has been challenging to target maladaptive generalized memories without affecting adaptive memories. Synapse-specific long-term plasticity underlying memory involves the targeting of plasticity-related proteins (PRPs) to activated synapses. If distinct tags and PRPs are used for different forms of plasticity, one could selectively remove distinct forms of memory. Using a stimulation paradigm in which associative long-term facilitation (LTF) occurs at one input and non-associative LTF at another input to the same postsynaptic neuron in an Aplysia sensorimotor preparation, we found that each form of LTF is reversed by inhibiting distinct isoforms of protein kinase M (PKM), putative PRPs, in the postsynaptic neuron. A dominant-negative (dn) atypical PKM selectively reversed associative LTF, while a dn classical PKM selectively reversed non-associative LTF. Although both PKMs are formed from calpain-mediated cleavage of protein kinase C (PKC) isoforms, each form of LTF is sensitive to a distinct dn calpain expressed in the postsynaptic neuron. Associative LTF is blocked by dn classical calpain, whereas non-associative LTF is blocked by dn small optic lobe (SOL) calpain. Interfering with a putative synaptic tag, the adaptor protein KIBRA, which protects the atypical PKM from degradation, selectively erases associative LTF. Thus, the activity of distinct PRPs and tags in a postsynaptic neuron contribute to the maintenance of different forms of synaptic plasticity at separate inputs, allowing for selective reversal of synaptic plasticity and providing a cellular basis for developing therapeutic strategies for selectively reversing maladaptive memories. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of tularemia cases focusing on the oculoglandular form.

PubMed

Eren Gok, Sebnem; Kocagul Celikbas, Aysel; Baykam, Nurcan; Atay Buyukdemirci, Ayse; Eroglu, Mustafa Necati; Evren Kemer, Ozlem; Dokuzoguz, Basak

2014-10-15

Tularemia is a zoonotic disease caused by Francisella tularensis. The oculoglandular form is one of the rarest forms. In this study, evaluated tularemia patients, focusing on the ocular form and the efficacy of early antibiotic therapy. During a tularemia outbreak, the epidemiological and clinical findings, laboratory assays, and drugs used for the treatment of 48 patients were recorded prospectively. The diagnosis of tularemia was confirmed with microagglutination test (MAT) as well as clinical findings. The mean age of the subject was 48.6 years; 23 (47.9%) of them were female. Thirty-six (81.25%) patients had clinical presentation compatible with oropharyngeal tularemia, seven (14.58%) with oculoglandular tularemia, and two (4.1%) with ulceroglandular tularemia. The most common symptoms were fever (91.6%) and sore throat (81.2%), and the most common findings were lymphadenopathy (91.6%) and tonsillopharyngitis (81.2%). In the oculoglandular form, fever, lymphadenopathy, periorbital edema, conjunctival injection, and chemosis were found. The most distinctive ophthalmic feature was follicular conjunctivitis and conjunctival epithelial defects. Forty-five cases had positive serological results with MAT. All the patients were treated with antibiotics considered effective against F. tularensis, and topical antimicrobial treatment was given to the patients with oculoglandular tularemia. Twenty-six (54.16%) patients, who were admitted within three weeks of the onset of symptoms, recovered without sequel. During tularemia outbreaks, ocular involvement should be considered carefully. The early administration of appropriate treatment will be more effective in resolving the infection and preventing complications. Along with systemic antibiotic therapy, topical treatment will help recovery.

[Update Churg-Strauss syndrome].

PubMed

Moosig, F; Hellmich, B

2012-11-01

The Churg-Strauss syndrome (CSS) is the rarest subtype of the so-called anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) and has the lowest frequency of ANCA-positivity (around 30%). In addition to asthma and blood eosinophilia, CSS is characterized by end-organ damage, which can be caused by either vasculitis and/or tissue infiltration of eosinophilic granulocytes. The CSS shares many etiological and clinical features of other hypereosinophilic syndromes. Recently, a distinct genetic background could be demonstrated for both the ANCA-positive and ANCA-negative subtypes of CSS as compared to the other two forms of AAV. Among other cytokines, interleukin-5 (IL-5) could be identified as a key mediator of eosinophilia. Therefore, recent clinical trials in CSS aimed to target IL-5. Outside of clinical trials, treatment of CSS is adapted to disease stage and activity, as recommended for other types of AAV.

Orienting hypnosis.

PubMed

Hope, Anna E; Sugarman, Laurence I

2015-01-01

This article presents a new frame for understanding hypnosis and its clinical applications. Despite great potential to transform health and care, hypnosis research and clinical integration is impaired in part by centuries of misrepresentation and ignorance about its demonstrated efficacy. The authors contend that advances in the field are primarily encumbered by the lack of distinct boundaries and definitions. Here, hypnosis, trance, and mind are all redefined and grounded in biological, neurological, and psychological phenomena. Solutions are proposed for boundary and language problems associated with hypnosis. The biological role of novelty stimulating an orienting response that, in turn, potentiates systemic plasticity forms the basis for trance. Hypnosis is merely the skill set that perpetuates and influences trance. This formulation meshes with many aspects of Milton Erickson's legacy and Ernest Rossi's recent theory of mind and health. Implications of this hypothesis for clinical skills, professional training, and research are discussed.

Advances in clinical and molecular understanding of the FMR1 premutation and fragile X-associated tremor/ataxia syndrome

PubMed Central

Hagerman, Randi; Hagerman, Paul

2014-01-01

Summary Fragile X syndrome, the leading heritable form of cognitive impairment, is caused by epigenetic silencing of the fragile X (FMR1) gene consequent to large expansions (>200 repeats) of a non-coding CGG-repeat element. Smaller, “premutation” expansions (55–200 repeats) can give rise to a family of neurodevelopmental (ADHD, autism spectrum disorder, seizure disorder) and neurodegenerative (FXTAS) clinical phenotypes through an entirely distinct molecular mechanism involving increased FMR1 mRNA production and toxicity. Basic cellular, animal, and human studies have helped to elucidate the underlying RNA toxicity mechanism, while clinical research is providing a more nuanced picture of the spectrum of clinical involvement. Whereas advances on both mechanistic and clinical fronts are driving new approaches to targeted treatment, two important issues/needs are emerging: to define the extent to which the mechanisms contributing to FXTAS also contribute to other neurodegenerative and medical disorders, and to redefine FXTAS in light of its differing presentations and associated features. PMID:23867198

Medical teachers conceptualize a distinctive form of clinical knowledge.

PubMed

Barrett, J; Yates, L; McColl, G

2015-05-01

For over four decades, there have been efforts to specify the types of knowledge that medical students need, how that knowledge is acquired and how its constituent parts are related. It is one of the areas of continuing concern underlying medical education reform. Despite their importance to medical students' learning and development, the perspectives of medical teachers in hospitals are not always considered in such discourse. This study sought to generate an understanding of these teachers' values, perspectives and approaches by listening to them and seeing them in their everyday teaching work, finding and understanding the meanings they bring to the work of medical teaching in hospitals. In interviews, all of the teachers talked more about the optimal forms of knowledge that are important for students than they talked about the form of the teaching itself. Many revealed to students what knowledge they do and do not value. They had a particular way of thinking about clinical knowledge as existing in the people and the places in which the teaching and the clinical practice happen, and represented this as 'real' knowledge. By implication, there is other knowledge in medical education or in students' heads that is not real and needs to be transformed. Their values, practices and passions add texture and vitality to existing ways of thinking about the characteristics of clinical knowledge, how it is depicted in the discourse and the curriculum and how it is more dynamically related to other knowledge than is suggested in traditional conceptualizations of knowledge relationships.

Contesting the science/ethics distinction in the review of clinical research

PubMed Central

Dawson, Angus J; Yentis, Steve M

2007-01-01

Recent policy in relation to clinical research proposals in the UK has distinguished between two types of review: scientific and ethical. This distinction has been formally enshrined in the recent changes to research ethics committee (REC) structure and operating procedures, introduced as the UK response to the EU Directive on clinical trials. Recent reviews and recommendations have confirmed the place of the distinction and the separate review processes. However, serious reservations can be mounted about the science/ethics distinction and the policy of separate review that has been built upon it. We argue here that, first, the science/ethics distinction is incoherent, and, second, that RECs should not only be permitted to consider a study's science, but that they have anobligation do so. PMID:17329389

Redescription of Hepatozoon felis (Apicomplexa: Hepatozoidae) based on phylogenetic analysis, tissue and blood form morphology, and possible transplacental transmission

PubMed Central

2013-01-01

Background A Hepatozoon parasite was initially reported from a cat in India in 1908 and named Leucocytozoon felis domestici. Although domestic feline hepatozoonosis has since been recorded from Europe, Africa, Asia and America, its description, classification and pathogenesis have remained vague and the distinction between different species of Hepatozoon infecting domestic and wild carnivores has been unclear. The aim of this study was to carry out a survey on domestic feline hepatozoonosis and characterize it morphologically and genetically. Methods Hepatozoon sp. DNA was amplified by PCR from the blood of 55 of 152 (36%) surveyed cats in Israel and from all blood samples of an additional 19 cats detected as parasitemic by microscopy during routine hematologic examinations. Hepatozoon sp. forms were also characterized from tissues of naturally infected cats. Results DNA sequencing determined that all cats were infected with Hepatozoon felis except for two infected by Hepatozoon canis. A significant association (p = 0.00001) was found between outdoor access and H. felis infection. H. felis meronts containing merozoites were characterized morphologically from skeletal muscles, myocardium and lungs of H. felis PCR-positive cat tissues and development from early to mature meront was described. Distinctly-shaped gamonts were observed and measured from the blood of these H. felis infected cats. Two fetuses from H. felis PCR-positive queens were positive by PCR from fetal tissue including the lung and amniotic fluid, suggesting possible transplacental transmission. Genetic analysis indicated that H. felis DNA sequences from Israeli cats clustered together with the H. felis Spain 1 and Spain 2 sequences. These cat H. felis sequences clustered separately from the feline H. canis sequences, which grouped with Israeli and foreign dog H. canis sequences. H. felis clustered distinctly from Hepatozoon spp. of other mammals. Feline hepatozoonosis caused by H. felis is mostly sub-clinical as a high proportion of the population is infected with no apparent overt clinical manifestations. Conclusions This study aimed to integrate new histopathologic, hematologic, clinical, epidemiological and genetic findings on feline hepatozoonosis and promote the understanding of this infection. The results indicate that feline infection is primarily caused by a morphologically and genetically distinct species, H. felis, which has predilection to infecting muscular tissues, and is highly prevalent in the cat population studied. The lack of previous comprehensively integrated data merits the redescription of this parasite elucidating its parasitological characteristics. PMID:23587213

The sleeping brain in Parkinson's disease: A focus on REM sleep behaviour disorder and related parasomnias for practicing neurologists.

PubMed

Bhidayasiri, Roongroj; Sringean, Jirada; Rattanachaisit, Watchara; Truong, Daniel D

2017-03-15

Sleep disorders are identified as common non-motor symptoms of Parkinson's disease (PD) and recently this recognition has been expanded to include parasomnias, encompassing not only REM sleep behaviour disorder (RBD), but also other non-REM forms. RBD, a prototypical parasomnia in PD, exists even in the prodromal stage of the disease, and is characterized by the presence of dream enactment behaviours occurring alongside a loss of normal skeletal muscle atonia during REM sleep. In contrast, non-REM parasomnias are more frequently observed in the late stage PD. However, the development of these disorders often overlaps and it is not uncommon for PD patients to meet the criteria for more than one type of parasomnias, thus making a clinical distinction challenging for practicing neurologists who are not sleep specialists. Indeed, clinical recognition of the predominant form of parasomnia does not just depend on video-polysomnography, but also on an individual physician's clinical acumen in delineating pertinent clinical history to determine the most likely diagnosis and proceed accordingly. In this review article, we highlight the various forms of parasomnias that have been reported in PD, including, but not limited to, RBD, with a focus on clinical symptomatology and implications for clinical practice. In addition, we review the differences in PD-related parasomnias compared to those seen in general populations. With advances in sleep research and better technology for ambulatory home monitoring, it is likely that many unanswered questions on PD-related parasomnias will soon be resolved resulting in better management of this nocturnal challenge in PD. Copyright © 2017 Elsevier B.V. All rights reserved.

Guillain-Barré Syndrome, variants & forms fruste: Reclassification with new criteria.

PubMed

Hiew, Fu Liong; Ramlan, Rahmansah; Viswanathan, Shanthi; Puvanarajah, Santhi

2017-07-01

This study aimed to evaluate the clinical and electrophysiological characteristics of various distinctive classical and localised Guillain-Barré syndrome (GBS) subtypes. Clinical characteristics and electrophysiological data of sixty-one consecutive patients admitted between 2012 and 2015 were systematically analysed and reclassified according to the new GBS clinical classification. Neurophysiology was evaluated with Hadden et al.'s vs recently proposed Rajabally et al.'s criteria. Functional severity and clinical outcome of various GBS subtypes were ascertained. All patients initially identified as GBS or related disorders can be sub-classified into having classical GBS (41, 67%), classic Miller-Fisher Syndrome (MFS) (6, 10%), Pharyngeal-cervical-brachial (PCB) (3, 5%), paraparetic GBS (4, 7%), bifacial weakness with paresthesia (3, 5%), acute ophthalmoparesis (AO) (1, 2%) and overlap syndrome (3, 5%): one (2%) with GBS/Bickerstaff brainstem encephalitis overlap and 2 (3%) with GBS/MFS overlap. Greater proportion of axonal classical GBS (67% vs 55%, p=0.372) seen with Rajabally et al.'s criteria and a predominantly axonal form of paraparetic variant (75%) independent of electrodiagnostic criteria were more representative of Asian GBS cohort. Classical GBS patients had lowest admission and discharge Medical Research Council Sum Score (MRCSS), greater functional disability and longest length of in-patient stay. Twenty (20/21, 95%) patients who needed mechanical ventilation had classical GBS. Patients required repeated dose of intravenous immunoglobulin (5/6, 3%) or plasma exchange (4/4, 100%) more frequently had axonal form of classical GBS. Phenotype recognition based on new GBS clinical classification, supported by electrodiagnostic study permits more precise clinical subtypes determination and outcome prognostication. Copyright © 2017 Elsevier B.V. All rights reserved.

Usher syndrome in four siblings from a consanguineous family of Pakistani origin.

PubMed

Trop, I; Schloss, M D; Polomeno, R; Der Kaloustian, V

1995-04-01

Usher syndrome is a heterogeneous group of disorders of autosomal recessive inheritance characterized by retinitis pigmentosa and congenital sensorineural hearing loss. Two types are accepted clinically: type I is associated with profound congenital deafness with progressive pigmentary retinopathy and total loss of vestibular function. Type II is a milder form, with moderate-to-profound hearing loss and a milder form of retinitis pigmentosa. Vestibular function is preserved. A total of five loci have been identified as accounting for the two distinct phenotypic presentations. We describe a consanguineous family of Pakistani origin whose four children all are affected with Usher syndrome type I. DNA analysis showed non-linkage to any of the loci already identified as tightly linked to the Usher syndrome type I.

Matrix Metalloproteinases and their Tissue Inhibitors in Cardiac Amyloidosis: Relationship to Structural, Functional Myocardial Changes and to Light Chain Amyloid Deposition

PubMed Central

Biolo, Andreia; Ramamurthy, Sujata; Connors, Lawreen H.; O'Hara, Carl J.; Meier-Ewert, Hans K.; Hoo, Pamela T. Soo; Sawyer, Douglas B.; Seldin, David S.; Sam, Flora

2009-01-01

Background Cardiac amyloidosis is characterized by amyloid infiltration resulting in extracellular matrix (ECM) disruption. Amyloid cardiomyopathy due to immunoglobulin light chain protein (AL-CMP) deposition, has an accelerated clinical course and a worse prognosis compared to non-light chain cardiac amyloidoses i.e., forms associated with wild-type or mutated transthyretin (TTR). We therefore tested the hypothesis that determinants of proteolytic activity of the ECM, the matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), would have distinct patterns and contribute to the pathogenesis of AL-CMP vs. TTR. Methods / Results We studied 40 patients with systemic amyloidosis: 10 AL-CMP patients, 20 patients with TTR-associated forms of cardiac amyloidosis, i.e. senile systemic amyloidois (SSA, involving wild-type TTR) or mutant TTR (ATTR), and 10 patients with AL amyloidosis without cardiac involvement. Serum MMP-2 and −9, TIMP-1, −2 and −4, brain natriuretic peptide (BNP) values and echocardiography were determined. AL-CMP and SSA-ATTR groups had similar degrees of increased left ventricular wall thickness (LVWT). However, BNP, MMP-9 and TIMP-1 levels were distinctly elevated accompanied by marked diastolic dysfunction in the AL-CMP group vs. no or minimal increases in the SSA-ATTR group. BNP, MMPs and TIMPs were not correlated with the degree of LVWT but were correlated to each other and to measures of diastolic dysfunction. Immunostaining of human endomyocardial biopsies showed diffuse expression of MMP-9 and TIMP-1 in AL-CMP and limited expression in SSA or ATTR hearts. Conclusions Despite comparable LVWT with TTR-related cardiac amyloidosis, AL-CMP patients have higher BNP, MMPs and TIMPs, which correlated with diastolic dysfunction. These findings suggest a relationship between light chains and ECM proteolytic activation that may play an important role in the functional and clinical manifestations of AL-CMP, distinct from the other non-light chain cardiac amyloidoses. PMID:19808299

Comparative genomic analysis of clinical and environmental Vibrio vulnificus isolates revealed biotype 3 evolutionary relationships.

PubMed

Koton, Yael; Gordon, Michal; Chalifa-Caspi, Vered; Bisharat, Naiel

2014-01-01

In 1996 a common-source outbreak of severe soft tissue and bloodstream infections erupted among Israeli fish farmers and fish consumers due to changes in fish marketing policies. The causative pathogen was a new strain of Vibrio vulnificus, named biotype 3, which displayed a unique biochemical and genotypic profile. Initial observations suggested that the pathogen erupted as a result of genetic recombination between two distinct populations. We applied a whole genome shotgun sequencing approach using several V. vulnificus strains from Israel in order to study the pan genome of V. vulnificus and determine the phylogenetic relationship of biotype 3 with existing populations. The core genome of V. vulnificus based on 16 draft and complete genomes consisted of 3068 genes, representing between 59 and 78% of the whole genome of 16 strains. The accessory genome varied in size from 781 to 2044 kbp. Phylogenetic analysis based on whole, core, and accessory genomes displayed similar clustering patterns with two main clusters, clinical (C) and environmental (E), all biotype 3 strains formed a distinct group within the E cluster. Annotation of accessory genomic regions found in biotype 3 strains and absent from the core genome yielded 1732 genes, of which the vast majority encoded hypothetical proteins, phage-related proteins, and mobile element proteins. A total of 1916 proteins (including 713 hypothetical proteins) were present in all human pathogenic strains (both biotype 3 and non-biotype 3) and absent from the environmental strains. Clustering analysis of the non-hypothetical proteins revealed 148 protein clusters shared by all human pathogenic strains; these included transcriptional regulators, arylsulfatases, methyl-accepting chemotaxis proteins, acetyltransferases, GGDEF family proteins, transposases, type IV secretory system (T4SS) proteins, and integrases. Our study showed that V. vulnificus biotype 3 evolved from environmental populations and formed a genetically distinct group within the E-cluster. The unique epidemiological circumstances facilitated disease outbreak and brought this genotype to the attention of the scientific community.

Infantile bilateral glaucoma in a child with ectodermal dysplasia.

PubMed

Callea, Michele; Vinciguerra, Agatino; Willoughby, Colin E; Deroma, Laura; Clarich, Gabriella

2013-01-01

Ectodermal dysplasia is a rare disease which affects at least two ectodermal-derived structures such as hair, nails, skin, sweat glands and teeth. Approximately 200 different conditions have been classified as an ectodermal dysplasia and X-linked hypohidrotic ectodermal dysplasia (XHED) represents the commonest form. Clinically, XHED is characterized by hypotrichosis, hypohidrosis and hypodontia. A variety of ocular manifestations have been reported in XHED, the most common being dryness of eyes due to tear deficiency and instability of the film secondary to the absence of meibomian gland function. Here we report a child with the distinctive clinical features of XHED confirmed with molecular diagnosis who presented with infantile bilateral glaucoma, in addition to the classical ocular involvement in XHED.

Experiences of faith group members using new reproductive and genetic technologies: A qualitative interview study.

PubMed

Scully, Jackie Leach; Banks, Sarah; Song, Robert; Haq, Jackie

2017-04-01

This paper explores the experiences of members of faith groups deciding whether or not to use new reproductive or genetic technologies (NRGTs). It is based on 16 in-depth, semi-structured interviews with people with direct experience of NRGTs. Participants identified as members of Christian or Muslim faith traditions and had been faced with deciding whether or not to make use of novel forms of fertility treatment or genetic testing. The findings show that members of faith groups may experience specific barriers of access, and distinctive ethical difficulties, when considering the use of different forms of NRGTs. Both Christian and Muslim interviewees reported difficulties in obtaining information on the official faith teaching, or found that their faith group had not yet crafted an official position. Participants' needs for information, and the opportunity to discuss the faith implications of their clinical choices, were not being met in either the clinic or the faith setting. This paper concludes that clinics should indicate more clearly their acknowledgement of patients' faith concerns. Appropriate training is needed for both healthcare professionals and chaplains, while faith groups should be encouraged to engage with healthcare providers to ensure that guidance is available to their members.

Tumor heterogeneity in small cell lung cancer defined and investigated in pre-clinical mouse models

PubMed Central

Shue, Yan Ting; Lim, Jing Shan

2018-01-01

Small cell lung carcinoma (SCLC) is a fast-growing, highly metastatic form of lung cancer. A major difference between SCLC and other forms of lung cancer is that SCLC tumors often respond well to chemotherapy initially; unfortunately, resistant tumors rapidly recur. In addition, despite a large number of clinical trials with a variety of therapeutic agents, little progress has been achieved in the past three decades in improving the survival of SCLC patients. These clinical observations indicate that SCLC tumors have a high degree of plasticity and rapid adaptability to changes in growth conditions. Here we consider recent evidence pointing to several levels of heterogeneity in SCLC that may explain the ability of these tumors to adjust to different microenvironment and therapeutics. In particular, we review new data pointing to the existence of several subpopulations of tumor cells that interact with each other to promote tumor growth. We also discuss how SCLC tumors that look similar at the histopathological level may actually represent distinct subtypes of tumors and how these differences impact the response to specific therapeutic agents. A better understanding of genetic and cellular heterogeneity will guide the development of personalized approaches to help SCLC patients. PMID:29535910

Non-invasive prenatal diagnosis using cell-free fetal DNA technology: applications and implications.

PubMed

Hall, Alison; Bostanci, A; Wright, C F

2010-01-01

Cell-free fetal DNA and RNA circulating in maternal blood can be used for the early non-invasive prenatal diagnosis (NIPD) of an increasing number of genetic conditions, both for pregnancy management and to aid reproductive decision-making. Here we present a brief review of the scientific and clinical status of the technology, and an overview of key ethical, legal and social issues raised by the analysis of cell-free fetal DNA for NIPD. We suggest that the less invasive nature of the technology brings some distinctive issues into focus, such as the possibility of broader uptake of prenatal diagnosis and access to the technology directly by the consumer via the internet, which have not been emphasised in previous work in this area. We also revisit significant issues that are familiar from previous debates about prenatal testing. Since the technology seems to transect existing distinctions between screening and diagnostic tests, there are important implications for the form and process involved in obtaining informed consent or choice. This analysis forms part of the work undertaken by a multidisciplinary group of experts which made recommendations about the implementation of this technology within the UK National Health Service. Copyright 2010 S. Karger AG, Basel.

Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy

PubMed Central

Lesage, Suzanne; Drouet, Valérie; Majounie, Elisa; Deramecourt, Vincent; Jacoupy, Maxime; Nicolas, Aude; Cormier-Dequaire, Florence; Hassoun, Sidi Mohamed; Pujol, Claire; Ciura, Sorana; Erpapazoglou, Zoi; Usenko, Tatiana; Maurage, Claude-Alain; Sahbatou, Mourad; Liebau, Stefan; Ding, Jinhui; Bilgic, Basar; Emre, Murat; Erginel-Unaltuna, Nihan; Guven, Gamze; Tison, François; Tranchant, Christine; Vidailhet, Marie; Corvol, Jean-Christophe; Krack, Paul; Leutenegger, Anne-Louise; Nalls, Michael A.; Hernandez, Dena G.; Heutink, Peter; Gibbs, J. Raphael; Hardy, John; Wood, Nicholas W.; Gasser, Thomas; Durr, Alexandra; Deleuze, Jean-François; Tazir, Meriem; Destée, Alain; Lohmann, Ebba; Kabashi, Edor; Singleton, Andrew; Corti, Olga; Brice, Alexis; Lesage, Suzanne; Tison, François; Vidailhet, Marie; Corvol, Jean-Christophe; Agid, Yves; Anheim, Mathieu; Bonnet, Anne-Marie; Borg, Michel; Broussolle, Emmanuel; Damier, Philippe; Destée, Alain; Dürr, Alexandra; Durif, Franck; Krack, Paul; Klebe, Stephan; Lohmann, Ebba; Martinez, Maria; Pollak, Pierre; Rascol, Olivier; Tranchant, Christine; Vérin, Marc; Viallet, François; Brice, Alexis; Lesage, Suzanne; Majounie, Elisa; Tison, François; Vidailhet, Marie; Corvol, Jean Christophe; Nalls, Michael A.; Hernandez, Dena G.; Gibbs, J. Raphael; Dürr, Alexandra; Arepalli, Sampath; Barker, Roger A.; Ben-Shlomo, Yoav; Berg, Daniela; Bettella, Francesco; Bhatia, Kailash; de Bie, Rob M.A.; Biffi, Alessandro; Bloem, Bastiaan R.; Bochdanovits, Zoltan; Bonin, Michael; Lesage, Suzanne; Tison, François; Vidailhet, Marie; Corvol, Jean-Christophe; Agid, Yves; Anheim, Mathieu; Bonnet, Anne-Marie; Borg, Michel; Broussolle, Emmanuel; Damier, Philippe; Destée, Alain; Dürr, Alexandra; Durif, Franck; Krack, Paul; Klebe, Stephan; Lohmann, Ebba; Martinez, Maria; Pollak, Pierre; Rascol, Olivier; Tranchant, Christine; Vérin, Marc; Bras, Jose M.; Brockmann, Kathrin; Brooks, Janet; Burn, David J.; Charlesworth, Gavin; Chen, Honglei; Chinnery, Patrick F.; Chong, Sean; Clarke, Carl E.; Cookson, Mark R.; Counsell, Carl; Damier, Philippe; Dartigues, Jean-François; Deloukas, Panos; Deuschl, Günther; Dexter, David T.; van Dijk, Karin D.; Dillman, Allissa; Dong, Jing; Durif, Frank; Edkins, Sarah; Escott-Price, Valentina; Evans, Jonathan R.; Foltynie, Thomas; Gao, Jianjun; Gardner, Michelle; Goate, Alison; Gray, Emma; Guerreiro, Rita; Harris, Clare; van Hilten, Jacobus J.; Hofman, Albert; Hollenbeck, Albert; Holmans, Peter; Holton, Janice; Hu, Michèle; Huang, Xuemei; Huber, Heiko; Hudson, Gavin; Hunt, Sarah E.; Huttenlocher, Johanna; Illig, Thomas; Jónsson, Pálmi V.; Kilarski, Laura L.; Jansen, Iris E.; Lambert, Jean-Charles; Langford, Cordelia; Lees, Andrew; Lichtner, Peter; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; Lubbe, Steven; Lungu, Codrin; Martinez, María; Mätzler, Walter; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morrison, Karen E.; Mudanohwo, Ese; O’Sullivan, Sean S.; Owen, Michael J.; Pearson, Justin; Perlmutter, Joel S.; Pétursson, Hjörvar; Plagnol, Vincent; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Saad, Mohamad; Simón-Sánchez, Javier; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Schulte, Claudia; Sharma, Manu; Shaw, Karen; Sheerin, Una-Marie; Shoulson, Ira; Shulman, Joshua; Sidransky, Ellen; Spencer, Chris C.A.; Stefánsson, Hreinn; Stefánsson, Kári; Stockton, Joanna D.; Strange, Amy; Talbot, Kevin; Tanner, Carlie M.; Tashakkori-Ghanbaria, Avazeh; Trabzuni, Daniah; Traynor, Bryan J.; Uitterlinden, André G.; Velseboer, Daan; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams-Gray, Caroline H.; Winder-Rhodes, Sophie; Wurster, Isabel; Williams, Nigel; Morris, Huw R.; Heutink, Peter; Hardy, John; Wood, Nicholas W.; Gasser, Thomas; Singleton, Andrew B.; Brice, Alexis

2016-01-01

Autosomal-recessive early-onset parkinsonism is clinically and genetically heterogeneous. The genetic causes of approximately 50% of autosomal-recessive early-onset forms of Parkinson disease (PD) remain to be elucidated. Homozygozity mapping and exome sequencing in 62 isolated individuals with early-onset parkinsonism and confirmed consanguinity followed by data mining in the exomes of 1,348 PD-affected individuals identified, in three isolated subjects, homozygous or compound heterozygous truncating mutations in vacuolar protein sorting 13C (VPS13C). VPS13C mutations are associated with a distinct form of early-onset parkinsonism characterized by rapid and severe disease progression and early cognitive decline; the pathological features were striking and reminiscent of diffuse Lewy body disease. In cell models, VPS13C partly localized to the outer membrane of mitochondria. Silencing of VPS13C was associated with lower mitochondrial membrane potential, mitochondrial fragmentation, increased respiration rates, exacerbated PINK1/Parkin-dependent mitophagy, and transcriptional upregulation of PARK2 in response to mitochondrial damage. This work suggests that loss of function of VPS13C is a cause of autosomal-recessive early-onset parkinsonism with a distinctive phenotype of rapid and severe progression. PMID:26942284

Mutation in WDR4 impairs tRNA m(7)G46 methylation and causes a distinct form of microcephalic primordial dwarfism.

PubMed

Shaheen, Ranad; Abdel-Salam, Ghada M H; Guy, Michael P; Alomar, Rana; Abdel-Hamid, Mohamed S; Afifi, Hanan H; Ismail, Samira I; Emam, Bayoumi A; Phizicky, Eric M; Alkuraya, Fowzan S

2015-09-28

Primordial dwarfism is a state of extreme prenatal and postnatal growth deficiency, and is characterized by marked clinical and genetic heterogeneity. Two presumably unrelated consanguineous families presented with an apparently novel form of primordial dwarfism in which severe growth deficiency is accompanied by distinct facial dysmorphism, brain malformation (microcephaly, agenesis of corpus callosum, and simplified gyration), and severe encephalopathy with seizures. Combined autozygome/exome analysis revealed a novel missense mutation in WDR4 as the likely causal variant. WDR4 is the human ortholog of the yeast Trm82, an essential component of the Trm8/Trm82 holoenzyme that effects a highly conserved and specific (m(7)G46) methylation of tRNA. The human mutation and the corresponding yeast mutation result in a significant reduction of m(7)G46 methylation of specific tRNA species, which provides a potential mechanism for primordial dwarfism associated with this lesion, since reduced m(7)G46 modification causes a growth deficiency phenotype in yeast. Our study expands the number of biological pathways underlying primordial dwarfism and adds to a growing list of human diseases linked to abnormal tRNA modification.

SEMANTIC DEMENTIA AND PERSISTING WERNICKE’S APHASIA: LINGUISTIC AND ANATOMICAL PROFILES

PubMed Central

Ogar, JM; Baldo, JV; Wilson, SM; Brambati, SM; Miller, BL; Dronkers, NF; Gorno-Tempini, ML

2011-01-01

Few studies have directly compared the clinical and anatomical characteristics of patients with progressive aphasia to those of patients with aphasia caused by stroke. In the current study we examined fluent forms of aphasia in these two groups, specifically the semantic dementia (SD) and persisting Wernicke's aphasia (WA) due to stroke. We compared 10 patients with SD to 10 age- and education-matched patients with WA in three language domains: language comprehension (single words and sentences), spontaneous speech and visual semantics. Neuroanatomical involvement was analyzed using disease-specific image analysis techniques: voxel-based morphometry (VBM) for patients with SD and overlays of lesion masks in patients with WA. Patients with SD and WA were both impaired on tasks that involved visual semantics, but patients with SD were less impaired in spontaneous speech and sentence comprehension. The anatomical findings showed that different regions were most affected in the two disorders: the left anterior temporal lobe in SD and the left posterior middle temporal gyrus in chronic WA. This study highlights that the two syndromes classically associated with language comprehension deficits in aphasia due to stroke and neurodegenerative disease are clinically distinct, most likely due to distinct distributions of damage in the temporal lobe. PMID:21315437

Distinct bone marrow blood vessels differentially regulate haematopoiesis.

PubMed

Itkin, Tomer; Gur-Cohen, Shiri; Spencer, Joel A; Schajnovitz, Amir; Ramasamy, Saravana K; Kusumbe, Anjali P; Ledergor, Guy; Jung, Yookyung; Milo, Idan; Poulos, Michael G; Kalinkovich, Alexander; Ludin, Aya; Kollet, Orit; Shakhar, Guy; Butler, Jason M; Rafii, Shahin; Adams, Ralf H; Scadden, David T; Lin, Charles P; Lapidot, Tsvee

2016-04-21

Bone marrow endothelial cells (BMECs) form a network of blood vessels that regulate both leukocyte trafficking and haematopoietic stem and progenitor cell (HSPC) maintenance. However, it is not clear how BMECs balance these dual roles, and whether these events occur at the same vascular site. We found that mammalian bone marrow stem cell maintenance and leukocyte trafficking are regulated by distinct blood vessel types with different permeability properties. Less permeable arterial blood vessels maintain haematopoietic stem cells in a low reactive oxygen species (ROS) state, whereas the more permeable sinusoids promote HSPC activation and are the exclusive site for immature and mature leukocyte trafficking to and from the bone marrow. A functional consequence of high permeability of blood vessels is that exposure to blood plasma increases bone marrow HSPC ROS levels, augmenting their migration and differentiation, while compromising their long-term repopulation and survival. These findings may have relevance for clinical haematopoietic stem cell transplantation and mobilization protocols.

Sm-p80-Based Schistosomiasis Vaccine: Preparation for Human Clinical Trials.

PubMed

Siddiqui, Afzal A; Siddiqui, Sabrina Z

2017-03-01

Mass antiparasitic drug administration programs and other control strategies have made important contributions in reducing the global prevalence of helminths. Schistosomiasis, however, continues to spread to new geographic areas. The advent of a viable vaccine and its deployment, coupled with existing control efforts, is expected to make significant headway towards sustained schistosomiasis control. In 2016, Science ranked the schistosomiasis vaccine as one of the top 10 vaccines that needs to be urgently developed. A vaccine that is effective against geographically distinct forms of intestinal/hepatic and urinary disease is essential to make a meaningful impact in global reduction of the disease burden. In this opinion article, we focus on salient features of schistosomiasis vaccines in different phases of the clinical development pipeline and highlight the Sm-p80-based vaccine which is now being prepared for human clinical trials. Copyright © 2016 Elsevier Ltd. All rights reserved.

Somatic copy number alterations in gastric adenocarcinomas among Asian and Western patients

PubMed Central

Corso, Giovanni; Ryu, Min-Hee; Kang, Yoon-Koo; Roviello, Franco; Saksena, Gordon; Peng, Shouyong; Shivdasani, Ramesh A.; Bass, Adam J.; Beroukhim, Rameen

2017-01-01

Gastric cancer, a leading worldwide cause of cancer mortality, shows high geographic and ethnic variation in incidence rates, which are highest in East Asia. The anatomic locations and clinical behavior also differ by geography, leading to the controversial idea that Eastern and Western forms of the disease are distinct. In view of these differences, we investigated whether gastric cancers from Eastern and Western patients show distinct genomic profiles. We used high-density profiling of somatic copy-number aberrations to analyze the largest collection to date of gastric adenocarcinomas and utilized genotyping data to rigorously annotate ethnic status. The size of this collection allowed us to accurately identify regions of significant copy-number alteration and separately to evaluate tumors arising in Eastern and Western patients. Among molecular subtypes classified by The Cancer Genome Atlas, the frequency of gastric cancers showing chromosomal instability was modestly higher in Western patients. After accounting for this difference, however, gastric cancers arising in Easterners and Westerners have highly similar somatic copy-number patterns. Only one genomic event, focal deletion of the phosphatase gene PTPRD, was significantly enriched in Western cases, though also detected in Eastern cases. Thus, despite the different risk factors and clinical features, gastric cancer appears to be a fundamentally similar disease in both populations and the divergent clinical outcomes cannot be ascribed to different underlying structural somatic genetic aberrations. PMID:28426752

Interobserver agreement on Poser's and the new McDonald's diagnostic criteria for multiple sclerosis.

PubMed

Zipoli, V; Portaccio, E; Siracusa, G; Pracucci, G; Sorbi, S; Amato, M P

2003-10-01

We assessed the interobserver agreement on the diagnosis of multiple sclerosis (MS) in a study sample consisting of 41 MS (15 relapsing remitting, two secondary progressive, five primary progressive and 19 presenting their first clinical attack) and three non-MS cases. Clinical and paraclinical information was recorded in standardized forms. Four neurologists were asked to make a diagnosis using Poser's and McDonald's criteria and to assess MRI scans according to the McDonald's guidelines. In terms of the kappa statistic (kappa), we found a moderate agreement on the overall diagnosis using both Poser's and McDonald's criteria (kappa, respectively 0.57 and 0.52). As for distinct diagnostic categories, we observed a moderate to substantial agreement for the three McDonald categories (range of kappa values 0.49-0.64) and a fair to substantial agreement for the nine Poser categories (range of kappa values 0.37-0.67). Taking into account clinical information, the agreement on dissemination over time was substantially higher (kappa = 0.69) than that found on dissemination over space (kappa = 0.46). In contrast, for MRI assessment, the agreement for spatial dissemination was substantial (kappa = 0.74) compared with the fair agreement (kappa = 0.25) yielded by dissemination over time. The new McDonald's criteria yield a good overall diagnostic reliability, and compare favourably with Poser's classification in terms of agreement on distinct diagnostic categories.

Discrete forms of amylose are synthesized by isoforms of GBSSI in pea.

PubMed

Edwards, Anne; Vincken, Jean-Paul; Suurs, Luc C J M; Visser, Richard G F; Zeeman, Sam; Smith, Alison; Martin, Cathie

2002-08-01

Amyloses with distinct molecular masses are found in the starch of pea embryos compared with the starch of pea leaves. In pea embryos, a granule-bound starch synthase protein (GBSSIa) is required for the synthesis of a significant portion of the amylose. However, this protein seems to be insignificant in the synthesis of amylose in pea leaves. cDNA clones encoding a second isoform of GBSSI, GBSSIb, have been isolated from pea leaves. Comparison of GBSSIa and GBSSIb activities shows them to have distinct properties. These differences have been confirmed by the expression of GBSSIa and GBSSIb in the amylose-free mutant of potato. GBSSIa and GBSSIb make distinct forms of amylose that differ in their molecular mass. These differences in product specificity, coupled with differences in the tissues in which GBSSIa and GBSSIb are most active, explain the distinct forms of amylose found in different tissues of pea. The shorter form of amylose formed by GBSSIa confers less susceptibility to the retrogradation of starch pastes than the amylose formed by GBSSIb. The product specificity of GBSSIa could provide beneficial attributes to starches for food and nonfood uses.

Discrete Forms of Amylose Are Synthesized by Isoforms of GBSSI in PeaW⃞

PubMed Central

Edwards, Anne; Vincken, Jean-Paul; Suurs, Luc C. J. M.; Visser, Richard G. F.; Zeeman, Sam; Smith, Alison; Martin, Cathie

2002-01-01

Amyloses with distinct molecular masses are found in the starch of pea embryos compared with the starch of pea leaves. In pea embryos, a granule-bound starch synthase protein (GBSSIa) is required for the synthesis of a significant portion of the amylose. However, this protein seems to be insignificant in the synthesis of amylose in pea leaves. cDNA clones encoding a second isoform of GBSSI, GBSSIb, have been isolated from pea leaves. Comparison of GBSSIa and GBSSIb activities shows them to have distinct properties. These differences have been confirmed by the expression of GBSSIa and GBSSIb in the amylose-free mutant of potato. GBSSIa and GBSSIb make distinct forms of amylose that differ in their molecular mass. These differences in product specificity, coupled with differences in the tissues in which GBSSIa and GBSSIb are most active, explain the distinct forms of amylose found in different tissues of pea. The shorter form of amylose formed by GBSSIa confers less susceptibility to the retrogradation of starch pastes than the amylose formed by GBSSIb. The product specificity of GBSSIa could provide beneficial attributes to starches for food and nonfood uses. PMID:12172021

Connecting drug delivery reality to smart materials design.

PubMed

Grainger, David W

2013-09-15

Inflated claims to both design and mechanistic novelty in drug delivery and imaging systems, including most nanotechnologies, are not supported by the generally poor translation of these systems to clinical efficacy. The "form begets function" design paradigm is seductive but perhaps over-simplistic in translation to pharmaceutical efficacy. Most innovations show few clinically important distinctions in their therapeutic benefits in relevant preclinical disease and delivery models, despite frequent claims to the contrary. Long-standing challenges in drug delivery issues must enlist more realistic, back-to-basics approaches to address fundamental materials properties in complex biological systems, preclinical test beds, and analytical methods to more reliably determine fundamental pharmaceutical figures of merit, including drug carrier purity and batch-batch variability, agent biodistribution, therapeutic index (safety), and efficacy. Copyright © 2013 Elsevier B.V. All rights reserved.

Teaching pediatric communication skills to medical students.

PubMed

Frost, Katherine A; Metcalf, Elizabeth P; Brooks, Rachel; Kinnersley, Paul; Greenwood, Stephen R; Powell, Colin Ve

2015-01-01

Delivering effective clinical pediatric communication skills training to undergraduate medical students is a distinct and important challenge. Pediatric-specific communication skills teaching is complex and under-researched. We report on the development of a scenario-based pediatric clinical communication skills program as well as students' assessment of this module. We designed a pediatric clinical communication skills program and delivered it five times during one academic year via small-group teaching. Students were asked to score the workshop in eight domains (learning objectives, complexity, interest, competencies, confidence, tutors, feedback, and discussion) using 5-point Likert scales, along with free text comments that were grouped and analyzed thematically, identifying both the strengths of the workshop and changes suggested to improve future delivery. Two hundred and twenty-one of 275 (80%) student feedback forms were returned. Ninety-six percent of students' comments were positive or very positive, highlighting themes such as the timing of teaching, relevance, group sizes, and the use of actors, tutors, and clinical scenarios. Scenario-based teaching of clinical communication skills is positively received by students. Studies need to demonstrate an impact on practice, performance, development, and sustainability of communications training.

[Cyclothymic obsessive-compulsive disorder. Clinical characteristics of a neglected and under-recognized entity].

PubMed

Hantouche, E G; Demonfaucon, C; Angst, J; Perugi, G; Allilaire, J F; Akiskal, H S

2002-04-13

Clinical research is largely focused on depressive comorbidity in obsessional compulsive disorder (OCD). However some recent publications have suggested that bipolar comorbidity occurs in authentic OCD and its presence has a differential impact on the clinical picture and course of OCD. Recent data from the collaborative survey conducted with AFTOC (French Association of patients suffering from OCD) have revealed a high rate of bipolar comorbidity in OCD: 30% for hypomania and 50% for cyclothymia. The present paper presents further comparative analyses between OCD with (n = 302) versus without cyclothymia (n = 272). The sub-group "Cyclothymic OCD" is characterized by a different clinical picture (higher frequency of aggressive, impulsive, religious and sexual obsessions, and compulsions of control, hoarding, repetition), episodic course, higher rate of major depressive episodes (with more intensity and recurrence) associated with higher rates of suicide attempts and psychiatric admissions, and less favorable response to anti-OCD treatments. These data suggested that cyclothymic OCD could represent a specific distinct variant form of OCD. More vigilance is needed toward this entity which is largely under-recognized in clinical practice.

Clinical validity of prototype personality disorder ratings in adolescents.

PubMed

Defife, Jared A; Haggerty, Greg; Smith, Scott W; Betancourt, Luis; Ahmed, Zain; Ditkowsky, Keith

2015-01-01

A growing body of research shows that personality pathology in adolescents is clinically distinctive and frequently stable into adulthood. A reliable and useful method for rating personality pathology in adolescent patients has the potential to enhance conceptualization, dissemination, and treatment effectiveness. The aim of this study is to examine the clinical validity of a prototype matching approach (derived from the Shedler Westen Assessment Procedure-Adolescent Version) for quantifying personality pathology in an adolescent inpatient sample. Sixty-six adolescent inpatients and their parents or legal guardians completed forms of the Child Behavior Checklist (CBCL) assessing emotional and behavioral problems. Clinical criterion variables including suicide history, substance use, and fights with peers were also assessed. Patients' individual and group therapists on the inpatient unit completed personality prototype ratings. Prototype diagnoses demonstrated substantial reliability (median intraclass correlation coefficient =.75) across independent ratings from individual and group therapists. Personality prototype ratings correlated with the CBCL scales and clinical criterion variables in anticipated and meaningful ways. As seen in prior research with adult samples, prototype personality ratings show clinical validity across independent clinician raters previously unfamiliar with the approach, and they are meaningfully related to clinical symptoms, behavioral problems, and adaptive functioning.

Clinical Validity of Prototype Personality Disorder Ratings in Adolescents

PubMed Central

DeFife, Jared A.; Haggerty, Greg; Smith, Scott W.; Betancourt, Luis; Ahmed, Zain; Ditkowsky, Keith

2015-01-01

A growing body of research shows that personality pathology in adolescents is clinically distinctive and frequently stable into adulthood. A reliable and useful method for rating personality pathology in adolescent patients has the potential to enhance conceptualization, dissemination, and treatment effectiveness. The aim of this study is to examine the clinical validity of a prototype matching approach (derived from the Shedler Westen Assessment Procedure – Adolescent Version) for quantifying personality pathology in an adolescent inpatient sample. Sixty-six adolescent inpatients and their parents or legal guardians completed forms of the Child Behavior Checklist (CBCL) assessing emotional and behavioral problems. Clinical criterion variables including suicide history, substance use, and fights with peers were also assessed. Patients’ individual and group therapists on the inpatient unit completed personality prototype ratings. Prototype diagnoses demonstrated substantial reliability (median ICC = .75) across independent ratings from individual and group therapists. Personality prototype ratings correlated with the CBCL scales and clinical criterion variables in anticipated and meaningful ways. As seen in prior research with adult samples, prototype personality ratings show clinical validity across independent clinician raters previously unfamiliar with the approach, and they are meaningfully related to clinical symptoms, behavioral problems, and adaptive functioning. PMID:25457971

Glial tumors with neuronal differentiation.

PubMed

Park, Chul-Kee; Phi, Ji Hoon; Park, Sung-Hye

2015-01-01

Immunohistochemical studies for neuronal differentiation in glial tumors revealed subsets of tumors having both characteristics of glial and neuronal lineages. Glial tumors with neuronal differentiation can be observed with diverse phenotypes and histologic grades. The rosette-forming glioneuronal tumor of the fourth ventricle and papillary glioneuronal tumor have been newly classified as distinct disease entities. There are other candidates for classification, such as the glioneuronal tumor without pseudopapillary architecture, glioneuronal tumor with neuropil-like islands, and the malignant glioneuronal tumor. The clinical significance of these previously unclassified tumors should be confirmed. Copyright © 2015 Elsevier Inc. All rights reserved.

On the Distinction between Regular and Irregular Inflectional Morphology: Evidence from Dinka

ERIC Educational Resources Information Center

Ladd, D. Robert; Remijsen, Bert; Manyang, Caguor Adong

2009-01-01

Discussions of the psycholinguistic significance of regularity in inflectional morphology generally deal with languages in which regular forms can be clearly identified and revolve around whether there are distinct processing mechanisms for regular and irregular forms. We present a detailed description of Dinka's notoriously irregular noun number…

[The usefulness of routine laboratory tests in the evaluation of sudden threat of pregnant woman and fetus in pre-eclampsia].

PubMed

Malarewicz, Andrzej; Gruszka, Olga; Szymkiewicz, Jadwiga; Rogala, Jerzy

2006-04-01

The fact that the progress of pre-eclampsia is highly unpredictable is the reason to run necessary monitoring, among others, by means of laboratory tests. Their aim is to determine explicitly if the pregnancy can be continued and terminated naturally or should be terminated by pre-term induced delivery or Caesarean section. There is a wide range of laboratory investigations recommended in pregnancy complicated by pre-eclampsia. The results reported in the literature though are controversial and inexplicit. The purpose of the research was to verify routine lab tests results used in decision making for emergency termination of pregnancy as a result of increased threatening clinical symptoms and to evaluate their usefulness in decision making to start delivery. The investigation covered 152 women who were divided into three groups. One consisted of 62 pregnant women with light form of pre-eclampsia, the other of 24 pregnant women with severe form of pre-eclampsia. The control group consisted of 66 healthy pregnant women. All pregnant women with pre-eclampsia diagnosed delivered by Caesarean section. The decision to perform the operation was based on biophysical findings of the fetus. At the moment of decision-making, blood was drawn for laboratory testing of the following parameters: systemic blood, coagulation parameters, total protein and protein fractios, non-protein nitrogen blood components, glucose, electrolytes, indicating enzymes and excretory enzymes of protein metabolism, lipid fractions. Routine lab tests performed in pre-eclampsia do not indicate distinct abnormalities the moment fetus life threatening clinical symptoms occur that enforce the decision of immediate delivery, the exception are the indicating enzymes. Acute clinical symptoms that endanger fetus life in pre-eclampsia correlate with distinct activity of AspAT, AIAT and LDH. Laboratory tests are of no prognostic value in the prediction of sudden worsening of the fetus condition in pre-eclampsia.

Cyclothymic OCD: a distinct form?

PubMed

Hantouche, E G; Angst, J; Demonfaucon, C; Perugi, G; Lancrenon, S; Akiskal, H S

2003-06-01

Clinical research on the comorbidity of obsessive compulsive disorder (OCD) and other anxiety disorders has largely focused on depression. However in practice, resistant or severe OCD patients not infrequently suffer from a masked or hidden comorbid bipolar disorder. The rate of bipolar comorbidity in OCD was systematically explored among 453 members of the French Association of patients suffering from OCD (AFTOC) as well as a psychiatric sample of OCD out-patients (n=175). As previous research by us has shown the epidemiologic and clinical sample to be similar, we combined them in the present analyses (n=628). To assess mood disorder comorbidity, we used structured self-rated questionnaires for major depression, hypomania and mania (DSM-IV criteria), self-rated Angst's checklist of Hypomania and that for the Cyclothymic Temperament (French version developed by Akiskal and Hantouche). According to DSM-IV definitions of hypomania/mania, 11% of the total combined sample was classified as bipolar (3% BP-I and 8% BP-II). When dimensionally rated, 30% obtained a cut-off score >/=10 on the Hypomania checklist and 50% were classified as cyclothymic. Comparative analyses were conducted between OCD with (n=302) versus without cyclothymia (n=272). In contrast to non-cyclothymics, the cyclothymic OCD patients were characterized by more severe OCD syndromes (higher frequencies of aggressive, impulsive, religious and sexual obsessions, compulsions of control, hoarding, repetition); more episodic course; greater rates of manic/hypomanic and major depressive episodes (with higher intensity and recurrence) associated with higher rates of suicide attempts and psychiatric admissions; and finally, a less favorable response to anti-OCD antidepressants and elevated rate of mood switching with aggressive behavior. Hypomania and cyclothymia were not confirmed by diagnostic interview by a clinician. Our data extend previous research on "OCD-bipolar comorbidity" as a highly prevalent and largely under-recognized and untreated class of OCD patients. Furthermore, our data suggest that "cyclothymic OCD" could represent a distinct form of OCD. More attention should be paid to it in research and clinical practice.

Uncovering the hidden risk architecture of the schizophrenias: confirmation in three independent genome-wide association studies.

PubMed

Arnedo, Javier; Svrakic, Dragan M; Del Val, Coral; Romero-Zaliz, Rocío; Hernández-Cuervo, Helena; Fanous, Ayman H; Pato, Michele T; Pato, Carlos N; de Erausquin, Gabriel A; Cloninger, C Robert; Zwir, Igor

2015-02-01

The authors sought to demonstrate that schizophrenia is a heterogeneous group of heritable disorders caused by different genotypic networks that cause distinct clinical syndromes. In a large genome-wide association study of cases with schizophrenia and controls, the authors first identified sets of interacting single-nucleotide polymorphisms (SNPs) that cluster within particular individuals (SNP sets) regardless of clinical status. Second, they examined the risk of schizophrenia for each SNP set and tested replicability in two independent samples. Third, they identified genotypic networks composed of SNP sets sharing SNPs or subjects. Fourth, they identified sets of distinct clinical features that cluster in particular cases (phenotypic sets or clinical syndromes) without regard for their genetic background. Fifth, they tested whether SNP sets were associated with distinct phenotypic sets in a replicable manner across the three studies. The authors identified 42 SNP sets associated with a 70% or greater risk of schizophrenia, and confirmed 34 (81%) or more with similar high risk of schizophrenia in two independent samples. Seventeen networks of SNP sets did not share any SNP or subject. These disjoint genotypic networks were associated with distinct gene products and clinical syndromes (i.e., the schizophrenias) varying in symptoms and severity. Associations between genotypic networks and clinical syndromes were complex, showing multifinality and equifinality. The interactive networks explained the risk of schizophrenia more than the average effects of all SNPs (24%). Schizophrenia is a group of heritable disorders caused by a moderate number of separate genotypic networks associated with several distinct clinical syndromes.

[Molecular basis of Rett syndrome: A current look].

PubMed

Pantaleón F, Gretta; Juvier R, Tamara

2015-01-01

Rett syndrome (RS) is a neurodevelopmental disorder that exclusively affects girls, and occurs along with autism. It is very uncommon, and has five distinct forms, one classic and the others atypical, which generally compromise manual skills, language, and mobility, and widely associated with the appearance of stereotypy and early epilepsy. With the aim of updating the information about RS, a search was performed in the computer data bases of PubMed, Hinari, SCIELO and Medline, as well as consulting other web sites including OMIM, ORPHANET, GeneMap, Genetests, Proteins and Gene, using the descriptors "Síndrome de Rett", "genes y Síndrome de Rett", "Rett Syndrome gene", "Rett Syndrome", "Rett Syndrome gene therapy", and "Rett Syndrome review". Of the 1,348 articles found, 42 articles were selected, which reported 3 genes causing the syndrome: MECP2, CDKL5 and FOXG. The MECP2 gene is mutated in 80% of patients with classic RS, as well as in 40% of those affected by any of its atypical forms. RS with early epilepsy and the congenital variant are mainly due to variations in the CDKL5 and FOXG1 genes, respectively. The diagnosis of RS is based on clinical criteria. However, the advances in molecular biology and genetics have opened a wide range of possibilities for diagnosing the different clinical forms that could not be classified before. Molecular analysis can help confirm the clinical criteria and provided information as regards the prognosis of the patient. Copyright © 2015. Publicado por Elsevier España, S.L.U.

Case reports of juvenile GM1 gangliosidosisis type II caused by mutation in GLB1 gene.

PubMed

Karimzadeh, Parvaneh; Naderi, Samaneh; Modarresi, Farzaneh; Dastsooz, Hassan; Nemati, Hamid; Farokhashtiani, Tayebeh; Shamsian, Bibi Shahin; Inaloo, Soroor; Faghihi, Mohammad Ali

2017-07-17

Type II or juvenile GM1-gangliosidosis is an autosomal recessive lysosomal storage disorder, which is clinically distinct from infantile form of the disease by the lack of characteristic cherry-red spot and hepatosplenomegaly. The disease is characterized by slowly progressive neurodegeneration and mild skeletal changes. Due to the later age of onset and uncharacteristic presentation, diagnosis is frequently puzzled with other ataxic and purely neurological disorders. Up to now, 3-4 types of GM1-gangliosidosis have been reported and among them type I is the most common phenotype with the age of onset around 6 months. Various forms of GM1-gangliosidosis are caused by GLB1 gene mutations but severity of the disease and age of onset are directly related to the position and the nature of deleterious mutations. However, due to its unique genetic cause and overlapping clinical features, some researchers believe that GM1 gangliosidosis represents an overlapped disease spectrum instead of four distinct types. Here, we report a less frequent type of autosomal recessive GM1 gangliosidosis with perplexing clinical presentation in three families in the southwest part of Iran, who are unrelated but all from "Lurs" ethnic background. To identify disease-causing mutations, Whole Exome Sequencing (WES) utilizing next generation sequencing was performed. Four patients from three families were investigated with the age of onset around 3 years old. Clinical presentations were ataxia, gate disturbances and dystonia leading to wheelchair-dependent disability, regression of intellectual abilities, and general developmental regression. They all were born in consanguineous families with no previous documented similar disease in their parents. A homozygote missense mutation in GLB1 gene (c. 601 G > A, p.R201C) was found in all patients. Using Sanger sequencing this identified mutation was confirmed in the proband, their parents, grandparents, and extended family members, confirming its autosomal recessive pattern of inheritance. Our study identified a rare pathogenic missense mutation in GLB1 gene in patients with complex neurodevelopmental findings, which can extend the list of differential diagnoses for childhood ataxia in Iranian patients.

[Expression of c-kit in North African nasopharyngeal carcinomas: correlation with age and LMP1].

PubMed

Charfi, S; Khabir, A; Ayadi, L; Mseddi, M; Makni, H; Gorbel, A; Daoud, J; Frikha, M; Jlidi, R; Busson, P; Boudawara, T S

2007-09-01

To determine the level and prognostic significance of c-kit expression in the two age groups of North African nasopharyngeal carcinomas. A retrospective study of 99 NPC specimens from Tunisian patients was investigated by immunohistochemistry. Immunohistochemical data were correlated with Epstein-Barr virus LMP1 expression and pathological, clinical and survival parameters. c-kit was detected in 79% of the cases for patients under 30 years of age (juvenile form) but in only 56% of specimens in patients over 30 years (P=0.039) and was significantly over-expressed for patients with lymph node involvement (P=0.015). LMP1 score was 5.78 (+/-1.84) for c-kit negative tumors compared to 8,23 (+/-2.39) for c-kit positive tumors (P=0.002). Multivariate analysis including age, lymph nodes involvement and LMP1 expression as co-variables, showed that only age (P=0.027) and LMP1 expression (P=0.005) were significantly correlated to the c-kit expression. c-kit is highly expressed in the juvenile form of North African nasopharyngeal carcinomas. There is a significant association between LMP1 and c-kit expression. The contrasted levels of C-kit expression in the two age groups strengthen the hypothesis that these clinical forms result from distinct oncogenic mechanisms.

Clinical, biochemical and molecular aspects of cerebellar ataxia and Coenzyme Q10 deficiency.

PubMed

Montero, Raquel; Pineda, Mercé; Aracil, Asun; Vilaseca, Maria-Antonia; Briones, Paz; Sánchez-Alcázar, José-Antonio; Navas, Plácido; Artuch, Rafael

2007-01-01

Coenzyme Q(10) (CoQ) deficiency is an autosomal recessive disorder presenting five phenotypes: a myopathic form, a severe infantile neurological syndrome associated with nephritic syndrome, an ataxic variant, Leigh syndrome and a pure myopathic form. The third is the most common phenotype related with CoQ deficiency and it will be the focus of this review. This new syndrome presents muscle CoQ deficiency associated with cerebellar ataxia and cerebellar atrophy as the main neurological signs. Biochemically, the hallmark of CoQ deficiency syndrome is a decreased CoQ concentration in muscle and/or fibroblasts. There is no molecular evidence of the enzyme or gene involved in primary CoQ deficiencies associated with cerebellar ataxia, although recently a family has been reported with mutations at COQ2 gene who present a distinct phenotype. Patients with primary CoQ deficiency may benefit from CoQ supplementation, although the clinical response to this therapy varies even among patients with similar phenotypes. Some present an excellent response to CoQ while others show only a partial improvement of some symptoms and signs. CoQ deficiency is the mitochondrial encephalomyopathy with the best clinical response to CoQ supplementation, highlighting the importance of an early identification of this disorder.

Independent but coordinated trials: insights from the practice-based Opportunities for Weight Reduction Trials Collaborative Research Group.

PubMed

Yeh, Hsin-Chieh; Clark, Jeanne M; Emmons, Karen E; Moore, Reneé H; Bennett, Gary G; Warner, Erica T; Sarwer, David B; Jerome, Gerald J; Miller, Edgar R; Volger, Sheri; Louis, Thomas A; Wells, Barbara; Wadden, Thomas A; Colditz, Graham A; Appel, Lawrence J

2010-08-01

The National Heart, Lung, and Blood Institute (NHLBI) funded three institutions to conduct effectiveness trials of weight loss interventions in primary care settings. Unlike traditional multi-center clinical trials, each study was established as an independent trial with a distinct protocol. Still, efforts were made to coordinate and standardize several aspects of the trials. The three trials formed a collaborative group, the 'Practice-based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group.' We describe the common and distinct features of the three trials, the key characteristics of the collaborative group, and the lessons learned from this novel organizational approach. The Collaborative Research Group consists of three individual studies: 'Be Fit, Be Well' (Washington University in St. Louis/Harvard University), 'POWER Hopkins' (Johns Hopkins), and 'POWER-UP' (University of Pennsylvania). There are a total of 15 participating clinics with ~1100 participants. The common primary outcome is change in weight at 24 months of follow-up, but each protocol has trial-specific elements including different interventions and different secondary outcomes. A Resource Coordinating Unit at Johns Hopkins provides administrative support. The Collaborative Research Group established common components to facilitate potential cross-site comparisons. The main advantage of this approach is to develop and evaluate several interventions, when there is insufficient evidence to test one or two approaches, as would be done in a traditional multi-center trial. The challenges of the organizational design include the complex decision-making process, the extent of potential data pooling, time intensive efforts to standardize reports, and the additional responsibilities of the DSMB to monitor three distinct protocols.

Measuring up to speech intelligibility.

PubMed

Miller, Nick

2013-01-01

Improvement or maintenance of speech intelligibility is a central aim in a whole range of conditions in speech-language therapy, both developmental and acquired. Best clinical practice and pursuance of the evidence base for interventions would suggest measurement of intelligibility forms a vital role in clinical decision-making and monitoring. However, what should be measured to gauge intelligibility and how this is achieved and relates to clinical planning continues to be a topic of debate. This review considers the strengths and weaknesses of selected clinical approaches to intelligibility assessment, stressing the importance of explanatory, diagnostic testing as both a more sensitive and a clinically informative method. The worth of this, and any approach, is predicated, though, on awareness and control of key design, elicitation, transcription and listening/listener variables to maximize validity and reliability of assessments. These are discussed. A distinction is drawn between signal-dependent and -independent factors in intelligibility evaluation. Discussion broaches how these different perspectives might be reconciled to deliver comprehensive insights into intelligibility levels and their clinical/educational significance. The paper ends with a call for wider implementation of best practice around intelligibility assessment. © 2013 Royal College of Speech and Language Therapists.

Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy.

PubMed

Lesage, Suzanne; Drouet, Valérie; Majounie, Elisa; Deramecourt, Vincent; Jacoupy, Maxime; Nicolas, Aude; Cormier-Dequaire, Florence; Hassoun, Sidi Mohamed; Pujol, Claire; Ciura, Sorana; Erpapazoglou, Zoi; Usenko, Tatiana; Maurage, Claude-Alain; Sahbatou, Mourad; Liebau, Stefan; Ding, Jinhui; Bilgic, Basar; Emre, Murat; Erginel-Unaltuna, Nihan; Guven, Gamze; Tison, François; Tranchant, Christine; Vidailhet, Marie; Corvol, Jean-Christophe; Krack, Paul; Leutenegger, Anne-Louise; Nalls, Michael A; Hernandez, Dena G; Heutink, Peter; Gibbs, J Raphael; Hardy, John; Wood, Nicholas W; Gasser, Thomas; Durr, Alexandra; Deleuze, Jean-François; Tazir, Meriem; Destée, Alain; Lohmann, Ebba; Kabashi, Edor; Singleton, Andrew; Corti, Olga; Brice, Alexis

2016-03-03

Autosomal-recessive early-onset parkinsonism is clinically and genetically heterogeneous. The genetic causes of approximately 50% of autosomal-recessive early-onset forms of Parkinson disease (PD) remain to be elucidated. Homozygozity mapping and exome sequencing in 62 isolated individuals with early-onset parkinsonism and confirmed consanguinity followed by data mining in the exomes of 1,348 PD-affected individuals identified, in three isolated subjects, homozygous or compound heterozygous truncating mutations in vacuolar protein sorting 13C (VPS13C). VPS13C mutations are associated with a distinct form of early-onset parkinsonism characterized by rapid and severe disease progression and early cognitive decline; the pathological features were striking and reminiscent of diffuse Lewy body disease. In cell models, VPS13C partly localized to the outer membrane of mitochondria. Silencing of VPS13C was associated with lower mitochondrial membrane potential, mitochondrial fragmentation, increased respiration rates, exacerbated PINK1/Parkin-dependent mitophagy, and transcriptional upregulation of PARK2 in response to mitochondrial damage. This work suggests that loss of function of VPS13C is a cause of autosomal-recessive early-onset parkinsonism with a distinctive phenotype of rapid and severe progression. Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Neurobiology of Alzheimer’s Disease: Integrated Molecular, Physiological, Anatomical, Biomarker, and Cognitive Dimensions

PubMed Central

Raskin, Joel; Cummings, Jeffrey; Hardy, John; Schuh, Kory; Dean, Robert A.

2015-01-01

Background: Alzheimer’s disease (AD), the most common form of dementia, is a progressive neurodegenerative disorder with interrelated molecular, physiological, anatomical, biomarker, and cognitive dimensions. Methods: This article reviews the biological changes (genetic, molecular, and cellular) underlying AD and their correlation with the clinical syndrome. Results: Dementia associated with AD is related to the aberrant production, processing, and clearance of beta-amyloid and tau. Beta-amyloid deposition in brain follows a distinct spatial progression starting in the basal neocortex, spreading throughout the hippocampus, and eventually spreading to the rest of the cortex. The spread of tau pathology through neural networks leads to a distinct and consistent spatial progression of neurofibrillary tangles, beginning in the transentorhinal and hippocampal region and spreading superolaterally to the primary areas of the neocortex. Synaptic dysfunction and cell death is shown by progressive loss of cerebral metabolic rate for glucose and progressive brain atrophy. Decreases in synapse number in the dentate gyrus of the hippocampus correlate with declining cognitive function. Amyloid changes are detectable in cerebrospinal fluid and with amyloid imaging up to 20 years prior to the onset of symptoms. Structural atrophy may be detectable via magnetic resonance imaging up to 10 years before clinical signs appear. Conclusion: This review highlights the progression of biological changes underlying AD and their association with the clinical syndrome. Many changes occur before overt symptoms are evident and biomarkers provide a means to detect AD pathology even in patients without symptoms. PMID:26412218

[Myotonic dystrophy - a new insight into a well-known disease].

PubMed

Lusakowska, Anna; Sułek-Piatkowska, Anna

2010-01-01

Myotonic dystrophy (DM), the most common dystrophy in adults, is an autosomal dominant disease characterized by a variety of multisystemic features. Two genetically distinct forms of DM are identified - type 1 (DM1), the classic form first described by Steinert, and type 2 (DM2), identified by Ricker. DM1 is caused by trinucleotide expansion of CTG in the myotonic dystrophy protein kinase gene, whereas in DM2 the expansion of tetranucleotide repeats (CCTG) in the zinc finger protein 9 gene was identified. Both mutations are dynamic and are located in non-coding parts of the genes. Phenotype variability of DM1 and DM2 is caused by a molecular mechanism due to mutated RNA toxicity. This paper reviews the clinical features of both types of myotonic dystrophies and summarizes current views on pathogenesis of myotonic dystrophy.

Temporal Resolution of Autophosphorylation for Normal and Oncogenic Forms of EGFR and Differential Effects of Gefitinib†

PubMed Central

Kim, Youngjoo; Li, Zhimin; Apetri, Mihaela; Luo, BeiBei; Settleman, Jeffrey E.; Anderson, Karen S.

2012-01-01

Epidermal growth factor receptor (EGFR) is a member of the ErbB family of receptor tyrosine kinases (RTK). EGFR overexpression or mutation in many different forms of cancers has highlighted its role as an important therapeutic target. Gefitinib, the first small molecule inhibitor of EGFR kinase function to be approved for the treatment of non-small cell lung cancer (NSCLC) by the FDA, demonstrates clinical activity primarily in patients with tumors that harbor somatic kinase domain mutations in EGFR. Here, we compare wild-type EGFR autophosphorylation kinetics to the L834R (also called L858R) EGFR form, one of the most common mutations in lung cancer patients. Using rapid chemical quench, time resolved electrospray mass spectrometry (ESI-MS) and western blot analyses, we examined the order of autophosphorylation in wild-type (WT) and L834R EGFR and the effect of gefitinib (Iressa ™) on the phosphorylation of individual tyrosines. These studies establish that there is a temporal order of autophosphorylation of key tyrosines involved in downstream signaling for WT EGFR and a loss of order for the oncogenic L834R mutant. These studies also reveal unique signature patterns of drug sensitivity for inhibition of tyrosine autophosphorylation by gefitinib; distinct for WT and oncogenic L834R mutant forms of EGFR. Fluorescence studies show that for WT EGFR, the binding affinity for gefitinib is weaker for the phosphorylated protein while for the oncogenic mutant, L834R EGFR, the binding affinity of gefitinib is substantially enhanced and likely contributes to the efficacy observed clinically. This mechanistic information is important in understanding the molecular details underpinning clinical observations as well as to aid in the design of more potent and selective EGFR inhibitors. PMID:22657099

Cluster analysis of autoantibodies in 852 patients with systemic lupus erythematosus from a single center.

PubMed

Artim-Esen, Bahar; Çene, Erhan; Şahinkaya, Yasemin; Ertan, Semra; Pehlivan, Özlem; Kamali, Sevil; Gül, Ahmet; Öcal, Lale; Aral, Orhan; Inanç, Murat

2014-07-01

Associations between autoantibodies and clinical features have been described in systemic lupus erythematosus (SLE). Herein, we aimed to define autoantibody clusters and their clinical correlations in a large cohort of patients with SLE. We analyzed 852 patients with SLE who attended our clinic. Seven autoantibodies were selected for cluster analysis: anti-DNA, anti-Sm, anti-RNP, anticardiolipin (aCL) immunoglobulin (Ig)G or IgM, lupus anticoagulant (LAC), anti-Ro, and anti-La. Two-step clustering and Kaplan-Meier survival analyses were used. Five clusters were identified. A cluster consisted of patients with only anti-dsDNA antibodies, a cluster of anti-Sm and anti-RNP, a cluster of aCL IgG/M and LAC, and a cluster of anti-Ro and anti-La antibodies. Analysis revealed 1 more cluster that consisted of patients who did not belong to any of the clusters formed by antibodies chosen for cluster analysis. Sm/RNP cluster had significantly higher incidence of pulmonary hypertension and Raynaud phenomenon. DsDNA cluster had the highest incidence of renal involvement. In the aCL/LAC cluster, there were significantly more patients with neuropsychiatric involvement, antiphospholipid syndrome, autoimmune hemolytic anemia, and thrombocytopenia. According to the Systemic Lupus International Collaborating Clinics damage index, the highest frequency of damage was in the aCL/LAC cluster. Comparison of 10 and 20 years survival showed reduced survival in the aCL/LAC cluster. This study supports the existence of autoantibody clusters with distinct clinical features in SLE and shows that forming clinical subsets according to autoantibody clusters may be useful in predicting the outcome of the disease. Autoantibody clusters in SLE may exhibit differences according to the clinical setting or population.

Identification and Characterization of Unique Subgroups of Chronic Pain Individuals with Dispositional Personality Traits.

PubMed

Mehta, S; Rice, D; McIntyre, A; Getty, H; Speechley, M; Sequeira, K; Shapiro, A P; Morley-Forster, P; Teasell, R W

2016-01-01

Objective. The current study attempted to identify and characterize distinct CP subgroups based on their level of dispositional personality traits. The secondary objective was to compare the difference among the subgroups in mood, coping, and disability. Methods. Individuals with chronic pain were assessed for demographic, psychosocial, and personality measures. A two-step cluster analysis was conducted in order to identify distinct subgroups of patients based on their level of personality traits. Differences in clinical outcomes were compared using the multivariate analysis of variance based on cluster membership. Results. In 229 participants, three clusters were formed. No significant difference was seen among the clusters on patient demographic factors including age, sex, relationship status, duration of pain, and pain intensity. Those with high levels of dispositional personality traits had greater levels of mood impairment compared to the other two groups (p < 0.05). Significant difference in disability was seen between the subgroups. Conclusions. The study identified a high risk group of CP individuals whose level of personality traits significantly correlated with impaired mood and coping. Use of pharmacological treatment alone may not be successful in improving clinical outcomes among these individuals. Instead, a more comprehensive treatment involving psychological treatments may be important in managing the personality traits that interfere with recovery.

Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition.

PubMed

Wibowo, Ardian S; Singh, Mirage; Reeder, Kristen M; Carter, Joshua J; Kovach, Alexander R; Meng, Wuyi; Ratnam, Manohar; Zhang, Faming; Dann, Charles E

2013-09-17

Antifolates, folate analogs that inhibit vitamin B9 (folic acid)-using cellular enzymes, have been used over several decades for the treatment of cancer and inflammatory diseases. Cellular uptake of the antifolates in clinical use occurs primarily via widely expressed facilitative membrane transporters. More recently, human folate receptors (FRs), high affinity receptors that transport folate via endocytosis, have been proposed as targets for the specific delivery of new classes of antifolates or folate conjugates to tumors or sites of inflammation. The development of specific, FR-targeted antifolates would be accelerated if additional biophysical data, particularly structural models of the receptors, were available. Here we describe six distinct crystallographic models that provide insight into biological trafficking of FRs and distinct binding modes of folate and antifolates to these receptors. From comparison of the structures, we delineate discrete structural conformations representative of key stages in the endocytic trafficking of FRs and propose models for pH-dependent conformational changes. Additionally, we describe the molecular details of human FR in complex with three clinically prevalent antifolates, pemetrexed (also Alimta), aminopterin, and methotrexate. On the whole, our data form the basis for rapid design and implementation of unique, FR-targeted, folate-based drugs for the treatment of cancer and inflammatory diseases.

Semantic dementia and persisting Wernicke's aphasia: linguistic and anatomical profiles.

PubMed

Ogar, J M; Baldo, J V; Wilson, S M; Brambati, S M; Miller, B L; Dronkers, N F; Gorno-Tempini, M L

2011-04-01

Few studies have directly compared the clinical and anatomical characteristics of patients with progressive aphasia to those of patients with aphasia caused by stroke. In the current study we examined fluent forms of aphasia in these two groups, specifically semantic dementia (SD) and persisting Wernicke's aphasia (WA) due to stroke. We compared 10 patients with SD to 10 age- and education-matched patients with WA in three language domains: language comprehension (single words and sentences), spontaneous speech and visual semantics. Neuroanatomical involvement was analyzed using disease-specific image analysis techniques: voxel-based morphometry (VBM) for patients with SD and overlays of lesion digitized lesion reconstructions in patients with WA. Patients with SD and WA were both impaired on tasks that involved visual semantics, but patients with SD were less impaired in spontaneous speech and sentence comprehension. The anatomical findings showed that different regions were most affected in the two disorders: the left anterior temporal lobe in SD and the left posterior middle temporal gyrus in chronic WA. This study highlights that the two syndromes classically associated with language comprehension deficits in aphasia due to stroke and neurodegenerative disease are clinically distinct, most likely due to distinct distributions of damage in the temporal lobe. Copyright © 2010 Elsevier Inc. All rights reserved.

Ever-present threats from information technology: the Cyber-Paranoia and Fear Scale

PubMed Central

Mason, Oliver J.; Stevenson, Caroline; Freedman, Fleur

2014-01-01

Delusions involving technology, and specifically the internet, are increasingly common, and fear-reality statistics suggest computer-related fears are very widespread. These fears form a continuum from the widely understandable and realistic to the unrealistic, and frankly paranoid. The present study investigated the validity of this construct in a non-clinical population by constructing a novel self-report measure. The new Cyber-Paranoia and Fear Scale aims to measure the perception of information technology-related threats originating from or enabled by computers, smartphones, social networks, and digital surveillance. Psychometric properties of the new Cyber-Paranoia and Fear Scale are reported alongside an established measure of suspiciousness and paranoia in 181 participants including a sub-group of fifty information technology professionals. Exploratory factor analysis suggested the presence of two, related, dimensions that we term cyber-paranoia and cyber-fear. Both sub-scales were internally consistent and produced a normal distribution of scores. The relationships of the sub-scales with age, gender, trait paranoia, digital literacy, and digital inclusion are supportive of construct validity. The distinctiveness of ‘cyber-paranoia’ from general trait paranoia appears to mirror the clinical distinctiveness of ‘internet’ and other technology-fuelled delusions. Knowledge provision to increase technological proficiency and awareness may bring about a reduction in cyber-paranoia. PMID:25505431

Ever-present threats from information technology: the Cyber-Paranoia and Fear Scale.

PubMed

Mason, Oliver J; Stevenson, Caroline; Freedman, Fleur

2014-01-01

Delusions involving technology, and specifically the internet, are increasingly common, and fear-reality statistics suggest computer-related fears are very widespread. These fears form a continuum from the widely understandable and realistic to the unrealistic, and frankly paranoid. The present study investigated the validity of this construct in a non-clinical population by constructing a novel self-report measure. The new Cyber-Paranoia and Fear Scale aims to measure the perception of information technology-related threats originating from or enabled by computers, smartphones, social networks, and digital surveillance. Psychometric properties of the new Cyber-Paranoia and Fear Scale are reported alongside an established measure of suspiciousness and paranoia in 181 participants including a sub-group of fifty information technology professionals. Exploratory factor analysis suggested the presence of two, related, dimensions that we term cyber-paranoia and cyber-fear. Both sub-scales were internally consistent and produced a normal distribution of scores. The relationships of the sub-scales with age, gender, trait paranoia, digital literacy, and digital inclusion are supportive of construct validity. The distinctiveness of 'cyber-paranoia' from general trait paranoia appears to mirror the clinical distinctiveness of 'internet' and other technology-fuelled delusions. Knowledge provision to increase technological proficiency and awareness may bring about a reduction in cyber-paranoia.

Advances in combination therapy of lung cancer: Rationales, delivery technologies and dosage regimens.

PubMed

Wu, Lan; Leng, Donglei; Cun, Dongmei; Foged, Camilla; Yang, Mingshi

2017-08-28

Lung cancer is a complex disease caused by a multitude of genetic and environmental factors. The progression of lung cancer involves dynamic changes in the genome and a complex network of interactions between cancer cells with multiple, distinct cell types that form tumors. Combination therapy using different pharmaceuticals has been proven highly effective due to the ability to affect multiple cellular pathways involved in the disease progression. However, the currently used drug combination designs are primarily based on empirical clinical studies, and little attention has been given to dosage regimens, i.e. how administration routes, onsets, and durations of the combinations influence the therapeutic outcome. This is partly because combination therapy is challenged by distinct physicochemical properties and in vivo pharmacokinetics/pharmacodynamics of the individual pharmaceuticals, including small molecule drugs and biopharmaceuticals, which make the optimization of dosing and administration schedule challenging. This article reviews the recent advances in the design and development of combinations of pharmaceuticals for the treatment of lung cancer. Focus is primarily on rationales for the selection of specific combination therapies for lung cancer treatment, and state of the art of delivery technologies and dosage regimens for the combinations, tested in preclinical and clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular characterization and virus neutralization patterns of severe, non-epizootic forms of feline calicivirus infections resembling virulent systemic disease in cats in Switzerland and in Liechtenstein.

PubMed

Willi, Barbara; Spiri, Andrea M; Meli, Marina L; Samman, Ayman; Hoffmann, Karolin; Sydler, Titus; Cattori, Valentino; Graf, Felix; Diserens, Kevin A; Padrutt, Isabelle; Nesina, Stefanie; Berger, Alice; Ruetten, Maja; Riond, Barbara; Hosie, Margaret J; Hofmann-Lehmann, Regina

2016-01-15

Feline calicivirus (FCV) infections are associated with oral ulceration, chronic stomatitis and a limping syndrome. Epizootic outbreaks of virulent systemic disease (VSD) have been reported in the USA and Europe. Here, the molecular characterization and neutralization patterns of FCV isolates from cases of severe, non-epizootic infection associated with skin ulceration and edema are presented. Samples from eleven symptomatic cats, four in-contact cats and 27 cats with no contact with symptomatic cats were collected and tested for FCV, feline herpesvirus-1 (FHV-1), feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV). Phylogenetic analyses based on the capsid (VP1) gene of FCV and virus neutralization with antisera raised against four FCV vaccine strains were performed. Nine kittens and two adult cats in two shelters and two veterinary clinics in four geographically distinct locations in Switzerland and Liechtenstein were affected. The cats showed fever, tongue and skin ulceration, head and paw edema, and occasionally jaundice, generalized edema and dyspnea. All symptomatic cats tested FCV-positive but were negative for FHV-1, FeLV and FIV, with the exception of one FIV-positive kitten. All kittens of one litter and both adult cats died. The disease did not spread to cats in the environment. Cats in the environment displayed phylogenetically distinct, but related, FCV strains. Virus neutralization patterns suggested that some cases might have been potentially prevented by vaccination with the optimal vaccine strain. In conclusion, clinicians should be aware of severe, non-epizootic forms of FCV infections with initial clinical presentations similar to VSD. Copyright © 2015 Elsevier B.V. All rights reserved.

Health, well-being, and psychopathology in a clinical population: Structure and discriminant validity of Mental Health Continuum Short Form (MHC-SF).

PubMed

van Erp Taalman Kip, Rogier M; Hutschemaekers, Giel J M

2018-03-30

The literature suggests a distinction between illness (negative health) and the ability to cope with challenges such as illness (positive health). The two continua model of mental health distinguishes psychiatric symptoms (illness) from well-being (positive health). Well-being consists of hedonic, eudaimonic, and social well-being, constituting one factor that is moderately correlated with psychopathology in the general population. In a mental health care population, we examined whether the three dimensions of well-being are distinguishable and whether well-being is also moderately correlated with symptoms. A representative sample of 1,069 patients (63% female, 47% male; mean age: 42 years) voluntarily completed the Mental Health Continuum-Short Form (MHC-SF), a 14-item test that assesses three components of well-being. Confirmatory factor analysis revealed a model with strong correlations between the three subscales of the MHC-SF, indicating poor discriminant validity. Furthermore, the MHC-SF was strongly correlated (r = -.71) with the symptomatic distress scale of the OQ-45. Exploratory factor analysis permitted a two-factor solution, providing support for the two continua model of mental health. However, the explained variance of the second factor (well-being) was meager in comparison with the first factor (psychopathology). The results of a canonic correlation did not confirm the two continua model, and only a model with one common canonical factor was significant. For patients with clinical levels of psychopathology, the level of well-being and psychopathology correlate much higher than in the general population. Well-being and psychopathology are so entwined that the supposed distinction should be seriously questioned. © 2018 Wiley Periodicals, Inc.

Temporal dynamics and longitudinal co-occurrence of depression and different anxiety syndromes in youth: Evidence for reciprocal patterns in a 3-year prospective study.

PubMed

Long, Erin E; Young, Jami F; Hankin, Benjamin L

2018-07-01

Depression is highly comorbid with anxiety in youth. It is frequently reported that anxiety precedes depression; however, evidence surrounding the temporal precedence of anxiety over depression is mixed. Many studies of anxiety-depression co-occurrence lump distinct forms of anxiety, obscuring information regarding trajectories of specific anxiety syndromes. This study sought to more accurately describe the development of anxiety and depression over time by moving beyond the question of temporal precedence to investigate a developmentally dynamic model of anxiety-depression co-occurrence. A community sample of 665 youth (M= 11.8, SD= 2.4; 55% female) completed repeated self-report measures of depression and anxiety (social, physical, and separation anxiety) over a 3-year longitudinal study. Prospective associations between distinct syndromes of anxiety with depression were analyzed using an autoregressive cross-lagged path model over four time points. Physical symptoms and depression symptoms reciprocally predicted each other, above and beyond the stability of either domain. Social anxiety and depression symptoms similarly predicted each other in a systematic pattern. Our study is limited in its generalizability to other forms of anxiety, like worry. Additional research is needed to determine whether similar patterns exist in clinical populations, and whether these processes maintain symptoms once they reach diagnostic levels. The development of syndromes of depression, physical, and social anxiety during childhood and adolescence occurs in a predictable, systematic reciprocal pattern, rather than sequentially and unidirectionally (i.e., anxiety syndromes precede depression). Results are clinically useful for predicting risk for disorder, and demonstrate the necessity of tracking symptom levels across domains. Copyright © 2018 Elsevier B.V. All rights reserved.

Estrogen receptors in gastric cancer: Advances and perspectives.

PubMed

Ur Rahman, Muhammad Saif; Cao, Jiang

2016-02-28

Worldwide, gastric cancer is one of the most common malignancies with high mortality. Various aspects of the development and progression of gastric cancer continue to be extensively investigated in order to further our understanding and provide more effective means for the prevention, diagnosis, and treatment of the disease. Estrogen receptors (ERs) are steroid hormone receptors that regulate cellular activities in many physiological and pathological processes in different tissues. There are two distinct forms of ERs, namely ERα and ERβ, with several alternative-splicing isoforms for each. They show distinct tissue distribution patterns and exert different biological functions. Dysregulation of ERs has been found to be associated closely with many diseases, including cancer. A number of studies have been conducted to investigate the role of ERs in gastric cancer, the possible mechanisms underlying these roles, and the clinical relevance of deregulated ERs in gastric cancer patients. To date, inconsistent associations of different ERs with gastric cancer have been reported. These inconsistencies may be caused by variations in in vitro cell models and clinical samples, including assay conditions and protocols with regard to different forms of ERs. Given the potential of the deregulated ERs as diagnostic/prognostic markers or therapeutic targets for gastric cancer, it will be important to identify/confirm the association of each ER isoform with gastric cancer, to determine the specific roles and interactions that these individual ER isoforms play under specific conditions in the development and/or progression of gastric cancer, and to elucidate precisely these mechanisms. In this review, we summarize the achievements from early ER studies in gastric cancer to the most up-to-date discoveries, with an effort to provide a comprehensive understanding of the role of ERs roles in gastric cancer and its possible mechanisms. Furthermore, we propose directions for future investigations.

Genetic Susceptibility to Chagas Disease: An Overview about the Infection and about the Association between Disease and the Immune Response Genes

PubMed Central

Ayo, Christiane Maria; Dalalio, Márcia Machado de Oliveira; Visentainer, Jeane Eliete Laguila; Reis, Pâmela Guimarães; Jarduli, Luciana Ribeiro; Alves, Hugo Vicentin; Sell, Ana Maria

2013-01-01

Chagas disease, which is caused by the flagellate parasite Trypanosoma cruzi, affects 8–10 million people in Latin America. The disease is endemic and is characterised by acute and chronic phases that develop in the indeterminate, cardiac, and/or gastrointestinal forms. The immune response during human T. cruzi infection is not completely understood, despite its role in driving the development of distinct clinical manifestations of chronic infection. Polymorphisms in genes involved in the innate and specific immune response are being widely studied in order to clarify their possible role in the occurrence or severity of disease. Here we review the role of classic and nonclassic MHC, KIR, and cytokine host genetic factors on the infection by T. cruzi and the clinical course of Chagas disease. PMID:24069594

Divergence of macrophage phagocytic and antimicrobial programs in leprosy.

PubMed

Montoya, Dennis; Cruz, Daniel; Teles, Rosane M B; Lee, Delphine J; Ochoa, Maria Teresa; Krutzik, Stephan R; Chun, Rene; Schenk, Mirjam; Zhang, Xiaoran; Ferguson, Benjamin G; Burdick, Anne E; Sarno, Euzenir N; Rea, Thomas H; Hewison, Martin; Adams, John S; Cheng, Genhong; Modlin, Robert L

2009-10-22

Effective innate immunity against many microbial pathogens requires macrophage programs that upregulate phagocytosis and direct antimicrobial pathways, two functions generally assumed to be coordinately regulated. We investigated the regulation of these key functions in human blood-derived macrophages. Interleukin-10 (IL-10) induced the phagocytic pathway, including the C-type lectin CD209 and scavenger receptors, resulting in phagocytosis of mycobacteria and oxidized low-density lipoprotein. IL-15 induced the vitamin D-dependent antimicrobial pathway and CD209, yet the cells were less phagocytic. The differential regulation of macrophage functional programs was confirmed by analysis of leprosy lesions: the macrophage phagocytosis pathway was prominent in the clinically progressive, multibacillary form of the disease, whereas the vitamin D-dependent antimicrobial pathway predominated in the self-limited form and in patients undergoing reversal reactions from the multibacillary to the self-limited form. These data indicate that macrophage programs for phagocytosis and antimicrobial responses are distinct and differentially regulated in innate immunity to bacterial infections.

Distinctive fungal and bacterial communities are associated with mats formed by ectomycorrhizal fungi

Treesearch

Laurel A. Kluber; Jane E. Smith; David D. Myrold

2011-01-01

The distinct rhizomorphic mats formed by ectomycorrhizal Piloderma fungi are common features of the organic soil horizons of coniferous forests of the Pacific Northwest. These mats have been found to cover 25-40% of the forest floor in some Douglas-fir stands, and are associated with physical and biochemical properties that distinguish them from...

Activity-Dependent Inhibitory Gating in Molecular Signaling Cascades Induces a Novel Form of Intermediate-Term Synaptic Facilitation in "Aplysia Californica"

ERIC Educational Resources Information Center

Fischbach, Soren; Kopec, Ashley M.; Carew, Thomas J.

2014-01-01

Mechanistically distinct forms of long-lasting plasticity and memory can be induced by a variety of different training patterns. Although several studies have identified distinct molecular pathways that are engaged during these different training patterns, relatively little work has explored potential interactions between pathways when they are…

A Guideline of Selecting and Reporting Intraclass Correlation Coefficients for Reliability Research.

PubMed

Koo, Terry K; Li, Mae Y

2016-06-01

Intraclass correlation coefficient (ICC) is a widely used reliability index in test-retest, intrarater, and interrater reliability analyses. This article introduces the basic concept of ICC in the content of reliability analysis. There are 10 forms of ICCs. Because each form involves distinct assumptions in their calculation and will lead to different interpretations, researchers should explicitly specify the ICC form they used in their calculation. A thorough review of the research design is needed in selecting the appropriate form of ICC to evaluate reliability. The best practice of reporting ICC should include software information, "model," "type," and "definition" selections. When coming across an article that includes ICC, readers should first check whether information about the ICC form has been reported and if an appropriate ICC form was used. Based on the 95% confident interval of the ICC estimate, values less than 0.5, between 0.5 and 0.75, between 0.75 and 0.9, and greater than 0.90 are indicative of poor, moderate, good, and excellent reliability, respectively. This article provides a practical guideline for clinical researchers to choose the correct form of ICC and suggests the best practice of reporting ICC parameters in scientific publications. This article also gives readers an appreciation for what to look for when coming across ICC while reading an article.

Allergic contact dermatitis from color film developers: clinical and histologic features.

PubMed

Brancaccio, R R; Cockerell, C J; Belsito, D; Ostreicher, R

1993-05-01

We evaluated two patients with allergic contact dermatitis that resulted from exposure to color film developers. A lichenoid eruption developed in one patient, whereas an eruption more characteristic of an acute spongiotic dermatitis developed in the second patient. Histologic findings in the first case were those of a "lichenoid dermatitis" but with features distinct from classic lichen planus. The biopsy specimens from the second patient showed a subacute spongiotic process with a bandlike infiltrate suggestive of an evolving lichenoid process. Contact allergy to color developers may result in eruptions similar to lichen planus. This process appears to evolve from an acute spongiotic dermatitis in its early phase to a lichenoid dermatitis in fully developed and more chronic forms. Although the histologic features are those of a "lichenoid" dermatitis, some features, such as the presence of spongiosis, eosinophils, and a less intense inflammatory infiltrate, may enable distinction between lichenoid allergic contact dermatitis and true lichen planus. In addition, clinicopathologic correlation with patch test results should permit accurate diagnosis in most cases.

Isolation and characterization of a novel herpesvirus from a free-ranging eastern grey kangaroo (Macropus giganteus).

PubMed

Vaz, Paola Karinna; Motha, Julian; McCowan, Christina; Ficorilli, Nino; Whiteley, Pam Lizette; Wilks, Colin Reginald; Hartley, Carol Anne; Gilkerson, James Rudkin; Browning, Glenn Francis; Devlin, Joanne Maree

2013-01-01

We isolated a macropodid herpesvirus from a free-ranging eastern grey kangaroo (Macropus giganteous) displaying clinical signs of respiratory disease and possibly neurologic disease. Sequence analysis of the herpesvirus glycoprotein G (gG) and glycoprotein B (gB) genes revealed that the virus was an alphaherpesvirus most closely related to macropodid herpesvirus 2 (MaHV-2) with 82.7% gG and 94.6% gB amino acid sequence identity. Serologic analyses showed similar cross-neutralization patterns to those of MaHV-2. The two viruses had different growth characteristics in cell culture. Most notably, this virus formed significantly larger plaques and extensive syncytia when compared with MaHV-2. No syncytia were observed for MaHV-2. Restriction endonuclease analysis of whole viral genomes demonstrated distinct restriction endonuclease cleavage patterns for all three macropodid herpesviruses. These studies suggest that a distinct macropodid alphaherpesvirus may be capable of infecting and causing disease in eastern grey kangaroos.

Surface modification of nanoparticles enables selective evasion of phagocytic clearance by distinct macrophage phenotypes

NASA Astrophysics Data System (ADS)

Qie, Yaqing; Yuan, Hengfeng; von Roemeling, Christina A.; Chen, Yuanxin; Liu, Xiujie; Shih, Kevin D.; Knight, Joshua A.; Tun, Han W.; Wharen, Robert E.; Jiang, Wen; Kim, Betty Y. S.

2016-05-01

Nanomedicine is a burgeoning industry but an understanding of the interaction of nanomaterials with the immune system is critical for clinical translation. Macrophages play a fundamental role in the immune system by engulfing foreign particulates such as nanoparticles. When activated, macrophages form distinct phenotypic populations with unique immune functions, however the mechanism by which these polarized macrophages react to nanoparticles is unclear. Furthermore, strategies to selectively evade activated macrophage subpopulations are lacking. Here we demonstrate that stimulated macrophages possess higher phagocytic activities and that classically activated (M1) macrophages exhibit greater phagocytic capacity than alternatively activated (M2) macrophages. We show that modification of nanoparticles with polyethylene-glycol results in decreased clearance by all macrophage phenotypes, but importantly, coating nanoparticles with CD47 preferentially lowers phagocytic activity by the M1 phenotype. These results suggest that bio-inspired nanoparticle surface design may enable evasion of specific components of the immune system and provide a rational approach for developing immune tolerant nanomedicines.

Structure and function of complex brain networks

PubMed Central

Sporns, Olaf

2013-01-01

An increasing number of theoretical and empirical studies approach the function of the human brain from a network perspective. The analysis of brain networks is made feasible by the development of new imaging acquisition methods as well as new tools from graph theory and dynamical systems. This review surveys some of these methodological advances and summarizes recent findings on the architecture of structural and functional brain networks. Studies of the structural connectome reveal several modules or network communities that are interlinked by hub regions mediating communication processes between modules. Recent network analyses have shown that network hubs form a densely linked collective called a “rich club,” centrally positioned for attracting and dispersing signal traffic. In parallel, recordings of resting and task-evoked neural activity have revealed distinct resting-state networks that contribute to functions in distinct cognitive domains. Network methods are increasingly applied in a clinical context, and their promise for elucidating neural substrates of brain and mental disorders is discussed. PMID:24174898

Chlamydia trachomatis from Australian Aboriginal people with trachoma are polyphyletic composed of multiple distinctive lineages

PubMed Central

Andersson, Patiyan; Harris, Simon R.; Smith, Helena M. B. Seth; Hadfield, James; O'Neill, Colette; Cutcliffe, Lesley T.; Douglas, Fiona P.; Asche, L. Valerie; Mathews, John D.; Hutton, Susan I.; Sarovich, Derek S.; Tong, Steven Y. C.; Clarke, Ian N.; Thomson, Nicholas R.; Giffard, Philip M.

2016-01-01

Chlamydia trachomatis causes sexually transmitted infections and the blinding disease trachoma. Current data on C. trachomatis phylogeny show that there is only a single trachoma-causing clade, which is distinct from the lineages causing urogenital tract (UGT) and lymphogranuloma venerum diseases. Here we report the whole-genome sequences of ocular C. trachomatis isolates obtained from young children with clinical signs of trachoma in a trachoma endemic region of northern Australia. The isolates form two lineages that fall outside the classical trachoma lineage, instead being placed within UGT clades of the C. trachomatis phylogenetic tree. The Australian trachoma isolates appear to be recombinants with UGT C. trachomatis genome backbones, in which loci that encode immunodominant surface proteins (ompA and pmpEFGH) have been replaced by those characteristic of classical ocular isolates. This suggests that ocular tropism and association with trachoma are functionally associated with some sequence variants of ompA and pmpEFGH. PMID:26912299

Acquired bilateral telangiectatic macules: a distinct clinical entity.

PubMed

Park, Ji-Hye; Lee, Dong Jun; Lee, Yoo-Jung; Jang, Yong Hyun; Kang, Hee Young; Kim, You Chan

2014-09-01

We evaluated 13 distinct patients with multiple telangiectatic pigmented macules confined mostly to the upper arms to determine if the clinical and histopathological features of these cases might represent a specific clinical entity. We retrospectively investigated the clinical, histopathologic, and immunohistochemical features of 13 patients with multiple telangiectatic pigmented macules on the upper arms who presented between January 2003 and December 2012. Epidermal pigmentation, melanogenic activity, melanocyte number, vascularity, epidermal thickness, and perivascular mast cell number of the specimens were evaluated. Clinically, the condition favored middle-aged men. On histopathologic examination, the lesional skin showed capillary proliferation and telangiectasia in the upper dermis. Histochemical and immunohistochemical analysis revealed basal hyperpigmentation and increased melanogenic activity in the lesional skin (P < .05). No significant difference in epidermal thickness or mast cell number was observed between the normal perilesional skin and the lesional skin. The clinical and histopathologic features of these lesions were relatively consistent in all patients. In addition, the features are quite distinct from other diseases. Based on clinical and histologic features, we suggest the name acquired bilateral telangiectatic macules for this new entity.

Boundary matters: clinical leadership and the distinctive disciplinary contribution of nursing to multidisciplinary care.

PubMed

McNamara, Martin S; Fealy, Gerard M; Casey, Mary; Geraghty, Ruth; Johnson, Maree; Halligan, Phil; Treacy, Pearl; Butler, Michelle

2011-12-01

To describe Irish nurses' views of clinical leadership and to describe their clinical leadership development needs. Nurses are often unclear about the precise nature of clinical leadership and its impact on the processes and outcomes of care and little is known about their self-perceived clinical leadership development needs. Seventeen focus group interviews were conducted with a purposive sample of 144 nurses from 13 practice settings. A conceptual lens was provided by the work of Bernstein and Young who emphasise the epistemological, practical and relational significance of boundaries and how they relate in fundamental ways to professionals' sense of their distinctive disciplinary identities and membership of specialised communities of practice. Focus group data were collected using semi-structured topic guides. Analysis was facilitated by NVivo 7© and interpretation was informed by a conceptual framework arising from the interplay of emerging themes and the literature review. The implications for clinical leadership development of two critical concepts, 'representing nursing' and 'compensatory action', are discussed in detail. Clinical leadership development should emphasise the development of all nurses as clinical leaders in the context of the delineation, clarification and articulation of their distinctive contribution in multidisciplinary care settings. Clinical leaders are recognised as practice experts and as leaders in their particular fields. Recognition and influence in and beyond the immediate context of care depends greatly on their ability to articulate the distinct nursing contribution to patient care. This ability provides an essential resource to resist the ongoing blurring, effacement and dilution of nurses' roles. © 2011 Blackwell Publishing Ltd.

21-Hydroxylase deficiency: an exemplary model of the contribution of molecular biology in the understanding and management of the disease.

PubMed

Forest, M G; Tardy, V; Nicolino, M; David, M; Morel, Y

2005-06-01

Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders caused by mutations in genes encoding the enzymes involved in one of the various steps of adrenal steroid synthesis. Steroid 21-hydroxylase deficiency (21-OHD) is responsible for over 95% of the 5 forms of CAH, and results due to enzymatic defect owing to mutation in the CYP21 gene. The disease has two major clinical presentations. The "classical" form is severe, and divided into a salt wasting (SW) and simple virilizing (SV) subgroups. In both, affected female fetuses undergo virilization of the external genitalia prenatally and present at birth with sexual ambiguity. In addition, in both sexes infants with SW CAH are at risk of life-threatening adrenal crisis without treatment. This is why it is so important to make a diagnosis and to counsel the families. The diagnosis is easy by measuring the plasma levels of 17-hydroxyprogesterone (17-OHP) in antenatal (amniotic fluid), or perinatal samples (peripheral blood). Confirmation by molecular genetic analysis is advised. The second form of 21-OHD is called "non classical" because the presentation is much less severe and the onset of clinical expression occurs long after birth, often in the peripubertal period, as non-specific symptoms of hyperandrogeny. The unambiguous diagnosis of the latter requires a simple short ACTH test, with the measurement of 17-OHP at 60 min. In both forms, the mutations on the gene CYP21 responsible for the disease are now well known and can be identified by molecular biology techniques. There is a good correlation between phenotypes and genotypes, due to variable amount of the 21-hydroxylase-enzyme activity left (null to 50-60%). SW, SV and NC forms are associated with distinct mutations or combination of mutations. Nowadays, by combining hormonal and molecular tests, it is possible to predict the clinical form of the disease in a given family in the context of a prenatal diagnosis, which can lead to a prenatal treatment. Therefore, 21-OHD genotyping also appears essential for a new approach of genetic counseling, prediction of clinical form after postnatal screening and to define the post-ACTH 17-OHP values indicating the cut-off lines between NC, heterozygote and normal subjects.

Drawing Disorders in Alzheimer's Disease and Other Forms of Dementia.

PubMed

Trojano, Luigi; Gainotti, Guido

2016-04-21

Drawing is a multicomponential process that can be impaired by many kinds of brain lesions. Drawing disorders are very common in Alzheimer's disease and other forms of dementia, and can provide clinical information for the distinction of the different dementing diseases. In our review we started from an overview of the neural and cognitive bases of drawing, and from a recollection of the drawing tasks more frequently used for assessing individuals with dementia. Then, we analyzed drawing disorders in dementia, paying special attention to those observed in Alzheimer's disease, from the prodromal stages of the amnesic mild cognitive impairment to the stages of full-blown dementia, both in the sporadic forms with late onset in the entorhino-hippocampal structures and in those with early onset in the posterior neocortical structures. We reviewed the drawing features that could differentiate Alzheimer's disease from vascular dementia and from the most frequent forms of degenerative dementia, namely frontotemporal dementia and Lewy body disease. Finally, we examined some peculiar aspects of drawing disorders in dementia, such as perseverations, rotations, and closing-in. We argue that a careful analysis of drawing errors helps to differentiate the different forms of dementia more than overall accuracy in drawing.

In vitro characterization of Leishmania (Viannia) braziliensis isolates from patients with different responses to Glucantime(®) treatment from Northwest Paraná, Brazil.

PubMed

Fernandes, Andrea Claudia Bekner Silva; Pedroso, Raíssa Bocchi; de Mello, Tatiane França Perles; Donatti, Lucélia; Venazzi, Eneide Aparecida Sabaini; Demarchi, Izabel Galhardo; Aristides, Sandra Mara Alessi; Lonardoni, Maria Valdrinez Campana; Silveira, Thaís Gomes Verzignassi

2016-08-01

Leishmaniasis is a group of diseases that presents various clinical manifestations. Many studies have shown that the parasite plays an important role in the clinical manifestations and prognosis of this disease. The cutaneous and mucosal forms of American tegumentary leishmaniasis (ATL) are associated with Leishmania (Viannia) braziliensis, which exhibits intraspecific genetic polymorphisms and various clinical manifestations. The present study focused on four different L. braziliensis strains that were isolated from patients with distinct Glucantime(®) treatment responses. The isolates were described based on their molecular, biological, and infective characteristics. Growth patterns in culture medium and different grow phases were analyzed, MID-Logarithimic (Mid-LOG), Logarithimic (LOG) and Stationary (STAT) phases. Complement resistance was evaluated using guinea pig serum. Infection to murine peritoneal macrophages, cytokine and nitric oxide were analyzed. Ultrastructural features were determined by transmission electron microscopy, and molecular characteristics were determined based on random amplified polymorphic DNA (RAPD). All of the L. braziliensis isolates showed typical growth and similar complement sensitivity patterns. Markedly lower infectivity indexes were observed for all strains in the LOG phase, with different cytokine profiles. The ultrastructure analysis revealed distinct differences between the MID-LOG, LOG, and STAT phases. The RAPD results showed a divergence between the isolates of the L. braziliensis. The in vitro characterization of L. braziliensis isolates from humans with different treatment responses using various parameters enabled us to observe differences among the isolates. Molecular and in vivo characterizations are currently under study to improve understanding of the parasite-host interaction that can imply in the clinical manifestation differences. Copyright © 2016 Elsevier Inc. All rights reserved.

Bartter and Gitelman syndromes: Spectrum of clinical manifestations caused by different mutations

PubMed Central

Al Shibli, Amar; Narchi, Hassib

2015-01-01

Bartter and Gitelman syndromes (BS and GS) are inherited disorders resulting in defects in renal tubular handling of sodium, potassium and chloride. Previously considered as genotypic and phenotypic heterogeneous diseases, recent evidence suggests that they constitute a spectrum of disease caused by different genetic mutations with the molecular defects of chloride reabsorption originating at different sites of the nephron in each condition. Although they share some characteristic metabolic abnormalities such as hypokalemia, metabolic alkalosis, hyperplasia of the juxtaglomerular apparatus with hyperreninemia, hyperaldosteronism, the clinical and laboratory manifestations may not always allow distinction between them. Diuretics tests, measuring the changes in urinary fractional excretion of chloride from baseline after administration of either hydrochlorothiazide or furosemide show very little change (< 2.3%) in the fractional excretion of chloride from baseline in GS when compared with BS, except when BS is associated with KCNJ1 mutations where a good response to both diuretics exists. The diuretic test is not recommended for infants or young children with suspected BS because of a higher risk of volume depletion in such children. Clinical symptoms and biochemical markers of GS and classic form of BS (type III) may overlap and thus genetic analysis may specify the real cause of symptoms. However, although genetic analysis is available, its use remains limited because of limited availability, large gene dimensions, lack of hot-spot mutations, heavy workup time and costs involved. Furthermore, considerable overlap exists between the different genotypes and phenotypes. Although BS and GS usually have distinct presentations and are associated with specific gene mutations, there remains considerable overlap between their phenotypes and genotypes. Thus, they are better described as a spectrum of clinical manifestations caused by different gene mutations. PMID:26140272

Miltefosine is effective against Candida albicans and Fusarium oxysporum nail biofilms in vitro.

PubMed

Machado Vila, Taissa Vieira; Sousa Quintanilha, Natália; Rozental, Sonia

2015-11-01

Onychomycosis is a fungal nail infection that represents ∼50 % of all nail disease cases worldwide. Clinical treatment with standard antifungals frequently requires long-term systemic therapy to avoid chronic disease. Onychomycosis caused by non-dermatophyte moulds, such as Fusarium spp., and yeasts, such as Candida spp., is particularly difficult to treat, possibly due to the formation of drug-resistant fungal biofilms on affected areas. Here, we show that the alkylphospholipid miltefosine, used clinically against leishmaniasis and cutaneous breast metastases, has potent activity against biofilms of Fusarium oxysporum and Candida albicans formed on human nail fragments in vitro. Miltefosine activity was compared with that of commercially available antifungals in the treatment of biofilms at two distinct developmental phases: formation and maturation (pre-formed biofilms). Drug activity towards biofilms formed on nail fragments and on microplate surfaces (microdilution assays) was evaluated using XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assays, and drug effects on fingernail biofilms were analysed by scanning electron microscopy (SEM). For F. oxysporum, miltefosine at 8 μg ml- 1 inhibited biofilm formation by 93%, whilst 256 μg ml- 1 reduced the metabolic activity of pre-formed nail biofilms by 93%. Treatment with miltefosine at 1000 μg ml- 1 inhibited biofilm formation by 89% and reduced the metabolic activity of pre-formed C. albicans biofilms by 99%. SEM analyses of biofilms formed on fingernail fragments showed a clear reduction in biofilm biomass after miltefosine treatment, in agreement with XTT results. Our results show that miltefosine has potential as a therapeutic agent against onychomycosis and should be considered for in vivo efficacy studies, especially in topical formulations for refractory disease treatment.

Semiconductor quantum dots: synthesis and water-solubilization for biomedical applications.

PubMed

Yu, William W

2008-10-01

Quantum dots (QDs) are generally nanosized inorganic particles. They have distinctive size-dependent optical properties due to their very small size (mostly < 10 nm). QDs are regarded as promising new fluorescent materials for biological labeling and imaging because of their superior properties compared with traditional organic molecular dyes. These properties include high quantum efficiency, long-term photostability and very narrow emission but broad absorption spectra. Recent developments in synthesizing high quality semiconductor QDs (mainly metal-chalcogenide compounds) and forming biocompatible structures for biomedical applications are discussed in this paper. This information may facilitate the research to create new materials/technologies for future clinical applications.

The joint in psoriatic arthritis.

PubMed

Mortezavi, Mahta; Thiele, Ralph; Ritchlin, Christopher

2015-01-01

Psoriatic arthritis (PsA), a chronic inflammatory joint disease associated with psoriasis, is notable for diversity in disease presentation, course and response to treatment. Equally varied are the types of musculoskeletal involvement which include peripheral and axial joint disease, dactylitis and enthesitis. In this review, we focus on the psoriatic joint and discuss pathways that underlie synovial, cartilage and bone inflammation and highlight key histopathologic features. The pivotal inflammatory mechanisms and pathobiology of PsA parallel findings in other forms of spondyloarthritis but are distinct from disease pathways described in rheumatoid synovitis and bone disease. The diagnosis of PsA from both a clinical and imaging perspective is also discussed.

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE syndrome).

PubMed

Hung, S C; Kung, Y Y; Lin, H Y

1999-07-01

A 63-year-old man presented with acute symmetrical polysynovitis associated with pitting edema of both the hands and feet. He was seronegative for rheumatoid factor and no radiologically evident erosion was noted in the joints of his hands and feet. Evaluation excluded congestive heart failure, nephrotic syndrome, and hypothyroidism as the cause of edema. Treatment with nonsteroidal anti-inflammatory drugs and low-dose steroids induced complete remission. The clinical manifestations of this patients were consistent with those of a distinctive, although rare, form of arthritis called remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. This syndrome has a good prognosis in elderly patients.

Eosinophilic Pustular Folliculitis in Children after Stem Cell Transplantation: An Eruption Distinct from Graft-Versus-Host Disease.

PubMed

Theiler, Martin; Oza, Vikash S; Mathes, Erin F; Dvorak, Christopher C; McCalmont, Timothy H; Yeh, Iwei; Sidbury, Robert; Cordoro, Kelly M

2017-05-01

Eosinophilic pustular folliculitis (EPF) is a rare cutaneous disorder that typically occurs in three clinical contexts: men, individuals who are immunosuppressed or have human immunodeficiency virus, and infants. A fourth subtype occurring 2 to 3 months after hematopoietic stem cell transplantation (HSCT) has recently been described in several adults. We report two cases of EPF arising in children after HSCT. It is important to recognize this form of EPF after HSCT and differentiate it from graft-versus-host disease since it responds readily to topical steroids and appears to have an excellent prognosis. © 2017 Wiley Periodicals, Inc.

Using pathology-specific laboratory profiles in Clinical Pathology to reduce inappropriate test requesting: two completed audit cycles

PubMed Central

2012-01-01

Background Systematic reviews have shown that, although well prepared, the Consensus Guidelines have failed to change clinical practice. In the healthcare district of Castelnovo né Monti (Reggio Emilia, Italy), it became necessary for the GPs and Clinical Pathologists to work together to jointly define laboratory profiles. Methods Observational study with two cycles of retrospective audit on test request forms, in a primary care setting. Objectives of the study were to develop pathology-specific laboratory profiles and to increase the number of provisional diagnoses on laboratory test request forms. A Multiprofessional Multidisciplinary Inter-hospital Work Team developed pathology-specific laboratory profiles for more effective test requesting. After 8 training sessions that used a combined strategy with multifaceted interventions, the 23 General Practitioners (GPs) in the trial district (Castelnovo nè Monti) tested the profiles; the 21 GPs in the Puianello district were the control group; all GPs in both districts participated in the trial. All laboratory tests for both healthcare districts are performed at the Laboratory located in the trial district. A baseline and a 1-year audit were performed in both districts on the GPs’ request forms. Results Seven pathology-specific laboratory profiles for outpatients were developed. In the year after the first audit cycle: 1) the number of tests requested in the trial district was distinctly lower than that in the previous year, with a decrease of about 5% (p < 0.001); 2) the provisional diagnosis on the request forms was 52.8% in the trial district and 42% in the control district (P < 0.001); 3) the decrease of the number of tests on each request form was much more marked in the trial district (8.73 vs. 10.77; p < 0.001). Conclusions The first audit cycle showed a significant decrease in the number of tests ordered only in the trial district. The combined strategy used in this study improved the prescriptive compliance of most of the GPs involved. The presence of the clinical pathologist is seen as an added value. PMID:22759353

Using pathology-specific laboratory profiles in clinical pathology to reduce inappropriate test requesting: two completed audit cycles.

PubMed

Baricchi, Roberto; Zini, Michele; Nibali, Maria Grazia; Vezzosi, Walter; Insegnante, Vincenzo; Manfuso, Clotilde; Polese, Alessandra; Costoli, Valmer; Spelti, Antonio; Formisano, Debora; Orlandini, Danilo; Nicolini, Fausto; Poli, Antonio

2012-07-03

Systematic reviews have shown that, although well prepared, the Consensus Guidelines have failed to change clinical practice. In the healthcare district of Castelnovo né Monti (Reggio Emilia, Italy), it became necessary for the GPs and Clinical Pathologists to work together to jointly define laboratory profiles. Observational study with two cycles of retrospective audit on test request forms, in a primary care setting. Objectives of the study were to develop pathology-specific laboratory profiles and to increase the number of provisional diagnoses on laboratory test request forms. A Multiprofessional Multidisciplinary Inter-hospital Work Team developed pathology-specific laboratory profiles for more effective test requesting. After 8 training sessions that used a combined strategy with multifaceted interventions, the 23 General Practitioners (GPs) in the trial district (Castelnovo nè Monti) tested the profiles; the 21 GPs in the Puianello district were the control group; all GPs in both districts participated in the trial. All laboratory tests for both healthcare districts are performed at the Laboratory located in the trial district. A baseline and a 1-year audit were performed in both districts on the GPs' request forms. Seven pathology-specific laboratory profiles for outpatients were developed. In the year after the first audit cycle: 1) the number of tests requested in the trial district was distinctly lower than that in the previous year, with a decrease of about 5% (p < 0.001); 2) the provisional diagnosis on the request forms was 52.8% in the trial district and 42% in the control district (P < 0.001); 3) the decrease of the number of tests on each request form was much more marked in the trial district (8.73 vs. 10.77; p < 0.001). The first audit cycle showed a significant decrease in the number of tests ordered only in the trial district. The combined strategy used in this study improved the prescriptive compliance of most of the GPs involved. The presence of the clinical pathologist is seen as an added value.

Teaching pediatric communication skills to medical students

PubMed Central

Frost, Katherine A; Metcalf, Elizabeth P; Brooks, Rachel; Kinnersley, Paul; Greenwood, Stephen R; Powell, Colin VE

2015-01-01

Background Delivering effective clinical pediatric communication skills training to undergraduate medical students is a distinct and important challenge. Pediatric-specific communication skills teaching is complex and under-researched. We report on the development of a scenario-based pediatric clinical communication skills program as well as students’ assessment of this module. Methods We designed a pediatric clinical communication skills program and delivered it five times during one academic year via small-group teaching. Students were asked to score the workshop in eight domains (learning objectives, complexity, interest, competencies, confidence, tutors, feedback, and discussion) using 5-point Likert scales, along with free text comments that were grouped and analyzed thematically, identifying both the strengths of the workshop and changes suggested to improve future delivery. Results Two hundred and twenty-one of 275 (80%) student feedback forms were returned. Ninety-six percent of students’ comments were positive or very positive, highlighting themes such as the timing of teaching, relevance, group sizes, and the use of actors, tutors, and clinical scenarios. Conclusion Scenario-based teaching of clinical communication skills is positively received by students. Studies need to demonstrate an impact on practice, performance, development, and sustainability of communications training. PMID:25653569

When Variability Matters More than Meaning: The Effect of Lexical Forms on Use of Phonemic Contrasts

ERIC Educational Resources Information Center

Thiessen, Erik D.

2011-01-01

During the first half of the 2nd year of life, infants struggle to use phonemic distinctions in label-object association tasks. Prior experiments have demonstrated that exposure to the phonemes in distinct lexical forms (e.g., /"d"/ and /"t"/ in "daddy" and "tiger", respectively) facilitates infants' use of phonemic contrasts but also that they…

A comparative study of nonwoven fabrics made with two distinctly different forms of greige cotton lint

USDA-ARS?s Scientific Manuscript database

Two sets of nonwoven fabrics of nominal 80 g/m2 density were produced on commercial equipment, using two distinctly different forms of greige cotton lint. One was a regular cotton taken from a randomly picked classical bale and the other was a uniquely pre-cleaned UltraCleanTM cotton produced by a w...

Evidence, research, knowledge: a call for conceptual clarity.

PubMed

Scott-Findlay, Shannon; Pollock, Carolee

2004-01-01

To dispel some of the conceptual confusion in the field of evidence-based practice that has resulted from the overlapping use of the terms research, evidence, and knowledge. Theoretical discussion. Often the terms research and knowledge are used as synonyms for evidence, but the overlap is never complete. The term evidence has long been understood to mean the findings of research. Recent attempts to broaden the definition of evidence to include clinical experience and experiential knowledge have been misguided. Broadening our understanding of the basis for clinical decision making and conceptualizing evidence are quite different tasks. Other factors (not other forms of evidence) do shape the clinical decision-making process, but they are not evidence. We might better term them knowledge. Confusing evidence with these other factors has hindered research and the improvement of clinical decision making in health care. We argue that this confusion results from the use of the term evidence when we really mean either research findings or knowledge. In this article, we have argued for specificity in the use of the term evidence. We urge the restriction of the term evidence to research findings, and while we acknowledge the importance of other influences on the clinical decision-making process, we insist that they are not evidence. The time has come to value personal experience and experiential knowledge for what they are-we should not have to disguise them as types of evidence for them to be deemed of any value. Being specific to language, the goal is to improve clinical decision making by increasing practitioners' reliance on research findings (evidence) while acknowledging (and valuing) the important part played by other forms of knowledge in the decision-making process. The distinctions are important.

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

Andermann, F.; Andermann, E.; Carpenter, S.

Most forms of neuronal ceroid lipofuscinosis (NCL) are autosomal recessive, and three genes have already been mapped: the infantile form (CLN 1); the juvenile form (CLN 3); and the early juvenile variant (CLN 5) on chromosomes 1, 16 and 13, respectively. Kufs` disease or adolescent-adult onset NCL is usually inherited as an autosomal recessive trait, and presents as three distinct clinical syndromes: progressive myoclonus epilepsy (PME) with onset in the early teens or around age 30; and onset of dementia with motor disability in the 30s. We have studied three families originating from different parts of the USA manifesting dominantlymore » inherited Kufs` disease. Granular osmophilic deposits (GROD) were found in brain, but storage in skin was not an obligatory feature. Six dominantly inherited PME families have been ascertained from three different regions of Spain. No storage was found in skin or muscle in any of these families. The mean age of onset in the American families is earlier, the clinical manifestations more severe, and the progression much more rapid that in the Spanish families. These findings would suggest the possibility of genetic heterogeneity involving two or more loci, or different mutations at the same gene locus. Genetic linkage studies have been carried out in a six-generation New Jersey family in an attempt to characterize the gene(s) responsible for this disorder. The infantile NCL locus on chromosome 1p (CLN1) and the juvenile NCL locus on chromosome 16p (CLN 3) have been excluded in this family. Further clinical, pathological and molecular genetic studies should lead to the clarification of the diagnostic approaches in this disorder.« less

Autism Spectrum Disorders as a Qualitatively Distinct Category from Typical Behavior in a Large, Clinically Ascertained Sample

ERIC Educational Resources Information Center

Frazier, Thomas W.; Youngstrom, Eric A.; Sinclair, Leslie; Kubu, Cynthia S.; Law, Paul; Rezai, Ali; Constantino, John N.; Eng, Charis

2010-01-01

The present study evaluated the hypothesis that autism spectrum disorders (ASDs) are best represented as a discrete category distinct from typical behavior within autism-affected families. The latent structure, categorical versus dimensional, of ASDs informs future diagnostic revisions, clinical assessment, and the design of future research. Data…

Identifying complications of interventional procedures from UK routine healthcare databases: a systematic search for methods using clinical codes.

PubMed

Keltie, Kim; Cole, Helen; Arber, Mick; Patrick, Hannah; Powell, John; Campbell, Bruce; Sims, Andrew

2014-11-28

Several authors have developed and applied methods to routine data sets to identify the nature and rate of complications following interventional procedures. But, to date, there has been no systematic search for such methods. The objective of this article was to find, classify and appraise published methods, based on analysis of clinical codes, which used routine healthcare databases in a United Kingdom setting to identify complications resulting from interventional procedures. A literature search strategy was developed to identify published studies that referred, in the title or abstract, to the name or acronym of a known routine healthcare database and to complications from procedures or devices. The following data sources were searched in February and March 2013: Cochrane Methods Register, Conference Proceedings Citation Index - Science, Econlit, EMBASE, Health Management Information Consortium, Health Technology Assessment database, MathSciNet, MEDLINE, MEDLINE in-process, OAIster, OpenGrey, Science Citation Index Expanded and ScienceDirect. Of the eligible papers, those which reported methods using clinical coding were classified and summarised in tabular form using the following headings: routine healthcare database; medical speciality; method for identifying complications; length of follow-up; method of recording comorbidity. The benefits and limitations of each approach were assessed. From 3688 papers identified from the literature search, 44 reported the use of clinical codes to identify complications, from which four distinct methods were identified: 1) searching the index admission for specified clinical codes, 2) searching a sequence of admissions for specified clinical codes, 3) searching for specified clinical codes for complications from procedures and devices within the International Classification of Diseases 10th revision (ICD-10) coding scheme which is the methodology recommended by NHS Classification Service, and 4) conducting manual clinical review of diagnostic and procedure codes. The four distinct methods identifying complication from codified data offer great potential in generating new evidence on the quality and safety of new procedures using routine data. However the most robust method, using the methodology recommended by the NHS Classification Service, was the least frequently used, highlighting that much valuable observational data is being ignored.

The fourth disease, 1900-2000.

PubMed

Weisse, M E

2001-01-27

Measles and scarlet fever were differentiated from one another in the 17th century. Rubella was accepted as the third distinct paediatric exanthem in 1881. Nil Filatow in 1885 and Clement Dukes in 1894 described two distinct forms of rubella, and in 1900 Dukes proposed that one of these forms of rubella was a separate entity which he called the fourth disease. For the past five decades, fourth disease has been considered a non-entity, perhaps a mild form of scarlet fever, but certainly not a distinct disease. In 1979 Keith Powell resurrected the idea of the fourth disease and argued that it was caused by exotoxin-producing Staphylococcus aureus. We present additional arguments for the existence of fourth disease, as well as information to link the disease to S. aureus.

Impact of Sleep Disorders, Quality of Life and Gastric Emptying in Distinct Subtypes of Functional Dyspepsia in Japan

PubMed Central

Yamawaki, Hiroshi; Shimpuku, Mayumi; Sato, Hitomi; Wakabayashi, Taiga; Maruki, Yuuta; Kodaka, Yasuhiro; Nagoya, Hiroyuki; Shindo, Tomotaka; Kawagoe, Tetsuro; Sakamoto, Choitsu

2014-01-01

Background/Aims The association between clinical symptoms, gastric emptying, quality of life and sleep disorders in distinct functional dyspepsia (FD) patients has not been studied yet in detail. Methods We enrolled 79 FD patients (postprandial distress syndrome [PDS], n = 65; epigastric pain syndrome [EPS], n = 47; EPS-PDS overlap, n = 33) and 44 healthy volunteers. Gastric motility was evaluated. We used Rome III criteria to evaluate clinical symptoms and State-Trait Anxiety Inventory (STAI) scores to determine anxiety status. Sleep disorder was evaluated using the Pittsburgh Sleep Quality Index scores. Results There were no significant differences in age, sex and Helicobacter pylori positivity between FD subtypes and healthy volunteers. The scores of Glasgow dyspepsia severity scores (GDSS), SF-8 and Pittsburgh Sleep Quality Index (PSQI) in distinct subtypes of FD patients were significantly different from those in healthy volunteers. However, there were not significant differences in these scores, Tmax and T1/2 among 3 subtypes of FD patients. PSQI score was significantly (P = 0.027, P = 0.002 and P = 0.039, respectively) associated with GDSS among EPS, PDS and EPS-PDS overlap patients. In addition, 8-item short form health survey (SF-8; Physical Component Score and Mental Component Score) was significantly associated with global PSQI score in PDS and EPS-PDS overlap patients. In contrast, SF-8 (Mental Component Score) only was significantly linked to global PSQI score in EPS patients. Conclusions Prevalences for sleep disorders, gastric motility and quality of life in 3 subtypes of FD patients were similar levels. In PDS and EPS-PDS overlap patients, SF-8 was significantly associated with global PSQI score. PMID:24466451

[Study on the area of pain and numbness in cases with lumbosacral radiculopathy].

PubMed

Kuraishi, Keita; Hanakita, Junya; Takahashi, Toshiyuki; Minami, Manabu; Watanabe, Mizuki; Uesaka, Toshio; Honda, Fumiaki

2012-10-01

In the clinical diagnosis of lumbosacral radicular symptoms, dermatome maps are commonly used, by which the segmental location of the affected nerve can be determined. However, the diagnosis is often difficult because the pattern of sensory disturbance does not necessarily match the patterns of classical dermatomes, and there are many dermatome maps made by different methods. The author examined the area of pain and numbness in cases of lumbosacral radiculopathy. Clinical features of pain and numbness in consecutive seventy three cases of lumbosacral radiculopathy were investigated (L3: n=13, L4-S1: n=20). Patients of L3 radiculopathy showed symptoms at the upper buttock and ventral surface of the thighs, knees and upper ventral surface of the legs. Patients of L4 radiculopathy showed symptoms at the ventro-lateral surfaces of the thigh and leg. The distinctive region, defined as the region having 100% superimposition, of L4 radiculopathy was the lateral part of the shin. Patients of L5 radiculopathy showed symptoms at the lateral surfaces of the thigh and leg. The distinctive region was the upper buttock. Patients of S1 radiculopathy showed symptoms at the lower buttock, dorso-lateral part of the leg and lateral part of the foot. The distinctive region was the lateral part of the calf. It was found that the regions of pain and numbness formed a continuous band-like zone from thigh to leg in 8% of L3, 45% of L4 and L5, and 35% of S1 radiculopathy. Using a visual analogue scale, the degree of leg pain was more severe than low back pain in 68% of the patients, but in 5% of patients, low back pain was more severe.

LRPPRC mutations cause a phenotypically distinct form of Leigh syndrome with cytochrome c oxidase deficiency.

PubMed

Debray, François-Guillaume; Morin, Charles; Janvier, Annie; Villeneuve, Josée; Maranda, Bruno; Laframboise, Rachel; Lacroix, Jacques; Decarie, Jean-Claude; Robitaille, Yves; Lambert, Marie; Robinson, Brian H; Mitchell, Grant A

2011-03-01

The natural history of all known patients with French-Canadian Leigh disease (Saguenay-Lac-St-Jean cytochrome c oxidase deficiency, MIM220111, SLSJ-COX), the largest known cohort of patients with a genetically homogeneous, nuclear encoded congenital lactic acidosis, was studied. 55 of 56 patients were homozygous for the A354V mutation in LRPPRC. One was a genetic compound (A354V/C1277Xdel8). Clinical features included developmental delay, failure to thrive, characteristic facial appearance and, in 90% of patients, acute crises that have not previously been detailed, either metabolic (fulminant lactic acidosis) and/or neurological (Leigh syndrome and/or stroke-like episodes). Survival ranged from 5 days to >30 years. 46/56 patients (82%) died, at a median age of 1.6 years. Of 73 crises, 38 (52%) were fatal. The immediate causes of death were multiple organ failure and/or Leigh disease. Major predictors of mortality during crises (p<0.005) were hyperglycaemia, hepatic cytolysis, and altered consciousness at admission. Compared to a group of SURF1-deficient Leigh syndrome patients assembled from the literature, SLSJ-COX is distinct by the occurrence of metabolic crises, leading to earlier and higher mortality (p=0.001). SLSJ-COX is clinically distinct, with acute fatal acidotic crises on a backdrop of chronic moderate developmental delay and hyperlactataemia. Leigh syndrome is common. Stroke-like episodes can occur. The Leigh syndrome of SLSJ-COX differs from that of SURF1-related COX deficiency. SLSJ-COX has a different spectrum of associated abnormalities, acidotic crises being particularly suggestive of LRPPRC related Leigh syndrome. Even among A354V homozygotes, pronounced differences in survival and severity occur, showing that other genetic and/or environmental factors can influence outcome.

[Arterial media calcification in patients with type 2 diabetes mellitus].

PubMed

Belovici, Maria Isabela; Pandele, G I

2008-01-01

Arterial calcification was previously viewed as an inevitable, passive, and degenerative process that occurred at the end stages of atherosclerosis. Recent studies, however, have demonstrated that calcification of arteries is a complex and regulated process. It may occur in conjunction with atherosclerosis or in an isolated form that is commonly associated with diabetes and renal failure. Higher artery calcium scores are associated with increased cardiovascular events, and some aspects of arterial calcification are similar to the biology of forming bone. Arterial calcification can thus be viewed as a distinct inflammatory arteriopathy, much like atherosclerosis and aneurysms, with its own contribution to cardiovascular morbidity and mortality. Current research involves efforts to define the complex interactions between cellular and molecular mediators of arterial calcification and, in particular, the role of endogenous calcification inhibitors. This review discusses the clinical relevance, cellular events, and suspected molecular pathways that control arterial calcification.

Role of the Yersinia pestis yersiniabactin iron acquisition system in the incidence of flea-borne plague.

PubMed

Sebbane, Florent; Jarrett, Clayton; Gardner, Donald; Long, Daniel; Hinnebusch, B Joseph

2010-12-17

Plague is a flea-borne zoonosis caused by the bacterium Yersinia pestis. Y. pestis mutants lacking the yersiniabactin (Ybt) siderophore-based iron transport system are avirulent when inoculated intradermally but fully virulent when inoculated intravenously in mice. Presumably, Ybt is required to provide sufficient iron at the peripheral injection site, suggesting that Ybt would be an essential virulence factor for flea-borne plague. Here, using a flea-to-mouse transmission model, we show that a Y. pestis strain lacking the Ybt system causes fatal plague at low incidence when transmitted by fleas. Bacteriology and histology analyses revealed that a Ybt-negative strain caused only primary septicemic plague and atypical bubonic plague instead of the typical bubonic form of disease. The results provide new evidence that primary septicemic plague is a distinct clinical entity and suggest that unusual forms of plague may be caused by atypical Y. pestis strains.

Thrombus Formation at High Shear Rates.

PubMed

Casa, Lauren D C; Ku, David N

2017-06-21

The final common pathway in myocardial infarction and ischemic stroke is occlusion of blood flow from a thrombus forming under high shear rates in arteries. A high-shear thrombus forms rapidly and is distinct from the slow formation of coagulation that occurs in stagnant blood. Thrombosis at high shear rates depends primarily on the long protein von Willebrand factor (vWF) and platelets, with hemodynamics playing an important role in each stage of thrombus formation, including vWF binding, platelet adhesion, platelet activation, and rapid thrombus growth. The prediction of high-shear thrombosis is a major area of biofluid mechanics in which point-of-care testing and computational modeling are promising future directions for clinically relevant research. Further research in this area will enable identification of patients at high risk for arterial thrombosis, improve prevention and treatment based on shear-dependent biological mechanisms, and improve blood-contacting device design to reduce thrombosis risk.

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

Sharp, J.; Wheeler, R.B.; Jaervelae, I.

The neuronal ceroid-lipofuscinoses (NCL) are a group of neurodegenerative disorders with an autosomal-recessive pattern of inheritance. There are 3 main categories of childhood NCL, namely, infantile, late-infantile, and juvenile NCL. These can be distinguished on the basis of age of onset, clinical course, and histopathology. A number of variant forms of NCL have also been mapped to chromosome areas 1p32 and 16p12, respectively. The gene for late-infantile NCL (LINCL), CLN2, has been excluded from both these loci, but its location is as yet unknown. Recently, CLN5, the gene for the Finnish variant form of LINCL, was mapped to 13q21.1-32. Usingmore » the 3 microsatellite markers which were most tightly linked to CLN5, we have excluded CLN2 from this region using a subset of 17 families. Thus, CLN2 represents a fourth distinct genetic locus involved in the pathogenesis of NCL. 6 refs., 1 fig., 1 tab.« less

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

Bonnefont, J.P.; Cepanec, C.; Leroux, J.P.

Carnitine palmitoyltransferase (CPT) II deficiency, an inherited disorder of mitochondrial long-chain fatty-acid (LCFA) oxidation, results in two distinct clinical act phenotypes, namely, an adult (muscular) form and an infantile (hepatocardiomuscular) form. The rationale of this phenotypic heterogeneity is poorly understood. The adult form of the disease is commonly ascribed to the Ser-113-Leu substitution in CPT II. Only few data are available regarding the molecular basis of the infantile form of the disease. We report herein a homozygous A-2399-C transversion predicting a Tyr-628-Ser substitution in a CPT II-deficient infant. In vitro expression of mutant cDNA in COS-1 cells demonstrated the responsibilitymore » of this mutation for the disease. Metabolic consequences of the Ser-113-Leu and Tyr-628-Ser substitutions were studied in fibroblasts. The Tyr-628-Ser substitution (infantile form) resulted in a 10% CPT II residual activity, markedly impairing LCFA oxidation, whereas the Ser-113-Leu substitution (adult form) resulted in a 20% CPT II residual activity, without consequence on LCFA oxidation. These data show that CPT II activity has to be reduced below a critical threshold in order for LCFA oxidation in fibroblasts to be impaired. The hypothesis that this critical threshold differs among tissues could provide a basis to explain phenotypic heterogeneity of CPT II deficiency. 32 refs., 5 figs.« less

Early- and late-onset Alzheimer disease: Are they the same entity?

PubMed

Tellechea, P; Pujol, N; Esteve-Belloch, P; Echeveste, B; García-Eulate, M R; Arbizu, J; Riverol, M

2018-05-01

Early-onset Alzheimer disease (EOAD), which presents in patients younger than 65 years, has frequently been described as having different features from those of late-onset Alzheimer disease (LOAD). This review analyses the most recent studies comparing the clinical presentation and neuropsychological, neuropathological, genetic, and neuroimaging findings of both types in order to determine whether EOAD and LOAD are different entities or distinct forms of the same entity. We observed consistent differences between clinical findings in EOAD and in LOAD. Fundamentally, the onset of EOAD is more likely to be marked by atypical symptoms, and cognitive assessments point to poorer executive and visuospatial functioning and praxis with less marked memory impairment. Alzheimer-type features will be more dense and widespread in neuropathology studies, with structural and functional neuroimaging showing greater and more diffuse atrophy extending to neocortical areas (especially the precuneus). In conclusion, available evidence suggests that EOAD and LOAD are 2 different forms of a single entity. LOAD is likely to be influenced by ageing-related processes. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Misconceptions regarding the pathogenicity of silicas and silicates.

PubMed

Feigin, D S

1989-01-01

Several inhaled substances, from occupational or other environmental exposure, produce significant pulmonary disease and abnormalities demonstrated by pulmonary imaging. Areas of controversy and misconception relate principally to the extent and nature of both the clinical disease and the imaging abnormalities specific to each substance. The size and shape of the inhaled particles is an important determinant of the nature and severity of the disease produced, with fibrous shapes usually being the most pathogenetic. Fibrogenicity is another important pathogenetic characteristic of talc and kaolin, as well as asbestos. Talc produces four distinct forms of pulmonary disease, depending not only on the other substances with which it is inhaled, but also whether it is inhaled or injected intravenously. When inhaled alone, talc does not appear to produce significant pulmonary fibrosis or malignancy. Kaolin, mica, fuller's earth, zeolite, and fiberglass all vary in disease production according to their shape and fibrogenicity. Silica, diatomaceous earth, and other forms of silica are all highly fibrogenic and thus produce clinically obvious disease with sufficient inhalation. The largest particles usually produce nodular patterns in the upper pulmonary fields, as is typical of silicosis. The fibrous particles are more likely to manifest themselves as interstitial patterns in the lower pulmonary fields.

The TcI and TcII Trypanosoma cruzi experimental infections induce distinct immune responses and cardiac fibrosis in dogs

PubMed Central

Duz, Ana Luiza Cassin; Vieira, Paula Melo de Abreu; Roatt, Bruno Mendes; Aguiar-Soares, Rodrigo Dian Oliveira; Cardoso, Jamille Mirelle de Oliveira; de Oliveira, Flávia Carvalho Bitencourt; Reis, Levi Eduardo Soares; Tafuri, Washington Luiz; Veloso, Vanja Maria; Reis, Alexandre Barbosa; Carneiro, Cláudia Martins

2014-01-01

Trypanosoma cruzi infection may be caused by different strains with distinct discrete typing units (DTUs) that can result in variable clinical forms of chronic Chagas disease. The present study evaluates the immune response and cardiac lesions in dogs experimentally infected with different T. cruzi strains with distinct DTUs, namely, the Colombian (Col) and Y strains of TcI and TcII DTU, respectively. During infection with the Col strain, increased levels of alanine aminotransferase, erythrocytes, haematocrit and haemoglobin were observed. In addition, CD8+ T-lymphocytes isolated from the peripheral blood produced higher levels of interleukin (IL)-4. The latter suggests that during the acute phase, infection with the Col strain may remain unnoticed by circulating mononuclear cells. In the chronic phase, a significant increase in the number of inflammatory cells was detected in the right atrium. Conversely, infection with the Y strain led to leucopoenia, thrombopoenia, inversion of the ratio of CD4+/CD8+ T-lymphocytes and alterations in monocyte number. The Y strain stimulated the production of interferon-γ by CD4+ and CD8+ T-lymphocytes and IL-4 by CD8+ T-cells. In the chronic phase, significant heart inflammation and fibrosis were observed, demonstrating that strains of different DTUs interact differently with the host. PMID:25591108

Differential Reprogramming of Isogenic Colorectal Cancer Cells by Distinct Activating KRAS Mutations

PubMed Central

2015-01-01

Oncogenic mutations of Ras at codons 12, 13, or 61, that render the protein constitutively active, are found in ∼16% of all cancer cases. Among the three major Ras isoforms, KRAS is the most frequently mutated isoform in cancer. Each Ras isoform and tumor type displays a distinct pattern of codon-specific mutations. In colon cancer, KRAS is typically mutated at codon 12, but a significant fraction of patients have mutations at codon 13. Clinical data suggest different outcomes and responsiveness to treatment between these two groups. To investigate the differential effects upon cell status associated with KRAS mutations we performed a quantitative analysis of the proteome and phosphoproteome of isogenic SW48 colon cancer cell lines in which one allele of the endogenous gene has been edited to harbor specific KRAS mutations (G12V, G12D, or G13D). Each mutation generates a distinct signature, with the most variability seen between G13D and the codon 12 KRAS mutants. One notable example of specific up-regulation in KRAS codon 12 mutant SW48 cells is provided by the short form of the colon cancer stem cell marker doublecortin-like Kinase 1 (DCLK1) that can be reversed by suppression of KRAS. PMID:25599653

Cranial dystonia, blepharospasm and hemifacial spasm: clinical features and treatment, including the use of botulinum toxin.

PubMed Central

Kraft, S P; Lang, A E

1988-01-01

Blepharospasm, the most frequent feature of cranial dystonia, and hemifacial spasm are two involuntary movement disorders that affect facial muscles. The cause of blepharospasm and other forms of cranial dystonia is not known. Hemifacial spasm is usually due to compression of the seventh cranial nerve at its exit from the brain stem. Cranial dystonia may result in severe disability. Hemifacial spasm tends to be much less disabling but may cause considerable distress and embarrassment. Patients affected with these disorders are often mistakenly considered to have psychiatric problems. Although the two disorders are quite distinct pathophysiologically, therapy with botulinum toxin has proven very effective in both. We review the clinical features, proposed pathophysiologic features, differential diagnosis and treatment, including the use of botulinum toxin, of cranial dystonia and hemifacial spasm. Images Fig. 2 Fig. 3 PMID:3052771

Bullous lichen planus - a review.

PubMed

Liakopoulou, Angeliki; Rallis, Efstathios

2017-03-31

Bullous lichen planus is a rare variant of lichen planus. It is characterized by vesicles or bullae, which usually develop in the context of pre-existing LP lesions. It is often misdiagnosed and should be differentiated from other subepidermal bullous diseases especially lichen planus pemphigoides. The diagnosis is based on clinical suspicion and is confirmed by histopathology and immunofluoresence. The clinical features of bullous lichen planus include typical lichen planus lesions, accompanied by the formation of bullae on the affected or perilesional skin. This is evident on histology, with alteration of the dermo-epidermal junction and intrabasal bullae as a consequence of extensive inflammation. The histologic features in conjunction with the negative immunofluoresence indicate that bullous lichen planus is a form of "hyper-reactive lichen planus" rather than a distinct entity. There is no standard treatment of bullous lichen planus. Topical and systemic corticosteroids, dapsone and acitretin have been described as effective choices.

MicroRNAs in Acute Kidney Injury.

PubMed

Jones, Timothy F; Bekele, Soliana; O'Dwyer, Michael J; Prowle, John R

2018-06-05

It is increasingly recognised that improved diagnosis, prognosis and treatment of acute kidney injury (AKI) requires an understanding of distinct underling cellular and molecular mechanisms (endotypes) that may distinguish overtly similar clinical AKI presentations. One important avenue of research is the post-transcriptional regulation of gene expression in response to kidney injury mediated by microRNAs. This mini-review summarises the use of microRNAs as diagnostic and prognostic biomarkers in AKI. The contribution of microRNAs to the pathophysiology of AKI will be highlighted along with the potential for therapeutic applications. Key Messages: While there is great potential for a better understanding of AKI, microRNAs form a complex regulatory network. Understanding the role and significance of microRNAs in the context of AKI and critical illness is a major endeavour in translational medicine, requiring the integration of clinical and experimental data. © 2018 S. Karger AG, Basel.

Caries Detection Methods Based on Changes in Optical Properties between Healthy and Carious Tissue

PubMed Central

Karlsson, Lena

2010-01-01

A conservative, noninvasive or minimally invasive approach to clinical management of dental caries requires diagnostic techniques capable of detecting and quantifying lesions at an early stage, when progression can be arrested or reversed. Objective evidence of initiation of the disease can be detected in the form of distinct changes in the optical properties of the affected tooth structure. Caries detection methods based on changes in a specific optical property are collectively referred to as optically based methods. This paper presents a simple overview of the feasibility of three such technologies for quantitative or semiquantitative assessment of caries lesions. Two of the techniques are well-established: quantitative light-induced fluorescence, which is used primarily in caries research, and laser-induced fluorescence, a commercially available method used in clinical dental practice. The third technique, based on near-infrared transillumination of dental enamel is in the developmental stages. PMID:20454579

Glioblastoma with oligodendroglioma component (GBM-O): molecular genetic and clinical characteristics.

PubMed

Appin, Christina L; Gao, Jingjing; Chisolm, Candace; Torian, Mike; Alexis, Dianne; Vincentelli, Cristina; Schniederjan, Matthew J; Hadjipanayis, Costas; Olson, Jeffrey J; Hunter, Stephen; Hao, Chunhai; Brat, Daniel J

2013-07-01

Glioblastoma (GBM) is an aggressive primary brain tumor with an average survival of approximately 1 year. A recently recognized subtype, glioblastoma with oligodendroglioma component (GBM-O), was designated by the World Health Organization (WHO) in 2007. We investigated GBM-Os for their clinical and molecular characteristics as compared to other forms of GBM. Tissue samples were used to determine EGFR, PTEN, and 1p and 19q status by fluorescence in situ hybridization (FISH); p53 and mutant IDH1 protein expression by immunohistochemistry (IHC); and MGMT promoter status by methylation-specific polymerase chain reaction (PCR). GBM-Os accounted for 11.9% of all GBMs. GBM-Os arose in younger patients compared to other forms of GBMs (50.7 years vs. 58.7 years, respectively), were more frequently secondary neoplasms, had a higher frequency of IDH1 mutations and had a lower frequency of PTEN deletions. Survival was longer in patients with GBM-Os compared to those with other GBMs, with median survivals of 16.2 and 8.1 months, respectively. Most of the survival advantage for GBM-O appeared to be associated with a younger age at presentation. Among patients with GBM-O, younger age at presentation and 1p deletion were most significant in conferring prolonged survival. Thus, GBM-O represents a subset of GBMs with distinctive morphologic, clinical and molecular characteristics. © 2013 The Authors; Brain Pathology © 2013 International Society of Neuropathology.

Diagnosis and Treatment of Nontuberculous Mycobacterial Lung Disease.

PubMed

Kwon, Yong-Soo; Koh, Won-Jung

2016-05-01

Nontuberculous mycobacteria (NTM) are ubiquitous organisms; their isolation from clinical specimens does not always indicate clinical disease. The incidence of NTM lung diseases has been increasing worldwide. Although the geographic diversity of NTM species is well known, Mycobacterium avium complex (MAC), M. abscessus complex (MABC), and M. kansasii are the most commonly encountered and important etiologic organisms. Two distinct types of NTM lung diseases have been reported, namely fibrocavitary and nodular bronchiectatic forms. For laboratory diagnosis of NTM lung diseases, both liquid and solid media cultures and species-level identification are strongly recommended to enhance growth detection and determine the clinical relevance of isolates. Treatment for NTM lung diseases consists of a multidrug regimen and a long course of therapy, lasting more than 12 months after negative sputum conversion. For MAC lung disease, several new macrolide-based regimens are now recommended. For nodular bronchiectatic forms of MAC lung diseases, an intermittent three-time-weekly regimen produces outcomes similar to those of daily therapy. Treatment of MABC lung disease is very difficult, requiring long-term use of parenteral agents in combination with new macrolides. Treatment outcomes are much better for M. massiliense lung disease than for M. abscessus lung disease. Thus, precise identification of species in MABC infection is needed for the prediction of antibiotic response. Likewise, increased efforts to improve treatment outcomes and develop new agents for NTM lung disease are needed.

Black Hawk Down?: Establishing Helicopter Parenting as a Distinct Construct from Other Forms of Parental Control during Emerging Adulthood

ERIC Educational Resources Information Center

Padilla-Walker, Laura M.; Nelson, Larry J.

2012-01-01

The purpose of the current study was to establish a measure of helicopter parenting that was distinct from other forms of parental control, and to examine parental and behavioral correlates of helicopter parenting. Participants included 438 undergraduate students from four universities in the United States (M[subscript age] = 19.65, SD = 2.00,…

Pregnancy-Related Anxiety: Evidence of Distinct Clinical Significance from a Prospective Longitudinal Study

PubMed Central

Blackmore, Emma Robertson; Gustafsson, Hanna; Gilchrist, Michelle; Wyman, Claire; O’Connor, Thomas G

2016-01-01

Background Pregnancy-related anxiety (PrA) has attracted considerable research attention, but questions remain about its distinctiveness from conventional constructs and measures. In a high psychosocial risk, ethnically diverse sample, we examine the degree to which PrA is distinct from continuous and diagnostic measures of anxiety and worry in terms of longitudinal course, associations with psychosocial and perinatal risk, and prediction of postnatal mood disturbance. Methods 345 women oversampled for prenatal anxiety and depression were selected from an urban obstetrics clinic serving a predominantly low-income, ethnically diverse population. PrA was assessed at 20 and 32 weeks gestation; anxiety and depression symptoms were assessed from questionnaire and from clinical interview at 20 and 32 weeks gestation and again at 2 and 6 months postnatally. Data relevant to psychosocial and obstetric risks were ascertained from interview, medical exam, and chart review. Results Two distinct factors of PrA were identified, indexing specific concerns about the child’s health and about the birth; these two PrA factors showed distinct longitudinal patterns in the prenatal period, and modest associations with general measures of anxiety and depression from questionnaire and clinical interview. PrA was also distinguished from conventional symptom measures in its associated features and prediction of birth weight and postnatal mood. Limitations The sample was at high psychosocial risk and ethnically diverse; findings may not generalize to other samples. Conclusions PrA can be distinguished from general measures of anxiety in pregnancy in terms of longitudinal course, associated features, and prediction to postnatal mood disturbance, and may warrant specific clinical attention. PMID:26999549

Detecting the Diversity of Mycoplasma and Ureaplasma Endosymbionts Hosted by Trichomonas vaginalis Isolates

PubMed Central

Ioannidis, Anastasios; Papaioannou, Panagiota; Magiorkinis, Emmanouil; Magana, Maria; Ioannidou, Vasiliki; Tzanetou, Konstantina; Burriel, Angeliki R.; Tsironi, Maria; Chatzipanagiotou, Stylianos

2017-01-01

Objectives: The symbiosis of Trichomonas vaginalis and Mycoplasma hominis is the first described association between two obligate human parasites. Trichomonas is the niche and the vector for the transmission of M. hominis infection. This clinically significant symbiosis may affect T. vaginalis virulence and susceptibility to treatment. The aims of this study were to investigate the intracellularly present Mycoplasma and Ureaplasma species in T. vaginalis strains isolated from the vaginal discharge of infected women as well as to trace the diversity pattern among the species detected in the isolated strains. Methods: Hundred pure T. vaginalis cultures were isolated from ~7,500 patient specimens presented with clinical purulent vaginitis. PCR and sequencing for Mycoplasma/Ureaplasma spp. were performed in DNA extracted from the pure cultures. In addition, vaginal discharge samples were cultured for the presence of M. hominis and U. urealyticum. Phylogenetic analysis assisted the identification of interspecies relationships between the Mycoplasma and Ureaplasma isolates. Results: Fifty four percentage of T. vaginalis isolates were harboring Mycoplasma spp. Phylogenetic analysis revealed three distinct clusters, two with already characterized M. hominis and Ureaplasma spp. (37% of total Mycoplasma spp.), whereas one group formed a distinct cluster matched with the newly identified species Candidatus Mycoplasma girerdii (59.3%) and one or more unknown Mycoplasma spp. (3.7%). Conclusions: T. vaginalis strains associated with vaginal infection might host intracellular mycoplasmas or ureaplasmas. Intracellular Mollicutes that remain undetected in the extracellular environment when conventional diagnostic methods are implemented may comprise either novel species, such as Candidatus M. giredii, or unknown species with yet unexplored clinical significance. PMID:28702014

Subtypes of depression and their overlap in a naturalistic inpatient sample of major depressive disorder.

PubMed

Musil, Richard; Seemüller, Florian; Meyer, Sebastian; Spellmann, Ilja; Adli, Mazda; Bauer, Michael; Kronmüller, Klaus-Thomas; Brieger, Peter; Laux, Gerd; Bender, Wolfram; Heuser, Isabella; Fisher, Robert; Gaebel, Wolfgang; Schennach, Rebecca; Möller, Hans-Jürgen; Riedel, Michael

2018-03-01

Subtyping depression is important in order to further delineate biological causes of depressive syndromes. The aim of this study was to evaluate clinical and outcome characteristics of distinct subtypes of depression and to assess proportion and features of patients fulfilling criteria for more than one subtype. Melancholic, atypical and anxious subtypes of depression were assessed in a naturalistic sample of 833 inpatients using DSM-IV specifiers based on operationalized criteria. Baseline characteristics and outcome criteria at discharge were compared between distinct subtypes and their overlap. A substantial proportion of patients (16%) were classified with more than one subtype of depression, 28% were of the distinct anxious, 7% of the distinct atypical and 5% of the distinct melancholic subtype. Distinct melancholic patients had shortest duration of episode, highest baseline depression severity, but were more often early improvers; distinct anxious patients had higher NEO-Five Factor Inventory (NEO-FFI) neuroticism scores compared with patients with unspecific subtype. Melancholic patients with overlap of anxious features had worse treatment outcome compared to distinct melancholic and distinct anxious subtype. Distinct subtypes differed in only few variables and patients with overlap of depression subtypes may have independent clinical and outcome characteristics. Studies investigating biological causes of subtypes of depression should take influence of features of other subtypes into account. Copyright © 2017 John Wiley & Sons, Ltd.

Rickettsia parkeri rickettsiosis and its clinical distinction from Rocky Mountain spotted fever.

PubMed

Paddock, Christopher D; Finley, Richard W; Wright, Cynthia S; Robinson, Howard N; Schrodt, Barbara J; Lane, Carole C; Ekenna, Okechukwu; Blass, Mitchell A; Tamminga, Cynthia L; Ohl, Christopher A; McLellan, Susan L F; Goddard, Jerome; Holman, Robert C; Openshaw, John J; Sumner, John W; Zaki, Sherif R; Eremeeva, Marina E

2008-11-01

Rickettsia parkeri rickettsiosis, a recently identified spotted fever transmitted by the Gulf Coast tick (Amblyomma maculatum), was first described in 2004. We summarize the clinical and epidemiological features of 12 patients in the United States with confirmed or probable disease attributable to R. parkeri and comment on distinctions between R. parkeri rickettsiosis and other United States rickettsioses. Clinical specimens from patients in the United States who reside within the range of A. maculatum for whom an eschar or vesicular rash was described were evaluated by > or =1 laboratory assays at the Centers for Disease Control and Prevention (Atlanta, GA) to identify probable or confirmed infection with R. parkeri. During 1998-2007, clinical samples from 12 patients with illnesses epidemiologically and clinically compatible with R. parkeri rickettsiosis were submitted for diagnostic evaluation. Using indirect immunofluorescence antibody assays, immunohistochemistry, polymerase chain reaction assays, and cell culture isolation, we identified 6 confirmed and 6 probable cases of infection with R. parkeri. The aggregate clinical characteristics of these patients revealed a disease similar to but less severe than classically described Rocky Mountain spotted fever. Closer attention to the distinct clinical features of the various spotted fever syndromes that exist in the United States and other countries of the Western hemisphere, coupled with more frequent use of specific confirmatory assays, may unveil several unique diseases that have been identified collectively as Rocky Mountain spotted fever during the past century. Accurate assessments of these distinct infections will ultimately provide a more valid description of the currently recognized distribution, incidence, and case-fatality rate of Rocky Mountain spotted fever.

How discordant morphological and molecular evolution among microorganisms can revise our notions of biodiversity on earth

PubMed Central

Lahr, Daniel J. G.; Laughinghouse, H. Dail; Oliverio, Angela; Gao, Feng; Katz, Laura A.

2014-01-01

Microscopy has revealed a tremendous diversity of bacterial and eukaryotic forms. More recent molecular analyses show discordance in estimates of biodiversity based on morphological analyses. Moreover, phylogenetic analyses of the diversity of microbial forms have revealed evidence of convergence at scales as large as interdomain – i.e. convergent forms shared between bacteria and eukaryotes. Here, we highlight examples of such discordance, focusing on exemplary lineages such as testate amoebae, ciliates and cyanobacteria, which have long histories of morphological study. We discuss examples in two categories: 1) morphologically identical (or highly similar) individuals that are genetically distinct and 2) morphologically distinct individuals that are genetically distinct. We argue that hypotheses about discordance can be tested using the concept of neutral morphologies, or more broadly neutral phenotypes, as a null hypothesis. PMID:25156897

The Pathogenesis of Pulmonary Sarcoidosis and Implications for Treatment.

PubMed

Patterson, Karen C; Chen, Edward S

2018-06-01

Thoracic sarcoidosis is the most common form of sarcoidosis, encompassing a heterogeneous group of patients with a wide range of clinical features and associated outcomes. The distinction between isolated thoracic lymphadenopathy and pulmonary involvement matters. Morbidity is often higher, and long-term outcomes are worse for the latter. Although inflammatory infiltrates in pulmonary sarcoidosis may resolve, persistent disease activity is common and can result in lung fibrosis. Given the distinct clinical features and natural history of pulmonary sarcoidosis, its pathogenesis may differ in important ways from other sarcoidosis manifestations. This review highlights recent advances in the pathogenesis of pulmonary sarcoidosis, including the nature of the sarcoidosis antigen, the role of serum amyloid A and other host factors that contribute to alterations in innate immunity, factors that shape adaptive T-cell profiles in the lung, and how these mechanisms influence the maintenance of granulomatous inflammation in sarcoidosis. We discuss questions raised by recent findings, including the role of innate immunity in the pathogenesis, the meaning of immune cell exhaustion, and mechanisms that may contribute to lung fibrosis in sarcoidosis. We conclude with a reflection on when and how immunosuppressive therapies may be helpful for pulmonary sarcoidosis, a consideration of nonpharmacologic management strategies, and a survey of potential novel therapeutic targets for this vexing disease. Copyright © 2017 American College of Chest Physicians. All rights reserved.

Two different streams form the dorsal visual system: anatomy and functions.

PubMed

Rizzolatti, Giacomo; Matelli, Massimo

2003-11-01

There are two radically different views on the functional role of the dorsal visual stream. One considers it as a system involved in space perception. The other is of a system that codes visual information for action organization. On the basis of new anatomical data and a reconsideration of previous functional and clinical data, we propose that the dorsal stream and its recipient parietal areas form two distinct functional systems: the dorso-dorsal stream (d-d stream) and the ventro-dorsal stream (v-d stream). The d-d stream is formed by area V6 (main d-d extrastriate visual node) and areas V6A and MIP of the superior parietal lobule. Its major functional role is the control of actions "on line". Its damage leads to optic ataxia. The v-d stream is formed by area MT (main v-d extrastriate visual node) and by the visual areas of the inferior parietal lobule. As the d-d stream, v-d stream is responsible for action organization. It, however, also plays a crucial role in space perception and action understanding. The putative mechanisms linking action and perception in the v-d stream is discussed.

Genotypic and phenotypic diversity of Lactobacillus rhamnosus clinical isolates, their comparison with strain GG and their recognition by complement system

PubMed Central

Douillard, François P.; Ritari, Jarmo; Paulin, Lars; Järvinen, Hanna M.; Rasinkangas, Pia; Haapasalo, Karita; Meri, Seppo; Jarva, Hanna; de Vos, Willem M.

2017-01-01

Lactobacillus rhamnosus strains are ubiquitous in fermented foods, and in the human body where they are commensals naturally present in the normal microbiota composition of gut, vagina and skin. However, in some cases, Lactobacillus spp. have been implicated in bacteremia. The aim of the study was to examine the genomic and immunological properties of 16 clinical blood isolates of L. rhamnosus and to compare them to the well-studied L. rhamnosus probiotic strain GG. Blood cultures from bacteremic patients were collected at the Helsinki University Hospital laboratory in 2005–2011 and L. rhamnosus strains were isolated and characterized by genomic sequencing. The capacity of the L. rhamnosus strains to activate serum complement was studied using immunological assays for complement factor C3a and the terminal pathway complement complex (TCC). Binding of complement regulators factor H and C4bp was also determined using radioligand assays. Furthermore, the isolated strains were evaluated for their ability to aggregate platelets and to form biofilms in vitro. Genomic comparison between the clinical L. rhamnosus strains showed them to be clearly different from L. rhamnosus GG and to cluster in two distinct lineages. All L. rhamnosus strains activated complement in serum and none of them bound complement regulators. Four out of 16 clinical blood isolates induced platelet aggregation and/or formed more biofilms than L. rhamnosus GG, which did not display platelet aggregation activity nor showed strong biofilm formation. These findings suggest that clinical L. rhamnosus isolates show considerable heterogeneity but are clearly different from L. rhamnosus GG at the genomic level. All L. rhamnosus strains are still normally recognized by the human complement system. PMID:28493885

Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants.

PubMed

Pareja, Fresia; Geyer, Felipe C; Marchiò, Caterina; Burke, Kathleen A; Weigelt, Britta; Reis-Filho, Jorge S

2016-01-01

Triple-negative breast cancers (TNBCs), defined by lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12-17% of breast cancers and are clinically perceived as a discrete breast cancer subgroup. Nonetheless, TNBC has been shown to constitute a vastly heterogeneous disease encompassing a wide spectrum of entities with marked genetic, transcriptional, histological and clinical differences. Although most TNBCs are high-grade tumors, there are well-characterized low-grade TNBCs that have an indolent clinical course, whose natural history, molecular features and optimal therapy vastly differ from those of high-grade TNBCs. Secretory and adenoid cystic carcinomas are two histologic types of TNBCs underpinned by specific fusion genes; these tumors have an indolent clinical behavior and lack all of the cardinal molecular features of high-grade triple-negative disease. Recent studies of rare entities, including lesions once believed to constitute mere benign breast disease (e.g., microglandular adenosis), have resulted in the identification of potential precursors of TNBC and suggested the existence of a family of low-grade triple-negative lesions that, despite having low-grade morphology and indolent clinical behavior, have been shown to harbor the complex genomic landscape of common forms of TNBC, and may progress to high-grade disease. In this review, we describe the heterogeneity of TNBC and focus on the histologic and molecular features of low-grade forms of TNBC. Germane to addressing the challenges posed by the so-called triple-negative disease is the realization that TNBC is merely a descriptive term, and that low-grade types of TNBC may be driven by distinct sets of genetic alterations.

Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants

PubMed Central

Pareja, Fresia; Geyer, Felipe C; Marchiò, Caterina; Burke, Kathleen A; Weigelt, Britta; Reis-Filho, Jorge S

2016-01-01

Triple-negative breast cancers (TNBCs), defined by lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12–17% of breast cancers and are clinically perceived as a discrete breast cancer subgroup. Nonetheless, TNBC has been shown to constitute a vastly heterogeneous disease encompassing a wide spectrum of entities with marked genetic, transcriptional, histological and clinical differences. Although most TNBCs are high-grade tumors, there are well-characterized low-grade TNBCs that have an indolent clinical course, whose natural history, molecular features and optimal therapy vastly differ from those of high-grade TNBCs. Secretory and adenoid cystic carcinomas are two histologic types of TNBCs underpinned by specific fusion genes; these tumors have an indolent clinical behavior and lack all of the cardinal molecular features of high-grade triple-negative disease. Recent studies of rare entities, including lesions once believed to constitute mere benign breast disease (e.g., microglandular adenosis), have resulted in the identification of potential precursors of TNBC and suggested the existence of a family of low-grade triple-negative lesions that, despite having low-grade morphology and indolent clinical behavior, have been shown to harbor the complex genomic landscape of common forms of TNBC, and may progress to high-grade disease. In this review, we describe the heterogeneity of TNBC and focus on the histologic and molecular features of low-grade forms of TNBC. Germane to addressing the challenges posed by the so-called triple-negative disease is the realization that TNBC is merely a descriptive term, and that low-grade types of TNBC may be driven by distinct sets of genetic alterations. PMID:28721389

Complex posttraumatic stress disorder: The need to consolidate a distinct clinical syndrome or to reevaluate features of psychiatric disorders following interpersonal trauma?

PubMed

Giourou, Evangelia; Skokou, Maria; Andrew, Stuart P; Alexopoulou, Konstantina; Gourzis, Philippos; Jelastopulu, Eleni

2018-03-22

Complex posttraumatic stress disorder (Complex PTSD) has been recently proposed as a distinct clinical entity in the WHO International Classification of Diseases, 11 th version, due to be published, two decades after its first initiation. It is described as an enhanced version of the current definition of PTSD, with clinical features of PTSD plus three additional clusters of symptoms namely emotional dysregulation, negative self-cognitions and interpersonal hardship, thus resembling the clinical features commonly encountered in borderline personality disorder (BPD). Complex PTSD is related to complex trauma which is defined by its threatening and entrapping context, generally interpersonal in nature. In this manuscript, we review the current findings related to traumatic events predisposing the above-mentioned disorders as well as the biological correlates surrounding them, along with their clinical features. Furthermore, we suggest that besides the present distinct clinical diagnoses (PTSD; Complex PTSD; BPD), there is a cluster of these comorbid disorders, that follow a continuum of trauma and biological severity on a spectrum of common or similar clinical features and should be treated as such. More studies are needed to confirm or reject this hypothesis, particularly in clinical terms and how they correlate to clinical entities' biological background, endorsing a shift from the phenomenologically only classification of psychiatric disorders towards a more biologically validated classification.

Pustular psoriasis: pathophysiology and current treatment perspectives

PubMed Central

Benjegerdes, Katie E; Hyde, Kimberly; Kivelevitch, Dario; Mansouri, Bobbak

2016-01-01

Psoriasis vulgaris is a chronic inflammatory disease that classically affects skin and joints and is associated with numerous comorbidities. There are several clinical subtypes of psoriasis including the uncommon pustular variants, which are subdivided into generalized and localized forms. Generalized forms of pustular psoriasis include acute generalized pustular psoriasis, pustular psoriasis of pregnancy, and infantile and juvenile pustular psoriasis. Localized forms include acrodermatitis continua of Hallopeau and palmoplantar pustular psoriasis. These subtypes vary in their presentations, but all have similar histopathologic characteristics. The immunopathogenesis of each entity remains to be fully elucidated and some debate exists as to whether these inflammatory pustular dermatoses should be classified as entities distinct from psoriasis vulgaris. Due to the rarity of these conditions and the questionable link to the common, plaque-type psoriasis, numerous therapies have shown variable results and most entities remain difficult to treat. With increasing knowledge of the pathogenesis of these variants of pustular psoriasis, the development and use of biologic and other immunomodulatory therapies holds promise for the future of successfully treating pustular variants of psoriasis. PMID:29387600

Multisystemic Disease Modeling of Liver-Derived Protein Folding Disorders Using Induced Pluripotent Stem Cells (iPSCs).

PubMed

Leung, Amy; Murphy, George J

2016-01-01

Familial transthyretin amyloidosis (ATTR) is an autosomal dominant protein-folding disorder caused by over 100 distinct mutations in the transthyretin (TTR) gene. In ATTR, protein secreted from the liver aggregates and forms fibrils in target organs, chiefly the heart and peripheral nervous system, highlighting the need for a model capable of recapitulating the multisystem complexity of this clinically variable disease. Here, we describe detailed methodologies for the directed differentiation of protein folding disease-specific iPSCs into hepatocytes that produce mutant protein, and neural-lineage cells often targeted in disease. Methodologies are also described for the construction of multisystem models and drug screening using iPSCs.

Potential roles for uncoupling proteins in HIV lipodystrophy.

PubMed

Nolan, David; Pace, Craig

2004-07-01

The 'HIV lipodystrophy syndrome' consists of several distinct components, including lipoatrophy (pathological subcutaneous fat loss), lipohypertrophy (abdominal/visceral adiposity), and metabolic complications including insulin resistance and dyslipidemia. Lipoatrophy appears to represent an adipose tissue-specific form of mitochondrial toxicity associated strongly with stavudine NRTI therapy, whilst the 'metabolic syndrome' phenotype is associated with HIV protease inhibitor therapy. In this context, the role of uncoupling proteins (UCPs) in modulating resting energy expenditure in response to elevated fatty acid flux associated with the 'metabolic syndrome' is supported by clinical data as well as findings of elevated adipose tissue UCP expression. The role of UCPs in this syndrome therefore exemplifies the multifactorial nature of these antiretroviral therapy complications.

[Frozen shoulder. Diagnosis and therapy].

PubMed

Schultheis, A; Reichwein, F; Nebelung, W

2008-11-01

The condition of shoulder stiffness is often called adhesive capsulitis or frozen shoulder. It is regarded as a distinct clinical entity showing a benign and regular course. The major clinical feature is significant reduction in both active and passive range of motion (ROM) accompanied by stage-dependent pain, allowing for a clinical diagnosis. There are primary and secondary forms, the former having an unknown etiology and increased occurrence in patients with metabolic disorders and the latter being seen with prior injury or operation. Three stages, each lasting 4-6 months, mark the clinical course. The progression of the disease is self-limiting and may occasionally resolve in partial restitution. In the first stage ("freezing"), the shoulder continuously loses passive motion and causes worsening pain. Continuing stiffness and improvements in pain and inflammation are characteristic of the second stage ("frozen"). In the third stage ("thawing"), restriction of shoulder motion decreases, and ROM increases. Treatment should be adjusted to these stages. Recommendations include analgesics and joint injections in the first stage and physiotherapy in combination with manual therapy in the second and third stages. In cases of failure, passive exercise under interscalene block, manipulation under general anesthesia, or arthroscopic arthrolysis should be considered.

Intense imagery movements: a common and distinct paediatric subgroup of motor stereotypies.

PubMed

Robinson, Sally; Woods, Martin; Cardona, Francesco; Baglioni, Valentina; Hedderly, Tammy

2014-12-01

The aim of this article is to describe a subgroup of children who presented with stereotyped movements in the context of episodes of intense imagery. This is of relevance to current discussions regarding the clinical usefulness of diagnosing motor stereotypies during development. The sample consisted of 10 children (nine males, one female; mean age 8y 6mo [SD 2y 5mo], range 6-15y). Referrals were from acute paediatricians, neurologists, and tertiary epilepsy services. Children were assessed by multidisciplinary teams with expertise in paediatric movement disorders. Stereotypies presented as paroxysmal complex movements involving upper and lower limbs. Imagery themes typically included computer games (60%), cartoons/films (40%), and fantasy scenes (30%). Comorbid developmental difficulties were reported for 80% of children. Brain imaging and electrophysiological investigations had been conducted for 50% of the children before referral to the clinic. The descriptive term 'intense imagery movements' (IIM) was applied if (after interview) the children reported engaging in acts of imagery while performing stereotyped movements. We believe these children may form a common and discrete stereotypy subgroup, with the concept of IIM being clinically useful to ensure the accurate diagnosis and clinical management of this paediatric movement disorder. © 2014 Mac Keith Press.

Evaluation of cellular immunological responses in mono- and polymorphic clinical forms of post-kala-azar dermal leishmaniasis in India.

PubMed

Kaushal, H; Bras-Gonçalves, R; Avishek, K; Kumar Deep, D; Petitdidier, E; Lemesre, J-L; Papierok, G; Kumar, S; Ramesh, V; Salotra, P

2016-07-01

Post-kala-azar dermal leishmaniasis (PKDL) is a chronic dermal complication that occurs usually after recovery from visceral leishmaniasis (VL). The disease manifests into macular, papular and/or nodular clinical types with mono- or polymorphic presentations. Here, we investigated differences in immunological response between these two distinct clinical forms in Indian PKDL patients. Peripheral blood mononuclear cells of PKDL and naive individuals were exposed in vitro to total soluble Leishmania antigen (TSLA). The proliferation index was evaluated using an enzyme-linked immunosorbent assay (ELISA)-based lymphoproliferative assay. Cytokines and granzyme B levels were determined by cytometric bead array. Parasite load in tissue biopsy samples of PKDL was quantified by quantitative polymerase chain reaction (qPCR). The proportion of different lymphoid subsets in peripheral blood and the activated T cell population were estimated using flow cytometry. The study demonstrated heightened cellular immune responses in the polymorphic PKDL group compared to the naive group. The polymorphic group showed significantly higher lymphoproliferation, increased cytokines and granzyme B levels upon TSLA stimulation, and a raised proportion of circulating natural killer (NK) T cells against naive controls. Furthermore, the polymorphic group showed a significantly elevated proportion of activated CD4(+) and CD8(+) T cells upon in-vitro TSLA stimulation. Thus, the polymorphic variants showed pronounced cellular immunity while the monomorphic form demonstrated a comparatively lower cellular response. Additionally, the elevated level of both activated CD4(+) and CD8(+) T cells, coupled with high granzyme B secretion upon in-vitro TSLA stimulation, indicated the role of cytotoxic cells in resistance to L. donovani infection in polymorphic PKDL. © 2016 British Society for Immunology.

Simultaneous analysis of multiple T helper subsets in leprosy reveals distinct patterns of Th1, Th2, Th17 and Tregs markers expression in clinical forms and reactional events.

PubMed

Azevedo, Michelle de Campos Soriani; Marques, Heloisa; Binelli, Larissa Sarri; Malange, Mariana Silva Vieira; Devides, Amanda Carreira; Silva, Eliane Aparecida; Fachin, Luciana Raquel Vincenzi; Ghidella, Cassio Cesar; Soares, Cleverson Teixeira; Garlet, Gustavo Pompermaier; Rosa, Patrícia Sammarco; Belone, Andrea de Farias Fernandes; Trombone, Ana Paula Favaro

2017-12-01

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. Previous studies have demonstrated that the difference among clinical forms of leprosy can be associated with the immune response of patients, mainly by T helper (Th) and regulatory T cells (Tregs). Then, aiming at clarifying the immune response, the expression of cytokines related to Th1, Th2, Th17 and Tregs profiles were evaluated by qPCR in 87 skin biopsies from leprosy patients. Additionally, cytokines and anti-PGL-1 antibodies were determined in serum by ELISA. The results showed that the expression of various targets (mRNA) related to Th1, Th2, Th17 and Tregs were significantly modulated in leprosy when compared with healthy individuals, suggesting the presence of a mixed profile. In addition, the targets related to Th1 predominated in the tuberculoid pole and side and Th2 and Tregs predominated in the lepromatous pole and side; however, Th17 targets showed a mixed profile. Concerning reactional events, Tregs markers were decreased and IL-15 was increased in reversal reaction and IL-17F, CCL20 and IL-8 in erythema nodosum leprosum, when compared with the respective non-reactional leprosy patients. Additionally, ELISA analysis demonstrated that IL-22, IL-6, IL-10 and anti-PGL-1 antibody levels were significantly higher in the serum of patients when compared with healthy individuals, and IL-10 and anti-PGL-1 antibodies were also increased in the lepromatous pole and side. Together, these results indicate that Th1, Th2 and Th17 are involved in the determination of clinical forms of leprosy and suggest that decreased Tregs activity may be involved in the pathogenesis of reactional events.

Selective photoswitching of the binuclear spin crossover compound {[Fe(bt)(NCS)2]2(bpm)} into two distinct macroscopic phases.

PubMed

Moussa, N Ould; Molnár, G; Bonhommeau, S; Zwick, A; Mouri, S; Tanaka, K; Real, J A; Bousseksou, A

2005-03-18

The low-spin (LS-LS, S = 0) diamagnetic form of the binuclear spin crossover complex {[Fe(bt)(NCS)(2)](2)(bpm)} was selectively photoconverted into two distinct macroscopic phases at different excitation wavelengths (1342 or 647.1 nm). These long-lived metastable phases have been identified, respectively, as the symmetry-broken paramagnetic form (HS-LS, S = 2) and the antiferromagnetically coupled (HS-HS, S = 0) high-spin form of the compound. The selectivity may be explained by the strong coupling of the primary excited states to the paramagnetic state.

The Roles of Cigarette Smoking and the Lung in the Transitions between Phases of Preclinical Rheumatoid Arthritis

PubMed Central

Sparks, Jeffrey A.; Karlson, Elizabeth W.

2016-01-01

While the etiology of rheumatoid arthritis (RA) remains to be fully elucidated, recent research has advanced the understanding of RA pathogenesis to the point where clinical trials for RA prevention are underway. The current paradigm for RA pathogenesis is that individuals progress through distinct preclinical stages prior to the onset of clinically apparent RA. These preclinical RA phases consist of genetic risk, local inflammation, presence of RA-related autoantibodies, asymptomatic systemic inflammation, and early non-specific symptoms prior to clinical seropositive RA. Epidemiologic studies have been important in forming hypotheses related to the biology occurring in preclinical RA. Specifically, studies associating cigarette smoking with overall RA risk as well as transitions between phases of preclinical RA were vital in helping to establish the lung as a potential important initiating site in the pathogenesis of seropositive RA. Herein, we review the epidemiology associating smoking with transitions in preclinical phases of RA as well as the recent literature supporting the lung as a critical site in RA pathogenesis. PMID:26951253

Quality of Life in Childhood Epilepsy in pediatric patients enrolled in a prospective, open-label clinical study with cannabidiol.

PubMed

Rosenberg, Evan C; Louik, Jay; Conway, Erin; Devinsky, Orrin; Friedman, Daniel

2017-08-01

Recent clinical trials indicate that cannabidiol (CBD) may reduce seizure frequency in pediatric patients with certain forms of treatment-resistant epilepsy. Many of these patients experience significant impairments in quality of life (QOL) in physical, mental, and social dimensions of health. In this study, we measured the caregiver-reported Quality of Life in Childhood Epilepsy (QOLCE) in a subset of patients enrolled in a prospective, open-label clinical study of CBD. Results from caregivers of 48 patients indicated an 8.2 ± 9.9-point improvement in overall patient QOLCE (p < 0.001) following 12 weeks of CBD. Subscores with improvement included energy/fatigue, memory, control/helplessness, other cognitive functions, social interactions, behavior, and global QOL. These differences were not correlated to changes in seizure frequency or adverse events. The results suggest that CBD may have beneficial effects on patient QOL, distinct from its seizure-reducing effects; however, further studies in placebo-controlled, double-blind trials are necessary to confirm this finding. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Revisiting DLB Diagnosis: A Consideration of Prodromal DLB and of the Diagnostic Overlap With Alzheimer Disease.

PubMed

McKeith, Ian; Taylor, John-Paul; Thomas, Alan; Donaghy, Paul; Kane, Joseph

2016-09-01

Efforts to clinically diagnose cases having dementia with Lewy bodies (DLB) identify those with a characteristic clinical syndrome (probable DLB) at the expense of missing an equal, if not greater, number of cases who have atypical presentations thought to be associated with coexisting Alzheimer pathologies. This article argues that further efforts should now be made to characterize this atypical group that constitutes cases previously identified postmortem as the Lewy body variant of Alzheimer disease (AD) or as AD with Lewy bodies. Since such fine distinction is unlikely to be achieved on clinical grounds alone, this new diagnostic category will require robust biomarker validation. Turning to a consideration of early/prodromal diagnosis of both typical and atypical DLB cases, it is suggested that there will be at least 3 prototypical forms-a mild cognitive impairment variant, associated with early visuoperceptual and attentional deficits; a delirium onset DLB with provoked or spontaneous delirium as the presenting features; and a psychiatric disorder DLB with its primary presentation as a late-onset affective disorder or psychosis. © The Author(s) 2016.

Application of Systems Theory in Longitudinal Studies on the Origin and Progression of Alzheimer's Disease.

PubMed

Lista, Simone; Khachaturian, Zaven S; Rujescu, Dan; Garaci, Francesco; Dubois, Bruno; Hampel, Harald

2016-01-01

This chapter questions the prevailing "implicit" assumption that molecular mechanisms and the biological phenotype of dominantly inherited early-onset alzheimer's disease (EOAD) could serve as a linear model to study the pathogenesis of sporadic late-onset alzheimer's disease (LOAD). Now there is growing evidence to suggest that such reductionism may not be warranted; these suppositions are not adequate to explain the molecular complexities of LOAD. For example, the failure of some recent amyloid-centric clinical trials, which were largely based on the extrapolations from EOAD biological phenotypes to the molecular mechanisms in the pathogenesis of LOAD, might be due to such false assumptions. The distinct difference in the biology of LOAD and EOAD is underscored by the presence of EOAD cases without evidence of familial clustering or Mendelian transmission and, conversely, the discovery and frequent reports of such clustering and transmission patterns in LOAD cases. The primary thesis of this chapter is that a radically different way of thinking is required for comprehensive explanations regarding the distinct complexities in the molecular pathogenesis of inherited and sporadic forms of Alzheimer's disease (AD). We propose using longitudinal analytical methods and the paradigm of systems biology (using transcriptomics, proteomics, metabolomics, and lipidomics) to provide us a more comprehensive insight into the lifelong origin and progression of different molecular mechanisms and neurodegeneration. Such studies should aim to clarify the role of specific pathophysiological and signaling pathways such as neuroinflammation, altered lipid metabolism, apoptosis, oxidative stress, tau hyperphosphorylation, protein misfolding, tangle formation, and amyloidogenic cascade leading to overproduction and reduced clearance of aggregating amyloid-beta (Aβ) species. A more complete understanding of the distinct difference in molecular mechanisms, signaling pathways, as well as comparability of the various forms of AD is of paramount importance. The development of knowledge and technologies for early detection and characterization of the disease across all stages will improve the predictions regarding the course of the disease, prognosis, and response to treatment. No doubt such advances will have a significant impact on the clinical management of both EOAD and LOAD patients. The approach propped here, combining longitudinal studies with the systems biology paradigm, will create a more effective and comprehensive framework for development of prevention therapies in AD.

Skin sensitization potency of methyl methacrylate in the local lymph node assay: comparisons with guinea-pig data and human experience.

PubMed

Betts, Catherine J; Dearman, Rebecca J; Heylings, Jon R; Kimber, Ian; Basketter, David A

2006-09-01

There is compelling evidence that contact allergens differ substantially (by 4 or 5 orders of magnitude) with respect to their inherent skin-sensitizing potency. Relative potency can now be measured effectively using the mouse local lymph node assay (LLNA) and such data form the basis of risk assessment and risk management strategies. Such determinations also facilitate distinctions being drawn between the prevalence of skin sensitization to a particular contact allergen and inherent potency. The distinction is important because chemicals that are implicated as common causes of contact allergy are not necessarily potent sensitizers. One example is provided by nickel that is undoubtedly a common cause of allergic contact dermatitis, but is a comparatively weak sensitizer in predictive tests. In an attempt to explore other examples of contact allergens where there may exist a discrepancy between prevalence and potency, we describe here analyses conducted with methyl methacrylate (MMA). Results of LLNA studies have been interpreted in the context of historical clinical data on occupational allergic contact dermatitis associated with exposure to MMA.

Telepsychotherapy and the Therapeutic Relationship: Principles, Advantages, and Case Examples.

PubMed

Kocsis, Barbara J; Yellowlees, Peter

2018-05-01

As the use of technology continues to expand within our mental healthcare system, there has been an increasing interest in conducting psychotherapy online using videoconferencing. Literature pertaining to telepsychotherapy has explored possible drawbacks of this modality on the therapeutic relationship, although several studies have shown that the efficacy of online psychotherapy is equivalent to in-person approaches. Little is written about the potential advantages to the psychotherapeutic relationship when psychotherapy is carried out over videoconferencing. The available literature was reviewed, as were the general principles of telepsychotherapy and the therapeutic relationship, followed by a more in-depth consideration of patient populations for whom telepsychotherapy may offer distinct advantages. The current literature, as well as our own clinical experience, suggests that telepsychotherapy may be effective for a broad range of patients, and it may offer distinct advantages in the building of a trusting psychotherapeutic relationship. Telepsychotherapy offers a novel way to reach and form strong psychotherapeutic relationships with many different types of patients, and it may foster therapeutic intimacy in ways that in-person psychotherapy cannot. More research is needed to further explore this unique modality.

Serrated pathway in colorectal carcinogenesis

PubMed Central

Yamane, Letícia; Scapulatempo-Neto, Cristovam; Reis, Rui Manuel; Guimarães, Denise Peixoto

2014-01-01

Serrated adenocarcinoma is a recently described subset of colorectal cancer (CRC), which account for about 10% of all CRCs and follows an alternative pathway in which serrated polyps replace the traditional adenoma as the precursor lesion to CRC. Serrated polyps form a heterogeneous group of colorectal lesions that includes hyperplastic polyps (HPs), sessile serrated adenoma (SSA), traditional serrated adenoma (TSA) and mixed polyps. HPs are the most common serrated polyp followed by SSA and TSA. This distinct histogenesis is believed to have a major influence in prevention strategies, patient prognosis and therapeutic impact. Genetically, serrated polyps exhibited also a distinct pattern, with KRAS and BRAF having an important contribution to its development. Two other molecular changes that have been implicated in the serrated pathway include microsatellite instability and the CpG island methylator phenotype. In the present review we will address the current knowledge of serrated polyps, clinical pathological features and will update the most recent findings of its molecular pathways. The understanding of their biology and malignancy potential is imperative to implement a surveillance approach in order to prevent colorectal cancer development. PMID:24627599

Molecular Perspectives for mu/delta Opioid Receptor Heteromers as Distinct, Functional Receptors

PubMed Central

Ong, Edmund W.; Cahill, Catherine M.

2014-01-01

Opioid receptors are the sites of action for morphine and the other opioid drugs. Abundant evidence now demonstrates that different opioid receptor types can physically associate to form heteromers. Understandings of the nature, behavior, and role of these opioid receptor heteromers are developing. Owing to their constituent monomers’ involvement in analgesia, mu/delta opioid receptor (M/DOR) heteromers have been a particular focus of attention. There is now considerable evidence demonstrating M/DOR to be an extant and physiologically relevant receptor species. Participating in the cellular environment as a distinct receptor type, M/DOR availability is complexly regulated and M/DOR exhibits unique pharmacology from that of other opioid receptors (ORs), including its constituents. M/DOR appears to have a range of actions that vary in a ligand- (or ligands-) dependent manner. These actions can meaningfully affect the clinical effects of opioid drugs: strategies targeting M/DOR may be therapeutically useful. This review presents and discusses developments in these understandings with a focus on the molecular nature and activity of M/DOR in the context of therapeutic potentials. PMID:24709907

Past, present, and prospects: Reflections 40 years on from the selective impairment of semantic memory (Warrington, 1975).

PubMed

McCarthy, Rosaleen A; Warrington, Elizabeth K

2016-10-01

We summarize the main findings and conclusions of Warrington's (1975) paper, The Selective Impairment of Semantic memory, a neuropsychological paper that described three cases with degenerative neurological conditions [Warrington, E. K. (1975). The selective impairment of semantic memory. The Quarterly Journal of Experimental Psychology, 27, 635-657]. We consider the developments that have followed from its publication and give a selective overview of the field in 2014. The initial impact of the paper was on neuropsychological investigations of semantic loss followed some 14 years later by the identification of Semantic Dementia (the condition shown by the original cases) as a distinctive form of degenerative disease with unique clinical and pathological characteristics. We discuss the distinction between disorders of semantic storage and refractory semantic access, the evidence for category- and modality-specific impairments of semantics, and the light that has been shed on the structure and organization of semantic memory. Finally we consider the relationship between semantic memory and the skills of reading and writing, phonological processing, and autobiographical memory.

The distinction between juvenile and adult-onset primary open-angle glaucoma

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

Wiggs, J.L.; Haines, J.L.; Damji, K.F.

1996-01-01

Because of the significant differences between the juvenile and adult forms of open-angle glaucoma, especially with regard to inheritance, prevalence, severity, and age of onset, we read with interest the recent publication by Morissette et al., describing a pedigree with a phenotype that overlaps the distinctive features of juvenile-onset open-angle glaucoma (JOAG) and adult-onset primary open-angle glaucoma (usually abbreviated as POAG or COAG). These authors conclude that a gene mapped to human chromosome 1q21-q31 (GLC1A) can be responsible for both juvenile and adult forms of open-angle glaucoma. The implications of such a result could be extremely important, in light ofmore » the high prevalence of the adult form of the disease. However, while the data presented in this report suggest that variable expressivity of the GLC1A gene may lead to a broader range of onset for this form of juvenile glaucoma, these data do not identify the GLC1A gene as an important cause of POAG. To prevent misleading interpretations of this and similar studies, we wish to clarify the distinction between the juvenile and adult forms of open-angle glaucoma. 8 refs.« less

Intraductal Tubulopapillary Neoplasm of the Pancreas: An Update From a Pathologist's Perspective.

PubMed

Rooney, Sarah L; Shi, Jiaqi

2016-10-01

-Intraductal tubulopapillary neoplasm (ITPN) is a rare intraductal epithelial neoplasm of the pancreas recently recognized as a distinct entity by the World Health Organization classification in 2010. It is defined as an intraductal, grossly visible, tubule-forming epithelial neoplasm with high-grade dysplasia and ductal differentiation without overt production of mucin. The diagnosis can be challenging owing to morphologic overlap with other intraductal lesions and its rarity. While recent advances in molecular genetic studies of ITPN have provided new tools to facilitate clinical diagnosis, the limited number of cases has yielded limited follow-up data to guide management. -To provide a clinical, pathologic, and molecular update on ITPN with respect to clinical presentation, imaging findings, histopathologic features, differential diagnosis, biological behavior, molecular characteristics, and treatment options. -Analysis of the pertinent literature (PubMed) and authors' research and clinical practice experience based on institutional and consultation materials. -Clinical presentation, imaging findings, histopathology, immunohistochemistry studies, molecular characteristics, prognosis, and treatment options of ITPN are reviewed. Important differential diagnoses with other intraductal neoplasms of the pancreas-especially intraductal papillary mucinous neoplasm-using histopathologic, molecular, and immunohistochemical studies, are discussed. Despite the recent progress, more studies are necessary to assess the biology and genetics of ITPN for a better understanding of the prognostic factors and treatment options.

CSF Hypocretin-1 Levels and Clinical Profiles in Narcolepsy and Idiopathic CNS Hypersomnia in Norway

PubMed Central

Heier, Mona Skard; Evsiukova, Tatiana; Vilming, Steinar; Gjerstad, Michaela D.; Schrader, Harald; Gautvik, Kaare

2007-01-01

Objective: To evaluate the relationship between CSF hypocretin-1 levels and clinical profiles in narcolepsy and CNS hypersomnia in Norwegian patients. Method: CSF hypocretin-1 was measured by a sensitive radioimmunoassay in 47 patients with narcolepsy with cataplexy, 7 with narcolepsy without cataplexy, 10 with idiopathic CNS hypersomnia, and a control group. Results: Low hypocretin-1 values were found in 72% of the HLA DQB1*0602 positive patients with narcolepsy and cataplexy. Patients with low CSF hypocretin-1 levels reported more extensive muscular involvement during cataplectic attacks than patients with normal levels. Hypnagogic hallucinations and sleep paralysis occurred more frequently in patients with cataplexy than in the other patient groups, but with no correlation to hypocretin-1 levels. Conclusion: About three quarters of the HLA DQB1*0602 positive patients with narcolepsy and cataplexy had low CSF hypocretin-1 values, and appear to form a distinct clinical entity. Narcolepsy without cataplexy could not be distinguished from idiopathic CNS hypersomnia by clinical symptoms or biochemical findings. Citation: Heier MS; Evsiukova T; Vilming S; Gjerstad MD; Schrader H; Gautvik K. CSF hypocretin-1 levels and clinical profiles in narcolepsy and idiopathic CNS hypersomnia in norway. SLEEP 2007;30(8):969-973. PMID:17702265

Amyloid polymorphisms constitute distinct clouds of conformational variants in different etiological subtypes of Alzheimer's disease.

PubMed

Rasmussen, Jay; Mahler, Jasmin; Beschorner, Natalie; Kaeser, Stephan A; Häsler, Lisa M; Baumann, Frank; Nyström, Sofie; Portelius, Erik; Blennow, Kaj; Lashley, Tammaryn; Fox, Nick C; Sepulveda-Falla, Diego; Glatzel, Markus; Oblak, Adrian L; Ghetti, Bernardino; Nilsson, K Peter R; Hammarström, Per; Staufenbiel, Matthias; Walker, Lary C; Jucker, Mathias

2017-12-05

The molecular architecture of amyloids formed in vivo can be interrogated using luminescent conjugated oligothiophenes (LCOs), a unique class of amyloid dyes. When bound to amyloid, LCOs yield fluorescence emission spectra that reflect the 3D structure of the protein aggregates. Given that synthetic amyloid-β peptide (Aβ) has been shown to adopt distinct structural conformations with different biological activities, we asked whether Aβ can assume structurally and functionally distinct conformations within the brain. To this end, we analyzed the LCO-stained cores of β-amyloid plaques in postmortem tissue sections from frontal, temporal, and occipital neocortices in 40 cases of familial Alzheimer's disease (AD) or sporadic (idiopathic) AD (sAD). The spectral attributes of LCO-bound plaques varied markedly in the brain, but the mean spectral properties of the amyloid cores were generally similar in all three cortical regions of individual patients. Remarkably, the LCO amyloid spectra differed significantly among some of the familial and sAD subtypes, and between typical patients with sAD and those with posterior cortical atrophy AD. Neither the amount of Aβ nor its protease resistance correlated with LCO spectral properties. LCO spectral amyloid phenotypes could be partially conveyed to Aβ plaques induced by experimental transmission in a mouse model. These findings indicate that polymorphic Aβ-amyloid deposits within the brain cluster as clouds of conformational variants in different AD cases. Heterogeneity in the molecular architecture of pathogenic Aβ among individuals and in etiologically distinct subtypes of AD justifies further studies to assess putative links between Aβ conformation and clinical phenotype.

Co-circulation of multiple hemorrhagic fever diseases with distinct clinical characteristics in Dandong, China.

PubMed

Chen, Zhi-Hai; Qin, Xin-Cheng; Song, Rui; Shen, Yi; Chen, Xiao-Ping; Wang, Wen; Zhao, Yong-Xiang; Zhang, Jing-Shan; He, Jin-Rong; Li, Ming-Hui; Zhao, Xue-Hua; Liu, De-Wei; Fu, Xiao-Kang; Tian, Di; Li, Xing-Wang; Xu, Jianguo; Plyusnin, Alexander; Holmes, Edward C; Zhang, Yong-Zhen

2014-01-01

Hemorrhagic fevers (HF) caused by viruses and bacteria are a major public health problem in China and characterized by variable clinical manifestations, such that it is often difficult to achieve accurate diagnosis and treatment. The causes of HF in 85 patients admitted to Dandong hospital, China, between 2011-2012 were determined by serological and PCR tests. Of these, 34 patients were diagnosed with Huaiyangshan hemorrhagic fever (HYSHF), 34 with Hemorrhagic Fever with Renal Syndrome (HFRS), one with murine typhus, and one with scrub typhus. Etiologic agents could not be determined in the 15 remaining patients. Phylogenetic analyses of recovered bacterial and viral sequences revealed that the causative infectious agents were closely related to those described in other geographical regions. As these diseases have no distinctive clinical features in their early stage, only 13 patients were initially accurately diagnosed. The distinctive clinical features of HFRS and HYSHF developed during disease progression. Enlarged lymph nodes, cough, sputum, and diarrhea were more common in HYSHF patients, while more HFRS cases presented with headache, sore throat, oliguria, percussion pain kidney area, and petechiae. Additionally, HYSHF patients displayed significantly lower levels of white blood cells (WBC), higher levels of creations kinase (CK) and alanine aminotransferase (ALT), while HFRS patients presented with an elevation of blood urea nitrogen (BUN) and creatinine (CREA). These clinical features will assist in the accurate diagnosis of both HYSHF and HFRS. Overall, our data reveal the complexity of pathogens causing HFs in a single Chinese hospital, and highlight the need for accurate early diagnosis and a better understanding of their distinctive clinical features.

Polymorphic Fibrillation of the Destabilized Fourth Fasciclin-1 Domain Mutant A546T of the Transforming Growth Factor-β-induced Protein (TGFBIp) Occurs through Multiple Pathways with Different Oligomeric Intermediates*

PubMed Central

Andreasen, Maria; Nielsen, Søren B.; Runager, Kasper; Christiansen, Gunna; Nielsen, Niels Chr.; Enghild, Jan J.; Otzen, Daniel E.

2012-01-01

Mutations in the transforming growth factor β-induced protein (TGFBIp) are linked to the development of corneal dystrophies in which abnormal protein deposition in the cornea leads to a loss of corneal transparency and ultimately blindness. Different mutations give rise to phenotypically distinct corneal dystrophies. Most mutations are located in the fourth fasciclin-1 domain (FAS1–4). The amino acid substitution A546T in the FAS1–4 domain is linked to the development of lattice corneal dystrophy with amyloid deposits in the superficial and deep stroma, classifying it as an amyloid disease. Here we provide a detailed description of the fibrillation of the isolated FAS1–4 domain carrying the A546T substitution. The A546T substitution leads to a significant destabilization of FAS1–4 and induces a partially folded structure with increased surface exposure of hydrophobic patches. The mutation also leads to two distinct fibril morphologies. Long straight fibrils composed of pure β-sheet structure are formed at lower concentrations, whereas short and curly fibrils containing a mixture of α-helical and β-sheet structures are formed at higher concentrations. The formation of short and curly fibrils is preceded by the formation of a small number of oligomeric species with high membrane permeabilization potential and rapid fibril formation. The long straight fibrils are formed more slowly and through progressively bigger oligomers that lose their membrane permeabilization potential as fibrillation proceeds beyond the lag phase. These different fibril classes and associated biochemical differences may lead to different clinical symptoms associated with the mutation. PMID:22893702

Multimodal immunogenic cancer cell death as a consequence of anticancer cytotoxic treatments

PubMed Central

Inoue, H; Tani, K

2014-01-01

Apoptotic cell death generally characterized by a morphologically homogenous entity has been considered to be essentially non-immunogenic. However, apoptotic cancer cell death, also known as type 1 programmed cell death (PCD), was recently found to be immunogenic after treatment with several chemotherapeutic agents and oncolytic viruses through the emission of various danger-associated molecular patterns (DAMPs). Extensive studies have revealed that two different types of immunogenic cell death (ICD) inducers, recently classified by their distinct actions in endoplasmic reticulum (ER) stress, can reinitiate immune responses suppressed by the tumor microenvironment. Indeed, recent clinical studies have shown that several immunotherapeutic modalities including therapeutic cancer vaccines and oncolytic viruses, but not conventional chemotherapies, culminate in beneficial outcomes, probably because of their different mechanisms of ICD induction. Furthermore, interests in PCD of cancer cells have shifted from its classical form to novel forms involving autophagic cell death (ACD), programmed necrotic cell death (necroptosis), and pyroptosis, some of which entail immunogenicity after anticancer treatments. In this review, we provide a brief outline of the well-characterized DAMPs such as calreticulin (CRT) exposure, high-mobility group protein B1 (HMGB1), and adenosine triphosphate (ATP) release, which are induced by the morphologically distinct types of cell death. In the latter part, our review focuses on how emerging oncolytic viruses induce different forms of cell death and the combinations of oncolytic virotherapies with further immunomodulation by cyclophosphamide and other immunotherapeutic modalities foster dendritic cell (DC)-mediated induction of antitumor immunity. Accordingly, it is increasingly important to fully understand how and which ICD inducers cause multimodal ICD, which should aid the design of reasonably multifaceted anticancer modalities to maximize ICD-triggered antitumor immunity and eliminate residual or metastasized tumors while sparing autoimmune diseases. PMID:23832118

Neurobehavioral Perspectives on the Distinction between Fear and Anxiety

ERIC Educational Resources Information Center

Perusini, Jennifer N.; Fanselow, Michael S.

2015-01-01

In this review, we discuss the usefulness of the distinction between fear and anxiety. The clinical use of the labels is ambiguous, often defining one in terms of the other. We first consider what a useful, objective, and scientifically valid definition would entail and then evaluate several fear/anxiety distinctions that have been made in the…

A genetically diverse but distinct North American population of Sarcocystis neurona includes an overrepresented clone described by 12 microsatellite alleles.

PubMed

Asmundsson, Ingrid M; Dubey, J P; Rosenthal, Benjamin M

2006-09-01

The population genetics and systematics of most coccidians remain poorly defined despite their impact on human and veterinary health. Non-recombinant parasite clones characterized by distinct transmission and pathogenesis traits persist in the coccidian Toxoplasma gondii despite opportunities for sexual recombination. In order to determine whether this may be generally true for tissue-cyst forming coccidia, and to address evolutionary and taxonomic problems within the genus Sarcocystis, we characterized polymorphic microsatellite markers in Sarcocystis neurona, the major causative agent of equine protozoal myeloencephalitis (EPM). Bayesian statistical modeling, phylogenetic reconstruction based on genotypic chord distances, and analyses of linkage disequilibrium were employed to examine the population structure within S. neurona and closely related Sarcocystis falcatula isolates from North and South America. North American S. neurona were clearly differentiated from those of South America and also from isolates of S. falcatula. Although S. neurona is characterized by substantial allelic and genotypic diversity typical of interbreeding populations, one genotype occurs with significantly excessive frequency; thus, some degree of asexual propagation of S. neurona clones may naturally occur. Finally, S. neurona isolated from disparate North American localities and diverse hosts (opossums, a Southern sea otter, and horses) comprise a single genetic population. Isolates associated with clinical neurological disease bear no obvious distinction as measured by these presumably neutral genetic markers.

Miscellaneous rare paratesticular tumors.

PubMed

Henley, J D; Ferry, J; Ulbright, T M

2000-11-01

A few uncommon but distinctive tumors may preferentially involve the paratestis. The 3 unusual tumors that represent the focus of this discussion are the ovarian-type epithelial tumors (OTET), the desmoplastic small round cell tumor (DSRCT), and the melanotic neuroectodermal tumor of infancy (MNTI). The OTETs are testicular homologues of their more common namesake counterparts that arise in the ovary. Most frequent of these are serous tumors of borderline malignancy, with fewer cases of serous carcinomas or other forms of mullerian differentiation. DSRCT is an increasingly recognized, aggressive, "small blue cell" neoplasm with distinctive clinical and pathologic features. These polyphenotypic tumors characteristically, but not invariably, arise in intimate association with the serosal membrane of the peritoneal cavity and harbor a signature translocation-t(11;22)(p13,q12). In the paratestis they often involve the surface of the epididymis. The MNTI is an enigmatic, histologically distinctive, low-grade neoplasm occasionally encountered in the epididymis. Recognition of its features is essential to avoid misdiagnosis as a more aggressive "small blue cell" neoplasm and consequent therapeutic mismanagement. Primary hematopoietic tumors of the paratesticular structures are rare. There appears to be a tendency for young men to have low-grade lymphomas with an indolent course and older patients to develop higher-grade tumors. Plasmacytoma and granulocytic sarcoma of the paratestis are even more rare and are often susceptible to misinterpretation. Finally, metastatic tumors and a variety of other very rare neoplasms are discussed.

Interaction vs. observation: distinctive modes of social cognition in human brain and behavior? A combined fMRI and eye-tracking study.

PubMed

Tylén, Kristian; Allen, Micah; Hunter, Bjørk K; Roepstorff, Andreas

2012-01-01

Human cognition has usually been approached on the level of individual minds and brains, but social interaction is a challenging case. Is it best thought of as a self-contained individual cognitive process aiming at an "understanding of the other," or should it rather be approached as an collective, inter-personal process where individual cognitive components interact on a moment-to-moment basis to form coupled dynamics? In a combined fMRI and eye-tracking study we directly contrasted these models of social cognition. We found that the perception of situations affording social contingent responsiveness (e.g., someone offering or showing you an object) elicited activations in regions of the right posterior temporal sulcus and yielded greater pupil dilation corresponding to a model of coupled dynamics (joint action). In contrast, the social-cognitive perception of someone "privately" manipulating an object elicited activation in medial prefrontal cortex, the right inferior frontal gyrus and right inferior parietal lobus, regions normally associated with Theory of Mind and with the mirror neuron system. Our findings support a distinction in social cognition between social observation and social interaction, and demonstrate that simple ostensive cues may shift participants' experience, behavior, and brain activity between these modes. The identification of a distinct, interactive mode has implications for research on social cognition, both in everyday life and in clinical conditions.

The War on Drugs That Wasn't: Wasted Whiteness, “Dirty Doctors,” and Race in Media Coverage of Prescription Opioid Misuse

PubMed Central

Netherland, Julie; Hansen, Helena B.

2016-01-01

The past decade in the U.S. has been marked by a media fascination with the white prescription opioid cum heroin user. In this paper, we contrast media coverage of white non-medical opioid users with that of black and brown heroin users to show how divergent representations lead to different public and policy responses. A content analysis of 100 popular press articles from 2001 and 2011 in which half describe heroin users and half describe prescription opioid users revealed a consistent contrast between criminalized urban black and Latino heroin injectors with sympathetic portrayals of suburban white prescription opioid users. Media coverage of the suburban and rural opioid “epidemic” of the 2000s helped draw a symbolic, and then legal, distinction between (urban) heroin addiction and (suburban and rural) prescription opioid addiction that is reminiscent of the legal distinction between crack cocaine and powder cocaine of the 1980s and 90s. This distinction reinforces the racialized deployment of the War on Drugs and is sustained by the lack of explicit discussion of race in the service of “color blind ideology.” We suggest potential correctives to these racially divergent patterns, in the form of socially responsible media practices and of clinical engagement with public policy. PMID:27272904

Pseudomonas aeruginosa Pore-Forming Exolysin and Type IV Pili Cooperate To Induce Host Cell Lysis

PubMed Central

Basso, Pauline; Ragno, Michel; Elsen, Sylvie; Reboud, Emeline; Golovkine, Guillaume; Bouillot, Stephanie; Huber, Philippe; Lory, Stephen; Faudry, Eric

2017-01-01

ABSTRACT   Clinical strains of Pseudomonas aeruginosa lacking the type III secretion system genes employ a toxin, exolysin (ExlA), for host cell membrane disruption. Here, we demonstrated that ExlA export requires a predicted outer membrane protein, ExlB, showing that ExlA and ExlB define a new active two-partner secretion (TPS) system of P. aeruginosa. In addition to the TPS signals, ExlA harbors several distinct domains, which include one hemagglutinin domain, five arginine-glycine-aspartic acid (RGD) motifs, and a C-terminal region lacking any identifiable sequence motifs. However, this C-terminal region is important for the toxic activity, since its deletion abolishes host cell lysis. Using lipid vesicles and eukaryotic cells, including red blood cells, we demonstrated that ExlA has a pore-forming activity which precedes cell membrane disruption of nucleated cells. Finally, we developed a high-throughput cell-based live-dead assay and used it to screen a transposon mutant library of an ExlA-producing P. aeruginosa clinical strain for bacterial factors required for ExlA-mediated toxicity. The screen resulted in the identification of proteins involved in the formation of type IV pili as being required for ExlA to exert its cytotoxic activity by promoting close contact between bacteria and the host cell. These findings represent the first example of cooperation between a pore-forming toxin of the TPS family and surface appendages in host cell intoxication. PMID:28119472

Cystic Neutrophilic Granulomatous Mastitis: Further Characterization of a Distinctive Histopathologic Entity Not Always Demonstrably Attributable to Corynebacterium Infection.

PubMed

D'Alfonso, Timothy M; Moo, Tracy-Ann; Arleo, Elizabeth K; Cheng, Esther; Antonio, Lilian B; Hoda, Syed A

2015-10-01

Granulomatous lobular mastitis (GLM) is an uncommon condition that typically occurs in parous, reproductive-aged women and can simulate malignancy on the basis of clinical and imaging features. A distinctive histologic pattern termed cystic neutrophilic granulomatous mastitis (CNGM) is seen in some cases of GLM and has been associated with Corynebacterium infection. We sought to further characterize the clinical, imaging, and histopathologic features of CNGM by studying 12 cases and attempted to establish the relationship of this disease with Corynebacterium infection. Patients were women ranging in age from 25 to 49 years (median: 34 y), and all presented with a palpable mass that was painful in half of the cases. In 2 of 9 cases, imaging was highly suspicious for malignancy (BI-RADS 5). CNGM was characterized by lobulocentric granulomas with mixed inflammation and clear vacuoles lined by neutrophils within granulomas. Gram-positive bacilli were identified in 5/12 cases. In 4 patients, the disease process worsened after the diagnostic core biopsy, with the development of a draining sinus in 2 cases. No growth of bacteria was seen in any microbial cultures. No bacterial DNA was identified by 16S rDNA polymerase chain reaction for 1 case that showed gram-positive bacilli on histology. Patients were treated with variable combinations of surgery, antibiotics, and steroids. The time to significant resolution of symptoms ranged from 2 weeks to 6 months. Similar to other forms of GLM, CNGM can mimic malignancy clinically and on imaging. When encountered in a needle core biopsy sample, recognition of the characteristic histologic pattern and its possible association with Corynebacterium infection can help guide treatment.

Two distinct β-sheet structures in Italian-mutant amyloid-beta fibrils: a potential link to different clinical phenotypes.

PubMed

Hubin, Ellen; Deroo, Stéphanie; Schierle, Gabriele Kaminksi; Kaminski, Clemens; Serpell, Louise; Subramaniam, Vinod; van Nuland, Nico; Broersen, Kerensa; Raussens, Vincent; Sarroukh, Rabia

2015-12-01

Most Alzheimer's disease (AD) cases are late-onset and characterized by the aggregation and deposition of the amyloid-beta (Aβ) peptide in extracellular plaques in the brain. However, a few rare and hereditary Aβ mutations, such as the Italian Glu22-to-Lys (E22K) mutation, guarantee the development of early-onset familial AD. This type of AD is associated with a younger age at disease onset, increased β-amyloid accumulation, and Aβ deposition in cerebral blood vessel walls, giving rise to cerebral amyloid angiopathy (CAA). It remains largely unknown how the Italian mutation results in the clinical phenotype that is characteristic of CAA. We therefore investigated how this single point mutation may affect the aggregation of Aβ1-42 in vitro and structurally characterized the resulting fibrils using a biophysical approach. This paper reports that wild-type and Italian-mutant Aβ both form fibrils characterized by the cross-β architecture, but with distinct β-sheet organizations, resulting in differences in thioflavin T fluorescence and solvent accessibility. E22K Aβ1-42 oligomers and fibrils both display an antiparallel β-sheet structure, in comparison with the parallel β-sheet structure of wild-type fibrils, characteristic of most amyloid fibrils described in the literature. Moreover, we demonstrate structural plasticity for Italian-mutant Aβ fibrils in a pH-dependent manner, in terms of their underlying β-sheet arrangement. These findings are of interest in the ongoing debate that (1) antiparallel β-sheet structure might represent a signature for toxicity, which could explain the higher toxicity reported for the Italian mutant, and that (2) fibril polymorphism might underlie differences in disease pathology and clinical manifestation.

Pathogenesis of canine distemper virus in experimentally infected raccoon dogs, foxes, and minks.

PubMed

Zhao, Jianjun; Shi, Ning; Sun, Yangang; Martella, Vito; Nikolin, Veljko; Zhu, Chunsheng; Zhang, Hailing; Hu, Bo; Bai, Xue; Yan, Xijun

2015-10-01

Canine distemper virus (CDV) infects a broad range of carnivores and causes a highly contagious disease with severe immunosuppression. The disease severity markedly varies in different species. To investigate the pathogenesis of CDV in raccoon dog (Nyctereutes procyonoides), fox (Vulpes vulpes) and mink (Neovison vison) species, three groups of CDV sero-negative animals were infected with CDV strain LN(10)1. This CDV strain belongs to the Asia-1 genotype, which is epidemiologically predominant in carnivores in China. CDV infection provoked marked differences in virulence in the three species that were studied. Raccoon dogs developed fever, severe conjunctivitis, and pathological lesions, with 100% (5/5) mortality and with high viral RNA loads in organs within 15 days post infection (dpi). In infected foxes, the onset of the disease was delayed, with 40% (2/5) mortality by 21 dpi. Infected minks developed only mild clinical signs and pathological lesions, and mortality was not observed. Raccoon dogs and foxes showed more severe immune suppression (lymphopenia, decreased lymphocyte proliferation, viremia and low-level virus neutralizing antibodies) than minks. We also observed a distinct pattern of cytokine mRNA transcripts at different times after infection. Decreased IFN-γ and IL-4 mRNA responses were evident in the animals with fatal disease, while up-regulation of these cytokines was observed in the animals surviving the infection. Increased TNF-α response was detected in animals with mild or severe clinical signs. Based on the results, we could distinguish three different patterns of disease after experimental CDV infection, e.g. a mild form in minks, a moderate form in foxes and a severe disease in raccoon dogs. The observed differences in susceptibility to CDV could be related to distinct host cytokine profiles. Comparative evaluation of CDV pathogenesis in various animal species is pivotal to generate models suitable for the evaluation of CDV-host interactions and of vaccine response. Copyright © 2015 Elsevier B.V. All rights reserved.

The picture superiority effect: support for the distinctiveness model.

PubMed

Mintzer, M Z; Snodgrass, J G

1999-01-01

The form change paradigm was used to explore the basis for the picture superiority effect. Recognition memory for studied pictures and words was tested in their study form or the alternate form. Form change cost was defined as the difference between recognition performance for same and different form items. Based on the results of Experiment 1 and previous studies, it was difficult to determine the relative cost for studied pictures and words due to a reversal of the mirror effect. We hypothesized that the reversed mirror effect results from subjects' basing their recognition decisions on their assumptions about the study form. Experiments 2 and 3 confirmed this hypothesis and generated a method for evaluating the relative cost for pictures and words despite the reversed mirror effect. More cost was observed for pictures than words, supporting the distinctiveness model of the picture superiority effect.

Color-binding errors during rivalrous suppression of form.

PubMed

Hong, Sang Wook; Shevell, Steven K

2009-09-01

How does a physical stimulus determine a conscious percept? Binocular rivalry provides useful insights into this question because constant physical stimulation during rivalry causes different visual experiences. For example, presentation of vertical stripes to one eye and horizontal stripes to the other eye results in a percept that alternates between horizontal and vertical stripes. Presentation of a different color to each eye (color rivalry) produces alternating percepts of the two colors or, in some cases, a color mixture. The experiments reported here reveal a novel and instructive resolution of rivalry for stimuli that differ in both form and color: perceptual alternation between the rivalrous forms (e.g., horizontal or vertical stripes), with both eyes' colors seen simultaneously in separate parts of the currently perceived form. Thus, the colors presented to the two eyes (a) maintain their distinct neural representations despite resolution of form rivalry and (b) can bind separately to distinct parts of the perceived form.

DNA methylation patterns of genes related to immune response in the different clinical forms of oral lichen planus.

PubMed

Cruz, Aline Fernanda; de Resende, Renata Gonçalves; de Lacerda, Júlio César Tanos; Pereira, Núbia Braga; Melo, Leonardo Augusto; Diniz, Marina Gonçalves; Gomes, Carolina Cavalieri; Gomez, Ricardo Santiago

2018-01-01

The oral lichen planus is a chronic inflammatory disease. Although its aetiology is not well understood, the role of T lymphocytes in its inflammatory events is recognised. Identifying the epigenetic mechanisms involved in the pathogenesis of this immune-mediated condition is fundamental for understanding the inflammatory reaction that occurs in the disease. The purpose of this work was to evaluate the methylation pattern of 21 immune response-related genes in the different clinical forms of oral lichen planus. A cross-sectional study was performed to analyse the DNA methylation patterns in three distinct groups of oral lichen planus: (i) reticular/plaque lesions; (ii) erosive lesions; (iii) normal oral mucosa (control group). After DNA extraction from biopsies, the samples were submitted to digestions by methylation-sensitive and methylation-dependent enzymes and double digestion. The relative percentage of methylated DNA for each gene was provided using real-time polymerase chain reaction arrays. Hypermethylation of the STAT5A gene was observed only in the control group (59.0%). A higher hypermethylation of the ELANE gene was found in reticular/plaque lesions (72.1%) compared to the erosive lesions (50.0%). Our results show variations in the methylation profile of immune response-related genes, according to the clinical type of oral lichen planus after comparing with the normal oral mucosa. Further studies are necessary to validate these findings using gene expression analysis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dermoid Cysts of the Floor of the Mouth: Two Case Reports

PubMed Central

Makos, Christos; Noussios, George; Peios, Marinos; Gougousis, Spyridon; Chouridis, Pantelis

2011-01-01

Dermoid cysts in the floor of the mouth may be congenital or acquired. The congenital form, according to the main theory, originates from embryonic cells of the 1st and 2nd branchial arch. The acquired form may be due to traumatic or iatrogenic causes and as a result of the occlusion of a sebaceous gland duct. Its occurrence is less and is estimated to be from 1.6 to 6.4% of the dermoid cysts of the body in adults and 0.29% of the head and neck tumors occurring in children. They may also be classified as anatomical and histological. Anatomically, they are divided into median genioglossal, median geniohyoid, and lateral cysts, while histologically they are divided into epidermoid, dermoid cysts and teratomas. Clinically, a distinction between supra and inferior type as well as between central and lateral type is proposed in relation to themylohyoidmuscle and themidline, respectively. Histologically, an estimation of dermoid, epidermoid, and teratoid cysts is reported. Enucleation via intraoral and/or extraoral approach is the method of treatment. Two case reports of dermoid cysts in the floor of the mouth are presented in this paper, and an evaluation with regard to pathology, clinical findings, differential diagnosis, and treatment is discussed. PMID:21922020

Hypoplasia-associated Severe Early Childhood Caries – A Proposed Definition

PubMed Central

Caufield, P.W.; Li, Y.; Bromage, T.G.

2012-01-01

We propose a new classification of severe early childhood caries (S-ECC): hypoplasia-associated severe early childhood caries (HAS-ECC). This form of caries affects mostly young children living at or below poverty, characterized by structurally damaged primary teeth that are particularly vulnerable to dental caries. These predisposing developmental dental defects are mainly permutations of enamel hypoplasia (EHP). Anthropologists and dental researchers consider EHP an indicator for infant and maternal stresses including malnutrition, a variety of illnesses, and adverse birthing conditions. Differentiation of HAS-ECC from other forms of early childhood caries is warranted because of its distinct etiology, clinical presentation, and eventual management. Defining HAS-ECC has important clinical implications: Therapies that control or prevent other types of caries are likely to be less effective with HAS-ECC because the structural integrity of the teeth is compromised prior to their emergence into the oral cavity. By the time these children present to the dentist, the treatment options often become limited to surgical management under general anesthesia. To prevent HAS-ECC, dentists must partner with other health providers to develop interventions that begin with pregnant mothers, with the aim of eliminating or ameliorating the covariates accompanying poverty, including better pre- and post-natal care and nutrition. PMID:22529242

The short-form version of the Depression Anxiety Stress Scales (DASS-21): construct validity and normative data in a large non-clinical sample.

PubMed

Henry, Julie D; Crawford, John R

2005-06-01

To test the construct validity of the short-form version of the Depression anxiety and stress scale (DASS-21), and in particular, to assess whether stress as indexed by this measure is synonymous with negative affectivity (NA) or whether it represents a related, but distinct, construct. To provide normative data for the general adult population. Cross-sectional, correlational and confirmatory factor analysis (CFA). The DASS-21 was administered to a non-clinical sample, broadly representative of the general adult UK population (N = 1,794). Competing models of the latent structure of the DASS-21 were evaluated using CFA. The model with optimal fit (RCFI = 0.94) had a quadripartite structure, and consisted of a general factor of psychological distress plus orthogonal specific factors of depression, anxiety, and stress. This model was a significantly better fit than a competing model that tested the possibility that the Stress scale simply measures NA. The DASS-21 subscales can validly be used to measure the dimensions of depression, anxiety, and stress. However, each of these subscales also taps a more general dimension of psychological distress or NA. The utility of the measure is enhanced by the provision of normative data based on a large sample.

Plasma 3-methoxy-4-hydroxyphenylglycol and homovanillic acid measurements in deficit and nondeficit forms of schizophrenia.

PubMed

Thibaut, F; Ribeyre, J M; Dourmap, N; Ménard, J F; Dollfus, S; Petit, M

1998-01-01

Discrepancies in the biochemical research on negative symptoms in schizophrenia may be ascribed to the lack of differentiation into primary and secondary negative symptoms. We have used Carpenter's criteria to define the deficit syndrome of schizophrenia as the presence of enduring and primary negative symptoms and measured catecholaminergic parameters in deficit as compared with nondeficit schizophrenics. We have investigated plasma homovanillic acid (pHVA) and 3-methoxy-4-hydroxyphenylglycol (pMHPG) concentrations in 34 DSM-III-R neuroleptic-treated schizophrenic patients who were classified into deficit (n = 14) and nondeficit (n = 20) forms of schizophrenia. All these patients were in a stable clinical and therapeutic status for the preceding 12 months. The 14 deficit schizophrenic patients had lower plasma levels of pHVA and higher plasma concentrations of pMHPG from 9 AM to 12 AM as compared with the 20 nondeficit schizophrenic patients. The two groups did not differ on any demographic, therapeutic, or clinical variable considered. Our data are consistent with the postulated distinct pathophysiological basis for the deficit syndrome of schizophrenia and suggest that opposite alterations in the pHVA or pMHPG levels may reflect specific changes in noradrenergic and dopaminergic functions in these deficit patients.

Matrix Metalloproteinases 2 and 9 Are Differentially Expressed in Patients with Indeterminate and Cardiac Clinical Forms of Chagas Disease

PubMed Central

Fares, Rafaelle Christine Gomes; Gomes, Juliana de Assis Silva; Garzoni, Luciana Ribeiro; Waghabi, Mariana Caldas; Saraiva, Roberto Magalhães; Medeiros, Nayara Ingrid; Oliveira-Prado, Roberta; Sangenis, Luiz Henrique Conde; Chambela, Mayara da Costa; de Araújo, Fernanda Fortes; Teixeira-Carvalho, Andréa; Damásio, Marcos Paulo; Valente, Vanessa Azevedo; Ferreira, Karine Silvestre; Sousa, Giovane Rodrigo; Rocha, Manoel Otávio da Costa

2013-01-01

Dilated chronic cardiomyopathy (DCC) from Chagas disease is associated with myocardial remodeling and interstitial fibrosis, resulting in extracellular matrix (ECM) changes. In this study, we characterized for the first time the serum matrix metalloproteinase 2 (MMP-2) and MMP-9 levels, as well as their main cell sources in peripheral blood mononuclear cells from patients presenting with the indeterminate (IND) or cardiac (CARD) clinical form of Chagas disease. Our results showed that serum levels of MMP-9 are associated with the severity of Chagas disease. The analysis of MMP production by T lymphocytes showed that CD8+ T cells are the main mononuclear leukocyte source of both MMP-2 and MMP-9 molecules. Using a new 3-dimensional model of fibrosis, we observed that sera from patients with Chagas disease induced an increase in the extracellular matrix components in cardiac spheroids. Furthermore, MMP-2 and MMP-9 showed different correlations with matrix proteins and inflammatory cytokines in patients with Chagas disease. Our results suggest that MMP-2 and MMP-9 show distinct activities in Chagas disease pathogenesis. While MMP-9 seems to be involved in the inflammation and cardiac remodeling of Chagas disease, MMP-2 does not correlate with inflammatory molecules. PMID:23856618

One target, different effects: a comparison of distinct therapeutic antibodies against the same targets.

PubMed

Shim, Hyunbo

2011-10-31

To date, more than 30 antibodies have been approved worldwide for therapeutic use. While the monoclonal antibody market is rapidly growing, the clinical use of therapeutic antibodies is mostly limited to treatment of cancers and immunological disorders. Moreover, antibodies against only five targets (TNF-α, HER2, CD20, EGFR, and VEGF) account for more than 80 percent of the worldwide market of therapeutic antibodies. The shortage of novel, clinically proven targets has resulted in the development of many distinct therapeutic antibodies against a small number of proven targets, based on the premise that different antibody molecules against the same target antigen have distinct biological and clinical effects from one another. For example, four antibodies against TNF-α have been approved by the FDA -- infliximab, adalimumab, golimumab, and certolizumab pegol -- with many more in clinical and preclinical development. The situation is similar for HER2, CD20, EGFR, and VEGF, each having one or more approved antibodies and many more under development. This review discusses the different binding characteristics, mechanisms of action, and biological and clinical activities of multiple monoclonal antibodies against TNF-α, HER-2, CD20, and EGFR and provides insights into the development of therapeutic antibodies.

Efficient isolation of human metapneumovirus using MNT-1, a human malignant melanoma cell line with early and distinct cytopathic effects.

PubMed

Sato, Ko; Watanabe, Oshi; Ohmiya, Suguru; Chiba, Fumiko; Suzuki, Akira; Okamoto, Michiko; Younghuang, Jiang; Hata, Akihiro; Nonaka, Hiroyuki; Kitaoka, Setsuko; Nagai, Yukio; Kawamura, Kazuhisa; Hayashi, Masahiro; Kumaki, Satoru; Suzuki, Tamio; Kawakami, Kazuyoshi; Nishimura, Hidekazu

2017-11-01

Isolation of human metapneumovirus (HMPV) from clinical specimens is currently inefficient because of the lack of a cell culture system in which a distinct cytopathic effect (CPE) occurs. The cell lines LLC-MK2, Vero and Vero E6 are used for isolation of HMPV; however, the CPE in these cell lines is subtle and usually requires a long observation period and sometimes blind passages. Thus, a cell line in which an early and distinct CPE occurs following HMPV inoculation is highly desired by clinical virology laboratories. In this study, it was demonstrated that, in the human malignant melanoma cell line MNT-1, obvious syncytium formation occurs shortly after inoculation with HMPV-positive clinical specimens. In addition, the growth and efficiency of isolation of HMPV were greater using MNT-1 than using any other conventional cell line. Addition of this cell line to our routine viral isolation system for clinical specimens markedly enhanced isolation frequency, allowing isolation-based surveillance. MNT-1 has the potential to facilitate clinical and epidemiological studies of HMPV. © 2017 The Societies and John Wiley & Sons Australia, Ltd.

Pragmatism and the Unlikely Influence of German Idealism on the Academy in the United States

ERIC Educational Resources Information Center

Ream, Todd C.

2007-01-01

In this article I argue that the subject-object distinction, operative in Continental Europe during the late-1700s and early-1800s, led to the religion-secular distinction in higher education in the United States. Many scholars believe the origins of the shifting nature of the religion-secular distinction resided with some form of influence that…

Evaluation of a new VMAT QA device, or the "X" and "O" array geometries.

PubMed

Feygelman, Vladimir; Zhang, Geoffrey; Stevens, Craig; Nelms, Benjamin E

2011-01-31

We introduce a logical process of three distinct phases to begin the evaluation of a new 3D dosimetry array. The array under investigation is a hollow cylinder phantom with diode detectors fixed in a helical shell forming an "O" axial detector cross section (ArcCHECK), with comparisons drawn to a previously studied 3D array with diodes fixed in two crossing planes forming an "X" axial cross section (Delta⁴). Phase I testing of the ArcCHECK establishes: robust relative calibration (response equalization) of the individual detectors, minor field size dependency of response not present in a 2D predecessor, and uncorrected angular response dependence in the axial plane. Phase II testing reveals vast differences between the two devices when studying fixed-width full circle arcs. These differences are primarily due to arc discretization by the TPS that produces low passing rates for the peripheral detectors of the ArcCHECK, but high passing rates for the Delta⁴. Similar, although less pronounced, effects are seen for the test VMAT plans modeled after the AAPM TG119 report. The very different 3D detector locations of the two devices, along with the knock-on effect of different percent normalization strategies, prove that the analysis results from the devices are distinct and noninterchangeable; they are truly measuring different things. The value of what each device measures, namely their correlation with--or ability to predict--clinically relevant errors in calculation and/or delivery of dose is the subject of future Phase III work.

Identification and individualized prediction of clinical phenotypes in bipolar disorders using neurocognitive data, neuroimaging scans and machine learning.

PubMed

Wu, Mon-Ju; Mwangi, Benson; Bauer, Isabelle E; Passos, Ives C; Sanches, Marsal; Zunta-Soares, Giovana B; Meyer, Thomas D; Hasan, Khader M; Soares, Jair C

2017-01-15

Diagnosis, clinical management and research of psychiatric disorders remain subjective - largely guided by historically developed categories which may not effectively capture underlying pathophysiological mechanisms of dysfunction. Here, we report a novel approach of identifying and validating distinct and biologically meaningful clinical phenotypes of bipolar disorders using both unsupervised and supervised machine learning techniques. First, neurocognitive data were analyzed using an unsupervised machine learning approach and two distinct clinical phenotypes identified namely; phenotype I and phenotype II. Second, diffusion weighted imaging scans were pre-processed using the tract-based spatial statistics (TBSS) method and 'skeletonized' white matter fractional anisotropy (FA) and mean diffusivity (MD) maps extracted. The 'skeletonized' white matter FA and MD maps were entered into the Elastic Net machine learning algorithm to distinguish individual subjects' phenotypic labels (e.g. phenotype I vs. phenotype II). This calculation was performed to ascertain whether the identified clinical phenotypes were biologically distinct. Original neurocognitive measurements distinguished individual subjects' phenotypic labels with 94% accuracy (sensitivity=92%, specificity=97%). TBSS derived FA and MD measurements predicted individual subjects' phenotypic labels with 76% and 65% accuracy respectively. In addition, individual subjects belonging to phenotypes I and II were distinguished from healthy controls with 57% and 92% accuracy respectively. Neurocognitive task variables identified as most relevant in distinguishing phenotypic labels included; Affective Go/No-Go (AGN), Cambridge Gambling Task (CGT) coupled with inferior fronto-occipital fasciculus and callosal white matter pathways. These results suggest that there may exist two biologically distinct clinical phenotypes in bipolar disorders which can be identified from healthy controls with high accuracy and at an individual subject level. We suggest a strong clinical utility of the proposed approach in defining and validating biologically meaningful and less heterogeneous clinical sub-phenotypes of major psychiatric disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Complex PTSD as proposed for ICD-11: validation of a new disorder in children and adolescents and their response to Trauma-Focused Cognitive Behavioral Therapy.

PubMed

Sachser, Cedric; Keller, Ferdinand; Goldbeck, Lutz

2017-02-01

To evaluate whether the symptoms of children and adolescents with clinically significant posttraumatic stress symptoms (PTSS) form classes consistent with the diagnostic criteria of complex PTSD (CPTSD) as proposed for the ICD-11, and to relate the emerging classes with treatment outcome of Trauma-Focused Cognitive Behavioral Therapy (TF-CBT). Latent classes analysis (LCA) was used to explore the symptom profiles of the clinical baseline assessment of N = 155 children and adolescents participating in a randomized controlled trial of TF-CBT. The treatment outcomes of patients with posttraumatic stress disorder (PTSD) and of patients with CPTSD were compared by a t-test for depended samples and a repeated-measures ANOVA. The LCA revealed two distinct classes: a PTSD class characterized by elevated core symptoms of PTSD (n = 62) and low symptoms of disturbances in self-organization versus a complex PTSD class with elevated PTSD core symptoms and elevated symptoms of disturbances in self-organization (n = 93). The Group × Time interaction regarding posttraumatic stress symptoms was not significant. Pre-post effect sizes regarding posttraumatic stress symptoms were large for both groups (PTSD: d = 2.81; CPTSD: d = 1.37). For disturbances in self-organization in the CPTSD class, we found medium to large effect sizes (d = 0.40-1.16) after treatment with TF-CBT. The results provide empirical evidence of the ICD-11 CPTSD and PTSD distinction in a clinical sample of children and adolescents. In terms of relative improvement from their respective baseline posttraumatic stress symptoms, patients with PTSD and CPTSD responded equally to TF-CBT; however, those with CPTSD ended treatment with clinically and statistically greater symptoms than those with PTSD. © 2016 Association for Child and Adolescent Mental Health.

Evaluating social (pragmatic) communication disorder.

PubMed

Mandy, William; Wang, Adele; Lee, Irene; Skuse, David

2017-10-01

Social (pragmatic) communication disorder (SPCD) is a new diagnosis introduced by DSM-5, characterised by problems with verbal and nonverbal social communication. It is currently unclear whether SPCD is a valid diagnostic category, because little is known about the characteristics of those who meet its criteria. We sought to identify and describe cases of SPCD, to contribute to debates about its validity. We investigated whether the symptoms of SPCD cluster together to form a coherent syndrome that is distinct from autism spectrum disorder (ASD) in terms of its core and associated features. Participants were young people (N = 1,081, age range = 4-18 years) who had attended a specialist social communication disorders clinic for children with fluent language and normal-range intelligence. Standardised parent-report data were collected using the Developmental, Dimensional and Diagnostic Interview (3Di), Child Communication Checklist (CCC) and Strengths and Difficulties Questionnaire (SDQ). An algorithm was designed using 3Di and CCC items to implement DSM-5 SPCD criteria. Eighty-eight young people met our criteria for SPCD, with 801 meeting DSM-5 ASD criteria and the remaining 192 having neither SPCD nor ASD ('clinical comparison group'). The core symptoms of SPCD co-occurred to a moderate degree (average interitem correlation = .22). SPCD cases had autistic social difficulties that were intermediate between ASD and the clinical comparison group. SPCD was associated with high rates of nonautistic psychopathology, with 63.5% scoring in the abnormal range of the SDQ's Total Problems scale. We did not find evidence that SPCD is qualitatively distinct from ASD. Rather, it appears to lie on the borderlands of the autism spectrum, describing those with autistic traits that fall just below the threshold for an ASD diagnosis. SPCD may have clinical utility for identifying people with autistic traits that are insufficiently severe for ASD diagnosis, but who nevertheless require support. © 2017 Association for Child and Adolescent Mental Health.

Langerhans cell histiocytosis manifesting as recurrent simultaneous bilateral spontaneous pneumothorax in early infancy.

PubMed

Alavi, Samin; Ashena, Zahra; Paydar, Afshin; Hemmati, Nadereh

2007-12-01

Langerhans cell histiocytosis (LCH) is a rare disorder characterized by infiltration of either single or multiple organs by a distinct cell type that is S-100 and CD1a positive and contains ultrastructural Birbeck granules on electron microscopy. Historically, LCH included four main clinical forms: Letter-Siwe disease, Hand-Schuller-Christian disease, eosinophilic granuloma (together grouped as histiocytosis) and Hashimoto-Pritzker disease. The writing group of the Histiocytotic Society in 1987 proposed the uniform term of 'Langerhans cell histiocytosis' to encompass all the aforementioned eponymous forms. Lung involvement occurs in up to half of all children with multisystem disease and usually parallels overall disease activity. Spontaneous pneumothorax (SP) occurs in approximately 10% of children with pulmonary disease and may be a fatal complication. Patients with pulmonary LCH are likely predisposed to the development of pneumothorax based on destructive changes in the lung parenchyma. Here, we report a case of multisystem LCH in which the patient presented at 2 months of age because of simultaneous bilateral pneumothorax.

Primary Ovarian Insufficiency: X chromosome defects and autoimmunity.

PubMed

Persani, Luca; Rossetti, Raffaella; Cacciatore, Chiara; Bonomi, Marco

2009-08-01

Premature ovarian failure (POF) is a primary ovarian defect characterized by absent menarche or premature depletion of ovarian follicles before the age of 40 years. However, in several instances the distinction between definitive or intermittent POF may be difficult on clinical bases, therefore the more appropriate term Primary Ovarian Insufficiency (POI) has been recently proposed and will be used in this review. POI is a heterogeneous disorder affecting approximately 1% of women <40 years. The most severe forms present with absent pubertal development and primary amenorrhea, whereas forms with post-pubertal onset are characterized by disappearance of menstrual cycles (secondary amenorrhea) associated with a defective folliculogenesis. POI is generally characterized by low levels of gonadal hormones (estrogens and inhibins) and high levels of gonadotropins (LH and FSH) (hypergonadotropic amenorrhea). Heterogeneity of POI is reflected by the variety of possible causes, including autoimmunity, toxics, drugs, as well as genetic defects. Several data indicate that POI has a strong genetic component. In this manuscript we discuss the X chromosome abnormalities that are associated with POI.

Cyber victimization by peers: Prospective associations with adolescent social anxiety and depressive symptoms.

PubMed

Landoll, Ryan R; La Greca, Annette M; Lai, Betty S; Chan, Sherilynn F; Herge, Whitney M

2015-07-01

Peer victimization that occurs via electronic media, also termed cybervictimization, is a growing area of concern for adolescents. The current study evaluated the short-term prospective relationship between cybervictimization and adolescents' symptoms of social anxiety and depression over a six-week period. Participants were 839 high-school aged adolescents (14-18 years; 58% female; 73% Hispanic White), who completed measures of traditional peer victimization, cybervictimization, depression, and social anxiety at two time points. Findings supported the distinctiveness of cybervictimization as a unique form of peer victimization. Furthermore, only cybervictimization was associated with increased levels of depressive symptoms over time, and only relational victimization was associated with increased social anxiety over time, after controlling for the comorbidity of social anxiety and depression among youth. Cybervictimization appears to be a unique form of victimization that contributes to adolescents' depressive symptoms and may be important to target in clinical and preventive interventions for adolescent depression. Copyright © 2015 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Impaired self-reflection in psychiatric disorders among adults: a proposal for the existence of a network of semi independent functions.

PubMed

Dimaggio, Giancarlo; Vanheule, Stijn; Lysaker, Paul H; Carcione, Antonino; Nicolò, Giuseppe

2009-09-01

Self-reflection plays a key role in healthy human adaptation. Self-reflection might involve different capacities which may be impaired to different degrees relatively independently of one another. Variation in abilities for different forms of self-reflection are commonly seen as key aspects of many adult mental disorders. Yet little has been written about whether there are different kinds of deficits in self-reflection found in mental illness, how those deficits should be distinguished from one another and how to characterize the extent to which they are interrelated. We review clinical and experimental literature and suggest four different forms of deficits in self-reflection: (a) sense of ownership of one's own thoughts and actions, (b) emotional awareness, (c) distinction between fantasy and reality and (d) the integration of a range of different views of oneself and others. We propose how these different impairments in self-reflection are linked with one another.

Muscle ischaemia associated with NXP2 autoantibodies: a severe subtype of juvenile dermatomyositis.

PubMed

Aouizerate, Jessie; De Antonio, Marie; Bader-Meunier, Brigitte; Barnerias, Christine; Bodemer, Christine; Isapof, Arnaud; Quartier, Pierre; Melki, Isabelle; Charuel, Jean-Luc; Bassez, Guillaume; Desguerre, Isabelle; Gherardi, Romain K; Authier, François-Jérôme; Gitiaux, Cyril

2018-05-01

Myositis-specific autoantibodies (MSAs) are increasingly used to delineate distinct subgroups of JDM. The aim of our study was to explore without a priori hypotheses whether MSAs are associated with distinct clinical-pathological changes and severity in a monocentric JDM cohort. Clinical, biological and histological findings from 23 JDM patients were assessed. Twenty-six histopathological parameters were subjected to multivariate analysis. Autoantibodies included anti-NXP2 (9/23), anti-TIF1γ (4/23), anti-MDA5 (2/23), no MSAs (8/23). Multivariate analysis yielded two histopathological clusters. Cluster 1 (n = 11) showed a more severe and ischaemic pattern than cluster 2 (n = 12) assessed by: total score severity ⩾ 20 (100.0% vs 25.0%); visual analogic score ⩾6 (100.0% vs 25.0%); the vascular domain score >1 (100.0% vs 41.7%); microinfarcts (100% vs 58.3%); ischaemic myofibrillary loss (focal punched-out vacuoles) (90.9 vs 25%); and obvious capillary loss (81.8% vs 16.7). Compared with cluster 2, patients in cluster 1 had strikingly more often anti-NXP2 antibodies (7/11 vs 2/12), more pronounced muscle weakness, more gastrointestinal involvement and required more aggressive treatment. Furthermore, patients with anti-NXP2 antibodies, mostly assigned in the first cluster, also displayed more severe muscular disease, requiring more aggressive treatment and having a lower remission rate during the follow-up period. Marked muscle ischaemic involvement and the presence of anti-NXP2 autoantibodies are associated with more severe forms of JDM.

Latent autoimmune diabetes of the adult: current knowledge and uncertainty

PubMed Central

Laugesen, E; Østergaard, J A; Leslie, R D G

2015-01-01

Patients with adult-onset autoimmune diabetes have less Human Leucocyte Antigen (HLA)-associated genetic risk and fewer diabetes-associated autoantibodies compared with patients with childhood-onset Type 1 diabetes. Metabolic changes at diagnosis reflect a broad clinical phenotype ranging from diabetic ketoacidosis to mild non-insulin-requiring diabetes, also known as latent autoimmune diabetes of the adult (LADA). This latter phenotype is the most prevalent form of adult-onset autoimmune diabetes and probably the most prevalent form of autoimmune diabetes in general. Although LADA is associated with the same genetic and immunological features as childhood-onset Type 1 diabetes, it also shares some genetic features with Type 2 diabetes, which raises the question of genetic heterogeneity predisposing to this form of the disease. The potential value of screening patients with adult-onset diabetes for diabetes-associated autoantibodies to identify those with LADA is emphasized by their lack of clinically distinct features, their different natural history compared with Type 2 diabetes and their potential need for a dedicated management strategy. The fact that, in some studies, patients with LADA show worse glucose control than patients with Type 2 diabetes, highlights the need for further therapeutic studies. Challenges regarding classification, epidemiology, genetics, metabolism, immunology, clinical presentation and treatment of LADA were discussed at a 2014 workshop arranged by the Danish Diabetes Academy. The presentations and discussions are summarized in this review, which sets out the current ideas and controversies surrounding this form of diabetes. What’s new? Latent autoimmune diabetes of the adult (LADA) is an autoimmune diabetes defined by adult-onset, presence of diabetes associated autoantibodies, and no insulin treatment requirement for a period after diagnosis. Immunologically, glutamic acid decarboxylase 65 autoantibodies are by far the most common autoantibody in adult-onset diabetes. LADA is the most prevalent form of adult-onset autoimmune diabetes and probably the most prevalent form of autoimmune diabetes in general. LADA shares genetic features with both type 1 and type 2 diabetes. Phenotypically, LADA patients are often misdiagnosed as having type 2 diabetes. LADA patients generally have worse HbA1c levels than type 2 diabetes patients. Clinically, LADA patients tend to have a lower mean age at diabetes onset, lower body mass index and more frequent need for insulin treatment than patients with type 2 diabetes. Management of LADA may require a dedicated strategy, yet currently there is a paucity of randomized controlled trial data. PMID:25601320

Subgroup Analysis in Burnout: Relations Between Fatigue, Anxiety, and Depression

PubMed Central

van Dam, Arno

2016-01-01

Several authors have suggested that burned out patients do not form a homogeneous group and that subgroups should be considered. The identification of these subgroups may contribute to a better understanding of the burnout construct and lead to more specific therapeutic interventions. Subgroup analysis may also help clarify whether burnout is a distinct entity and whether subgroups of burnout overlap with other disorders such as depression and chronic fatigue syndrome. In a group of 113 clinically diagnosed burned out patients, levels of fatigue, depression, and anxiety were assessed. In order to identify possible subgroups, we performed a two-step cluster analysis. The analysis revealed two clusters that differed from one another in terms of symptom severity on the three aforementioned measures. Depression appeared to be the strongest predictor of group membership. These results are considered in the light of the scientific debate on whether burnout can be distinguished from depression and whether burnout subtyping is useful. Finally, implications for clinical practice and future research are discussed. PMID:26869983

An exploration of the value of the role of the mentor and mentoring in midwifery.

PubMed

Moran, Margaret; Banks, David

2016-05-01

This research project aimed to examine the perceived value sign-off mentors (SOMs) in midwifery have for their role. Using a phenomenological approach, the results were drawn from in-depth interviews. The project included a literature review, methodology, results and discussion. The results indicate that mentors enjoy their role and they see themselves as essentials to the delivery of pre-registration midwifery programmes and for the supervision and assessment of student midwives. Mentors are not sure if student midwives value their sign-off mentor, or whether senior management is aware of the sign-off role and its value. This project also confirms previous findings from other studies, particularly the problem of finding time to complete student assessment paper work, support students in clinical practice and whether there are enough SOMs within clinical practice. The study does not conclude that the issues raised are distinctive to midwifery, potentially all of the points raised translate to the various forms of nursing practice. Copyright © 2016 Elsevier Ltd. All rights reserved.

Validation of a quality-of-life instrument for patients with nonmelanoma skin cancer.

PubMed

Rhee, John S; Matthews, B Alex; Neuburg, Marcy; Logan, Brent R; Burzynski, Mary; Nattinger, Ann B

2006-01-01

To validate a disease-specific quality-of-life instrument--the Skin Cancer Index--intended to measure quality-of-life issues relevant to patients with nonmelanoma skin cancer. Internal reliability, convergent and divergent validity with existing scales, and factor analyses were performed in a cross-sectional study of 211 patients presenting with cervicofacial nonmelanoma skin cancer to a dermatologic surgery clinic. Factor analyses of the Skin Cancer Index confirmed a multidimensional scale with 3 distinct subscales-emotional, social, and appearance. Excellent internal validity of the 3 subscales was demonstrated. Substantial evidence was observed for convergent validity with the Dermatology Life Quality Index, Rosenberg Self-Esteem Scale, Lerman's Cancer Worry Scale, and Medical Outcomes Survey Short-Form 12 domains for vitality, emotion, social function, and mental health. These findings validate a new disease-specific quality-of-life instrument for patients with cervicofacial nonmelanoma skin cancer. Studies on the responsiveness of the Skin Cancer Index to clinical intervention are currently under way.

Meningococcal disease: recognition, treatment, and prevention.

PubMed

Herf, C; Nichols, J; Fruh, S; Holloway, B; Anderson, C U

1998-08-01

Meningococcal disease is an infection caused by Neisseria meningitidis, a gram-negative diplococcus that is the leading cause of bacterial meningitis in children and young adults in the United States, with an estimated 2,600 cases reported each year. N. meningitidis infection rates are highest in children 3 to 12 months of age. Four distinct clinical situations are associated with meningococcal infection. The most common is asymptomatic nasopharyngeal colonization. Benign bacteremia is discovered in the absence of classical clinical findings of meningococcemia, but blood cultures are positive for N. meningitidis. Meningitis, the most common pathologic presentation, is associated with fever, headache, and nuchal rigidity. The mortality rate is about 5% in children and 10% to 15% in adults. Meningococcemia, the most severe form of infection, may involve petechial rash, hypotension, and disseminated intravascular coagulation. It is a fulminant condition that can, if untreated, progress from initial symptoms to coma and death in 12 to 48 hours. Spread of these endemic cases can be controlled by administering prophylactic antibiotics to close contacts of patients.

Genetic polymorphism of Malassezia furfur isolates from Han and Tibetan ethnic groups in China using DNA fingerprinting.

PubMed

Zhang, Hao; Zhang, Ruifeng; Ran, Yuping; Dai, Yaling; Lu, Yao; Wang, Peng

2010-12-01

Reported isolation rates of Malassezia yeast from human skin show geographic variations. In China, the populations of the Han (1,182.95 million) and Tibetan (5.41 million) ethnic groups are distributed over 9.6 and 3.27 million square kilometers respectively, making biodiversity research feasible and convenient. Malassezia furfur clinical strains (n = 29) isolated from different individuals, with or without associated dermatoses, of these two ethnic groups (15 Han and 12 Tibetan) were identified and analyzed with DNA fingerprinting using single primers specific to minisatellites. Using the Bionumerics software, we found that almost all M. furfur clinical isolates and type strains formed five distinct group clusters according to their associated skin diseases and the ethnic groups of the patients. These findings are the first to focus on the genetic diversity and relatedness of M. furfur in the Tibetan and Han ethnic groups in China and reveal genetic variation associated with related diseases, host ethnicity and geographic origin.

Monitoring sinew contraction during formation of tissue-engineered fibrin-based ligament constructs.

PubMed

Paxton, Jennifer Z; Wudebwe, Uchena N G; Wang, Anqi; Woods, Daniel; Grover, Liam M

2012-08-01

The ability to study the gross morphological changes occurring during tissue formation is vital to producing tissue-engineered structures of clinically relevant dimensions in vitro. Here, we have used nondestructive methods of digital imaging and optical coherence tomography to monitor the early-stage formation and subsequent maturation of fibrin-based tissue-engineered ligament constructs. In addition, the effect of supplementation with essential promoters of collagen synthesis, ascorbic acid (AA) and proline (P), has been assessed. Contraction of the cell-seeded fibrin gel occurs unevenly within the first 5 days of culture around two fixed anchor points before forming a longitudinal ligament-like construct. AA+P supplementation accelerates gel contraction in the maturation phase of development, producing ligament-like constructs with a higher collagen content and distinct morphology to that of unsupplemented constructs. These studies highlight the importance of being able to control the methods of tissue formation and maturation in vitro to enable the production of tissue-engineered constructs with suitable replacement tissue characteristics for repair of clinical soft-tissue injuries.

Highlights of the Global HIV-1 CSF Escape Consortium Meeting, 9 June 2016, Bethesda, MD, USA.

PubMed

Joseph, Jeymohan; Cinque, Paola; Colosi, Deborah; Dravid, Ameet; Ene, Luminita; Fox, Howard; Gabuzda, Dana; Gisslen, Magnus; Beth Joseph, Sarah; Letendre, Scott; Mukerji, Shibani S; Nath, Avindra; Perez-Valero, Ignacio; Persaud, Deborah; Price, Richard W; Rao, Vasudev R; Sacktor, Ned; Swanstrom, Ronald; Winston, Alan; Wojna, Valerie; Wright, Edwina; Spudich, Serena

2016-10-05

CSF HIV escape is a recently recognised phenomenon that suggests that despite suppressive treatment, HIV RNA may be detected in the CNS compartment in some individuals. In rare cases this is associated with clinical neurological disease, while in most cases, neurological consequences are not apparent. Attempts at characterising the biological substrates of CSF escape and further investigating the neurological consequences need to be made to better understand the implications of this condition for the HIV cure agenda as well as for clinical outcomes. The Global CSF HIV-1 Escape Consortium meeting, convened by the US National Institute of Mental Health, was a first step to gather investigators from diverse sites to discuss opportunities for future collaborative work on this emerging issue. To better understand CSF HIV escape and allow cross-site data reconciliation, it will be useful to reach a consensus set of definitions of the distinct forms of CSF escape, without which concerted cross-site efforts are difficult.

Identification of Distinct Psychosis Biotypes Using Brain-Based Biomarkers.

PubMed

Clementz, Brett A; Sweeney, John A; Hamm, Jordan P; Ivleva, Elena I; Ethridge, Lauren E; Pearlson, Godfrey D; Keshavan, Matcheri S; Tamminga, Carol A

2016-04-01

Clinical phenomenology remains the primary means for classifying psychoses despite considerable evidence that this method incompletely captures biologically meaningful differentiations. Rather than relying on clinical diagnoses as the gold standard, this project drew on neurobiological heterogeneity among psychosis cases to delineate subgroups independent of their phenomenological manifestations. A large biomarker panel (neuropsychological, stop signal, saccadic control, and auditory stimulation paradigms) characterizing diverse aspects of brain function was collected on individuals with schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis (N=711), their first-degree relatives (N=883), and demographically comparable healthy subjects (N=278). Biomarker variance across paradigms was exploited to create nine integrated variables that were used to capture neurobiological variance among the psychosis cases. Data on external validating measures (social functioning, structural magnetic resonance imaging, family biomarkers, and clinical information) were collected. Multivariate taxometric analyses identified three neurobiologically distinct psychosis biotypes that did not respect clinical diagnosis boundaries. The same analysis procedure using clinical DSM diagnoses as the criteria was best described by a single severity continuum (schizophrenia worse than schizoaffective disorder worse than bipolar psychosis); this was not the case for biotypes. The external validating measures supported the distinctiveness of these subgroups compared with clinical diagnosis, highlighting a possible advantage of neurobiological versus clinical categorization schemes for differentiating psychotic disorders. These data illustrate how multiple pathways may lead to clinically similar psychosis manifestations, and they provide explanations for the marked heterogeneity observed across laboratories on the same biomarker variables when DSM diagnoses are used as the gold standard.

Intracellular Membrane Association of the Aplysia cAMP Phosphodiesterase Long and Short Forms via Different Targeting Mechanisms*

PubMed Central

Kim, Kun-Hyung; Jun, Yong-Woo; Park, Yongsoo; Lee, Jin-A; Suh, Byung-Chang; Lim, Chae-Seok; Lee, Yong-Seok; Kaang, Bong-Kiun; Jang, Deok-Jin

2014-01-01

Phosphodiesterases (PDEs) play key roles in cAMP compartmentalization, which is required for intracellular signaling processes, through specific subcellular targeting. Previously, we showed that the long and short forms of Aplysia PDE4 (ApPDE4), which are localized to the membranes of distinct subcellular organelles, play key roles in 5-hydroxytryptamine-induced synaptic facilitation in Aplysia sensory and motor synapses. However, the molecular mechanism of the isoform-specific distinct membrane targeting was not clear. In this study, we further investigated the molecular mechanism of the membrane targeting of the ApPDE4 long and short forms. We found that the membrane targeting of the long form was mediated by hydrophobic interactions, mainly via 16 amino acids at the N-terminal region, whereas the short form was targeted solely to the plasma membrane, mainly by nonspecific electrostatic interactions between their N termini and the negatively charged lipids such as the phosphatidylinositol polyphosphates PI4P and PI(4,5)P2, which are embedded in the inner leaflet of the plasma membrane. Moreover, oligomerization of the long or short form by interaction of their respective upstream conserved region domains, UCR1 and UCR2, enhanced their plasma membrane targeting. These results suggest that the long and short forms of ApPDE4 are distinctly targeted to intracellular membranes through their direct association with the membranes via hydrophobic and electrostatic interactions, respectively. PMID:25077971

Morphological and molecular dissection of wild rices from eastern India suggests distinct speciation between O. rufipogon and O. nivara populations.

PubMed

Samal, Rashmita; Roy, Pritesh Sundar; Sahoo, Auromira; Kar, Meera Kumari; Patra, Bhaskar Chandra; Marndi, Bishnu Charan; Gundimeda, Jwala Narasimha Rao

2018-02-09

The inter relationships between the two progenitors is interesting as both wild relatives are known to be the great untapped gene reservoirs. The debate continues on granting a separate species status to Oryza nivara. The present study was conducted on populations of Oryza rufipogon and Oryza nivara from Eastern India employing morphological and molecular characteristics. The cluster analysis of the data on morphological traits could clearly classify the two wild forms into two separate discrete groups without any overlaps i.e. lack of intermediate forms, suggesting the non-sympatric existence of the wild forms. Amplification of hyper variable regions of the genome could reveal 144 alleles suggesting high genetic diversity values (average He = 0.566). Moreover, with 42.37% of uncommon alleles between the two wild relatives, the molecular variance analysis (AMOVA) could detect only 21% of total variation (p < 0.001) among them and rest 59% was within them. The population structure analysis clearly classified these two wild populations into two distinct sub-populations (K = 2) without any overlaps i.e. lack of intermediate forms, suggesting the non-sympatric existence of the wild forms. Clear differentiation into two distinct groups indicates that O. rufipogon and O. nivara could be treated as two different species.

What nephrolopathologists need to know about antiphospholipid syndrome-associated nephropathy: Is it time for formulating a classification for renal morphologic lesions?

PubMed

Mubarak, Muhammed; Nasri, Hamid

2014-01-01

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder which commonly affects kidneys. Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO) and Web of Science have been searched. There is sufficient epidemiological, clinical and histopathological evidence to show that antiphospholipid syndrome is a distinctive lesion caused by antiphospholipid antibodies in patients with different forms of antiphospholipid syndrome. It is now time to devise a classification for an accurate diagnosis and prognostication of the disease. Now that the morphological lesions of APSN are sufficiently well characterized, it is prime time to devise a classification which is of diagnostic and prognostic utility in this disease.

What nephrolopathologists need to know about antiphospholipid syndrome-associated nephropathy: Is it time for formulating a classification for renal morphologic lesions?

PubMed Central

Mubarak, Muhammed; Nasri, Hamid

2014-01-01

Context: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder which commonly affects kidneys. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO) and Web of Science have been searched. Results: There is sufficient epidemiological, clinical and histopathological evidence to show that antiphospholipid syndrome is a distinctive lesion caused by antiphospholipid antibodies in patients with different forms of antiphospholipid syndrome. It is now time to devise a classification for an accurate diagnosis and prognostication of the disease. Conclusions: Now that the morphological lesions of APSN are sufficiently well characterized, it is prime time to devise a classification which is of diagnostic and prognostic utility in this disease. PMID:24644536

Production of a Pyrrole Antibiotic by a Marine Bacterium1

PubMed Central

Burkholder, Paul R.; Pfister, Robert M.; Leitz, Frederick H.

1966-01-01

Evidence is presented for the isolation and identification of bacteria able to synthesize an unusual antibiotic containing five bromine atoms per molecule. The identification and taxonomic position of these bacteria was made by use of a computer in conjunction with traditional methods. These microorganisms and closely related strains have been isolated on various occasions from tropical water in the vicinity of Puerto Rico. One bacterium, a pseudomonad, has been given the name Pseudomonas bromoutilis because of its distinctive capability. The antibiotic has been extracted, purified, and obtained in crystal form, and its structure has been determined. Although clinical tests of its properties were not encouraging, it may be of significant value and interest from an ecological standpoint. Images Fig. 1 PMID:4380876

Multiple Sub-Epidermal Calcified Nodule Mimicking Eruptive Xanthoma: A Case Report and Review of the Literature

PubMed Central

Ozuguz, Pinar; Balta, Ilknur; Bozkurt, Ozlem; Unverdi, Hatice; Dostbil, Ahmet

2013-01-01

Sub-epidermal calcified nodule (SCN) is an uncommon form of idiopathic calcinosis. It usually occurs in children, particularly in the head and neck region, presenting as a solitary, painless, yellow-white nodule with papillomatous features. These lesions occur twice as common in males compared with females. The pathogenesis is uncertain, but the clinical and histological features of this lesion are distinctive. We report a case of 22-year-old man with multiple nodules bilaterally located on the dorsum of hands simulating eruptive xanthoma. Histopathological examination of one of the excised lesion confirmed the diagnosis showing epidermal and sub-epidermal deposition of calcium. This paper presents a review of the literature and adds a new case of SCN. PMID:24082201

The unique entity of nodular lymphocyte-predominant Hodgkin lymphoma: current approaches to diagnosis and management.

PubMed

Hawkes, Eliza A; Wotherspoon, Andrew; Cunningham, David

2012-03-01

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare disease constituting only 3-8% of all Hodgkin lymphoma. It has a distinct histological and clinical presentation as well as significantly different natural history compared to the classical form of Hodgkin lymphoma. Presenting most often as early-stage disease, NLPHL is characterized by frequent relapses, but paradoxically an overall good prognosis. The approach to management should therefore reflect this pattern and focus on attaining prolonged remissions, with long-term follow-up paramount. Due to the rarity of the disease, few prospective data exist. Options for treatment include radiotherapy, chemotherapy or combined chemotherapy plus radiotherapy and targeted anti-CD20 antibody therapy, as well as observation in selected patients.

STS-67 sunset and earth limb view

NASA Image and Video Library

1995-03-17

STS067-709-007 (2-18 March 1995) --- This shot, taken just after sunset, shows several distinct layers of gases in the atmosphere on the Earth’s limb. The distinct colors formed by the amount of scattered light that passes through these gases.

Clinical Characteristics of Mixed Arteriovenous Leg Ulcers: A Descriptive Study.

PubMed

Marin, Joseph A; Woo, Kevin Y

The purpose of this study was to identify the clinical characteristics of mixed arteriovenous leg ulcers (MLU) that differentiated them from venous leg ulcers (VLU). Secondary analysis of data from larger electronic database. The sample comprised 1007 persons with lower extremity ulcers. Two hundred sixty three individuals with MLU were compared to 744 individuals with VLU; their ankle brachial indices were 0.51-0.90 and 0.91-.30 respectively. Subjects were drawn from community care settings from across Canada. Data concerning baseline demographic and pertinent clinical characteristics including ulcer history were collected using multiple validated instruments. The Leg Ulcer Assessment Tool was used to collect demographic and pertinent medical history, The Short Form Health Survey 12 and the Euro Wuol 5D (EQ-5D) were used to measure health related quality of life, the numeric pain scales was used to measure character and intensity of pain. Groups were compared using χ or Mann-Whitney U. Individuals with MLU were significantly older, has lower body mass index, a history of smoking, and more comorbid conditions than subjects with VLU. In many cases, clinical presentation was indicative of significant arterial insufficiency including cool extremities, shiny, cracked and inelastic skin, impaired capillary refill, and weak pedal pulses. Ulcer pain was highly prevalent, but overall pain rating was similar between groups. Mixed arteriovenous leg ulcers were associated with lower health related quality of life, greater mobility impairments, and more deficits in self-care and usual activities. Greater knowledge and understanding of the distinct characteristics of MLU is critical for appropriate screening, prevention, assessment and management of persons with this form of leg ulcer. Pain and health related quality of life factors are important considerations when evaluating and managing these patients.

Bacteria form tellurium nanocrystals

USGS Publications Warehouse

Oremland, R.S.

2007-01-01

A team of researchers have found two bacterial species that produce tellurium oxyanions as respiratory electron acceptors for growth, leaving elemental tellurium in the form of nanoparticles. The crystals from the two organisms exhibit distinctively different structures. Bacillus selenitireducens initially forms nanorods that cluster together to form rosettes. Sulfurospirillum barnesii forms irregularly-shaped nanospheres that coalesce into larger composite aggregates.

Factor analysis in the Genetics of Asthma International Network family study identifies five major quantitative asthma phenotypes.

PubMed

Pillai, S G; Tang, Y; van den Oord, E; Klotsman, M; Barnes, K; Carlsen, K; Gerritsen, J; Lenney, W; Silverman, M; Sly, P; Sundy, J; Tsanakas, J; von Berg, A; Whyte, M; Ortega, H G; Anderson, W H; Helms, P J

2008-03-01

Asthma is a clinically heterogeneous disease caused by a complex interaction between genetic susceptibility and diverse environmental factors. In common with other complex diseases the lack of a standardized scheme to evaluate the phenotypic variability poses challenges in identifying the contribution of genes and environments to disease expression. To determine the minimum number of sets of features required to characterize subjects with asthma which will be useful in identifying important genetic and environmental contributors. Methods Probands aged 7-35 years with physician diagnosed asthma and symptomatic siblings were identified in 1022 nuclear families from 11 centres in six countries forming the Genetics of Asthma International Network. Factor analysis was used to identify distinct phenotypes from questionnaire, clinical, and laboratory data, including baseline pulmonary function, allergen skin prick test (SPT). Five distinct factors were identified:(1) baseline pulmonary function measures [forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC)], (2) specific allergen sensitization by SPT, (3) self-reported allergies, (4) symptoms characteristic of rhinitis and (5) symptoms characteristic of asthma. Replication in symptomatic siblings was consistent with shared genetic and/or environmental effects, and was robust across age groups, gender, and centres. Cronbach's alpha ranged from 0.719 to 0.983 suggesting acceptable internal scale consistencies. Derived scales were correlated with serum IgE, methacholine PC(20), age and asthma severity (interrupted sleep). IgE correlated with all three atopy-related factors, the strongest with the SPT factor whereas severity only correlated with baseline lung function, and with symptoms characteristic of rhinitis and of asthma. In children and adolescents with established asthma, five distinct sets of correlated patient characteristics appear to represent important aspects of the disease. Factor scores as quantitative traits may be better phenotypes in epidemiological and genetic analyses than those categories derived from the presence or absence of combinations of +ve SPTs and/or elevated IgE.

Delineation of Two Clinically and Molecularly Distinct Subgroups of Posterior Fossa Ependymoma

PubMed Central

Witt, Hendrik; Mack, Stephen C.; Ryzhova, Marina; Bender, Sebastian; Sill, Martin; Isserlin, Ruth; Benner, Axel; Hielscher, Thomas; Milde, Till; Remke, Marc; Jones, David T.W.; Northcott, Paul A.; Garzia, Livia; Bertrand, Kelsey C.; Wittmann, Andrea; Yao, Yuan; Roberts, Stephen S.; Massimi, Luca; Van Meter, Tim; Weiss, William A.; Gupta, Nalin; Grajkowska, Wiesia; Lach, Boleslaw; Cho, Yoon-Jae; von Deimling, Andreas; Kulozik, Andreas E.; Witt, Olaf; Bader, Gary D.; Hawkins, Cynthia E.; Tabori, Uri; Guha, Abhijit; Rutka, James T.; Lichter, Peter; Korshunov, Andrey

2014-01-01

Summary Despite the histological similarity of ependymomas from throughout the neuroaxis, the disease likely comprises multiple independent entities, each with a distinct molecular pathogenesis. Transcriptional profiling of two large independent cohorts of ependymoma reveals the existence of two demographically, transcriptionally, genetically, and clinically distinct groups of posterior fossa (PF) ependymomas. Group A patients are younger, have laterally located tumors with a balanced genome, and are much more likely to exhibit recurrence, metastasis at recurrence, and death compared with Group B patients. Identification and optimization of immunohistochemical (IHC) markers for PF ependymoma subgroups allowed validation of our findings on a third independent cohort, using a human ependymoma tissue microarray, and provides a tool for prospective prognostication and stratification of PF ependymoma patients. PMID:21840481

Clinical and laboratory features of children with community-acquired pneumonia are associated with distinct radiographic presentations.

PubMed

Falup-Pecurariu, Oana G; Diez-Domingo, Javier; Esposito, Susanna; Finn, Adam; Rodrigues, Fernanda; Spoulou, Vana; Syrogiannopoulos, George A; Usonis, Vytautas; Greenberg, David

2018-07-01

Chest radiographs from children with community-acquired pneumonia (CAP) were categorized into three distinct presentations and each presentation was correlated to clinical and laboratory findings. Children < 59 months with CAP presenting to pediatric emergency rooms during two years were enrolled prospectively in eight centers across Europe. Clinical and laboratory data were documented and radiographs obtained from patients. Of the 1107 enrolled patients, radiographs were characterized as 74.9% alveolar CAP, 8.9% non-alveolar CAP, and 16.3% clinical CAP. Alveolar CAP patients had significantly higher rates of fever (90.7%), vomiting (27.6%), and abdominal pain (18.6%), while non-alveolar CAP patients presented more with cough (96.9%). A model using independent parameters that characterize alveolar, non-alveolar, and clinical CAP demonstrated that alveolar CAP patients were significantly older (OR = 1.02) and had significantly lower oxygen saturation than non-alveolar CAP patients (OR = 0.54). Alveolar CAP patients had significantly higher mean WBC (17,760 ± 8539.68 cells/mm 3 ) and ANC (11.5 ± 7.5 cells/mm 3 ) than patients categorized as non-alveolar CAP (WBC 15,160 ± 5996 cells/mm 3 , ANC 9.2 ± 5.1 cells/mm 3 ) and clinical CAP (WBC 13,180 ± 5892, ANC 7.3 ± 4.7). Alveolar CAP, non-alveolar CAP, and clinical CAP are distinct entities differing not only by chest radiographic appearance but also in clinical and laboratory characteristics. Alveolar CAP has unique characteristics, which suggest association with bacterial etiology. Trial number 3075 (Soroka Hospital, Israel) What is Known: • Community-acquired pneumonia in children is diagnosed based on clinical and radiological definitions. • Radiological criteria were standardized by WHO-SICR and have been utilized in vaccine studies. What is New: • Correlation between the WHO-SICR radiological definitions and clinical and laboratory parameters has not been studied. • Using the WHO-SICR radiological definitions for alveolar community-acquired pneumonia (CAP) and non-alveolar CAP and the study definition for clinical CAP, it was found that the groups are distinct, differing clinically and in laboratory parameters.

Investigations of Potential Phenotypes of Foot Osteoarthritis: Cross‐Sectional Analysis From the Clinical Assessment Study of the Foot

PubMed Central

Marshall, Michelle; Thomas, Martin J.; Menz, Hylton B.; Myers, Helen L.; Thomas, Elaine; Downes, Thomas; Peat, George; Roddy, Edward

2016-01-01

Objective To investigate the existence of distinct foot osteoarthritis (OA) phenotypes based on pattern of joint involvement and comparative symptom and risk profiles. Methods Participants ages ≥50 years reporting foot pain in the previous year were drawn from a population‐based cohort. Radiographs were scored for OA in the first metatarsophalangeal (MTP) joint, first and second cuneometatarsal, navicular first cuneiform, and talonavicular joints according to a published atlas. Chi‐square tests established clustering, and odds ratios (ORs) examined symmetry and pairwise associations of radiographic OA in the feet. Distinct underlying classes of foot OA were investigated by latent class analysis (LCA) and their association with symptoms and risk factors was assessed. Results In 533 participants (mean age 64.9 years, 55.9% female) radiographic OA clustered across both feet (P < 0.001) and was highly symmetrical (adjusted OR 3.0, 95% confidence interval 2.1, 4.2). LCA identified 3 distinct classes of foot OA: no or minimal foot OA (64%), isolated first MTP joint OA (22%), and polyarticular foot OA (15%). After adjustment for age and sex, polyarticular foot OA was associated with nodal OA, increased body mass index, and more pain and functional limitation compared to the other classes. Conclusion Patterning of radiographic foot OA has provided insight into the existence of 2 forms of foot OA: isolated first MTP joint OA and polyarticular foot OA. The symptom and risk factor profiles in individuals with polyarticular foot OA indicate a possible distinctive phenotype of foot OA, but further research is needed to explore the characteristics of isolated first MTP joint and polyarticular foot OA. PMID:26238801

Clinical profile, treatment, and visual outcome of ampiginous choroiditis.

PubMed

Jyotirmay, Biswas; Jafferji, Shafiq S; Sudharshan, Sridharan; Kalpana, Badami

2010-01-01

To report the clinical profile and management of patients diagnosed to have ampiginous choroiditis in a tertiary care referral centre in India. Retrospective cohort study. Twenty-six eyes of 16 patients were included in the study, which was diagnosed as choroiditis, serpiginous choroiditis, and acute posterior multifocal placoid pigment epitheliopathy (APMPPE) or ampiginous choroiditis. Those who were initially diagnosed as having other forms of choroiditis were later classified as having ampiginous choroiditis clinically. Systemic steroids and immunosuppressives were the mainstay of therapy. There was a male preponderance (7:3). Age at presentation ranged from 22 years to 57 years with a (median 34 years); 81% had bilateral involvement and 35% had recurrences. Vision improved or maintained in 24 eyes, whereas it deteriorated in 2 eyes due to subretinal fibrosis and macula involvement, respectively. Resolution of lesions and improvement or stability of vision can occur with administration of timely steroids and immunosuppressive therapy. Regular follow-up is necessary to monitor the disease progression, recurrences, and involvement of the other eye. Ampiginous choroiditis is a separate disease entity due to its distinct clinical features. It is a disease with multiple relapses, which can be effectively controlled with a combination of immunosuppressive therapy, and a good visual acuity can be maintained on long-term follow-up.

A new method for distinguishing colony social forms of the fire ant Solenopsis invicta

USDA-ARS?s Scientific Manuscript database

Two distinct forms of colony social organization occur in the fire ant Solenopsis invicta: Colonies of the monogyne social form are headed by a single egg-laying queen, whereas those of the polygyne social form contain multiple egg-laying queens. This major difference in social organization is ass...

Color synesthesia. Insight into perception, emotion, and consciousness

PubMed Central

Safran, Avinoam B.; Sanda, Nicolae

2015-01-01

Purpose of review Synesthesia is an extraordinary perceptual phenomenon, in which individuals experience unusual percepts elicited by the activation of an unrelated sensory modality or by a cognitive process. Emotional reactions are commonly associated. The condition prompted philosophical debates on the nature of perception and impacted the course of art history. It recently generated a considerable interest among neuroscientists, but its clinical significance apparently remains underevaluated. This review focuses on the recent studies regarding variants of color synesthesia, the commonest form of the condition. Recent findings Synesthesia is commonly classified as developmental and acquired. Developmental forms predispose to changes in primary sensory processing and cognitive functions, usually with better performances in certain aspects and worse in others, and to heightened creativity. Acquired forms of synesthesia commonly arise from drug ingestion or neurological disorders, including thalamic lesions and sensory deprivation (e.g., blindness). Cerebral exploration using structural and functional imaging has demonstrated distinct patterns in cortical activation and brain connectivity for controls and synesthetes. Artworks of affected painters are most illustrative of the nature of synesthetic experiences. Summary Results of the recent investigations on synesthesia offered a remarkable insight into the mechanisms of perception, emotion and consciousness, and deserve attention both from neuroscientists and from clinicians. PMID:25545055

Color synesthesia. Insight into perception, emotion, and consciousness.

PubMed

Safran, Avinoam B; Sanda, Nicolae

2015-02-01

Synesthesia is an extraordinary perceptual phenomenon, in which individuals experience unusual percepts elicited by the activation of an unrelated sensory modality or by a cognitive process. Emotional reactions are commonly associated. The condition prompted philosophical debates on the nature of perception and impacted the course of art history. It recently generated a considerable interest among neuroscientists, but its clinical significance apparently remains underevaluated. This review focuses on the recent studies regarding variants of color synesthesia, the commonest form of the condition. Synesthesia is commonly classified as developmental and acquired. Developmental forms predispose to changes in primary sensory processing and cognitive functions, usually with better performances in certain aspects and worse in others, and to heightened creativity. Acquired forms of synesthesia commonly arise from drug ingestion or neurological disorders, including thalamic lesions and sensory deprivation (e.g., blindness). Cerebral exploration using structural and functional imaging has demonstrated distinct patterns in cortical activation and brain connectivity for controls and synesthetes. Artworks of affected painters are most illustrative of the nature of synesthetic experiences. Results of the recent investigations on synesthesia offered a remarkable insight into the mechanisms of perception, emotion and consciousness, and deserve attention both from neuroscientists and from clinicians.

Tocotrienols in health and disease: the other half of the natural vitamin E family

PubMed Central

Sen, Chandan K.; Khanna, Savita; Roy, Sashwati

2007-01-01

Tocochromanols encompass a group of compounds with vitamin E activity essential for human nutrition. Structurally, natural vitamin E includes eight chemically distinct molecules: α-, β-, γ- and δ-tocopherol; and α-, β-, γ- and δ-tocotrienol. Symptoms caused by α-tocopherol deficiency can be alleviated by tocotrienols. Thus, tocotrienols may be viewed as being members of the natural vitamin E family not only structurally but also functionally. Palm oil and rice bran oil represent two major nutritional sources of natural tocotrienol. Taken orally, tocotrienols are bioavailable to all vital organs. The tocotrienol forms of natural vitamin E possesses powerful hypocholesterolemic, anti-cancer and neuroprotective properties that are often not exhibited by tocopherols. Oral tocotrienol protects against stroke-associated brain damage in vivo. Disappointments with outcomes-based clinical studies testing the efficacy of α-tocopherol need to be handled with caution and prudence recognizing the untapped opportunities offered by the other forms of natural vitamin E. Although tocotrienols represent half of the natural vitamin E family, work on tocotrienols account for roughly 1% of the total literature on vitamin E. The current state of knowledge warrants strategic investment into investigating the lesser known forms of vitamin E. PMID:17507086

Integrating Single-System Design Research into the Clinical Practice Class

ERIC Educational Resources Information Center

Cooper, Marlene G.

2006-01-01

Clinical practice and research are generally taught separately in Master of Social Work programs by faculty with distinct areas of expertise. This paper discusses the teaching of single-subject design research methodology by clinical faculty, in the clinical practice class. Examples from student papers demonstrate the effectiveness of integrating…

Prostitution

PubMed Central

Sawa, R.J.

1987-01-01

A review of the literature discloses that prostitutes are distinguishable into distinct classes, each with distinct clinical implications. The spectre of AIDS suggests that we review the implications of the health risks associated with this profession. This article discusses the potential causes, health problems, and treatment of prostitutes. PMID:21263810

Chaperone expression profiles correlate with distinct physiological states of Plasmodium falciparum in malaria patients

PubMed Central

2010-01-01

Background Molecular chaperones have been shown to be important in the growth of the malaria parasite Plasmodium falciparum and inhibition of chaperone function by pharmacological agents has been shown to abrogate parasite growth. A recent study has demonstrated that clinical isolates of the parasite have distinct physiological states, one of which resembles environmental stress response showing up-regulation of specific molecular chaperones. Methods Chaperone networks operational in the distinct physiological clusters in clinical malaria parasites were constructed using cytoscape by utilizing their clinical expression profiles. Results Molecular chaperones show distinct profiles in the previously defined physiologically distinct states. Further, expression profiles of the chaperones from different cellular compartments correlate with specific patient clusters. While cluster 1 parasites, representing a starvation response, show up-regulation of organellar chaperones, cluster 2 parasites, which resemble active growth based on glycolysis, show up-regulation of cytoplasmic chaperones. Interestingly, cytoplasmic Hsp90 and its co-chaperones, previously implicated as drug targets in malaria, cluster in the same group. Detailed analysis of chaperone expression in the patient cluster 2 reveals up-regulation of the entire Hsp90-dependent pro-survival circuitries. In addition, cluster 2 also shows up-regulation of Plasmodium export element (PEXEL)-containing Hsp40s thought to have regulatory and host remodeling roles in the infected erythrocyte. Conclusion In all, this study demonstrates an intimate involvement of parasite-encoded chaperones, PfHsp90 in particular, in defining pathogenesis of malaria. PMID:20719001

Intracystic breast carcinoma. An important differential diagnosis in postmenopausal patients presenting with a rapidly growing breast cyst. Management and literature review.

PubMed

Salemis, Nikolaos S

2018-03-16

Intracystic breast carcinoma is a rare clinical entity accounting for 0.5-2% of all breast cancers. It represents a distinctive clinical form rather a histological subtype of breast cancer and can either be in situ or invasive tumor. We herein describe a rare case of intracystic breast carcinoma arising from the wall of a cyst in a postmenopausal patient, who presented with a rapidly growing complex breast cyst. Diagnostic evaluation and management of the patient are discussed along with a review of the literature. Complex breast cysts may represent a diagnostic and therapeutic challenge. An underlying malignancy has been reported in 21-31% of the cases. Preoperative diagnosis is challenging. Complex breast cysts with thick wall, thick inner septations, and intracystic solid components should undergo histological evaluation in order to rule out an underlying malignancy. The cytological analysis may be inconclusive. Ultrasound-guided biopsy is the diagnostic modality of choice. The correlation of clinical features, with imaging and histopathological findings is very important for the optimal treatment. In cases of discordance, a complete surgical excision is necessary with careful assessment of the extent of the disease and appropriate treatment.

[Azelaic acid 15% gel in the treatment of acne vulgaris. Combined results of two double-blind clinical comparative studies].

PubMed

Gollnick, Harald P M; Graupe, Klaus; Zaumseil, Rolf-Peter

2004-10-01

Topical measures are still the mainstay in the therapy of mild-to-moderate acne vulgaris. Azelaic acid 20% in a cream formulation has been established as an efficacious and safe topical drug for 15 years. A new non-alcoholic hydrogel formulation containing 15% azelaic acid was clinically tested against two standard drugs--5% benzoyl peroxide (BPO) and 1% clindamycin. In two independent, randomized, blinded comparative trials 15% azelaic acid gel was clinically tested against 5% benzoyl peroxide (BPO) gel in 351 patients and against 1% clindamycin gel in 229 patients. The drugs were applied b.i.d. for 4 months. Azelaic acid 15% gel proved to be as effective as BPO and clindamycin with median % reduction of the inflamed lesion (papules and pustules) of 70%, and 71% respectively. The azelaic acid gel was well-tolerated, the side effects (local burning and irritation) were distinctly less than with BPO but more pronounced than with clindamycin. Despite these side effects, the treatment was well-accepted by the majority of patients. Azelaic acid gel is an effective topical monotherapy for mild-to-moderate acne vulgaris; its new gel form is an enrichment of acne therapy.

Peripheral Neuropathy: A Practical Approach to Diagnosis and Symptom Management.

PubMed

Watson, James C; Dyck, P James B

2015-07-01

Peripheral neuropathy is one of the most prevalent neurologic conditions encountered by physicians of all specialties. Physicians are faced with 3 distinct challenges in caring for patients with peripheral neuropathy: (1) how to efficiently and effectively screen (in less than 2 minutes) an asymptomatic patient for peripheral neuropathy when they have a disorder in which peripheral neuropathy is highly prevalent (eg, diabetes mellitus), (2) how to clinically stratify patients presenting with symptoms of neuropathy to determine who would benefit from specialty consultation and what testing is appropriate for those who do not need consultation, and (3) how to treat the symptoms of painful peripheral neuropathy. In this concise review, we address these 3 common clinical scenarios. Easily defined clinical patterns of involvement are used to identify patients in need of neurologic consultation, the yield of laboratory and other diagnostic testing is reviewed for the evaluation of length-dependent, sensorimotor peripheral neuropathies (the most common form of neuropathy), and an algorithmic approach with dosing recommendations is provided for the treatment of neuropathic pain associated with peripheral neuropathy. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Is remitting seronegative symmetrical synovitis with pitting edema (RS3PE) a subset of rheumatoid arthritis?

PubMed

Yao, Qingping; Su, Xiangqian; Altman, Roy D

2010-08-01

To contrast and compare the spectrum of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) with rheumatoid arthritis (RA) using an illustrative case. The relevant English literature of RS3PE was searched using the keywords "RS3PE" alone and in combination with terms such as neoplasia and rheumatic disease. Original and review articles were reviewed and the clinical setting was exemplified with a case report. RS3PE initially was reported to represent a form of RA. However, RS3PE has clinical features that are different from both early- and late-onset RA, such as lack of bony erosions and rheumatoid factor. RS3PE is thought to involve vascular endothelial growth factor, suggesting an infectious etiology, generally has an excellent prognosis, and is associated with neoplasia not commonly seen in RA, and the RA associated human leukocyte antigen (HLA) DRB1 genotype is absent. Based on the clinical, laboratory, suspected infectious etiology, genetic differences, and types of associated malignancies, RS3PE appears to be a distinct entity rather than a subset of RA. Copyright 2010 Elsevier Inc. All rights reserved.

Organizing the public health-clinical health interface: theoretical bases.

PubMed

St-Pierre, Michèle; Reinharz, Daniel; Gauthier, Jacques-Bernard

2006-01-01

This article addresses the issue of the interface between public health and clinical health within the context of the search for networking approaches geared to a more integrated delivery of health services. The articulation of an operative interface is complicated by the fact that the definition of networking modalities involves complex intra- and interdisciplinary and intra- and interorganizational systems across which a new transversal dynamics of intervention practices and exchanges between service structures must be established. A better understanding of the situation is reached by shedding light on the rationale underlying the organizational methods that form the bases of the interface between these two sectors of activity. The Quebec experience demonstrates that neither the structural-functionalist approach, which emphasizes remodelling establishment structures and functions as determinants of integration, nor the structural-constructivist approach, which prioritizes distinct fields of practice in public health and clinical health, adequately serves the purpose of networking and integration. Consequently, a theoretical reframing is imperative. In this regard, structuration theory, which fosters the simultaneous study of methods of inter-structure coordination and inter-actor cooperation, paves the way for a better understanding of the situation and, in turn, to the emergence of new integration possibilities.

Subjective and clinical assessment criteria suggestive for five clinical patterns discernible in nonspecific neck pain patients. A Delphi-survey of clinical experts.

PubMed

Dewitte, Vincent; Peersman, Wim; Danneels, Lieven; Bouche, Katie; Roets, Arne; Cagnie, Barbara

2016-12-01

Nonspecific neck pain patients form a heterogeneous group with different musculoskeletal impairments. Classifying nonspecific neck pain patients into subgroups based on clinical characteristics might lead to more comprehensive diagnoses and can guide effective management. To establish consensus among a group of experts regarding the clinical criteria suggestive of a clinical dominance of 'articular', 'myofascial', 'neural', 'central' and 'sensorimotor control' dysfunction patterns distinguishable in patients with nonspecific neck pain. Delphi study. A focus group with 10 academic experts was organized to elaborate on the different dysfunction patterns discernible in neck pain patients. Consecutively, a 3-round online Delphi-survey was designed to obtain consensual symptoms and physical examination findings for the 5 distinct dysfunction patterns resulting from the focus group. A total of 21 musculoskeletal physical therapists from Belgium and the Netherlands experienced in assessing and treating neck pain patients completed the 3-round Delphi-survey. Respectively, 33 (response rate, 100.0%), 27 (81.8%) and 21 (63.6%) respondents replied to rounds 1, 2 and 3. Eighteen 'articular', 16 'myofascial', 20 'neural', 18 'central' and 10 'sensorimotor control' clinical indicators reached a predefined ≥80% consensus level. These indicators suggestive of a clinical dominance of 'articular', 'myofascial', 'neural', 'central', and 'sensorimotor control' dysfunction patterns may help clinicians to assess and diagnose patients with nonspecific neck pain. Future validity testing is needed to determine how these criteria may help to improve the outcome of physical therapy interventions in nonspecific neck pain patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identification of Distinct Psychosis Biotypes Using Brain-Based Biomarkers

PubMed Central

Clementz, Brett A.; Sweeney, John A.; Hamm, Jordan P.; Ivleva, Elena I.; Ethridge, Lauren E.; Pearlson, Godfrey D.; Keshavan, Matcheri S.; Tamminga, Carol A.

2017-01-01

Objective Clinical phenomenology remains the primary means for classifying psychoses despite considerable evidence that this method incompletely captures biologically meaningful differentiations. Rather than relying on clinical diagnoses as the gold standard, this project drew on neurobiological heterogeneity among psychosis cases to delineate subgroups independent of their phenomenological manifestations. Method A large biomarker panel (neuropsychological, stop signal, saccadic control, and auditory stimulation paradigms) characterizing diverse aspects of brain function was collected on individuals with schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis (N=711), their first-degree relatives (N=883), and demographically comparable healthy subjects (N=278). Biomarker variance across paradigms was exploited to create nine integrated variables that were used to capture neurobiological variance among the psychosis cases. Data on external validating measures (social functioning, structural magnetic resonance imaging, family biomarkers, and clinical information) were collected. Results Multivariate taxometric analyses identified three neurobiologically distinct psychosis biotypes that did not respect clinical diagnosis boundaries. The same analysis procedure using clinical DSM diagnoses as the criteria was best described by a single severity continuum (schizophrenia worse than schizoaffective disorder worse than bipolar psychosis); this was not the case for biotypes. The external validating measures supported the distinctiveness of these subgroups compared with clinical diagnosis, highlighting a possible advantage of neurobiological versus clinical categorization schemes for differentiating psychotic disorders. Conclusions These data illustrate how multiple pathways may lead to clinically similar psychosis manifestations, and they provide explanations for the marked heterogeneity observed across laboratories on the same biomarker variables when DSM diagnoses are used as the gold standard. PMID:26651391

Enhancing the Alignment of the Preclinical and Clinical Stroke Recovery Research Pipeline: Consensus-Based Core Recommendations From the Stroke Recovery and Rehabilitation Roundtable Translational Working Group.

PubMed

Corbett, Dale; Carmichael, S Thomas; Murphy, Timothy H; Jones, Theresa A; Schwab, Martin E; Jolkkonen, Jukka; Clarkson, Andrew N; Dancause, Numa; Weiloch, Tadeusz; Johansen-Berg, Heidi; Nilsson, Michael; McCullough, Louise D; Joy, Mary T

2017-08-01

Stroke recovery research involves distinct biological and clinical targets compared to the study of acute stroke. Guidelines are proposed for the pre-clinical modeling of stroke recovery and for the alignment of pre-clinical studies to clinical trials in stroke recovery.

Genetic structure and evolution of the Leishmania genus in Africa and Eurasia: what does MLSA tell us.

PubMed

El Baidouri, Fouad; Diancourt, Laure; Berry, Vincent; Chevenet, François; Pratlong, Francine; Marty, Pierre; Ravel, Christophe

2013-01-01

Leishmaniasis is a complex parasitic disease from a taxonomic, clinical and epidemiological point of view. The role of genetic exchanges has been questioned for over twenty years and their recent experimental demonstration along with the identification of interspecific hybrids in natura has revived this debate. After arguing that genetic exchanges were exceptional and did not contribute to Leishmania evolution, it is currently proposed that interspecific exchanges could be a major driving force for rapid adaptation to new reservoirs and vectors, expansion into new parasitic cycles and adaptation to new life conditions. To assess the existence of gene flows between species during evolution we used MLSA-based (MultiLocus Sequence Analysis) approach to analyze 222 Leishmania strains from Africa and Eurasia to accurately represent the genetic diversity of this genus. We observed a remarkable congruence of the phylogenetic signal and identified seven genetic clusters that include mainly independent lineages which are accumulating divergences without any sign of recent interspecific recombination. From a taxonomic point of view, the strong genetic structuration of the different species does not question the current classification, except for species that cause visceral forms of leishmaniasis (L. donovani, L. infantum and L. archibaldi). Although these taxa cause specific clinical forms of the disease and are maintained through different parasitic cycles, they are not clearly distinct and form a continuum, in line with the concept of species complex already suggested for this group thirty years ago. These results should have practical consequences concerning the molecular identification of parasites and the subsequent therapeutic management of the disease.

Collaboration and entanglement: An actor-network theory analysis of team-based intraprofessional care for patients with advanced heart failure

PubMed Central

McDougall, A.; Goldszmidt, M.; Kinsella, E.A.; Smith, S.; Lingard, L.

2017-01-01

Despite calls for more interprofessional and intraprofessional team-based approaches in healthcare, we lack sufficient understanding of how this happens in the context of patient care teams. This multi-perspective, team-based interview study examined how medical teams negotiated collaborative tensions. From 2011 to 2013, 50 patients across five sites in three Canadian provinces were interviewed about their care experiences and were asked to identify members of their health care teams. Patient-identified team members were subsequently interviewed to form 50 “Team Sampling Units” (TSUs), consisting of 209 interviews with patients, caregivers and healthcare providers. Results are gathered from a focused analysis of 13 TSUs where intraprofessional collaborative tensions involved treating fluid overload, or edema, a common HF symptom. Drawing on actor-network theory (ANT), the analysis focused on intraprofessional collaboration between specialty care teams in cardiology and nephrology. The study found that despite a shared narrative of common purpose between cardiology teams and nephrology teams, fluid management tools and techniques formed sites of collaborative tension. In particular, care activities involved asynchronous clinical interpretations, geographically distributed specialist care, fragmented forms of communication, and uncertainty due to clinical complexity. Teams ‘disentangled’ fluid in order to focus on its physiological function and mobilisation. Teams also used distinct ‘framings’ of fluid management that created perceived collaborative tensions. This study advances collaborative entanglement as a conceptual framework for understanding, teaching, and potentially ameliorating some of the tensions that manifest during intraprofessional care for patients with complex, chronic disease. PMID:27490299

Attitude May Be Everything, But Is Everything an Attitude? Cognitive Distortions May Not Be Evaluations of Rape.

PubMed

Nunes, Kevin L; Hermann, Chantal A; White, Kristen; Pettersen, Cathrine; Bumby, Kurt

2018-02-01

Cognitive distortions are often referred to as attitudes toward rape in theory, research, and clinical practice pertaining to sexual aggression. In the social-psychological literature, however, attitudes are typically defined as evaluations; thus, in this context, attitudes toward rape are considered evaluations of rape (e.g., rape is negative vs. positive). The purpose of the current study was to explore whether a widely used measure of cognitive distortions (RAPE Scale; Bumby, 1996) assesses evaluation of rape, and, if not, whether evaluation of rape and the cognitions assessed by the RAPE Scale are independently associated with sexually aggressive behavior. Participants (660 male undergraduate students) completed the RAPE Scale as well as measures of evaluation of rape and sexually aggressive behavior. An exploratory factor analysis revealed that the RAPE Scale items formed a correlated but distinct factor from the Evaluation of Rape Scale items. Regression analyses indicated that the Evaluation of Rape Scale and the RAPE Scale had small to moderate independent associations with self-report measures of sexually aggressive behavior. Our results suggest that evaluation of rape may be distinct from cognitive distortions regarding rape, and both evaluation and cognitive distortions may be relevant for understanding sexual violence.

Manually Operatable On-Chip Bistable Pneumatic Microstructures for Microfluidic Manipulations

PubMed Central

Chen, A.; Pan, T.

2014-01-01

Bistable microvalves are of particular interest because of their distinct nature requiring energy consumption only during the transition between the open and closed states. This characteristic can be highly advantageous in reducing the number of external inputs and the complexity of control circuitries for microfluidic devices as contemporary lab-on-a-chip platforms are transferring from research settings to low-resource environments with high integratability and small form factor. In this paper, we first present manually operatable, on-chip bistable pneumatic microstructures (BPM) for microfluidic manipulation. The structural design and operation of the BPM devices can be readily integrated into any pneumatically powered microfluidic network consisting of pneumatic and fluidic channels. It is mainly comprised of a vacuum activation chamber (VAC) and a pressure release chamber (PRC), which users have direct control through finger pressing to switch between bistable vacuum state (VS) or atmospheric state (AS). We have integrated multiple BPM devices into a 4-to-1 microfluidic multiplexor to demonstrate on-chip digital flow switching from different sources. Furthermore, we have shown its clinical relevance in a point-of-care diagnostic chip that process blood samples to identify the distinct blood types (A/B/O) on chip. PMID:25007840

Novel staphylococcal species that form part of a Staphylococcus aureus-related complex: the non-pigmented Staphylococcus argenteus sp. nov. and the non-human primate-associated Staphylococcus schweitzeri sp. nov.

PubMed

Tong, Steven Y C; Schaumburg, Frieder; Ellington, Matthew J; Corander, Jukka; Pichon, Bruno; Leendertz, Fabian; Bentley, Stephen D; Parkhill, Julian; Holt, Deborah C; Peters, Georg; Giffard, Philip M

2015-01-01

We define two novel species of the genus Staphylococcus that are phenotypically similar to and have near identical 16S rRNA gene sequences to Staphylococcus aureus. However, compared to S. aureus and each other, the two species, Staphylococcus argenteus sp. nov. (type strain MSHR1132(T) = DSM 28299(T) = SSI 89.005(T)) and Staphylococcus schweitzeri sp. nov. (type strain FSA084(T) = DSM 28300(T) = SSI 89.004(T)), demonstrate: 1) at a whole-genome level considerable phylogenetic distance, lack of admixture, average nucleotide identity <95 %, and inferred DNA-DNA hybridization <70 %; 2) different profiles as determined by MALDI-TOF MS; 3) a non-pigmented phenotype for S. argenteus sp. nov.; 4) S. schweitzeri sp. nov. is not detected by standard nucA PCR; 5) distinct peptidoglycan types compared to S. aureus; 6) a separate ecological niche for S. schweitzeri sp. nov.; and 7) a distinct clinical disease profile for S. argenteus sp. nov. compared to S. aureus. © 2015 IUMS.

Clustering of adversity in young adults on disability pension due to mental disorders: a latent class analysis.

PubMed

Joensuu, Matti; Mattila-Holappa, Pauliina; Ahola, Kirsi; Ervasti, Jenni; Kivimäki, Mika; Kivekäs, Teija; Koskinen, Aki; Vahtera, Jussi; Virtanen, Marianna

2016-02-01

Mental disorders are the leading cause of work disability among young adults. This study examined whether distinct classes could be identified among young adults on the basis of medical history before receiving a disability pension due to a mental disorder. Medical history was obtained from pension applications and attached medical certificates for 1163 individuals aged 18-34 years who, in 2008, received a disability pension due to a mental disorder. Using latent class analysis, 10 clinical and individual adversities and their associations with sex, age and diagnostic category were examined. Three classes were identified: childhood adversity (prevalence, 33%), comorbidity (23%), and undefined (44%). The childhood adversity class was characterized by adverse events and symptoms reported during childhood and it associated with depressive disorders. The comorbidity class was characterized by comorbid mental disorders, suicide attempts and substance abuse and associated with younger age and bipolar disorder. The undefined class formed no distinct profile; individuals in this class had the lowest number of adversities and it associated with psychotic disorders. The identification of subgroups characterized by childhood circumstances and comorbidity may help planning of prevention and support practices for young adults with mental disorders and risk of work disability.

Manually operatable on-chip bistable pneumatic microstructures for microfluidic manipulations.

PubMed

Chen, Arnold; Pan, Tingrui

2014-09-07

Bistable microvalves are of particular interest because of their distinct nature of requiring energy consumption only during the transition between the open and closed states. This characteristic can be highly advantageous in reducing the number of external inputs and the complexity of control circuitries since microfluidic devices as contemporary lab-on-a-chip platforms are transferring from research settings to low-resource environments with high integrability and a small form factor. In this paper, we first present manually operatable, on-chip bistable pneumatic microstructures (BPMs) for microfluidic manipulation. The structural design and operation of the BPM devices can be readily integrated into any pneumatically powered microfluidic network consisting of pneumatic and fluidic channels. It is mainly composed of a vacuum activation chamber (VAC) and a pressure release chamber (PRC), of which users have direct control through finger pressing to switch either to the bistable vacuum state (VS) or the atmospheric state (AS). We have integrated multiple BPM devices into a 4-to-1 microfluidic multiplexor to demonstrate on-chip digital flow switching from different sources. Furthermore, we have shown its clinical relevance in a point-of-care diagnostic chip that processes blood samples to identify the distinct blood types (A/B/O) on-chip.

Interaction vs. observation: distinctive modes of social cognition in human brain and behavior? A combined fMRI and eye-tracking study

PubMed Central

Tylén, Kristian; Allen, Micah; Hunter, Bjørk K.; Roepstorff, Andreas

2012-01-01

Human cognition has usually been approached on the level of individual minds and brains, but social interaction is a challenging case. Is it best thought of as a self-contained individual cognitive process aiming at an “understanding of the other,” or should it rather be approached as an collective, inter-personal process where individual cognitive components interact on a moment-to-moment basis to form coupled dynamics? In a combined fMRI and eye-tracking study we directly contrasted these models of social cognition. We found that the perception of situations affording social contingent responsiveness (e.g., someone offering or showing you an object) elicited activations in regions of the right posterior temporal sulcus and yielded greater pupil dilation corresponding to a model of coupled dynamics (joint action). In contrast, the social-cognitive perception of someone “privately” manipulating an object elicited activation in medial prefrontal cortex, the right inferior frontal gyrus and right inferior parietal lobus, regions normally associated with Theory of Mind and with the mirror neuron system. Our findings support a distinction in social cognition between social observation and social interaction, and demonstrate that simple ostensive cues may shift participants' experience, behavior, and brain activity between these modes. The identification of a distinct, interactive mode has implications for research on social cognition, both in everyday life and in clinical conditions. PMID:23267322

A homozygous founder missense variant in arylsulfatase G abolishes its enzymatic activity causing atypical Usher syndrome in humans.

PubMed

Khateb, Samer; Kowalewski, Björn; Bedoni, Nicola; Damme, Markus; Pollack, Netta; Saada, Ann; Obolensky, Alexey; Ben-Yosef, Tamar; Gross, Menachem; Dierks, Thomas; Banin, Eyal; Rivolta, Carlo; Sharon, Dror

2018-01-04

PurposeWe aimed to identify the cause of disease in patients suffering from a distinctive, atypical form of Usher syndrome.MethodsWhole-exome and genome sequencing were performed in five patients from three families of Yemenite Jewish origin, suffering from distinctive retinal degeneration phenotype and sensorineural hearing loss. Functional analysis of the wild-type and mutant proteins was performed in human fibrosarcoma cells.ResultsWe identified a homozygous founder missense variant, c.133G>T (p.D45Y) in arylsulfatase G (ARSG). All patients shared a distinctive retinal phenotype with ring-shaped atrophy along the arcades engirdling the fovea, resulting in ring scotoma. In addition, patients developed moderate to severe sensorineural hearing loss. Both vision and hearing loss appeared around the age of 40 years. The identified variant affected a fully conserved amino acid that is part of the catalytic site of the enzyme. Functional analysis of the wild-type and mutant proteins showed no basal activity of p.D45Y.ConclusionHomozygosity for ARSG-p.D45Y in humans leads to protein dysfunction, causing an atypical combination of late-onset Usher syndrome. Although there is no evidence for generalized clinical manifestations of lysosomal storage diseases in this set of patients, we cannot rule out the possibility that mild and late-onset symptoms may appear.GENETICS in MEDICINE advance online publication, 4 January 2018; doi:10.1038/gim.2017.227.

Generation of novel bone forming cells (monoosteophils) from the cathelicidin-derived peptide LL-37 treated monocytes.

PubMed

Zhang, Zhifang; Shively, John E

2010-11-15

Bone generation and maintenance involve osteoblasts, osteoclasts, and osteocytes which originate from unique precursors and rely on key growth factors for differentiation. However, an incomplete understanding of bone forming cells during wound healing has led to an unfilled clinical need such as nonunion of bone fractures. Since circulating monocytes are often recruited to sites of injury and may differentiate into various cell types including osteoclasts, we investigated the possibility that circulating monocytes in the context of tissue injury may also contribute to bone repair. In particular, we hypothesized that LL-37 (produced from hCAP-18, cathelicidin), which recruits circulating monocytes during injury, may play a role in bone repair. Treatment of monocytes from blood with LL-37 for 6 days resulted in their differentiation to large adherent cells. Growth of LL-37-differentiated monocytes on osteologic discs reveals bone-like nodule formation by scanning electron microscopy (SEM). In vivo transplantation studies in NOD/SCID mice show that LL-37-differentiated monocytes form bone-like structures similar to endochondral bone formation. Importantly, LL-37-differentiated monocytes are distinct from conventional monocyte-derived osteoclasts, macrophages, and dendritic cells and do not express markers of the mesenchymal stem cells (MSC) lineage, distinguishing them from the conventional precursors of osteoblasts. Furthermore, LL-37 differentiated monocytes express intracellular proteins of both the osteoblast and osteoclast lineage including osteocalcin (OC), osteonectin (ON), bone sialoprotein II (BSP II), osteopontin (OP), RANK, RANKL, MMP-9, tartrate resistant acid phosphatase (TRAP), and cathepsin K (CK). Blood derived monocytes treated with LL-37 can be differentiated into a novel bone forming cell that functions both in vitro and in vivo. We propose the name monoosteophil to indicate their monocyte derived lineage and their bone forming phenotype. These cells may have wide ranging implications in the clinic including repair of broken bones and treatment of osteoporosis.

[Managment of acute low back pain without trauma - an algorithm].

PubMed

Melcher, Carolin; Wegener, Bernd; Jansson, Volkmar; Mutschler, Wolf; Kanz, Karl-Georg; Birkenmaier, Christof

2018-05-14

Low back pain is a common problem for primary care providers, outpatient clinics and A&E departments. The predominant symptoms are those of so-called "unspecific back pain", but serious pathologies can be concealed by the clinical signs. Especially less experienced colleagues have problems in treating these patients, as - despite the multitude of recommendations and guidelines - there is no generally accepted algorithm. After a literature search (Medline/Cochrane), 158 articles were selected from 15,000 papers and classified according to their level of evidence. These were attuned to the clinical guidelines of the orthopaedic and pain-physician associations in Europe, North America and overseas and the experience of specialists at LMU Munich, in order to achieve consistency with literature recommendations, as well as feasibility in everyday clinical work and optimised with practical relevance. An algorithm was formed to provide the crucial differential diagnosis of lumbar back pain according to its clinical relevance and to provide a plan of action offering reasonable diagnostic and therapeutic steps. As a consequence of distinct binary decisions, low back patients should be treated at any given time according to the guidelines, with emergencies detected, unnecessary diagnostic testing and interventions averted and reasonable treatment initiated pursuant to the underlying pathology. In the context of the available evidence, a clinical algorithm has been developed that translates the complex diagnostic testing of acute low back pain into a transparent, structured and systematic guideline. Georg Thieme Verlag KG Stuttgart · New York.

An exploratory investigation of purging disorder.

PubMed

Smith, Kathryn E; Crowther, Janis H

2013-01-01

Purging Disorder (PD) is an understudied pattern of behaviors within the Eating Disorder Not Otherwise Specified (EDNOS) category. Such categorization may suggest that PD is not clinically significant as other eating disorders. However, evidence has suggested that PD is associated with significant impairments in psychosocial functioning and well-being. Despite the apparent clinical significance of PD, it remains to be determined if PD is distinct from other clinically significant eating disorders. The present study sought to assess the phenomenology, clinical significance, and distinctiveness of PD. Group scores on measures of eating pathology, body image disturbance, and psychological correlates were compared using MANOVA among a female undergraduate sample (N=94) meeting diagnostic criteria for PD (n=20), Bulimia Nervosa (BN; n=35), restrained eating (n=18), and healthy controls (n=21). Overall, results indicated the PD group reported less severe symptoms than BN but more severe symptoms than controls. The PD and restraint groups were similar on most variables (including subjective binge behavior), with the exception of perfectionism and hunger. Findings support the conceptualization of PD as existing along a spectrum of bulimic spectrum disorders rather than as a distinct diagnostic category. Copyright © 2012 Elsevier Ltd. All rights reserved.

Two Forms of Philosophical Argument or Critique

ERIC Educational Resources Information Center

Marshall, James D.

2004-01-01

In this paper the author looks at two forms of philosophical argument or critique. These are derived by himself from the work of the late Kantian scholar, Stephan Korner who, in his book "What is Philosophy?" (1969), draws a number of distinctions between different forms of "philosophical" argument or critique. The two forms of derived argument,…

Rural-Urban Differences in Environmental Concern in Canada

ERIC Educational Resources Information Center

Huddart-Kennedy, Emily; Beckley, Thomas M.; McFarlane, Bonita L.; Nadeau, Solange

2009-01-01

Distinctions between rural and urban populations are well documented in environmental sociology literature. Rural and urban places may exert different influences on participation in environmentally supportive behavior (ESB) as well as on other forms of environmental concern (EC). The influence of these distinct geographies may be due to present…

Hidden species complexes within distinctive taxa: the case of Epanthidium bicoloratum (Smith) (Hymenoptera: Megachilidae)

USDA-ARS?s Scientific Manuscript database

Epanthidium bicoloratum (Smith) differs from all other Neotropical Anthidiini in the distinctive tegula, which is narrowed posteriorly forming a slender wedge. Examination of material standing under this name revealed that it represents a species complex that includes three new cryptic species, E. ...

Nursing's ways of knowing and dual process theories of cognition.

PubMed

Paley, John; Cheyne, Helen; Dalgleish, Len; Duncan, Edward A S; Niven, Catherine A

2007-12-01

This paper is a comparison of nursing's patterns of knowing with the systems identified by cognitive science, and evaluates claims about the equal-status relation between scientific and non-scientific knowledge. Ever since Carper's seminal paper in 1978, it has been taken for granted in the nursing literature that there are ways of knowing, or patterns of knowing, that are not scientific. This idea has recently been used to argue that the concept of evidence, typically associated with evidence-based practice, is inappropriately restricted because it is identified exclusively with scientific research. The paper reviews literature in psychology which appears to draw a comparable distinction between rule-based, analytical cognitive processes and other forms of cognitive processing which are unconscious, holistic and intuitive. There is a convincing parallel between the 'patterns of knowing' distinction in nursing and the 'cognitive processing' distinction in psychology. However, there is an important difference in the way the relation between different forms of knowing (or cognitive processing) is depicted. In nursing, it is argued that the different patterns of knowing have equal status and weight. In cognitive science, it is suggested that the rule-based, analytical form of cognition has a supervisory and corrective function with respect to the other forms. Scientific reasoning and evidence-based knowledge have epistemological priority over the other forms of nursing knowledge. The implications of this claim for healthcare practice are briefly indicated.

Adoptive T-cell therapy for Leukemia.

PubMed

Garber, Haven R; Mirza, Asma; Mittendorf, Elizabeth A; Alatrash, Gheath

2014-01-01

Allogeneic stem cell transplantation (alloSCT) is the most robust form of adoptive cellular therapy (ACT) and has been tremendously effective in the treatment of leukemia. It is one of the original forms of cancer immunotherapy and illustrates that lymphocytes can specifically recognize and eliminate aberrant, malignant cells. However, because of the high morbidity and mortality that is associated with alloSCT including graft-versus-host disease (GvHD), refining the anti-leukemia immunity of alloSCT to target distinct antigens that mediate the graft-versus-leukemia (GvL) effect could transform our approach to treating leukemia, and possibly other hematologic malignancies. Over the past few decades, many leukemia antigens have been discovered that can separate malignant cells from normal host cells and render them vulnerable targets. In concert, the field of T-cell engineering has matured to enable transfer of ectopic high-affinity antigen receptors into host or donor cells with greater efficiency and potency. Many preclinical studies have demonstrated that engineered and conventional T-cells can mediate lysis and eradication of leukemia via one or more leukemia antigen targets. This evidence now serves as a foundation for clinical trials that aim to cure leukemia using T-cells. The recent clinical success of anti-CD19 chimeric antigen receptor (CAR) cells for treating patients with acute lymphoblastic leukemia and chronic lymphocytic leukemia displays the potential of this new therapeutic modality. In this review, we discuss some of the most promising leukemia antigens and the novel strategies that have been implemented for adoptive cellular immunotherapy of lymphoid and myeloid leukemias. It is important to summarize the data for ACT of leukemia for physicians in-training and in practice and for investigators who work in this and related fields as there are recent discoveries already being translated to the patient setting and numerous accruing clinical trials. We primarily focus on ACT that has been used in the clinical setting or that is currently undergoing preclinical testing with a foreseeable clinical endpoint.

Integrated tumor and germline whole-exome sequencing identifies mutations in MAPK and PI3K pathway genes in an adolescent with rosette-forming glioneuronal tumor of the fourth ventricle

PubMed Central

Lin, Frank Y.; Bergstrom, Katie; Person, Richard; Bavle, Abhishek; Ballester, Leomar Y.; Scollon, Sarah; Raesz-Martinez, Robin; Jea, Andrew; Birchansky, Sherri; Wheeler, David A.; Berg, Stacey L.; Chintagumpala, Murali M.; Adesina, Adekunle M.; Eng, Christine; Roy, Angshumoy; Plon, Sharon E.; Parsons, D. Williams

2016-01-01

The integration of genome-scale studies such as whole-exome sequencing (WES) into the clinical care of children with cancer has the potential to provide insight into the genetic basis of an individual's cancer with implications for clinical management. This report describes the results of clinical tumor and germline WES for a patient with a rare tumor diagnosis, rosette-forming glioneuronal tumor of the fourth ventricle (RGNT). Three pathogenic gene alterations with implications for clinical care were identified: somatic activating hotspot mutations in FGFR1 (p.N546K) and PIK3CA (p.H1047R) and a germline pathogenic variant in PTPN11 (p.N308S) diagnostic for Noonan syndrome. The molecular landscape of RGNT is not well-described, but these data are consistent with prior observations regarding the importance of the interconnected MAPK and PI3K/AKT/mTOR signaling pathways in this rare tumor. The co-occurrence of FGFR1, PIK3CA, and PTPN11 alterations provides further evidence for consideration of RGNT as a distinct molecular entity from pediatric low-grade gliomas and suggests potential therapeutic strategies for this patient in the event of tumor recurrence as novel agents targeting these pathways enter pediatric clinical trials. Although RGNT has not been definitively linked with cancer predisposition syndromes, two prior cases have been reported in patients with RASopathies (Noonan syndrome and neurofibromatosis type 1 [NF1]), providing an additional link between these tumors and the mitogen-activated protein kinase (MAPK) signaling pathway. In summary, this case provides an example of the potential for genome-scale sequencing technologies to provide insight into the biology of rare tumors and yield both tumor and germline results of potential relevance to patient care. PMID:27626068

Faces forming traces: neurophysiological correlates of learning naturally distinctive and caricatured faces.

PubMed

Schulz, Claudia; Kaufmann, Jürgen M; Kurt, Alexander; Schweinberger, Stefan R

2012-10-15

Distinctive faces are easier to learn and recognise than typical faces. We investigated effects of natural vs. artificial distinctiveness on performance and neural correlates of face learning. Spatial caricatures of initially non-distinctive faces were created such that their rated distinctiveness matched a set of naturally distinctive faces. During learning, we presented naturally distinctive, caricatured, and non-distinctive faces for later recognition among novel faces, using different images of the same identities at learning and test. For learned faces, an advantage in performance was observed for naturally distinctive and caricatured over non-distinctive faces, with larger benefits for naturally distinctive faces. Distinctive and caricatured faces elicited more negative occipitotemporal ERPs (P200, N250) and larger centroparietal positivity (LPC) during learning. At test, earliest distinctiveness effects were again seen in the P200. In line with recent research, N250 and LPC were larger for learned than for novel faces overall. Importantly, whereas left hemispheric N250 was increased for learned naturally distinctive faces, right hemispheric N250 responded particularly to caricatured novel faces. We conclude that natural distinctiveness induces benefits to face recognition beyond those induced by exaggeration of a face's idiosyncratic shape, and that the left hemisphere in particular may mediate recognition across different images. Copyright © 2012 Elsevier Inc. All rights reserved.

Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

PubMed

Rice, Thomas W; Ishwaran, Hemant; Blackstone, Eugene H; Hofstetter, Wayne L; Kelsen, David P; Apperson-Hansen, Carolyn

2016-11-01

We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was "pinched," with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved. © 2016 International Society for Diseases of the Esophagus.

Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals

PubMed Central

Rice, Thomas W.; Ishwaran, Hemant; Blackstone, Eugene H.; Hofstetter, Wayne L.; Kelsen, David P.; Apperson-Hansen, Carolyn

2017-01-01

SUMMARY We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was “pinched,” with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved. PMID:27905171

Hereditary motor and sensory neuropathies or Charcot-Marie-Tooth diseases: an update.

PubMed

Tazir, Meriem; Hamadouche, Tarik; Nouioua, Sonia; Mathis, Stephane; Vallat, Jean-Michel

2014-12-15

Hereditary motor and sensory neuropathies (HMSN) or Charcot-Marie-Tooth (CMT) diseases are the most common degenerative disorders of the peripheral nervous system. However, the frequency of the different subtypes varies within distinct populations. Although more than seventy clinical and genetic forms are known to date, more than 80% of CMT patients in Western countries have genetic abnormalities associated with PMP22, MPZ, MFN2 and GJB1. Given the considerable genetic heterogeneity of CMT, we emphasize the interest of both clinical and pathological specific features such that focused genetic testing could be performed. In this regard, peripheral nerve lesions in GDAP1 mutations (AR CMT1A), such as mitochondrial abnormalities, have been newly demonstrated. Otherwise, while demyelinating autosomal recessive CMT used to be classified as CMT4 (A, B, C …), we propose a simplified classification such as AR CMT1 (A, B, C …), and AR CMT2 for axonal forms. Also, we stress that next generation sequencing techniques, now considered to be the most efficient methods of genetic testing in CMT, will be helpful in molecular diagnosis and research of new genes involved. Finally, while no effective therapy is known to date, ongoing new therapeutic trials such as PXT3003 (a low dose combination of the three already approved drugs baclofen, naltrexone, and D-sorbitol) give hopes for potential curative treatment. Copyright © 2014 Elsevier B.V. All rights reserved.

Functional Studies of Tyrosine Hydroxylase Missense Variants Reveal Distinct Patterns of Molecular Defects in Dopa-Responsive Dystonia

PubMed Central

Fossbakk, Agnete; Kleppe, Rune; Knappskog, Per M; Martinez, Aurora; Haavik, Jan

2014-01-01

Congenital tyrosine hydroxylase deficiency (THD) is found in autosomal-recessive Dopa-responsive dystonia and related neurological syndromes. The clinical manifestations of THD are variable, ranging from early-onset lethal disease to mild Parkinson disease-like symptoms appearing in adolescence. Until 2014, approximately 70 THD patients with a total of 40 different disease-related missense mutations, five nonsense mutations, and three mutations in the promoter region of the tyrosine hydroxylase (TH) gene have been reported. We collected clinical and biochemical data in the literature for all variants, and also generated mutant forms of TH variants previously not studied (N = 23). We compared the in vitro solubility, thermal stability, and kinetic properties of the TH variants to determine the cause(s) of their impaired enzyme activity, and found great heterogeneity in all these properties among the mutated forms. Some TH variants had specific kinetic anomalies and phenylalanine hydroxylase, and Dopa oxidase activities were measured for variants that showed signs of altered substrate binding. p.Arg233His, p.Gly247Ser, and p.Phe375Leu had shifted substrate specificity from tyrosine to phenylalanine and Dopa, whereas p.Cys359Phe had an impaired activity toward these substrates. The new data about pathogenic mechanisms presented are expected to contribute to develop individualized therapy for THD patients. PMID:24753243

Pauci- and Multibacillary Leprosy: Two Distinct, Genetically Neglected Diseases

PubMed Central

Gaschignard, Jean; Grant, Audrey Virginia; Thuc, Nguyen Van; Orlova, Marianna; Cobat, Aurélie; Huong, Nguyen Thu; Ba, Nguyen Ngoc; Thai, Vu Hong; Abel, Laurent; Schurr, Erwin; Alcaïs, Alexandre

2016-01-01

After sustained exposure to Mycobacterium leprae, only a subset of exposed individuals develops clinical leprosy. Moreover, leprosy patients show a wide spectrum of clinical manifestations that extend from the paucibacillary (PB) to the multibacillary (MB) form of the disease. This “polarization” of leprosy has long been a major focus of investigation for immunologists because of the different immune response in these two forms. But while leprosy per se has been shown to be under tight human genetic control, few epidemiological or genetic studies have focused on leprosy subtypes. Using PubMed, we collected available data in English on the epidemiology of leprosy polarization and the possible role of human genetics in its pathophysiology until September 2015. At the genetic level, we assembled a list of 28 genes from the literature that are associated with leprosy subtypes or implicated in the polarization process. Our bibliographical search revealed that improved study designs are needed to identify genes associated with leprosy polarization. Future investigations should not be restricted to a subanalysis of leprosy per se studies but should instead contrast MB to PB individuals. We show the latter approach to be the most powerful design for the identification of genetic polarization determinants. Finally, we bring to light the important resource represented by the nine-banded armadillo model, a unique animal model for leprosy. PMID:27219008

Two distinct forms of functional lateralization in the human brain

PubMed Central

Gotts, Stephen J.; Jo, Hang Joon; Wallace, Gregory L.; Saad, Ziad S.; Cox, Robert W.; Martin, Alex

2013-01-01

The hemispheric lateralization of certain faculties in the human brain has long been held to be beneficial for functioning. However, quantitative relationships between the degree of lateralization in particular brain regions and the level of functioning have yet to be established. Here we demonstrate that two distinct forms of functional lateralization are present in the left vs. the right cerebral hemisphere, with the left hemisphere showing a preference to interact more exclusively with itself, particularly for cortical regions involved in language and fine motor coordination. In contrast, right-hemisphere cortical regions involved in visuospatial and attentional processing interact in a more integrative fashion with both hemispheres. The degree of lateralization present in these distinct systems selectively predicted behavioral measures of verbal and visuospatial ability, providing direct evidence that lateralization is associated with enhanced cognitive ability. PMID:23959883

Medical History as an Introduction to Clinical Reasoning.

ERIC Educational Resources Information Center

Maulitz, Russell C.; And Others

1983-01-01

An elective course in the history of medicine focuses on clinical thinking using the case study method. Course goals include: student recognition of clinical reasoning as a historical process; understanding of distinctions between disease categories and etiological frameworks; and different conceptualizations (etiological and syndromic) of…

Is it meaningful to distinguish between generalized and specific Internet addiction? Evidence from a cross-cultural study from Germany, Sweden, Taiwan and China.

PubMed

Montag, Christian; Bey, Katharina; Sha, Peng; Li, Mei; Chen, Ya-Fei; Liu, Wei-Yin; Zhu, Yi-Kang; Li, Chun-Bo; Markett, Sebastian; Keiper, Julia; Reuter, Martin

2015-03-01

It has been hypothesized that two distinctive forms of Internet addiction exist. Here, generalized Internet addiction refers to the problematic use of the Internet covering a broad range of Internet-related activities. In contrast, specific forms of Internet addiction target the problematic use of distinct online activities such as excessive online video gaming or activities in social networks. The present study investigates the relationship between generalized and specific Internet addiction in a cross-cultural study encompassing data from China, Taiwan, Sweden and Germany in n = 636 participants. In this study, we assessed - besides generalized Internet addiction - addictive behavior in the domains of online video gaming, online shopping, online social networks and online pornography. The results confirm the existence of distinct forms of specific Internet addiction. One exception, however, was established in five of the six samples under investigation: online social network addiction correlates in large amounts with generalized Internet addiction. In general, it is of importance to distinguish between generalized and specific Internet addiction. Copyright © 2014 Wiley Publishing Asia Pty Ltd.

Contrasting Specializations for Facial Motion Within the Macaque Face-Processing System

PubMed Central

Fisher, Clark; Freiwald, Winrich A.

2014-01-01

SUMMARY Facial motion transmits rich and ethologically vital information [1, 2], but how the brain interprets this complex signal is poorly understood. Facial form is analyzed by anatomically distinct face patches in the macaque brain [3, 4], and facial motion activates these patches and surrounding areas [5, 6]. Yet it is not known whether facial motion is processed by its own distinct and specialized neural machinery, and if so, what that machinery’s organization might be. To address these questions, we used functional magnetic resonance imaging (fMRI) to monitor the brain activity of macaque monkeys while they viewed low- and high-level motion and form stimuli. We found that, beyond classical motion areas and the known face patch system, moving faces recruited a heretofore-unrecognized face patch. Although all face patches displayed distinctive selectivity for face motion over object motion, only two face patches preferred naturally moving faces, while three others preferred randomized, rapidly varying sequences of facial form. This functional divide was anatomically specific, segregating dorsal from ventral face patches, thereby revealing a new organizational principle of the macaque face-processing system. PMID:25578903

The Genetic Challenges and Opportunities in Advanced Heart Failure

PubMed Central

Hannah-Shmouni, Fady; Seidelmann, Sara B.; Sirrs, Sandra; Mani, Arya; Jacoby, Daniel

2017-01-01

The causes of heart failure are diverse. Inherited causes represent an important clinical entity and can be divided into 2 major categories: familial and metabolic cardiomyopathies. The distinct features that might be present in early disease states can become broadly overlapping with other diseases, such as in the case of inherited cardiomyopathies (ie, familial hypertrophic cardiomyopathy or mitochondrial diseases). In this review article, we focus on genetic issues related to advanced heart failure. Because of the emerging importance of this topic and its breadth, we sought to focus our discussion on the known genetic forms of heart failure syndromes, genetic testing, and newer data on pharmacogenetics and therapeutics in the treatment of heart failure, to primarily encourage clinicians to place a priority on the diagnosis and treatment of these potentially treatable conditions. PMID:26518444

Noninvasive in situ evaluation of osteogenic differentiation by time-resolved laser-induced fluorescence spectroscopy.

PubMed

Ashjian, Peter; Elbarbary, Amir; Zuk, Patricia; DeUgarte, Daniel A; Benhaim, Prosper; Marcu, Laura; Hedrick, Marc H

2004-01-01

The clinical implantation of bioengineered tissues requires an in situ nondestructive evaluation of the quality of tissue constructs developed in vitro before transplantation. Time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) is demonstrated here to noninvasively monitor the formation of osteogenic extracellular matrix (ECM) produced by putative stem cells (PLA cells) derived from human adipose tissue. We show that this optical spectroscopy technique can assess the relative expression of collagens (types I, III, IV, and V) within newly forming osteogenic ECM. The results are consistent with those obtained by conventional histochemical techniques (immunofluorescence and Western blot) and demonstrate that TR-LIFS is a potential tool for monitoring the expression of distinct collagen types and the formation of collagen cross-links in intact tissue constructs.

Familial atrophia maculosa varioliformis cutis: an ultrastructural study.

PubMed

Dall'Oglio, F; Nasca, M R; Taparelli, F; Bacchelli, B; Micali, G

2001-01-01

Atrophia maculosa varioliformis cutis is a rare and distinctive form of idiopathic facial macular noninflammatory atrophy that may rarely be observed in members of the same family. We describe two brothers, ages 14 and 16 years, with spontaneously appearing, asymptomatic, varioliform and linear atrophic lesions. Their past medical history was positive for varicella occurring in childhood without residual facial scarring. Routine laboratory investigations and screening for circulating autoantibodies were negative. Both patients were concordant for HLA A2 and DQ4.1. Routine and ultrastructural histologic examination of a punch biopsy specimen showed the presence of scarce, small, fragmented elastic fibers and compact collagen bundles associated with hypertrophic fibroblasts in the dermis. Our patients remained clinically stable, untreated, over a 2-year follow-up period. No long-term follow-up data have previously been reported.

Ethics in sports medicine.

PubMed

Dunn, Warren R; George, Michael S; Churchill, Larry; Spindler, Kurt P

2007-05-01

Physicians have struggled with the medical ramifications of athletic competition since ancient Greece, where rational medicine and organized athletics originated. Historically, the relationship between sport and medicine was adversarial because of conflicts between health and sport. However, modern sports medicine has emerged with the goal of improving performance and preventing injury, and the concept of the "team physician" has become an integral part of athletic culture. With this distinction come unique ethical challenges because the customary ethical norms for most forms of clinical practice, such as confidentiality and patient autonomy, cannot be translated easily into sports medicine. The particular areas of medical ethics that present unique challenges in sports medicine are informed consent, third parties, advertising, confidentiality, drug use, and innovative technology. Unfortunately, there is no widely accepted code of sports medicine ethics that adequately addresses these issues.

Gallbladder cancer: review of a rare orphan gastrointestinal cancer with a focus on populations of New Mexico.

PubMed

Nemunaitis, Jacklyn M; Brown-Glabeman, Ursa; Soares, Heloisa; Belmonte, Jessica; Liem, Ben; Nir, Itzhak; Phuoc, Victor; Gullapalli, Rama R

2018-06-18

Gallbladder cancer is a rare malignancy of the biliary tract with a poor prognosis, frequently presenting at an advanced stage. While rare in the United States overall, gallbladder cancer has an elevated incidence in geographically distinct locations of the globe including Chile, North India, Korea, Japan and the state of New Mexico in the United States. People with Native American ancestry have a much elevated incidence of gallbladder cancer compared to Hispanic and non-Hispanic white populations of New Mexico. Gallbladder cancer is also one of the few bi-gendered cancers with an elevated female incidence compared to men. Similar to other gastrointestinal cancers, gallbladder cancer etiology is likely multi-factorial involving a combination of genomic, immunological, and environmental factors. Understanding the interplay of these unique epidemiological factors is crucial in improving the prevention, early detection, and treatment of this lethal disease. Previous studies have failed to identify a distinct genomic mutational profile in gallbladder cancers, however, work to identify promising clinically actionable targets is this form of cancer is ongoing. Examples include, interest in the HER2/Neu signaling pathway and the recognition that chronic inflammation plays a crucial role in gallbladder cancer pathogenesis. In this review, we provide a comprehensive overview of gallbladder cancer epidemiology, risk factors, pathogenesis, and treatment with a specific focus on the rural and Native American populations of New Mexico. We conclude this review by discussing future research directions with the goal of improving clinical outcomes for patients of this lethal malignancy.

Fluctuating cognition in dementia with Lewy bodies and Alzheimer's disease is qualitatively distinct

PubMed Central

Bradshaw, J; Saling, M; Hopwood, M; Anderson, V; Brodtmann, A

2004-01-01

Objectives: To document and illustrate qualitative features of fluctuating cognition as described by care givers of patients with probable dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). To determine whether the quality of the fluctuations differs between DLB and AD. To examine the clinical utility of two recently developed rating scales. Methods: Care givers of 13 patients with early probable DLB and 12 patients with early probable AD were interviewed using the Clinician Assessment of Fluctuation and the One Day Fluctuation Assessment Scale, both developed recently. Descriptions of fluctuating cognition were recorded verbatim, analysed, and rated. Results: Descriptions of fluctuating cognition in DLB had a spontaneous, periodic, transient quality, which appeared to reflect an interruption in the ongoing flow of awareness or attention that impacted on functional abilities. Descriptions of fluctuations in AD frequently highlighted episodes of memory failure, or a more enduring state shift in the form of "good" and "bad" days, typically occurring in response to the cognitive demands of the immediate environment. These qualitative differences could be detected reliably by independent raters, but were not always captured in standard severity scores. Conclusion: Fluctuations occuring in DLB have particular characteristics that are distinguishable from fluctuations occurring in AD. Interpretation and application of the fluctuation criterion continues to limit the diagnostic sensitivity of the consensus criteria for DLB. Findings suggest that explicit documentation and a wider appreciation of these distinctions could improve the reliability with which less experienced clinicians identify this core diagnostic feature in the clinical setting. PMID:14966152

Comparison of the immune responses associated with experimental bovine mastitis caused by different strains of Escherichia coli.

PubMed

Blum, Shlomo E; Heller, Elimelech D; Jacoby, Shamay; Krifucks, Oleg; Leitner, Gabriel

2017-05-01

We studied the mammary immune response to different mammary pathogenic Escherichia coli (MPEC) strains in cows, hypothesising that the dynamics of response would differ. E. coli is a major aetiologic agent of acute clinical bovine mastitis of various degrees of severity with specific strains being associated with persistent infections. We compared challenge with three distinct pathogenic MPEC strains (VL2874, VL2732 and P4), isolated from different forms of mastitis (per-acute, persistent and acute, respectively). A secondary objective was to verify the lack of mammary pathogenicity of an environmental isolate (K71) that is used for comparison against MPEC in genomic and phenotypic studies. Twelve cows were challenged by intra-mammary infusion with one of the strains. Cellular and chemokine responses and bacterial culture follow-up were performed for 35 d. All cows challenged by any of the MPEC strains developed clinical mastitis. Differences were found in the intensity and duration of response, in somatic cell count, secreted cytokines (TNF-α, IL-6 and IL-17) and levels of milk leucocyte membrane Toll-like receptor 4 (TLR4). A sharp decrease of TLR4 on leucocytes was observed concomitantly to peak bacterial counts in milk. Intra-mammary infusion of strain K71 did not elicit inflammation and bacteria were not recovered from milk. Results suggest some differences in the mammary immune response to distinct MPEC strains that could be correlated to their previously observed pathogenic traits. This is also the first report of an E. coli strain that is non-pathogenic to the bovine mammary gland.

Translocations and mutations involving the nucleophosmin (NPM1) gene in lymphomas and leukemias.

PubMed

Falini, Brunangelo; Nicoletti, Ildo; Bolli, Niccolò; Martelli, Maria Paola; Liso, Arcangelo; Gorello, Paolo; Mandelli, Franco; Mecucci, Cristina; Martelli, Massimo Fabrizio

2007-04-01

Nucleophosmin (NPM) is a ubiquitously expressed nucleolar phoshoprotein which shuttles continuously between the nucleus and cytoplasm. Many findings have revealed a complex scenario of NPM functions and interactions, pointing to proliferative and growth-suppressive roles of this molecule. The gene NPM1 that encodes for nucleophosmin (NPM1) is translocated or mutated in various lymphomas and leukemias, forming fusion proteins (NPM-ALK, NPM-RARalpha, NPM-MLF1) or NPM mutant products. Here, we review the structure and functions of NPM, as well as the biological, clinical and pathological features of human hematologic malignancies with NPM1 gene alterations. NPM-ALK indentifies a new category of T/Null lymphomas with distinctive molecular and clinico-pathological features, that is going to be included as a novel disease entity (ALK+ anaplastic large cell lymphoma) in the new WHO classification of lymphoid neoplasms. NPM1 mutations occur specifically in about 30% of adult de novo AML and cause aberrant cytoplasmic expression of NPM (hence the term NPMc+ AML). NPMc+ AML associates with normal karyotpe, and shows wide morphological spectrum, multilineage involvement, a unique gene expression signature, a high frequency of FLT3-internal tandem duplications, and distinctive clinical and prognostic features. The availability of specific antibodies and molecular techniques for the detection of NPM1 gene alterations has an enormous impact in the biological study diagnosis, prognostic stratification, and monitoring of minimal residual disease of various lymphomas and leukemias. The discovery of NPM1 gene alterations also represents the rationale basis for development of molecular targeted drugs.

Fellowship training: a qualitative study of scope and purpose across one department of medicine.

PubMed

Karpinski, Jolanta; Ajjawi, Rola; Moreau, Katherine

2017-11-21

Fellowship training follows certification in a primary specialty or subspecialty and focusses on distinct and advanced clinical and/or academic skills. This phase of medical education is growing in prevalence, but has been an "invisible phase of postgraduate training" lacking standards for education and accreditation, as well as funding. We aimed to explore fellowship programs and examine the reasons to host and participate in fellowship training, seeking to inform the future development of fellowship education. During the 2013-14 academic year, we conducted interviews and focus groups to examine the current status of fellowship training from the perspectives of division heads, fellowship directors and current fellows at the Department of Medicine, University of Ottawa, Canada. Descriptive statistics were used to depict the prevailing status of fellowship training. A process of data reduction, data analysis and conclusions/verifications was performed to analyse the quantitative data. We interviewed 16 division heads (94%), 15 fellowship directors (63%) and 8 fellows (21%). We identified three distinct types of fellowships. Individualized fellowships focus on the career goals of the trainee and/or the recruitment goals of the division. Clinical fellowships focus on the attainment of clinical expertise over and above the competencies of residency. Research fellowships focus on research productivity. Participants identified a variety of reasons to offer fellowships: improve academic productivity; improve clinical productivity; share/develop enhanced clinical expertise; recruit future faculty members/attain an academic position; enhance the reputation of the division/department/trainee; and enhance the scholarly environment. Fellowships serve a variety of purposes which benefit both individual trainees as well as the academic enterprise. Fellowships can be categorized within a distinct taxonomy: individualized; clinical; and research. Each type of fellowship may serve a variety of purposes, and each may need distinct support and resources. Further research is needed to catalogue the operational requirements for hosting and undertaking fellowship training, and establish recommendations for educational and administrative policy and processes in this new phase of postgraduate education.

Distinct genetic difference between the Duffy binding protein (PkDBPαII) of Plasmodium knowlesi clinical isolates from North Borneo and Peninsular Malaysia.

PubMed

Fong, Mun-Yik; Rashdi, Sarah A A; Yusof, Ruhani; Lau, Yee-Ling

2015-02-21

Plasmodium knowlesi is one of the monkey malaria parasites that can cause human malaria. The Duffy binding protein of P. knowlesi (PkDBPαII) is essential for the parasite's invasion into human and monkey erythrocytes. A previous study on P. knowlesi clinical isolates from Peninsular Malaysia reported high level of genetic diversity in the PkDBPαII. Furthermore, 36 amino acid haplotypes were identified and these haplotypes could be separated into allele group I and allele group II. In the present study, the PkDBPαII of clinical isolates from the Malaysian states of Sarawak and Sabah in North Borneo was investigated, and compared with the PkDBPαII of Peninsular Malaysia isolates. Blood samples from 28 knowlesi malaria patients were used. These samples were collected between 2011 and 2013 from hospitals in North Borneo. The PkDBPαII region of the isolates was amplified by PCR, cloned into Escherichia coli, and sequenced. The genetic diversity, natural selection and phylogenetics of PkDBPαII haplotypes were analysed using MEGA5 and DnaSP ver. 5.10.00 programmes. Forty-nine PkDBPαII sequences were obtained. Comparison at the nucleotide level against P. knowlesi strain H as reference sequence revealed 58 synonymous and 102 non-synonymous mutations. Analysis on these mutations showed that PkDBPαII was under purifying (negative) selection. At the amino acid level, 38 different PkDBPαII haplotypes were identified. Twelve of the 28 blood samples had mixed haplotype infections. Phylogenetic analysis revealed that all the haplotypes were in allele group I, but they formed a sub-group that was distinct from those of Peninsular Malaysia. Wright's FST fixation index indicated high genetic differentiation between the North Borneo and Peninsular Malaysia haplotypes. This study is the first to report the genetic diversity and natural selection of PkDBPαII of P. knowlesi from Borneo Island. The PkDBPαII haplotypes found in this study were distinct from those from Peninsular Malaysia. This difference may not be attributed to geographical separation because other genetic markers studied thus far such as the P. knowlesi circumsporozoite protein gene and small subunit ribosomal RNA do not display such differentiation. Immune evasion may possibly be the reason for the differentiation.

Demographics and clinical characteristics of primary lateral sclerosis: case series and a review of literature.

PubMed

Ramanathan, Ramnath Santosh; Rana, Sandeep

2018-02-01

Primary lateral sclerosis (PLS) is a form of motor neuron disease involving only upper motor neurons. In some patients presenting as PLS, the disease progresses to involve lower motor neurons and thereby converting to amyotrophic lateral sclerosis (ALS). However, pure forms of PLS do exist. Our aim was to study epidemiological and clinical characteristics of pure PLS patients treated at our neuromuscular clinic. We retrospectively reviewed 15 patients from July 2011 to October 2014 with PLS treated at the neuromuscular disorder clinic at our hospital. Data collection included patient demographics, age and site of onset, duration of symptoms and duration of follow-up. We also studied clinical features such as bulbar involvement; pseudobulbar affect; depression; spasms/pain; bladder involvement; diagnostic work up, in other words, MRI; brain/electromyography findings; clinical course, namely years to wheelchair; and need for gastrostomy tube requirement baclofen pump placement. We also tried to find a correlation between PLS and environmental factors such as urban/suburban/rural living, consumption of well water, socioeconomic status/occupation and history of trauma. Male-to-female ratio was 1:2, mean age at onset of symptoms was 58.6 years, with the oldest patient being an 84-year-old female at the time of onset of symptoms. Mean duration of follow-up was 51 months. Mean duration of symptoms was 77.4 months. About eight (53%) patients presented with bulbar symptoms in the form of spastic speech and dysphagia, pseudobulbar affect, developed depression and had bladder involvement. Seven (47%) patients presented with symmetric spasticity in the extremities. A third of the patients required baclofen for spasticity and a third required gastrostomy tube placement for dysphagia. None of them had abnormal neuroimaging or electrodiagnostic testing. Only one patient had history of trauma. About half of the patients were from lower socioeconomic status as well as middle class. One of the patients had consumed well water during younger years and three (20%) patients lived in the rural area. Though on review of literature there is no clear consensus about the existence of PLS as a distinct disease entity, we believe that there are rare cases of motor neuron disease with progressive upper motor neuron symptoms that throughout their course never convert to ALS. Our series highlights the demographic and clinical features of these patients and underscores the longer survival of these patients when compared with ALS.

Differentiation of High-Functioning Autism and Asperger's Disorder Based on Neuromotor Behaviour

ERIC Educational Resources Information Center

Nayate, Ashwini; Tonge, Bruce J.; Bradshaw, John L.; McGinley, Jennifer L.; Iansek, Robert; Rinehart, Nicole J.

2012-01-01

Autism and Asperger's disorder (AD) are characterised by impairments in social interaction, stereotypic behaviours or restricted interests. Although currently listed as distinct clinical disorders, the validity of their distinction remains controversial. This study examined gait in children with autism and AD. Eleven children with high-functioning…

Function does not follow form in gene regulatory circuits.

PubMed

Payne, Joshua L; Wagner, Andreas

2015-08-20

Gene regulatory circuits are to the cell what arithmetic logic units are to the chip: fundamental components of information processing that map an input onto an output. Gene regulatory circuits come in many different forms, distinct structural configurations that determine who regulates whom. Studies that have focused on the gene expression patterns (functions) of circuits with a given structure (form) have examined just a few structures or gene expression patterns. Here, we use a computational model to exhaustively characterize the gene expression patterns of nearly 17 million three-gene circuits in order to systematically explore the relationship between circuit form and function. Three main conclusions emerge. First, function does not follow form. A circuit of any one structure can have between twelve and nearly thirty thousand distinct gene expression patterns. Second, and conversely, form does not follow function. Most gene expression patterns can be realized by more than one circuit structure. And third, multifunctionality severely constrains circuit form. The number of circuit structures able to drive multiple gene expression patterns decreases rapidly with the number of these patterns. These results indicate that it is generally not possible to infer circuit function from circuit form, or vice versa.

Functional map of arrestin binding to phosphorylated opsin, with and without agonist.

PubMed

Peterhans, Christian; Lally, Ciara C M; Ostermaier, Martin K; Sommer, Martha E; Standfuss, Jörg

2016-06-28

Arrestins desensitize G protein-coupled receptors (GPCRs) and act as mediators of signalling. Here we investigated the interactions of arrestin-1 with two functionally distinct forms of the dim-light photoreceptor rhodopsin. Using unbiased scanning mutagenesis we probed the individual contribution of each arrestin residue to the interaction with the phosphorylated apo-receptor (Ops-P) and the agonist-bound form (Meta II-P). Disruption of the polar core or displacement of the C-tail strengthened binding to both receptor forms. In contrast, mutations of phosphate-binding residues (phosphosensors) suggest the phosphorylated receptor C-terminus binds arrestin differently for Meta II-P and Ops-P. Likewise, mutations within the inter-domain interface, variations in the receptor-binding loops and the C-edge of arrestin reveal different binding modes. In summary, our results indicate that arrestin-1 binding to Meta II-P and Ops-P is similarly dependent on arrestin activation, although the complexes formed with these two receptor forms are structurally distinct.

Neuropathological Phenotype of a Distinct Form of Lissencephaly Associated with Mutations in "TUBA1A"

ERIC Educational Resources Information Center

Fallet-Bianco, Catherine; Loeuillet, Laurence; Poirier, Karine; Loget, Philippe; Chapon, Francoise; Pasquier, Laurent; Saillour, Yoann; Beldjord, Cherif; Chelly, Jamel; Francis, Fiona

2008-01-01

Lissencephalies are congenital malformations responsible for epilepsy and mental retardation in children. A number of distinct lissencephaly syndromes have been characterized, according to the aspect and the topography of the cortical malformation, the involvement of other cerebral structures and the identified genetic defect. A mutation in…

Expanding the Concepts in Protein Structure-Function Relationships and Enzyme Kinetics: Teaching Using Morpheeins

ERIC Educational Resources Information Center

Lawrence, Sarah H.; Jaffe, Eileen K.

2008-01-01

A morpheein is a homo-oligomeric protein that can exist as an ensemble of physiologically significant and functionally distinct alternate quaternary assemblies. Morpheeins exist in nature and use conformational equilibria between different tertiary structures to form distinct oligomers as a means of regulating their function. Notably, alternate…

Language Reflects "Core" Cognition: A New Theory about the Origin of Cross-Linguistic Regularities

ERIC Educational Resources Information Center

Strickland, Brent

2017-01-01

The underlying structures that are common to the world's languages bear an intriguing connection with early emerging forms of "core knowledge" (Spelke & Kinzler, 2007), which are frequently studied by infant researchers. In particular, grammatical systems often incorporate distinctions (e.g., the mass/count distinction) that reflect…

New Directions in Measuring Reactive and Proactive Aggression: Validation of a Teacher Questionnaire

ERIC Educational Resources Information Center

Polman, Hanneke; de Castro, Bram Orobio; Thomaes, Sander; van Aken, Marcel

2009-01-01

The well-known distinction between reactive and proactive aggression is theoretically important but empirically controversial. Recently, aggression researchers have argued that we should separate the form and function of aggression to make a clearer distinction between reactive and proactive aggression. This article describes the validation of a…

Neuronal migration disorders in microcephalic osteodysplastic primordial dwarfism type I/III.

PubMed

Juric-Sekhar, Gordana; Kapur, Raj P; Glass, Ian A; Murray, Mitzi L; Parnell, Shawn E; Hevner, Robert F

2011-04-01

Microcephalic osteodysplastic primordial dwarfism (MOPD) is a rare microlissencephaly syndrome, with at least two distinct phenotypic and genetic types. MOPD type II is caused by pericentrin mutations, while types I and III appear to represent a distinct entity (MOPD I/III) with variably penetrant phenotypes and unknown genetic basis. The neuropathology of MOPD I/III is little understood, especially in comparison to other forms of lissencephaly. Here, we report postmortem brain findings in an 11-month-old female infant with MOPD I/III. The cerebral cortex was diffusely pachygyric, with a right parietal porencephalic lesion. Histologically, the cortex was abnormally thick and disorganized. Distinct malformations were observed in different cerebral lobes, as characterized using layer-specific neuronal markers. Frontal cortex was severely disorganized and coated with extensive leptomeningeal glioneuronal heterotopia. Temporal cortex had a relatively normal 6-layered pattern, despite cortical thickening. Occipital cortex was variably affected. The corpus callosum was extremely hypoplastic. Brainstem and cerebellar malformations were also present, as well as old necrotic foci. Findings in this case suggest that the cortical malformation in MOPD I/III is distinct from other forms of pachygyria-lissencephaly.

Distinct subtypes of behavioral-variant frontotemporal dementia based on patterns of network degeneration

PubMed Central

Ranasinghe, Kamalini G; Rankin, Katherine P; Pressman, Peter S; Perry, David C; Lobach, Iryna V; Seeley, William W; Coppola, Giovanni; Karydas, Anna M; Grinberg, Lea T; Shany-Ur, Tal; Lee, Suzee E; Rabinovici, Gil D; Rosen, Howard J; Gorno-Tempini, Maria Luisa; Boxer, Adam L; Miller, Zachary A; Chiong, Winston; DeMay, Mary; Kramer, Joel H; Possin, Katherine L; Sturm, Virginia E; Bettcher, Brianne M; Neylan, Michael; Zackey, Diana D; Nguyen, Lauren A; Ketelle, Robin; Block, Nikolas; Wu, Teresa Q; Dallich, Alison; Russek, Natanya; Caplan, Alyssa; Geschwind, Daniel H; Vossel, Keith A; Miller, Bruce L

2016-01-01

Importance Clearer delineation of the phenotypic heterogeneity within behavioral variant frontotemporal dementia (bvFTD) will help uncover underlying biological mechanisms, and will improve clinicians’ ability to predict disease course and design targeted management strategies. Objective To identify subtypes of bvFTD syndrome based on distinctive patterns of atrophy defined by selective vulnerability of specific functional networks targeted in bvFTD, using statistical classification approaches. Design, Setting and Participants In this retrospective observational study, 104 patients meeting the Frontotemporal Dementia Consortium consensus criteria for bvFTD were evaluated at the Memory and Aging Center of Department of Neurology at University of California, San Francisco. Patients underwent a multidisciplinary clinical evaluation, including clinical demographics, genetic testing, symptom evaluation, neurological exam, neuropsychological bedside testing, and socioemotional assessments. Ninety patients underwent structural Magnetic Resonance Imaging at their earliest evaluation at the memory clinic. From each patients’ structural imaging, the mean volumes of 18 regions of interest (ROI) comprising the functional networks specifically vulnerable in bvFTD, including the ‘salience network’ (SN), with key nodes in the frontoinsula and pregenual anterior cingulate, and the ‘semantic appraisal network’ (SAN) anchored in the anterior temporal lobe and subgenual cingulate, were estimated. Principal component and cluster analyses of ROI volumes were used to identify patient clusters with anatomically distinct atrophy patterns. Main Outcome Measures We evaluated brain morphology and other clinical features including presenting symptoms, neurologic exam signs, neuropsychological performance, rate of dementia progression, and socioemotional function in each patient cluster. Results We identified four subgroups of bvFTD patients with distinct anatomic patterns of network degeneration, including two separate salience network–predominant subgroups: frontal/temporal (SN-FT), and frontal (SN-F), and a semantic appraisal network–predominant group (SAN), and a subcortical–predominant group. Subgroups demonstrated distinct patterns of cognitive, socioemotional, and motor symptoms, as well as genetic compositions and estimated rates of disease progression. Conclusions Divergent patterns of vulnerability in specific functional network components make an important contribution to clinical heterogeneity of bvFTD. The data-driven anatomical classification identifies biologically meaningful phenotypes and provides a replicable approach to disambiguate the bvFTD syndrome. PMID:27429218

Synergies and Distinctions between Computational Disciplines in Biomedical Research: Perspective from the Clinical and Translational Science Award Programs

PubMed Central

Bernstam, Elmer V.; Hersh, William R.; Johnson, Stephen B.; Chute, Christopher G.; Nguyen, Hien; Sim, Ida; Nahm, Meredith; Weiner, Mark; Miller, Perry; DiLaura, Robert P.; Overcash, Marc; Lehmann, Harold P.; Eichmann, David; Athey, Brian D.; Scheuermann, Richard H.; Anderson, Nick; Starren, Justin B.; Harris, Paul A.; Smith, Jack W.; Barbour, Ed; Silverstein, Jonathan C.; Krusch, David A.; Nagarajan, Rakesh; Becich, Michael J.

2010-01-01

Clinical and translational research increasingly requires computation. Projects may involve multiple computationally-oriented groups including information technology (IT) professionals, computer scientists and biomedical informaticians. However, many biomedical researchers are not aware of the distinctions among these complementary groups, leading to confusion, delays and sub-optimal results. Although written from the perspective of clinical and translational science award (CTSA) programs within academic medical centers, the paper addresses issues that extend beyond clinical and translational research. The authors describe the complementary but distinct roles of operational IT, research IT, computer science and biomedical informatics using a clinical data warehouse as a running example. In general, IT professionals focus on technology. The authors distinguish between two types of IT groups within academic medical centers: central or administrative IT (supporting the administrative computing needs of large organizations) and research IT (supporting the computing needs of researchers). Computer scientists focus on general issues of computation such as designing faster computers or more efficient algorithms, rather than specific applications. In contrast, informaticians are concerned with data, information and knowledge. Biomedical informaticians draw on a variety of tools, including but not limited to computers, to solve information problems in health care and biomedicine. The paper concludes with recommendations regarding administrative structures that can help to maximize the benefit of computation to biomedical research within academic health centers. PMID:19550198

Schizophrenia-like symptoms in narcolepsy type 1: shared and distinctive clinical characteristics.

PubMed

Plazzi, Giuseppe; Fabbri, Chiara; Pizza, Fabio; Serretti, Alessandro

2015-01-01

The occurrence of psychotic symptoms in narcolepsy type 1 (NT1) has been reported as responsible for delayed diagnosis due to the misdiagnosis of schizophrenia. This study aimed to identify shared and distinctive clinical characteristics between NT1 and schizophrenia, with the focus on psychotic symptoms. A total of 28 NT1 and 21 schizophrenia patients were included. Hallucination characteristics and PANSS (Positive and Negative Syndrome Scale), HRSD (Hamilton Rating Scale for Depression), DES (Dissociative Experiences Scale), and STAI (State-Trait Anxiety Inventory) scores were collected. Symptom overlap was investigated by χ(2), Fisher's or t tests and multiple logistic regression models. Hallucinations and illusions frequently occurred in both diseases. Unimodal hallucinations were more common in schizophrenia (p = 6.30e-07) and multimodal hallucinations in NT1, but no clear difference was identified in their sensory modality. Hypnagogic/hypnopompic hallucinations were typical of NT1 (p = 5.22e-07), and 25% of NT1 patients exhibited some degree of insight deficit. Hypnagogic/hypnopompic hallucinations, unimodal hallucinations and PANSS score were the most distinctive clinical characteristics. Clinical overlap was found in the dissociative and anxiety domains, while higher depressive scores were observed in schizophrenia. The overlap between NT1 and schizophrenia should be further investigated under a clinical and pathogenetic point of view to improve diagnostic and therapeutic approaches. © 2015 S. Karger AG, Basel.

Ethical responsibilities toward indirect and collateral participants in pragmatic clinical trials.

PubMed

Smalley, Jaye Bea; Merritt, Maria W; Al-Khatib, Sana M; McCall, Debbe; Staman, Karen L; Stepnowsky, Carl

2015-10-01

Pragmatic clinical trials are designed to inform decision makers about the benefits, burdens, and risks of health interventions in real-world settings. Pragmatic clinical trials often use for research purposes data collected in the course of clinical practice. The distinctive features of pragmatic clinical trials demand fresh thinking about what is required to act properly toward people affected by their conduct, in ways that go beyond ensuring the protection of rights and welfare for "human research subjects" under conventional research ethics regulations. To stimulate such work, we propose to distinguish among categories of research participants in pragmatic clinical trials as follows: Direct participants: (1) individuals being directly intervened upon and/or (2) individuals from whom personal identifiable data are being collected for the purposes of the pragmatic clinical trial. Indirect participants: individuals who are (1) not identified as direct participants and (2) whose rights and welfare may be affected by the intervention through their routine exposure to the environment in which the intervention is being deployed. Collateral participants: patient groups and other stakeholder communities who may be otherwise affected by the occurrence and findings of the pragmatic clinical trial. We illustrate these distinctions with case examples and discuss the distinctive responsibilities of researchers and pragmatic clinical trial leadership toward each type of participant. We suggest that pragmatic clinical trial investigators, institutional review boards, health systems leaders, and others engaged in the research enterprise work together to identify these participants. For indirect participants, risks and benefits to which they are exposed should be weighed to ensure that their rights and welfare are protected accordingly, and communication strategies should be considered to help them make well-informed decisions. Collateral participants could provide input on the design, planning, and conduct of a pragmatic clinical trial and offer insights regarding the best way to communicate the trial's results to their constituencies. © The Author(s) 2015.

Molecular subgroups of adult medulloblastoma: a long-term single-institution study.

PubMed

Zhao, Fu; Ohgaki, Hiroko; Xu, Lei; Giangaspero, Felice; Li, Chunde; Li, Peng; Yang, Zhijun; Wang, Bo; Wang, Xingchao; Wang, Zhenmin; Ai, Lin; Zhang, Jing; Luo, Lin; Liu, Pinan

2016-07-01

Recent transcriptomic approaches have demonstrated that there are at least 4 distinct subgroups in medulloblastoma (MB); however, survival studies of molecular subgroups in adult MB have been inconclusive because of small sample sizes. The aim of this study is to investigate the molecular subgroups in adult MB and identify their clinical and prognostic implications in a large, single-institution cohort. We determined gene expression profiles for 13 primary adult MBs. Bioinformatics tools were used to establish distinct molecular subgroups based on the most informative genes in the dataset. Immunohistochemistry with subgroup-specific antibodies was then used for validation within an independent cohort of 201 formalin-fixed MB tumors, in conjunction with a systematic analysis of clinical and histological characteristics. Three distinct molecular variants of adult MB were identified: the SHH, WNT, and group 4 subgroups. Validation of these subgroups in the 201-tumor cohort by immunohistochemistry identified significant differences in subgroup-specific demographics, histology, and metastatic status. The SHH subgroup accounted for the majority of the tumors (62%), followed by the group 4 subgroup (28%) and the WNT subgroup (10%). Group 4 tumors had significantly worse progression-free and overall survival compared with tumors of the other molecular subtypes. We have identified 3 subgroups of adult MB, characterized by distinct expression profiles, clinical features, pathological features, and prognosis. Clinical variables incorporated with molecular subgroup are more significantly informative for predicting adult patient outcome. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Clustering of self-organizing map identifies five distinct medulloblastoma subgroups.

PubMed

Cao, Changjun; Wang, Wei; Jiang, Pucha

2016-01-01

Medulloblastoma is one the most malignant paediatric brain tumours. Molecular subgrouping these medulloblastomas will not only help identify specific cohorts for certain treatment but also improve confidence in prognostic prediction. Currently, there is a consensus of the existences of four distinct subtypes of medulloblastoma. We proposed a novel bioinformatics method, clustering of self-organizing map, to determine the subgroups and their molecular diversity. Microarray expression profiles of 46 medulloblastoma samples were analysed and five clusters with distinct demographics, clinical outcome and transcriptional profiles were identified. The previously reported Wnt subgroup was identified as expected. Three other novel subgroups were proposed for later investigation. Our findings underscore the value of SOM clustering for discovering the medulloblastoma subgroups. When the suggested subdivision has been confirmed in large cohorts, this method should serve as a part of routine classification of clinical samples.

Preschool Children Use Linguistic Form Class and Pragmatic Cues To Interpret Generics.

ERIC Educational Resources Information Center

Gelman, Susan A.; Raman, Lakshmi

2003-01-01

Five studies examined preschoolers' understanding of linguistic form class and pragmatic context in presence of a single exemplar or multiexemplars. Data indicated that by 2 years, children use linguistic form class, and by age 3, use pragmatic context. Young children have begun to understand the distinction between generic and nongeneric noun…

Custer's Last Sitcom: "Decolonized Viewing of the Sitcom's "Indian""

ERIC Educational Resources Information Center

Tahmahkera, Dustin

2008-01-01

Playing Indian is one of the oldest and most pervasive forms of American cultural expression, indeed one of the oldest forms of affinity with American culture at the national level. This form of expression is "central to efforts to imagine and materialize distinctive American identities." Enacting redface has historically aided European Americans…

Brisk deep-tendon reflexes as a distinctive phenotype in an Argentinean spinocerebellar ataxia type 2 pedigree.

PubMed

Rosa, Alberto L; Molina, Irma; Kowaljow, Valeria; Conde, Cecilia B

2006-01-01

Slow saccades, postural/intention tremor, peripheral neuropathy, and decreased deep-tendon reflexes are valuable neurological signs for clinical suspicion of spinocerebellar ataxia type 2 (SCA2). We report the presence of abnormally brisk deep-tendon reflexes in nonsymptomatic carriers and mildly and severely affected subjects of a large Argentinean SCA2 pedigree. The identification of this distinctive SCA2 phenotype in an entire pedigree reinforces the current concept that clinical algorithms are of limited value as indicators for genetic testing in SCA. Combined with published pedigrees of SCA2 manifesting as levodopa-responsive parkinsonism, this finding suggests that modifier genes could influence the clinical phenotype of SCA2. Copyright (c) 2005 Movement Disorder Society.

Clinical Perspective: What Do Addison and Cushing Tell Us About Glucocorticoid Action?

PubMed

Harris, Charles

2015-01-01

This chapter is distinct from the others in its clinical subject matter. I will attempt to outline the major points of interest in glucocorticoids clinically. To aid the illustration in the evaluation of a patient with Cushing disease I have created a case study.

Cross-reactive and pre-existing antibodies to therapeutic antibodies—Effects on treatment and immunogenicity

PubMed Central

van Schie, Karin A; Wolbink, Gerrit-Jan; Rispens, Theo

2015-01-01

The potential for immunogenicity is an ever-present concern during the development of biopharmaceuticals. Therapeutic antibodies occasionally elicit an antibody response in patients, which can result in loss of response or adverse effects. However, antibodies that bind a drug are sometimes found in pre-treatment serum samples, with the amount depending on drug, assay, and patient population. This review summarizes published data on pre-existing antibodies to therapeutic antibodies, including rheumatoid factors, anti-allotype antibodies, anti-hinge antibodies, and anti-glycan antibodies. Unlike anti-idiotype antibodies elicited by the drug, pre-formed antibodies in general appear to have little consequences during treatment. In the few cases where (potential) clinical consequences were encountered, antibodies were characterized and found to bind a distinct, unusual epitope of the therapeutic. Immunogenicity testing strategies should therefore always include a proper level of antibody characterization, especially when pre-formed antibodies are present. This minimizes false-positives, particularly due to rheumatoid factors, and helps to judge the potential threat in case a genuine pre-dose antibody reactivity is identified. PMID:25962087

[Uveitic Secondary Glaucoma].

PubMed

Lommatzsch, Claudia; Heinz, Carsten

2018-05-01

An intraocular pressure increase with development of glaucomatous damage is a common complication of uveitis. The prevalence has a wide range depending on various factors such as the underlying uveitis type and the duration of the disease. Pathogenetically, a distinction must be made between a secondary angle closure component and the more frequently occurring open-angle glaucoma. In diagnostics, in addition to the clinical optic nerve head assessment, perimetry and tonometry, the use of imaging examination equipment, such as OCT and HRT, are recommended. In the context of uveitic glaucoma, it must be considered in the evaluation, because the glaucoma-typical changes are generally less pronounced or can be concealed by retinal swelling in comparison with other forms of glaucoma. Therapeutically, drug therapy in the form of eye drops continues to be a first-line recommendation, with the use of topical carbonic anhydrase inhibitors or beta-blockers primarily preferred, depending on the contraindications. An operative therapy follows after unsuccessful or inadequate conservative therapy: the adequate surgical technique depends on the respective finding and includes actually techniques such as filtering procedures and glaucoma drainage devices. Georg Thieme Verlag KG Stuttgart · New York.

The inclusion of child pornography in the DSM-5 diagnostic criteria for pedophilia: conceptual and practical problems.

PubMed

First, Michael B

2011-01-01

The proposal to add use of child pornography to Criterion B of pedophilia is in direct conflict with the newly proposed distinction between paraphilia and paraphilic disorder, muddying rather than clarifying the diagnostic definition of pedophilia. The proposal to distinguish paraphilic disorder from paraphilia derives from the fact that the diagnostic criteria for the paraphilias have two components: Criterion A, defining the presence of a paraphilic erotic interest, and Criterion B, requiring clinically significant distress, impairment, or acting out the paraphilia with a nonconsenting person. Meeting Criteria A and B is necessary for a diagnosis of paraphilic disorder; meeting only Criterion A indicates a paraphilia. Use of pornography is better placed within Criterion A, perhaps as an example of a behavioral manifestation of pedophilia. If the Sexual and Gender Identity Disorders Work Group's true intent was to add a third prong to Criterion B, then the criterion must be modified to restrict it to the use of illegal forms of pornography (i.e., visual depictions of real children), excluding written or aural forms or virtual images.

Transient regional osteoporosis.

PubMed

Cano-Marquina, Antonio; Tarín, Juan J; García-Pérez, Miguel-Ángel; Cano, Antonio

2014-04-01

Transient regional osteoporosis (TRO) is a disease that predisposes to fragility fracture in weight bearing joints of mid-life women and men. Pregnant women may also suffer the process, usually at the hip. The prevalence of TRO is lower than the systemic form, associated with postmenopause and advanced age, but may be falsely diminished by under-diagnosis. The disease may be uni- or bilateral, and may migrate to distinct joints. One main feature of TRO is spontaneous recovery. Pain and progressive limitation in the functionality of the affected joint(s) are key symptoms. In the case of the form associated with pregnancy, difficulties in diagnosis derive from the relatively young age at presentation and from the clinical overlapping with the frequent aches during gestation. Densitometric osteoporosis in the affected region is not always present, but bone marrow edema, with or without joint effusion, is detected by magnetic resonance. There are not treatment guidelines, but the association of antiresorptives to symptomatic treatment seems to be beneficial. Surgery or other orthopedic interventions can be required for specific indications, like hip fracture, intra-medullary decompression, or other. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Live imaging and genetic analysis of mouse notochord formation reveals regional morphogenetic mechanisms.

PubMed

Yamanaka, Yojiro; Tamplin, Owen J; Beckers, Anja; Gossler, Achim; Rossant, Janet

2007-12-01

The node and notochord have been extensively studied as signaling centers in the vertebrate embryo. The morphogenesis of these tissues, particularly in mouse, is not well understood. Using time-lapse live imaging and cell lineage tracking, we show the notochord has distinct morphogenetic origins along the anterior-posterior axis. The anterior head process notochord arises independently of the node by condensation of dispersed cells. The trunk notochord is derived from the node and forms by convergent extension. The tail notochord forms by node-derived progenitors that actively migrate toward the posterior. We also reveal distinct genetic regulation within these different regions. We show that Foxa2 compensates for and genetically interacts with Noto in the trunk notochord, and that Noto has an evolutionarily conserved role in regulating axial versus paraxial cell fate. Therefore, we propose three distinct regions within the mouse notochord, each with unique morphogenetic origins.

Architecture of the Mammalian Golgi

PubMed Central

Klumperman, Judith

2011-01-01

Since its first visualization in 1898, the Golgi has been a topic of intense morphological research. A typical mammalian Golgi consists of a pile of stapled cisternae, the Golgi stack, which is a key station for modification of newly synthesized proteins and lipids. Distinct stacks are interconnected by tubules to form the Golgi ribbon. At the entrance site of the Golgi, the cis-Golgi, vesicular tubular clusters (VTCs) form the intermediate between the endoplasmic reticulum and the Golgi stack. At the exit site of the Golgi, the trans-Golgi, the trans-Golgi network (TGN) is the major site of sorting proteins to distinct cellular locations. Golgi functioning can only be understood in light of its complex architecture, as was revealed by a range of distinct electron microscopy (EM) approaches. In this article, a general concept of mammalian Golgi architecture, including VTCs and the TGN, is described. PMID:21502307

Direct neural pathways convey distinct visual information to Drosophila mushroom bodies

PubMed Central

Vogt, Katrin; Aso, Yoshinori; Hige, Toshihide; Knapek, Stephan; Ichinose, Toshiharu; Friedrich, Anja B; Turner, Glenn C; Rubin, Gerald M; Tanimoto, Hiromu

2016-01-01

Previously, we demonstrated that visual and olfactory associative memories of Drosophila share mushroom body (MB) circuits (Vogt et al., 2014). Unlike for odor representation, the MB circuit for visual information has not been characterized. Here, we show that a small subset of MB Kenyon cells (KCs) selectively responds to visual but not olfactory stimulation. The dendrites of these atypical KCs form a ventral accessory calyx (vAC), distinct from the main calyx that receives olfactory input. We identified two types of visual projection neurons (VPNs) directly connecting the optic lobes and the vAC. Strikingly, these VPNs are differentially required for visual memories of color and brightness. The segregation of visual and olfactory domains in the MB allows independent processing of distinct sensory memories and may be a conserved form of sensory representations among insects. DOI: http://dx.doi.org/10.7554/eLife.14009.001 PMID:27083044

Tocotrienols: The Emerging Face of Natural Vitamin E

PubMed Central

Sen, Chandan K.; Khanna, Savita; Rink, Cameron; Roy, Sashwati

2012-01-01

Natural vitamin E includes eight chemically distinct molecules: α-, β-, γ- and δ-tocopherol; and α-, β-, γ- and δ-tocotrienol. In the current literature, more than 95% of all studies on vitamin E are directed towards the specific study of α-tocopherol. The other forms of natural vitamin E remain poorly understood. The abundance of α-tocopherol in the human body and the comparable efficiency of all vitamin E molecules as antioxidants, led biologists to neglect the non-tocopherol vitamin E molecules as topics for basic and clinical research. Recent developments warrant a serious reconsideration of this conventional wisdom. The tocotrienol subfamily of natural vitamin E possesses powerful neuroprotective, anti-cancer and cholesterol lowering properties that are often not exhibited by tocopherols. Current developments in vitamin E research clearly indicate that members of the vitamin E family are not redundant with respect to their biological functions. α-Tocotrienol, γ-tocopherol, and δ-tocotrienol have emerged as vitamin E molecules with functions in health and disease that are clearly distinct from that of α-tocopherol. At nanomolar concentration, α-tocotrienol, not α-tocopherol, prevents neurodegeneration. On a concentration basis, this finding represents the most potent of all biological functions exhibited by any natural vitamin E molecule. Recently it has been suggested that the safe dose of various tocotrienols for human consumption is 200-1000 mg/d. A rapidly expanding body of evidence support that members of the vitamin E family are functionally unique. In recognition of this fact, title claims in manuscripts should be limited to the specific form of vitamin E studied. For example, evidence for toxicity of a specific form of tocopherol in excess may not be used to conclude that high-dosage “vitamin E” supplementation may increase all-cause mortality. Such conclusion incorrectly implies that tocotrienols are toxic as well under conditions where tocotrienols were not even considered. The current state of knowledge warrants strategic investment into the lesser known forms of vitamin E. This will enable prudent selection of the appropriate vitamin E molecule for studies addressing a specific health need. PMID:17628176

Holoclone Forming Cells from Pancreatic Cancer Cells Enrich Tumor Initiating Cells and Represent a Novel Model for Study of Cancer Stem Cells

PubMed Central

Tan, Lei; Sui, Xin; Deng, Hongkui; Ding, Mingxiao

2011-01-01

Background Pancreatic cancer is one of the direct causes of cancer-related death. High level of chemoresistance is one of the major obstacles of clinical treatment. In recent years, cancer stem cells have been widely identified and indicated as the origin of chemoresistance in multi-types of solid tumors. Increasing evidences suggest that cancer stem cells reside in the cells capable of forming holoclones continuously. However, in pancreatic cancer, holoclone-forming cells have not been characterized yet. Therefore, the goal of our present study was to indentify the holoclone-forming pancreatic cancer stem cells and develop an in vitro continuous colony formation system, which will greatly facilitate the study of pancreatic cancer stem cells. Methodology/Principal Findings Pancreatic cancer cell line BxPC3 was submitted to monoclonal cultivation to generate colonies. Based on the morphologies, colonies were classified and analyzed for their capacities of secondary colony formation, long-term survival in vitro, tumor formation in vivo, and drug resistance. Flowcytometry and quantitative RT-PCR were performed to detect the expression level of cancer stem cells associated cell surface markers, regulatory genes and microRNAs in distinct types of colonies. Three types of colonies with distinct morphologies were identified and termed as holo-, mero-, and paraclones, in which only holoclones generated descendant colonies of all three types in further passages. Compared to mero- and paraclones, holoclones possessed higher capacities of long-term survival, tumor initiation, and chemoresistance. The preferential expression of cancer stem cells related marker (CXCR4), regulatory genes (BMI1, GLI1, and GLI2) and microRNAs (miR-214, miR-21, miR-221, miR-222 and miR-155) in holoclones were also highlighted. Conclusions/Significance Our results indicate that the pancreatic tumor-initiating cells with high level of chemoresistance were enriched in holoclones derived from BxPC3 cell line. Generation of holoclones can serve as a novel model for studying cancer stem cells, and attribute to developing new anti-cancer drugs. PMID:21826251

HSAN1 mutations in serine palmitoyltransferase reveal a close structure-function-phenotype relationship.

PubMed

Bode, Heiko; Bourquin, Florence; Suriyanarayanan, Saranya; Wei, Yu; Alecu, Irina; Othman, Alaa; Von Eckardstein, Arnold; Hornemann, Thorsten

2016-03-01

Hereditary sensory and autonomic neuropathy type 1 (HSAN1) is a rare autosomal dominant inherited peripheral neuropathy caused by mutations in the SPTLC1 and SPTLC2 subunits of serine palmitoyltransferase (SPT). The mutations induce a permanent shift in the substrate preference from L-serine to L-alanine, which results in the pathological formation of atypical and neurotoxic 1-deoxy-sphingolipids (1-deoxySL). Here we compared the enzymatic properties of 11 SPTLC1 and six SPTLC2 mutants using a uniform isotope labelling approach. In total, eight SPT mutants (STPLC1p.C133W, p.C133Y, p.S331F, p.S331Y and SPTLC2p.A182P, p.G382V, p.S384F, p.I504F) were associated with increased 1-deoxySL synthesis. Despite earlier reports, canonical activity with l-serine was not reduced in any of the investigated SPT mutants. Three variants (SPTLC1p.S331F/Y and SPTLC2p.I505Y) showed an increased canonical activity and increased formation of C20 sphingoid bases. These three mutations are associated with an exceptionally severe HSAN1 phenotype, and increased C20 sphingosine levels were also confirmed in plasma of patients. A principal component analysis of the analysed sphingoid bases clustered the mutations into three separate entities. Each cluster was related to a distinct clinical outcome (no, mild and severe HSAN1 phenotype). A homology model based on the protein structure of the prokaryotic SPT recapitulated the same grouping on a structural level. Mutations associated with the mild form clustered around the active site, whereas mutations associated with the severe form were located on the surface of the protein. In conclusion, we showed that HSAN1 mutations in SPT have distinct biochemical properties, which allowed for the prediction of the clinical symptoms on the basis of the plasma sphingoid base profile. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Assessment of various parameters to improve MALDI-TOF MS reference spectra libraries constructed for the routine identification of filamentous fungi.

PubMed

Normand, Anne-Cécile; Cassagne, Carole; Ranque, Stéphane; L'ollivier, Coralie; Fourquet, Patrick; Roesems, Sam; Hendrickx, Marijke; Piarroux, Renaud

2013-04-08

The poor reproducibility of matrix-assisted desorption/ionization time-of-flight (MALDI-TOF) spectra limits the effectiveness of the MALDI-TOF MS-based identification of filamentous fungi with highly heterogeneous phenotypes in routine clinical laboratories. This study aimed to enhance the MALDI-TOF MS-based identification of filamentous fungi by assessing several architectures of reference spectrum libraries. We established reference spectrum libraries that included 30 filamentous fungus species with various architectures characterized by distinct combinations of the following: i) technical replicates, i.e., the number of analyzed deposits for each culture used to build a reference meta-spectrum (RMS); ii) biological replicates, i.e., the number of RMS derived from the distinct subculture of each strain; and iii) the number of distinct strains of a given species. We then compared the effectiveness of each library in the identification of 200 prospectively collected clinical isolates, including 38 species in 28 genera.Identification effectiveness was improved by increasing the number of both RMS per strain (p<10-4) and strains for a given species (p<10-4) in a multivariate analysis. Addressing the heterogeneity of MALDI-TOF spectra derived from filamentous fungi by increasing the number of RMS obtained from distinct subcultures of strains included in the reference spectra library markedly improved the effectiveness of the MALDI-TOF MS-based identification of clinical filamentous fungi.

Virtual libraries of tetrapyrrole macrocycles. Combinatorics, isomers, product distributions, and data mining.

PubMed

Taniguchi, Masahiko; Du, Hai; Lindsey, Jonathan S

2011-09-26

A software program (PorphyrinViLiGe) has been developed to enumerate the type and relative amounts of substituted tetrapyrrole macrocycles in a virtual library formed by one of four different classes of reactions. The classes include (1) 4-fold reaction of n disubstituted heterocycles (e.g., pyrroles or diiminoisoindolines) to form β-substituted porphyrins, β-substituted tetraazaporphyrins, or α- or β-substituted phthalocyanines; (2) combination of m aminoketones and n diones to form m × n pyrroles, which upon 4-fold reaction give β-substituted porphyrins; (3) derivatization of an 8-point tetrapyrrole scaffold with n reagents, and (4) 4-fold reaction of n aldehydes and pyrrole to form meso-substituted porphyrins. The program accommodates variable ratios of reactants, reversible or irreversible reaction (reaction classes 1 and 2), and degenerate modes of formation. Pólya's theorem (for enumeration of cyclic entities) has also been implemented and provides validation for reaction classes 3 and 4. The output includes the number and identity of distinct reaction-accessible substituent combinations, the number and identity of isomers thereof, and the theoretical mass spectrum. Provisions for data mining enable assessment of the number of products having a chosen pattern of substituents. Examples include derivatization of an octa-substituted phthalocyanine with eight reagents to afford a library of 2,099,728 members (yet only 6435 distinct substituent combinations) and reversible reaction of six distinct disubstituted pyrroles to afford 2649 members (yet only 126 distinct substituent combinations). In general, libraries of substituted tetrapyrrole macrocycles occupy a synthetically accessible region of chemical space that is rich in isomers (>99% or 95% for the two examples, respectively).

Humic Acids as Therapeutic Compounds in Lead Intoxication.

PubMed

Krempaská, Klára; Vaško, Ladislav; Vašková, Janka

2016-01-01

The toxicity of lead and its compounds is well known, causing anemia by inhibiting the synthesis of porphyrins. The neurotoxic effects, particularly in the young, alter the structure of cell membranes and DNA. Chronic exposure to lead has adverse effects on the body by disrupting the mechanisms of energy production and tissue damage, in particular in its links with thiol groups and competition for binding sites with zinc. This review is therefore a description of the mechanism of lead toxicity as well as of possible interventions for the detoxification of the body. Part of the clinical intervention is the provision of chelates that form insoluble complexes with lead and eliminate the load in tissues. Most of these chelating agents have a number of side effects. It is therefore not surprising that active compounds with distinctive antioxidant and chelating properties are being sought after. The possibility of administering lower amounts, and the corresponding decrease in side effects, would be important for clinical practice. Both prospective studies and our initial studies on humic acids have highlighted positive effects based on their antioxidant and chelating properties.

[Sample preparation and bioanalysis in mass spectrometry].

PubMed

Bourgogne, Emmanuel; Wagner, Michel

2015-01-01

The quantitative analysis of compounds of clinical interest of low molecular weight (<1000 Da) in biological fluids is currently in most cases performed by liquid chromatography-mass spectrometry (LC-MS). Analysis of these compounds in biological fluids (plasma, urine, saliva, hair...) is a difficult task requiring a sample preparation. Sample preparation is a crucial part of chemical/biological analysis and in a sense is considered the bottleneck of the whole analytical process. The main objectives of sample preparation are the removal of potential interferences, analyte preconcentration, and converting (if needed) the analyte into a more suitable form for detection or separation. Without chromatographic separation, endogenous compounds, co-eluted products may affect a quantitative method in mass spectrometry performance. This work focuses on three distinct parts. First, quantitative bioanalysis will be defined, different matrices and sample preparation techniques currently used in bioanalysis by mass spectrometry of/for small molecules of clinical interest in biological fluids. In a second step the goals of sample preparation will be described. Finally, in a third step, sample preparation strategies will be made either directly ("dilute and shoot") or after precipitation.

The role of cerebellar circuitry alterations in the pathophysiology of autism spectrum disorders

PubMed Central

Mosconi, Matthew W.; Wang, Zheng; Schmitt, Lauren M.; Tsai, Peter; Sweeney, John A.

2015-01-01

The cerebellum has been repeatedly implicated in gene expression, rodent model and post-mortem studies of autism spectrum disorder (ASD). How cellular and molecular anomalies of the cerebellum relate to clinical manifestations of ASD remains unclear. Separate circuits of the cerebellum control different sensorimotor behaviors, such as maintaining balance, walking, making eye movements, reaching, and grasping. Each of these behaviors has been found to be impaired in ASD, suggesting that multiple distinct circuits of the cerebellum may be involved in the pathogenesis of patients' sensorimotor impairments. We will review evidence that the development of these circuits is disrupted in individuals with ASD and that their study may help elucidate the pathophysiology of sensorimotor deficits and core symptoms of the disorder. Preclinical studies of monogenetic conditions associated with ASD also have identified selective defects of the cerebellum and documented behavioral rescues when the cerebellum is targeted. Based on these findings, we propose that cerebellar circuits may prove to be promising targets for therapeutic development aimed at rescuing sensorimotor and other clinical symptoms of different forms of ASD. PMID:26388713

Clinical nurse specialist practice domains and evidence-based practice competencies: a matrix of influence.

PubMed

Kring, Daria L

2008-01-01

The purpose of this article is to describe master's-level evidence-based practice (EBP) competencies as determined by a national consensus panel and present an EBP matrix that illustrates the influence that the clinical nurse specialist (CNS) practice can have on driving EBP change. Evidence-based practice is a growing and necessary paradigm for nursing care. The ACE Star Model conceptualizes the knowledge transformation that must occur in an EBP environment as 5 distinct points: discovery, summary, translation, integration, and evaluation. Master's-level EBP competencies based on these 5 steps were established by a national consensus panel. The CNS's practice can be organized around 5 domains: expert practitioner, researcher, consultant, educator, and leader. The master's-level EBP competencies can be transposed on a crosswalk of the ACE Star Model and the 5 CNS practice domains to form a matrix representing the influence that CNSs can have over the EBP process. Each competency falls well within the practice domains of the CNS, making the CNS an ideal person to lead the EBP movement forward, providing tangible outcomes to further demonstrate the need for the CNS role.

Unilateral pigmentary retinopathy--a review of literature and case presentation.

PubMed

Stamate, Alina-Cristina; Burcea, Marian; Zemba, Mihail

2016-01-01

To report a rare case of unilateral pigmentary retinopathy and describe the clinical and visual field characteristics of this particular case. We present the case of a 30-year-old male patient with a gradual loss of the visual field on his left eye (LE) for the past 10 years, with further gradual painless loss of his central visual field in the last year, and no similar symptoms in his right eye. His past medical and ocular history were unremarkable. No family history of acquired or inherited diseases was determined. Based on the history, clinical findings, and visual field examination, the diagnosis of unilateral pigmentary retinopathy was established. Visual acuity and visual field in the left eye (LE) were severely affected, while in the right eye (RE), they were completely normal. In this case, distinct features of pigmentary retinopathy were observed only in one eye, with the fellow eye being unaffected. The diagnosis requires a long follow-up period, visual field and electrophysiological testing to rule out a delayed onset of a bilateral form of pigmentary retinopathy.

Modeling Alzheimer’s disease in transgenic rats

PubMed Central

2013-01-01

Alzheimer’s disease (AD) is the most common form of dementia. At the diagnostic stage, the AD brain is characterized by the accumulation of extracellular amyloid plaques, intracellular neurofibrillary tangles and neuronal loss. Despite the large variety of therapeutic approaches, this condition remains incurable, since at the time of clinical diagnosis, the brain has already suffered irreversible and extensive damage. In recent years, it has become evident that AD starts decades prior to its clinical presentation. In this regard, transgenic animal models can shed much light on the mechanisms underlying this “pre-clinical” stage, enabling the identification and validation of new therapeutic targets. This paper summarizes the formidable efforts to create models mimicking the various aspects of AD pathology in the rat. Transgenic rat models offer distinctive advantages over mice. Rats are physiologically, genetically and morphologically closer to humans. More importantly, the rat has a well-characterized, rich behavioral display. Consequently, rat models of AD should allow a more sophisticated and accurate assessment of the impact of pathology and novel therapeutics on cognitive outcomes. PMID:24161192

Chronic pancreatitis in Eastern India: Experience from a tertiary care center.

PubMed

Jha, Ashish Kumar; Goenka, Mahesh Kumar; Goenka, Usha

2017-03-01

There is a wide variation in the clinical presentation of chronic pancreatitis (CP) in the different parts of India. Data regarding the clinical profile of CP from eastern India are scarce. We describe the clinical and demographic profiles of patients with CP in eastern India. Consecutive patients were evaluated for the clinical presentation, etiology and complication of CP. One hundred and thirty-nine patients with CP (mean age 39.57±14.88 years; M/F 3.48:1) were included. Idiopathic CP (50.35%) was the most common etiology followed by alcohol (33.81%); 68.34% had calcific CP and 31.65% had noncalcific CP. The median duration of symptoms was 24 (1-240) months. Pain was the most common symptom, being present in 93.52% of the patients. Diabetes, steatorrhea and pseudocyst were present in 45.32%, 14.38% and 7.19% of the cases, respectively. Moderate to severe anemia was revealed in 16.53% of the patients. Benign biliary stricture was diagnosed in 19.42% of the cases (symptomatic in 6.47%). The common radiological findings were the following: pancreatic calculi (68.34%), dilated pancreatic duct (PD) (58.99%), parenchymal atrophy (25.89%) and PD stricture (23.74%). In our center, idiopathic CP followed by alcoholic CP was the most frequent form of CP. Tropical CP was distinctly uncommon.

Clinically assisted hydration and the Liverpool Care Pathway: Catholic ethics and clinical evidence.

PubMed

Nowarska, Anna

2015-08-01

The Liverpool Care Pathway for the Dying Patient (LCP), a framework introduced for providing comfortable care at the last stage of life, has recently become highly contentious. Among the most serious allegations levelled against it, has been that the LCP may be used as a covert form of euthanasia by withdrawal of clinically assisted hydration (CAH). This concern has been raised, in particular by a number of Catholic medical professionals, who have asserted that the LCP is incompatible with Catholic ethics. This paper examines the key Catholic ethical principles relevant to treatment and care towards the end of life (the sanctity/inviolability of life principle, the distinction between ordinary and extraordinary means). Relevant current clinical evidence regarding CAH in relation to terminal thirst, dehydration, prolongation of life and possible negative impacts on the dying is also scrutinised. It is argued that for some patients at the very end of life it may be permissible and even desirable to withhold or withdraw it. Thus, as administration of CAH may become extraordinary, forgoing it in some situations is fully compatible with Catholic ethics. The article therefore concludes that the stance of the LCP in respect of provision of CAH is fully in alignment with Catholic teaching. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A survey of Australasian obstetric anaesthesia audit.

PubMed

Smith, S J; Cyna, A M; Simmons, S W

1999-08-01

In order to develop a minimal obstetric anaesthesia dataset based on current Australasian clinical audit best practice, we carried out a postal survey of 69 Australasian anaesthetic departments covering an obstetric service. We asked about data being collected, specifically concerning the high risk obstetric patient, epidural analgesia and postoperative anaesthetic review. Examples of any data collection forms were requested. Of the 66 responses, 35 departments (53%) were not collecting any audit data. Twenty-six of the 31 departments (84%) performing obstetric anaesthesia audit responded to our follow-up telephone survey. Eighteen departments believed that there had been an improvement in patient care as a result of their audit and 13 felt that the benefits outweighed the costs involved. However, only six departments (9%) had performed an audit cycle. The importance of feedback to patients or hospital staff and the incidence of post dural puncture headache (PDPH) were cited by some as priorities for obstetric anaesthesia audit. There was however no consistency as to what data should be collected. Many responses suggested a perceived need to collect clinical data without knowing what to do with it. Our survey has highlighted confusion between three distinct objectives; a dataset for obstetric anaesthesia record keeping, data required for continuing patient management in hospital and, a specific minimal dataset for clinical audit purposes. We conclude that current Australasian obstetric anaesthesia audit strategies are inadequate to develop a minimal dataset for cost-effective clinical audit.

Composite Calderas: The Long and Short of it

NASA Astrophysics Data System (ADS)

Gravley, D. M.; Hasegawa, T.; Nakagawa, M.; Wilson, C. J.

2006-12-01

Calderas formed in supereruptions are normally linked to a single magma body. However, caldera formation, regional tectonics, and multiple magma bodies may interact to form composite structures with complex geometries. The term composite caldera is often used without reference as to whether the `composite' is in time or space. Three examples of composite caldera styles from New Zealand and Japan show field, geophysical, geochemical and isotopic evidence to suggest that current models for the size, shape and evolution of calderas may be too simplistic. In our examples, multiple separate magma bodies distributed in either space or time, or both, may play a significant role in composite caldera formation. Multiple, clustered collapse events incremental in time: Akan caldera in Hokkaido appears to be a single, rectangular shaped caldera. However, the identification of 17 eruptive units spanning >1 Myr suggests that the caldera evolved incrementally over time and space. New gravity data shows that the caldera is actually a daisy-chain of 3 distinct collapse structures that can be correlated, using lithic componentry, to 3 major geochemical groups in the eruptive products. Multiple, clustered collapse events in a single eruption sequence: Shikotsu caldera in Hokkaido was originally thought to have formed following the eruption of a single large zoned magma chamber. However, the caldera-related deposits are characterized by several geochemically distinct pumice types that can not have been accommodated in a single magma system. Our studies suggest that the variations in pumice compositions are consistent with multiple distinct magma bodies feeding coeval eruptions from several vent sources within an area that collapsed to form a single caldera. Paired calderas with linking eruption-related regional faulting: Rotorua and Ohakuri calderas in New Zealand are 30 km apart and formed in close succession during a complex but virtually continuous eruption sequence at ca. 240 ka. The distinct calderas are joined in dumb-bell fashion by an intervening zone of eruption-related and immediately post-eruptive faulting and collapse.

Immunotherapy of cancer: from monoclonal to oligoclonal cocktails of anti‐cancer antibodies: IUPHAR Review 18

PubMed Central

Carvalho, Silvia; Levi‐Schaffer, Francesca; Sela, Michael

2016-01-01

Antibody‐based therapy of cancer employs monoclonal antibodies (mAbs) specific to soluble ligands, membrane antigens of T‐lymphocytes or proteins located at the surface of cancer cells. The latter mAbs are often combined with cytotoxic regimens, because they block survival of residual fractions of tumours that evade therapy‐induced cell death. Antibodies, along with kinase inhibitors, have become in the last decade the mainstay of oncological pharmacology. However, partial and transient responses, as well as emergence of tumour resistance, currently limit clinical application of mAbs. To overcome these hurdles, oligoclonal antibody mixtures are being tested in animal models and in clinical trials. The first homo‐combination of two mAbs, each engaging a distinct site of HER2, an oncogenic receptor tyrosine kinase (RTK), has been approved for treatment of breast cancer. Likewise, a hetero‐combination of antibodies to two distinct T‐cell antigens, PD1 and CTLA4, has been approved for treatment of melanoma. In a similar vein, additive or synergistic anti‐tumour effects observed in animal models have prompted clinical testing of hetero‐combinations of antibodies simultaneously engaging distinct RTKs. We discuss the promise of antibody cocktails reminiscent of currently used mixtures of chemotherapeutics and highlight mechanisms potentially underlying their enhanced clinical efficacy. PMID:26833433

Clinical and epidemiological features of leishmaniasis in northwestern-Argentina through a retrospective analysis of recent cases.

PubMed

García Bustos, María F; González-Prieto, Gabriela; Ramos, Federico; Mora, María C; Hashiguchi, Yoshihisa; Parodi, Cecilia; Basombrío, Miguel A; Moreno, Sonia; Monroig, Sibila; Beckar, Josefina; Jaime, Daniela; Sajama, Jesús; Yeo, Matthew; Marco, Jorge D; Locatelli, Fabricio M; Barrio, Alejandra

2016-02-01

Leishmaniasis is a parasitic disease caused by hemoflagellates of the genus Leishmania and is transmitted to humans by the bite of infected phlebotomine sandflies. Depending on the Leishmania species, the disease has different clinical forms including cutaneous, mucocutaneous, and visceral manifestations. Previous studies performed in endemic zones of northwestern-Argentina, during epidemic outbreaks, have been important for detecting patients suffering from the acute phase of the disease, but have not given a complete representation of the clinical and epidemiological features in the region. Furthermore, due to the resurgence of leishmaniasis worldwide and in particular the large increase of international tourism to the region, it seems pertinent to update the current epidemiological and clinical profile of leishmaniasis in northwestern-Argentina. Here we present a retrospective analysis of 95 Leishmania positive cases, presenting between 2000 and 2014. Patients were derived from hospitals and diagnosed in our lab at the University of Salta, located in a non-endemic area in Salta, Argentina. We detected numerous extensive mucocutaneous cases (34/95, 35.8%) distinct from mucosal affected patients, some instances originating in locations with no previously reported human cases. Additionally patients suffering from concomitant diseases, besides leishmaniasis, were assessed. These included Chagas disease, syphilis, deep mycoses, tuberculosis, toxoplasmosis and intestinal parasitosis. This study updates the clinical and epidemiological features of leishmaniasis in northwestern-Argentina, and discusses the implications and management strategy for patients who acquire the disease in this region. Copyright © 2015 Elsevier B.V. All rights reserved.

A typology of longitudinal integrated clerkships.

PubMed

Worley, Paul; Couper, Ian; Strasser, Roger; Graves, Lisa; Cummings, Beth-Ann; Woodman, Richard; Stagg, Pamela; Hirsh, David

2016-09-01

Longitudinal integrated clerkships (LICs) represent a model of the structural redesign of clinical education that is growing in the USA, Canada, Australia and South Africa. By contrast with time-limited traditional block rotations, medical students in LICs provide comprehensive care of patients and populations in continuing learning relationships over time and across disciplines and venues. The evidence base for LICs reveals transformational professional and workforce outcomes derived from a number of small institution-specific studies. This study is the first from an international collaborative formed to study the processes and outcomes of LICs across multiple institutions in different countries. It aims to establish a baseline reference typology to inform further research in this field. Data on all LIC and LIC-like programmes known to the members of the international Consortium of Longitudinal Integrated Clerkships were collected using a survey tool developed through a Delphi process and subsequently analysed. Data were collected from 54 programmes, 44 medical schools, seven countries and over 15 000 student-years of LIC-like curricula. Wide variation in programme length, student numbers, health care settings and principal supervision was found. Three distinct typological programme clusters were identified and named according to programme length and discipline coverage: Comprehensive LICs; Blended LICs, and LIC-like Amalgamative Clerkships. Two major approaches emerged in terms of the sizes of communities and types of clinical supervision. These referred to programmes based in smaller communities with mainly family physicians or general practitioners as clinical supervisors, and those in more urban settings in which subspecialists were more prevalent. Three distinct LIC clusters are classified. These provide a foundational reference point for future studies on the processes and outcomes of LICs. The study also exemplifies a collaborative approach to medical education research that focuses on typology rather than on individual programme or context. © 2016 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin.

PubMed

Bhagwat, Shripad V; Gokhale, Prafulla C; Crew, Andrew P; Cooke, Andy; Yao, Yan; Mantis, Christine; Kahler, Jennifer; Workman, Jennifer; Bittner, Mark; Dudkin, Lorina; Epstein, David M; Gibson, Neil W; Wild, Robert; Arnold, Lee D; Houghton, Peter J; Pachter, Jonathan A

2011-08-01

The phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway is frequently activated in human cancers, and mTOR is a clinically validated target. mTOR forms two distinct multiprotein complexes, mTORC1 and mTORC2, which regulate cell growth, metabolism, proliferation, and survival. Rapamycin and its analogues partially inhibit mTOR through allosteric binding to mTORC1, but not mTORC2, and have shown clinical utility in certain cancers. Here, we report the preclinical characterization of OSI-027, a selective and potent dual inhibitor of mTORC1 and mTORC2 with biochemical IC(50) values of 22 nmol/L and 65 nmol/L, respectively. OSI-027 shows more than 100-fold selectivity for mTOR relative to PI3Kα, PI3Kβ, PI3Kγ, and DNA-PK. OSI-027 inhibits phosphorylation of the mTORC1 substrates 4E-BP1 and S6K1 as well as the mTORC2 substrate AKT in diverse cancer models in vitro and in vivo. OSI-027 and OXA-01 (close analogue of OSI-027) potently inhibit proliferation of several rapamycin-sensitive and -insensitive nonengineered and engineered cancer cell lines and also, induce cell death in tumor cell lines with activated PI3K-AKT signaling. OSI-027 shows concentration-dependent pharmacodynamic effects on phosphorylation of 4E-BP1 and AKT in tumor tissue with resulting tumor growth inhibition. OSI-027 shows robust antitumor activity in several different human xenograft models representing various histologies. Furthermore, in COLO 205 and GEO colon cancer xenograft models, OSI-027 shows superior efficacy compared with rapamycin. Our results further support the important role of mTOR as a driver of tumor growth and establish OSI-027 as a potent anticancer agent. OSI-027 is currently in phase I clinical trials in cancer patients. ©2011 AACR

Switching to aripiprazole for the treatment of residual mutism resulted in distinct clinical courses in two catatonic schizophrenia cases.

PubMed

Muneoka, Katsumasa; Kanahara, Nobuhisa; Kimura, Shou

2017-01-01

The efficacy of a partial agonist for the dopamine D 2 receptor, aripiprazole, for catatonia in schizophrenia has been reported. We report distinct clinical courses in challenging aripiprazole to treat residual mutism after severe catatonic symptoms improved. In the first case, mutism was successfully treated when the patient was switched from olanzapine to aripiprazole. In contract, switching to aripiprazole from risperidone aggravated auditory hallucinations in the second case. We will discuss the benefits and risks of using aripiprazole for the treatment of catatonic schizophrenia and the possibility of dopamine supersensitivity psychosis.

Unraveling the Complexity of Critical Consciousness, Political Efficacy, and Political Action among Marginalized Adolescents

ERIC Educational Resources Information Center

Diemer, Matthew A.; Rapa, Luke J.

2016-01-01

This research examines the complex patterns by which distinct dimensions of critical consciousness may lead marginalized adolescents toward distinct forms of political action. Structural equation modeling was applied to nationally representative data from the Civic Education Study (2,811 ninth graders; M[subscript age] = 14.6), first establishing…

Development of the Distinct Multiple Intelligences in Primary Students through Interest Centers

ERIC Educational Resources Information Center

Dueñas Macías, Fredy Alonso

2013-01-01

This article reports on an action research study that focused on developing the distinct multiple intelligences of an English class of fifth graders through interest centers at a Colombian school. A multiple intelligences questionnaire, an open-ended observation form, and a student mini-report sheet were used to collect data. Findings revealed…

Distress and Empathy: Two Qualitatively Distinct Vicarious Emotions with Different Motivational Consequences.

ERIC Educational Resources Information Center

Batson, C. Daniel; And Others

The construct of empathy may be located conceptually at several different points in a network of social cognition and vicarious emotion. This paper discusses one specific form of emotional empathy, empathy in response to perceiving another person in need. First, evidence is reviewed suggesting that there are at least two distinct types of…

Modality in Amele and Other Papuan Languages.

ERIC Educational Resources Information Center

Roberts, John R.

1990-01-01

Data are presented from Amele and other Papuan languages to show how the medial verb form is marked for a binary distinction of realis versus irrealis modality. It is demonstrated that in these languages realis-irrealis distinction interacts with categories of tense and mood marked on the final verb to divide them into domains of realis and…

Biologically distinct subsets of nevi

PubMed Central

ROGERS, Tova; MARINO, Maria L.; RACITI, Patricia; JAIN, Manu; BUSAM, Klaus J.; MARCHETTI, Michael A.; MARGHOOB, Ashfaq A.

2017-01-01

Melanocytic nevi (MN) encompass a range of benign tumors with varying microscopic and macroscopic features. Their development is a multifactorial process under genetic and environmental influences. The clinical importance of MN lies in distinguishing them from melanoma and in recognizing their associations with melanoma risk and cancer syndromes. Historically, the distinction between the different types of MN, as well as between MN and melanoma, was based on clinical history, gross morphology, and histopathological features. While histopathology with clinical correlation remains the gold standard for differentiating and diagnosing melanocytic lesions, in some cases, this may not be possible. The use of dermoscopy has allowed for the assessment of subsurface skin structures and has contributed to the clinical evaluation and classification of MN. Genetic profiling, while still in its early stages, has the greatest potential to refine the classification of MN by clarifying their developmental processes, biological behaviors, and relationships to melanoma. Here we review the most salient clinical, dermoscopic, histopathological, and genetic features of different MN subgroups. PMID:27119653

Insight in pediatric obsessive-compulsive disorder: associations with clinical presentation.

PubMed

Storch, Eric A; Milsom, Vanessa A; Merlo, Lisa J; Larson, Michael; Geffken, Gary R; Jacob, Marni L; Murphy, Tanya K; Goodman, Wayne K

2008-08-15

Insight has emerged as a significant treatment outcome predictor in adult obsessive-compulsive disorder (OCD), with some suggesting that OCD with poor insight represents a distinct clinical subtype. Despite its clinical relevance, limited data exist on insight in pediatric OCD patients. The present study investigated the relation between poor insight and clinical characteristics among children and adolescents with OCD (N=78, ages 6-20 years). Forty-five percent of the sample (n=35) was considered to have low levels of insight into their symptoms, as determined by clinician rating on item 11 of the Children's Yale-Brown Obsessive-Compulsive Scale. Pearson product-moment correlations showed a significant, inverse relation between insight and OCD severity. Relative to the high insight group, parents of patients with low insight reported higher levels of OCD-related impairment and family accommodation. These findings suggest that OCD with poor insight may represent a distinct clinical feature that may require more intensive and multimodal treatment approaches.

Whole exome sequencing is necessary to clarify ID/DD cases with de novo copy number variants of uncertain significance: Two proof-of-concept examples.

PubMed

Giorgio, Elisa; Ciolfi, Andrea; Biamino, Elisa; Caputo, Viviana; Di Gregorio, Eleonora; Belligni, Elga Fabia; Calcia, Alessandro; Gaidolfi, Elena; Bruselles, Alessandro; Mancini, Cecilia; Cavalieri, Simona; Molinatto, Cristina; Cirillo Silengo, Margherita; Ferrero, Giovanni Battista; Tartaglia, Marco; Brusco, Alfredo

2016-07-01

Whole exome sequencing (WES) is a powerful tool to identify clinically undefined forms of intellectual disability/developmental delay (ID/DD), especially in consanguineous families. Here we report the genetic definition of two sporadic cases, with syndromic ID/DD for whom array-Comparative Genomic Hybridization (aCGH) identified a de novo copy number variant (CNV) of uncertain significance. The phenotypes included microcephaly with brachycephaly and a distinctive facies in one proband, and hypotonia in the legs and mild ataxia in the other. WES allowed identification of a functionally relevant homozygous variant affecting a known disease gene for rare syndromic ID/DD in each proband, that is, c.1423C>T (p.Arg377*) in the Trafficking Protein Particle Complex 9 (TRAPPC9), and c.154T>C (p.Cys52Arg) in the Very Low Density Lipoprotein Receptor (VLDLR). Four mutations affecting TRAPPC9 have been previously reported, and the present finding further depicts this syndromic form of ID, which includes microcephaly with brachycephaly, corpus callosum hypoplasia, facial dysmorphism, and overweight. VLDLR-associated cerebellar hypoplasia (VLDLR-CH) is characterized by non-progressive congenital ataxia and moderate-to-profound intellectual disability. The c.154T>C (p.Cys52Arg) mutation was associated with a very mild form of ataxia, mild intellectual disability, and cerebellar hypoplasia without cortical gyri simplification. In conclusion, we report two novel cases with rare causes of autosomal recessive ID, which document how interpreting de novo array-CGH variants represents a challenge in consanguineous families; as such, clinical WES should be considered in diagnostic testing. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Pock forming ability of fowl pox virus isolated from layer chicken and its adaptation in chicken embryo fibroblast cell culture

PubMed Central

Gilhare, Varsha Rani; Hirpurkar, S. D.; Kumar, Ashish; Naik, Surendra Kumar; Sahu, Tarini

2015-01-01

Aim: The objective of the present study was to examine pock forming ability of field strain and vaccine strain of fowl pox virus (FPV) in chorioallantoic membrane (CAM) of embryonated chicken eggs and its adaptation in chicken embryo fibroblast (CEF) cell culture. Materials and Methods: Dry scabs were collected from 25 affected birds in glycerin-saline and preserved at 4°C until processed. Virus was isolated in 10-day-old embryonated chicken eggs by dropped CAM method. The identity of the virus is confirmed by clinical findings of affected birds, pock morphology and histopathology of infected CAM. In addition one field isolate and vaccine strain of FPV was adapted to CEF cell culture. CEF cell culture was prepared from 9-day-old embryonated chicken eggs. Result: Clinical symptoms observed in affected birds include pox lesion on comb, wattle, eyelids and legs, no internal lesions were observed. All field isolates produced similar findings in CAM. Pocks produced by field isolates ranged from 3 mm to 5 mm at the third passage while initial passages edematous thickening and necrosis of CAM was observed. Pocks formed by lyophilized strain were ranges from 0.5 mm to 2.5 mm in diameter scattered all over the membrane at the first passage. Intra-cytoplasmic inclusion bodies are found on histopathology of CAM. At third passage level, the CEF inoculated with FPV showed characteristic cytopathic effect (CPE) included aggregation of cells, syncytia and plaque formation. Conclusion: FPV field isolates and vaccine strain produced distinct pock lesions on CAMs. Infected CAM showed intracytoplasmic inclusion bodies. The CEF inoculated with FPV field isolate as well as a vaccine strain showed characteristic CPE at third passage level. PMID:27047081

Pock forming ability of fowl pox virus isolated from layer chicken and its adaptation in chicken embryo fibroblast cell culture.

PubMed

Gilhare, Varsha Rani; Hirpurkar, S D; Kumar, Ashish; Naik, Surendra Kumar; Sahu, Tarini

2015-03-01

The objective of the present study was to examine pock forming ability of field strain and vaccine strain of fowl pox virus (FPV) in chorioallantoic membrane (CAM) of embryonated chicken eggs and its adaptation in chicken embryo fibroblast (CEF) cell culture. Dry scabs were collected from 25 affected birds in glycerin-saline and preserved at 4°C until processed. Virus was isolated in 10-day-old embryonated chicken eggs by dropped CAM method. The identity of the virus is confirmed by clinical findings of affected birds, pock morphology and histopathology of infected CAM. In addition one field isolate and vaccine strain of FPV was adapted to CEF cell culture. CEF cell culture was prepared from 9-day-old embryonated chicken eggs. Clinical symptoms observed in affected birds include pox lesion on comb, wattle, eyelids and legs, no internal lesions were observed. All field isolates produced similar findings in CAM. Pocks produced by field isolates ranged from 3 mm to 5 mm at the third passage while initial passages edematous thickening and necrosis of CAM was observed. Pocks formed by lyophilized strain were ranges from 0.5 mm to 2.5 mm in diameter scattered all over the membrane at the first passage. Intra-cytoplasmic inclusion bodies are found on histopathology of CAM. At third passage level, the CEF inoculated with FPV showed characteristic cytopathic effect (CPE) included aggregation of cells, syncytia and plaque formation. FPV field isolates and vaccine strain produced distinct pock lesions on CAMs. Infected CAM showed intracytoplasmic inclusion bodies. The CEF inoculated with FPV field isolate as well as a vaccine strain showed characteristic CPE at third passage level.

Psychopathological profile of patients with different forms of bruxism.

PubMed

Bayar, Gurkan Rasit; Tutuncu, Recep; Acikel, Cengizhan

2012-02-01

The aim of the current study was to evaluate the prevalence of psychopathological symptoms in patients who self-reported different forms of bruxism by means of clinical and anamnestic diagnostic criteria. Eighty-five participants were divided into four groups as sleep bruxers (12), awake bruxers (24), sleep-awake bruxers (33), and non-bruxers (16). A self-report symptom inventory questionnaire (Symptom Checklist-90-Revised (SCL-90-R)) was filled out by all groups to determine their psychopathological symptoms. As regards mean psychopathological scores, patients with sleep-awake bruxism endorsed the highest scores. In addition, patients with awake bruxism showed higher scores than patients with sleep bruxism and non-bruxism in most SCL-90-R subscales. Kruskal-Wallis test revealed significant differences between groups in any of the SCL-90-R subscales, except for the psychoticism subscale. Mann-Whitney test followed by Bonferroni's test correction between non-bruxer and sleep-awake bruxer groups revealed significant differences in depression, anxiety, hostility, phobic anxiety, paranoid ideation, global severity index, positive symptom distress index, and positive symptom total in all SCL-90-R subscales. Statistical analysis of our study showed that differences between groups were significant in all SCL-90-R subscales except for the psychoticism subscale. Better distinction of bruxism forms may help to develop new treatment strategies for bruxism disorder.

Necroptosis in cardiovascular disease - a new therapeutic target.

PubMed

Gupta, Kartik; Phan, Noel; Wang, Qiwei; Liu, Bo

2018-05-01

Contrary to the apoptosis-necrosis binary view of cell death, recent experimental evidence demonstrates that several forms of necrosis, represented by necroptosis, are regulated or programmed in nature. Multiple death stimuli known to be associated with cardiovascular disease are capable of causing either apoptosis or necroptosis. Whether a cell dies from apoptosis or necroptosis has distinct consequences on inflammation. It is known that apoptosis, a non-lytic form of death mediated by the caspase family of proteases, does not generally evoke an immune response. Necroptosis, on the other hand, is a lytic form of cell death. Due to the rapid loss of plasma membrane integrity, cells dying from necroptosis release proinflammatory intracellular contents and subsequently cause inflammation. Our review delineates various genetic and biochemical evidence that demonstrates a compelling role of necroptosis in the pathogenesis and/or progression of cardiovascular disease including myocardial infarction, atherosclerosis, and aortic aneurysm. Through recent studies of necroptosis in cardiovascular diseases, we attempt to discuss the role of necroptosis in vascular inflammation as well as the potential of necroptosis inhibitors in future clinical management of cardiovascular events. Inhibiting necroptosis in the vasculature has an overall protective role and necroptosis may represent a new therapeutic target to prevent the development and progression of cardiovascular diseases. Copyright © 2018 Elsevier Ltd. All rights reserved.

Molecular basis of activation of endopeptidase activity of botulinum neurotoxin type E.

PubMed

Kukreja, Roshan V; Sharma, Shashi K; Singh, Bal Ram

2010-03-23

Botulinum neurotoxins (BoNTs) are a group of large proteins that are responsible for the clinical syndrome of botulism. The seven immunologically distinct serotypes of BoNTs (A-G), each produced by various strains of Clostridium botulinum, act on the neuromuscular junction by blocking the release of the neurotransmitter acetylcholine, thereby resulting in flaccid muscle paralysis. BoNTs are synthesized as single inactive polypeptide chains that are cleaved by endogenous or exogenous proteases to generate the active dichain form of the toxin. Nicking of the single chain BoNT/E to the dichain form is associated with 100-fold increase in toxicity. Here we investigated the activation mechanism of botulinum neurotoxin type E upon nicking and subsequent reduction of disulfide bond. It was observed that nicking of BoNT/E significantly enhances its endopeptidase activity and that at the physiological temperature of 37 degrees C the reduced form of nicked BoNT/E adopts a dynamically flexible conformation resulting from the exposure of hydrophobic segments and facilitating optimal cleavage of its substrate SNAP-25. Such reduction-induced increase in the flexibility of the polypeptide folding provides a rationale for the mechanism of BoNT/E endopeptidase against its intracellular substrate, SNAP-25, and complements current understanding of the mechanistics of interaction between the substrate and BoNT endopeptidase.

Steroid Hormone Vitamin D: Implications for Cardiovascular Disease.

PubMed

Demer, Linda L; Hsu, Jeffrey J; Tintut, Yin

2018-05-25

Understanding of vitamin D physiology is important because about half of the population is being diagnosed with deficiency and treated with supplements. Clinical guidelines were developed based on observational studies showing an association between low serum levels and increased cardiovascular risk. However, new randomized controlled trials have failed to confirm any cardiovascular benefit from supplementation in the general population. A major concern is that excess vitamin D is known to cause calcific vasculopathy and valvulopathy in animal models. For decades, administration of vitamin D has been used in rodents as a reliable experimental model of vascular calcification. Technically, vitamin D is a misnomer. It is not a true vitamin because it can be synthesized endogenously through ultraviolet exposure of the skin. It is a steroid hormone that comes in 3 forms that are sequential metabolites produced by hydroxylases. As a fat-soluble hormone, the vitamin D-hormone metabolites must have special mechanisms for delivery in the aqueous bloodstream. Importantly, endogenously synthesized forms are carried by a binding protein, whereas dietary forms are carried within lipoprotein particles. This may result in distinct biodistributions for sunlight-derived versus supplement-derived vitamin D hormones. Because the cardiovascular effects of vitamin D hormones are not straightforward, both toxic and beneficial effects may result from current recommendations. © 2018 American Heart Association, Inc.

Anti-MDA5 autoantibodies in juvenile dermatomyositis identify a distinct clinical phenotype: a prospective cohort study

PubMed Central

2014-01-01

Introduction The aim of this study was to define the frequency and associated clinical phenotype of anti-MDA5 autoantibodies in a large UK based, predominantly Caucasian, cohort of patients with juvenile dermatomyositis (JDM). Methods Serum samples and clinical data were obtained from 285 patients with JDM recruited to the UK Juvenile Dermatomyositis Cohort and Biomarker Study. The presence of anti-MDA5 antibodies was determined by immunoprecipitation and confirmed by ELISA using recombinant MDA5 protein. Results were compared with matched clinical data, muscle biopsies (scored by an experienced paediatric neuropathologist) and chest imaging (reviewed by an experienced paediatric radiologist). Results Anti-MDA5 antibodies were identified in 7.4% of JDM patients and were associated with a distinct clinical phenotype including skin ulceration (P = 0.03) oral ulceration (P = 0.01), arthritis (P <0.01) and milder muscle disease both clinically (as determined by Childhood Myositis Assessment Score (P = 0.03)) and histologically (as determined by a lower JDM muscle biopsy score (P <0.01)) than patients who did not have anti-MDA5 antibodies. A greater proportion of children with anti-MDA5 autoantibodies achieved disease inactivity at two years post-diagnosis according to PRINTO criteria (P = 0.02). A total of 4 out of 21 children with anti-MDA5 had interstitial lung disease; none had rapidly progressive interstitial lung disease. Conclusions Anti-MDA5 antibodies can be identified in a small but significant proportion of patients with JDM and identify a distinctive clinical sub-group. Screening for anti-MDA5 autoantibodies at diagnosis would be useful to guide further investigation for lung disease, inform on prognosis and potentially confirm the diagnosis, as subtle biopsy changes could otherwise be missed. PMID:24989778

The AQUA-FONTIS study: protocol of a multidisciplinary, cross-sectional and prospective longitudinal study for developing standardized diagnostics and classification of non-thyroidal illness syndrome

PubMed Central

Dietrich, Johannes W; Stachon, Axel; Antic, Biljana; Klein, Harald H; Hering, Steffen

2008-01-01

Background Non-thyroidal illness syndrome (NTIS) is a characteristic functional constellation of thyrotropic feedback control that frequently occurs in critically ill patients. Although this condition is associated with significantly increased morbidity and mortality, there is still controversy on whether NTIS is caused by artefacts, is a form of beneficial adaptation, or is a disorder requiring treatment. Trials investigating substitution therapy of NTIS revealed contradictory results. The comparison of heterogeneous patient cohorts may be the cause for those inconsistencies. Objectives Primary objective of this study is the identification and differentiation of different functional states of thyrotropic feedback control in order to define relevant evaluation criteria for the prognosis of affected patients. Furthermore, we intend to assess the significance of an innovative physiological index approach (SPINA) in differential diagnosis between NTIS and latent (so-called "sub-clinical") thyrotoxicosis. Secondary objective is observation of variables that quantify distinct components of NTIS in the context of independent predictors of evolution, survival or pathophysiological condition and influencing or disturbing factors like medication. Design The approach to a quantitative follow-up of non-thyroidal illness syndrome (AQUA FONTIS study) is designed as both a cross-sectional and prospective longitudinal observation trial in critically ill patients. Patients are observed in at least two evaluation points with consecutive assessments of thyroid status, physiological and clinical data in additional weekly observations up to discharge. A second part of the study investigates the neuropsychological impact of NTIS and medium-term outcomes. The study design incorporates a two-module structure that covers a reduced protocol in form of an observation trial before patients give informed consent. Additional investigations are performed if and after patients agree in participation. Trial Registration ClinicalTrials.gov NCT00591032 PMID:18851740

Development and Retrospective Clinical Assessment of a Patient-Specific Closed-Form Integro-Differential Equation Model of Plasma Dilution.

PubMed

Atlas, Glen; Li, John K-J; Amin, Shawn; Hahn, Robert G

2017-01-01

A closed-form integro-differential equation (IDE) model of plasma dilution (PD) has been derived which represents both the intravenous (IV) infusion of crystalloid and the postinfusion period. Specifically, PD is mathematically represented using a combination of constant ratio, differential, and integral components. Furthermore, this model has successfully been applied to preexisting data, from a prior human study, in which crystalloid was infused for a period of 30 minutes at the beginning of thyroid surgery. Using Euler's formula and a Laplace transform solution to the IDE, patients could be divided into two distinct groups based on their response to PD during the infusion period. Explicitly, Group 1 patients had an infusion-based PD response which was modeled using an exponentially decaying hyperbolic sine function, whereas Group 2 patients had an infusion-based PD response which was modeled using an exponentially decaying trigonometric sine function. Both Group 1 and Group 2 patients had postinfusion PD responses which were modeled using the same combination of hyperbolic sine and hyperbolic cosine functions. Statistically significant differences, between Groups 1 and 2, were noted with respect to the area under their PD curves during both the infusion and postinfusion periods. Specifically, Group 2 patients exhibited a response to PD which was most likely consistent with a preoperative hypovolemia. Overall, this IDE model of PD appears to be highly "adaptable" and successfully fits clinically-obtained human data on a patient-specific basis, during both the infusion and postinfusion periods. In addition, patient-specific IDE modeling of PD may be a useful adjunct in perioperative fluid management and in assessing clinical volume kinetics, of crystalloid solutions, in real time.

Development and Retrospective Clinical Assessment of a Patient-Specific Closed-Form Integro-Differential Equation Model of Plasma Dilution

PubMed Central

Atlas, Glen; Li, John K-J; Amin, Shawn; Hahn, Robert G

2017-01-01

A closed-form integro-differential equation (IDE) model of plasma dilution (PD) has been derived which represents both the intravenous (IV) infusion of crystalloid and the postinfusion period. Specifically, PD is mathematically represented using a combination of constant ratio, differential, and integral components. Furthermore, this model has successfully been applied to preexisting data, from a prior human study, in which crystalloid was infused for a period of 30 minutes at the beginning of thyroid surgery. Using Euler’s formula and a Laplace transform solution to the IDE, patients could be divided into two distinct groups based on their response to PD during the infusion period. Explicitly, Group 1 patients had an infusion-based PD response which was modeled using an exponentially decaying hyperbolic sine function, whereas Group 2 patients had an infusion-based PD response which was modeled using an exponentially decaying trigonometric sine function. Both Group 1 and Group 2 patients had postinfusion PD responses which were modeled using the same combination of hyperbolic sine and hyperbolic cosine functions. Statistically significant differences, between Groups 1 and 2, were noted with respect to the area under their PD curves during both the infusion and postinfusion periods. Specifically, Group 2 patients exhibited a response to PD which was most likely consistent with a preoperative hypovolemia. Overall, this IDE model of PD appears to be highly “adaptable” and successfully fits clinically-obtained human data on a patient-specific basis, during both the infusion and postinfusion periods. In addition, patient-specific IDE modeling of PD may be a useful adjunct in perioperative fluid management and in assessing clinical volume kinetics, of crystalloid solutions, in real time. PMID:29123436

Self creation and the limitless void of dissociation: the 'as if' personality.

PubMed

McFarland Solomon, Hester

2004-11-01

The concept of the 'as if' personality has been used variously in analytic literature without having formed part of a clinically based theoretical development over time. The author discusses the bases of her notion of the 'as if' personality, as observed across a number of patients and supervised patients in intensive, long term analytic treatment. In this composite clinical picture, a grouping of elements that form a particular kind of defence of the self is identified in certain patients with an exceptional capacity for creative engagement in the world, surpassing expectations given their background. The picture includes the presence of physical breakdown and illness, as psychic suffering arising from early narcissistic wounding and from a physical, emotional and/or sexual abusive familial environment, was held for too long in bodily memory but not in mind. A distinction is made between the 'as if' personality, the persona and the false self. The 'as if' personality concerns the action of defensive dissociation deriving from very early experiences of internalizing the presence of an absent object, creating the sense of an internal void at the core of the self. At the same time, the self is capable of acts of self creation through a succession of identifications and internalizations with other sources of environmental nourishment, which substitute for, and are constructed around, the original sense of internal emptiness. Thus are restored, but only up to a point, the resources of the originally diminished self. Until these resources have been used up, the self is often able to excel in activities to an exceptional degree. The countertransference is shown to be the means of both useful but often perilously obtained clinical experience and information, supporting the work along the hazardous analytic journey.

Modern Radiotherapy Concepts and the Impact of Radiation on Immune Activation

PubMed Central

Deloch, Lisa; Derer, Anja; Hartmann, Josefin; Frey, Benjamin; Fietkau, Rainer; Gaipl, Udo S.

2016-01-01

Even though there is extensive research carried out in radiation oncology, most of the clinical studies focus on the effects of radiation on the local tumor tissue and deal with normal tissue side effects. The influence of dose fractionation and timing particularly with regard to immune activation is not satisfactorily investigated so far. This review, therefore, summarizes current knowledge on concepts of modern radiotherapy (RT) and evaluates the potential of RT for immune activation. Focus is set on radiation-induced forms of tumor cell death and consecutively the immunogenicity of the tumor cells. The so-called non-targeted, abscopal effects can contribute to anti-tumor responses in a specific and systemic manner and possess the ability to target relapsing tumor cells as well as metastases. The impact of distinct RT concepts on immune activation is outlined and pre-clinical evidence and clinical observations on RT-induced immunity will be discussed. Knowledge on the radiosensitivity of immune cells as well as clinical evidence for enhanced immunity after RT will be considered. While stereotactic ablative body radiotherapy seem to have a beneficial outcome over classical RT fractionation in pre-clinical animal models, in vitro model systems suggest an advantage for classical fractionated RT for immune activation. Furthermore, the optimal approach may differ based on the tumor site and/or genetic signature. These facts highlight that clinical trials are urgently needed to identify whether high-dose RT is superior to induce anti-tumor immune responses compared to classical fractionated RT and in particular how the outcome is when RT is combined with immunotherapy in selected tumor entities. PMID:27379203

Rapid-Response Impulsivity: Definitions, Measurement Issues, and Clinical Implications

PubMed Central

Hamilton, Kristen R.; Littlefield, Andrew K.; Anastasio, Noelle C.; Cunningham, Kathryn A.; Fink, Latham H.; Wing, Victoria C.; Mathias, Charles W.; Lane, Scott D.; Schutz, Christian; Swann, Alan C.; Lejuez, C.W.; Clark, Luke; Moeller, F. Gerard; Potenza, Marc N.

2015-01-01

Impulsivity is a multi-faceted construct that is a core feature of multiple psychiatric conditions and personality disorders. However, progress in understanding and treating impulsivity in the context of these conditions is limited by a lack of precision and consistency in its definition and assessment. Rapid-response-impulsivity (RRI) represents a tendency toward immediate action that occurs with diminished forethought and is out of context with the present demands of the environment. Experts from the International Society for Research on Impulsivity (InSRI) met to discuss and evaluate RRI-measures in terms of reliability, sensitivity, and validity with the goal of helping researchers and clinicians make informed decisions about the use and interpretation of findings from RRI-measures. Their recommendations are described in this manuscript. Commonly-used clinical and preclinical RRI-tasks are described, and considerations are provided to guide task selection. Tasks measuring two conceptually and neurobiologically distinct types of RRI, “refraining from action initiation” (RAI) and “stopping an ongoing action” (SOA) are described. RAI and SOA-tasks capture distinct aspects of RRI that may relate to distinct clinical outcomes. The InSRI group recommends that: 1) selection of RRI-measures should be informed by careful consideration of the strengths, limitations, and practical considerations of the available measures; 2) researchers use both RAI and SOA tasks in RRI studies to allow for direct comparison of RRI types and examination of their associations with clinically relevant measures; and, 3) similar considerations should be made for human and non-human studies in an effort to harmonize and integrate pre-clinical and clinical research. PMID:25867840

Development and Testing of the Collaboration in the Clinical Learning Environment (CCLE) Tool

ERIC Educational Resources Information Center

Hooven, Katie J.

2016-01-01

The purpose of this study was to develop and psychometrically test the Collaboration in the Clinical Learning Environment (CCLE) Tool. The researcher acknowledged two distinct populations that required input into this particular tool development: staff nurses who work on floors that are considered clinical learning environments for students, and…

General Anesthetics and Molecular Mechanisms of Unconsciousness

PubMed Central

Forman, Stuart A.; Chin, Victor A.

2013-01-01

General anesthetic agents are unique in clinical medicine, because they are the only drugs used to produce unconsciousness as a therapeutic goal. In contrast to older hypotheses that assumed all general anesthetics produce their central nervous system effects through a common mechanism, we outline evidence that general anesthesia represents a number of distinct pharmacological effects that are likely mediated by different neural circuits, and perhaps via different molecular targets. Within the context of this neurobiological framework, we review recent molecular pharmacological and transgenic animal studies. These studies reveal that different groups of general anesthetics, which can be discerned based on their clinical features, produce unconsciousness via distinct molecular targets and therefore via distinct mechanisms. We further postulate that different types of general anesthetics selectively disrupt different critical steps (perhaps in different neuronal circuits) in the processing of sensory information and memory that results in consciousness. PMID:18617817

Cell Cycle Dynamics and Quorum Sensing in Candida albicans Chlamydospores Are Distinct from Budding and Hyphal Growth

PubMed Central

Martin, Stephen W.; Douglas, Lois M.; Konopka, James B.

2005-01-01

The regulation of morphogenesis in the human fungal pathogen Candida albicans is under investigation to better understand how the switch between budding and hyphal growth is linked to virulence. Therefore, in this study we examined the ability of C. albicans to undergo a distinct type of morphogenesis to form large thick-walled chlamydospores whose role in infection is unclear, but they act as a resting form in other species. During chlamydospore morphogenesis, cells switch to filamentous growth and then develop elongated suspensor cells that give rise to chlamydospores. These filamentous cells were distinct from true hyphae in that they were wider and were not inhibited by the quorum-sensing factor farnesol. Instead, farnesol increased chlamydospore production, indicating that quorum sensing can also have a positive role. Nuclear division did not occur across the necks of chlamydospores, as it does in budding. Interestingly, nuclei divided within the suspensor cells, and then one daughter nucleus subsequently migrated into the chlamydospore. Septins were not detected near mitotic nuclei but were localized at chlamydospore necks. At later stages, septins localized throughout the chlamydospore plasma membrane and appeared to form long filamentous structures. Deletion of the CDC10 or CDC11 septins caused greater curvature of cells growing in a filamentous manner and morphological defects in suspensor cells and chlamydospores. These studies identify aspects of chlamydospore morphogenesis that are distinct from bud and hyphal morphogenesis. PMID:16002645

The temporal characteristics of humpback whale songs

NASA Astrophysics Data System (ADS)

Au, Whitlow W. L.; Lammers, Marc O.; Stimpert, Alison; Schotten, Michiel

2005-09-01

Songs sung by male humpback whales consist of distinct, pulsed sounds that are designated as units. Units are produced in some sequence to form a phrase, a repeated set of phrases forms a theme, and repeated themes form a song. A song can last from minutes to hours. The songs of eight humpback whales were recorded with a vertical array of five hydrophones spaced 7 m apart with the array located within 100 m of the whales. At least seven distinct units were identified aurally from this data set obtained during the 2002 winter humpback whale session in Hawaii. Four distinct recurring themes were found in the songs, and for each whale at least two themes were recorded. The average duration of each unit sampled and the silent interval following the unit were determined in order to describe the temporal characteristics of the songs. From the data the temporal consistency and cadence control of unit production by each humpback whale and between whales were determined. Understanding the temporal and spectral characteristics of units within songs and how these units vary between whales could ultimately help in the design of computer algorithms to automatically identify individual whales.

Fabp4-CreER lineage tracing reveals two distinctive coronary vascular populations.

PubMed

He, Lingjuan; Tian, Xueying; Zhang, Hui; Wythe, Joshua D; Zhou, Bin

2014-11-01

Over the last two decades, genetic lineage tracing has allowed for the elucidation of the cellular origins and fates during both embryogenesis and in pathological settings in adults. Recent lineage tracing studies using Apln-CreER tool indicated that a large number of post-natal coronary vessels do not form from pre-existing vessels. Instead, they form de novo after birth, which represents a coronary vascular population (CVP) distinct from the pre-existing one. Herein, we present new coronary vasculature lineage tracing results using a novel tool, Fabp4-CreER. Our results confirm the distinct existence of two unique CVPs. The 1(st) CVP, which is labelled by Fabp4-CreER, arises through angiogenic sprouting of pre-existing vessels established during early embryogenesis. The 2(nd) CVP is not labelled by Fabp4, suggesting that these vessels form de novo, rather than through expansion of the 1(st) CVP. These results support the de novo formation of vessels in the post-natal heart, which has implications for studies in cardiovascular disease and heart regeneration. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Aggregates and Superaggregates of Soot with Four Distinct Fractal Morphologies

NASA Technical Reports Server (NTRS)

Sorensen, C. M.; Kim, W.; Fry, D.; Chakrabarti, A.

2004-01-01

Soot formed in laminar diffusion flames of heavily sooting fuels evolves through four distinct growth stages which give rise to four distinct aggregate fractal morphologies. These results were inferred from large and small angle static light scattering from the flames, microphotography of the flames, and analysis of soot sampled from the flames. The growth stages occur approximately over four successive orders of magnitude in aggregate size. Comparison to computer simulations suggests that these four growth stages involve either diffusion limited cluster aggregation or percolation in either three or two dimensions.

[Improving wound healing after nose surgery by combined administration of xylometazoline and dexpanthenol].

PubMed

Kehrl, W; Sonnemann, U

2000-03-01

The aim of this study was the examination of efficacy and tolerability of an application-form of the new combination of Xylometazoline with Dexpanthenol (Nasic) versus Xylometazoline alone. Randomized verum controlled parallel-group-comparison of two weeks treatment of a nasal-spray. 61 inpatients with the diagnosis Rhinitis following nasal operation were included in this study and 30 patients were treated with verum and placebo each. The assessment of nasal-breathing-resistance according to scores was defined as target-parameter. Confirmatory statistical analysis was carried out according to Wilcoxon-Mann-Whitney-U two-sided at alpha < or = 0.05. The superiority of the combination of Xylometazoline-Dexpanthenol nasal-spray versus Xylometazoline nasal spray could be proven for the target-parameter as clinically relevant and statistically significant. The clinically proven efficacy is emphasized by good tolerability of both treatments. Due to easy handling of the nasal-spray a good compliance was confirmed. Distinct improvement of symptoms in patients following nasal operations underlines the efficacy of both medications. With respect to the tolerability therapy with the combination is more beneficial in comparison to the alternative therapy. The result of this controlled clinical study confirms that the combination Xylometazoline-Dexpanthenol is an enlargement and improvement of effective medicinal treatment of rhinitis following nasal operation in comparison to therapy with Xylometazoline alone.

Knowing and acting in the clinical workplace: trainees' perspectives on modelling and feedback.

PubMed

Stegeman, J H; Schoten, E J; Terpstra, O T

2013-10-01

In this article we discuss clinical workplace learning using a dual approach: a theoretical one and an empirical one. Drawing on the philosophical work of Aristotle, Polanyi and Schön we posit that the 'knowing and acting' underpinning day-to-day medical practice is personal and embraces by nature a tacit dimension. Consequently, imparting and acquiring this knowledge type necessitates personal interaction between trainer and trainee. The tacit dimension particularly influences modelling and feedback. In our empirical exploration we explore these educational routes in two disparate disciplines: surgery and paediatrics. We use a longitudinal design with in-depth interviewing. Our conclusion on modelling is: modelling is a dynamic and fragmented process reflecting discipline bound characteristics and working styles. On feedback it is: 'feedback' serves as vehicle for three distinctive forms of commenting on performance, each holding a specific power of expression for learning. We propose to view clinical workplace learning as: an interactive master-apprenticeship model encompassing modelling and feedback as natural educational routes. We conceptualise modelling and feedback as 'function' of interaction (developing grounded theory). Modelling function and feedback function may serve to study these routes as didactical components of ongoing interaction between trainer and trainee rather than an educator-driven series of unrelated events.

Computerized measurement of facial expression of emotions in schizophrenia.

PubMed

Alvino, Christopher; Kohler, Christian; Barrett, Frederick; Gur, Raquel E; Gur, Ruben C; Verma, Ragini

2007-07-30

Deficits in the ability to express emotions characterize several neuropsychiatric disorders and are a hallmark of schizophrenia, and there is need for a method of quantifying expression, which is currently done by clinical ratings. This paper presents the development and validation of a computational framework for quantifying emotional expression differences between patients with schizophrenia and healthy controls. Each face is modeled as a combination of elastic regions, and expression changes are modeled as a deformation between a neutral face and an expressive face. Functions of these deformations, known as the regional volumetric difference (RVD) functions, form distinctive quantitative profiles of expressions. Employing pattern classification techniques, we have designed expression classifiers for the four universal emotions of happiness, sadness, anger and fear by training on RVD functions of expression changes. The classifiers were cross-validated and then applied to facial expression images of patients with schizophrenia and healthy controls. The classification score for each image reflects the extent to which the expressed emotion matches the intended emotion. Group-wise statistical analysis revealed this score to be significantly different between healthy controls and patients, especially in the case of anger. This score correlated with clinical severity of flat affect. These results encourage the use of such deformation based expression quantification measures for research in clinical applications that require the automated measurement of facial affect.

Improving the clinical correlation of multiple sclerosis black hole volume change by paired-scan analysis.

PubMed

Tam, Roger C; Traboulsee, Anthony; Riddehough, Andrew; Li, David K B

2012-01-01

The change in T 1-hypointense lesion ("black hole") volume is an important marker of pathological progression in multiple sclerosis (MS). Black hole boundaries often have low contrast and are difficult to determine accurately and most (semi-)automated segmentation methods first compute the T 2-hyperintense lesions, which are a superset of the black holes and are typically more distinct, to form a search space for the T 1w lesions. Two main potential sources of measurement noise in longitudinal black hole volume computation are partial volume and variability in the T 2w lesion segmentation. A paired analysis approach is proposed herein that uses registration to equalize partial volume and lesion mask processing to combine T 2w lesion segmentations across time. The scans of 247 MS patients are used to compare a selected black hole computation method with an enhanced version incorporating paired analysis, using rank correlation to a clinical variable (MS functional composite) as the primary outcome measure. The comparison is done at nine different levels of intensity as a previous study suggests that darker black holes may yield stronger correlations. The results demonstrate that paired analysis can strongly improve longitudinal correlation (from -0.148 to -0.303 in this sample) and may produce segmentations that are more sensitive to clinically relevant changes.

Current Advances in Thyroid Cancer Management. Are We Ready for the Epidemic Rise of Diagnoses?

PubMed

Rusinek, Dagmara; Chmielik, Ewa; Krajewska, Jolanta; Jarzab, Michal; Oczko-Wojciechowska, Malgorzata; Czarniecka, Agnieszka; Jarzab, Barbara

2017-08-22

A rising incidence of thyroid cancers (TCs) mainly small tumors, observed during recent years, lead to many controversies regarding treatment strategies. TCs represent a distinct molecular background and clinical outcome. Although in most cases TCs are characterized by a good prognosis, there are some aggressive forms, which do not respond to standard treatment. There are still some questions, which have to be resolved to avoid dangerous simplifications in the clinical management. In this article, we focused on the current advantages in preoperative molecular diagnostic tests and histopathological examination including noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). We discussed the controversies regarding the extent of thyroid surgery and adjuvant radioiodine therapy, as well as new treatment modalities for radioiodine-refractory differentiated thyroid cancer (RR-DTC). Considering medullary thyroid cancer (MTC), we analyzed a clinical management based on histopathology and RET (ret proto-oncogene) mutation genotype, disease follow-up with a special attention to serum calcitonin doubling time as an important prognostic marker, and targeted therapy applied in advanced MTC. In addition, we provided some data regarding anaplastic thyroid cancer (ATC), a highly lethal neoplasm, which lead to death in nearly 100% of patients due to the lack of effective treatment options.

Global absenteeism and presenteeism in mental health patients referred through primary care.

PubMed

Bailey, S Kathleen; Haggarty, John; Kelly, Sara

2015-01-01

Disability from mental health (MH) symptoms impairs workers' functioning. Most of what is known about the MH of workers relates to their experiences after intervention or work absence. To profile the clinical symptoms, self-reported absenteeism and presenteeism and treatment response of workers with MH symptoms at the point of accessing MH care and compare the characteristics of patients referred with or without problems related to work. Analysis of 11 years of patient data collected in a Shared Mental Health Care (SMHC) clinic referred within a primary care setting in Ontario, Canada. Multiple regression with MH disorders was used to predict absenteeism and presenteeism. Absenteeism and presenteeism were assessed using the 12-item self-administered version of the WHO-DAS 2. Symptom profiles were assessed with the Patient Health Questionnaire (PHQ). Some psychiatric disorders (depression, somatization, anxiety) contributed more to predicting absenteeism and presenteeism than others. Patients referred with work-related problems differed from the general SMHC population in terms of sex and type and number of symptoms. Treatment response was good in both groups after a mean of three treatment visits. Patients with work-related mental health complaints formed a distinct clinical group that benefitted equally from the intervention(s) provided by SMHC.

Acute dynamin inhibition dissects synaptic vesicle recycling pathways that drive spontaneous and evoked neurotransmission

PubMed Central

Chung, ChiHye; Barlyko, Barbara; Leitz, Jeremy; Liu, Xinran; Kavalali, Ege T.

2010-01-01

Synapses maintain synchronous, asynchronous and spontaneous forms of neurotransmission that are distinguished by their Ca2+-dependence and time course. Despite recent advances in our understanding of the mechanisms that underlie these three forms of release, it remains unclear whether they originate from the same vesicle population or arise from distinct vesicle pools with diverse propensities for release. Here, we used a reversible inhibitor of dynamin, dynasore, to dissect the vesicle pool dynamics underlying the three forms of neurotransmitter release in hippocampal GABAergic inhibitory synapses. In dynasore, evoked synchronous release and asynchronous neurotransmission detected after activity showed marked and unrecoverable depression within seconds. In contrast, spontaneous release remained intact after intense stimulation in dynasore or during prolonged (~1 hour) application of dynasore at rest, suggesting that separate recycling pathways maintain evoked and spontaneous synaptic vesicle trafficking. In addition, simultaneous imaging of spectrally separable styryl dyes revealed that in a given synapse vesicles that recycle spontaneously and in response to activity do not mix. These findings suggest that evoked synchronous and asynchronous release originate from the same vesicle pool that recycles rapidly in a dynamin-dependent manner, while a distinct vesicle pool sustains spontaneous release independent of dynamin activation. This result lends further support to the notion that synapses harbor distinct vesicle populations with divergent release properties that maintain independent forms of neurotransmission. PMID:20107062

Meteorite Dichotomy Implies that Jupiter Formed Early

NASA Astrophysics Data System (ADS)

Kruijer, T. S.; Burkhardt, C.; Budde, G.; Kleine, T.

2018-05-01

Meteorites derive from two distinct nebular reservoirs that co-existed and remained spatially separated between 1 and 3–4 Ma after CAIs. This can most easily be explained if Jupiter acted as a barrier and formed early, within less than 1 Ma.

Affect is a form of cognition: A neurobiological analysis

PubMed Central

Duncan, Seth; Barrett, Lisa Feldman

2008-01-01

In this paper, we suggest that affect meets the traditional definition of “cognition” such that the affect–cognition distinction is phenomenological, rather than ontological. We review how the affect–cognition distinction is not respected in the human brain, and discuss the neural mechanisms by which affect influences sensory processing. As a result of this sensory modulation, affect performs several basic “cognitive” functions. Affect appears to be necessary for normal conscious experience, language fluency, and memory. Finally, we suggest that understanding the differences between affect and cognition will require systematic study of how the phenomenological distinction characterising the two comes about, and why such a distinction is functional. PMID:18509504

Prevalence and spatial distribution of intraerythrocytic parasite(s) in Puget Sound rockfish (Sebastes emphaeus) from the San Juan Archipelago, Washington (USA)

USGS Publications Warehouse

Van Der Straaten, N.; Jacobson, A.; Halos, D.; Hershberger, P.; Kocan, A.A.; Kocan, R.

2005-01-01

Two morphologically distinct forms of an intraerythrocytic parasite(s) were detected by microscopic observation of Giemsa-stained blood films in 45.7% of 119 rockfish (Sebastes emphaeus) from the San Juan Archipelago (Washington State, U.S.A.). Infection prevalence for both forms was 53% in males, 44% in females, and 33% in fish of undetermined gender. A binucleate "ring-stage" was present at all 4 geographic sites, with a mean prevalence of 45.7%, while mean prevalence of a larger gamont-like form from the same sites was 5.1%. The relationship of the 2 forms to each other could not be determined. Neither schizogony nor binary fission was evident in any of the infected erythrocytes and the parasites contained no obvious pigment. The possibility of the 2 morphologic forms being 2 distinct species is supported by the observation that no difference in parasitemia was seen in the binucleate form among sites (1.6-1.9%), while parasitemia of the gamont-like form varied significantly among sites, ranging from a high of 4% to a low of 0.1%. Taxonomic status of either form could not be determined at this time based on limited existing morphologic data. ?? American Society of Parasitologists 2005.

Online discourse on fibromyalgia: text-mining to identify clinical distinction and patient concerns.

PubMed

Park, Jungsik; Ryu, Young Uk

2014-10-07

The purpose of this study was to evaluate the possibility of using text-mining to identify clinical distinctions and patient concerns in online memoires posted by patients with fibromyalgia (FM). A total of 399 memoirs were collected from an FM group website. The unstructured data of memoirs associated with FM were collected through a crawling process and converted into structured data with a concordance, parts of speech tagging, and word frequency. We also conducted a lexical analysis and phrase pattern identification. After examining the data, a set of FM-related keywords were obtained and phrase net relationships were set through a web-based visualization tool. The clinical distinction of FM was verified. Pain is the biggest issue to the FM patients. The pains were affecting body parts including 'muscles,' 'leg,' 'neck,' 'back,' 'joints,' and 'shoulders' with accompanying symptoms such as 'spasms,' 'stiffness,' and 'aching,' and were described as 'sever,' 'chronic,' and 'constant.' This study also demonstrated that it was possible to understand the interests and concerns of FM patients through text-mining. FM patients wanted to escape from the pain and symptoms, so they were interested in medical treatment and help. Also, they seemed to have interest in their work and occupation, and hope to continue to live life through the relationships with the people around them. This research shows the potential for extracting keywords to confirm the clinical distinction of a certain disease, and text-mining can help objectively understand the concerns of patients by generalizing their large number of subjective illness experiences. However, it is believed that there are limitations to the processes and methods for organizing and classifying large amounts of text, so these limits have to be considered when analyzing the results. The development of research methodology to overcome these limitations is greatly needed.

Complete Occlusion of a Subcutaneous Pyelovesical Bypass Graft (Detour® System) Caused by Uric Acid Stone Formation.

PubMed

Wilhelm, Konrad; Schultze-Seemann, Wolfgang; Miernik, Arkadiusz

2017-01-01

Subcutaneous pyelovesical bypass graft (SPBG) is a urinary diversion treatment option for ureteral obstruction. Initially its use was limited to palliative care patients. However, the indication profile has been extended to selected patients with benign conditions causing ureteral obstruction and hydronephrosis. Occlusion of SPBGs is rarely reported and mostly related to infections. We describe the clinical case of a patient with SPBG after iatrogenic ureteral stricture who was not suitable for other reconstructive treatment forms due to distinct retroperitoneal scarring after multiple previous surgeries. Several months after the SPBG insertion, the patient developed complete occlusion of the system with uric acid stone material. Sufficient endoscopic intervention was not feasible. After forced chemolitholysis, the stone mass could be completely dissolved. Since then the patient has remained symptom-free. © 2014 S. Karger AG, Basel.

[Pharmacogenetics in the treatment of tobacco addiction].

PubMed

Quaak, M; van Schooten, F J; van Schayck, C P

2013-01-01

Smokers vary in their genetic susceptibility to become addicted to smoking and probably also in their reaction to smoking cessation pharmacotherapies. To provide an overview of the developments on the pharmacogenetics of the treatment of tobacco addiction. Review article describing the biological processes associated with tobacco addiction, and the influence of genetic variants on smoking behavior and the efficacy of smoking cessation therapies. Several (combinations of) genetic variants in smoking-related genes influence nicotine dependence. Moreover, several genetic variants in smoking- and treatment-related genes seem to influence the efficacy of smoking cessation therapies which are distinctive for the different forms of pharmacotherapy, especially when they have a different mechanism-of-action. Much progress has been made in unraveling the (pharmaco)genetics of tobacco addiction, but much still remains to be done before genetically tailored smoking cessation therapy can be implemented in clinical practice.

Cutis laxa and fatal pulmonary hypertension: a newly recognized syndrome?

PubMed Central

Brunetti-Pierri, Nicola; Piccolo, Pasquale; Morava, Eva; Wevers, Ron A.; McGuirk, Megan; Johnson, Yvette R.; Urban, Zsolt; Dishop, Megan K.; Potocki, Lorraine

2015-01-01

Cutis laxa is a connective tissue disorder with distinctive lax, redundant, and inelastic skin. It is a genetically heterogenous disorder with autosomal dominant and recessive patterns of inheritance. We report a patient with cutis laxa supported by clinical, microscopic, and ultrastructural findings. Molecular analysis of fibulin-4 and -5, of the α2 subunit of the V-type H+ ATPase, and of the component of the oligomeric Golgi complex 7 (COG7) genes excluded the type I and type II autosomal recessive forms of cutis laxa, and congenital disorders of glycosylation associated with cutis laxa. Remarkably, our patient also presented severe and lethal pulmonary hypertension as a newborn. This case with cutis laxa, severe pulmonary hypertension, and no detectable mutations in fibulin-4 and -5 genes may represent a previously unrecognized syndrome. PMID:21285876

Chicken pox outbreak in the Intensive Care Unit of a tertiary care hospital: Lessons learnt the hard way.

PubMed

Sarit, Sharma; Shruti, Sharma; Deepinder, Chhina; Chhina, R S

2015-12-01

Varicella-zoster virus (VZV) causes 2 clinically and epidemiologically distinct forms of diseases. Chickenpox (varicella) is the disease that results from primary infection with the VZV. Herpes zoster (HZ) results from the reactivation of VZV latently infecting the dorsal root ganglia. We are reporting an outbreak of varicella infection among the health care workers (HCWs) in the Intensive Care Unit (ICU) of a tertiary care hospital. We found transmission of varicella among eight HCWs of pulmonary ICU. They had a history of contact with a patient having HZ infection. Investigation of the outbreak was conducted as per guidelines. Better dissemination of information on disease transmission, isolation of infected patients inside the hospital, and adequate protection (including vaccination) for susceptible employees are important to prevent such outbreaks.

Clinical differentiation of parkinsonian syndromes: prognostic and therapeutic relevance.

PubMed

Christine, Chadwick W; Aminoff, Michael J

2004-09-15

Parkinson disease is the most common cause of parkinsonism, but other causes should always be excluded because they have a different prognosis, respond differently to medical treatment, and should not be managed by surgical means. However, diagnosis, even by experts, is challenging; one autopsy series showed an error rate of 24%. Distinction between various diagnostic possibilities depends on the history and examination findings. The use of certain medications, the rapid rate of disease progression, early onset of falling, the presence of certain dysautonomic symptoms, cognitive or behavioral changes, or a history of poor response to dopaminergic therapy may suggest an atypical form of parkinsonism. Postural hypotension, dementia, supranuclear ophthalmoparesis, or early postural instability should alert the examiner to consider an atypical cause of parkinsonism. Tests of autonomic function and brain imaging are often helpful in distinguishing these diseases. Copyright 2004 Elsevier Inc.

Good intentions and received wisdom are not good enough: the need for controlled trials in public health.

PubMed

Macintyre, Sally

2011-07-01

In the 1970s Archie Cochrane noted that many healthcare procedures and forms of organisation lacked evidence of effectiveness and efficiency, and argued for improved methods of evaluation, moving from clinical opinion and observation to randomised controlled trials (RCTs). His arguments gradually became accepted in medicine, but there has been considerable resistance among policymakers and researchers to their application to social and public health interventions. This essay argues that opposition to RCTs in public health is often based on a false distinction between healthcare and community settings, and sometimes on a misunderstanding of the principles of RCTs in health care. It suggests that just as in medicine, good intentions and received wisdom are not a sufficient basis for making public policy and allocating public funds for social or health improvement.

Achondrogenesis type I. A familial subvariant?

PubMed Central

Lauder, I; Ellis, H A; Ashcroft, T; Burridge, A

1976-01-01

The clinical, pathological, and radiological features of 2 male sibs with a severe and lethal form of micromelic dwarfism are desribed. The family also includes 2 normal sibs. The histological and radiological appearances suggested a diagnosis of achondrogenesis type I, but the markedly deficient ossification of the skull and the presence of intrauterine rib fractures were atypical. These changes have been observed in two other families with 2 or more infants with suspected achondrogenesis, raising the possibility that these familial cases may be a subvariant of achondrogesis or even a distinct disease entity. The disease appears to be inherited as an autosomal recessive and death occurs shortly after birth because of severe pulmonary hypoplasia. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 FIG. 6 FIG. 7 FIG. 8 FIG. 9 FIG. 10 FIG. 11 PMID:962365

Egosyntonic and egodystonic: accounting for continuities and discontinuities between personality traits and personality disorders.

PubMed

Paris, Joel

2015-02-01

Egosyntonic and egodystonic features describe differences between trait-based and state-based mental disorders. Many diagnoses, most particularly personality disorder (PD), show both features. These complex forms of psychopathology are an amalgam of traits and symptoms in which both egosyntonicity and egodystonicity can be present but vary in prominence. This distinction might help resolve the long-standing controversy as to whether PDs are best classified using dimensions or categories. Narrative review. PDs in which egosyntonic features tend to predominate can be understood as amplified trait profiles. PDs associated with highly egodystonic clinical symptoms that more closely resemble major mental disorders may be usefully classified using both categories and dimensions. PDs with stronger egosyntonic features are more suitable for dimensional diagnosis. When egodystonic symptoms are more prominent, categorical diagnoses can be useful.

Mutations of the tyrosinase gene in patients with oculocutaneous albinism from various ethnic groups in Israel

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

Gershoni-Baruch, R.; Rosenmann, A.; Droetto, S.

1994-04-01

The authors have analyzed the tyrosinase (TYR) gene in 38 unrelated patients with oculocutaneous albinism (OCA), derived from several different ethnic groups of the diverse population of Israel. They detected TYR gene mutations in 23 of the 34 patients with apparent type I (i.e., tyrosinase-deficient) OCA and in none of the patients with other clinical forms of albinism. Among Moroccan Jews with type IA (i.e., tyrosinase-negative) OCA, they detected a highly predominant mutant allele containing a missense substitution, Gly47Asp (G47D). This mutation occurs on the same haplotype as in patients from the Canary Islands and Puerto Rico, suggesting that themore » G47D mutation in these ethnically distinct populations may stem from a common origin. 28 refs., 1 fig., 2 tabs.« less

Is the lumbar modifier useful in surgical decision making?: defining two distinct Lenke 1A curve patterns.

PubMed

Miyanji, Firoz; Pawelek, Jeff B; Van Valin, Scott E; Upasani, Vidyadhar V; Newton, Peter O

2008-11-01

Retrospective review of adolescent idiopathic scoliosis (AIS) patients. To investigate the clinical deformity and radiographic features of Lenke 1A and 1B curves to determine if the "A" and "B" lumbar modifiers actually describe 2 distinct curve patterns. The Lenke classification system attempts to address some of the shortcomings of the King-Moe classification system by providing a more comprehensive, reliable, and treatment-based categorization of all AIS deformities. Although this classification is useful in determining which regions of the spine should be fused, it does not necessarily divide AIS curves into distinct patterns. A critical analysis of the clinical deformity, radiographic features, and surgical treatment of AIS patients with Lenke 1A and 1B right thoracic curves was performed. Lenke 1A curves were differentiated according to the L4 coronal plane tilt. Analysis of variance and Pearson chi analysis were used to perform statistical comparisons between the individual curve patterns (P < or = 0.05). Ninety-three patients with preoperative and 2-year postoperative data were included in this analysis (65 Lenke 1A, and 28 Lenke 1B). Thirty-three patients were subdivided as 1A-L (L4 tilted to the left) and 32 patients were subdivided as 1A-R (L4 tilted to the right). The interobserver reliability for determining the direction of L4 tilt was excellent (kappa = 0.94, P < or = 0.001). Patients with 1A-L curves were similar to patients with 1B curves with respect to the L4 tilt and the location of the stable vertebra (most often in the thoracolumbar junction). In contrast, patients with 1A-R curves had a more distal stable vertebra (most often L3 or L4). The surgical treatment also differed between these 2 groups with regards to the lowest instrumented vertebra (LIV). 1A-L and 1B curves were similar with a median LIV of T12, whereas the 1A-R curves had a more distal median LIV of L2 (P = 0.01). Two Lenke 1A curve patterns can be described based on the direction of the L4 tilt. This distinction has ramifications regarding selection of fusion levels and assessing surgical outcomes. The A and B lumbar modifiers do not describe 2 distinct curve types within the Lenke 1 group; however, the tilt direction of L4 does allow subdivision of the Lenke 1A curves into 2 distinguishable patterns (1A-R and 1A-L). The 1A-L curves are similar to 1B curves and different in form and treatment from the 1A-R pattern.

How Do Physicians Become Medical Experts? A Test of Three Competing Theories: Distinct Domains, Independent Influence and Encapsulation Models

ERIC Educational Resources Information Center

Violato, Claudio; Gao, Hong; O'Brien, Mary Claire; Grier, David; Shen, E.

2018-01-01

The distinction between basic sciences and clinical knowledge which has led to a theoretical debate on how medical expertise is developed has implications for medical school and lifelong medical education. This longitudinal, population based observational study was conducted to test the fit of three theories--knowledge encapsulation, independent…

A suite of engineered GFP molecules for oligomeric scaffolding

DOE PAGES

Leibly, David J.; Arbing, Mark A.; Pashkov, Inna; ...

2015-08-13

Applications ranging from synthetic biology to protein crystallization could be advanced by facile systems for connecting multiple proteins together in predefined spatial relationships. One approach to this goal is to engineer many distinct assembly forms of a single carrier protein or scaffold, to which other proteins of interest can then be readily attached. In this work we chose GFP as a scaffold and engineered many alternative oligomeric forms, driven by either specific disulfide bond formation or metal ion addition. We generated a wide range of spatial arrangements of GFP subunits from 11 different oligomeric variants, and determined their X-ray structuresmore » in a total of 33 distinct crystal forms. Furthermore, some of the oligomeric GFP variants show geometric polymorphism depending on conditions, while others show considerable geometric rigidity. Potential future applications of this system are discussed.« less

Spinal muscular atrophy associated with progressive myoclonus epilepsy.

PubMed

Topaloglu, Haluk; Melki, Judith

2016-09-01

A rare syndrome characterized by lower motor neuron disease associated with progressive myoclonic epilepsy, referred to as "spinal muscular atrophy associated with progressive myoclonic epilepsy" (SMA-PME), has been described in childhood and is inherited as an autosomal recessive trait. SMA-PME is caused by mutation in the ASAH1 gene encoding acid ceramidase. Ceramide and the metabolites participate in various cellular events as lipid mediators. The catabolism of ceramide in mammals occurs in lysosomes through the activity of ceramidase. Three different ceramidases (acid, neutral and alkaline) have been identified and appear to play distinct roles in sphingolipid metabolism. The enzymatic activity of acid ceramidase is deficient in two rare inherited disorders; Farber disease and SMA-PME. Farber disease is a very rare and severe autosomal recessive condition with a distinct clinical phenotype. The marked difference in disease manifestations may explain why Farber and SMA-PME diseases were not previously suspected to be allelic conditions. The precise molecular mechanism underlying the phenotypic differences remains to be clarified. Recently, a condition with mutation in CERS1, the gene encoding ceramide synthase 1, has been identified as a novel form of PME. This finding underlies the essential role of enzymes regulating either the synthesis (CERS1) or degradation (ASAH1) of ceramide, and the link between defects in ceramide metabolism and PME.

Selective estrogen receptor modulators and risk for coronary heart disease.

PubMed

Cano, A; Hermenegildo, C; Oviedo, P; Tarín, J J

2007-04-01

Coronary heart disease (CHD) is the leading cause of death in women in most countries. Atherosclerosis is the main biological process determining CHD. Clinical data support the notion that CHD is sensitive to estrogens, but debate exists concerning the effects of the hormone on atherosclerosis and its complications. Selective estrogen receptor modulators (SERMs) are compounds capable of binding the estrogen receptor to induce a functional profile distinct from estrogens. The possibility that SERMs may shift the estrogenic balance on cardiovascular risk towards a more beneficial profile has generated interest in recent years. There is considerable information on the effects of SERMs on distinct areas that are crucial in atherogenesis. The complexity derived from the diversity of variables affecting their mechanism of action plus the differences between compounds make it difficult to delineate one uniform trend for SERMs. The present picture, nonetheless, is one where SERMs seem less powerful than estrogens in atherosclerosis protection, but more gentle with advanced forms of the disease. The recent publication of the Raloxifene Use for The Heart (RUTH) study has confirmed a neutral effect for raloxifene. Prothrombotic states may favor occlusive thrombi at sites occupied by atheromatous plaques. Platelet activation has received attention as an important determinant of arterial thrombogenesis. Although still sparse, available evidence globally suggests neutral or beneficial effects for SERMs.

Bilateral lambdoid and sagittal synostosis (BLSS): a unique craniosynostosis syndrome or predictable craniofacial phenotype?

PubMed

Hing, Anne V; Click, Eleanor S; Holder, Ursula; Seto, Marianne L; Vessey, Kyle; Gruss, Joseph; Hopper, Richard; Cunningham, Michael L

2009-05-01

Multisutural craniosynostosis that includes bilateral lambdoid and sagittal synostosis (BLSS) results in a very characteristic head shape with frontal bossing, turribrachycephaly, biparietal narrowing, occipital concavity, and inferior displacement of the ears. This entity has been reported both in the genetics literature as craniofacial dyssynostosis and in the surgical literature as "Mercedes Benz" syndrome. Craniofacial dyssynostosis was first described in 1976 by Dr. Neuhauser when he presented a series of seven patients with synostosis of the sagittal and lambdoid sutures, short stature, and developmental delay. Over the past 30 years nine additional patients with craniofacial dyssynostosis have been reported in the literature adding to the growing evidence for a distinct craniosynostosis syndrome. The term "Mercedes Benz" syndrome was coined by Moore et al. in 1998 due to the characteristic appearance of the fused sutures on three-dimensional CT imaging. In contrast to the aforementioned reported cases of craniofacial dyssynostosis, all three patients had normal development. Recently, there have been several case reports of patients with BLSS and distinct chromosomal anomalies. These findings suggest that BLSS is a heterogeneous disorder perhaps with syndromic, chromosomal, and isolated forms. In this manuscript we will present the largest series of patients with BLSS and review clinical, CT, and molecular findings.

Dendritic cells in transplantation and immune-based therapies.

PubMed

Young, James W; Merad, Miriam; Hart, Derek N J

2007-01-01

Dendritic cells (DCs) are specialized, bone marrow-derived leukocytes critical to the onset of both innate and adaptive immunity. The divisions of labor among distinct human DC subtypes achieve the most effective balance between steady-state tolerance and the induction of innate and adaptive immunity against pathogens, tumors, and other insults. Maintenance of tolerance in the steady state is an active process involving resting or semimature DCs. Breakdowns in this homeostasis can result in autoimmunity. Perturbation of the steady state should first lead to the onset of innate immunity mediated by rapid responders in the form of plasmacytoid and monocyte-derived DC stimulators and natural killer (NK) and NK T-cell responders. These innate effectors then provide additional inflammatory cytokines, including interferon-gamma, which support the activation and maturation of resident and circulating populations of DCs. These are critical to the onset and expansion of adaptive immunity, including Th1, Th2, and cytotoxic T-lymphocyte responses. Rodent models are now revealing important data about distinct DC precursors, homeostasis of tissue-resident DCs, and DC turnover in response to inflammation and pathological conditions like graft-versus-host disease. The use of defined DC subtypes to stimulate both innate and adaptive immunity, either in combination or in a prime-boost vaccine sequence, may prove most useful clinically by harnessing both effector cell compartments.

The three-year naturalistic course of major depressive disorder, dysthymic disorder and double depression.

PubMed

Rhebergen, Didi; Beekman, Aartjan Tf; Graaf, Ron de; Nolen, Willem A; Spijker, Jan; Hoogendijk, Witte J; Penninx, Brenda Wjh

2009-06-01

Recent studies support a distinction between acute and chronic forms of depression, which contrasts the single-disease hypothesis for depressive disorders. Insight into the (determinants of) the 3-year naturalistic course of major depressive disorder (MDD), dysthymic disorder (Dysth) and double depression (DD) may contribute to this debate. Data were derived from NEMESIS, an epidemiologic survey in the adult population of the Netherlands. 400 Respondents who met the Composite International Diagnostic Interview (CIDI) criteria of MDD and/or Dysth were selected. Cox proportional hazards analyses and Linear Mixed Models were conducted to examine 3-year course trajectories of MDD, Dysth and DD and determinants for course. Adjusted analyses showed similar course trajectories for Dysth and DD, which were significantly worse than the course for MDD. Determinants of unfavorable course were neuroticism and poor functioning. Attrition was higher among persons with Dysth. However, since attrition is generally associated with poorer outcome, this would indicate that differences in course may even have been larger in reality. Dysth and DD involve a similar course which is worse than the course of MDD only. These results do not support a distinction between Dysth and DD. Duration of symptoms and level of functioning may serve as two clinically relevant classifying dimensions within the broad category of depressive disorders.

Dissociable Frontostriatal White Matter Connectivity Underlies Reward and Motor Impulsivity

PubMed Central

Hampton, William H.; Alm, Kylie H.; Venkatraman, Vinod; Nugiel, Tehila; Olson, Ingrid R.

2017-01-01

Dysfunction of cognitive control often leads to impulsive decision-making in clinical and healthy populations. Some research suggests that a generalized cognitive control mechanism underlies the ability to modulate various types of impulsive behavior, while other evidence suggests different forms of impulsivity are dissociable, and rely on distinct neural circuitry. Past research consistently implicates several brain regions, such as the striatum and portions of the prefrontal cortex, in impulsive behavior. However the ventral and dorsal striatum are distinct in regards to function and connectivity. Nascent evidence points to the importance of frontostriatal white matter connectivity in impulsivity, yet it remains unclear whether particular tracts relate to different control behaviors. Here we used probabilistic tractography of diffusion imaging data to relate ventral and dorsal frontostriatal connectivity to reward and motor impulsivity measures. We found a double dissociation such that individual differences in white matter connectivity between the ventral striatum and the ventromedial prefrontal cortex and dorsolateral prefrontal cortex was associated with reward impulsivity, as measured by delay discounting, whereas connectivity between dorsal striatum and supplementary motor area was associated with motor impulsivity, but not vice versa. Our findings suggest that (a) structural connectivity can is associated with a large amount of behavioral variation; (b) different types of impulsivity are driven by dissociable frontostriatal neural circuitry. PMID:28189592

Autoimmune Subepidermal Bullous Diseases of the Skin and Mucosae: Clinical Features, Diagnosis, and Management.

PubMed

Amber, Kyle T; Murrell, Dedee F; Schmidt, Enno; Joly, Pascal; Borradori, Luca

2018-02-01

Autoimmune subepidermal blistering diseases of the skin and mucosae constitute a large group of sometimes devastating diseases, encompassing bullous pemphigoid, gestational pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, and anti-p200 pemphigoid. Their clinical presentation is polymorphic. These autoimmune blistering diseases are associated with autoantibodies that target distinct components of the basement membrane zone of stratified epithelia. These autoantigens represent structural proteins important for maintenance of dermo-epidermal integrity. Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering disease of the skin and mucosae. Although the disease typically presents with a generalized blistering eruption associated with itch, atypical variants with either localized bullous lesions or "non-bullous" presentations are observed in approximately 20% of patients. A peculiar form of BP typically associated with pregnancy is pemphigoid gestationis. In anti-p200 pemphigoid, patients present with tense blisters on erythematosus or normal skin resembling BP, with a predilection for acral surfaces. These patients have antibodies targeting the 200-kDa basement membrane protein. Epidermolysis bullosa is a rare autoimmune blistering disease associated with autoantibodies against type VII collagen that can have several phenotypes including a classical form mimicking dystrophic epidermolysis bullosa, an inflammatory presentation mimicking BP, or mucous membrane pemphigoid-like lesions. Mucous membrane pemphigoid (MMP) is the term agreed upon by international consensus for an autoimmune blistering disorder, which affects one or more mucous membrane and may involve the skin. The condition involves a number of different autoantigens in the basement membrane zone. It may result in severe complications from scarring, such as blindness and strictures. Diagnosis of these diseases relies on direct immunofluorescence microscopy studies and immunoserological assays. Management of affected patients is often challenging. We will here review the clinical and immunopathological features as well as the pathophysiology of this group of organ-specific autoimmune diseases. Finally, we will discuss the diagnostic approach and the principles of management in clinical practice.

Crystalline glucosamine sulfate in the management of knee osteoarthritis: efficacy, safety, and pharmacokinetic properties

PubMed Central

Girolami, Federica; Persiani, Stefano

2012-01-01

Glucosamine is an amino monosaccharide and a natural constituent of glycosaminoglycans in articular cartilage. When administered exogenously, it is used for the treatment of osteoarthritis as a prescription drug or a dietary supplement. The latter use is mainly supported by its perception as a cartilage building block, but it actually exerts specific pharmacologic effects, mainly decreasing interleukin 1-induced gene expression by inhibiting the cytokine intracellular signaling cascade in general and nuclear factor-kappa B (NF-kB) activation in particular. As a whole, the use of glucosamine in the management of osteoarthritis is supported by the clinical trials performed with the original prescription product, that is, crystalline glucosamine sulfate. This is the stabilized form of glucosamine sulfate, while other formulations or different glucosamine salts (e.g. hydrochloride) have never been shown to be effective. In particular, long-term pivotal trials of crystalline glucosamine sulfate 1500 mg once daily have shown significant and clinically relevant improvement of pain and function limitation (symptom-modifying effect) in knee osteoarthritis. Continuous administration for up to 3 years resulted in significant reduction in the progression of joint structure changes compared with placebo as assessed by measuring radiologic joint space narrowing (structure-modifying effect). The two effects combined may suggest a disease-modifying effect that was postulated based on an observed decrease in the risk of undergoing total joint replacement in the follow up of patients receiving the product for at least 12 months in the pivotal trials. The safety of the drug was good in clinical trials and in the postmarketing surveillance. Crystalline glucosamine sulfate 1500 mg once daily is therefore recommended in the majority of clinical practice guidelines and was found to be cost effective in pharmacoeconomic analyses. Compared with other glucosamine formulations, salts, or dosage forms, the prescription product achieves higher plasma and synovial fluid concentrations that are above the threshold for a pharmacologically relevant effect, and may therefore justify its distinct therapeutic characteristics. PMID:22850875

The lid wiper and muco-cutaneous junction anatomy of the human eyelid margins: an in vivo confocal and histological study

PubMed Central

Knop, Erich; Knop, Nadja; Zhivov, Andrey; Kraak, Robert; Korb, Donald R; Blackie, Caroline; Greiner, Jack V; Guthoff, Rudolf

2011-01-01

The inner border of the eyelid margin is critically important for ocular surface integrity because it guarantees the thin spread of the tear film. Its exact morphology in the human is still insufficiently known. The histology in serial sections of upper and lower lid margins in whole-mount specimens from 10 human body donors was compared to in vivo confocal microscopy of eight eyes with a Heidelberg retina-tomograph (HRT II) and attached Rostock cornea module. Behind the posterior margin of the Meibomian orifices, the cornified epidermis stopped abruptly and was replaced by a continuous layer of para-keratinized (pk) cells followed by discontinuous pk cells. The pk cells covered the muco-cutaneous junction (MCJ), the surface of which corresponded to the line of Marx (0.2–0.3 mm wide). Then a stratified epithelium with a conjunctival structure of cuboidal cells, some pk cells, and goblet cells formed an epithelial elevation of typically about 100 μm initial thickness (lid wiper). This continued for 0.3–1.5 mm and formed a slope. The MCJ and lid wiper extended all along the lid margin from nasal to temporal positions in the upper and lower lids. Details of the epithelium and connective tissue were also detectable using the Rostock cornea module. The human inner lid border has distinct zones. Due to its location and morphology, the epithelial lip of the lid wiper appears a suitable structure to spread the tear film and is distinct from the MCJ/line of Marx. Better knowledge of the lid margin appears important for understanding dry eye disease and its morphology can be analysed clinically by in vivo confocal microscopy. PMID:21413985

[North African and Southeast Asian nasopharyngeal carcinomas: between the resemblance and the dissemblance].

PubMed

Ayadi, W; Khabir, A; Hadhri-Guiga, B; Fki, L; Toumi, N; Siala, W; Charfi, S; Fendri, A; Makni, H; Boudawara, T; Ghorbel, A; Gargouri, A; Jlidi, R; Gargouri, R; Busson, P; Drira, M; Daoud, J; Frikha, M; Hammami, A; Karray-Hakim, H

2010-04-01

Nasopharyngeal carcinoma (NPC) is an unusual head and neck cancer because of its unequal geographical distribution and its consistent association with the Epstein-Barr virus (EBV). This malignant tumor poses a serious public health problem in many countries, especially in Southeast Asia and North Africa where the recorded incidence are highest. During the past decade, a growing number of studies were undertaken to define the molecular basis of NPC. However, the analysis of several clinical and biological parameters of North African and Southeast Asian NPCs has shown notable differences, suggesting that they could result from a distinct combination of etiological factors. One intriguing characteristic of North African NPC, concerns its bimodal age distribution with a secondary peak of incidence in the range of 15-25 years, not observed in Asian NPC. In this juvenile form of NPC, immuno-histochemistry assay has shown that the two key proteins controlling the apoptotic-survival balance p53 and Bcl-2 are less frequently expressed whereas the transmembrane tyrosine-kinase receptor c-kit and the main EBV oncoprotein LMP1 were more abundant. In addition, the EBV serological alterations are less informative for the diagnosis of the juvenile compared to the adult form. In addition, most North African NPCs contain EBV strains with genetic polymorphisms distinct from those described in the Southeast Asia series (predominance of F, D, H1-H2, XhoI+ and f, C, H, XhoI- respectively). In contrast, studies relating on tumor chromosomal alterations or aberrant promoter methylation result in data very similar to those obtained from the Southeast Asia series, supporting the concept of a common molecular basis for all NPC regardless of patient geographic origin.

Carbonyl Stress in Aging Process: Role of Vitamins and Phytochemicals as Redox Regulators

PubMed Central

Ergin, Volkan; Hariry, Reza Ebrahimi; Karasu, Çimen

2013-01-01

There is a growing scientific agreement that the cellular redox regulators such as antioxidants, particularly the natural polyphenolic forms, may help lower the incidence of some pathologies, including metabolic diseases like diabetes and diabesity, cardiovascular and neurodegenerative abnormalities, and certain cancers or even have anti-aging properties. The recent researches indicate that the degree of metabolic modulation and adaptation response of cells to reductants as well as oxidants establish their survival and homeostasis, which is linked with very critical balance in imbalances in cellular redox capacity and signaling, and that might be an answer the questions why some antioxidants or phytochemicals potentially could do more harm than good, or why some proteins lose their function by increase interactions with glyco- and lipo-oxidation mediates in the cells (carbonyl stress). Nonetheless, pursue of healthy aging has led the use of antioxidants as a means to disrupt age-associated physiological dysfunctions, dysregulated metabolic processes or prevention of many age-related diseases. Although it is still early to define their exact clinical benefits for treating age-related disease, a diet rich in polyphenolic or other forms of antioxidants does seem to offer hope in delaying the onset of age-related disorders. It is now clear that any deficiency in antioxidant vitamins, inadequate enzymatic antioxidant defenses can distinctive for many age-related disease, and protein carbonylation can used as an indicator of oxidative stress associated diseases and aging status. This review examines antioxidant compounds and plant polyphenols as redox regulators in health, disease and aging processes with hope that a better understanding of the many mechanisms involved with these distinct compounds, which may lead to better health and novel treatment approaches for age-related diseases. PMID:24124633

Attachment area of fibres from the horns of lateral meniscus: anatomic study with special reference to the positional relationship of anterior cruciate ligament.

PubMed

Fujishiro, Hitomi; Tsukada, Sachiyuki; Nakamura, Tomomasa; Nimura, Akimoto; Mochizuki, Tomoyuki; Akita, Keiichi

2017-02-01

Although studies support the clinical importance of the fibres from the horns of lateral meniscus (LM), few studies have investigated the detailed anatomy. This anatomic study was conducted to analyse the structural details of LM with special reference to (1) the attachment area of the fibres from the anterior and posterior horns and (2) the positional relationship between these fibres and the anterior cruciate ligament (ACL). A total of 24 cadaveric knees were used in the macroscopic investigation, and six knees were used in the histological investigation. Micro-computed tomography analysis was also performed to assess the anatomy of the posteriormost fibre from the posterior horn of LM. Based on the macroscopic investigations, the outer fibres from the anterior horn of LM extended to ACL and seemed to intermingle with ACL fibres. However, the histological investigations showed a distinct border between the fibres and ACL. The inner fibres from the anterior horn of LM attached to the lateral intercondylar tubercle serving as a lateral margin of ACL attachment. Fibres from the posterior horn of LM were separated into anterolateral and posteromedial crura which attached to the posterior aspect of the lateral and medial intercondylar tubercles, respectively. These two crura formed the posterior margin of the ACL attachment, except for the central part of ACL. The outer fibres from the anterior horn of LM adjoined ACL. The inner fibres from the anterior horn of LM and two crura from the posterior horn of LM formed the border of the attachment area of ACL. The distinctive fibre anatomy from LM could provide a surgical landmark during arthroscopic surgery.

Carbonyl stress in aging process: role of vitamins and phytochemicals as redox regulators.

PubMed

Ergin, Volkan; Hariry, Reza Ebrahimi; Karasu, Cimen

2013-10-01

There is a growing scientific agreement that the cellular redox regulators such as antioxidants, particularly the natural polyphenolic forms, may help lower the incidence of some pathologies, including metabolic diseases like diabetes and diabesity, cardiovascular and neurodegenerative abnormalities, and certain cancers or even have anti-aging properties. The recent researches indicate that the degree of metabolic modulation and adaptation response of cells to reductants as well as oxidants establish their survival and homeostasis, which is linked with very critical balance in imbalances in cellular redox capacity and signaling, and that might be an answer the questions why some antioxidants or phytochemicals potentially could do more harm than good, or why some proteins lose their function by increase interactions with glyco- and lipo-oxidation mediates in the cells (carbonyl stress). Nonetheless, pursue of healthy aging has led the use of antioxidants as a means to disrupt age-associated physiological dysfunctions, dysregulated metabolic processes or prevention of many age-related diseases. Although it is still early to define their exact clinical benefits for treating age-related disease, a diet rich in polyphenolic or other forms of antioxidants does seem to offer hope in delaying the onset of age-related disorders. It is now clear that any deficiency in antioxidant vitamins, inadequate enzymatic antioxidant defenses can distinctive for many age-related disease, and protein carbonylation can used as an indicator of oxidative stress associated diseases and aging status. This review examines antioxidant compounds and plant polyphenols as redox regulators in health, disease and aging processes with hope that a better understanding of the many mechanisms involved with these distinct compounds, which may lead to better health and novel treatment approaches for age-related diseases.

Creative Exercises in General Chemistry: A Student-Centered Assessment

ERIC Educational Resources Information Center

Lewis, Scott E.; Shaw, Janet L.; Freeman, Kathryn A.

2010-01-01

Creative exercises (CEs) are a form of assessment in which students are given a prompt and asked to write down as many distinct, correct, and relevant facts about the prompt as they can. Students receive credit for each fact that they include that is related to the prompt and distinct from the other facts they list. With CEs, students have an…

Neuronal migration disorders in microcephalic osteodysplastic primordial dwarfism type I/III

PubMed Central

Juric-Sekhar, Gordana; Kapur, Raj P.; Glass, Ian A.; Murray, Mitzi L.; Parnell, Shawn E.

2011-01-01

Microcephalic osteodysplastic primordial dwarfism (MOPD) is a rare microlissencephaly syndrome, with at least two distinct phenotypic and genetic types. MOPD type II is caused by pericentrin mutations, while types I and III appear to represent a distinct entity (MOPD I/III) with variably penetrant phenotypes and unknown genetic basis. The neuropathology of MOPD I/III is little understood, especially in comparison to other forms of lissencephaly. Here, we report postmortem brain findings in an 11-month-old female infant with MOPD I/III. The cerebral cortex was diffusely pachygyric, with a right parietal porencephalic lesion. Histologically, the cortex was abnormally thick and disorganized. Distinct malformations were observed in different cerebral lobes, as characterized using layer-specific neuronal markers. Frontal cortex was severely disorganized and coated with extensive leptomeningeal glioneuronal heterotopia. Temporal cortex had a relatively normal 6-layered pattern, despite cortical thickening. Occipital cortex was variably affected. The corpus callosum was extremely hypoplastic. Brainstem and cerebellar malformations were also present, as well as old necrotic foci. Findings in this case suggest that the cortical malformation in MOPD I/III is distinct from other forms of pachygyria–lissencephaly. PMID:20857301

Independent but Coordinated Trials: Insights from the Practice Based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group

PubMed Central

Yeh, Hsin-Chieh; Clark, Jeanne M.; Emmons, Karen M.; Moore, Renee H.; Bennett, Gary G; Warner, Erica T.; Sarwer, Davis B.; Jerome, Gerald J; Miller, Edgar R; Volger, Sheri; Louis, Thomas A.; Wells, Barbara; Wadden, Thomas A.; Colditz, Graham A.; Appel, Lawrence J.

2011-01-01

Background The National Heart, Lung, and Blood Institute (NHLBI) funded three institutions to conduct effectiveness trials of weight loss interventions in primary care settings. Unlike traditional multi-center clinical trials, each study was established as an independent trial with a distinct protocol. Still, efforts were made to coordinate and standardize several aspects of the trials. The three trials formed a collaborative group, the “Practice Based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group.” Purpose We describe the common and distinct features of the three trials, the key characteristics of the collaborative group, and the lessons learned from this novel organizational approach. Methods The Collaborative Research Group consists of three individual studies: “Be Fit, Be Well“(Washington University in St. Louis/Harvard University), “POWER Hopkins” (Johns Hopkins), and “POWER-UP” (University of Pennsylvania). There are a total of 15 participating clinics with ~1,100 participants. The common primary outcome is change in weight at 24 months of follow-up, but each protocol has trial-specific elements including different interventions and different secondary outcomes. A Resource Coordinating Unit at Johns Hopkins provides administrative support. Results The Collaborative Research Group established common components to facilitate potential cross-site comparisons. The main advantage of this approach is to develop and evaluate several interventions, when there is insufficient evidence to test one or two approaches, as would be done in a traditional multi-center trial. Limitations The challenges of the organizational design include the complex decision making process, the extent of potential data pooling, time intensive efforts to standardize reports, and the additional responsibilities of the DSMB to monitor three distinct protocols. Conclusions The POWER Trials Collaborative Research Group is a case study of an alternative organizational model to conduct independent, yet coordinated trials. Such a model is increasingly being used in NHLBI supported trials , especially given the interest in comparative effectiveness research. Nevertheless, the ultimate utility of this model will not be fully understood until the trials are completed. PMID:20573639

Online Soil Science Lesson 3: Soil Forming Factors

USDA-ARS?s Scientific Manuscript database

This lesson explores the five major factors of soil formation, namely: 1) climate; 2) organisms; 3) time; 4) topography; and 5) parent material and their influence in forming soil. The distinction between active and passive factors, moisture and temperature regimes, organism and topographic influen...

Two Forms of Spoken Repetition in a Girl with Autism

ERIC Educational Resources Information Center

Stribling, Penny; Rae, John; Dickerson, Paul

2007-01-01

Background: The talk of persons with autistic spectrum disorders (ASD) often features distinctive forms of repetition (echophenomena). Although often characterized as meaningless or inappropriate, there is evidence that such practices can sometimes have communicative functions. Aims: To investigate the interactional organization of repetition…

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

PubMed Central

Friedrich, O.; Reid, M. B.; Van den Berghe, G.; Vanhorebeek, I.; Hermans, G.; Rich, M. M.; Larsson, L.

2015-01-01

Critical illness polyneuropathies (CIP) and myopathies (CIM) are common complications of critical illness. Several weakness syndromes are summarized under the term intensive care unit-acquired weakness (ICUAW). We propose a classification of different ICUAW forms (CIM, CIP, sepsis-induced, steroid-denervation myopathy) and pathophysiological mechanisms from clinical and animal model data. Triggers include sepsis, mechanical ventilation, muscle unloading, steroid treatment, or denervation. Some ICUAW forms require stringent diagnostic features; CIM is marked by membrane hypoexcitability, severe atrophy, preferential myosin loss, ultrastructural alterations, and inadequate autophagy activation while myopathies in pure sepsis do not reproduce marked myosin loss. Reduced membrane excitability results from depolarization and ion channel dysfunction. Mitochondrial dysfunction contributes to energy-dependent processes. Ubiquitin proteasome and calpain activation trigger muscle proteolysis and atrophy while protein synthesis is impaired. Myosin loss is more pronounced than actin loss in CIM. Protein quality control is altered by inadequate autophagy. Ca2+ dysregulation is present through altered Ca2+ homeostasis. We highlight clinical hallmarks, trigger factors, and potential mechanisms from human studies and animal models that allow separation of risk factors that may trigger distinct mechanisms contributing to weakness. During critical illness, altered inflammatory (cytokines) and metabolic pathways deteriorate muscle function. ICUAW prevention/treatment is limited, e.g., tight glycemic control, delaying nutrition, and early mobilization. Future challenges include identification of primary/secondary events during the time course of critical illness, the interplay between membrane excitability, bioenergetic failure and differential proteolysis, and finding new therapeutic targets by help of tailored animal models. PMID:26133937

Trial Watch

PubMed Central

Vacchelli, Erika; Eggermont, Alexander; Fridman, Wolf Hervé; Galon, Jérôme; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2013-01-01

Adoptive cell transfer (ACT) represents a prominent form of immunotherapy against malignant diseases. ACT is conceptually distinct from dendritic cell-based approaches (which de facto constitute cellular vaccines) and allogeneic transplantation (which can be employed for the therapy of hematopoietic tumors) as it involves the isolation of autologous lymphocytes exhibiting antitumor activity, their expansion/activation ex vivo and their reintroduction into the patient. Re-infusion is most often performed in the context of lymphodepleting regimens (to minimize immunosuppression by host cells) and combined with immunostimulatory interventions, such as the administration of Toll-like receptor agonists. Autologous cells that are suitable for ACT protocols can be isolated from tumor-infiltrating lymphocytes or generated by engineering their circulating counterparts for the expression of transgenic tumor-specific T-cell receptors. Importantly, lymphocytes can be genetically modified prior to re-infusion for increasing their persistence in vivo, boosting antitumor responses and minimizing side effects. Moreover, recent data indicate that exhausted antitumor T lymphocytes may be rejuvenated in vitro by exposing them to specific cytokine cocktails, a strategy that might considerably improve the clinical success of ACT. Following up the Trial Watch that we published on this topic in the third issue of OncoImmunology (May 2012), here we summarize the latest developments in ACT-related research, covering both high-impact studies that have been published during the last 13 months and clinical trials that have been initiated in the same period to assess the antineoplastic profile of this form of cellular immunotherapy. PMID:23762803

Controlling new knowledge: Genomic science, governance and the politics of bioinformatics.

PubMed

Salter, Brian; Salter, Charlotte

2017-04-01

The rise of bioinformatics is a direct response to the political difficulties faced by genomics in its quest to be a new biomedical innovation, and the value of bioinformatics lies in its role as the bridge between the promise of genomics and its realization in the form of health benefits. Western scientific elites are able to use their close relationship with the state to control and facilitate the emergence of new domains compatible with the existing distribution of epistemic power - all within the embrace of public trust. The incorporation of bioinformatics as the saviour of genomics had to be integrated with the operation of two key aspects of governance in this field: the definition and ownership of the new knowledge. This was achieved mainly by the development of common standards and by the promotion of the values of communality, open access and the public ownership of data to legitimize and maintain the governance power of publicly funded genomic science. Opposition from industry advocating the private ownership of knowledge has been largely neutered through the institutions supporting the science-state concordat. However, in order for translation into health benefits to occur and public trust to be assured, genomic and clinical data have to be integrated and knowledge ownership agreed upon across the separate and distinct governance territories of scientist, clinical medicine and society. Tensions abound as science seeks ways of maintaining its control of knowledge production through the negotiation of new forms of governance with the institutions and values of clinicians and patients.

Congenital Shunts of the Portal Venous System: Case-series of Uncommon Shunts.

PubMed

Santos, Liliana; Nobre, Susana; Laezza, Nadia; Cunha, Catarina; Gonçalves, Isabel; Lopes, Maria F

Congenital shunts of the portal venous system are rare entities that can present in children with clinical heterogeneity. To evaluate the clinical course of children with uncommon shunts presenting to our institution and examine the available literature on this topic. Medical records of children with rare forms of congenital shunts were retrospectively reviewed for demographics, symptoms, management, and outcome between 2003 and 2016. Three female patients with congenital shunts, including a congenital mesenterico-portal Rex shunt (n = 1) and congenital portosystemic shunts (CPSS) (n = 2), were referred for surgical evaluation between ages 4 and 9. Median follow-up was 8 years (range, 6-13 years). One asymptomatic patient did not require treatment and remained disease-free during long-term follow-up. The other 2 patients with CPSS and unusual symptoms, including liver focal nodular hyperplasia (FNH) in infancy (n = 1) and bleeding from esophageal varices (n = 1), showed subsequent progression to liver nodules that were managed by endovascular shunt occlusion. One patient showed symptom resolution and the other showed stable lesions at last follow-up. Literature yielded descriptions of two cases of congenital mesenterico-portal Rex shunt, one case of coincident CPSS and FNH in infancy, but zero reports of bleeding from esophageal varices. This case series examines each distinct patient's presentation, discusses the diagnosis, management and outcome and compares findings while discussing literature on this topic. A high index of suspicion and familiarity with unusual forms and treatment options is required to allow timely diagnosis and appropriate treatment.

Polymorphisms in Fibronectin Binding Protein A of Staphylococcus Aureus are Associated with Infection of Cardiovascular Devices

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

Lower, Steven; Lamlertthon, Supaporn; Casillas-Ituarte, Nadia

Medical implants, like cardiovascular devices, improve the quality of life for countless individuals but may become infected with bacteria like Staphylococcus aureus. Such infections take the form of a bio-film, a structured community of bacterial cells adherent to the surface of a solid substrate. Every bio-film begins with an attractive force or bond between bacterium and substratum. We used atomic force microscopy to probe experimentally forces between a fibronectin-coated surface (i.e., proxy for an implanted cardiac device) and fibronectin-binding receptors on the surface of individual living bacteria from each of 80 clinical isolates of S. aureus. These isolates originated frommore » humans with infected cardiac devices (CDI; n = 26), uninfected cardiac devices (n = 20), and the anterior nares of asymptomatic subjects (n = 34). CDI isolates exhibited a distinct bindingforce signature and had speci!c single amino acid polymorphisms in fibronectin-binding protein A corresponding to E652D, H782Q, and K786N. In silico molecular dynamics simulations demonstrate that residues D652, Q782, and N786 in fibronectin-binding protein A form extra hydrogen bonds with fibronectin, complementing the higher binding force and energy measured by atomic force microscopy for the CDI isolates. This study is significant, because it links pathogenic bacteria biofilms from the length scale of bonds acting across a nanometer-scale space to the clinical presentation of disease at the human dimension.« less

Influence of Genetic Ancestry on INDEL Markers of NFKβ1, CASP8, PAR1, IL4 and CYP19A1 Genes in Leprosy Patients.

PubMed

Pinto, Pablo; Salgado, Claudio; Santos, Ney Pereira Carneiro; Santos, Sidney; Ribeiro-dos-Santos, Ândrea

2015-01-01

Leprosy is an insidious infectious disease caused by the obligate intracellular bacteria Mycobacterium leprae, and host genetic factors can modulate the immune response and generate distinct categories of leprosy susceptibility that are also influenced by genetic ancestry. We investigated the possible effects of CYP19A1 [rs11575899], NFKβ1 [rs28362491], IL1α [rs3783553], CASP8 [rs3834129], UGT1A1 [rs8175347], PAR1 [rs11267092], CYP2E1 [INDEL 96pb] and IL4 [rs79071878] genes in a group of 141 leprosy patients and 180 healthy individuals. The INDELs were typed by PCR Multiplex in ABI PRISM 3130 and analyzed with GeneMapper ID v3.2. The NFKβ1, CASP8, PAR1 and IL4 INDELs were associated with leprosy susceptibility, while NFKβ1, CASP8, PAR1 and CYP19A1 were associated with the MB (Multibacilary) clinical form of leprosy. NFKβ1 [rs28362491], CASP8 [rs3834129], PAR1 [rs11267092] and IL4 [rs79071878] genes are potential markers for susceptibility to leprosy development, while the INDELs in NFKβ1, CASP8, PAR1 and CYP19A1 (rs11575899) are potential markers for the severe clinical form MB. Moreover, all of these markers are influenced by genetic ancestry, and European contribution increases the risk to leprosy development, in other hand an increase in African contribution generates protection against leprosy.

Trial Watch: Adoptive cell transfer for anticancer immunotherapy.

PubMed

Vacchelli, Erika; Eggermont, Alexander; Fridman, Wolf Hervé; Galon, Jérôme; Tartour, Eric; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2013-05-01

Adoptive cell transfer (ACT) represents a prominent form of immunotherapy against malignant diseases. ACT is conceptually distinct from dendritic cell-based approaches (which de facto constitute cellular vaccines) and allogeneic transplantation (which can be employed for the therapy of hematopoietic tumors) as it involves the isolation of autologous lymphocytes exhibiting antitumor activity, their expansion/activation ex vivo and their reintroduction into the patient. Re-infusion is most often performed in the context of lymphodepleting regimens (to minimize immunosuppression by host cells) and combined with immunostimulatory interventions, such as the administration of Toll-like receptor agonists. Autologous cells that are suitable for ACT protocols can be isolated from tumor-infiltrating lymphocytes or generated by engineering their circulating counterparts for the expression of transgenic tumor-specific T-cell receptors. Importantly, lymphocytes can be genetically modified prior to re-infusion for increasing their persistence in vivo, boosting antitumor responses and minimizing side effects. Moreover, recent data indicate that exhausted antitumor T lymphocytes may be rejuvenated in vitro by exposing them to specific cytokine cocktails, a strategy that might considerably improve the clinical success of ACT. Following up the Trial Watch that we published on this topic in the third issue of OncoImmunology (May 2012), here we summarize the latest developments in ACT-related research, covering both high-impact studies that have been published during the last 13 months and clinical trials that have been initiated in the same period to assess the antineoplastic profile of this form of cellular immunotherapy.

Macrobenthic diversity in protected, disturbed, and newly formed intertidal wetlands of a subtropical estuary in China.

PubMed

Lv, Weiwei; Ma, Chang-An; Huang, Youhui; Yang, Yang; Yu, Ji; Zhang, Mingqing; Zhao, Yunlong

2014-12-15

In this study, intertidal macrobenthic diversity in protected, disturbed, and newly formed wetlands of Yangtze estuary was assessed using PRIMER 5.2 based on species diversity and species relatedness. We observed high diversity in nature reserves and low diversity in adjacent disturbed and newly formed wetlands. These diversity data were then integrated with historical data to detect the variation in macrobenthic diversity over the past two decades. The integrated data indicated that the intertidal macrobenthic diversity sharply decreased in heavy reclamation tidal flats whereas markedly increased in non-disturbed nature reserve and newly formed wetland. Benthic health was observed with the departure degree of average taxonomic distinctness (Δ(+)) and variation in taxonomic distinctness (Λ(+)) from the simulated 95% confidence funnel. All the habitats were subjected to different levels of human interference, except Jiuduansha and Beigangbeisha. The degradation of intertidal wetland in Yangtze estuary was mainly attributed to land reclamation, overgrazing, and overfishing. Copyright © 2014 Elsevier Ltd. All rights reserved.

ISOZYMES OF ACID PHOSPHATASE IN NORMAL AND CALMETTE-GUÉRIN BACILLUS-INDUCED RABBIT ALVEOLAR MACROPHAGES

PubMed Central

Axline, S. G.

1968-01-01

The acid phosphatase activity of normal alveolar and BCG-induced alveolar macrophages has been examined. Five electrophoretically distinct forms of acid phosphatase have been identified in both normal and BCG-induced macrophages. The acid phosphatases can be divided into two major categories. One category, containing four distinct forms, is readily solubilized after repeated freezing and thawing or mechanical disruption The second category, containing one form, is firmly bound to the lysosomal membrane and can be solubilized by treatment of the lysosomal fraction with Triton X-100. The Triton-extractable acid phosphatase and the predominant aqueous soluble acid phosphatase have been shown to differ in the degree of membrane binding, in solubility, in net charge, and in molecular weight. The two pre-dominant phosphatases possess identical pH optimum and do not differ in response to enzyme inhibitors. BCG stimulation has been shown to result in a nearly twofold increase in acid phosphatase activity. A nearly proportionate increase in the major acid phosphatase forms has been observed. PMID:4878908

[A comparison of the properties of bacteriocins formed by Lactococcus lactis subsp. lactis strains of diverse origin].

PubMed

Stoianova, L G; Egorov, N S; Fedorova, G B; Katrukha, G S; Netrusov, A I

2007-01-01

Bacteriocins formed by four strains of Lactococcus lactis subsp. lactis have been studied and compared: 729 (a natural strain isolated from milk), 1605 (a mutant of strain 729), F-116 (a recombinant obtained by fusing of protoplasts of the two related strain 729 and 1605), and a nisin-forming strain obtained by adaptive selection at Moscow State University. Antimicrobial activity studies revealed differences between the strains in the effects on individual groups of microorganisms; the activities of the strains were also distinct from that of Nisaplin (a commercial preparation of the bacteriocin nisin). Methods for isolation and purification of bacteriocins have been developed, making it possible to obtain individual components of antibiotic complexes as chromatographically pure preparations. Bacteriocins formed by the strains of Lactococcus lactis subsp. lactis have been identified and differences in their biological and physicochemical properties, established. A novel potent broad-spectrum antibiotic substance distinct from nisin has been isolated from the recombinant strain F-116.

Distinct neuroanatomical bases of episodic and semantic memory performance in Alzheimer's disease.

PubMed

Hirni, Daniela I; Kivisaari, Sasa L; Monsch, Andreas U; Taylor, Kirsten I

2013-04-01

Alzheimer's disease (AD) neurofibrillary pathology begins in the medial perirhinal cortex (mPRC) before spreading to the entorhinal cortex (ERC) and hippocampus (HP) in anterior medial temporal lobe (aMTL). While the role of the ERC/HP complex in episodic memory formation is well-established, recent research suggests that the PRC is required to form semantic memories of individual objects. We aimed to test whether commonly used clinical measures of episodic and semantic memory are distinctly associated with ERC/HP and mPRC integrity, respectively, in healthy mature individuals and very early AD patients. One hundred thirty normal controls, 32 amnestic mild cognitive impairment patients, some of whom are in the earliest (i.e., preclinical) stages of AD, and ten early-stage AD patients received neuropsychological testing and high-resolution anatomic and diffusion MRI. Voxel-based regression analyses tested for regions where episodic memory (delayed recall scores on the California Verbal Learning and Rey Osterrieth Complex Figure Tests) and semantic memory (Boston Naming Test, category fluency) performance correlated with gray matter (GM) regions of interest and whole-brain fractional anisotropy (FA) voxel values. When controlling for the opposing memory performance, poorer episodic memory performance was associated with reduced bilateral ERC/HP GM volume and related white matter integrity, but not with mPRC GM volume. Poor semantic memory performance was associated with both reduced left mPRC and ERC/HP GM volume, as well as reduced FA values in white matter tracts leading to the PRC. These results indicate a partial division of labor within the aMTL and suggest that mPRC damage in very early AD may be detectable with common clinical tests of semantic memory if episodic memory performance is controlled. Copyright © 2013 Elsevier Ltd. All rights reserved.

Distinct Subtypes of Microparticle-containing Immune Complexes Are Associated with Disease Activity, Damage, and Carotid Intima-media Thickness in Systemic Lupus Erythematosus.

PubMed

Fortin, Paul R; Cloutier, Nathalie; Bissonnette, Vincent; Aghdassi, Ellie; Eder, Lihi; Simonyan, David; Laflamme, Nathalie; Boilard, Eric

2016-11-01

Microparticles (MP) are small extracellular vesicles present in body fluids. MP originate from different cellular lineages, principally from platelets in blood, and may expose phosphatidylserine (PS). In systemic lupus erythematosus (SLE), MP harbor immunoglobulin G (IgG), thereby forming MP-containing immune complexes (mpIC). We aimed to verify an association between SLE disease activity, damage, and surrogate markers of atherosclerosis and MP harboring IgG, taking into account the platelet origin and PS exposure of MP. MP expressing surface IgG, platelet antigen (CD41+), and PS were quantified using flow cytometry in plasma of 191 women with SLE. Carotid ultrasounds (US) were available in 113 patients. Spearman correlation analysis was used to analyze whether levels of MP were associated with the following outcomes: SLE Disease Activity Index 2000 (SLEDAI-2K), Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), and carotid US plaques and intima-media thickness (CIMT) as surrogates for vascular damage. We found CD41+ MP harboring IgG present in SLE. A positive correlation was found between SLEDAI-2K and levels of CD41+ MP harboring IgG and exposing (p = 0.027) and non-exposing PS (p = 0.001). Conversely, SDI (p = 0.024) and CIMT (p = 0.016) correlated with concentrations of CD41- MP harboring IgG and exposing PS. Associations were independent of low-density lipoprotein cholesterol level, body mass index, and antimalarial drug use. Different subtypes of mpIC are produced in SLE and are associated with distinct clinical characteristics such as disease activity and vascular damage. The assessment of MP subtypes might serve for the design of predictive markers of disease activity and vascular damage in patients.

CDKL5 and ARX mutations are not responsible for early onset severe myoclonic epilepsy in infancy.

PubMed

Nabbout, Rima; Depienne, Christel; Chipaux, Mathilde; Girard, Benoit; Souville, Isabelle; Trouillard, Oriane; Dulac, Olivier; Chelly, Jamel; Afenjar, Alexandra; Héron, Delphine; Leguern, Eric; Beldjord, Cherif; Bienvenu, Thierry; Bahi-Buisson, Nadia

2009-11-01

Severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome (DS) is a distinctive epilepsy syndrome often associated with de novo mutations in the SCN1A gene. However, 25-30% patients with SMEI/DS are negative for SCN1A mutation screening, suggesting that other molecular mechanisms may account for these disorders. Given the overlapping and heterogeneous clinical features of CDKL5- and ARX-related epilepsies and SMEI/DS, we postulated that CDKL5 mutations in females and ARX mutations gene in males may be associated with early onset seizures forms of SMEI/DS. Twenty-eight patients with early onset SMEI/DS before 6 months negative for SCN1A mutational screening were selected and screened for mutations in the ARX gene in males (n=14) or the CDKL5 gene in females (n=14). No mutations in either gene were found except one intronic variation of uncertain pathogenicity in the CDKL5 gene. All patients started seizures at mean age of 3.48 months. Thirteen patients had familial history of epilepsy or febrile seizures. Patients evolved toward refractory epilepsy with generalized tonic clonic seizures (18/28) and myoclonia (23/28) and severe neurological impairment with autistic features (13/28), ataxia (14/28) and spasticity (5/28). No patient ever exhibited infantile spasms, dystonia, or Rett-like features. Our results illustrate that mutation screening of ARX and CDKL5 is not effective in patients selected on the basis of clinical signs associated to early onset SMEI/DS. In addition, they might reflect that other phenotypic features associated with CDKL5 mutations (Rett-like features, infantile spasm) or ARX mutations (dystonia, spasticity) are more distinctive. 2009 Elsevier B.V. All rights reserved.

Two distinct symptom-based phenotypes of depression in epilepsy yield specific clinical and etiological insights.

PubMed

Rayner, Genevieve; Jackson, Graeme D; Wilson, Sarah J

2016-11-01

Depression is common but underdiagnosed in epilepsy. A quarter of patients meet criteria for a depressive disorder, yet few receive active treatment. We hypothesize that the presentation of depression is less recognizable in epilepsy because the symptoms are heterogeneous and often incorrectly attributed to the secondary effects of seizures or medication. Extending the ILAE's new phenomenological approach to classification of the epilepsies to include psychiatric comorbidity, we use data-driven profiling of the symptoms of depression to perform a preliminary investigation of whether there is a distinctive symptom-based phenotype of depression in epilepsy that could facilitate its recognition in the neurology clinic. The psychiatric and neuropsychological functioning of 91 patients with focal epilepsy was compared with that of 77 healthy controls (N=168). Cluster analysis of current depressive symptoms identified three clusters: one comprising nondepressed patients and two symptom-based phenotypes of depression. The 'Cognitive' phenotype (base rate=17%) was characterized by symptoms taking the form of self-critical cognitions and dysphoria and was accompanied by pervasive memory deficits. The 'Somatic' phenotype (7%) was characterized by vegetative depressive symptoms and anhedonia and was accompanied by greater anxiety. It is hoped that identification of the features of these two phenotypes will ultimately facilitate improved detection and diagnosis of depression in patients with epilepsy and thereby lead to appropriate and timely treatment, to the benefit of patient wellbeing and the potential efficacy of treatment of the seizure disorder. This article is part of a Special Issue entitled "The new approach to classification: Rethinking cognition and behavior in epilepsy". Copyright © 2016 Elsevier Inc. All rights reserved.

Differentiating Bipolar Disorder–Not Otherwise Specified and Severe Mood Dysregulation

PubMed Central

Towbin, Kenneth; Axelson, David; Leibenluft, Ellen; Birmaher, Boris

2013-01-01

Objective Bipolar Disorder–Not Otherwise Specified (BP-NOS) and Severe Mood Dysregulation (SMD) are severe mood disorders that were both defined to address questions about the diagnosis of bipolar disorder (BD) in youth. SMD and BP-NOS are distinct phenotypes that differ in clinical presentation and longitudinal course. The purpose of this review is to inform clinicians about the clinical features of the two phenotypes and about the research literature distinguishing them. Method We review the literature on SMD as studied in the National Institute of Mental Health Intramural Research Program and on BP-NOS in youth. For BP-NOS, we focus on the phenotype defined in the Course of Bipolar Youth (COBY) study, since this has received the most study. Results SMD is characterized by impairing, chronic irritability without distinct manic episodes. Most commonly, BP-NOS is characterized by manic, mixed or hypomanic episodes that are too short to meet DSM-IV-TR duration criterion. Research provides strong, albeit suggestive, evidence that SMD is not a form of BD; the most convincing evidence are longitudinal data indicating that youth with SMD are not at high risk to develop BD as they age. The BP-NOS phenotype appears to be on a diagnostic continuum with BD type I and type II. BP-NOS and BD- type I subjects have similar symptom and family history profiles, and youth with BP-NOS are at high risk to develop BD as they age. Currently, little research guides treatment for either phenotype. Conclusions Pressing research needs include identifying effective treatments for these phenotypes, ascertaining biomarkers that predict conversion from BP-NOS to BD, elucidating associations between SMD and other disorders, and defining the neural circuitry mediating each condition. PMID:23622848

Health technology adoption and the politics of governance in the UK.

PubMed

Milewa, Timothy

2006-12-01

The manner in which clinical and cost-effectiveness data are used to inform decisions about the funding and availability of drugs, therapies and medical devices is inherently politicised within collectively financed systems of health care. The National Institute for Health and Clinical Excellence (NICE) was established by the British government in 1999 to reach evidence-based decisions on whether selected health technologies should be made available by the National Health Service in England and Wales. But NICE is also required to involve a broad range of interested parties in the decision-making process, provide detailed rationales for its rulings and defend appeals from aggrieved parties. Debates about the emergence of "deliberative" forms of policy governance--based upon participation by a broad range of stakeholders rather than reliance on scientific, bureaucratic or political expertise alone--are thus particularly apposite. This article draws on a study of decision-making within NICE by focusing upon the tenor and orientation of deliberation about the adoption of health technologies. Does such deliberation take place upon a level playing field for different interests? Or do implicit parameters and understandings in the deliberative process tend to privilege some interests by structuring debate and attendant outcomes? Findings suggest that deliberative assumptions and parameters pertaining to fluid and contestable ideas of transparent reasoning and domain competence both reflect and shape relationships of influence and marginality among participants. Broader analytical implications centre on a distinction between "deliberative democracy" and "democratic deliberation". The extent to which this distinction is acknowledged and addressed in policy and practise will have marked implications for the substantive nature of attempts to broaden involvement in decision-making within public sector bodies such as NICE.

Is there anything distinctive about epileptic deja vu?

PubMed

Warren-Gash, Charlotte; Zeman, Adam

2014-02-01

Déjà vu can occur as an aura of temporal lobe epilepsy and in some psychiatric conditions but is also common in the general population. It is unclear whether any clinical features distinguish pathological and physiological forms of déjà vu. 50 epileptic patients with ictal déjà vu, 50 non-epileptic patients attending general neurology clinics and 50 medical students at Edinburgh University were recruited. Data were collected on demographic factors, the experience of déjà vu using a questionnaire based on Sno's Inventory for Déjà Vu Experiences Assessment, symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale as well as seizure characteristics, anti-epileptic medications, handedness, EEG and neuroimaging findings for epileptic patients. 73.5% of neurology patients, 88% of students and (by definition) all epilepsy patients had experienced déjà vu. The experience of déjà vu itself was similar in the three groups. Epileptic déjà vu occurred more frequently and lasted somewhat longer than physiological déjà vu. Epilepsy patients were more likely to report prior fatigue and concentrated activity, associated derealisation, olfactory and gustatory hallucinations, physical symptoms such as headaches, abdominal sensations and fear. After controlling for study group, anxiety and depression scores were not associated with déjà vu frequency. Déjà vu is common and qualitatively similar whether it occurs as an epileptic aura or normal phenomenon. However ictal déjà vu occurs more frequently and is accompanied by several distinctive features. It is distinguished primarily by 'the company it keeps'.

Subtypes of medulloblastoma have distinct developmental origins

PubMed Central

Gibson, Paul; Tong, Yiai; Robinson, Giles; Thompson, Margaret C.; Currle, D. Spencer; Eden, Christopher; Kranenburg, Tanya A.; Hogg, Twala; Poppleton, Helen; Martin, Julie; Finkelstein, David; Pounds, Stanley; Weiss, Aaron; Patay, Zoltan; Scoggins, Matthew; Ogg, Robert; Pei, Yanxin; Yang, Zeng-Jie; Brun, Sonja; Lee, Youngsoo; Zindy, Frederique; Lindsey, Janet C.; Taketo, Makoto M.; Boop, Frederick A.; Sanford, Robert A.; Gajjar, Amar; Clifford, Steven C.; Roussel, Martine F.; McKinnon, Peter J.; Gutmann, David H.; Ellison, David W.; Wechsler-Reya, Robert; Gilbertson, Richard J.

2010-01-01

Medulloblastoma encompasses a collection of clinically and molecularly diverse tumor subtypes that together comprise the most common malignant childhood brain tumor1–4. These tumors are thought to arise within the cerebellum, with approximately 25% originating from granule neuron precursor cells (GNPCs) following aberrant activation of the Sonic Hedgehog pathway (hereafter, SHH-subtype)3–8. The pathological processes that drive heterogeneity among the other medulloblastoma subtypes are not known, hindering the development of much needed new therapies. Here, we provide evidence that a discrete subtype of medulloblastoma that contains activating mutations in the WNT pathway effector CTNNB1 (hereafter, WNT-subtype)1,3,4, arises outside the cerebellum from cells of the dorsal brainstem. We found that genes marking human WNT-subtype medulloblastomas are more frequently expressed in the lower rhombic lip (LRL) and embryonic dorsal brainstem than in the upper rhombic lip (URL) and developing cerebellum. Magnetic resonance imaging (MRI) and intra-operative reports showed that human WNT-subtype tumors infiltrate the dorsal brainstem, while SHH-subtype tumors are located within the cerebellar hemispheres. Activating mutations in Ctnnb1 had little impact on progenitor cell populations in the cerebellum, but caused the abnormal accumulation of cells on the embryonic dorsal brainstem that included aberrantly proliferating Zic1+ precursor cells. These lesions persisted in all mutant adult mice and in 15% of cases in which Tp53 was concurrently deleted, progressed to form medulloblastomas that recapitulated the anatomy and gene expression profiles of human WNT-subtype medulloblastoma. We provide the first evidence that subtypes of medulloblastoma have distinct cellular origins. Our data provide an explanation for the marked molecular and clinical differences between SHH and WNT-subtype medulloblastomas and have profound implications for future research and treatment of this important childhood cancer. PMID:21150899

Novel homozygous missense mutation in GAN associated with Charcot-Marie-Tooth disease type 2 in a large consanguineous family from Israel.

PubMed

Aharoni, Sharon; Barwick, Katy E S; Straussberg, Rachel; Harlalka, Gaurav V; Nevo, Yoram; Chioza, Barry A; McEntagart, Meriel M; Mimouni-Bloch, Aviva; Weedon, Michael; Crosby, Andrew H

2016-11-16

CMT-2 is a clinically and genetically heterogeneous group of peripheral axonal neuropathies characterized by slowly progressive weakness and atrophy of distal limb muscles resulting from length-dependent motor and sensory neurodegeneration. Classical giant axonal neuropathy (GAN) is an autosomal recessively inherited progressive neurodegenerative disorder of the peripheral and central nervous systems, typically diagnosed in early childhood and resulting in death by the end of the third decade. Distinctive phenotypic features are the presence of "kinky" hair and long eyelashes. The genetic basis of the disease has been well established, with over 40 associated mutations identified in the gene GAN, encoding the BTB-KELCH protein gigaxonin, involved in intermediate filament regulation. An Illumina Human CytoSNP-12 array followed by whole exome sequence analysis was used to identify the disease associated gene mutation in a large consanguineous family diagnosed with Charcot-Marie-Tooth disease type 2 (CMT-2) from which all but one affected member had straight hair. Here we report the identification of a novel GAN missense mutation underlying the CMT-2 phenotype observed in this family. Although milder forms of GAN, with and without the presence of kinky hair have been reported previously, a phenotype distinct from that was investigated in this study. All family members lacked common features of GAN, including ataxia, nystagmus, intellectual disability, seizures, and central nervous system involvement. Our findings broaden the spectrum of phenotypes associated with GAN mutations and emphasize a need to proceed with caution when providing families with diagnostic or prognostic information based on either clinical or genetic findings alone.

Emotion regulation and heterogeneity in attention-deficit/hyperactivity disorder.

PubMed

Musser, Erica D; Galloway-Long, Hilary S; Frick, Paul J; Nigg, Joel T

2013-02-01

How best to capture heterogeneity in attention-deficit/hyperactivity disorder (ADHD) using biomarkers has been elusive. This study evaluated whether emotion reactivity and regulation provide a means to achieve this. Participants were classified into three groups: children with ADHD plus low prosocial behavior (hypothesized to be high in callous/unemotional traits; n = 21); children with ADHD with age-appropriate prosocial behavior (n = 54); and typically developing children (n = 75). Children completed a task with four conditions: negative induction, negative suppression, positive induction, and positive suppression of affect. The task required children to view an emotion-laden film clip, while either facially mimicking (induction) or masking (suppression) the emotion of the main character. Parasympathetic and sympathetic nervous system activity were assessed via respiratory sinus arrhythmia (RSA) and cardiac pre-ejection period (PEP), respectively. Symptoms of anxiety, conduct, and oppositional defiant disorders were treated as covariates. The ADHD-typical-prosocial group displayed atypically elevated parasympathetic reactivity (emotion dysregulation) during positive induction, along with increased sympathetic activity (elevated arousal) across conditions. In contrast, the ADHD-low-prosocial group displayed reduced parasympathetic reactivity and reduced sympathetic activity (low emotional arousal) across baseline and task conditions. Thus, both ADHD groups had altered patterns of autonomic functioning, but in two distinct forms. Although ADHD is heterogeneous clinically, results suggest that ADHD is also heterogeneous with regard to physiological indices of emotion and regulation. Future studies of emotion, regulation, and ADHD should take this into account. Further study of physiological responding in ADHD may yield clinically and etiologically distinct domains or groups. Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Common and Distinctive Patterns of Cognitive Dysfunction in Children With Benign Epilepsy Syndromes.

PubMed

Cheng, Dazhi; Yan, Xiuxian; Gao, Zhijie; Xu, Keming; Zhou, Xinlin; Chen, Qian

2017-07-01

Childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes are the most common forms of benign epilepsy syndromes. Although cognitive dysfunctions occur in children with both childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes, the similarity between their patterns of underlying cognitive impairments is not well understood. To describe these patterns, we examined multiple cognitive functions in children with childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes. In this study, 43 children with childhood absence epilepsy, 47 children with benign childhood epilepsy with centrotemporal spikes, and 64 control subjects were recruited; all received a standardized assessment (i.e., computerized test battery) assessing processing speed, spatial skills, calculation, language ability, intelligence, visual attention, and executive function. Groups were compared in these cognitive domains. Simple regression analysis was used to analyze the effects of epilepsy-related clinical variables on cognitive test scores. Compared with control subjects, children with childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes showed cognitive deficits in intelligence and executive function, but performed normally in language processing. Impairment in visual attention was specific to patients with childhood absence epilepsy, whereas impaired spatial ability was specific to the children with benign childhood epilepsy with centrotemporal spikes. Simple regression analysis showed syndrome-related clinical variables did not affect cognitive functions. This study provides evidence of both common and distinctive cognitive features underlying the relative cognitive difficulties in children with childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes. Our data suggest that clinicians should pay particular attention to the specific cognitive deficits in children with childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes, to allow for more discriminative and potentially more effective interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

Is "Learning" episodic memory? Distinct cognitive and neuroanatomic correlates of immediate recall during learning trials in neurologically normal aging and neurodegenerative cohorts.

PubMed

Casaletto, K B; Marx, G; Dutt, S; Neuhaus, J; Saloner, R; Kritikos, L; Miller, B; Kramer, J H

2017-07-28

Although commonly interpreted as a marker of episodic memory during neuropsychological exams, relatively little is known regarding the neurobehavior of "total learning" immediate recall scores. Medial temporal lobes are clearly associated with delayed recall performances, yet immediate recall may necessitate networks beyond traditional episodic memory. We aimed to operationalize cognitive and neuroanatomic correlates of total immediate recall in several aging syndromes. Demographically-matched neurologically normal adults (n=91), individuals with Alzheimer's disease (n=566), logopenic variant primary progressive aphasia (PPA) (n=34), behavioral variant frontotemporal dementia (n=97), semantic variant PPA (n=71), or nonfluent/agrammatic variant PPA (n=39) completed a neurocognitive battery, including the CVLT-Short Form trials 1-4 Total Immediate Recall; a majority subset also completed a brain MRI. Regressions covaried for age and sex, and MMSE in cognitive and total intracranial volume in neuroanatomic models. Neurologically normal adults demonstrated a heterogeneous pattern of cognitive associations with total immediate recall (executive, speed, delayed recall), such that no singular cognitive or neuroanatomic correlate uniquely predicted performance. Within the clinical cohorts, there were syndrome-specific cognitive and neural associations with total immediate recall; e.g., semantic processing was the strongest cognitive correlate in svPPA (partial r=0.41), while frontal volumes was the only meaningful neural correlate in bvFTD (partial r=0.20). Medial temporal lobes were not independently associated with total immediate recall in any group (ps>0.05). Multiple neurobehavioral systems are associated with "total learning" immediate recall scores that importantly differ across distinct clinical syndromes. Conventional memory networks may not be sufficient or even importantly contribute to total immediate recall in many syndromes. Interpreting learning scores as equivalent to episodic memory may be erroneous. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phenotypic and genotypic characterization of biofilm formation among Staphylococcus aureus isolates from clinical specimens, an Atomic Force Microscopic (AFM) study.

PubMed

Bazari, Pelin Aslani Menareh; Honarmand Jahromy, Sahar; Zare Karizi, Shohreh

2017-09-01

Staphylococcus aureus is a major cause of nosocomial infections. Biofilm formation is an important factor for bacterial pathogenesis. Its mechanisms are complex and include of many genes depends on expression of icaADBC operon involved in the synthesis of a polysaccharide intercellular adhesion. The aim of study was to investigate biofilm forming ability of Staphylococcus aureus strains by phenotypic and genotypic methods. Also Atomic Force microscope (AFM) was used to visualize biofilm formation. 140 Isolates were collected from clinical specimens of patients in Milad Hospital, Tehran and diagnosed by biochemical tests. The ability of strains to produce slime was evaluated by CRA method. For diagnosing of bacterial EPS, Indian ink staining were used and finally biofilm surface of 3 isolates observed by AFM. The prevalence of icaA and icaD genes was determined by PCR. By CRA method 15% of samples considered as positive slime producers, 44.28% as intermediate and 40.71% indicative as negative slime producers. 118 staphylococcus aureus strains showed a distinct halo transparent zone but 22 strains showed no halo zone. AFM analysis of Slime positive isolates showed a distinct and complete biofilm formation. In slime negative strain, there was not observed biofilm. The prevalence of icaA, icaD genes was 44.2% and 10% of the isolates had both genes simultaneously. There is a relationship between exopolysaccharide layer and biofilm formation of Staphylococcus aureus isolates. The presence of icaAD genes among isolates is not associated with in vitro formation of biofilm. AFM is a useful tool for observation of bacterial biofilm formation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Conducting multicenter research in healthcare simulation: Lessons learned from the INSPIRE network.

PubMed

Cheng, Adam; Kessler, David; Mackinnon, Ralph; Chang, Todd P; Nadkarni, Vinay M; Hunt, Elizabeth A; Duval-Arnould, Jordan; Lin, Yiqun; Pusic, Martin; Auerbach, Marc

2017-01-01

Simulation-based research has grown substantially over the past two decades; however, relatively few published simulation studies are multicenter in nature. Multicenter research confers many distinct advantages over single-center studies, including larger sample sizes for more generalizable findings, sharing resources amongst collaborative sites, and promoting networking. Well-executed multicenter studies are more likely to improve provider performance and/or have a positive impact on patient outcomes. In this manuscript, we offer a step-by-step guide to conducting multicenter, simulation-based research based upon our collective experience with the International Network for Simulation-based Pediatric Innovation, Research and Education (INSPIRE). Like multicenter clinical research, simulation-based multicenter research can be divided into four distinct phases. Each phase has specific differences when applied to simulation research: (1) Planning phase , to define the research question, systematically review the literature, identify outcome measures, and conduct pilot studies to ensure feasibility and estimate power; (2) Project Development phase , when the primary investigator identifies collaborators, develops the protocol and research operations manual, prepares grant applications, obtains ethical approval and executes subsite contracts, registers the study in a clinical trial registry, forms a manuscript oversight committee, and conducts feasibility testing and data validation at each site; (3) Study Execution phase , involving recruitment and enrollment of subjects, clear communication and decision-making, quality assurance measures and data abstraction, validation, and analysis; and (4) Dissemination phase , where the research team shares results via conference presentations, publications, traditional media, social media, and implements strategies for translating results to practice. With this manuscript, we provide a guide to conducting quantitative multicenter research with a focus on simulation-specific issues.

76 FR 44566 - Endangered and Threatened Wildlife and Plants; 12-Month Finding on a Petition To List the Frigid...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-26

... years after Baker (1927) first described the species, the fossil form was reclassified as distinct from..., identification of the fossil form used fossil shell characterics only. In 1985, Terrence Frest (1985, p. 4.... Prior to this, the species was thought to only occur in fossil form. What were thought to be additional...

Examining leisure event opportunities of Isle Royale National Park: bridging the gap between social process and spatial form

Treesearch

Chad D. Pierskalla; Dorothy H. Anderson; David W. Lime

2000-01-01

To manage various recreation opportunities, managers and planners must consider the spatial and temporal scale of social process when identifying opportunities on base maps. However, analyses of social process and spatial form are often treated as two distinct approaches--sociological and geographical approaches. A sociologist might control for spatial form by adopting...

Distinct forms of mitochondrial TOM-TIM supercomplexes define signal-dependent states of preprotein sorting.

PubMed

Chacinska, Agnieszka; van der Laan, Martin; Mehnert, Carola S; Guiard, Bernard; Mick, David U; Hutu, Dana P; Truscott, Kaye N; Wiedemann, Nils; Meisinger, Chris; Pfanner, Nikolaus; Rehling, Peter

2010-01-01

Mitochondrial import of cleavable preproteins occurs at translocation contact sites, where the translocase of the outer membrane (TOM) associates with the presequence translocase of the inner membrane (TIM23) in a supercomplex. Different views exist on the mechanism of how TIM23 mediates preprotein sorting to either the matrix or inner membrane. On the one hand, two TIM23 forms were proposed, a matrix transport form containing the presequence translocase-associated motor (PAM; TIM23-PAM) and a sorting form containing Tim21 (TIM23(SORT)). On the other hand, it was reported that TIM23 and PAM are permanently associated in a single-entity translocase. We have accumulated distinct transport intermediates of preproteins to analyze the translocases in their active, preprotein-carrying state. We identified two different forms of active TOM-TIM23 supercomplexes, TOM-TIM23(SORT) and TOM-TIM23-PAM. These two supercomplexes do not represent separate pathways but are in dynamic exchange during preprotein translocation and sorting. Depending on the signals of the preproteins, switches between the different forms of supercomplex and TIM23 are required for the completion of preprotein import.

Profiling of ARDS pulmonary edema fluid identifies a metabolically distinct subset.

PubMed

Rogers, Angela J; Contrepois, Kévin; Wu, Manhong; Zheng, Ming; Peltz, Gary; Ware, Lorraine B; Matthay, Michael A

2017-05-01

There is considerable biological and physiological heterogeneity among patients who meet standard clinical criteria for acute respiratory distress syndrome (ARDS). In this study, we tested the hypothesis that there exists a subgroup of ARDS patients who exhibit a metabolically distinct profile. We examined undiluted pulmonary edema fluid obtained at the time of endotracheal intubation from 16 clinically phenotyped ARDS patients and 13 control patients with hydrostatic pulmonary edema. Nontargeted metabolic profiling was carried out on the undiluted edema fluid. Univariate and multivariate statistical analyses including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were conducted to find discriminant metabolites. Seven-hundred and sixty unique metabolites were identified in the pulmonary edema fluid of these 29 patients. We found that a subset of ARDS patients (6/16, 38%) presented a distinct metabolic profile with the overrepresentation of 235 metabolites compared with edema fluid from the other 10 ARDS patients, whose edema fluid metabolic profile was indistinguishable from those of the 13 control patients with hydrostatic edema. This "high metabolite" endotype was characterized by higher concentrations of metabolites belonging to all of the main metabolic classes including lipids, amino acids, and carbohydrates. This distinct group with high metabolite levels in the edema fluid was also associated with a higher mortality rate. Thus metabolic profiling of the edema fluid of ARDS patients supports the hypothesis that there is considerable biological heterogeneity among ARDS patients who meet standard clinical and physiological criteria for ARDS. Copyright © 2017 the American Physiological Society.

Profiling of ARDS pulmonary edema fluid identifies a metabolically distinct subset

PubMed Central

Contrepois, Kévin; Wu, Manhong; Zheng, Ming; Peltz, Gary; Ware, Lorraine B.; Matthay, Michael A.

2017-01-01

There is considerable biological and physiological heterogeneity among patients who meet standard clinical criteria for acute respiratory distress syndrome (ARDS). In this study, we tested the hypothesis that there exists a subgroup of ARDS patients who exhibit a metabolically distinct profile. We examined undiluted pulmonary edema fluid obtained at the time of endotracheal intubation from 16 clinically phenotyped ARDS patients and 13 control patients with hydrostatic pulmonary edema. Nontargeted metabolic profiling was carried out on the undiluted edema fluid. Univariate and multivariate statistical analyses including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were conducted to find discriminant metabolites. Seven-hundred and sixty unique metabolites were identified in the pulmonary edema fluid of these 29 patients. We found that a subset of ARDS patients (6/16, 38%) presented a distinct metabolic profile with the overrepresentation of 235 metabolites compared with edema fluid from the other 10 ARDS patients, whose edema fluid metabolic profile was indistinguishable from those of the 13 control patients with hydrostatic edema. This “high metabolite” endotype was characterized by higher concentrations of metabolites belonging to all of the main metabolic classes including lipids, amino acids, and carbohydrates. This distinct group with high metabolite levels in the edema fluid was also associated with a higher mortality rate. Thus metabolic profiling of the edema fluid of ARDS patients supports the hypothesis that there is considerable biological heterogeneity among ARDS patients who meet standard clinical and physiological criteria for ARDS. PMID:28258106

Assessment of various parameters to improve MALDI-TOF MS reference spectra libraries constructed for the routine identification of filamentous fungi

PubMed Central

2013-01-01

Background The poor reproducibility of matrix-assisted desorption/ionization time-of-flight (MALDI-TOF) spectra limits the effectiveness of the MALDI-TOF MS-based identification of filamentous fungi with highly heterogeneous phenotypes in routine clinical laboratories. This study aimed to enhance the MALDI-TOF MS-based identification of filamentous fungi by assessing several architectures of reference spectrum libraries. Results We established reference spectrum libraries that included 30 filamentous fungus species with various architectures characterized by distinct combinations of the following: i) technical replicates, i.e., the number of analyzed deposits for each culture used to build a reference meta-spectrum (RMS); ii) biological replicates, i.e., the number of RMS derived from the distinct subculture of each strain; and iii) the number of distinct strains of a given species. We then compared the effectiveness of each library in the identification of 200 prospectively collected clinical isolates, including 38 species in 28 genera. Identification effectiveness was improved by increasing the number of both RMS per strain (p<10-4) and strains for a given species (p<10-4) in a multivariate analysis. Conclusion Addressing the heterogeneity of MALDI-TOF spectra derived from filamentous fungi by increasing the number of RMS obtained from distinct subcultures of strains included in the reference spectra library markedly improved the effectiveness of the MALDI-TOF MS-based identification of clinical filamentous fungi. PMID:23565856

Contextual and temporal clinical guidelines.

PubMed Central

Guarnero, A.; Marzuoli, M.; Molino, G.; Terenziani, P.; Torchio, M.; Vanni, K.

1998-01-01

In this paper, we propose an approach for managing clinical guidelines. We sketch a modular architecture, allowing us to separate conceptually distinct aspects in the management and use of clinical guidelines. In particular, we describe the clinical guidelines knowledge representation module and we sketch the acquisition module. The main focus of the paper is the definition of an expressive formalism for representing clinical guidelines, which allows one to deal with the context dependent character of clinical guidelines and takes into account different temporal aspects. PMID:9929306

Neurobehavioral perspectives on the distinction between fear and anxiety

PubMed Central

Perusini, Jennifer N.

2015-01-01

In this review, we discuss the usefulness of the distinction between fear and anxiety. The clinical use of the labels is ambiguous, often defining one in terms of the other. We first consider what a useful, objective, and scientifically valid definition would entail and then evaluate several fear/anxiety distinctions that have been made in the neurobiological literature. A strong distinction should specify the difference in conditions that lead to fear versus anxiety. Additionally, fear and anxiety should generate distinct sets of behaviors. Ideally, the two states should be supported by distinguishable neuroanatomical circuits. Such a conceptualization would be consistent with the National Institute of Mental Health's Research Domain Criteria (RDoc). The majority of neurobiological approaches to the fear versus anxiety distinction fail to differentiate the two states in terms of behavior, often using the exact same behavioral measures as indicators. Of the two that do, only Predatory Imminence Theory provides a distinction both in terms of cause and effect. Indeed, that approach provides a ready distinction of anxiety, fear, and panic in terms of both antecedent conditions and response selection rules. Additionally, it appeals to distinct neural circuits to generate these modes of action. PMID:26286652

Spheroid-forming subpopulation of breast cancer cells demonstrates vasculogenic mimicry via hsa-miR-299–5p regulated de novo expression of osteopontin

PubMed Central

Shevde, Lalita A; Metge, Brandon J; Mitra, Aparna; Xi, Yaguang; Ju, Jingfang; King, Judy A; Samant, Rajeev S

2010-01-01

Abstract The growth of cancer cells as multicellular spheroids has frequently been reported to mimic the in vivo tumour architecture and physiology and has been utilized to study antitumour drugs. In order to determine the distinctive characteristics of the spheroid-derived cells compared to the corresponding monolayer-derived cells, we enriched multicellular spheroid-forming subpopulations of cells from three human breast cancer cell lines (MCF7, MCF10AT and MCF10DCIS.com). These spheroid-derived cells were injected into female athymic nude mice to assess their tumorigenic potential and were profiled for their characteristic miRNA signature. We discovered that the spheroid-derived cells expressed increased levels of osteopontin (OPN), an oncogenic protein that has been clinically correlated with increased tumour burden and adverse prognosis in patients with breast cancer metastasis. Our studies further show that increased OPN levels are brought about in part, by decreased levels of hsa-mir-299–5p in the spheroid-forming population from all three cell lines. Moreover, the spheroid-forming cells can organize into vascular structures in response to nutritional limitation; these structures recapitulate a vascular phenotype by the expression of endothelial markers CD31, Angiopoeitin-1 and Endoglin. In this study, we have validated that hsa-mir-299–5p targets OPN; de novo expression of OPN in turn plays a critical role in enhancing proliferation, tumorigenicity and the ability to display vasculogenic mimicry of the spheroid-forming cells. PMID:19538464

fMRI Reveals Distinct CNS Processing during Symptomatic and Recovered Complex Regional Pain Syndrome in Children

ERIC Educational Resources Information Center

Lebel, A.; Becerra, L.; Wallin, D.; Moulton, E. A.; Morris, S.; Pendse, G.; Jasciewicz, J.; Stein, M.; Aiello-Lammens, M.; Grant, E.; Berde, C.; Borsook, D.

2008-01-01

Complex regional pain syndrome (CRPS) in paediatric patients is clinically distinct from the adult condition in which there is often complete resolution of its signs and symptoms within several months to a few years. The ability to compare the symptomatic and asymptomatic condition in the same individuals makes this population interesting for the…

Etiological Distinctions between Aggressive and Non-Aggressive Antisocial Behavior: Results from a Nuclear Twin Family Model

ERIC Educational Resources Information Center

Burt, S. Alexandra; Klump, Kelly L.

2012-01-01

A recent meta-analysis of 103 studies Burt ("Clinical Psychology Review," 29:163-178, 2009a) highlighted the presence of etiological distinctions between aggressive (AGG) and non-aggressive rule-breaking (RB) dimensions of antisocial behavior, such that AGG was more heritable than was RB, whereas RB was more influenced by the shared…

Different disease subtypes with distinct clinical expression in familial Mediterranean fever: results of a cluster analysis.

PubMed

Akar, Servet; Solmaz, Dilek; Kasifoglu, Timucin; Bilge, Sule Yasar; Sari, Ismail; Gumus, Zeynep Zehra; Tunca, Mehmet

2016-02-01

The aim of this study was to evaluate whether there are clinical subgroups that may have different prognoses among FMF patients. The cumulative clinical features of a large group of FMF patients [1168 patients, 593 (50.8%) male, mean age 35.3 years (s.d. 12.4)] were studied. To analyse our data and identify groups of FMF patients with similar clinical characteristics, a two-step cluster analysis using log-likelihood distance measures was performed. For clustering the FMF patients, we evaluated the following variables: gender, current age, age at symptom onset, age at diagnosis, presence of major clinical features, variables related with therapy and family history for FMF, renal failure and carriage of M694V. Three distinct groups of FMF patients were identified. Cluster 1 was characterized by a high prevalence of arthritis, pleuritis, erysipelas-like erythema (ELE) and febrile myalgia. The dosage of colchicine and the frequency of amyloidosis were lower in cluster 1. Patients in cluster 2 had an earlier age of disease onset and diagnosis. M694V carriage and amyloidosis prevalence were the highest in cluster 2. This group of patients was using the highest dose of colchicine. Patients in cluster 3 had the lowest prevalence of arthritis, ELE and febrile myalgia. The frequencies of M694V carriage and amyloidosis were lower in cluster 3 than the overall FMF patients. Non-response to colchicine was also slightly lower in cluster 3. Patients with FMF can be clustered into distinct patterns of clinical and genetic manifestations and these patterns may have different prognostic significance. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Otofaciocervical syndrome and metachondromatosis in a girl: Presentation of a novel association and remarks on clinical variability of branchial-arch disorders.

PubMed

Salinas-Torres, Victor M; Salinas-Torres, Rafael A

2016-06-01

Otofaciocervical syndrome (OFCS) is a rare disorder characterized by facial, ear, branchial, and musculoskeletal anomalies, along with hearing loss and mild intellectual disability. Clinically, its distinction from branchiootorenal syndrome can be difficult. To date, the coexistence of OFCS and metachondromatosis has not been reported. Here, we describe a sporadic patient with both OFCS and metachondromatosis. This novel association prompts us to do some remarks on the clinical variability of branchial-arch disorders; in fact, our observations are consistent with the highly variable expressivity of OFCS and illustrate the need of a more accurate characterization of these branchial-arch disorders. In the meantime, involvement of clavicles, scapulae and shoulders remains a distinctive feature of OFCS. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Asperger syndrome: evolution of the concept and current clinical data].

PubMed

Aussilloux, C; Baghdadli, A

2008-05-01

Although Asperger syndrome is described by international classifications as a category of pervasive developmental disorder (PDD), its validity as a specific entity distinct from autistic disorders remains controversial. The syndrome, first described by Hans Asperger, could not be distinguished from high functioning autism (onset, symptoms, outcome...). However, international classifications propose a distinction between the two syndromes based on a delayed onset, the absence of speech delay, the presence of motor disorders and a better outcome in Asperger syndrome. This categorical differentiation is not confirmed by current studies and in the absence of biological markers, no clinical, neuropsychological or epidemiological criteria makes it possible to distinguish high functioning autism from Asperger syndrome. From a clinical perspective, it is nevertheless of interest to isolate Asperger syndrome from other autistic disorders to propose specific assessment and therapy.

Pros and cons in the search for extraterrestrial intelligence.

PubMed

Kantha, S S

1996-03-01

I propose a new term, 'galactic organism with distinct intelligence', for the extraterrestrial forms, with which humans can make contact. This is because, among the three existing terms: (a) 'the search for extraterrestrial intelligence' 'excludes biology and is inelegant'; (b) 'extraterrestrial' does not distinguish between the micro-organisms and highly-evolved intelligent life-forms; and (c) 'unidentified flying object' projects a sense of mysticism. On the presence of galactic organisms with distinct intelligence, scientists belong to three camps. Astronomers, physicists and some biochemists belong to the believers group. Evolutionists are in the doubters category. The third camp is represented by the 'uncommitted'. Approaches for contacting galactic organisms with distinct intelligence would take three steps. These are: (a) radioastronomical observations in the galaxy and interstellar space for the presence of organic matter; (b) initiating radio contact and listening to any transmitted message, as set out by the search for extraterrestrial intelligence program, and (c) landing instruments and humans in the galaxy.

Funnel for localizing biological cell placement and arrangement

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

Soscia, David; Benett, William J.; Mukerjee, Erik V.

2018-03-06

The present disclosure relates to a funnel apparatus for channeling cells onto a plurality of distinct, closely spaced regions of a seeding surface. The funnel apparatus has a body portion having an upper surface and a lower surface. The body portion forms a plurality of flow paths, at least one of which is shaped to have a decreasing cross-sectional area from the upper surface to the lower surface. The flow paths are formed at the lower surface to enable cells deposited into the flow paths at the upper surface of the funnel apparatus to be channeled into a plurality ofmore » distinct, closely spaced regions on the seeding surface positioned adjacent the lower surface.« less

A distinctive type of infantile inflammatory myopathy with abnormal myonuclei.

PubMed

Sripathi, N; Karpati, G; Carpenter, S

1996-03-01

Four infants developed progressive muscle weakness after a normal initial postnatal development. All patients had a moderate elevation of serum creatine kinase (CK) activity. Muscle biopsies revealed, in addition to myopathic features, endomysial and perivascular inflammation. Electron microscopy disclosed prominent myonuclear abnormalities. Corticosteroids in 3 patients were moderately beneficial. This appears to be a clinicopathologically distinct form of inflammatory myopathy of infants.

Identifying Molecular Targets for Chemoprevention in a Rat Model

DTIC Science & Technology

2007-06-01

accompanied by a reactive stromal proliferation resulting in a distinct thickening of the thin muscular layer surrounding individual glands. These...accompanied by reactive stromal proliferation, resulting in a distinct thickening of the thin muscular layer surrounding individual glands. These proliferations...epithelial cells forming solid bridges and circular apolar lumina. The lesions filled the glandular lumen but did not show distension with foci of

Distinct Single but Not Necessarily Repeated Tetanization Is Required to Induce Hippocampal Late-LTP in the Rat CA1

ERIC Educational Resources Information Center

Sajikumar, Sreedharan; Navakkode, Sheeja; Frey, Julietta U.

2008-01-01

The protein synthesis-dependent form of hippocampal long-term potentiation (late-LTP) is thought to underlie memory. Its induction requires a distinct stimulation strength, and the common opinion is that only repeated tetani result in late-LTP whereas as single tetanus only reveals a transient early-LTP. Properties of LTP induction were compared…

Cooperation between human fibrocytes and endothelial colony forming cells increases angiogenesis via CXCR4 pathway

PubMed Central

Smadja, David M.; Dorfmüller, Peter; Bieche, Ivan; Guerin, Coralie; Badoual, Cécile; Boscolo, Elisa; Kambouchner, Marianne; Cazes, Aurélie; Mercier, Olaf; Humbert, Marc; Gaussem, Pascale; Bischoff, Joyce; Israël-Biet, Dominique

2016-01-01

Background Fibrotic diseases of the lung are associated with a vascular remodeling process. Fibrocytes (Fy) are a distinct population of blood-borne cells that coexpress hematopoietic cell antigens and fibroblast markers, which have been shown to contribute to organ fibrosis. The purpose of this study was to test the hypothesis that Fy might cooperate with endothelial colony forming cells to induce angiogenesis. Methods/Results We successfully isolated Fy from blood of idiopathic pulmonary fibrosis (IPF) patients, which were further characterized by flow cytometry, Reverse Transcriptase quantitative-PCR (RTQ-PCR), and confocal analysis. We investigated the interaction between Fy and cord blood derived endothelial colony forming cells (ECFC) angiogenic potential in vitro and in vivo in a Matrigel implant model. Compared to fibroblast culture media, secreted media from Fy increase ECFC proliferation and their differentiation ability via SDF-1/CXCR4 pathway. IPF-Fy co-implanted with human ECFC in a matrigel plug in immunodeficient mice formed functional microvascular beds, whereas fibroblasts did not. Evaluation of implants after 2 weeks revealed an extensive network of blood vessels containing erythrocytes. CXCR4 blockade significantly inhibited blood vessel formation in the implants. The clinical relevance of these data was confirmed by the high expression level of CXCR4 in vessels close to fibrotic areas in biopsy specimens from patients with IPF, in contrast to control lungs. Conclusions Circulating Fy might be contribute to the intense remodeling of the pulmonary vasculature in patients with IPF. PMID:25103869

Applications of Polymers as Pharmaceutical Excipients in Solid Oral Dosage Forms.

PubMed

Debotton, Nir; Dahan, Arik

2017-01-01

Over the last few decades, polymers have been extensively used as pharmaceutical excipients in drug delivery systems. Pharmaceutical polymers evolved from being simply used as gelatin shells comprising capsule to offering great formulation advantages including enabling controlled/slow release and specific targeting of drugs to the site(s) of action (the "magic bullets" concept), hence hold a significant clinical promise. Oral administration of solid dosage forms (e.g., tablets and capsules) is the most common and convenient route of drug administration. When formulating challenging molecules into solid oral dosage forms, polymeric pharmaceutical excipients permit masking undesired physicochemical properties of drugs and consequently, altering their pharmacokinetic profiles to improve the therapeutic effect. As a result, the number of synthetic and natural polymers available commercially as pharmaceutical excipients has increased dramatically, offering potential solutions to various difficulties. For instance, the different polymers may allow increased solubility, swellability, viscosity, biodegradability, advanced coatings, pH dependency, mucodhesion, and inhibition of crystallization. The aim of this article is to provide a wide angle prospect of the different uses of pharmaceutical polymers in solid oral dosage forms. The various types of polymeric excipients are presented, and their distinctive role in oral drug delivery is emphasized. The comprehensive know-how provided in this article may allow scientists to use these polymeric excipients rationally, to fully exploit their different features and potential influence on drug delivery, with the overall aim of making better drug products. © 2016 Wiley Periodicals, Inc.

POLG1 mutations and stroke like episodes: a distinct clinical entity rather than an atypical MELAS syndrome.

PubMed

Cheldi, Antonella; Ronchi, Dario; Bordoni, Andreina; Bordo, Bianca; Lanfranconi, Silvia; Bellotti, Maria Grazia; Corti, Stefania; Lucchini, Valeria; Sciacco, Monica; Moggio, Maurizio; Baron, Pierluigi; Comi, Giacomo Pietro; Colombo, Antonio; Bersano, Anna

2013-01-15

POLG1 mutations have been associated with MELAS-like phenotypes. However given several clinical differences it is unknown whether POLG1 mutations are possible causes of MELAS or give raise to a distinct clinical and genetic entity, named POLG1-associated encephalopathy. We describe a 74 years old man carrying POLG1 mutations presenting with strokes, myopathy and ragged red fibers with some atypical aspects for MELAS such as late onset, lack of cerebral calcification and presence of frontal and occipital MRI lesions better consistent with the POLG associated-encephalopathy spectrum. The lack of available data hampers a definite diagnosis in our patient as well as makes it difficult to compare MELAS, which is a clearly defined clinical syndrome, with POLG1-associated encephalopathy, which is so far a purely molecularly defined syndrome with a quite heterogeneous clinical picture. However, the present report contributes to expand the phenotypic spectrum of POLG1 mutations underlining the importance of searching POLG1 mutations in patients with mitochondrial signs and MELAS like phenotypes but negative for common mtDNA mutations.

Comparison of motivational interviewing with acceptance and commitment therapy: a conceptual and clinical review.

PubMed

Bricker, Jonathan; Tollison, Sean

2011-10-01

Motivational Interviewing (MI) and Acceptance and Commitment Therapy (ACT) are two emerging therapies that focus on commitment to behavior change. The aim was to provide the first systematic comparison of MI with ACT. A systematic comparison was undertaken of MI and ACT at the conceptual level, with a focus on their philosophical and theoretical bases, and at the clinical level, with a focus on the therapeutic relationship, use of language in therapy, and use of values in therapy. Conceptually, MI and ACT have distinct philosophical bases. MI's theoretical basis focuses on language content, whereas ACT's theoretical basis focuses on language process. Clinically, ACT and MI have distinct approaches to the therapeutic relationship, fundamentally different foci on client language, and different uses of client values to motivate behavior change. ACT, but not MI, directly targets the willingness to experience thoughts, feelings, and sensations. Despite their conceptual and clinical differences, MI and ACT are complementary interventions. Collaborations between MI and ACT researchers may yield fruitful cross-fertilization research on core processes and clinical outcomes.

Comparison of Motivational Interviewing with Acceptance and Commitment Therapy: A conceptual and clinical review

PubMed Central

Bricker, J.B.; Tollison, S.J.

2011-01-01

Background Motivational Interviewing (MI) and Acceptance and Commitment Therapy (ACT) are two emerging therapies that focus on commitment to behavior change. Aim Provide the first systematic comparison of MI with ACT. Methods A systematic comparison of MI and ACT at the conceptual level, with a focus on their philosophical and theoretical bases, and at the clinical level, with a focus on the therapeutic relationship, use of language in therapy, and use of values in therapy. Results Conceptually, MI & ACT have distinct philosophical bases. MI’s theoretical basis focuses on language content, whereas ACT’s theoretical basis focuses on language process. Clinically, ACT and MI have distinct approaches to the therapeutic relationship, fundamentally different foci on client language, and different uses of client values to motivate behavior change. ACT, but not MI, directly targets the willingness to experience thoughts, feelings, and sensations. Conclusions Despite their conceptual and clinical differences, MI and ACT are complementary interventions. Collaborations between MI and ACT researchers may yield fruitful cross-fertilization research on core processes and clinical outcomes. PMID:21338532

Nanostructured Alloys as an Alternative to Copper-Beryllium

DTIC Science & Technology

2014-11-19

2014 Presented by Jonathan McCrea Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection of...unclassified c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Advanced Materials Integran Technologies...requirements for current and future copper-beryllium alloy needs/ applications ● Demonstrate with three distinct product forms :  1) Bulk material for

The Therapeutic Process in Clinical Social Work.

ERIC Educational Resources Information Center

Siporin, Max

1983-01-01

Suggests that current outmoded and inadequate conceptions of the therapeutic process are a major obstacle to the advancement of clinical social work practice. Presents an integrative ecosystem model that expresses the distinctive social work concern with person, situation, and helping relationship, in their reciprocal psychodynamic and…