M-protein-positive chronic active Epstein-Barr virus infection: features mimicking HIV-1 infection.

PubMed

Imashuku, Shinsaku; Azuma, Naoto; Kanegane, Hirokazu; Kasahara, Yoshihito

2009-09-01

Chronic active Epstein-Barr virus infection (CAEBV) is a unique and fatal lymphoproliferative disease (LPD), which often shows high serum IgG and/or IgE. The significance of such immunoglobulin abnormalities in CAEBV has not been fully evaluated and discussed. In addition, such clinical features mimic HIV-1 infection. We report here a case of CAEBV with M-protein detected which may shed a new light on the pathogenesis of this disease.

A preliminary evaluation of the validity of binge-eating disorder defining features in a community-based sample.

PubMed

Klein, Kelly M; Forney, K Jean; Keel, Pamela K

2016-05-01

Little empirical attention has been paid to the DSM-5 definition of binge-eating disorder (BED), particularly to the associated features of binge episodes. The present study sought to determine how the associated features and undue influence of weight/shape on self-evaluation contribute to evidence of a clinically significant eating disorder. Secondary analyses were conducted on data (N = 80; 76.3% women, 76.3% Caucasian, ages 18-43) collected through an epidemiological study of eating patterns. Descriptive statistics were used to report the sample prevalence of the features, independently and in combination. Correlations and alpha reliability were employed to examine relationships among associated features, distress regarding bingeing, and clinical diagnosis. Regression models and receiver-operating characteristic (ROC) curves were used to determine the utility of the features for explaining variance in distress. Internal consistency reliability for indicators was low, and several features demonstrated low or nonsignificant associations with distress and diagnosis. Feeling disgusted/depressed/guilty was the only unique predictor of distress (p = 0.001). For the ROC curves, three features was the best threshold for predicting distress. Results support the need to refine the features to ensure better detection of clinically significant eating pathology for research inclusion and treatment of the illness. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:524-528). © 2015 Wiley Periodicals, Inc.

Chronic Effects of Mild Neurotrauma: Putting the Cart Before the Horse?

PubMed Central

Castellani, Rudy J.; Perry, George; Iverson, Grant L.

2015-01-01

Accumulation of phosphorylated tau (p-tau) is accepted by many as a long-term consequence of repetitive mild neurotrauma, based largely on brain findings in boxers (dementia pugilistica) and, more recently, former professional athletes, military service members, and others exposed to repetitive head trauma. The pathogenic construct is also largely accepted and suggests that repetitive head trauma (typically concussions or subconcussive forces) acts on brain parenchyma to produce a deleterious neuroinflammatory cascade, encompassing p-tau templating, trans-synaptic neurotoxicity, progressive neurodegenerative disease, and associated clinical features. Some caution before accepting these concepts and assumptions is warranted, however. The association between history of concussion and findings of p-tau at autopsy is unclear. Concussions and subconcussive head trauma exposure are poorly defined in available cases and the clinical features reported in CTE are not at present distinguishable from other disorders. Because control groups are limited, the idea that p-tau drives the disease process via protein templating or some other mechanism is preliminary. Much additional research in CTE is needed to determine if it has unique neuropathology and clinical features, the extent to which the neuropathologic alterations cause the clinical features, and whether it can be identified accurately in a living person. PMID:25933385

Lupus erythematosus/lichen planus overlap syndrome: successful treatment with acitretin.

PubMed

Lospinoso, D J; Fernelius, C; Edhegard, K D; Finger, D R; Arora, N S

2013-07-01

Lupus erythematosus/lichen planus overlap syndrome is a rare disorder combining the clinical, histological and immunopathological features of both lupus erythematosus (LE) and lichen planus (LP). Cutaneous lesions mostly affect the distal arms, legs, face and trunk. Palmoplantar involvement is felt to be characteristic of this condition. Plaques are often painful, centrally atrophic, bluish-red to hypopigmented in color, large, and scaly. On biopsy of clinically ambiguous lesions, histopathological features of one or both processes can be found, obscuring the diagnosis and complicating prognosis and treatment. Thus, direct immunofluorescence has become an essential tool in helping to diagnose this condition. In this report we describe the unique clinical and immunohistopathological manifestations of lupus erythematosus/lichen planus overlap syndrome along with a successful response to treatment with acitretin.

Pedunculated and telangiectatic merkel cell carcinoma: an unusual clinical presentation.

PubMed

Errichetti, Enzo; Piccirillo, Angelo; Ricciuti, Federico; Ricciuti, Francesco

2013-05-01

Merkel cell carcinoma (MCC) is an uncommon aggressive neuroendocrine tumor of the skin that classically presents on chronic sun-damaged skin as a skin-colored, red or violaceous, firm and nontender papule or nodule with a smooth and shiny surface. Ulcerations can be observed very seldom and only in very advanced lesions. We present a unique case of a MCC presenting with two unusual clinical features: The Telangiectatic surface and the pedunculated aspect.

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

PubMed

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

2011-01-01

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

An Eye-Tracking Study of Multiple Feature Value Category Structure Learning: The Role of Unique Features

PubMed Central

Liu, Zhiya; Song, Xiaohong; Seger, Carol A.

2015-01-01

We examined whether the degree to which a feature is uniquely characteristic of a category can affect categorization above and beyond the typicality of the feature. We developed a multiple feature value category structure with different dimensions within which feature uniqueness and typicality could be manipulated independently. Using eye tracking, we found that the highest attentional weighting (operationalized as number of fixations, mean fixation time, and the first fixation of the trial) was given to a dimension that included a feature that was both unique and highly typical of the category. Dimensions that included features that were highly typical but not unique, or were unique but not highly typical, received less attention. A dimension with neither a unique nor a highly typical feature received least attention. On the basis of these results we hypothesized that subjects categorized via a rule learning procedure in which they performed an ordered evaluation of dimensions, beginning with unique and strongly typical dimensions, and in which earlier dimensions received higher weighting in the decision. This hypothesis accounted for performance on transfer stimuli better than simple implementations of two other common theories of category learning, exemplar models and prototype models, in which all dimensions were evaluated in parallel and received equal weighting. PMID:26274332

An Eye-Tracking Study of Multiple Feature Value Category Structure Learning: The Role of Unique Features.

PubMed

Liu, Zhiya; Song, Xiaohong; Seger, Carol A

2015-01-01

We examined whether the degree to which a feature is uniquely characteristic of a category can affect categorization above and beyond the typicality of the feature. We developed a multiple feature value category structure with different dimensions within which feature uniqueness and typicality could be manipulated independently. Using eye tracking, we found that the highest attentional weighting (operationalized as number of fixations, mean fixation time, and the first fixation of the trial) was given to a dimension that included a feature that was both unique and highly typical of the category. Dimensions that included features that were highly typical but not unique, or were unique but not highly typical, received less attention. A dimension with neither a unique nor a highly typical feature received least attention. On the basis of these results we hypothesized that subjects categorized via a rule learning procedure in which they performed an ordered evaluation of dimensions, beginning with unique and strongly typical dimensions, and in which earlier dimensions received higher weighting in the decision. This hypothesis accounted for performance on transfer stimuli better than simple implementations of two other common theories of category learning, exemplar models and prototype models, in which all dimensions were evaluated in parallel and received equal weighting.

Frequency and clinical features of patients who attempted suicide by Hara-Kiri in Japan.

PubMed

Kato, Koji; Kimoto, Keitaro; Kimoto, Kousuke; Takahashi, Yuki; Sato, Reiko; Matsumoto, Hideo

2014-09-01

Hara-kiri is a unique Japanese custom, primarily stemming from the manners and customs that a samurai held. The aim of the present study was to investigate the clinical features of individuals who attempted suicide by hara-kiri. We enrolled 647 patients who had attempted suicide. Clinical features were compared between those who had employed hara-kiri and those who had used other methods. 25 of the 647 subjects had attempted suicide by hara-kiri. The ratio of men to women and the proportion of patients with mood disorders were significantly higher in the hara-kiri group than in the other methods group. The average length of stay in either the hospital or in the intensive care unit was also longer in the hara-kiri group than in the other methods group. Hara-kiri is an original Japanese method of attempting suicide, and suicide attempts by hara-kiri may be aimed at maintaining a reputation or taking responsibility. © 2014 American Academy of Forensic Sciences.

Citation Sentiment Analysis in Clinical Trial Papers

PubMed Central

Xu, Jun; Zhang, Yaoyun; Wu, Yonghui; Wang, Jingqi; Dong, Xiao; Xu, Hua

2015-01-01

In scientific writing, positive credits and negative criticisms can often be seen in the text mentioning the cited papers, providing useful information about whether a study can be reproduced or not. In this study, we focus on citation sentiment analysis, which aims to determine the sentiment polarity that the citation context carries towards the cited paper. A citation sentiment corpus was annotated first on clinical trial papers. The effectiveness of n-gram and sentiment lexicon features, and problem-specified structure features for citation sentiment analysis were then examined using the annotated corpus. The combined features from the word n-grams, the sentiment lexicons and the structure information achieved the highest Micro F-score of 0.860 and Macro-F score of 0.719, indicating that it is feasible to use machine learning methods for citation sentiment analysis in biomedical publications. A comprehensive comparison between citation sentiment analysis of clinical trial papers and other general domains were conducted, which additionally highlights the unique challenges within this domain. PMID:26958274

Anterior ankle impingement syndromes.

PubMed

Umans, Hilary R; Cerezal, Luiz

2008-06-01

Ankle impingement syndromes are painful conditions that may complicate ankle trauma and are characterized by chronic, progressive pain, swelling, and limitation of movement. These disorders are subclassified according to anatomical location about the tibiotalar joint. This article reviews the various forms of anterior ankle impingement, detailing the unique clinical features, anatomical considerations, pathoetiology, and imaging findings for each.

The Congenital Heart Surgeons Society Datacenter: unique attributes as a research organization.

PubMed

Caldarone, Christopher A; Williams, William G

2010-01-01

Over the last 25 years, the Congenital Heart Surgeons Society (CHSS) has evolved from an informal club to a mature organization. A central feature of the CHSS has been dedication to evaluating outcomes of congenital heart surgery across a wide array of clinical diagnoses. These research activities have been orchestrated through the CHSS Datacenter, which has developed a unique organizational structure that has strengths and weaknesses in comparison to other research organizational structures (e.g., prospective randomized trials, registries, etc). This review will highlight the unique attributes of the CHSS Datacenter with emphasis on the Datacenter's strengths and weaknesses in comparison to other organizational structures. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Pedunculated and Telangiectatic Merkel Cell Carcinoma: An Unusual Clinical Presentation

PubMed Central

Errichetti, Enzo; Piccirillo, Angelo; Ricciuti, Federico; Ricciuti, Francesco

2013-01-01

Merkel cell carcinoma (MCC) is an uncommon aggressive neuroendocrine tumor of the skin that classically presents on chronic sun-damaged skin as a skin-colored, red or violaceous, firm and nontender papule or nodule with a smooth and shiny surface. Ulcerations can be observed very seldom and only in very advanced lesions. We present a unique case of a MCC presenting with two unusual clinical features: The Telangiectatic surface and the pedunculated aspect. PMID:23723504

Clinical, immunophenotypic, and molecular characteristics of well-differentiated systemic mastocytosis.

PubMed

Álvarez-Twose, Iván; Jara-Acevedo, María; Morgado, José Mário; García-Montero, Andrés; Sánchez-Muñoz, Laura; Teodósio, Cristina; Matito, Almudena; Mayado, Andrea; Caldas, Carolina; Mollejo, Manuela; Orfao, Alberto; Escribano, Luis

2016-01-01

Well-differentiated systemic mastocytosis (WDSM) is a rare variant of systemic mastocytosis (SM) characterized by bone marrow (BM) infiltration by mature-appearing mast cells (MCs) often lacking exon 17 KIT mutations. Because of its rarity, the clinical and biological features of WDSM remain poorly defined. We sought to determine the clinical, biological, and molecular features of a cohort of 33 patients with mastocytosis in the skin in association with BM infiltration by well-differentiated MCs and to establish potential diagnostic criteria for WDSM. Thirty-three patients with mastocytosis in the skin plus BM aggregates of round, fully granulated MCs lacking strong CD25 and CD2 expression in association with clonal MC features were studied. Our cohort of patients showed female predominance (female/male ratio, 4:1) and childhood onset of the disease (91%) with frequent familial aggregation (39%). Skin involvement was heterogeneous, including maculopapular (82%), nodular (6%), and diffuse cutaneous (12%) mastocytosis. KIT mutations were detected in only 10 (30%) of 33 patients, including the KIT D816V (n = 5), K509I (n = 3), N819Y (n = 1), and I817V (n = 1) mutations. BM MCs displayed a unique immunophenotypic pattern consisting of increased light scatter features, overexpression of cytoplasmic carboxypeptidase, and aberrant expression of CD30, together with absent (79%) or low (21%) positivity for CD25, CD2, or both. Despite only 9 (27%) of 33 patients fulfilling the World Health Organization criteria for SM, our findings allowed us to establish the systemic nature of the disease, which fit with the definition of WDSM. WDSM represents a rare clinically and molecularly heterogeneous variant of SM that requires unique diagnostic criteria to avoid a misdiagnosis of cutaneous mastocytosis per current World Health Organization criteria. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

An Interesting Case of Oral Inverted Ductal Papilloma.

PubMed

Berridge, Natasha; Kumar, Mahesh

2016-12-01

Ductal papillomas are rare benign papillary tumours of the minor salivary glands. Previously they have been classified into three subtypes: inverted ductal papilloma (IDP), sialadenoma papilliferum and intraductal papilloma. The oral inverted ductal papilloma is the least common of these lesions, with 48 cases reported to date in a search of the English-language literature. We describe an interesting case of oral IDP and highlight the pertinent clinical and histopathological features. Importantly, unlike the histologically similar inverted papilloma (IP) of the nose and paranasal sinuses, oral IDP is a completely benign lesion and is not associated with malignant change. Clinical relevance: This case report aims to raise awareness of the lesion, oral inverted ductal papilloma (IDP). We outline the clinical features and unique histopathology of oral IDP so that clinicians may correctly diagnose such a lesion and implement appropriate treatment.

Competitive Advantage of PET/MRI

PubMed Central

Jadvar, Hossein; Colletti, Patrick M.

2013-01-01

Multimodality imaging has made great strides in the imaging evaluation of patients with a variety of diseases. Positron emission tomography/computed tomography (PET/CT) is now established as the imaging modality of choice in many clinical conditions, particularly in oncology. While the initial development of combined PET/magnetic resonance imaging (PET/MRI) was in the preclinical arena, hybrid PET/MR scanners are now available for clinical use. PET/MRI combines the unique features of MRI including excellent soft tissue contrast, diffusion-weighted imaging, dynamic contrast-enhanced imaging, fMRI and other specialized sequences as well as MR spectroscopy with the quantitative physiologic information that is provided by PET. Most evidence for the potential clinical utility of PET/MRI is based on studies performed with side-by-side comparison or software-fused MRI and PET images. Data on distinctive utility of hybrid PET/MRI are rapidly emerging. There are potential competitive advantages of PET/MRI over PET/CT. In general, PET/MRI may be preferred over PET/CT where the unique features of MRI provide more robust imaging evaluation in certain clinical settings. The exact role and potential utility of simultaneous data acquisition in specific research and clinical settings will need to be defined. It may be that simultaneous PET/MRI will be best suited for clinical situations that are disease-specific, organ-specific, related to diseases of the children or in those patients undergoing repeated imaging for whom cumulative radiation dose must be kept as low as reasonably achievable. PET/MRI also offers interesting opportunities for use of dual modality probes. Upon clear definition of clinical utility, other important and practical issues related to business operational model, clinical workflow and reimbursement will also be resolved. PMID:23791129

Competitive advantage of PET/MRI.

PubMed

Jadvar, Hossein; Colletti, Patrick M

2014-01-01

Multimodality imaging has made great strides in the imaging evaluation of patients with a variety of diseases. Positron emission tomography/computed tomography (PET/CT) is now established as the imaging modality of choice in many clinical conditions, particularly in oncology. While the initial development of combined PET/magnetic resonance imaging (PET/MRI) was in the preclinical arena, hybrid PET/MR scanners are now available for clinical use. PET/MRI combines the unique features of MRI including excellent soft tissue contrast, diffusion-weighted imaging, dynamic contrast-enhanced imaging, fMRI and other specialized sequences as well as MR spectroscopy with the quantitative physiologic information that is provided by PET. Most evidence for the potential clinical utility of PET/MRI is based on studies performed with side-by-side comparison or software-fused MRI and PET images. Data on distinctive utility of hybrid PET/MRI are rapidly emerging. There are potential competitive advantages of PET/MRI over PET/CT. In general, PET/MRI may be preferred over PET/CT where the unique features of MRI provide more robust imaging evaluation in certain clinical settings. The exact role and potential utility of simultaneous data acquisition in specific research and clinical settings will need to be defined. It may be that simultaneous PET/MRI will be best suited for clinical situations that are disease-specific, organ-specific, related to diseases of the children or in those patients undergoing repeated imaging for whom cumulative radiation dose must be kept as low as reasonably achievable. PET/MRI also offers interesting opportunities for use of dual modality probes. Upon clear definition of clinical utility, other important and practical issues related to business operational model, clinical workflow and reimbursement will also be resolved. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Feasibility of streamlining an interactive Bayesian-based diagnostic support tool designed for clinical practice

NASA Astrophysics Data System (ADS)

Chen, Po-Hao; Botzolakis, Emmanuel; Mohan, Suyash; Bryan, R. N.; Cook, Tessa

2016-03-01

In radiology, diagnostic errors occur either through the failure of detection or incorrect interpretation. Errors are estimated to occur in 30-35% of all exams and contribute to 40-54% of medical malpractice litigations. In this work, we focus on reducing incorrect interpretation of known imaging features. Existing literature categorizes cognitive bias leading a radiologist to an incorrect diagnosis despite having correctly recognized the abnormal imaging features: anchoring bias, framing effect, availability bias, and premature closure. Computational methods make a unique contribution, as they do not exhibit the same cognitive biases as a human. Bayesian networks formalize the diagnostic process. They modify pre-test diagnostic probabilities using clinical and imaging features, arriving at a post-test probability for each possible diagnosis. To translate Bayesian networks to clinical practice, we implemented an entirely web-based open-source software tool. In this tool, the radiologist first selects a network of choice (e.g. basal ganglia). Then, large, clearly labeled buttons displaying salient imaging features are displayed on the screen serving both as a checklist and for input. As the radiologist inputs the value of an extracted imaging feature, the conditional probabilities of each possible diagnosis are updated. The software presents its level of diagnostic discrimination using a Pareto distribution chart, updated with each additional imaging feature. Active collaboration with the clinical radiologist is a feasible approach to software design and leads to design decisions closely coupling the complex mathematics of conditional probability in Bayesian networks with practice.

A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers.

PubMed

Berger, Ashton C; Korkut, Anil; Kanchi, Rupa S; Hegde, Apurva M; Lenoir, Walter; Liu, Wenbin; Liu, Yuexin; Fan, Huihui; Shen, Hui; Ravikumar, Visweswaran; Rao, Arvind; Schultz, Andre; Li, Xubin; Sumazin, Pavel; Williams, Cecilia; Mestdagh, Pieter; Gunaratne, Preethi H; Yau, Christina; Bowlby, Reanne; Robertson, A Gordon; Tiezzi, Daniel G; Wang, Chen; Cherniack, Andrew D; Godwin, Andrew K; Kuderer, Nicole M; Rader, Janet S; Zuna, Rosemary E; Sood, Anil K; Lazar, Alexander J; Ojesina, Akinyemi I; Adebamowo, Clement; Adebamowo, Sally N; Baggerly, Keith A; Chen, Ting-Wen; Chiu, Hua-Sheng; Lefever, Steve; Liu, Liang; MacKenzie, Karen; Orsulic, Sandra; Roszik, Jason; Shelley, Carl Simon; Song, Qianqian; Vellano, Christopher P; Wentzensen, Nicolas; Weinstein, John N; Mills, Gordon B; Levine, Douglas A; Akbani, Rehan

2018-04-09

We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks. Pathway analysis identified subtypes with high leukocyte infiltration, raising potential implications for immunotherapy. Using 16 key molecular features, we identified five prognostic subtypes and developed a decision tree that classified patients into the subtypes based on just six features that are assessable in clinical laboratories. Copyright © 2018 Elsevier Inc. All rights reserved.

The Physics and Mathematics of MRI

NASA Astrophysics Data System (ADS)

Ansorge, Richard; Graves, Martin

2016-10-01

Magnetic Resonance Imaging is a very important clinical imaging tool. It combines different fields of physics and engineering in a uniquely complex way. MRI is also surprisingly versatile, `pulse sequences' can be designed to yield many different types of contrast. This versatility is unique to MRI. This short book gives both an in depth account of the methods used for the operation and construction of modern MRI systems and also the principles of sequence design and many examples of applications. An important additional feature of this book is the detailed discussion of the mathematical principles used in building optimal MRI systems and for sequence design. The mathematical discussion is very suitable for undergraduates attending medical physics courses. It is also more complete than usually found in alternative books for physical scientists or more clinically orientated works.

A rare case of an aggressive osteoblastoma of the squamous temporal bone: a unique presentation with literature review.

PubMed

Mohanty, Sujata; Rani, Amita; Urs, A B; Dabas, Jitender

2014-10-01

Aggressive osteoblastoma is a rare osteoid tissue forming tumour commonly affecting the spine with predilection for the posterior elements. Calvarial involvement is extremely rare with only two reported cases in the literature. Due to its overlapping clinical, radiographic and histological features with ossifying fibroma, benign osteoblastoma and osteosarcoma, it is very difficult accurately to diagnose this lesion at an early stage. A rare case of an aggressive osteoblastoma of the squamous temporal bone in a young male is presented here which was misdiagnosed twice before reaching the final diagnosis by correlating clinical, radiographic and histopathological features. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Progesterone for Neuroprotection in Pediatric Traumatic Brain Injury

PubMed Central

Robertson, Courtney L.; Fidan, Emin; Stanley, Rachel M.; MHSA; Noje, Corina; Bayir, Hülya

2016-01-01

Objective To provide an overview of the preclinical literature on progesterone for neuroprotection after traumatic brain injury (TBI), and to describe unique features of developmental brain injury that should be considered when evaluating the therapeutic potential for progesterone treatment after pediatric TBI. Data Sources National Library of Medicine PubMed literature review. Data Selection The mechanisms of neuroprotection by progesterone are reviewed, and the preclinical literature using progesterone treatment in adult animal models of TBI are summarized. Unique features of the developing brain that could either enhance or limit the efficacy of neuroprotection by progesterone are discussed, and the limited preclinical literature using progesterone after acute injury to the developing brain is described. Finally, the current status of clinical trials of progesterone for adult TBI is reviewed. Data Extraction and Synthesis Progesterone is a pleotropic agent with beneficial effects on secondary injury cascades that occur after TBI, including cerebral edema, neuroinflammation, oxidative stress, and excitotoxicity. More than 40 studies have used progesterone for treatment after TBI in adult animal models, with results summarized in tabular form. However, very few studies have evaluated progesterone in pediatric animal models of brain injury. To date, two human Phase II trials of progesterone for adult TBI have been published, and two multi-center Phase III trials are underway. Conclusions The unique features of the developing brain from that of a mature adult brain make it necessary to independently study progesterone in clinically relevant, immature animal models of TBI. Additional preclinical studies could lead to the development of a novel neuroprotective therapy that could reduce the long-term disability in head-injured children, and could potentially provide benefit in other forms of pediatric brain injury (global ischemia, stroke, statue epilepticus). PMID:25581631

Diagnostic Dilemma: Cerebellopontine Angle Lipoma Versus Dermoid Cyst

PubMed Central

Bertot, Brandon; Boghani, Zain; Britz, Gavin

2017-01-01

Both lipomas and dermoid cysts of the cerebellopontine angle are rare tumors. These tumors differ in their embryological origin but share similar features on imaging. Both of these congenital lesions can be found in the cerebellopontine angle (CPA), and symptomatic clinical presentation is dictated by the location of the lesion. This paper demonstrates a unique case in which a CPA lipoma was misidentified as a dermoid cyst, leading to surgical intervention. Further, the paper provides a literature review of CPA lipomas and dermoid cysts to aid readers in further differentiating between these two unique tumors. PMID:29399424

Indolent small intestinal CD4+ T-cell lymphoma is a distinct entity with unique biologic and clinical features.

PubMed

Margolskee, Elizabeth; Jobanputra, Vaidehi; Lewis, Suzanne K; Alobeid, Bachir; Green, Peter H R; Bhagat, Govind

2013-01-01

Enteropathy-associated T-cell lymphomas (EATL) are rare and generally aggressive types of peripheral T-cell lymphomas. Rare cases of primary, small intestinal CD4+ T-cell lymphomas with indolent behavior have been described, but are not well characterized. We describe morphologic, phenotypic, genomic and clinical features of 3 cases of indolent primary small intestinal CD4+ T-cell lymphomas. All patients presented with diarrhea and weight loss and were diagnosed with celiac disease refractory to a gluten free diet at referring institutions. Small intestinal biopsies showed crypt hyperplasia, villous atrophy and a dense lamina propria infiltrate of small-sized CD4+ T-cells often with CD7 downregulation or loss. Gastric and colonic involvement was also detected (n = 2 each). Persistent, clonal TCRβ gene rearrangement products were detected at multiple sites. SNP array analysis showed relative genomic stability, early in disease course, and non-recurrent genetic abnormalities, but complex changes were seen at disease transformation (n = 1). Two patients are alive with persistent disease (4.6 and 2.5 years post-diagnosis), despite immunomodulatory therapy; one died due to bowel perforation related to large cell transformation 11 years post-diagnosis. Unique pathobiologic features warrant designation of indolent small intestinal CD4+ T-cell lymphoma as a distinct entity, greater awareness of which would avoid misdiagnosis as EATL or an inflammatory disorder, especially celiac disease.

Concise Review: The Periosteum: Tapping into a Reservoir of Clinically Useful Progenitor Cells

PubMed Central

Chang, Hana

2012-01-01

Elucidation of the periosteum and its regenerative potential has become a hot topic in orthopedics. Yet few review articles address the unique features of periosteum-derived cells, particularly in light of translational therapies and engineering solutions inspired by the periosteum's remarkable regenerative capacity. This review strives to define periosteum-derived cells in light of cumulative research in the field; in addition, it addresses clinical translation of current insights, hurdles to advancement, and open questions in the field. First, we examine the periosteal niche and its inhabitant cells and the key characteristics of these cells in the context of mesenchymal stem cells and their relevance for clinical translation. We compare periosteum-derived cells with those derived from the marrow niche in in vivo studies, addressing commonalities as well as features unique to periosteum cells that make them potentially ideal candidates for clinical application. Thereafter, we review the differentiation and tissue-building properties of periosteum cells in vitro, evaluating their efficacy in comparison with marrow-derived cells. Finally, we address a new concept of banking periosteum and periosteum-derived cells as a novel alternative to currently available autogenic umbilical blood and perinatal tissue sources of stem cells for today's population of aging adults who were “born too early” to bank their own perinatal tissues. Elucidating similarities and differences inherent to multipotent cells from distinct tissue niches and their differentiation and tissue regeneration capacities will facilitate the use of such cells and their translation to regenerative medicine. PMID:23197852

Network Analysis of Associations between Serum Interferon Alpha Activity, Autoantibodies, and Clinical Features in Systemic Lupus Erythematosus

PubMed Central

Weckerle, Corinna E.; Franek, Beverly S.; Kelly, Jennifer A.; Kumabe, Marissa; Mikolaitis, Rachel A.; Green, Stephanie L.; Utset, Tammy O.; Jolly, Meenakshi; James, Judith A.; Harley, John B.; Niewold, Timothy B.

2010-01-01

Background Interferon-alpha (IFN-α) is a primary pathogenic factor in systemic lupus erythematosus (SLE), and high IFN-α levels may be associated with particular clinical manifestations. The prevalence of individual clinical and serologic features differs significantly by ancestry. We used multivariate and network analyses to detect associations between clinical and serologic disease manifestations and serum IFN-α activity in a large diverse SLE cohort. Methods 1089 SLE patients were studied (387 African-American, 186 Hispanic-American, and 516 European-American). Presence or absence of ACR clinical criteria for SLE, autoantibodies, and serum IFN-α activity data were analyzed in univariate and multivariate models. Iterative multivariate logistic regression was performed in each background separately to establish the network of associations between variables that were independently significant following Bonferroni correction. Results In all ancestral backgrounds, high IFN-α activity was associated with anti-Ro and anti-dsDNA antibodies (p-values 4.6×10−18 and 2.9 × 10−16 respectively). Younger age, non-European ancestry, and anti-RNP were also independently associated with increased serum IFN-α activity (p≤6.7×10−4). We found 14 unique associations between variables in network analysis, and only 7 of these associations were shared by more than one ancestral background. Associations between clinical criteria were different in different ancestral backgrounds, while autoantibody-IFN-α relationships were similar across backgrounds. IFN-α activity and autoantibodies were not associated with ACR clinical features in multivariate models. Conclusions Serum IFN-α activity was strongly and consistently associated with autoantibodies, and not independently associated with clinical features in SLE. IFN-α may be more relevant to humoral tolerance and initial pathogenesis than later clinical disease manifestations. PMID:21162028

Nanoparticles for Cardiovascular Imaging and Therapeutic Delivery, Part 1: Compositions and Features.

PubMed

Stendahl, John C; Sinusas, Albert J

2015-10-01

Imaging agents made from nanoparticles are functionally versatile and have unique properties that may translate to clinical utility in several key cardiovascular imaging niches. Nanoparticles exhibit size-based circulation, biodistribution, and elimination properties different from those of small molecules and microparticles. In addition, nanoparticles provide versatile platforms that can be engineered to create both multimodal and multifunctional imaging agents with tunable properties. With these features, nanoparticulate imaging agents can facilitate fusion of high-sensitivity and high-resolution imaging modalities and selectively bind tissues for targeted molecular imaging and therapeutic delivery. Despite their intriguing attributes, nanoparticulate imaging agents have thus far achieved only limited clinical use. The reasons for this restricted advancement include an evolving scope of applications, the simplicity and effectiveness of existing small-molecule agents, pharmacokinetic limitations, safety concerns, and a complex regulatory environment. This review describes general features of nanoparticulate imaging agents and therapeutics and discusses challenges associated with clinical translation. A second, related review to appear in a subsequent issue of JNM highlights nuclear-based nanoparticulate probes in preclinical cardiovascular imaging. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Hyperhidrosis in naïve purpose-bred beagle dogs (Canis familiaris).

PubMed

Carrier, Catherine A; Seeman, Jennifer L; Hoffmann, Guenther

2011-05-01

This case study details the unusual clinical findings in a unique paw-pad disorder that recently emerged among 2 male and 1 female naïve purpose-bred beagle dogs (Canis familiaris) newly received into our facility. During acclimation period physical examinations, the affected dogs demonstrated constantly moist, soft paw pads on all 4 feet. No information was available regarding the epidemiology and pathogenesis of this pad condition in beagle dogs. Here, we report the results of physical examination, clinical chemistry analysis, hematology, histopathology, detailed observations, and novel testing techniques performed during the acclimation period. Histopathology of several sections of affected footpads was compared with that of an age-matched dog with clinically normal paw pads. We describe the morphologic features of a distinctive cutaneous canine footpad condition and discuss the possible differential diagnoses. The histologic and clinical features were most consistent with those of hyperhidrosis; to our knowledge, this report is the first description of hyperhidrosis as a distinct condition in purpose-bred beagle dogs.

Hyperhidrosis in Naïve Purpose-Bred Beagle Dogs (Canis familiaris)

PubMed Central

Carrier, Catherine A; Seeman, Jennifer L; Hoffmann, Guenther

2011-01-01

This case study details the unusual clinical findings in a unique paw-pad disorder that recently emerged among 2 male and 1 female naïve purpose-bred beagle dogs (Canis familiaris) newly received into our facility. During acclimation period physical examinations, the affected dogs demonstrated constantly moist, soft paw pads on all 4 feet. No information was available regarding the epidemiology and pathogenesis of this pad condition in beagle dogs. Here, we report the results of physical examination, clinical chemistry analysis, hematology, histopathology, detailed observations, and novel testing techniques performed during the acclimation period. Histopathology of several sections of affected footpads was compared with that of an age-matched dog with clinically normal paw pads. We describe the morphologic features of a distinctive cutaneous canine footpad condition and discuss the possible differential diagnoses. The histologic and clinical features were most consistent with those of hyperhidrosis; to our knowledge, this report is the first description of hyperhidrosis as a distinct condition in purpose-bred beagle dogs. PMID:21640037

MicroRNA Gene Regulatory Networks in Peripheral Nerve Sheath Tumors

DTIC Science & Technology

2012-09-01

chondrosarcoma are identified based on the unique histology, cell of origin, clinical features and site distribution. The following are the major... Chondrosarcoma Chondrosarcoma is a cancer composed of cells derived from transformed cells that produce cartilage. Peripheral chondrosarcoma is a malignant...biosynthesis. This is in line with gene expression analyses previously performed in osteochondroma and chondrosarcoma samples showing modulation of

Unusual presentation of childhood Systemic Lupus Erythematosus

PubMed Central

Kumar, Sathish; Agarwal, Indira

2007-01-01

Bullous systemic lupus erythematosus is a rare blistering condition with a distinctive combination of clinical, histological and immunopathologic features that together constitute a unique bullous disease phenotype. It is often associated with autoimmunity to type VII collagen. Here we report a child who presented with bullous systemic lupus erythematosus. Rapid resolution of the blisters occurred following treatment with dapsone. PMID:18028550

Primary milia localized to the vulva.

PubMed

Adotama, Prince; Susa, Joseph; Glass, Donald A

2014-04-16

Multiple primary milia were found on the vulva of a 52-year-old woman who was referred to the dermatology clinic by her gynecologist. These lesions are commonly distributed on the face and rarely occur in this location without antecedent trauma. This report demonstrates the unique presentation of primary milia in the genital region and explores the diagnostic features and treatment methods of these lesions.

Use of Animal Models to Develop Antiaddiction Medications

PubMed Central

Gardner, Eliot L.

2008-01-01

Although addiction is a uniquely human phenomenon, some of its pathognomonic features can be modeled at the animal level. Such features include the euphoric “high” produced by acute administration of addictive drugs; the dysphoric “crash” produced by acute withdrawal, drug-seeking, and drug-taking behaviors; and relapse to drug-seeking behavior after achieving successful abstinence. Animal models exist for each of these features. In this review, I focus on various animal models of addiction and how they can be used to search for clinically effective antiaddiction medications. I conclude by noting some of the new and novel medications that have been developed preclinically using such models and the hope for further developments along such lines. PMID:18803910

Addressing narcissistic personality features in the context of medical care: integrating diverse perspectives to inform clinical practice.

PubMed

Magidson, J F; Collado-Rodriguez, A; Madan, A; Perez-Camoirano, N A; Galloway, S K; Borckardt, J J; Campbell, W K; Miller, J D

2012-04-01

Narcissistic personality disorder (NPD) is characterized by an unrealistic need for admiration, lack of empathy toward others, and feelings of superiority. NPD presents a unique and significant challenge in clinical practice, particularly in medical settings with limited provider contact time, as health professionals treat individuals who often require excessive admiration and have competing treatment needs. This practice review highlights real case examples across three distinct medically oriented clinical settings (inpatient and outpatient behavioral medicine and a Level I trauma center) to demonstrate the difficult and compromising situations that providers face when treating patients with general medical conditions and comorbid narcissistic personality features. The main goal of this article is to discuss the various challenges and obstacles associated with these cases in medical settings and discuss some strategies that may prove successful. A second goal is to bridge diverse conceptualizations of narcissism/NPD through the discussion of theoretical and empirical perspectives that can inform understanding of the clinical examples. Despite differing perspectives regarding the underlying motivation of narcissistic behavior, this practice review highlights that these paradigms can be integrated when sharing the same ultimate goal: to improve delivery of care across medically oriented clinical settings for patients with narcissistic features.

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

PubMed

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

2013-06-01

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

A pediatric intramedullary spinal cord tumor with unusual solid-cystic and papillary features: a case report.

PubMed

Iwasaki, Takeshi; Kato, Masako; Horie, Yasushi; Kato, Shinsuke; Akatsuka, Keiichi; Watanabe, Takashi; Kuwamoto, Satoshi; Murakami, Ichiro; Hayashi, Kazuhiko

2011-12-01

Spinal cord tumors are rare in children. We report a novel case of pediatric intramedullary spinal cord tumor with unusual solid-cystic and papillary features. Clinically, the patient presented at the age of 3 years with motor deficit and urinary incontinence, and MRI demonstrated multilocular cystic lesions in the thoracic spine. Histologically the tumor consisted of solid, sheet-like components and branching papillary structures, and immunohistochemistry demonstrated positive reactivity for epithelial membrane antigen, cytokeratins (7, AE1/3, CAM5.2), E-cadherin and transthyretin, and negativity for GFAP, S-100 protein, synaptophysin and neurofilament. These histological and immunohistochemical findings appeared to be unique, and were not compatible with the features of classical ependymoma or choroid plexus papilloma. The clinical behavior, characterized by relatively rapid tumor regrowth after surgical resection and a relatively high MIB-1 labeling index, suggest that this tumor might have had moderate malignant potential. This pediatric case appears to be particularly informative with regard to the tumor biology or tumorigenesis of intramedullary spinal cord tumor with unusual solid-cystic and papillary features. © 2011 Japanese Society of Neuropathology.

Neurologic and developmental features of the Smith-Magenis syndrome (del 17p11.2).

PubMed

Gropman, Andrea L; Duncan, Wallace C; Smith, Ann C M

2006-05-01

The Smith-Magenis syndrome is a rare, complex multisystemic disorder featuring, mental retardation and multiple congenital anomalies caused by a heterozygous interstitial deletion of chromosome 17p11.2. The phenotype of Smith-Magenis syndrome is characterized by a distinct pattern of features including infantile hypotonia, generalized complacency and lethargy in infancy, minor skeletal (brachycephaly, brachydactyly) and craniofacial features, ocular abnormalities, middle ear and laryngeal abnormalities including hoarse voice, as well as marked early expressive speech and language delays, psychomotor and growth retardation, and a 24-hour sleep disturbance. A striking neurobehavioral pattern of stereotypies, hyperactivity, polyembolokoilamania, onychotillomania, maladaptive and self-injurious and aggressive behavior is observed with increasing age. The diagnosis of Smith-Magenis syndrome is based upon the clinical recognition of a constellation of physical, developmental, and behavioral features in combination with a sleep disorder characterized by inverted circadian rhythm of melatonin secretion. Many of the features of Smith-Magenis syndrome are subtle in infancy and early childhood, and become more recognizable with advancing age. Infants are described as looking "cherubic" with a Down syndrome-like appearance, whereas with age the facial appearance is that of relative prognathism. Early diagnosis requires awareness of the often subtle clinical and neurobehavioral phenotype of the infant period. Speech delay with or without hearing loss is common. Most children are diagnosed in mid-childhood when the features of the disorder are most recognizable and striking. While improvements in cytogenetic analysis help to bring cases to clinical recognition at an earlier age, this review seeks to increase clinical awareness about Smith-Magenis syndrome by presenting the salient features observed at different ages including descriptions of the neurologic and behavioral features. Detailed review of the circadian rhythm disturbance unique to Smith-Magenis syndrome is presented. Suggestions for management of the behavioral and sleep difficulties are discussed in the context of the authors' personal experience in the setting of an ongoing Smith-Magenis syndrome natural history study.

Trigger learning and ECG parameter customization for remote cardiac clinical care information system.

PubMed

Bashir, Mohamed Ezzeldin A; Lee, Dong Gyu; Li, Meijing; Bae, Jang-Whan; Shon, Ho Sun; Cho, Myung Chan; Ryu, Keun Ho

2012-07-01

Coronary heart disease is being identified as the largest single cause of death along the world. The aim of a cardiac clinical information system is to achieve the best possible diagnosis of cardiac arrhythmias by electronic data processing. Cardiac information system that is designed to offer remote monitoring of patient who needed continues follow up is demanding. However, intra- and interpatient electrocardiogram (ECG) morphological descriptors are varying through the time as well as the computational limits pose significant challenges for practical implementations. The former requires that the classification model be adjusted continuously, and the latter requires a reduction in the number and types of ECG features, and thus, the computational burden, necessary to classify different arrhythmias. We propose the use of adaptive learning to automatically train the classifier on up-to-date ECG data, and employ adaptive feature selection to define unique feature subsets pertinent to different types of arrhythmia. Experimental results show that this hybrid technique outperforms conventional approaches and is, therefore, a promising new intelligent diagnostic tool.

Targeted and Nontargeted α-Particle Therapies.

PubMed

McDevitt, Michael R; Sgouros, George; Sofou, Stavroula

2018-06-04

α-Particle irradiation of cancerous tissue is increasingly recognized as a potent therapeutic option. We briefly review the physics, radiobiology, and dosimetry of α-particle emitters, as well as the distinguishing features that make them unique for radiopharmaceutical therapy. We also review the emerging clinical role of α-particle therapy in managing cancer and recent studies on in vitro and preclinical α-particle therapy delivered by antibodies, other small molecules, and nanometer-sized particles. In addition to their unique radiopharmaceutical characteristics, the increased availability and improved radiochemistry of α-particle radionuclides have contributed to the growing recent interest in α-particle radiotherapy. Targeted therapy strategies have presented novel possibilities for the use of α-particles in the treatment of cancer. Clinical experience has already demonstrated the safe and effective use of α-particle emitters as potent tumor-selective drugs for the treatment of leukemia and metastatic disease.

Targeted and Nontargeted α-Particle Therapies

PubMed Central

McDevitt, Michael R.; Sgouros, George; Sofou, Stavroula

2018-01-01

α-Particle irradiation of cancerous tissue is increasingly recognized as a potent therapeutic option. We briefly review the physics, radiobiology, and dosimetry of α-particle emitters, as well as the distinguishing features that make them unique for radiopharmaceutical therapy. We also review the emerging clinical role of α-particle therapy in managing cancer and recent studies on in vitro and preclinical α-particle therapy delivered by antibodies, other small molecules, and nanometer-sized particles. In addition to their unique radiopharmaceutical characteristics, the increased availability and improved radiochemistry of α-particle radionuclides have contributed to the growing recent interest in α-particle radiotherapy. Targeted therapy strategies have presented novel possibilities for the use of α-particles in the treatment of cancer. Clinical experience has already demonstrated the safe and effective use of α-particle emitters as potent tumor-selective drugs for the treatment of leukemia and metastatic disease. PMID:29345977

Interface, information, interaction: a narrative review of design and functional requirements for clinical decision support.

PubMed

Miller, Kristen; Mosby, Danielle; Capan, Muge; Kowalski, Rebecca; Ratwani, Raj; Noaiseh, Yaman; Kraft, Rachel; Schwartz, Sanford; Weintraub, William S; Arnold, Ryan

2018-05-01

Provider acceptance and associated patient outcomes are widely discussed in the evaluation of clinical decision support systems (CDSSs), but critical design criteria for tools have generally been overlooked. The objective of this work is to inform electronic health record alert optimization and clinical practice workflow by identifying, compiling, and reporting design recommendations for CDSS to support the efficient, effective, and timely delivery of high-quality care. A narrative review was conducted from 2000 to 2016 in PubMed and The Journal of Human Factors and Ergonomics Society to identify papers that discussed/recommended design features of CDSSs that are associated with the success of these systems. Fourteen papers were included as meeting the criteria and were found to have a total of 42 unique recommendations; 11 were classified as interface features, 10 as information features, and 21 as interaction features. Features are defined and described, providing actionable guidance that can be applied to CDSS development and policy. To our knowledge, no reviews have been completed that discuss/recommend design features of CDSS at this scale, and thus we found that this was important for the body of literature. The recommendations identified in this narrative review will help to optimize design, organization, management, presentation, and utilization of information through presentation, content, and function. The designation of 3 categories (interface, information, and interaction) should be further evaluated to determine the critical importance of the categories. Future work will determine how to prioritize them with limited resources for designers and developers in order to maximize the clinical utility of CDSS. This review will expand the field of knowledge and provide a novel organization structure to identify key recommendations for CDSS.

Pathological features of polyneuropathy in three dogs.

PubMed

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

2013-01-01

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

Basal cell carcinoma induced by therapeutic radiation for tinea capitis-clinicopathological study.

PubMed

Oshinsky, Shlomit; Baum, Sharon; Huszar, Monica; Debby, Assaf; Barzilai, Aviv

2018-02-21

An increased prevalence of aggressive histological subtypes, such as micronodular and morpheaform, has been seen, irrespective of the clinical course, in basal cell carcinoma (BCC) following irradiation for tinea capitis. The aim of this study was to assess the histopathological features of BCCs among patients irradiated for tinea capitis and correlate them with the clinical course. The medical records and BCC biopsy specimens of individuals who were previously irradiated for tinea capitis were reviewed. Demographic data and clinical characteristics were retrieved. Biopsy specimens were evaluated for histological subtype classification and additional histopathological features. A telephone survey was conducted to assess the clinical behaviour of the tumours. Thirty-one patients (17 male; 14 female) were included. The average age at time of first biopsy was 56 years. The total number of lesions was 185, with 80% of subjects showing multiple lesions. The nodular subtype was the most prevalent, followed by superficial, micronodular and mixed tumours. One-third of the BCCs could be classified as aggressive histologically. Stromal fibroplasia and melanin deposits were common. There was no mortality related to BCC. None of the 17 patients who completed the survey had evidence of local invasiveness or metastases. BCCs following radiation therapy for tinea capitis show unique histological characteristics related to aggressive behaviour. These aggressive features did not reflect the clinical behaviour in the current cohort. © 2018 John Wiley & Sons Ltd.

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

PubMed

Shimizu, Jun; Mimori, Tsuneyo

2014-01-01

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

Prevalence of Posttraumatic Stress Disorder in Remotely Piloted Aircraft Operators in the United States Air Force

DTIC Science & Technology

2016-05-24

common feature of the depressive and anxiety disorders: a test of the revised integrative hierarchical model in a national sample. J Abnorm Psychol...proliferation of this unique form of warfare, concerns have been raised regarding the psychological impact such operations have on RPA operators directly...and clinical interviews utilizing the Clinician Administered Psychological Survey to determine the nature of the respondents’ stressful military

Cognitive and motor symptoms in dementia: focus on dementia with Lewy bodies.

PubMed

Lingler, Jennifer Hagerty; Kaufer, Daniel I

2002-09-01

To describe the clinical syndrome called dementia with Lewy bodies (DLB) and highlight its common and unique characteristics with respect to diagnosis and management. Review of the scientific literature including psychiatric literature, reports of clinical trials, and clinical practice guidelines. DLB is a clinical and histopathologic disease, which is second only to Alzheimer's disease (AD) as a cause of dementia in older adults. The clinical syndrome of DLB includes cognitive and motor deterioration reminiscent of symptoms associated with AD and Parkinson's disease (PD) respectively. The late life intersection of cognitive and motor symptoms can present significant challenges in the primary care setting. Recognizing key features of common neurodegenerative disorders is essential to accurately diagnosing and appropriately treating the growing population of older adults who suffer from AD, PD, and DLB.

A clinically viable capsule endoscopy video analysis platform for automatic bleeding detection

NASA Astrophysics Data System (ADS)

Yi, Steven; Jiao, Heng; Xie, Jean; Mui, Peter; Leighton, Jonathan A.; Pasha, Shabana; Rentz, Lauri; Abedi, Mahmood

2013-02-01

In this paper, we present a novel and clinically valuable software platform for automatic bleeding detection on gastrointestinal (GI) tract from Capsule Endoscopy (CE) videos. Typical CE videos for GI tract run about 8 hours and are manually reviewed by physicians to locate diseases such as bleedings and polyps. As a result, the process is time consuming and is prone to disease miss-finding. While researchers have made efforts to automate this process, however, no clinically acceptable software is available on the marketplace today. Working with our collaborators, we have developed a clinically viable software platform called GISentinel for fully automated GI tract bleeding detection and classification. Major functional modules of the SW include: the innovative graph based NCut segmentation algorithm, the unique feature selection and validation method (e.g. illumination invariant features, color independent features, and symmetrical texture features), and the cascade SVM classification for handling various GI tract scenes (e.g. normal tissue, food particles, bubbles, fluid, and specular reflection). Initial evaluation results on the SW have shown zero bleeding instance miss-finding rate and 4.03% false alarm rate. This work is part of our innovative 2D/3D based GI tract disease detection software platform. While the overall SW framework is designed for intelligent finding and classification of major GI tract diseases such as bleeding, ulcer, and polyp from the CE videos, this paper will focus on the automatic bleeding detection functional module.

PET image reconstruction using multi-parametric anato-functional priors

NASA Astrophysics Data System (ADS)

Mehranian, Abolfazl; Belzunce, Martin A.; Niccolini, Flavia; Politis, Marios; Prieto, Claudia; Turkheimer, Federico; Hammers, Alexander; Reader, Andrew J.

2017-08-01

In this study, we investigate the application of multi-parametric anato-functional (MR-PET) priors for the maximum a posteriori (MAP) reconstruction of brain PET data in order to address the limitations of the conventional anatomical priors in the presence of PET-MR mismatches. In addition to partial volume correction benefits, the suitability of these priors for reconstruction of low-count PET data is also introduced and demonstrated, comparing to standard maximum-likelihood (ML) reconstruction of high-count data. The conventional local Tikhonov and total variation (TV) priors and current state-of-the-art anatomical priors including the Kaipio, non-local Tikhonov prior with Bowsher and Gaussian similarity kernels are investigated and presented in a unified framework. The Gaussian kernels are calculated using both voxel- and patch-based feature vectors. To cope with PET and MR mismatches, the Bowsher and Gaussian priors are extended to multi-parametric priors. In addition, we propose a modified joint Burg entropy prior that by definition exploits all parametric information in the MAP reconstruction of PET data. The performance of the priors was extensively evaluated using 3D simulations and two clinical brain datasets of [18F]florbetaben and [18F]FDG radiotracers. For simulations, several anato-functional mismatches were intentionally introduced between the PET and MR images, and furthermore, for the FDG clinical dataset, two PET-unique active tumours were embedded in the PET data. Our simulation results showed that the joint Burg entropy prior far outperformed the conventional anatomical priors in terms of preserving PET unique lesions, while still reconstructing functional boundaries with corresponding MR boundaries. In addition, the multi-parametric extension of the Gaussian and Bowsher priors led to enhanced preservation of edge and PET unique features and also an improved bias-variance performance. In agreement with the simulation results, the clinical results also showed that the Gaussian prior with voxel-based feature vectors, the Bowsher and the joint Burg entropy priors were the best performing priors. However, for the FDG dataset with simulated tumours, the TV and proposed priors were capable of preserving the PET-unique tumours. Finally, an important outcome was the demonstration that the MAP reconstruction of a low-count FDG PET dataset using the proposed joint entropy prior can lead to comparable image quality to a conventional ML reconstruction with up to 5 times more counts. In conclusion, multi-parametric anato-functional priors provide a solution to address the pitfalls of the conventional priors and are therefore likely to increase the diagnostic confidence in MR-guided PET image reconstructions.

[Golimumab].

PubMed

Hayashi, Taichi

2013-07-01

Golimumab is one of the TNF-inhibitors, having an efficacy and safety profile comparable to other TNF-inhibitors. In addition, golimumab is a fully human monoclonal antibody, has several unique features, such as neutralizing antibodies are difficult to generate. In clinical trials carried out in Japan, the efficacy and safety of administration of golimumab 100 mg every 4 weeks is shown, and golimumab blood concentration related to efficacy have been pointed out. From these, golimumab is considered a useful drug in every step of the treatment of rheumatoid arthritis. This section reviews the clinical trials of golimumab, and consider the useful use of golimumab.

Innovative strategies for early clinical R&D.

PubMed

Butz, Robert F; Morelli, Gaetano

2008-01-01

Developments in translational medicine and regulatory initiatives associated with the FDA's Critical Path Initiative are creating new opportunities for innovation in early clinical R&D. The introduction of the exploratory IND process allows small, 'phase 0' clinical trials to be conducted prior to traditional phase I trials - sometimes requiring considerably less chemistry, manufacturing and controls, or preclinical support. Phase 0 clinical trials involving subtherapeutic, yet pharmacologically active, dose levels can provide an early demonstration of clinical proof of concept; such demonstration is of particular importance to small pharmaceutical and early-stage biotechnology companies. However, these opportunities for rapid entry into the clinic must be balanced by a consideration of the unique risks associated with first-in-human clinical trials, and by accounting for public concerns regarding drug safety in general. This feature review discusses how innovative clinical strategies can be used effectively in early drug development.

Dual Candida albicans and Cryptococcus neoformans fungaemia in an AIDS presenter: a unique disease association in the highly active antiretroviral therapy (HAART) era.

PubMed

Manfredi, Roberto; Calza, Leonardo; Chiodo, Francesco

2002-12-01

A case report of a patient who discovered his HIV infection concurrently with an advanced immunodeficiency and a dual Candida albicans and Cryptococcus neoformans fungaemia is discussed with reference to the changing epidemiology and clinical features of HIV infection and AIDS in the highly active antiretroviral therapy (HAART) era. The tendency to develop multiple concomitant AIDS-defining illnesses at the time of first hospitalisation seems to be an increasing feature in patients who remain unaware of or neglect their HIV disease and who are still at risk of opportunist infections even with the availability of HAART.

Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan.

PubMed

Teede, H; Deeks, A; Moran, L

2010-06-30

Polycystic ovary syndrome (PCOS) is of clinical and public health importance as it is very common, affecting up to one in five women of reproductive age. It has significant and diverse clinical implications including reproductive (infertility, hyperandrogenism, hirsutism), metabolic (insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, adverse cardiovascular risk profiles) and psychological features (increased anxiety, depression and worsened quality of life). Polycystic ovary syndrome is a heterogeneous condition and, as such, clinical and research agendas are broad and involve many disciplines. The phenotype varies widely depending on life stage, genotype, ethnicity and environmental factors including lifestyle and bodyweight. Importantly, PCOS has unique interactions with the ever increasing obesity prevalence worldwide as obesity-induced insulin resistance significantly exacerbates all the features of PCOS. Furthermore, it has clinical implications across the lifespan and is relevant to related family members with an increased risk for metabolic conditions reported in first-degree relatives. Therapy should focus on both the short and long-term reproductive, metabolic and psychological features. Given the aetiological role of insulin resistance and the impact of obesity on both hyperinsulinaemia and hyperandrogenism, multidisciplinary lifestyle improvement aimed at normalising insulin resistance, improving androgen status and aiding weight management is recognised as a crucial initial treatment strategy. Modest weight loss of 5% to 10% of initial body weight has been demonstrated to improve many of the features of PCOS. Management should focus on support, education, addressing psychological factors and strongly emphasising healthy lifestyle with targeted medical therapy as required. Monitoring and management of long-term metabolic complications is also an important part of routine clinical care. Comprehensive evidence-based guidelines are needed to aid early diagnosis, appropriate investigation, regular screening and treatment of this common condition. Whilst reproductive features of PCOS are well recognised and are covered here, this review focuses primarily on the less appreciated cardiometabolic and psychological features of PCOS.

Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan

PubMed Central

2010-01-01

Polycystic ovary syndrome (PCOS) is of clinical and public health importance as it is very common, affecting up to one in five women of reproductive age. It has significant and diverse clinical implications including reproductive (infertility, hyperandrogenism, hirsutism), metabolic (insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, adverse cardiovascular risk profiles) and psychological features (increased anxiety, depression and worsened quality of life). Polycystic ovary syndrome is a heterogeneous condition and, as such, clinical and research agendas are broad and involve many disciplines. The phenotype varies widely depending on life stage, genotype, ethnicity and environmental factors including lifestyle and bodyweight. Importantly, PCOS has unique interactions with the ever increasing obesity prevalence worldwide as obesity-induced insulin resistance significantly exacerbates all the features of PCOS. Furthermore, it has clinical implications across the lifespan and is relevant to related family members with an increased risk for metabolic conditions reported in first-degree relatives. Therapy should focus on both the short and long-term reproductive, metabolic and psychological features. Given the aetiological role of insulin resistance and the impact of obesity on both hyperinsulinaemia and hyperandrogenism, multidisciplinary lifestyle improvement aimed at normalising insulin resistance, improving androgen status and aiding weight management is recognised as a crucial initial treatment strategy. Modest weight loss of 5% to 10% of initial body weight has been demonstrated to improve many of the features of PCOS. Management should focus on support, education, addressing psychological factors and strongly emphasising healthy lifestyle with targeted medical therapy as required. Monitoring and management of long-term metabolic complications is also an important part of routine clinical care. Comprehensive evidence-based guidelines are needed to aid early diagnosis, appropriate investigation, regular screening and treatment of this common condition. Whilst reproductive features of PCOS are well recognised and are covered here, this review focuses primarily on the less appreciated cardiometabolic and psychological features of PCOS. PMID:20591140

Bronchoalveolar carcinoma: current treatment and future trends.

PubMed

Laskin, Janessa J

2004-12-01

Bronchoalveolar carcinoma (BAC) is a subtype of non-small-cell lung cancer (NSCLC) with unique clinical and pathologic characteristics. The most recent classification system defines BAC as a primary lung cancer that tends to be peripheral and grow in a lepedic fashion along the alveolar septae without parenchymal invasion. Most of the clinical information on BAC comes from retrospective institutional reviews; however, recent studies have focused more specifically on BAC. In particular, clinical trials of molecular-targeted anticancer therapies against the epidermal growth factor receptor have led to a deeper understanding of the distinct features of this cancer and suggest that BAC may require a therapeutic paradigm different from that of other NSCLCs.

The syndrome of perisylvian polymicrogyria with congenital arthrogryposis.

PubMed

Poduri, Annapurna; Chitsazzadeh, Vida; D'Arrigo, Stefano; Fedrizzi, Ermellina; Pantaleoni, Chiara; Riva, Daria; Busse, Claudia; Küster, Helmut; Duplessis, Adre; Gaitanis, John; Sahin, Mustafa; Garganta, Cheryl; Topcu, Meral; Dies, Kira A; Barry, Brenda J; Partlow, Jennifer; Barkovich, A James; Walsh, Christopher A; Chang, Bernard S

2010-08-01

Bilateral perisylvian polymicrogyria (BPP) is a well-recognized malformation of cortical development commonly associated with epilepsy, cognitive impairment, and oromotor apraxia. Reports have suggested the association of BPP with arthrogryposis multiplex congenita. We sought to investigate the clinical, electrophysiological, and neuroradiological features of this combined syndrome to determine if there are unique features that distinguish BPP with arthrogryposis from BPP alone. Cases of BPP with congenital arthrogryposis were identified from a large research database of individuals with polymicrogyria. Clinical features (including oromotor function, seizures, and joint contractures), MR brain imaging, and results of neuromuscular testing were reviewed. Ten cases of BPP with congenital arthrogryposis were identified. Most cases had some degree of oromotor apraxia. Only a few had seizures, but a majority of cases were still young children. Electrophysiological studies provided evidence for lower motor neuron or peripheral nervous system involvement. On brain imaging, bilateral polymicrogyria (PMG) centered along the Sylvian fissures was seen, with variable extension frontally or parietally; no other cortical malformations were present. We did not identify obvious neuroimaging features that distinguish this syndrome from that of BPP without arthrogryposis. The clinical and neuroimaging features of the syndrome of BPP with congenital arthrogryposis appear similar to those seen in cases of isolated BPP without joint contractures, but electrophysiological studies often demonstrate coexistent lower motor neuron or peripheral nervous system pathology. These findings suggest that BPP with arthrogryposis may have a genetic etiology with effects at two levels of the neuraxis. Copyright 2009 Elsevier B.V. All rights reserved.

Multiple Symmetrical Lipomatosis--a mitochondrial disorder of brown fat.

PubMed

Plummer, C; Spring, P J; Marotta, R; Chin, J; Taylor, G; Sharpe, D; Athanasou, N A; Thyagarajan, D; Berkovic, S F

2013-07-01

Multiple Symmetrical Lipomatosis (MSL) is an unusual disorder characterized by the development of axial lipomas in adulthood. The pathoetiology of lipoma tissue in MSL remains unresolved. Seven patients with MSL were followed for a mean period of 12 years (8-20 years). All patients had cervical lipomas ranging from subtle lesions to disfiguring masses; six patients had peripheral neuropathy and five had proximal myopathy. Myoclonus, cerebellar ataxia and additional lipomas were variably present. All patients showed clinical progression. Muscle histopathology was consistent with mitochondrial disease. Five patients were positive for mtDNA point mutation m.8344A>G, three of whom underwent lipoma resection--all samples were positive for uncoupling protein-1 mRNA (unique to brown fat). Lipoma from one case stained positive for adipocyte fatty-acid protein-2 (unique to brown fat and immature adipocytes). This long-term study hallmarks the phenotypic heterogeneity of MSL's associated clinical features. The clinical, genetic and molecular findings substantiate the hypothesis that lipomas in MSL are due to a mitochondrial disorder of brown fat. Copyright © 2013 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Nonaggressive systemic mastocytosis (SM) without skin lesions associated with insect-induced anaphylaxis shows unique features versus other indolent SM.

PubMed

Alvarez-Twose, Iván; Zanotti, Roberta; González-de-Olano, David; Bonadonna, Patrizia; Vega, Arantza; Matito, Almudena; Sánchez-Muñoz, Laura; Morgado, José Mário; Perbellini, Omar; García-Montero, Andrés; De Matteis, Giovanna; Teodósio, Cristina; Rossini, Maurizio; Jara-Acevedo, María; Schena, Donatella; Mayado, Andrea; Zamò, Alberto; Mollejo, Manuela; Sánchez-López, Paula; Cabañes, Nieves; Orfao, Alberto; Escribano, Luis

2014-02-01

Indolent systemic mastocytosis (ISM) without skin lesions (ISMs(-)) shows a higher prevalence in males, lower serum baseline tryptase levels, and KIT mutation more frequently restricted to bone marrow (BM) mast cells (MCs) than ISM with skin lesions (ISMs(+)). Interestingly, in almost one-half of ISMs(-) patients, MC-mediator release episodes are triggered exclusively by insects. We aimed to determine the clinical and laboratory features of ISMs(-) associated with insect-induced anaphylaxis (insectISMs(-)) versus other patients with ISM. A total of 335 patients presenting with MC activation syndrome, including 143 insectISMs(-), 72 ISMs(-) triggered by other factors (otherISMs(-)), 56 ISMs(+), and 64 nonclonal MC activation syndrome, were studied. Compared with otherISMs(-) and ISMs(+) patients, insectISMs(-) cases showed marked male predominance (78% vs 53% and 46%; P < .001), a distinct pattern of MC-related symptoms, and significantly lower median serum baseline tryptase levels (22.4 vs 28.7 and 45.8 μg/L; P ≤ .009). Moreover, insectISMs(-) less frequently presented BM MC aggregates (46% vs 70% and 81%; P ≤ .001), and they systematically showed MC-restricted KIT mutation. ISMs(-) patients with anaphylaxis triggered exclusively by insects display clinical and laboratory features that are significantly different from other ISM cases, including other ISMs(-) and ISMs(+) patients, suggesting that they represent a unique subgroup of ISM with a particularly low BM MC burden in the absence of adverse prognostic factors. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

The clavicle: Normal and abnormal

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

Kumar, R.; Madewell, J.E.; Swischuk, L.E.

1989-07-01

The clavicle is an unusual long bone with many unique embryologic features. It is often involved in congenital and acquired disorders. Traumatic, inflammatory, neoplastic, metabolic and many other miscellaneous lesions may also affect the bone. Because of its ligamentous attachments and the presence of articulations at both ends, the clavicle can also be involved in arthritic diseases. This article illustrates the radiographic manifestations of many of the disorders of the clavicle that are commonly encountered in clinical practice.

Effective, clinically feasible and sustainable: Key design features of psycho-educational and supportive care interventions to promote individualised self-management in cancer care.

PubMed

Schofield, Penelope; Chambers, Suzanne

2015-05-01

As the global burden of cancer increases healthcare services will face increasing challenges in meet the complex needs of these patients, their families and the communities in which they live. This raises the question of how to meet patient need where direct clinical contact may be constrained or not readily available. Patients and families require resources and skills to manage their illness outside of the hospital setting within their own communities. To propose a framework for the development and delivery of psycho-educational and supportive care interventions drawing on theoretical principles of behaviour change and evidence-based interventions, and based on extensive experience in developing and testing complex interventions in oncology. At the core of this intervention framework are considerations of efficiency: interventions are designed to cater for individuals' unique needs; to place minimal demands on the health system infrastructure and to be rapidly disseminated into usual care if successful. There are seven key features: 1) Targeting cancer type and stage; 2) Tailoring to unique individual needs; 3) Promotion of patient self-management of their disease and treatment side effects; 4) Efficient delivery of the intervention; 5) Training and adherence to protocol; 6) Ensuring the intervention is evidence-based; 7) Confirming stakeholder acceptability of the intervention. A case study of a randomised controlled trial which tested psycho-educational oncology interventions using this framework is presented. These interventions were designed to cater for individuals' unique needs and promote self-management while placing minimal demands on the acute health care setting. Innovative ways to realise the potentially major impact that psycho-educational and supportive care interventions can have on psychological morbidity, coping, symptoms and quality of life in serious and chronic illness are needed. This framework, which is driven by theory, evidence, and experience, is designed to ensure that interventions are effective, clinically feasible and sustainable.

Melanotic MiT family translocation neoplasms: Expanding the clinical and molecular spectrum of this unique entity of tumors.

PubMed

Saleeb, Rola M; Srigley, John R; Sweet, Joan; Doucet, Cedric; Royal, Virginie; Chen, Ying-Bei; Brimo, Fadi; Evans, Andrew

2017-11-01

MiT family translocation tumors are a group of neoplasms characterized by translocations involving MiT family transcription factors. The translocation renal cell carcinomas, TFE3 (Xp11.2) and TFEB (t6;11) are known members of this family. Melanotic Xp11 translocation renal cancer is a more recently described entity. To date only 14 cases have been described. It is characterized by a distinct set of features including a nested epithelioid morphology, melanin pigmentation, labeling for markers of melanocytic differentiation, lack of labeling for markers of renal tubular differentiation, predominance in a younger age population and association with aggressive clinical behavior. There are noted similarities between that entity and TFE3 associated PEComas. There are no cases reported of equivalent melanotic TFEB translocation renal cancer. We report 2 rare cases of melanotic translocation renal neoplasms. The first is a melanotic TFE3 translocation renal cancer with an indolent clinical course, occurring in a patient more than 3-decades older than the usual average age in which such tumors have been described. The other case is, to our knowledge, the first reported melanotic TFEB translocation cancer of the kidney. Both cases exhibit the same H&E morphology as previously reported in melanotic translocation renal cancers and label accordingly with HMB45 and Melan-A. While the TFE3 melanotic tumor lacked any evidence of renal tubular differentiation, the TFEB melanotic cancer exhibited some staining for renal tubular markers. Based on the unique features noted above, these two cases expand the clinical and molecular spectrum of the melanotic translocation renal cancers. Copyright © 2017 Elsevier GmbH. All rights reserved.

Acute respiratory infection case definitions for young children: a systematic review of community-based epidemiologic studies in South Asia.

PubMed

Roth, Daniel E; Gaffey, Michelle F; Smith-Romero, Evelyn; Fitzpatrick, Tiffany; Morris, Shaun K

2015-12-01

To explore the variability in childhood acute respiratory infection case definitions for research in low-income settings where there is limited access to laboratory or radiologic investigations. We conducted a systematic review of community-based, longitudinal studies in South Asia published from January 1990 to August 2013, in which childhood acute respiratory infection outcomes were reported. Case definitions were classified by their label (e.g. pneumonia, acute lower respiratory infection) and clinical content 'signatures' (array of clinical features that would be always present, conditionally present or always absent among cases). Case definition heterogeneity was primarily assessed by the number of unique case definitions overall and by label. We also compared case definition-specific acute respiratory infection incidence rates for studies reporting incidence rates for multiple case definitions. In 56 eligible studies, we found 124 acute respiratory infection case definitions. Of 90 case definitions for which clinical content was explicitly defined, 66 (73%) were unique. There was a high degree of content heterogeneity among case definitions with the same label, and some content signatures were assigned multiple labels. Within studies for which incidence rates were reported for multiple case definitions, variation in content was always associated with a change in incidence rate, even when the content differed by a single clinical feature. There has been a wide variability in case definition label and content combinations to define acute upper and lower respiratory infections in children in community-based studies in South Asia over the past two decades. These inconsistencies have important implications for the synthesis and translation of knowledge regarding the prevention and treatment of childhood acute respiratory infection. © 2015 John Wiley & Sons Ltd.

Comprehensive clinical studies in 34 patients with molecularly defined UPD(14)pat and related conditions (Kagami–Ogata syndrome)

PubMed Central

Kagami, Masayo; Kurosawa, Kenji; Miyazaki, Osamu; Ishino, Fumitoshi; Matsuoka, Kentaro; Ogata, Tsutomu

2015-01-01

Paternal uniparental disomy 14 (UPD(14)pat) and epimutations and microdeletions affecting the maternally derived 14q32.2 imprinted region lead to a unique constellation of clinical features such as facial abnormalities, small bell-shaped thorax with a coat-hanger appearance of the ribs, abdominal wall defects, placentomegaly, and polyhydramnios. In this study, we performed comprehensive clinical studies in patients with UPD(14)pat (n=23), epimutations (n=5), and microdeletions (n=6), and revealed several notable findings. First, a unique facial appearance with full cheeks and a protruding philtrum and distinctive chest roentgenograms with increased coat-hanger angles to the ribs constituted the pathognomonic features from infancy through childhood. Second, birth size was well preserved, with a median birth length of ±0 SD (range, −1.7 to +3.0 SD) and a median birth weight of +2.3 SD (range, +0.1 to +8.8 SD). Third, developmental delay and/or intellectual disability was invariably present, with a median developmental/intellectual quotient of 55 (range, 29–70). Fourth, hepatoblastoma was identified in three infantile patients (8.8%), and histological examination in two patients showed a poorly differentiated embryonal hepatoblastoma with focal macrotrabecular lesions and well-differentiated hepatoblastoma, respectively. These findings suggest the necessity of an adequate support for developmental delay and periodical screening for hepatoblastoma in the affected patients, and some phenotypic overlap between UPD(14)pat and related conditions and Beckwith–Wiedemann syndrome. On the basis of our previous and present studies that have made a significant contribution to the clarification of underlying (epi)genetic factors and the definition of clinical findings, we propose the name ‘Kagami–Ogata syndrome' for UPD(14)pat and related conditions. PMID:25689926

Williams syndrome-specific neuroanatomical profile and its associations with behavioral features.

PubMed

Fan, Chun Chieh; Brown, Timothy T; Bartsch, Hauke; Kuperman, Joshua M; Hagler, Donald J; Schork, Andrew; Searcy, Yvonne; Bellugi, Ursula; Halgren, Eric; Dale, Anders M

2017-01-01

Williams Syndrome (WS) is a rare genetic disorder with unique behavioral features. Yet the rareness of WS has limited the number and type of studies that can be conducted in which inferences are made about how neuroanatomical abnormalities mediate behaviors. In this study, we extracted a WS-specific neuroanatomical profile from structural magnetic resonance imaging (MRI) measurements and tested its association with behavioral features of WS. Using a WS adult cohort (22 WS, 16 healthy controls), we modeled a sparse representation of a WS-specific neuroanatomical profile. The predictive performances are robust within the training cohort (10-fold cross-validation, AUC = 1.0) and accurately identify all WS individuals in an independent child WS cohort (seven WS, 59 children with diverse developmental status, AUC = 1.0). The WS-specific neuroanatomical profile includes measurements in the orbitofrontal cortex, superior parietal cortex, Sylvian fissures, and basal ganglia, and variability within these areas related to the underlying size of hemizygous deletion in patients with partial deletions. The profile intensity mediated the overall cognitive impairment as well as personality features related to hypersociability. Our results imply that the unique behaviors in WS were mediated through the constellation of abnormalities in cortical-subcortical circuitry consistent in child WS and adult WS. The robustness of the derived WS-specific neuroanatomical profile also demonstrates the potential utility of our approach in both clinical and research applications.

Borderline personality features and implicit shame-prone self-concept in middle childhood and early adolescence.

PubMed

Hawes, David J; Helyer, Rebekah; Herlianto, Eugene C; Willing, Jonah

2013-01-01

This study tested if children and adolescents with high levels of borderline personality features (BPF) exhibit the same shame-prone self-concept previously found to characterize adults with borderline personality disorder (Rüsch et al., 2007 ). Self-concept was indexed using the Implicit Association Test, in a community sample of children/adolescents aged 10 to 14 years (48% female; M age = 12.04 years). Common domains of child and adolescent psychopathology and core components of BPF were assessed using self-reports on the Strengths and Difficulties Questionnaire and the Borderline Personality Features Scale for Children. The identity problems component of BPF was found to significantly predict implicit levels of shame-prone self-concept, but only among girls. This effect was independent of the key dimensions of child and adolescent psychopathology that overlap with BPF-including features hyperactivity/inattention, disruptive behavior problems, and anxiety/depression-none of which were associated with shame-prone self-concept at the bivariate level or otherwise. The current findings provide preliminary evidence that self-schemas related to shame are uniquely associated with a core component of BPF in middle childhood and early adolescence and suggest that this correlate may apply uniquely to female individuals. These findings point to the identity problems component of BPF as a priority for future clinical and developmental research into mechanisms associated with BPF across childhood and adolescence.

[Hypersensitivity pneumonitis. A series of nine cases with surgical lung biopsy].

PubMed

Gómez Tejada, Ricardo A; Legarreta, Cora G; Enghelmayer, Juan Ignacio; Dianti, Milagros; Acuña, Silvana; Olmedo, Gloria

2017-01-01

In a series of nine patients with histopathological diagnosis of hypersensitivity pneumonitis, we retrospectively evaluated clinical data, exposure related factors, pulmonary function tests and chest computed tomography scans. A restrictive abnormality with reduction of diffusion capacity for carbon monoxide was mainly found. Chest scans showed fibrotic patterns in most cases; ground glass attenuation areas with mosaic pattern and consolidation in the rest. Exposure to avian antigens, cereal grains and air conditioners contaminated with fungi yeasts and bacteria, were suspected from clinical data in two-thirds of the cases. Since there are no unique features that allow differentiation from other interstitial lung diseases, a high clinical suspicion is required and a careful search of environmental exposure to possible antigens is needed that, together with clinical, radiological and pathological data, may lead to diagnosis.

Fanconi Anemia: A DNA repair disorder characterized by accelerated decline of the hematopoietic stem cell compartment and other features of aging.

PubMed

Brosh, Robert M; Bellani, Marina; Liu, Yie; Seidman, Michael M

2017-01-01

Fanconi Anemia (FA) is a rare autosomal genetic disorder characterized by progressive bone marrow failure (BMF), endocrine dysfunction, cancer, and other clinical features commonly associated with normal aging. The anemia stems directly from an accelerated decline of the hematopoietic stem cell compartment. Although FA is a complex heterogeneous disease linked to mutations in 19 currently identified genes, there has been much progress in understanding the molecular pathology involved. FA is broadly considered a DNA repair disorder and the FA gene products, together with other DNA repair factors, have been implicated in interstrand cross-link (ICL) repair. However, in addition to the defective DNA damage response, altered epigenetic regulation, and telomere defects, FA is also marked by elevated levels of inflammatory mediators in circulation, a hallmark of faster decline in not only other hereditary aging disorders but also normal aging. In this review, we offer a perspective of FA as a monogenic accelerated aging disorder, citing the latest evidence for its multi-factorial deficiencies underlying its unique clinical and cellular features. Published by Elsevier B.V.

Essential pitfalls in "essential” tremor

PubMed Central

Espay, AJ; Lang, AE; Erro, R; Merola, A; Fasano, A; Berardelli, A; Bhatia, KP

2016-01-01

While essential tremor has been considered the most common movement disorder, it has largely remained a diagnosis of exclusion: many tremor and non-tremor features must be absent for the clinical diagnosis to stand. The clinical features of “essential tremor” overlap with or may be part of other tremor disorders and, not surprisingly, this prevalent familial disorder has remained without a gene identified, without a consistent natural history, and without an acceptable pathology or pathophysiologic underpinning. The collective evidence suggests that under the rubric of essential tremor there exists multiple unique diseases, some of which represent cerebellar dysfunction, but for which there is no intrinsic “essence” other than a common oscillatory behavior on posture and action. One approach may be to use the term “essential tremor” only as a transitional node in the deep phenotyping of tremor disorders based on historical, phenomenological, and neurophysiological features, to facilitate its etiologic diagnosis or serve for future gene- and biomarker-discovery efforts. This approach deemphasizes essential tremor as a diagnostic entity and facilitates the understanding of the underlying disorders in order to develop biologically tailored diagnostic and therapeutic strategies. PMID:28116753

Quantitative forecasting of PTSD from early trauma responses: a Machine Learning application.

PubMed

Galatzer-Levy, Isaac R; Karstoft, Karen-Inge; Statnikov, Alexander; Shalev, Arieh Y

2014-12-01

There is broad interest in predicting the clinical course of mental disorders from early, multimodal clinical and biological information. Current computational models, however, constitute a significant barrier to realizing this goal. The early identification of trauma survivors at risk of post-traumatic stress disorder (PTSD) is plausible given the disorder's salient onset and the abundance of putative biological and clinical risk indicators. This work evaluates the ability of Machine Learning (ML) forecasting approaches to identify and integrate a panel of unique predictive characteristics and determine their accuracy in forecasting non-remitting PTSD from information collected within 10 days of a traumatic event. Data on event characteristics, emergency department observations, and early symptoms were collected in 957 trauma survivors, followed for fifteen months. An ML feature selection algorithm identified a set of predictors that rendered all others redundant. Support Vector Machines (SVMs) as well as other ML classification algorithms were used to evaluate the forecasting accuracy of i) ML selected features, ii) all available features without selection, and iii) Acute Stress Disorder (ASD) symptoms alone. SVM also compared the prediction of a) PTSD diagnostic status at 15 months to b) posterior probability of membership in an empirically derived non-remitting PTSD symptom trajectory. Results are expressed as mean Area Under Receiver Operating Characteristics Curve (AUC). The feature selection algorithm identified 16 predictors, present in ≥ 95% cross-validation trials. The accuracy of predicting non-remitting PTSD from that set (AUC = .77) did not differ from predicting from all available information (AUC = .78). Predicting from ASD symptoms was not better then chance (AUC = .60). The prediction of PTSD status was less accurate than that of membership in a non-remitting trajectory (AUC = .71). ML methods may fill a critical gap in forecasting PTSD. The ability to identify and integrate unique risk indicators makes this a promising approach for developing algorithms that infer probabilistic risk of chronic posttraumatic stress psychopathology based on complex sources of biological, psychological, and social information. Copyright © 2014 Elsevier Ltd. All rights reserved.

Responsibility after the apparent end: 'following-up' in clinical ethics consultation.

PubMed

Finder, Stuart G; Bliton, Mark J

2011-09-01

Clinical ethics literature typically presents ethics consultations as having clear beginnings and clear ends. Experience in actual clinical ethics practice, however, reflects a different characterization, particularly when the moral experiences of ethics consultants are included in the discussion. In response, this article emphasizes listening and learning about moral experience as core activities associated with clinical ethics consultation. This focus reveals that responsibility in actual clinical ethics practice is generated within the moral scope of an ethics consultant's activities as she or he encounters the unique and specific features that emerge from interactions with a specific patient, or family, or practitioner within a given situation and over time. A long-form narrative about an ethics consultant's interactions is interwoven with a more didactic discussion to highlight the theme of responsibility and to probe questions that arise regarding follow-up within the practice of clinical ethics consultation. © 2011 Blackwell Publishing Ltd.

Clinical characteristics of Staphylococcus epidermidis: a systematic review

PubMed Central

Namvar, Amirmorteza Ebrahimzadeh; Bastarahang, Sara; Abbasi, Niloufar; Ghehi, Ghazaleh Sheikhi; Farhadbakhtiarian, Sara; Arezi, Parastoo; Hosseini, Mahsa; Baravati, Sholeh Zaeemi; Jokar, Zahra; Chermahin, Sara Ganji

2014-01-01

Staphylococci are known as clustering Gram-positive cocci, nonmotile, non-spore forming facultatively anaerobic that classified in two main groups, coagulase-positive and coagulase-negative. Staphylococcus epidermidis with the highest percentage has the prominent role among coagulase-negative Staphylococci that is the most important reason of clinical infections. Due to various virulence factors and unique features, this microorganism is respected as a common cause of nosocomial infections. Because of potential ability in biofilm formation and colonization in different surfaces, also using of medical implant devices in immunocompromised and hospitalized patients the related infections have been increased. In recent decades the clinical importance and the emergence of methicillin-resistant Staphylococcus epidermidis strains have created many challenges in the treatment process. PMID:25285267

Three-dimensional echocardiography of congenital abnormalities of the left atrioventricular valve.

PubMed

Rice, Kathryn; Simpson, John

2015-03-01

Congenital abnormalities of the left atrioventricular (AV) valve are a significant diagnostic challenge. Traditionally, reliance has been placed on two-dimensional echocardiographic (2DE) imaging to guide recognition of the specific morphological features. Real-time 3DE can provide unique views of the left AV valve with the potential to improve understanding of valve morphology and function to facilitate surgical planning. This review illustrates the features of congenital abnormalities of the left AV valve assessed by 3DE. The similarities and differences in morphology between different lesions are described, both with respect to the valve itself and supporting chordal apparatus. The potential advantages as well as limitations of this technique in clinical practice are outlined.

Nanogel Carrier Design for Targeted Drug Delivery

PubMed Central

Eckmann, D. M.; Composto, R. J.; Tsourkas, A.; Muzykantov, V. R.

2014-01-01

Polymer-based nanogel formulations offer features attractive for drug delivery, including ease of synthesis, controllable swelling and viscoelasticity as well as drug loading and release characteristics, passive and active targeting, and the ability to formulate nanogel carriers that can respond to biological stimuli. These unique features and low toxicity make the nanogels a favorable option for vascular drug targeting. In this review, we address key chemical and biological aspects of nanogel drug carrier design. In particular, we highlight published studies of nanogel design, descriptions of nanogel functional characteristics and their behavior in biological models. These studies form a compendium of information that supports the scientific and clinical rationale for development of this carrier for targeted therapeutic interventions. PMID:25485112

Immune-mediated statin myopathy.

PubMed

Loganathan, Priyadarshini; Oddis, Chester V; Aggarwal, Rohit

2016-01-01

Statin-induced necrotizing autoimmune myopathy (SINAM) is associated with a unique clinical 5 phenotype of severe proximal muscle weakness during or after exposure to statins in patients with high creatine kinase (CK) levels. Electromyography (EMG) and muscle biopsy reveal features of a necrotizing myopathy and the anti-HMGCR autoantibody is frequently detected. Treatment requires a combination of statin discontinuation as well as immunomodulatory or immunosuppressive therapy. HLA typing (HLADRB1*1101) is strongly associated with anti-10 HMGCR autoantibody positivity in statin-exposed patients. It is well documented that statin triggers autoimmune disease in those with a genetic susceptibility. With the commercial availability of an accurate ELISA test, the natural history of the disease and its phenotypic features are becoming increasingly understood.

Assessing the clinical utility of agoraphobia in the context of panic disorder.

PubMed

Schmidt, Norman B; Cromer, Kiara R

2008-01-01

In the DSM-IV, a panic disorder (PD) diagnosis includes specification of agoraphobia, which is primarily an index of situational avoidance due to fear of panic. No other anxiety diagnosis requires specification of level of avoidance. This raises the question as to whether agoraphobia provides unique information beyond the core features of PD (i.e., panic attacks and panic-related worry). The incremental validity of agoraphobia, defined using DSM-IV specifiers versus level of situational avoidance, was examined in relation to the expression and treatment of PD (N=146). Analyses indicate that agoraphobia status adds uniquely to the prediction of PD symptoms, impairment, and response to treatment. However, level of situational avoidance, defined either as a continuous or dichotomous variable, appears to have greater utility compared to the DSM-IV method of classifying agoraphobia. In summary, the agoraphobia specifier seems to have clinical utility but this could be improved by focusing on a dimensional assessment of situational avoidance.

Clinical and Molecular Aspects of an Informative Family with Neurofibromatosis Type 1 and Noonan Phenotype

PubMed Central

Stevenson, David A.; Viskochil, David H.; Rope, Alan F.; Carey, John C.

2011-01-01

NF-Noonan syndrome (NFNS) has been described as a unique phenotype, combining manifestations of neurofibromatosis type 1 (NF1) and Noonan syndromes, which are separate syndromes. Potential etiologies of NF-Noonan syndrome include a discrete syndrome of distinct etiology, co-segregation of two mutated common genes, variable clinical expressivity of NF1, and/or allelic heterogeneity. We present an informative family with an unusual NF1 mutation with variable features of NF1 and Noonan syndrome. We hypothesize that an NF1 mutant allele can lead to diagnostic manifestations of Noonan syndrome, supporting the hypothesis that NF1 allelic heterogeneity causes NFNS. PMID:16542390

Theophylline-Induced Seizures: Clinical and Pathophysiologic Aspects

PubMed Central

Nakada, Tsutomu; Kwee, Ingrid L.; Lerner, Alfred M.; Remler, Michael P.

1983-01-01

The clinical features and management of theophylline-induced seizures are not well appreciated in spite of their unique aspects. These seizures tend to occur in neurologically intact patients and leave no or only minor neurologic sequelae if controlled early. They begin with focal motor seizures with or without secondary generalization and are followed by stupor or coma. They are responsive only to adjustment of theophylline dosage. Should the motor phenomenon persist, it takes the form of epilepsia partialis continua. Extensive workup for a structural brain lesion may be unrewarding. The electroencephalogram typically shows periodic lateralized epileptiform discharges, which may provide a diagnostic clue. PMID:6858124

Auditory dysfunction in schizophrenia: integrating clinical and basic features

PubMed Central

Javitt, Daniel C.; Sweet, Robert A.

2015-01-01

Schizophrenia is a complex neuropsychiatric disorder that is associated with persistent psychosocial disability in affected individuals. Although studies of schizophrenia have traditionally focused on deficits in higher-order processes such as working memory and executive function, there is an increasing realization that, in this disorder, deficits can be found throughout the cortex and are manifest even at the level of early sensory processing. These deficits are highly amenable to translational investigation and represent potential novel targets for clinical intervention. Deficits, moreover, have been linked to specific structural abnormalities in post-mortem auditory cortex tissue from individuals with schizophrenia, providing unique insights into underlying pathophysiological mechanisms. PMID:26289573

Countertransference in Child and Adolescent Psychiatry-A Forgotten Concept?

PubMed Central

Rasic, Daniel

2010-01-01

Objectives: The purpose of this paper is to review the evolution of the concept of countertransference, its clinical utility and unique features in the child and adolescent psychiatry setting. Methods: This article employs a selective literature review of papers relevant to countertransference in general and in child and adolescent psychiatry. Results: Reviewed papers indicate that countertransference is a ubiquitous phenomenon in child and adolescent psychiatric practice and that it can have important clinical implications. Conclusions: Recognition and management of countertransference is a crucial skill in child and adolescent psychiatry. Recommendations are made regarding its incorporation in residency training and psychiatric practice. PMID:21037914

Human Papilloma Virus Associated Squamous Cell Carcinoma of the Head and Neck

PubMed Central

Ajila, Vidya; Shetty, Harish; Babu, Subhas; Shetty, Veena; Hegde, Shruthi

2015-01-01

Oral cancer is one of the commonest causes for mortality and morbidity with squamous cell carcinoma being the sixth most frequent malignant tumour worldwide. In addition to tobacco and alcohol, human papilloma virus (HPV) is associated with a proportion of head and neck cancers. As in cervical cancers, HPV types 16 and 18 are the cause of malignant transformation. HPV-positive cancers of head and neck have unique characteristics such as occurrence in a younger age group, distinct clinical and molecular features, and better prognosis as compared to HPV-negative carcinomas. They also possess the potential for prevention by using vaccination. The present review describes in detail the salient features of HPV associated oral squamous cell carcinoma (OSCC), its differences from HPV-negative OSCC, diagnostic features, and recent strategies in prevention and management. PMID:26483987

Human Papilloma Virus Associated Squamous Cell Carcinoma of the Head and Neck.

PubMed

Ajila, Vidya; Shetty, Harish; Babu, Subhas; Shetty, Veena; Hegde, Shruthi

2015-01-01

Oral cancer is one of the commonest causes for mortality and morbidity with squamous cell carcinoma being the sixth most frequent malignant tumour worldwide. In addition to tobacco and alcohol, human papilloma virus (HPV) is associated with a proportion of head and neck cancers. As in cervical cancers, HPV types 16 and 18 are the cause of malignant transformation. HPV-positive cancers of head and neck have unique characteristics such as occurrence in a younger age group, distinct clinical and molecular features, and better prognosis as compared to HPV-negative carcinomas. They also possess the potential for prevention by using vaccination. The present review describes in detail the salient features of HPV associated oral squamous cell carcinoma (OSCC), its differences from HPV-negative OSCC, diagnostic features, and recent strategies in prevention and management.

Systems-Level Annotation of a Metabolomics Data Set Reduces 25 000 Features to Fewer than 1000 Unique Metabolites.

PubMed

Mahieu, Nathaniel G; Patti, Gary J

2017-10-03

When using liquid chromatography/mass spectrometry (LC/MS) to perform untargeted metabolomics, it is now routine to detect tens of thousands of features from biological samples. Poor understanding of the data, however, has complicated interpretation and masked the number of unique metabolites actually being measured in an experiment. Here we place an upper bound on the number of unique metabolites detected in Escherichia coli samples analyzed with one untargeted metabolomics method. We first group multiple features arising from the same analyte, which we call "degenerate features", using a context-driven annotation approach. Surprisingly, this analysis revealed thousands of previously unreported degeneracies that reduced the number of unique analytes to ∼2961. We then applied an orthogonal approach to remove nonbiological features from the data using the 13 C-based credentialing technology. This further reduced the number of unique analytes to less than 1000. Our 90% reduction in data is 5-fold greater than previously published studies. On the basis of the results, we propose an alternative approach to untargeted metabolomics that relies on thoroughly annotated reference data sets. To this end, we introduce the creDBle database ( http://creDBle.wustl.edu ), which contains accurate mass, retention time, and MS/MS fragmentation data as well as annotations of all credentialed features.

[Randomized, controlled clinical trials with observational follow-up investigations for evaluating efficacy of antihyperglycaemic treatment. II. Features of and lessons from the follow-up investigations].

PubMed

Jermendy, György

2018-04-01

Although the outcomes of the follow-up investigation period of the randomized clinical studies for evaluating the efficacy of a treatment or an antidiabetic drug may be confounded or potentially biased by several factors, the results are widely accepted by the diabetes community. In line with the theory of metabolic memory or metabolic legacy, early and intensive antihyperglycaemic treatment should be provided for all diabetic patients as this strategy can result in beneficial effects even in the long run. The recent cardiovascular safety trials with new, innovative antidiabetic drugs differ in several aspects from the former efficacy studies. Ten cardiovascular safety trials were completed so far enabling to define their unique and common features. It can be anticipated that the era of randomized, controlled efficacy studies with observational follow-up investigations came to an end in diabetes research. Nowadays, cardiovascular safety trials are in the focus of clinical research in diabetology and results of several ongoing studies are expected with interest in the near future. Orv Hetil. 2018; 159(16): 615-619.

Primary central nervous system vasculitis and its mimicking diseases - clinical features, outcome, comorbidities and diagnostic results - A case control study.

PubMed

Becker, J; Horn, P A; Keyvani, K; Metz, I; Wegner, C; Brück, W; Heinemann, F M; Schwitalla, J C; Berlit, P; Kraemer, M

2017-05-01

To compare clinical features and outcome, imaging characteristics, biopsy results and laboratory findings in a cohort of 69 patients with suspected or diagnosed primary central nervous system vasculitis (PCNSV) in adults; to identify risk factors and predictive features for PCNSV. We performed a case-control-study including 69 patients referred with suspected PCNSV from whom 25 were confirmed by predetermined diagnostic criteria based on biopsy (72%) or angiography (28%). Forty-four patients turned out to have 15 distinct other diagnoses. Clinical and diagnostic data were compared between PCNSV and Non-PCNSV cohorts. Clinical presentation was not able to discriminate between PCNSV and its differential diagnoses. However, a worse clinical outcome was associated with PCNSV (p=0.005). Biopsy (p=0.004), contrast enhancement (p=0.000) or tumour-like mass lesion (p=0.008) in magnetic resonance imaging (MRI), intrathecal IgG increase (p=0.020), normal Duplex findings of cerebral arteries (p=0.022) and conventional angiography (p 0.010) were able to distinguish between the two cohorts. In a cohort of 69 patients with suspected PCNSV, a large number (64%) was misdiagnosed and partly received treatment, since mimicking diseases are very difficult to discriminate. Clinical presentation at manifestation does not help to differentiate PCNSV from its mimicking diseases. MRI and cerebrospinal fluid analysis are unlikely to be normal in PCNSV, though unspecific if pathological. Cerebral angiography and biopsy must complement other diagnostics when establishing the diagnosis in order to avoid misdiagnosis and mistreatment. German clinical trials register: http://drks-neu.uniklinik-freiburg.de/drks_web/, Unique identifier: DRKS00005347. Copyright © 2017 Elsevier B.V. All rights reserved.

Confetti-like Sparing

PubMed Central

Fitzpatrick, Richard E.; Goldman, Mitchel P.

2016-01-01

Diagnostic uncertainty when a patient presents with melasma-like Undings can lead to suboptimal treatment and inaccurate prognostic expectations. In this study, the authors present a unique clinical feature of melasma that they term the “Fitzpatrick macule” and test its Utility in establishing diagnostic certainty. The “Fitzpatrick macule” is a confetti-like macule of regularly pigmented skin located within a larger patch of melasma hyperpigmentation. To test its diagnostic Utility, the authors compared clinical photography of known cases of melasma with common mimickers, such as poikiloderma of Civatte and solar lentiginosis, and determined the positivity rate of the Fitzpatrick macule in each scenario. Their results show that 89.1 percent of clinical photographs of melasma were positive for the presence of Fitzpatrick macules compared to 1.1 percent that were negative. In contrast, 37.5 and 56.3 percent of clinical photographs of poikiloderma of Civatte were positive and negative for Fitzpatrick macules, respectively. Solar lentiginosis showed a 5.6 percent positivity and a 77.8 percent negativity for Fitzpatrick macules. The sensitivity and specificity of Fitzpatrick macules for melasma was 99 and 83 percent, respectively. In summary, the authors report a highly sensitive and specific clinical feature of melasma. In cases of diagnostic uncertainty, the presence of Fitzpatrick macules may aid in establishing a diagnosis of melasma. PMID:27047632

Loss of MeCP2 in the rat models regression, impaired sociability and transcriptional deficits of Rett syndrome

PubMed Central

Veeraragavan, Surabi; Wan, Ying-Wooi; Connolly, Daniel R.; Hamilton, Shannon M.; Ward, Christopher S.; Soriano, Sirena; Pitcher, Meagan R.; McGraw, Christopher M.; Huang, Sharon G.; Green, Jennie R.; Yuva, Lisa A.; Liang, Agnes J.; Neul, Jeffrey L.; Yasui, Dag H.; LaSalle, Janine M.; Liu, Zhandong; Paylor, Richard; Samaco, Rodney C.

2016-01-01

Mouse models of the transcriptional modulator Methyl-CpG-Binding Protein 2 (MeCP2) have advanced our understanding of Rett syndrome (RTT). RTT is a ‘prototypical’ neurodevelopmental disorder with many clinical features overlapping with other intellectual and developmental disabilities (IDD). Therapeutic interventions for RTT may therefore have broader applications. However, the reliance on the laboratory mouse to identify viable therapies for the human condition may present challenges in translating findings from the bench to the clinic. In addition, the need to identify outcome measures in well-chosen animal models is critical for preclinical trials. Here, we report that a novel Mecp2 rat model displays high face validity for modelling psychomotor regression of a learned skill, a deficit that has not been shown in Mecp2 mice. Juvenile play, a behavioural feature that is uniquely present in rats and not mice, is also impaired in female Mecp2 rats. Finally, we demonstrate that evaluating the molecular consequences of the loss of MeCP2 in both mouse and rat may result in higher predictive validity with respect to transcriptional changes in the human RTT brain. These data underscore the similarities and differences caused by the loss of MeCP2 among divergent rodent species which may have important implications for the treatment of individuals with disease-causing MECP2 mutations. Taken together, these findings demonstrate that the Mecp2 rat model is a complementary tool with unique features for the study of RTT and highlight the potential benefit of cross-species analyses in identifying potential disease-relevant preclinical outcome measures. PMID:27365498

Molecular classification of patients with grade II/III glioma using quantitative MRI characteristics.

PubMed

Bahrami, Naeim; Hartman, Stephen J; Chang, Yu-Hsuan; Delfanti, Rachel; White, Nathan S; Karunamuni, Roshan; Seibert, Tyler M; Dale, Anders M; Hattangadi-Gluth, Jona A; Piccioni, David; Farid, Nikdokht; McDonald, Carrie R

2018-06-02

Molecular markers of WHO grade II/III glioma are known to have important prognostic and predictive implications and may be associated with unique imaging phenotypes. The purpose of this study is to determine whether three clinically relevant molecular markers identified in gliomas-IDH, 1p/19q, and MGMT status-show distinct quantitative MRI characteristics on FLAIR imaging. Sixty-one patients with grade II/III gliomas who had molecular data and MRI available prior to radiation were included. Quantitative MRI features were extracted that measured tissue heterogeneity (homogeneity and pixel correlation) and FLAIR border distinctiveness (edge contrast; EC). T-tests were conducted to determine whether patients with different genotypes differ across the features. Logistic regression with LASSO regularization was used to determine the optimal combination of MRI and clinical features for predicting molecular subtypes. Patients with IDH wildtype tumors showed greater signal heterogeneity (p = 0.001) and lower EC (p = 0.008) within the FLAIR region compared to IDH mutant tumors. Among patients with IDH mutant tumors, 1p/19q co-deleted tumors had greater signal heterogeneity (p = 0.002) and lower EC (p = 0.005) compared to 1p/19q intact tumors. MGMT methylated tumors showed lower EC (p = 0.03) compared to the unmethylated group. The combination of FLAIR border distinctness, heterogeneity, and pixel correlation optimally classified tumors by IDH status. Quantitative imaging characteristics of FLAIR heterogeneity and border pattern in grade II/III gliomas may provide unique information for determining molecular status at time of initial diagnostic imaging, which may then guide subsequent surgical and medical management.

Whistleblowing and boundary violations: exposing a colleague in the forensic milieu.

PubMed

Peternelj-Taylor, Cindy

2003-09-01

The purpose of this article is to examine the phenomenon of whistleblowing as it relates to a reconstructed case study of an erotic boundary violation that emerged from a clinical situation in forensic psychiatric nursing practice. The unique features of this case are illustrated with the help of a model for decision making. Although the ramifications of exposing a colleague are many, it is argued that, in this particular case, it was morally and ethically the right thing to do.

Pediatric Thoracic Trauma: Recognition and Management.

PubMed

Reynolds, Stacy L

2018-05-01

Thoracic injuries account for less than one-tenth of all pediatric trauma-related injuries but comprise 14% of pediatric trauma-related deaths. Thoracic trauma includes injuries to the lungs, heart, aorta and great vessels, esophagus, tracheobronchial tree, and structures of the chest wall. Children have unique anatomic features that change the patterns of observed injury compared with adults. This review article outlines the clinical presentation, diagnostic testing, and management principles required to successfully manage injured children with thoracic trauma. Copyright © 2018 Elsevier Inc. All rights reserved.

Multidisciplinary education in geriatric medicine. Continuing experience at the Middlesex Hospital.

PubMed

Beynon, G P; Croker, J

1983-01-01

The unique feature about the course in teaching geriatric medicine to undergraduates at the Middlesex Hospital is its multidisciplinary nature. The course lasts for three weeks during the first or second clinical year and involves medical students together with student physiotherapists, nurses and occupational therapists. All take part in seminars, ward rounds and multidisciplinary case presentations. A full-time course organizer funded by the School of Nursing manages the course. Assessment includes MCQ and course evaluation questionnaire and an essay.

Photoacoustic microscopy and computed tomography: from bench to bedside

PubMed Central

Wang, Lihong V.; Gao, Liang

2014-01-01

Photoacoustic imaging (PAI) of biological tissue has seen immense growth in the past decade, providing unprecedented spatial resolution and functional information at depths in the optical diffusive regime. PAI uniquely combines the advantages of optical excitation and acoustic detection. The hybrid imaging modality features high sensitivity to optical absorption and wide scalability of spatial resolution with the desired imaging depth. Here we first summarize the fundamental principles underpinning the technology, then highlight its practical implementation, and finally discuss recent advances towards clinical translation. PMID:24905877

SERS-Based Prognosis of Kidney Transplant Outcome

NASA Astrophysics Data System (ADS)

Chi, Jingmao

Kidney transplant is the predominant procedure of all organ transplants around the world. The number of patients on the waiting list for a kidney is growing rapidly, yet the number of donations does not keep up with the fast-growing need. This thesis focuses on the surface-enhanced Raman scattering (SERS) analysis of urine samples for prognosis of kidney transplant outcome, which can potentially let patients have a more timely treatment as well as expand the organ pool for transplant. We have observed unique SERS spectral features from urine samples of kidney transplant recipients that have strong associations with the kidney acute rejection (AR) based on the analysis of urine one day after the transplant. Our ability to provide an early prognosis of transplant outcome is a significant advance over the current gold standard of clinical diagnosis, which occurs weeks or months after the surgical procedure. The SERS analysis has also been applied to urine samples from deceased kidney donors. Excellent classification ability was achieved when the enhanced PCA-LDA analysis was used to classify and identify urine samples from different cases. The sensitivity of the acute tubular necrosis (ATN) class is more than 90%, which can indicate the usable kidneys in the high failure risk category. This analysis can help clinicians identify usable kidneys which would be discarded using conventional clinic methods as high failure risk. To investigate the biomarkers that cause the unique SERS features, an HPLC-SERS-MS approach was established. The high-performance liquid chromatography (HPLC) was used to separate the urinary components to reduce the sample complexity. The mass spectrometry (MS) was used to determine the formulas and the structures of the biomarkers. The presence of 1-methyl-2-pyrrolidone (NMP) and adenine in urine samples were confirmed by both MS and SERS analysis. Succinylmonocholine, a metabolite of suxamethonium, has a potential to be the biomarker that causes the unique SERS spectral features that indicate kidney AR. By integrating SERS analysis with statistical and chemical analysis and with the promising outcomes, this research has made a significant contribution in exploring the frontier of SERS analysis in biomedical sensing and diagnosis.

Hallucinations: A Systematic Review of Points of Similarity and Difference Across Diagnostic Classes

PubMed Central

Waters, Flavie; Fernyhough, Charles

2017-01-01

Hallucinations constitute one of the 5 symptom domains of psychotic disorders in DSM-5, suggesting diagnostic significance for that group of disorders. Although specific featural properties of hallucinations (negative voices, talking in the third person, and location in external space) are no longer highlighted in DSM, there is likely a residual assumption that hallucinations in schizophrenia can be identified based on these candidate features. We investigated whether certain featural properties of hallucinations are specifically indicative of schizophrenia by conducting a systematic review of studies showing direct comparisons of the featural and clinical characteristics of (auditory and visual) hallucinations among 2 or more population groups (one of which included schizophrenia). A total of 43 articles were reviewed, which included hallucinations in 4 major groups (nonclinical groups, drug- and alcohol-related conditions, medical and neurological conditions, and psychiatric disorders). The results showed that no single hallucination feature or characteristic uniquely indicated a diagnosis of schizophrenia, with the sole exception of an age of onset in late adolescence. Among the 21 features of hallucinations in schizophrenia considered here, 95% were shared with other psychiatric disorders, 85% with medical/neurological conditions, 66% with drugs and alcohol conditions, and 52% with the nonclinical groups. Additional differences rendered the nonclinical groups somewhat distinctive from clinical disorders. Overall, when considering hallucinations, it is inadvisable to give weight to the presence of any featural properties alone in making a schizophrenia diagnosis. It is more important to focus instead on the co-occurrence of other symptoms and the value of hallucinations as an indicator of vulnerability. PMID:27872259

An information management system for patients with tuberculosis: usability assessment with end-users.

PubMed

Darby, Jonathan; Black, Jim; Morrison, David; Buising, Kirsty

2012-01-01

Information systems with clinical decision support (CDS) offer great potential to assist the co-ordination of patients with chronic diseases and to improve patient care. Despite this, few have entered routine clinical use. Tuberculosis (TB) is an infection of public health importance. It has complex interactions with many comorbid conditions, requires close supervised care and prolonged treatment for effective cure. These features make it suitable for use with an information management system with CDS features. In close consultation with key stakeholders, a clinical application was developed for the management of TB patients in Victoria. A formal usability assessment using semi-structured case-scenario based exercises was performed. Subjects were 12 individuals closely involved in the care of TB patients, including Infectious Diseases and Respiratory Physicians, and Public Health Nurses. Two researchers conducted the sessions, independently analysed responses and discrepancies compared to the voice record for validity. Despite varied computer experience, responses were positive regarding user interface and content. Data location was not always intuitive, however this improved with familiarity of the program. Decision support was considered valuable, with useful suggestions for expansion of these features. Automated reporting for correspondence and notification to the Health Department were felt worth the initial investment in data entry. An important workflow-based issue regarding dismissal of alerts and several errors were detected. Usability assessment validated many design elements of the system, provided a unique insight into workflow issues faced by users and hopefully will impact on its ultimate clinical utility.

The anatomy of decision support during inpatient care provider order entry (CPOE): Empirical observations from a decade of CPOE experience at Vanderbilt

PubMed Central

Miller, Randolph A.; Waitman, Lemuel R.; Chen, Sutin; Rosenbloom, S. Trent

2006-01-01

The authors describe a pragmatic approach to the introduction of clinical decision support at the point of care, based on a decade of experience in developing and evolving Vanderbilt’s inpatient “WizOrder” care provider order entry (CPOE) system. The inpatient care setting provides a unique opportunity to interject CPOE-based decision support features that restructure clinical workflows, deliver focused relevant educational materials, and influence how care is delivered to patients. From their empirical observations, the authors have developed a generic model for decision support within inpatient CPOE systems. They believe that the model’s utility extends beyond Vanderbilt, because it is based on characteristics of end-user workflows and on decision support considerations that are common to a variety of inpatient settings and CPOE systems. The specific approach to implementing a given clinical decision support feature within a CPOE system should involve evaluation along three axes: what type of intervention to create (for which the authors describe 4 general categories); when to introduce the intervention into the user’s workflow (for which the authors present 7 categories), and how disruptive, during use of the system, the intervention might be to end-users’ workflows (for which the authors describe 6 categories). Framing decision support in this manner may help both developers and clinical end-users plan future alterations to their systems when needs for new decision support features arise. PMID:16290243

Histopathological characterization of corrosion product associated adverse local tissue reaction in hip implants: a study of 285 cases.

PubMed

Ricciardi, Benjamin F; Nocon, Allina A; Jerabek, Seth A; Wilner, Gabrielle; Kaplowitz, Elianna; Goldring, Steven R; Purdue, P Edward; Perino, Giorgio

2016-01-01

Adverse local tissue reaction (ALTR), characterized by a heterogeneous cellular inflammatory infiltrate and the presence of corrosion products in the periprosthetic soft tissues, has been recognized as a mechanism of failure in total hip replacement (THA). Different histological subtypes may have unique needs for longitudinal clinical follow-up and complication rates after revision arthroplasty. The purpose of this study was to describe the histological patterns observed in the periprosthetic tissue of failed THA in three different implant classes due to ALTR and their association with clinical features of implant failure. Consecutive patients presenting with ALTR from three major hip implant classes (N = 285 cases) were identified from our prospective Osteolysis Tissue Database and Repository. Clinical characteristics including age, sex, BMI, length of implantation, and serum metal ion levels were recorded. Retrieved synovial tissue morphology was graded using light microscopy. Clinical characteristics and features of synovial tissue analysis were compared between the three implant classes. Histological patterns of ALTR identified from our observations and the literature were used to classify each case. The association between implant class and histological patterns was compared. Our histological analysis demonstrates that ALTR encompasses three main histological patterns: 1) macrophage predominant, 2) mixed lymphocytic and macrophagic with or without features of associated with hypersensitivity/allergy or response to particle toxicity (eosinophils/mast cells and/or lymphocytic germinal centers), and 3) predominant sarcoid-like granulomas. Implant classification was associated with histological pattern of failure, and the macrophagic predominant pattern was more common in implants with metal-on-metal bearing surfaces (MoM HRA and MoM LHTHA groups). Duration of implantation and composition of periprosthetic cellular infiltrates was significantly different amongst the three implant types examined suggesting that histopathological features of ALTR may explain the variability of clinical implant performance in these cases. ALTR encompasses a diverse range of histological patterns, which are reflective of both the implant configuration independent of manufacturer and clinical features such as duration of implantation. The macrophagic predominant pattern and its mechanism of implant failure represent an important subgroup of ALTR which could become more prominent with increased length of implantation.

Qualitative and Quantitative Features of Music Reported to Support Peak Mystical Experiences during Psychedelic Therapy Sessions

PubMed Central

Barrett, Frederick S.; Robbins, Hollis; Smooke, David; Brown, Jenine L.; Griffiths, Roland R.

2017-01-01

Psilocybin is a classic (serotonergic) hallucinogen (“psychedelic” drug) that may occasion mystical experiences (characterized by a profound feeling of oneness or unity) during acute effects. Such experiences may have therapeutic value. Research and clinical applications of psychedelics usually include music listening during acute drug effects, based on the expectation that music will provide psychological support during the acute effects of psychedelic drugs, and may even facilitate the occurrence of mystical experiences. However, the features of music chosen to support the different phases of drug effects are not well-specified. As a result, there is currently neither real guidance for the selection of music nor standardization of the music used to support clinical trials with psychedelic drugs across various research groups or therapists. A description of the features of music found to be supportive of mystical experience will allow for the standardization and optimization of the delivery of psychedelic drugs in both research trials and therapeutic contexts. To this end, we conducted an anonymous survey of individuals with extensive experience administering psilocybin or psilocybin-containing mushrooms under research or therapeutic conditions, in order to identify the features of commonly used musical selections that have been found by therapists and research staff to be supportive of mystical experiences within a psilocybin session. Ten respondents yielded 24 unique recommendations of musical stimuli supportive of peak effects with psilocybin, and 24 unique recommendations of musical stimuli supportive of the period leading up to a peak experience. Qualitative analysis (expert rating of musical and music-theoretic features of the recommended stimuli) and quantitative analysis (using signal processing and music-information retrieval methods) of 22 of these stimuli yielded a description of peak period music that was characterized by regular, predictable, formulaic phrase structure and orchestration, a feeling of continuous movement and forward motion that slowly builds over time, and lower perceptual brightness when compared to pre peak music. These results provide a description of music that may be optimally supportive of peak psychedelic experiences. This description can be used to guide the selection and composition of music for future psychedelic research and therapy sessions. PMID:28790944

Qualitative and Quantitative Features of Music Reported to Support Peak Mystical Experiences during Psychedelic Therapy Sessions.

PubMed

Barrett, Frederick S; Robbins, Hollis; Smooke, David; Brown, Jenine L; Griffiths, Roland R

2017-01-01

Psilocybin is a classic (serotonergic) hallucinogen ("psychedelic" drug) that may occasion mystical experiences (characterized by a profound feeling of oneness or unity) during acute effects. Such experiences may have therapeutic value. Research and clinical applications of psychedelics usually include music listening during acute drug effects, based on the expectation that music will provide psychological support during the acute effects of psychedelic drugs, and may even facilitate the occurrence of mystical experiences. However, the features of music chosen to support the different phases of drug effects are not well-specified. As a result, there is currently neither real guidance for the selection of music nor standardization of the music used to support clinical trials with psychedelic drugs across various research groups or therapists. A description of the features of music found to be supportive of mystical experience will allow for the standardization and optimization of the delivery of psychedelic drugs in both research trials and therapeutic contexts. To this end, we conducted an anonymous survey of individuals with extensive experience administering psilocybin or psilocybin-containing mushrooms under research or therapeutic conditions, in order to identify the features of commonly used musical selections that have been found by therapists and research staff to be supportive of mystical experiences within a psilocybin session. Ten respondents yielded 24 unique recommendations of musical stimuli supportive of peak effects with psilocybin, and 24 unique recommendations of musical stimuli supportive of the period leading up to a peak experience. Qualitative analysis (expert rating of musical and music-theoretic features of the recommended stimuli) and quantitative analysis (using signal processing and music-information retrieval methods) of 22 of these stimuli yielded a description of peak period music that was characterized by regular, predictable, formulaic phrase structure and orchestration, a feeling of continuous movement and forward motion that slowly builds over time, and lower perceptual brightness when compared to pre peak music. These results provide a description of music that may be optimally supportive of peak psychedelic experiences. This description can be used to guide the selection and composition of music for future psychedelic research and therapy sessions.

Pitt-Hopkins Syndrome: A Review of Current Literature, Clinical Approach, and 23-Patient Case Series.

PubMed

Goodspeed, Kimberly; Newsom, Cassandra; Morris, Mary Ann; Powell, Craig; Evans, Patricia; Golla, Sailaja

2018-03-01

Pitt-Hopkins syndrome (PTHS) is a rare, genetic disorder caused by a molecular variant of TCF4 which is involved in embryologic neuronal differentiation. PTHS is characterized by syndromic facies, psychomotor delay, and intellectual disability. Other associated features include early-onset myopia, seizures, constipation, and hyperventilation-apneic spells. Many also meet criteria for autism spectrum disorder. Here the authors present a series of 23 PTHS patients with molecularly confirmed TCF4 variants and describe 3 unique individuals. The first carries a small deletion but does not exhibit the typical facial features nor the typical pattern of developmental delay. The second exhibits typical facial features, but has attained more advanced motor and verbal skills than other reported cases to date. The third displays typical features of PTHS, however inherited a large chromosomal duplication involving TCF4 from his unaffected father with somatic mosaicism. To the authors' knowledge, this is the first chromosomal duplication case reported to date.

Elevated anti-Mullerian hormone in lean women may not indicate polycystic ovarian syndrome.

PubMed

Bradbury, Rachel A; Lee, Paul; Smith, Howard C

2017-10-01

Polycystic ovarian syndrome (PCOS) is a heterogeneous disorder with clinical features shared with functional hypogonadotrophic hypogonadism (FHH). To investigate the usefulness of an elevated (>40 pmol/L) anti-Mullerian hormone (AMH) in identifying PCOS and distinguishing PCOS from FHH. 141 patients with an elevated AMH and body mass index either <20 kg/m 2 (lean) or >30 kg/m 2 (obese) were selected and three subgroups analysed - obese, lean, lean with suspected FHH. FHH was diagnosed clinically, incorporating diet, weight and exercise history; confirmatory tests included pituitary MRIs, progestin challenges and endometrial thickness measurements. PCOS features of oligo/anovulation, polycystic ovarian morphology (PCOm) and hyperandrogenism were determined by clinical history, pelvic ultrasound, free androgen index and physical examination, respectively. Features of PCOS and blood levels of AMH, follicle-stimulating hormone, luteinising hormone, sex hormone binding globulin (SHBG) and testosterone were compared between subgroups. Of 141 patients with elevated AMH, 76 were obese and 65 lean. Greater than one-third of lean women had the clinical picture of FHH. Elevated AMH predicted PCOm and menstrual irregularity across all subgroups but uniquely associated with hyperandrogenism in the obese. Median AMH levels were similar among FHH and non-FHH women. Median SHBG levels were significantly higher (111 ± 73 vs 56 ± 31, P < 0.001) in lean women with FHH compared to those without FHH. PCOS and FHH share common features of elevated AMH levels, oligo-anovulation and polycystic ovarian morphology. AMH did not assist in differentiating FHH from PCOS. A higher SHBG level shows promise as a discriminatory finding in FHH. © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Survey on multisensory feedback virtual reality dental training systems.

PubMed

Wang, D; Li, T; Zhang, Y; Hou, J

2016-11-01

Compared with traditional dental training methods, virtual reality training systems integrated with multisensory feedback possess potentials advantages. However, there exist many technical challenges in developing a satisfactory simulator. In this manuscript, we systematically survey several current dental training systems to identify the gaps between the capabilities of these systems and the clinical training requirements. After briefly summarising the components, functions and unique features of each system, we discuss the technical challenges behind these systems including the software, hardware and user evaluation methods. Finally, the clinical requirements of an ideal dental training system are proposed. Future research/development areas are identified based on an analysis of the gaps between current systems and clinical training requirements. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Oral Ulcers in Juvenile-Onset Systemic Lupus Erythematosus: A Review of the Literature.

PubMed

Rodsaward, Pongsawat; Prueksrisakul, Titipong; Deekajorndech, Tawatchai; Edwards, Steven W; Beresford, Michael W; Chiewchengchol, Direkrit

2017-12-01

Oral ulcers are the most common mucosal sign in juvenile-onset systemic lupus erythematosus (JSLE). The ulcers are one of the key clinical features; however, the terminology of oral ulcers, especially in JSLE patients, is often vague and ill-defined. In fact, there are several clinical manifestations of oral ulcers in JSLE, and some lesions occur when the disease is active, indicating that early management of the disease should be started. Oral ulcers are classified as lupus erythematosus (LE) specific, where the lesional biopsy shows a unique pattern of mucosal change in LE, and LE nonspecific, where the ulcers and their histopathological findings can be found in other oral diseases. Here, the clinical manifestations, diagnosis and management of oral ulcers in JSLE patients are reviewed.

The conduct of practice-based research in community clinics compared to private practices: similarities, differences, and challenges

PubMed Central

Gillette, Jane; Cunha-Cruz, Joana; Gilbert, Ann; Speed-McIntyre, Pollene; Zhou, Lingmei; DeRouen, Timothy

2013-01-01

Practice-based research should be performed in all practice settings if the results are to be applied to all settings. However, some practice settings, such as community clinics, have unique features that may make the conduct of such research more challenging. The purpose of this article is to describe and compare the similarities and unique challenges related to conducting research in community clinics compared to private practices within the Northwest Practice-Based REsearch Collaborative in Evidence-Based DENTistry (PRECEDENT) network. Information was obtained from meetings with general dentists, a survey of general dentists (N = 253), and a clinical examination and record review of a systemic random sample of patients visiting community clinics and private practices. (N = 1903)—all part of a dental practice-based research network. The processes of conducting research, the dentist and patient sociodemographic characteristics, the prevalence of oral diseases, and the dental treatments received in community clinics and private practices were compared. Both community clinics and private practices have the clinical treatment of the patients as their priority and have time constraints on research. The processes of research training, obtaining informed consent, and collecting, transmitting, and securely maintaining research data are also similar. The patient populations and treatment needs differ substantially between community clinics and private practices, with a higher prevalence of dental caries and higher restorative treatment needs in the community clinic patients. The process of study participant selection and follow-up for research and the dentist and staff work arrangements also vary between the two practice settings. Although community clinic patients and their dental healthcare providers have different research needs and challenges than their counterparts in private practice, practice-based research can be successfully PMID:25429251

Distinct contributions of functional and deep neural network features to representational similarity of scenes in human brain and behavior

PubMed Central

Greene, Michelle R; Baldassano, Christopher; Fei-Fei, Li; Beck, Diane M; Baker, Chris I

2018-01-01

Inherent correlations between visual and semantic features in real-world scenes make it difficult to determine how different scene properties contribute to neural representations. Here, we assessed the contributions of multiple properties to scene representation by partitioning the variance explained in human behavioral and brain measurements by three feature models whose inter-correlations were minimized a priori through stimulus preselection. Behavioral assessments of scene similarity reflected unique contributions from a functional feature model indicating potential actions in scenes as well as high-level visual features from a deep neural network (DNN). In contrast, similarity of cortical responses in scene-selective areas was uniquely explained by mid- and high-level DNN features only, while an object label model did not contribute uniquely to either domain. The striking dissociation between functional and DNN features in their contribution to behavioral and brain representations of scenes indicates that scene-selective cortex represents only a subset of behaviorally relevant scene information. PMID:29513219

Distinct contributions of functional and deep neural network features to representational similarity of scenes in human brain and behavior.

PubMed

Groen, Iris Ia; Greene, Michelle R; Baldassano, Christopher; Fei-Fei, Li; Beck, Diane M; Baker, Chris I

2018-03-07

Inherent correlations between visual and semantic features in real-world scenes make it difficult to determine how different scene properties contribute to neural representations. Here, we assessed the contributions of multiple properties to scene representation by partitioning the variance explained in human behavioral and brain measurements by three feature models whose inter-correlations were minimized a priori through stimulus preselection. Behavioral assessments of scene similarity reflected unique contributions from a functional feature model indicating potential actions in scenes as well as high-level visual features from a deep neural network (DNN). In contrast, similarity of cortical responses in scene-selective areas was uniquely explained by mid- and high-level DNN features only, while an object label model did not contribute uniquely to either domain. The striking dissociation between functional and DNN features in their contribution to behavioral and brain representations of scenes indicates that scene-selective cortex represents only a subset of behaviorally relevant scene information.

Three-dimensional echocardiography of congenital abnormalities of the left atrioventricular valve

PubMed Central

Rice, Kathryn

2015-01-01

Congenital abnormalities of the left atrioventricular (AV) valve are a significant diagnostic challenge. Traditionally, reliance has been placed on two-dimensional echocardiographic (2DE) imaging to guide recognition of the specific morphological features. Real-time 3DE can provide unique views of the left AV valve with the potential to improve understanding of valve morphology and function to facilitate surgical planning. This review illustrates the features of congenital abnormalities of the left AV valve assessed by 3DE. The similarities and differences in morphology between different lesions are described, both with respect to the valve itself and supporting chordal apparatus. The potential advantages as well as limitations of this technique in clinical practice are outlined. PMID:26693328

Mesial frontal lobe epilepsy.

PubMed

Unnwongse, Kanjana; Wehner, Tim; Foldvary-Schaefer, Nancy

2012-10-01

Mesial frontal lobe epilepsies can be divided into epilepsies arising from the anterior cingulate gyrus and those of the supplementary sensorimotor area. They provide diagnostic challenges because they often lack lateralizing or localizing features on clinical semiology and interictal and ictal scalp electroencephalographic (EEG) recordings. A number of unique semiologic features have been described over the last decade in patients with mesial frontal lobe epilepsy (FLE). There are few reports of applying advanced neurophysiologic techniques such as electrical source imaging, magnetoencephalography, EEG/functional magnetic resonance imaging, or analysis of high-frequency oscillations in patients with mesial FLE. Despite these diagnostic challenges, it seems that patients with mesial FLE benefit from epilepsy surgery to the same extent or even better than patients with FLE do, as a whole.

Sudden death in spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type.

PubMed

Dias, Cristina; Cairns, Robyn; Patel, Millan S

2009-01-01

The spondylo-meta-epiphyseal dysplasias are an expanding group of skeletal dysplasias with specific features differentiating each subtype. We review the precocious carpal mineralization, unique metacarpal shape, triangular distal phalanges and mushroom cloud-shaped proximal phalanges present at an early age in spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type (SMED SL-AC) and report two patients with clinical and radiographic features consistent with SMED SL-AC, who died suddenly because of spinal cord compression. The patients presented are female siblings, providing further evidence for autosomal recessive inheritance. Cervical cord compression is found in half of reported patients and is the major cause of mortality. SMED SL-AC should be added to the list of genetic causes of sudden death. Radiological features in the hand may be used in the first few years of life to support an early diagnosis and thus allow for prevention of premature demise.

Quebec platelet disorder: features, pathogenesis and treatment.

PubMed

Diamandis, Maria; Veljkovic, D Kika; Maurer-Spurej, Elisabeth; Rivard, Georges E; Hayward, Catherine P M

2008-03-01

Quebec platelet disorder (QPD) is a rare, autosomal-dominant, inherited bleeding disorder that is associated with unique abnormalities in fibrinolysis. Its hallmark features are delayed-onset bleeding following hemostatic challenges that responds to fibrinolytic inhibitor therapy and increased expression and storage of the fibrinolytic enzyme urokinase plasminogen activator in platelets, without increased plasma urokinase plasminogen activator or systemic fibrinolysis. The increased urokinase plasminogen activator in QPD platelets is only partially inhibited, and, as a result, there is intraplatelet generation of plasmin, and secondary degradation of many platelet alpha-granule proteins. During clot formation, the urokinase plasminogen activator released by QPD platelets leads to platelet-dependent increased fibrinolysis, and this is postulated to be a major contributor to QPD bleeding. The focus of the present review is to summarize the current state of knowledge on QPD, including the history of this disorder, its clinical and laboratory features, and recommended approaches for its diagnosis and treatment.

Telangiectatic oncocytoma: a previously undescribed variant of renal oncocytoma.

PubMed

Xiao, Guang-Qian; Ko, Huai-Bin Mabel; Unger, Pamela

2013-07-01

To identify, describe, and investigate the clinical, radiologic, and pathologic features of 8 cases of telangiectatic oncocytoma. Fifty-three consecutive renal oncocytomas were reviewed for the telangiectatic pathologic features that were subsequently correlated with the demographic, clinical, and radiographic findings. Telangiectatic oncocytoma accounted for 15% of the 53 renal oncocytomas collected in the past 7 years in our institution. On radiology, almost all presented as an enhancing mass and were suspicious for or consistent with a renal malignant tumor. Grossly, the tumors ranged from 2.4 to 6.0 cm (mean, 3.5 cm) and macroscopically were hemorrhagic spongy or multicystic masses without a central stellate scar. Microscopically, they were characterized by variably sized blood-distended spaces (<0.1-mm to 2- to 3-mm blood lakes) lined by typical oncocytoma cells and without evidence of degenerative changes. With its unique radiologic and pathologic presentations in comparison with classic renal oncocytoma, it is important to recognize this new variant of renal oncocytoma.

Blood-brain barrier dysfunction in brain diseases: clinical experience.

PubMed

Schoknecht, Karl; Shalev, Hadar

2012-11-01

The blood-brain barrier, a unique feature of the cerebral vasculature, is gaining attention as a feature in common neurologic disorders including stroke, traumatic brain injury, epilepsy, and schizophrenia. Although acute blood-brain barrier dysfunction can induce cerebral edema, seizures, or neuropsychiatric symptoms, epileptogenesis and cognitive decline are among the chronic effects. The mechanisms underlying blood-brain barrier dysfunction are diverse and may range from physical endothelial damage in traumatic brain injury to degradation of extracellular matrix proteins via matrix metalloproteinases as part of an inflammatory response. Clinically, blood-brain barrier dysfunction is often detected using contrast-enhanced imaging. However, these techniques do not give any insights into the underlying mechanism. Elucidating the specific pathways of blood-brain barrier dysfunction at different time points and in different brain diseases using novel imaging techniques promises a more accurate blood-brain barrier terminology as well as new treatment options and personalized treatment. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Ebolavirus: An Overview of Molecular and Clinical Pathogenesis.

PubMed

Vine, Veronica; Scott, Dana P; Feldmann, Heinz

2017-01-01

Ebolaviruses cause severe, often fatal hemorrhagic fever in Central, East, and West Africa. Until recently, they have been viewed as rare but highly pathogenic infections with regional, but limited, global public health impact. This view has changed with the emergence of the first epidemic of Ebola hemorrhagic fever in West Africa. In this chapter we provide an introduction of the pathogenesis of ebolaviruses as well as a description of clinical disease features. We also describe the current animal models used in ebolavirus research, detailing each model's unique strengths and weaknesses. We focus on Ebola virus representing the type species Zaire ebolavirus of the genus Ebolavirus, as most work relates to this pathogen.

Clinical-Physiological Considerations in Patients Undergoing Staged Palliation for a Functionally Single Ventricle.

PubMed

Penny, Daniel J; Krishnamurthy, Rajesh

2016-08-01

The objectives of this review are to discuss the pathophysiology of the circulation with a functionally univentricular heart, with a focus on the unique physiologic characteristics, which provide the underpinnings for the management of these complex patients. MEDLINE and PubMed. The circulation of the patient with a functionally univentricular heart displays unique physiologic characteristics, which are quite different from those of the normal biventricular circulation. There are profound differences within the heart itself in terms of ventricular function, interventricular interactions, and myocardial architecture, which are likely to have significant implications for the efficiency of ventricular ejection and metabolism. The coupling between the systemic ventricle and the aorta also displays unique features. The 3D orientation of the Fontan anastomosis itself can profoundly impact cardiac output, although the "portal" pulmonary arterial bed is a crucial determinant of overall cardiovascular function. As a result, disease-specific approaches to improve cardiovascular function are required at all stages during the care of these complex patients.

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

PubMed

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

2014-09-01

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

The management of nonunion and malunion of the distal humerus--a 30-year experience.

PubMed

Jupiter, Jesse B

2008-01-01

This personal series of nonunions of the distal humerus reviews unique features of this problem, categorizes them according to unique anatomic features, and presents pitfalls and pearls in the management of these complex reconstructive problems.

Arima syndrome caused by CEP290 specific variant and accompanied with pathological cilium; clinical comparison with Joubert syndrome and its related diseases.

PubMed

Itoh, Masayuki; Ide, Shuhei; Iwasaki, Yuji; Saito, Takashi; Narita, Keishi; Dai, Hongmei; Yamakura, Shinji; Furue, Takeki; Kitayama, Hirotsugu; Maeda, Keiko; Takahashi, Eihiko; Matsui, Kiyoshi; Goto, Yu-Ichi; Takeda, Sen; Arima, Masataka

2018-04-01

Arima syndrome (AS) is a rare disease and its clinical features mimic those of Joubert syndrome or Joubert syndrome-related diseases (JSRD). Recently, we clarified the AS diagnostic criteria and its severe phenotype. However, genetic evidence of AS remains unknown. We explored causative genes of AS and compared the clinical and genetic features of AS with the other JSRD. We performed genetic analyses of 4 AS patients of 3 families with combination of whole-exome sequencing and Sanger sequencing. Furthermore, we studied cell biology with the cultured fibroblasts of 3 AS patients. All patients had a specific homozygous variant (c.6012-12T>A, p.Arg2004Serfs*7) or compound heterozygous variants (c.1711+1G>A; c.6012-12T>A, p.Gly570Aspfs*19;Arg2004Serfs*7) in centrosomal protein 290 kDa (CEP290) gene. These unique variants lead to abnormal splicing and premature termination. Morphological analysis of cultured fibroblasts from AS patients revealed a marked decrease of the CEP290-positive cell number with significantly longer cilium and naked and protruded ciliary axoneme without ciliary membrane into the cytoplasm. AS resulted in cilia dysfunction from centrosome disruption. The unique variant of CEP290 could be strongly linked to AS pathology. Here, we provided AS specific genetic evidence, which steers the structure and functions of centrosome that is responsible for normal ciliogenesis. This is the first report that has demonstrated the molecular basis of Arima syndrome. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Abnormal brain magnetic resonance imaging in two patients with Smith-Magenis syndrome.

PubMed

Maya, Idit; Vinkler, Chana; Konen, Osnat; Kornreich, Liora; Steinberg, Tamar; Yeshaya, Josepha; Latarowski, Victoria; Shohat, Mordechai; Lev, Dorit; Baris, Hagit N

2014-08-01

Smith-Magenis syndrome (SMS) is a clinically recognizable contiguous gene syndrome ascribed to an interstitial deletion in chromosome 17p11.2. Seventy percent of SMS patients have a common deletion interval spanning 3.5 megabases (Mb). Clinical features of SMS include characteristic mild dysmorphic features, ocular anomalies, short stature, brachydactyly, and hypotonia. SMS patients have a unique neurobehavioral phenotype that includes intellectual disability, self-injurious behavior and severe sleep disturbance. Little has been reported in the medical literature about anatomical brain anomalies in patients with SMS. Here we describe two patients with SMS caused by the common deletion in 17p11.2 diagnosed using chromosomal microarray (CMA). Both patients had a typical clinical presentation and abnormal brain magnetic resonance imaging (MRI) findings. One patient had subependymal periventricular gray matter heterotopia, and the second had a thin corpus callosum, a thin brain stem and hypoplasia of the cerebellar vermis. This report discusses the possible abnormal MRI images in SMS and reviews the literature on brain malformations in SMS. Finally, although structural brain malformations in SMS patients are not a common feature, we suggest baseline routine brain imaging in patients with SMS in particular, and in patients with chromosomal microdeletion/microduplication syndromes in general. Structural brain malformations in these patients may affect the decision-making process regarding their management. © 2014 Wiley Periodicals, Inc.

Reduced Plasmodium Parasite Burden Associates with CD38+ CD4+ T Cells Displaying Cytolytic Potential and Impaired IFN-γ Production

PubMed Central

Burel, Julie G.; Apte, Simon H.; Groves, Penny L.; Klein, Kerenaftali; McCarthy, James S.; Doolan, Denise L.

2016-01-01

Using a unique resource of samples from a controlled human malaria infection (CHMI) study, we identified a novel population of CD4+ T cells whose frequency in the peripheral blood was inversely correlated with parasite burden following P. falciparum infection. These CD4+ T cells expressed the multifunctional ectoenzyme CD38 and had unique features that distinguished them from other CD4+ T cells. Specifically, their phenotype was associated with proliferation, activation and cytotoxic potential as well as significantly impaired production of IFN-γ and other cytokines and reduced basal levels of activated STAT1. A CD38+ CD4+ T cell population with similar features was identified in healthy uninfected individuals, at lower frequency. CD38+ CD4+ T cells could be generated in vitro from CD38- CD4+ T cells after antigenic or mitogenic stimulation. This is the first report of a population of CD38+ CD4+ T cells with a cytotoxic phenotype and markedly impaired IFN-γ capacity in humans. The expansion of this CD38+ CD4+ T population following infection and its significant association with reduced blood-stage parasite burden is consistent with an important functional role for these cells in protective immunity to malaria in humans. Their ubiquitous presence in humans suggests that they may have a broad role in host-pathogen defense. Trial Registration ClinicalTrials.gov clinical trial numbers ACTRN12612000814875, ACTRN12613000565741 and ACTRN12613001040752 PMID:27662621

The value of the study of natural history in genetic disorders and congenital anomaly syndromes.

PubMed Central

Hall, J G

1988-01-01

The study of the natural history of genetic disorders and syndromes with congenital anomalies and dysmorphic features is a challenging and often neglected area. There are many reasons to pursue this type of research but it requires special clinical skills and a considerable amount of hard work. Setting up protocols and collecting data is complex and time consuming. Frequently, helpful clues for a particular disorder come from the study of the natural history of other disorders. Older affected subjects and unique cases with unusual features are often most important in unravelling the 'normal' course of a disease or recognising the basic defect. The study of natural history from individual patients and their records is complementary to population or registry based studies because it identifies individual variations and clinical heterogeneity. The understanding of the natural history of a particular disorder is of importance both to the affected person and their family and to the physicians caring for them. It is also useful to the basic researcher trying to determine the pathogenetic mechanism causing the disorder. In many ways, clinical geneticists have learned the art of caring for patients, as well as the challenges of clinical genetics, by becoming apprentices to and studying in depth specific disease entities. PMID:3050091

Comparing Presenting Clinical Features in 48 Children With Microscopic Polyangiitis to 183 Children Who Have Granulomatosis With Polyangiitis (Wegener's): An ARChiVe Cohort Study.

PubMed

Cabral, David A; Canter, Debra L; Muscal, Eyal; Nanda, Kabita; Wahezi, Dawn M; Spalding, Steven J; Twilt, Marinka; Benseler, Susanne M; Campillo, Sarah; Charuvanij, Sirirat; Dancey, Paul; Eberhard, Barbara A; Elder, Melissa E; Hersh, Aimee; Higgins, Gloria C; Huber, Adam M; Khubchandani, Raju; Kim, Susan; Klein-Gitelman, Marisa; Kostik, Mikhail M; Lawson, Erica F; Lee, Tzielan; Lubieniecka, Joanna M; McCurdy, Deborah; Moorthy, Lakshmi N; Morishita, Kimberly A; Nielsen, Susan M; O'Neil, Kathleen M; Reiff, Andreas; Ristic, Goran; Robinson, Angela B; Sarmiento, Angelyne; Shenoi, Susan; Toth, Mary B; Van Mater, Heather A; Wagner-Weiner, Linda; Weiss, Jennifer E; White, Andrew J; Yeung, Rae S M

2016-10-01

To uniquely classify children with microscopic polyangiitis (MPA), to describe their demographic characteristics, presenting clinical features, and initial treatments in comparison to patients with granulomatosis with polyangiitis (Wegener's) (GPA). The European Medicines Agency (EMA) classification algorithm was applied by computation to categorical data from patients recruited to the ARChiVe (A Registry for Childhood Vasculitis: e-entry) cohort, with the data censored to November 2015. The EMA algorithm was used to uniquely distinguish children with MPA from children with GPA, whose diagnoses had been classified according to both adult- and pediatric-specific criteria. Descriptive statistics were used for comparisons. In total, 231 of 440 patients (64% female) fulfilled the classification criteria for either MPA (n = 48) or GPA (n = 183). The median time to diagnosis was 1.6 months in the MPA group and 2.1 months in the GPA group (ranging to 39 and 73 months, respectively). Patients with MPA were significantly younger than those with GPA (median age 11 years versus 14 years). Constitutional features were equally common between the groups. In patients with MPA compared to those with GPA, pulmonary manifestations were less frequent (44% versus 74%) and less severe (primarily, hemorrhage, requirement for supplemental oxygen, and pulmonary failure). Renal pathologic features were frequently found in both groups (75% of patients with MPA versus 83% of patients with GPA) but tended toward greater severity in those with MPA (primarily, nephrotic-range proteinuria, requirement for dialysis, and end-stage renal disease). Airway/eye involvement was absent among patients with MPA, because these GPA-defining features preclude a diagnosis of MPA within the EMA algorithm. Similar proportions of patients with MPA and those with GPA received combination therapy with corticosteroids plus cyclophosphamide (69% and 78%, respectively) or both drugs in combination with plasmapheresis (19% and 22%, respectively). Other treatments administered, ranging in decreasing frequency from 13% to 3%, were rituximab, methotrexate, azathioprine, and mycophenolate mofetil. Younger age at disease onset and, perhaps, both gastrointestinal manifestations and more severe kidney disease seem to characterize the clinical profile in children with MPA compared to those with GPA. Delay in diagnosis suggests that recognition of these systemic vasculitides is suboptimal. Compared with adults, initial treatment regimens in children were comparable, but the complete reversal of female-to-male disease prevalence ratios is a provocative finding. © 2016, American College of Rheumatology.

Challenges and practical approaches with word sense disambiguation of acronyms and abbreviations in the clinical domain.

PubMed

Moon, Sungrim; McInnes, Bridget; Melton, Genevieve B

2015-01-01

Although acronyms and abbreviations in clinical text are used widely on a daily basis, relatively little research has focused upon word sense disambiguation (WSD) of acronyms and abbreviations in the healthcare domain. Since clinical notes have distinctive characteristics, it is unclear whether techniques effective for acronym and abbreviation WSD from biomedical literature are sufficient. The authors discuss feature selection for automated techniques and challenges with WSD of acronyms and abbreviations in the clinical domain. There are significant challenges associated with the informal nature of clinical text, such as typographical errors and incomplete sentences; difficulty with insufficient clinical resources, such as clinical sense inventories; and obstacles with privacy and security for conducting research with clinical text. Although we anticipated that using sophisticated techniques, such as biomedical terminologies, semantic types, part-of-speech, and language modeling, would be needed for feature selection with automated machine learning approaches, we found instead that simple techniques, such as bag-of-words, were quite effective in many cases. Factors, such as majority sense prevalence and the degree of separateness between sense meanings, were also important considerations. The first lesson is that a comprehensive understanding of the unique characteristics of clinical text is important for automatic acronym and abbreviation WSD. The second lesson learned is that investigators may find that using simple approaches is an effective starting point for these tasks. Finally, similar to other WSD tasks, an understanding of baseline majority sense rates and separateness between senses is important. Further studies and practical solutions are needed to better address these issues.

A pathophysiologic approach for subacute encephalopathy with seizures in alcoholics (SESA) syndrome.

PubMed

Choi, Jun Yong; Kwon, Jiwon; Bae, Eun-Kee

2014-09-01

Subacute encephalopathy with seizures in alcoholics (SESA) syndrome is a unique disease entity characterized by typical clinical and electroencephalographic (EEG) features in the setting of chronic alcoholism. We present two patients with distinctive serial MRI and EEG findings which suggest a clue to the underlying pathophysiologic mechanisms of SESA syndrome. Two patients with chronic alcoholism and alcoholic liver cirrhosis presented with generalized seizures and confused mental status. Brain MRI demonstrated restricted diffusion, increased T2-weighted signal intensity, and hyperperfusion in the presumed seizure focus and nearby posterior regions of the cerebral hemispheres. EEG showed periodic lateralized epileptiform discharges which were prominent in the posterior regions of the cerebral hemispheres ipsilateral to the side of brain MRI abnormalities. Even after patients clinically improved, these brain abnormalities persisted with progressive atrophic changes on follow-up brain MRI. These patients had not only the distinguishing clinical and EEG features of SESA syndrome, but also showed novel brain MRI abnormalities. These changes on MRI displayed characteristics of seizure-related changes. The posterior dominance of abnormalities on MRI and EEG suggests that the pathophysiologic mechanisms of SESA syndrome may share those of posterior reversible encephalopathy syndrome. Copyright © 2014 Elsevier Ltd. All rights reserved.

Enduring sexual dysfunction after treatment with antidepressants, 5α-reductase inhibitors and isotretinoin: 300 cases.

PubMed

Healy, David; Le Noury, Joanna; Mangin, Derelie

2018-05-01

To investigate clinical reports of post-SSRI sexual dysfunction (PSSD), post-finasteride syndrome (PFS) and enduring sexual dysfunction following isotretinoin. Data from RxISK.org, a global adverse event reporting website, have been used to establish the clinical features, demographic details and clinical trajectories of syndromes of persistent sexual difficulties following three superficially different treatment modalities.RESULTSWe report on 300 cases of enduring sexual dysfunction from 37 countries following 14 different drugs comprised of serotonin reuptake inhibiting antidepressants, 5α-reductase inhibitors and isotretinoin. While reports of certain issues were unique to the antidepressants, such as the onset of premature ejaculation and persistent genital arousal disorder (PGAD), there was also a significant overlap in symptom profile between the drug groups, with common features including genital anaesthesia, pleasureless or weak orgasm, loss of libido and impotence. Secondary consequences included relationship breakdown and impaired quality of life.CONCLUSIONSThese data point to a legacy syndrome or syndromes comprising a range of disturbances to sexual function. More detailed studies will require developments in coding systems that recognise the condition(s). Further exploration of these tardive sexual syndromes may yield greater understanding of tardive syndromes in general.

Cluster Headache: Epidemiology, Pathophysiology, Clinical Features, and Diagnosis

PubMed Central

Wei, Diana Yi-Ting; Yuan Ong, Jonathan Jia; Goadsby, Peter James

2018-01-01

Cluster headache is a primary headache disorder affecting up to 0.1% of the population. Patients suffer from cluster headache attacks lasting from 15 to 180 min up to 8 times a day. The attacks are characterized by the severe unilateral pain mainly in the first division of the trigeminal nerve, with associated prominent unilateral cranial autonomic symptoms and a sense of agitation and restlessness during the attacks. The male-to-female ratio is approximately 2.5:1. Experimental, clinical, and neuroimaging studies have advanced our understanding of the pathogenesis of cluster headache. The pathophysiology involves activation of the trigeminovascular complex and the trigeminal-autonomic reflex and accounts for the unilateral severe headache, the prominent ipsilateral cranial autonomic symptoms. In addition, the circadian and circannual rhythmicity unique to this condition is postulated to involve the hypothalamus and suprachiasmatic nucleus. Although the clinical features are distinct, it may be misdiagnosed, with patients often presenting to the otolaryngologist or dentist with symptoms. The prognosis of cluster headache remains difficult to predict. Patients with episodic cluster headache can shift to chronic cluster headache and vice versa. Longitudinally, cluster headache tends to remit with age with less frequent bouts and more prolonged periods of remission in between bouts. PMID:29720812

Cluster Headache: Epidemiology, Pathophysiology, Clinical Features, and Diagnosis.

PubMed

Wei, Diana Yi-Ting; Yuan Ong, Jonathan Jia; Goadsby, Peter James

2018-04-01

Cluster headache is a primary headache disorder affecting up to 0.1% of the population. Patients suffer from cluster headache attacks lasting from 15 to 180 min up to 8 times a day. The attacks are characterized by the severe unilateral pain mainly in the first division of the trigeminal nerve, with associated prominent unilateral cranial autonomic symptoms and a sense of agitation and restlessness during the attacks. The male-to-female ratio is approximately 2.5:1. Experimental, clinical, and neuroimaging studies have advanced our understanding of the pathogenesis of cluster headache. The pathophysiology involves activation of the trigeminovascular complex and the trigeminal-autonomic reflex and accounts for the unilateral severe headache, the prominent ipsilateral cranial autonomic symptoms. In addition, the circadian and circannual rhythmicity unique to this condition is postulated to involve the hypothalamus and suprachiasmatic nucleus. Although the clinical features are distinct, it may be misdiagnosed, with patients often presenting to the otolaryngologist or dentist with symptoms. The prognosis of cluster headache remains difficult to predict. Patients with episodic cluster headache can shift to chronic cluster headache and vice versa. Longitudinally, cluster headache tends to remit with age with less frequent bouts and more prolonged periods of remission in between bouts.

Enduring sexual dysfunction after treatment with antidepressants, 5α-reductase inhibitors and isotretinoin: 300 cases

PubMed Central

Healy, David; Le Noury, Joanna; Mangin, Derelie

2018-01-01

OBJECTIVE: To investigate clinical reports of post-SSRI sexual dysfunction (PSSD), post-finasteride syndrome (PFS) and enduring sexual dysfunction following isotretinoin. METHODS: Data from RxISK.org, a global adverse event reporting website, have been used to establish the clinical features, demographic details and clinical trajectories of syndromes of persistent sexual difficulties following three superficially different treatment modalities. RESULTS We report on 300 cases of enduring sexual dysfunction from 37 countries following 14 different drugs comprised of serotonin reuptake inhibiting antidepressants, 5α-reductase inhibitors and isotretinoin. While reports of certain issues were unique to the antidepressants, such as the onset of premature ejaculation and persistent genital arousal disorder (PGAD), there was also a significant overlap in symptom profile between the drug groups, with common features including genital anaesthesia, pleasureless or weak orgasm, loss of libido and impotence. Secondary consequences included relationship breakdown and impaired quality of life. CONCLUSIONS These data point to a legacy syndrome or syndromes comprising a range of disturbances to sexual function. More detailed studies will require developments in coding systems that recognise the condition(s). Further exploration of these tardive sexual syndromes may yield greater understanding of tardive syndromes in general. PMID:29733030

Clinical features and sera anti-aquaporin 4 antibody positivity in patients with demyelinating disorders of the central nervous system from Tianjin, China.

PubMed

Yang, Chun-Sheng; Zhang, Da-Qi; Wang, Jing-Hua; Jin, Wei-Na; Li, Min-Shu; Liu, Jie; Zhang, Cun-Jin; Li, Ting; Shi, Fu-Dong; Yang, Li

2014-01-01

To investigate the clinical characteristics and sera anti-aquaporin 4 (AQP4) antibody positivity in patients with inflammatory demyelinating disorders (IDDs) of the central nervous system (CNS) in Tianjin, China. We retrospectively evaluated 234 patients with IDDs including neuromyelitis optica (NMO), recurrent optic neuritis (rON), longitudinally extensive transverse myelitis (LETM), clinically isolated syndrome (CIS), and multiple sclerosis (MS) groups. Sera from 217 patients were determined for AQP4-Ab. The clinical characteristics and sera anti-AQP4 positivity were compared. The IDDS comprised 63 MS, 51 NMO, 56 LETM, 10 rON, and 54 CIS. Compared with MS, NMO had a higher frequency of occurrence in women, intractable hiccup and nausea (IHN), medullospinal lesion, longitudinally extensive spinal cord lesions (LESCL) and bilateral ON, disease onset at a later age, and worsening residual disability. AQP4-Ab-positive rates were 84.1% and 69% in NMO and NMO spectrum disorders (NMOSD), respectively, whereas it was undetectable in all of the MS sera samples. We comprehensively contrast the distinct clinical features of MS, NMO, and NMOSD in our center. A sensitive AQP4-Ab assay is necessary for the early diagnosis of NMOSD in our patients. Neither medullospinal lesion nor IHN is unique in NMO. © 2013 John Wiley & Sons Ltd.

A descriptive analysis of 14 cases of progressive-psuedorheumatoid-arthropathy of childhood from south India: review of literature in comparison with juvenile idiopathic arthritis.

PubMed

Ekbote, Alka V; Danda, Debashish; Kumar, Sathish; Danda, Sumita; Madhuri, Vrisha; Gibikote, Sridhar

2013-06-01

Progressive-psuedorheumatoid-arthropathy of childhood (PPAC) is an autosomal recessive single gene skeletal dysplasia involving joints. The gene attributed to its cause is WNT1-inducible-signaling pathway protein3 (WISP3). To study the clinical and radiographic presentation of PPAC in Indian patients and to compare with described features of PPAC and Juvenile Idiopathic Arthritis (JIA) from published literature. All cases (n = 14) of PPAC seen in the Rheumatology and Clinical Genetics outpatient clinic between 2008 and 2011 with classical, clinical, and radiological features were studied. The demographic and clinical data were obtained from medical records of the outpatient visits. Slight female preponderance (57%) and history of consanguinity in parents (43%) was observed in this group. The median age at onset was 4.5 years (range from birth to 9 years of age). Early presentation below the age of 3 years was seen in 3/14 patients (21%) in this group. The growth of all the patients fell below the 3rd percentile for the age. Historically, hip joint involvement was the most common presenting feature; however, elbow, wrist, knees, feet, spine, shoulder joints and small joints, namely proximal interphalangeal (PIP), distal interphalangeal (DIP), metacarpophalangeal (MCP), metatarsophalangeal joints (MTP), and interphalangeal joints (IP) of the feet, were also involved, either clinically or radiologically in varying proportions. Platyspondyly was noted in all. Molecular analysis of the WISP3 gene identified mutations in all the 5 individuals in whom it was done. This descriptive case series of PPAC from India reports distinctly differentiating clinical, radiological, and molecular markers in contrast with classically described features of JIA, its mimic. Early presentation (age of onset below 3 years) with involvement of interphalangeal joints seen in three patients (21%) was a unique finding, with missense WISP3 gene mutations in all of them. Timely diagnosis of this entity can spare the patient from unnecessary investigations and toxic medications. Copyright © 2013 Elsevier Inc. All rights reserved.

Hallucinations: A Systematic Review of Points of Similarity and Difference Across Diagnostic Classes.

PubMed

Waters, Flavie; Fernyhough, Charles

2017-01-01

Hallucinations constitute one of the 5 symptom domains of psychotic disorders in DSM-5, suggesting diagnostic significance for that group of disorders. Although specific featural properties of hallucinations (negative voices, talking in the third person, and location in external space) are no longer highlighted in DSM, there is likely a residual assumption that hallucinations in schizophrenia can be identified based on these candidate features. We investigated whether certain featural properties of hallucinations are specifically indicative of schizophrenia by conducting a systematic review of studies showing direct comparisons of the featural and clinical characteristics of (auditory and visual) hallucinations among 2 or more population groups (one of which included schizophrenia). A total of 43 articles were reviewed, which included hallucinations in 4 major groups (nonclinical groups, drug- and alcohol-related conditions, medical and neurological conditions, and psychiatric disorders). The results showed that no single hallucination feature or characteristic uniquely indicated a diagnosis of schizophrenia, with the sole exception of an age of onset in late adolescence. Among the 21 features of hallucinations in schizophrenia considered here, 95% were shared with other psychiatric disorders, 85% with medical/neurological conditions, 66% with drugs and alcohol conditions, and 52% with the nonclinical groups. Additional differences rendered the nonclinical groups somewhat distinctive from clinical disorders. Overall, when considering hallucinations, it is inadvisable to give weight to the presence of any featural properties alone in making a schizophrenia diagnosis. It is more important to focus instead on the co-occurrence of other symptoms and the value of hallucinations as an indicator of vulnerability. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

DRESS syndrome with thrombotic microangiopathy revealing a Noonan syndrome: Case report.

PubMed

Bobot, Mickaël; Coen, Matteo; Simon, Clémentine; Daniel, Laurent; Habib, Gilbert; Serratrice, Jacques

2018-04-01

The life-threatening drug rash with eosinophilia and systemic symptoms (DRESS) syndrome occurs most commonly after exposure to drugs, clinical features mimic those found with other serious systemic disorders. It is rarely associated with thrombotic microangiopathy. We describe the unique case of a 44-year-old man who simultaneously experienced DRESS syndrome with thrombotic microangiopathy (TMA) after a 5 days treatment with fluindione. Clinical evaluation leads to the discovery of an underlying lymphangiomatosis, due to a Noonan syndrome. The anticoagulant was withdrawn, and corticosteroids (1 mg/kg/day) and acenocoumarol were started. Clinical improvement ensued. At follow-up the patient is well. The association of DRESS with TMA is a rare condition; we believe that the presence of the underlying Noonan syndrome could have been the trigger. Moreover, we speculate about the potential interrelations between these entities.

Personalized medicine in psychiatry.

PubMed

Wium-Andersen, Ida Kim; Vinberg, Maj; Kessing, Lars Vedel; McIntyre, Roger S

2017-01-01

Personalized medicine is a model in which a patient's unique clinical, genetic, and environmental characteristics are the basis for treatment and prevention. Aim, method, and results: This review aims to describe the current tools, phenomenological features, clinical risk factors, and biomarkers used to provide personalized medicine. Furthermore, this study describes the target areas in which they can be applied including diagnostics, treatment selection and response, assessment of risk of side-effects, and prevention. Personalized medicine in psychiatry is challenged by the current taxonomy, where the diagnostic categories are broad and great biological heterogeneity exists within each category. There is, thus, a gap between the current advanced research prospects and clinical practice, and the current taxonomy is, thus, a poor basis for biological research. The discussion proposes possible solutions to narrow this gap and to move psychiatric research forward towards personalized medicine.

Edoxaban for the long-term treatment of venous thromboembolism: rationale and design of the Hokusai-venous thromboembolism study--methodological implications for clinical trials.

PubMed

Raskob, G; Büller, H; Prins, M; Segers, A; Shi, M; Schwocho, L; van Kranen, R; Mercuri, M

2013-07-01

New oral anticoagulants may simplify long-term therapy by eliminating the need for laboratory monitoring. Edoxaban is an oral, direct inhibitor of factor Xa that is given in a fixed dose once daily. The Hokusai-VTE study is a randomized, double-blind trial to evaluate whether initial low molecular weight heparin (LMWH) followed by edoxaban (60 mg once daily) is non-inferior to LMWH followed by warfarin (International Normalized Ratio of 2.0-3.0) for the prevention of recurrent thromboembolism in patients with acute symptomatic venous thromboembolism (VTE). The primary efficacy outcome is symptomatic recurrent VTE during the 12-month study period. The principal safety outcome is clinically relevant bleeding (major or non-major) occurring during or within 3 days of stopping study treatment. A clinical events committee adjudicates all suspected outcome events. A unique study design feature is the flexible treatment duration of between 3 and 12 months to simulate usual clinical practice, and enabled by: (i) double-blinding to minimize bias that could occur if knowledge of the patient's treatment influenced the duration of therapy; and (ii) follow-up for 12 months of all patients and inclusion in the primary efficacy analysis, regardless of the duration of therapy received. A second innovative design feature is the strategy for achieving an appropriate time in therapeutic range in the warfarin group, with central tracking for each participating center and feedback to the investigators. The standard methods combined with innovative design features should achieve study results that are both scientifically valid and relevant to clinical practice. © 2013 International Society on Thrombosis and Haemostasis.

Association Between Patient- Centered Medical Home Features and Satisfaction With Family Medicine Residency Training in the US.

PubMed

Carney, Patricia A; Waller, Elaine; Dexter, Eve; Marino, Miguel; Rosener, Stephanie E; Green, Larry A; Jones, Geoffrey; M Keister, J Drew; Dostal, Julie A; Jones, Samuel M; Eiff, M Patrice

2016-11-01

Primary care residencies are undergoing dramatic changes because of changing health care systems and evolving demands for updated training models. We examined the relationships between residents' exposures to patient-centered medical home (PCMH) features in their assigned continuity clinics and their satisfaction with training. Longitudinal surveys were collected annually from residents evaluating satisfaction with training using a 5-point Likert-type scale (1=very unsatisfied to 5=very satisfied) from 2007 through 2011, and the presence or absence of PCMH features were collected from 24 continuity clinics during the same time period. Odds ratios on residents' overall satisfaction were compared according to whether they had no exposure to PCMH features, some exposure (1-2 years), or full exposure (all 3 or more years). Fourteen programs and 690 unique residents provided data to this study. Resident satisfaction with training was highest with full exposure for integrated case management compared to no exposure, which occurred in 2010 (OR=2.85, 95% CI=1.40, 5.80). Resident satisfaction was consistently statistically lower with any or full exposure (versus none) to expanded clinic hours in 2007 and 2009 (eg, OR for some exposure in 2009 was 0.31 95% CI=0.19, 0.51, and OR for full exposure 0.28 95% CI=0.16, 0.49). Resident satisfaction for many electronic health record (EHR)-based features tended to be significantly lower with any exposure (some or full) versus no exposure over the study period. For example, the odds ratio for resident satisfaction was significantly lower with any exposure to electronic health records in continuity practice in 2008, 2009, and 2010 (OR for some exposure in 2008 was 0.36; 95% CI=0.19, 0.70, with comparable results in 2009, 2010). Resident satisfaction with training was inconsistently correlated with exposure to features of PCMH. No correlation between PCMH exposure and resident satisfaction was sustained over time.

How Much Do We Know about Adult-onset Primary Tics? Prevalence, Epidemiology, and Clinical Features.

PubMed

Robakis, Daphne

2017-01-01

Tic disorders are generally considered to be of pediatric onset; however, reports of adult-onset tics exist in the literature. Tics can be categorized as either primary or secondary, with the latter being the larger group in adults. Primary or idiopathic tics that arise in adulthood make up a subset of tic disorders whose epidemiologic and clinical features have not been well delineated. Articles to be included in this review were identified by searching PubMed, SCOPUS, and Web of Science using the terms adult- and late-onset tics, which resulted in 120 unique articles. Duplicates were removed. Citing references were identified using Google Scholar; all references were reviewed for relevance. The epidemiologic characteristics, clinical phenomenology, and optimal treatment of adult-onset tics have not been ascertained. Twenty-six patients with adult-onset, primary tics were identified from prior case reports. The frequency of psychiatric comorbidities may be lower in adults than in children, and obsessive compulsive disorder was the most common comorbidity. Adult-onset primary tics tend to wax and wane, occur predominantly in males, are often both motor and phonic in the same individual, and are characterized by a poor response to treatment. We know little about adult-onset tic disorders, particularly ones without a secondary association or cause. They are not common, and from the limited data available, appear to share some but not all features with childhood tics. Further research will be important in gaining a better understanding of the epidemiology and clinical manifestations of this disorder.

How Much Do We Know about Adult-onset Primary Tics? Prevalence, Epidemiology, and Clinical Features

PubMed Central

Robakis, Daphne

2017-01-01

Background Tic disorders are generally considered to be of pediatric onset; however, reports of adult-onset tics exist in the literature. Tics can be categorized as either primary or secondary, with the latter being the larger group in adults. Primary or idiopathic tics that arise in adulthood make up a subset of tic disorders whose epidemiologic and clinical features have not been well delineated. Methods Articles to be included in this review were identified by searching PubMed, SCOPUS, and Web of Science using the terms adult- and late-onset tics, which resulted in 120 unique articles. Duplicates were removed. Citing references were identified using Google Scholar; all references were reviewed for relevance. Results The epidemiologic characteristics, clinical phenomenology, and optimal treatment of adult-onset tics have not been ascertained. Twenty-six patients with adult-onset, primary tics were identified from prior case reports. The frequency of psychiatric comorbidities may be lower in adults than in children, and obsessive compulsive disorder was the most common comorbidity. Adult-onset primary tics tend to wax and wane, occur predominantly in males, are often both motor and phonic in the same individual, and are characterized by a poor response to treatment. Discussion We know little about adult-onset tic disorders, particularly ones without a secondary association or cause. They are not common, and from the limited data available, appear to share some but not all features with childhood tics. Further research will be important in gaining a better understanding of the epidemiology and clinical manifestations of this disorder. PMID:28546883

Churg-Strauss syndrome with coexistence of eosinophilic vasculitis, granulomatous phlebitis and granulomatous dermatitis in bullous pemphigoid-like blisters.

PubMed

Ishibashi, Masafumi; Kudo, Saori; Yamamoto, Kyoko; Shimai, Nobuko; Chen, Ko-Ron

2011-03-01

The main histopathological features in the cutaneous lesions of Churg-Strauss syndrome (CSS) are dermal leukocytoclastic vasculitis with a variable eosinophilic infiltrate and non-vasculitic tissue eosinophilia with granuloma formation. This wide histopathological spectrum may account for the various skin manifestations of CSS. However, the unique histopathological combination of dermal eosinophilic vasculitis and subcutaneous granulomatous phlebitis accompanied by bulla formation has not been previously described. We report an unusual CSS case showing dermal necrotizing eosinophilic vasculitis and granulomatous phlebitis in purpuric lesions coupled with subepidermal blistering. The blisters showed dermal granulomatous dermatitis and eosinophilia without evidence of vasculitis. Dermal necrotizing eosinophilic vasculitis was characterized by fibrinoid alteration of the vessel wall, a prominent perivascular eosinophilic infiltrate, a few infiltrating histiocytes along the affected vessel wall, and the absence of neutrophilic infiltration. The underlying subcutaneous granulomatous phlebitis was characterized by an angiocentric histiocytic infiltrate surrounded by marked eosinophilic infiltrate. Deposition of cytotoxic proteins and radicals derived from eosinophils in the vessel walls and papillary dermis followed by a secondary granulomatous response may account for the unique clinical and histopathological features in this case. Copyright © 2010 John Wiley & Sons A/S.

Orally disintegrating dosage forms and taste-masking technologies; 2010.

PubMed

Douroumis, Dennis

2011-05-01

In the last decade the development of orally disintegrating tablets (ODTs) and thin-film platforms has grown enormously in the field of pharmaceutical industry. A wide variety of new masking technologies combined with the aforementioned platforms have been developed in order to mask the taste of bitter active substances and achieve patient compliance. The commercial success and viability of such products requires the development of robust formulations with excellent palatability, disintegration times, physicochemical stability and pharmacokinetic profiles. In this review, emerging taste-masking technologies applied to solid dosage form manufacturing are summarized. The unique features and principles of taste-masking approaches used with ODT platforms are discussed, including the advantages and limitations of each technology. A brief discussion is also included on the taste masking of thin-film technologies, owing to their similar applications and requirements. This review elucidates the unique features of current commercially available or highly promising ODT and thin-film technologies, along with taste-masking approaches used in the manufacturing of oral solid dosage forms. A better understanding of these drug delivery approaches will help researchers to select the appropriate platform, or to develop innovative products with improved safety, compliance and clinical value.

Common respiratory conditions of the newborn

PubMed Central

Gallacher, David J.; Hart, Kylie

2016-01-01

Key points Respiratory distress is a common presenting feature among newborn infants. Prompt investigation to ascertain the underlying diagnosis and appropriate subsequent management is important to improve outcomes. Many of the underlying causes of respiratory distress in a newborn are unique to this age group. A chest radiograph is crucial to assist in diagnosis of an underlying cause. Educational aims To inform readers of the common respiratory problems encountered in neonatology and the evidence-based management of these conditions. To enable readers to develop a framework for diagnosis of an infant with respiratory distress. The first hours and days of life are of crucial importance for the newborn infant as the infant adapts to the extra-uterine environment. The newborn infant is vulnerable to a range of respiratory diseases, many unique to this period of early life as the developing fluid-filled fetal lungs adapt to the extrauterine environment. The clinical signs of respiratory distress are important to recognise and further investigate, to identify the underlying cause. The epidemiology, diagnostic features and management of common neonatal respiratory conditions are covered in this review article aimed at all healthcare professionals who come into contact with newborn infants. PMID:27064402

Phosphaturic mesenchymal tumor, mixed connective tissue variant, of the mandible: report of a case and review of the literature.

PubMed

Woo, Victoria L; Landesberg, Regina; Imel, Erik A; Singer, Steven R; Folpe, Andrew L; Econs, Michael J; Kim, Taeyun; Harik, Lara R; Jacobs, Thomas P

2009-12-01

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome that results in renal phosphate wasting with hypophosphatemia. In most cases, the underlying cause of TIO is a small mesenchymal neoplasm that is often difficult to detect, resulting in delayed diagnosis. One such neoplasm is the phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT), an unusual entity with unique morphologic and biochemical features. Most of these tumors are found at appendicular sites with only rare cases reported in the jaws. We describe a PMTMCT involving the mandible in a patient with a protracted history of osteomalacia. A review of the current literature is provided with emphasis on the clinical and histologic features, etiopathogenesis, and management of PMTMCT in the setting of TIO.

Placenta and Placental Derivatives in Regenerative Therapies: Experimental Studies, History, and Prospects

PubMed Central

Prokopyuk, Volodymyr; Pogozhykh, Denys

2018-01-01

Placental structures, capable to persist in a genetically foreign organism, are a natural model of allogeneic engraftment carrying a number of distinctive properties. In this review, the main features of the placenta and its derivatives such as structure, cellular composition, immunological and endocrine aspects, and the ability to invasion and deportation are discussed. These features are considered from a perspective that determines the placental material as a unique source for regenerative cell therapies and a lesson for immunological tolerance. A historical overview of clinical applications of placental extracts, cells, and tissue components is described. Empirically accumulated data are summarized and compared with modern research. Furthermore, we define scopes and outlooks of application of placental cells and tissues in the rapidly progressing field of regenerative medicine. PMID:29535770

Phosphaturic mesenchymal tumor, mixed connective tissue variant, of the mandible: Report of a case and review of the literature

PubMed Central

Woo, Victoria L.; Landesberg, Regina; Imel, Erik A.; Singer, Steven R.; Folpe, Andrew L.; Econs, Michael J.; Kim, Taeyun; Harik, Lara R.; Jacobs, Thomas P.

2009-01-01

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome that results in renal phosphate wasting with hypophosphatemia. In most cases, the underlying cause of TIO is a small mesenchymal neoplasm that is often difficult to detect, resulting in delayed diagnosis. One such neoplasm is the phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT), an unusual entity with unique morphologic and biochemical features. The majority of these tumors are found at appendicular sites with only rare cases reported in the jaws. We describe a PMTMCT involving the mandible in a patient with a protracted history of osteomalacia. A review of the current literature is provided with emphasis on the clinical and histologic features, etiopathogenesis, and management of PMTMCT in the setting of TIO. PMID:19828339

SLEEP AND CIRCADIAN RHYTHM DISORDERS IN PARKINSON'S DISEASE.

PubMed

Gros, Priti; Videnovic, Aleksandar

2017-09-01

Sleep disorders are among the most challenging non-motor features of Parkinson's disease (PD) and significantly affect quality of life. Research in this field has gained recent interest among clinicians and scientists and is rapidly evolving. This review is dedicated to sleep and circadian dysfunction associated with PD. Most primary sleep disorders may co-exist with PD; majority of these disorders have unique features when expressed in the PD population. We discuss the specific considerations related to the common sleep problems in Parkinson's disease including insomnia, rapid eye movement sleep behavior disorder, restless legs syndrome, sleep disordered breathing, excessive daytime sleepiness and circadian rhythm disorders. Within each of these sleep disorders, we present updated definitions, epidemiology, etiology, diagnosis, clinical implications and management. Furthermore, areas of potential interest for further research are outlined.

Performing skin microbiome research: A method to the madness

PubMed Central

Kong, Heidi H.; Andersson, Björn; Clavel, Thomas; Common, John E.; Jackson, Scott A.; Olson, Nathan D.; Segre, Julia A.; Traidl-Hoffmann, Claudia

2017-01-01

Growing interest in microbial contributions to human health and disease has increasingly led investigators to examine the microbiome in both healthy skin and cutaneous disorders, including acne, psoriasis and atopic dermatitis. The need for common language, effective study design, and validated methods are critical for high-quality, standardized research. Features, unique to skin, pose particular challenges when conducting microbiome research. This review discusses microbiome research standards and highlights important factors to consider, including clinical study design, skin sampling, sample processing, DNA sequencing, control inclusion, and data analysis. PMID:28063650

A Comprehensive Pan-Cancer Molecular Study of Gynecologic and Breast Cancers. | Office of Cancer Genomics

Cancer.gov

We analyzed molecular data on 2,579 tumors from The Cancer Genome Atlas (TCGA) of four gynecological types plus breast. Our aims were to identify shared and unique molecular features, clinically significant subtypes, and potential therapeutic targets. We found 61 somatic copy-number alterations (SCNAs) and 46 significantly mutated genes (SMGs). Eleven SCNAs and 11 SMGs had not been identified in previous TCGA studies of the individual tumor types. We found functionally significant estrogen receptor-regulated long non-coding RNAs (lncRNAs) and gene/lncRNA interaction networks.

Exercise-induced bilateral rectus sheath hematomas presenting as acute abdominal pain with scrotal swelling and pressure: case report and review.

PubMed

Auten, Jonathan D; Schofer, Joel M; Banks, Steven L; Rooney, Timothy B

2010-04-01

Rectus sheath hematoma (RSH) is an uncommon but significant cause of acute abdominal pain in patients presenting to the Emergency Department. RSHs are often misdiagnosed as other more common causes of abdominal pain. This case describes a 23-year-old male presenting with acute abdominal pain, scrotal swelling, and associated scrotal pressure. The case highlights the uniqueness of this particular presentation and the clinical features, risk factors, diagnosis, and treatment of RSH. Published by Elsevier Inc.

Psychosomatic aspects of end-stage renal failure.

PubMed

Sensky, T

1993-01-01

End-stage renal failure (ESRD) is more than a typical chronic disease. Its treatment includes features which arguably make this condition unique. Selected psychosomatic aspects of ESRD are reviewed, including psychiatric morbidity, patients' adherence to their treatments, quality of life and the emotional impact on staff involved in treating patients with ESRD. Rather than presenting a comprehensive review of the results of published research, particular emphasis is laid on the critical appraisal of the methodology of published studies, to examine the extent to which these have provided answers to clinically important questions.

Trauma associated sleep disorder: a proposed parasomnia encompassing disruptive nocturnal behaviors, nightmares, and REM without atonia in trauma survivors.

PubMed

Mysliwiec, Vincent; O'Reilly, Brian; Polchinski, Jason; Kwon, Herbert P; Germain, Anne; Roth, Bernard J

2014-10-15

To characterize the clinical, polysomnographic and treatment responses of patients with disruptive nocturnal behaviors (DNB) and nightmares following traumatic experiences. A case series of four young male, active duty U.S. Army Soldiers who presented with DNB and trauma related nightmares. Patients underwent a clinical evaluation in a sleep medicine clinic, attended overnight polysomnogram (PSG) and received treatment. We report pertinent clinical and PSG findings from our patients and review prior literature on sleep disturbances in trauma survivors. DNB ranged from vocalizations, somnambulism to combative behaviors that injured bed partners. Nightmares were replays of the patient's traumatic experiences. All patients had REM without atonia during polysomnography; one patient had DNB and a nightmare captured during REM sleep. Prazosin improved DNB and nightmares in all patients. We propose Trauma associated Sleep Disorder (TSD) as a unique sleep disorder encompassing the clinical features, PSG findings, and treatment responses of patients with DNB, nightmares, and REM without atonia after trauma.

Unique Angiographic Appearances of Moyamoya Disease Detected with 3-Dimensional Rotational Digital Subtraction Angiography Imaging Showing the Hemodynamic Status.

PubMed

Karakama, Jun; Nariai, Tadashi; Hara, Shoko; Hayashi, Shihori; Sumita, Kazutaka; Inaji, Motoki; Tanaka, Yoji; Wagatsuma, Kei; Ishii, Kenji; Nemoto, Shigeru; Maehara, Taketoshi

2018-04-10

The aim of this study was to identify the unique morphological arterial features in patients with moyamoya disease on 3-dimensional rotational digital subtraction angiography. One hundred seven hemispheres of 58 consecutive patients with moyamoya disease that were analyzed with fused 3-dimensional images of internal carotid angiograms and vertebral angiograms that were marked with different colors were reviewed. Angiographic findings in the posterior watershed area were classified, and the utility of the classification was analyzed by comparing it with clinical presentations and quantitative hemodynamic parameters obtained with positron emission tomography. Two unique angiographic appearances were identified. A vacant vessel appearance (no arterial inflow despite absence of cortical infarction) was observed mostly in transient ischemic attack hemispheres. In hemispheres with a vacant vessel appearance, cerebral blood flow was decreased, cerebral blood volume was increased, and mean transit time was prolonged significantly (P = .00017, P = .0061, and P = .00026, respectively). A cocktail vessel appearance (mixture of carotid and vertebral arterial flow) was most commonly observed in asymptomatic cases, as well as in ischemic hemispheres. Cerebral blood volume increased and mean transit time was prolonged significantly (P = .036 and P = .014, respectively) in hemispheres with a cocktail vessel appearance. The trend of progression in hemodynamic severity in the order of normal appearance, cocktail vessel appearance, and vacant vessel appearance in the watershed area was statistically significant. Fused 3-dimensional digital subtraction angiography demonstrated unique angiographic features in the watershed area, and this represented the degree of cerebral hemodynamic impairment in moyamoya disease. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Extra-articular hip impingement: a narrative review of the literature

PubMed Central

Cheatham, Scott W.

2016-01-01

There is growing subgroup of patients with poor outcomes after hip arthroscopy for intra-articular pathology suggesting unrecognized cause(s) of impingement may exist. Extra-articular hip impingement (EHI) is an emerging group of conditions that have been associated with intra-articular causes of impingement and may be an unrecognized source of pain. EHI is caused by abnormal contact between the extra-articular regions of the proximal femur and pelvis. This review discusses the most common forms for EHI including: central iliopsoas impingement, subspine impingement, ischiofemoral impingement, and greater trochanteric-pelvic impingement. The clinical presentation of each pathology will be discussed since EHI conditions share similar clinical features as the intra-articular pathology but also contain some unique characteristics. PMID:27069266

Cardiac output monitoring using indicator-dilution techniques: basics, limits, and perspectives.

PubMed

Reuter, Daniel A; Huang, Cecil; Edrich, Thomas; Shernan, Stanton K; Eltzschig, Holger K

2010-03-01

The ability to monitor cardiac output is one of the important cornerstones of hemodynamic assessment for managing critically ill patients at increased risk for developing cardiac complications, and in particular in patients with preexisting cardiovascular comorbidities. For >30 years, single-bolus thermodilution measurement through a pulmonary artery catheter for assessment of cardiac output has been widely accepted as the "clinical standard" for advanced hemodynamic monitoring. In this article, we review this clinical standard, along with current alternatives also based on the indicator-dilution technique, such as the transcardiopulmonary thermodilution and lithium dilution techniques. In this review, not only the underlying technical principles and the unique features but also the limitations of each application of indicator dilution are outlined.

Occipital Intraosseous Hemangioma over Torcula: Unusual Presentation with Raised Intracranial Pressure.

PubMed

Rao, K V L N; Beniwal, Manish; Vazhayil, Vikas; Somanna, Sampath; Yasha, T C

2017-12-01

Hemangiomas of the bone are benign, uncommon, slow-growing lesions accounting for <1.0% of all bony neoplasms. Intraosseous occipital hemangiomas are rare, and occipital hemangiomas presenting with features of raised intracranial tension are, with only 2 cases reported to date. In this case report, we describe the unique case of a 30-year-old male patient presenting with raised intracranial pressure due to venous obstruction at the torcula. The patient underwent excision of the lesion and became symptom free. Although these are benign lesions, they can have a varied clinical presentation. An understanding of the different clinical presentations and surgical nuances in excising such tumors can lead to early diagnosis and good patient outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification Of Minangkabau Landscape Characters

NASA Astrophysics Data System (ADS)

Asrina, M.; Gunawan, A.; Aris, Munandar

2017-10-01

Minangkabau is one of cultures in indonesia which occupies landscape intact. Landscape of Minangkabau have a very close relationship with the culture of the people. Uniqueness of Minangkabau culture and landscape forming an inseparable characterunity. The landscape is necessarily identified to know the inherent landscape characters. The objective of this study was to identify the character of the Minangkabau landscape characterizes its uniqueness. The study was conducted by using descriptive method comprised literature review and field observasion. Observed the landscape characters comprised two main features, they were major and minor features. Indetification of the features was conducted in two original areas (darek) of the Minangkabau traditional society. The research results showed that major features or natural features of the landscape were predominantly landform, landcover, and hidrology. All luhak (districts) of Minangkabau showed similar main features such as hill, canyon, lake, valley, and forest. The existence of natural features such as hills, canyon and valleys characterizes the nature of minangkabau landscape. Minor features formed by Minangkabau cultural society were agricultural land and settlement. Rumah gadang (big house) is one of famous minor features characterizes the Minangkabau culture. In addition, several historical artefacts of building and others structure may strengthen uniqueness of the Minangkabau landscape character, such as The royal palace, inscription, and tunnels.

A Diagnosis to Consider in an Adult Patient with Facial Features and Intellectual Disability: Williams Syndrome.

PubMed

Doğan, Özlem Akgün; Şimşek Kiper, Pelin Özlem; Utine, Gülen Eda; Alikaşifoğlu, Mehmet; Boduroğlu, Koray

2017-03-01

Williams syndrome (OMIM #194050) is a rare, well-recognized, multisystemic genetic condition affecting approximately 1/7,500 individuals. There are no marked regional differences in the incidence of Williams syndrome. The syndrome is caused by a hemizygous deletion of approximately 28 genes, including ELN on chromosome 7q11.2. Prenatal-onset growth retardation, distinct facial appearance, cardiovascular abnormalities, and unique hypersocial behavior are among the most common clinical features. Here, we report the case of a patient referred to us with distinct facial features and intellectual disability, who was diagnosed with Williams syndrome at the age of 37 years. Our aim is to increase awareness regarding the diagnostic features and complications of this recognizable syndrome among adult health care providers. Williams syndrome is usually diagnosed during infancy or childhood, but in the absence of classical findings, such as cardiovascular anomalies, hypercalcemia, and cognitive impairment, the diagnosis could be delayed. Due to the multisystemic and progressive nature of the syndrome, accurate diagnosis is critical for appropriate care and screening for the associated morbidities that may affect the patient's health and well-being.

Methods, systems and devices for detecting threatening objects and for classifying magnetic data

DOEpatents

Kotter, Dale K [Shelley, ID; Roybal, Lyle G [Idaho Falls, ID; Rohrbaugh, David T [Idaho Falls, ID; Spencer, David F [Idaho Falls, ID

2012-01-24

A method for detecting threatening objects in a security screening system. The method includes a step of classifying unique features of magnetic data as representing a threatening object. Another step includes acquiring magnetic data. Another step includes determining if the acquired magnetic data comprises a unique feature.

Family-based risk factors for non-suicidal self-injury: Considering influences of maltreatment, adverse family-life experiences, and parent-child relational risk.

PubMed

Martin, Jodi; Bureau, Jean-François; Yurkowski, Kim; Fournier, Tania Renaud; Lafontaine, Marie-France; Cloutier, Paula

2016-06-01

The current investigation addressed the potential for unique influences of perceived childhood maltreatment, adverse family-life events, and parent-child relational trauma on the lifetime occurrence and addictive features of non-suicidal self-injury (NSSI). Participants included 957 undergraduate students (747 females; M = 20.14 years, SD = 3.88) who completed online questionnaires regarding the key variables under study. Although self-injuring youth reported more experiences with each family-based risk factor, different patterns of association were found when lifetime engagement in NSSI or its addictive features were under study. Perceived parent-child relational trauma was uniquely linked with NSSI behavior after accounting for perceived childhood maltreatment; adverse family-life events had an additional unique association. In contrast, perceived paternal maltreatment was uniquely related with NSSI's addictive features. Findings underline the importance of studying inter-related family-based risk factors of NSSI simultaneously for a comprehensive understanding of familial correlates of NSSI behavior and its underlying features. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

How Do Stress Exposure and Stress Regulation Relate to Borderline Personality Disorder?

PubMed Central

Bourvis, Nadège; Aouidad, Aveline; Cabelguen, Clémence; Cohen, David; Xavier, Jean

2017-01-01

Borderline personality disorder (BPD) is a severe and frequent disorder characterized by a pervasive pattern of instability affecting impulse control, emotional regulation, cognitive processing, self-image and interpersonal relationships. Patients’ personal histories are often marked by stressful or traumatic experiences, either unique or repeated. Moreover, while clinical signs of the disorder include both chronic and acute features, acute features are mostly triggered by acute stressful situations. Such features include transient cognitive distortion, intense anger, uncontrollable impulsivity, and self-harm behavior – including suicide – and contribute to the burden of the disease. In this paper, we review the various aspects (epidemiological, clinical, and physiological) contributing to the relationship between BDP and stress. In particular, we explore the statistical association between stress exposure and the emergence of BPD while taking into account other psychopathologies, such as post-traumatic stress disorder. Then, the different aspects of stress responses (namely, the phenomenological, behavioral, hormonal, neuro-vegetative and neural responses) are reviewed in BPD patients. Pathophysiological hypotheses are formulated to explain the differences in responses between BPD patients and healthy subjects and their relation to BPD symptoms. Although the pathogenesis remains uncertain, our conclusions seem to reflect a specific biological and neural pattern of altered stress perception and regulation in BPD. PMID:29250007

Dominant de novo DSP mutations cause erythrokeratodermia-cardiomyopathy syndrome

PubMed Central

Boyden, Lynn M.; Kam, Chen Y.; Hernández-Martín, Angela; Zhou, Jing; Craiglow, Brittany G.; Sidbury, Robert; Mathes, Erin F.; Maguiness, Sheilagh M.; Crumrine, Debra A.; Williams, Mary L.; Hu, Ronghua; Lifton, Richard P.; Elias, Peter M.; Green, Kathleen J.; Choate, Keith A.

2016-01-01

Disorders of keratinization (DOK) show marked genotypic and phenotypic heterogeneity. In most cases, disease is primarily cutaneous, and further clinical evaluation is therefore rarely pursued. We have identified subjects with a novel DOK featuring erythrokeratodermia and initially-asymptomatic, progressive, potentially fatal cardiomyopathy, a finding not previously associated with erythrokeratodermia. We show that de novo missense mutations clustered tightly within a single spectrin repeat of DSP cause this novel cardio-cutaneous disorder, which we term erythrokeratodermia-cardiomyopathy (EKC) syndrome. We demonstrate that DSP mutations in our EKC syndrome subjects affect localization of desmosomal proteins and connexin 43 in the skin, and result in desmosome aggregation, widening of intercellular spaces, and lipid secretory defects. DSP encodes desmoplakin, a primary component of desmosomes, intercellular adhesion junctions most abundant in the epidermis and heart. Though mutations in DSP are known to cause other disorders, our cohort features the unique clinical finding of severe whole-body erythrokeratodermia, with distinct effects on localization of desmosomal proteins and connexin 43. These findings add a severe, previously undescribed syndrome featuring erythrokeratodermia and cardiomyopathy to the spectrum of disease caused by mutation in DSP, and identify a specific region of the protein critical to the pathobiology of EKC syndrome and to DSP function in the heart and skin. PMID:26604139

How Do Stress Exposure and Stress Regulation Relate to Borderline Personality Disorder?

PubMed

Bourvis, Nadège; Aouidad, Aveline; Cabelguen, Clémence; Cohen, David; Xavier, Jean

2017-01-01

Borderline personality disorder (BPD) is a severe and frequent disorder characterized by a pervasive pattern of instability affecting impulse control, emotional regulation, cognitive processing, self-image and interpersonal relationships. Patients' personal histories are often marked by stressful or traumatic experiences, either unique or repeated. Moreover, while clinical signs of the disorder include both chronic and acute features, acute features are mostly triggered by acute stressful situations. Such features include transient cognitive distortion, intense anger, uncontrollable impulsivity, and self-harm behavior - including suicide - and contribute to the burden of the disease. In this paper, we review the various aspects (epidemiological, clinical, and physiological) contributing to the relationship between BDP and stress. In particular, we explore the statistical association between stress exposure and the emergence of BPD while taking into account other psychopathologies, such as post-traumatic stress disorder. Then, the different aspects of stress responses (namely, the phenomenological, behavioral, hormonal, neuro-vegetative and neural responses) are reviewed in BPD patients. Pathophysiological hypotheses are formulated to explain the differences in responses between BPD patients and healthy subjects and their relation to BPD symptoms. Although the pathogenesis remains uncertain, our conclusions seem to reflect a specific biological and neural pattern of altered stress perception and regulation in BPD.

Novel compound heterozygous DPH1 mutations in a patient with the unique clinical features of airway obstruction and external genital abnormalities.

PubMed

Nakajima, Junya; Oana, Shingo; Sakaguchi, Tomohiro; Nakashima, Mitsuko; Numabe, Hironao; Kawashima, Hisashi; Matsumoto, Naomichi; Miyake, Noriko

2018-04-01

The diphthamide biosynthesis 1 (DPH1) gene encodes one of the essential components of the enzyme catalyzing the first step of diphthamide formation on eukaryotic elongation factor 2 (EEF2). Diphthamide is the posttranslationally modified histidine residue on EEF2 that promotes protein chain elongation in the ribosome. DPH1 defects result in a failure of protein synthesis involving EEF2, leading to growth defects, embryonic lethality, and cell death. In humans, DPH1 mutations cause developmental delay with a short stature, dysmorphic features, and sparse hair, and are inherited in an autosomal recessive manner (MIM#616901). To date, only two homozygous missense mutations in DPH1 (c.17T>A, p.Met6Lys and c.701T>C, p.Leu234Pro) have been reported. We used WES to identify novel compound heterozygous mutations in DPH1 (c.289delG, p.Glu97Lysfs*8 and c.491T>C, p.Leu164Pro) in a patient from a nonconsanguineous family presenting with intellectual disability, a short stature, craniofacial abnormalities, and external genital abnormalities. The clinical phenotype of all patients with DPH1 mutations, including the current patient, revealed core features, although the external genital anomaly was newly recognized in our case.

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.

Epidemiology and outcomes of Endophthalmitis in chronic dialysis patients: a 13-year experience in a tertiary referral center in Taiwan.

PubMed

Kuo, George; Lu, Yueh-An; Sun, Wei-Chiao; Chen, Chao-Yu; Kao, Huang-Kai; Lin, YuJr; Lee, Chia-Hui; Hung, Cheng-Chieh; Tian, Ya-Chung; Hsu, Hsiang-Hao

2017-08-16

Endophthalmitis is a severe eye infection leading to disabling outcome. Because there were only a few case report illustrating endophthalmitis in chronic dialysis patient, we would like to investigate the epidemiology and clinical features of endophthalmitis in chronic dialysis patient in a tertiary referral center. We searched the health information system in the study hospital with ICD9 encoding endophthalmitis during Jan. 2002 to Dec. 2015. A total of 32 episodes of endophthalmitis occurred in chronic dialysis patients. We performed an 1:2 case-control match on propensity score. The demographic features, clinical manifestation, infection focus and visual outcome were recorded. Of the total of 32 patients, 25 were classified as endogenous endophthalmitis and another seven were exogenous. Most patients presented with ophthalmalgia (n = 32, 100%) and periocular swelling (n = 31, 96.8%), whereas half of the patients suffered blurred vision (n = 16, 50%). Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa were the most frequent causative pathogens. Dialysis vascular infection was also a possible unique focus for bacteremia. The visual acuity of the endogenous groups were less likely to improve in the chronic dialysis patients compared with control group. This is the first and the largest case series focusing on endophthalmitis in chronic dialysis patients. Our study showed different pathogen spectrum, an unique bacterial origin and worse visual outcome in these group of patients. Prompt referral to ophthalmologists when the patients present with suspicious symptoms (blurred vision, ophthalmalgia and periocular swelling) is crucial.

[Exploration on academic thoughts of four medical families of acupuncture-moxibustion of the LING, YAN, SHI and SHENG in northern Zhejiang Province].

PubMed

Chen, Feng

2013-12-01

The academic origin and characteristics of medical families of acupuncture-moxibustion in northern Zhejiang Province were explored in this paper. With acupuncture-moxibustion characteristic of medical families in northern Zhejiang Province such as the LING (see text), the YAN (see text), the SHI (see text) and the SHENG (see text) analyzed and arranged, it was found out that taking the Internal Canon of Medicine as theory basis, their academic thoughts comprehensively absorbed acupuncture-moxibustion theories in all ages, and they continuously made innovations through constant practices, resulting in academic thoughts that focusing on application of acupuncture-moxibustion in clinic, using moxibustion for deficient illness and adopting acupuncture-moxibustion and Chinese herbs for severe and acute patients. The academic thoughts of medical families of acupuncture and moxibustion in northern Zhejiang Province are featured by unique acupoint selection and ma nipulation, thorough moxibustion methods and combined application of Chinese herbs and acupuncture-moxibustion, which is a clinical system of diagnosis and treatment with typical Jiangnan features.

Vaginismus and subfertility: case reports on the association observed in clinical practice.

PubMed

Ramli, M; Nora, Mz; Roszaman, R; Hatta, S

2012-01-01

To analyse the features of patients with vaginismus first presented to a gynaecologist for infertility before being referred for psychiatric evaluation and management. The case series aim to provide some insight on features and presentations of Asian women with vaginismus. Vaginismus is characterised by persistent or recurrent difficulties in vaginal penetration despite the woman's wish for coitus. Avoidance, phobia, anticipatory fear of pain and involuntary pelvic muscle contraction are the most common symptoms. We report a series of cases of Malaysian women who had been suffering from vaginismus and 'infertility'. All the cases had never been attended to medically and there were long delays in seeking intervention. There was no history of traumatic sexual experience or any major psychiatric illness in these patients. Majority of the patients had prominent symptoms of anxiety. The cases illustrate that it is important to rule out the possibility of vaginismus among patients with infertility. The former have unique psychological features which require psychological interventions.

De Novo Truncating Variants in ASXL2 Are Associated with a Unique and Recognizable Clinical Phenotype.

PubMed

Shashi, Vandana; Pena, Loren D M; Kim, Katherine; Burton, Barbara; Hempel, Maja; Schoch, Kelly; Walkiewicz, Magdalena; McLaughlin, Heather M; Cho, Megan; Stong, Nicholas; Hickey, Scott E; Shuss, Christine M; Freemark, Michael S; Bellet, Jane S; Keels, Martha Ann; Bonner, Melanie J; El-Dairi, Maysantoine; Butler, Megan; Kranz, Peter G; Stumpel, Constance T R M; Klinkenberg, Sylvia; Oberndorff, Karin; Alawi, Malik; Santer, Rene; Petrovski, Slavé; Kuismin, Outi; Korpi-Heikkilä, Satu; Pietilainen, Olli; Aarno, Palotie; Kurki, Mitja I; Hoischen, Alexander; Need, Anna C; Goldstein, David B; Kortüm, Fanny

2016-10-06

The ASXL genes (ASXL1, ASXL2, and ASXL3) participate in body patterning during embryogenesis and encode proteins involved in epigenetic regulation and assembly of transcription factors to specific genomic loci. Germline de novo truncating variants in ASXL1 and ASXL3 have been respectively implicated in causing Bohring-Opitz and Bainbridge-Ropers syndromes, which result in overlapping features of severe intellectual disability and dysmorphic features. ASXL2 has not yet been associated with a human Mendelian disorder. In this study, we performed whole-exome sequencing in six unrelated probands with developmental delay, macrocephaly, and dysmorphic features. All six had de novo truncating variants in ASXL2. A careful review enabled the recognition of a specific phenotype consisting of macrocephaly, prominent eyes, arched eyebrows, hypertelorism, a glabellar nevus flammeus, neonatal feeding difficulties, hypotonia, and developmental disabilities. Although overlapping features with Bohring-Opitz and Bainbridge-Ropers syndromes exist, features that distinguish the ASXL2-associated condition from ASXL1- and ASXL3-related disorders are macrocephaly, absence of growth retardation, and more variability in the degree of intellectual disabilities. We were also able to demonstrate with mRNA studies that these variants are likely to exert a dominant-negative effect, given that both alleles are expressed in blood and the mutated ASXL2 transcripts escape nonsense-mediated decay. In conclusion, de novo truncating variants in ASXL2 underlie a neurodevelopmental syndrome with a clinically recognizable phenotype. This report expands the germline disorders that are linked to the ASXL genes. Copyright © 2016. Published by Elsevier Inc.

Melanotic Xp11 translocation renal cancer: report of a case with a unique intratumoral sarcoid-like reaction.

PubMed

Ritterhouse, Lauren L; Cykowski, Matthew D; Hassell, Lewis A; Slobodov, Gennady; Bane, Barbara L

2014-04-15

Melanotic Xp11 translocation renal cancer is a rare tumor belonging to the family of microphthalmia-associated transcription factor (MiTF)/transcription factor E (TFE) neoplasms. This tumor family also includes alveolar soft part sarcoma, perivascular epithelioid cell neoplasms, Xp11 translocation renal cell carcinoma, and melanoma. To date, six confirmed melanotic Xp11 translocation cancers (five renal, one ovarian) have been reported in the literature. Here, we report the clinical, histologic, immunohistochemical, and molecular features of a unique melanotic Xp11 translocation renal cancer arising in a 34-year-old African-American female. Histologically, the tumor was composed of epithelioid tumor cells arranged in a nested pattern. The cells had clear to eosinophilic granular cytoplasm, vesicular nuclear chromatin, and prominent nucleoli. Multifocal intracytoplasmic deposits of granular brown melanin pigment were identified and confirmed by Fontana-Masson stain. An unusual histologic feature, not previously reported in melanotic Xp11 translocation renal cancer, was a sarcoid-like granulomatous reaction consisting of tight epithelioid granulomas with lymphocytic cuffing, numerous giant cells, and calcifications. Nuclear transcription factor E3 expression was identified by immunohistochemistry and TFE3 rearrangement was confirmed by fluorescence in situ hybridization. Additional immunohistochemical findings included immunoreactivity for HMB45, cathepsin K, and progesterone receptor; negative staining was seen with actin, desmin, cytokeratins, epithelial membrane antigen, CD10, vimentin, and PAX-8. The patient is currently free of disease, two years following initial clinicoradiologic presentation and twenty-two months following partial nephrectomy without additional therapy. This report further expands the spectrum of morphologic and clinical findings previously described in melanotic Xp11 translocation renal cancer, a distinctive tumor showing overlapping features between Xp11 translocation renal cell carcinoma, melanoma, and perivascular epithelioid cell neoplasms. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/7225796341180634.

The biology, pathogenesis and clinical aspects of acute lymphoblastic leukemia in children with Down syndrome.

PubMed

Lee, P; Bhansali, R; Izraeli, S; Hijiya, N; Crispino, J D

2016-09-01

Children with Down syndrome (DS) are at a 20-fold increased risk for acute lymphoblastic leukemia (DS-ALL). Although the etiology of this higher risk of developing leukemia remains largely unclear, the recent identification of CRLF2 (cytokine receptor like factor 2) and JAK2 mutations and study of the effect of trisomy of Hmgn1 and Dyrk1a (dual-specificity tyrosine phosphorylation-regulated kinase 1A) on B-cell development have shed significant new light on the disease process. Here we focus on the clinical features, biology and genetics of ALL in children with DS. We review the unique characteristics of DS-ALL on both the clinical and molecular levels and discuss the differences in treatments and outcomes in ALL in children with DS compared with those without DS. The identification of new biological insights is expected to pave the way for novel targeted therapies.

[Clinical and genetic analysis of a patient with Treacher Collins syndrome in TCOF1 gene].

PubMed

Li, Hongbo; Zhang, Xu; Li, Zhenyue; Chen, Jing; Lu, Yu; Jia, Jingjie; Yuan, Huijun; Han, Dongyi

2012-05-01

To analyze the clinical and genetic features of a patient with Treacher Collins syndrome (TCS), and identify the mutation in TCOF1 gene. The medical history was taken, and general physical examinations and otological examinations were conducted in this patient. Genomic DNA was extracted from this patient and his parents and complete TCOF1 gene coding exons were amplified by specific PCR primers. Direct sequencing was carried out to identify the mutations. The raw data was analyzed with GeneTool software and molecular biological website. We detected a heterozygous c. 1639 delAG mutation in exon 11 of TCOF1, which resulted in a truncated protein lacking normal function. This mutation is a novel mutation and the second case identified in exon 11 of in TCS. TCS patient reported in this study has unique clinical phenotype. TCOF1 gene mutation is the specific risk factor.

DRESS syndrome with thrombotic microangiopathy revealing a Noonan syndrome

PubMed Central

Bobot, Mickaël; Coen, Matteo; Simon, Clémentine; Daniel, Laurent; Habib, Gilbert; Serratrice, Jacques

2018-01-01

Abstract Rationale: The life-threatening drug rash with eosinophilia and systemic symptoms (DRESS) syndrome occurs most commonly after exposure to drugs, clinical features mimic those found with other serious systemic disorders. It is rarely associated with thrombotic microangiopathy. Patient concerns: We describe the unique case of a 44-year-old man who simultaneously experienced DRESS syndrome with thrombotic microangiopathy (TMA) after a 5 days treatment with fluindione. Diagnoses: Clinical evaluation leads to the discovery of an underlying lymphangiomatosis, due to a Noonan syndrome. Intervetions: The anticoagulant was withdrawn, and corticosteroids (1 mg/kg/day) and acenocoumarol were started. Outcomes: Clinical improvement ensued. At follow-up the patient is well. Lessons: The association of DRESS with TMA is a rare condition; we believe that the presence of the underlying Noonan syndrome could have been the trigger. Moreover, we speculate about the potential interrelations between these entities. PMID:29642153

Interstitial granulomatous dermatitis with arthritis.

PubMed

Long, D; Thiboutot, D M; Majeski, J T; Vasily, D B; Helm, K F

1996-06-01

Interstitial granulomatous dermatitis with arthritis is an uncommon systemic disorder involving the cutaneous and musculoskeletal systems. The eruption may mimic other dermatoses including granuloma annulare, erythema chronicum migrans, and the inflammatory stage of morphea. Key histopathologic characteristics, along with clinical correlation, allow accurate diagnosis. We describe the clinical, serologic, and histologic features in three patients with interstitial granulomatous dermatitis with arthritis. Skin biopsy specimens were examined and correlated with the clinical and laboratory findings. Erythematous, annular, indurated plaques on the extremities were present in two women. An erythematous, papular eruption on the head and neck was present in a third patient. All patients had myalgia and migratory polyarthralgias of the extremities along with various serologic abnormalities. Histologic examination revealed a dense lymphohistiocytic interstitial infiltrate involving primarily the reticular dermis. Foci of necrobiotic collagen were present. Vasculitis was absent. Interstitial granulomatous dermatitis with arthritis is unique multisystem disease with variable cutaneous expression. Abnormal serologic findings indicate a possible connection to collagen vascular disease.

Native T1 mapping of the heart - a pictorial review.

PubMed

Germain, Philippe; El Ghannudi, Soraya; Jeung, Mi-Young; Ohlmann, Patrick; Epailly, Eric; Roy, Catherine; Gangi, Afshin

2014-01-01

T1 mapping is now a clinically feasible method, providing pixel-wise quantification of the cardiac structure's T1 values. Beyond focal lesions, well depicted by late gadolinium enhancement sequences, it has become possible to discriminate diffuse myocardial alterations, previously not assessable by noninvasive means. The strength of this method includes the high reproducibility and immediate clinical applicability, even without the use of contrast media injection (native or pre-contrast T1). The two most important determinants of native T1 augmentation are (1) edema related to tissue water increase (recent infarction or inflammation) and (2) interstitial space increase related to fibrosis (infarction scar, cardiomyopathy) or to amyloidosis. Conversely, lipid (Anderson-Fabry) or iron overload diseases are responsible for T1 reduction. In this pictorial review, the main features provided by native T1 mapping are discussed and illustrated, with a special focus on the awaited clinical purpose of this unique, promising new method.

Spectrum of Clinical Diseases Caused By Disorders of Primary Cilia

PubMed Central

Aygun, Meral Gunay-; Hildebrandt, Friedhelm

2011-01-01

The ciliopathies are a category of diseases caused by disruption of the physiological functions of cilia. Ciliary dysfunction results in a broad range of phenotypes, including renal, hepatic, and pancreatic cyst formation; situs abnormalities; retinal degeneration; anosmia; cerebellar or other brain anomalies; postaxial polydactyly; bronchiectasis; and infertility. The specific clinical features are dictated by the subtype, structure, distribution, and function of the affected cilia. This review highlights the clinical variability caused by dysfunction of motile and nonmotile primary cilia and emphasizes the genetic heterogeneity and phenotypic overlap that are characteristics of these disorders. There is a need for additional research to understand the shared and unique functions of motile and nonmotile cilia and the pathophysiology resulting from mutations in cilia, basal bodies, or centrosomes. Increased understanding of ciliary biology will improve the diagnosis and management of primary ciliary dyskinesia, syndromic ciliopathies, and cilia-related cystic diseases. PMID:21926397

Clinical and neuropathologic variation in neuronal intermediate filament inclusion disease

PubMed Central

Cairns, N.J.; Grossman, M.; Arnold, S.E.; Burn, D.J.; Jaros, E.; Perry, R.H.; Duyckaerts, C.; Stankoff, B.; Pillon, B.; Skullerud, K.; Cruz-Sanchez, F.F.; Bigio, E.H.; Mackenzie, I.R.A.; Gearing, M.; Juncos, J.L.; Glass, J.D.; Yokoo, H.; Nakazato, Y.; Mosaheb, S.; Thorpe, J.R.; Uryu, K.; Lee, V.M.-Y.; Trojanowski, J.Q.

2009-01-01

Background Recently described neuronal intermediate filament inclusion disease (NIFID) shows considerable clinical heterogeneity. Objective To assess the spectrum of the clinical and neuropathological features in 10 NIFID cases. Methods Retrospective chart and comprehensive neuropathological review of these NIFID cases was conducted. Results The mean age at onset was 40.8 (range 23 to 56) years, mean disease duration was 4.5 (range 2.7 to 13) years, and mean age at death was 45.3 (range 28 to 61) years. The most common presenting symptoms were behavioral and personality changes in 7 of 10 cases and, less often, memory loss, cognitive impairment, language deficits, and motor weakness. Extrapyramidal features were present in 8 of 10 patients. Language impairment, perseveration, executive dysfunction, hyperreflexia, and primitive reflexes were frequent signs, whereas a minority had buccofacial apraxia, supranuclear ophthalmoplegia, upper motor neuron disease (MND), and limb dystonia. Frontotemporal and caudate atrophy were common. Histologic changes were extensive in many cortical areas, deep gray matter, cerebellum, and spinal cord. The hallmark lesions of NIFID were unique neuronal IF inclusions detected most robustly by antibodies to neurofilament triplet proteins and α-internexin. Conclusion NIFID is a neuropathologically distinct, clinically heterogeneous variant of frontotemporal dementia (FTD) that may include parkinsonism or MND. Neuronal IF inclusions are the neuropathological signatures of NIFID that distinguish it from all other FTD variants including FTD with MND and FTD tauopathies. PMID:15505152

Reproducibility of radiomics for deciphering tumor phenotype with imaging

NASA Astrophysics Data System (ADS)

Zhao, Binsheng; Tan, Yongqiang; Tsai, Wei-Yann; Qi, Jing; Xie, Chuanmiao; Lu, Lin; Schwartz, Lawrence H.

2016-03-01

Radiomics (radiogenomics) characterizes tumor phenotypes based on quantitative image features derived from routine radiologic imaging to improve cancer diagnosis, prognosis, prediction and response to therapy. Although radiomic features must be reproducible to qualify as biomarkers for clinical care, little is known about how routine imaging acquisition techniques/parameters affect reproducibility. To begin to fill this knowledge gap, we assessed the reproducibility of a comprehensive, commonly-used set of radiomic features using a unique, same-day repeat computed tomography data set from lung cancer patients. Each scan was reconstructed at 6 imaging settings, varying slice thicknesses (1.25 mm, 2.5 mm and 5 mm) and reconstruction algorithms (sharp, smooth). Reproducibility was assessed using the repeat scans reconstructed at identical imaging setting (6 settings in total). In separate analyses, we explored differences in radiomic features due to different imaging parameters by assessing the agreement of these radiomic features extracted from the repeat scans reconstructed at the same slice thickness but different algorithms (3 settings in total). Our data suggest that radiomic features are reproducible over a wide range of imaging settings. However, smooth and sharp reconstruction algorithms should not be used interchangeably. These findings will raise awareness of the importance of properly setting imaging acquisition parameters in radiomics/radiogenomics research.

Follicular thyroid cancer and Hürthle cell carcinoma: challenges in diagnosis, treatment, and clinical management.

PubMed

Grani, Giorgio; Lamartina, Livia; Durante, Cosimo; Filetti, Sebastiano; Cooper, David S

2018-06-01

Follicular thyroid cancer is the second most common differentiated thyroid cancer histological type and has been overshadowed by its more common counterpart-papillary thyroid cancer-despite its unique biological behaviour and less favourable outcomes. In this Review, we comprehensively review the literature on follicular thyroid cancer to provide an evidence-based guide to the management of these tumours, to highlight the lack of evidence behind guideline recommendations, and to identify changes and challenges over the past decades in diagnosis, prognosis, and treatment. We highlight that correct identification of cancer in indeterminate cytological samples is challenging and ultrasonographic features can be misleading. Despite certain unique aspects of follicular thyroid cancer presentation and prognosis, no specific recommendations exist for follicular thyroid cancer and Hürthle cell carcinoma in evidence-based guidelines. Efforts should be made to stimulate additional research in this field. Copyright © 2018 Elsevier Ltd. All rights reserved.

Epidemic of poisoning caused by scopolamine disguised as Rohypnol tablets.

PubMed

Vallersnes, Odd Martin; Lund, Cathrine; Duns, Anne Kathrine; Netland, Hallstein; Rasmussen, Inge-André

2009-11-01

An epidemic of scopolamine poisonings occurred in Oslo in 2008 among users of illicit drugs, caused by fake Rohypnol pills. The clinical features, diagnostic process, and handling of the epidemic are presented. Suspected cases of scopolamine poisoning were extracted by reviewing registration forms from an ongoing prospective clinical study of acute poisonings in Oslo. Medical records of extracted contacts were examined and cases included according to specified clinical criteria. Forty-four cases of probable scopolamine poisoning were registered. Main clinical features were mydriasis, visual hallucinations, plucking behavior, agitation, and coma. No clinical diagnosis of anticholinergic syndrome was made prior to forensic analysis of the tablets, the most frequent diagnosis up to this point being unspecified drug-induced psychosis. Later in the epidemic, scopolamine poisoning became the dominating diagnosis. Ten patients were admitted to psychiatric hospitals, the rest recovered in medical units, or left health care against medical advice. Scopolamine poisonings are rare, but the resulting anticholinergic syndrome is well described. The syndrome was not recognized until the forensic analysis result strikingly changed how the patients were diagnosed and handled. A unique aspect of this epidemic was the intoxicating agent being scopolamine-containing tablets looking like Rohypnol, sold and used under the impression of being the latter. Recognizing the anticholinergic syndrome is important to provide proper treatment. Forensic analysis was the key to correct diagnosis in this outbreak, demonstrating its importance in verifying an epidemic of poisoning by fake drugs.

Characteristics of white coat hypertension in Chinese Han patients with type 2 diabetes mellitus.

PubMed

Zhou, Jianguang; Liu, Changyun; Shan, Peijia; Zhou, Yingqi; Xu, Erli; Ji, Yufeng

2014-01-01

This study documented the prevalence and clinical features of white coat hypertension (WCH) among Chinese Han patients with type 2 diabetes mellitus (T2DM). Clinic and ambulatory blood pressure (BP) measurements were compared in 856 patients with T2DM to determine the frequency of WCH (WCH was defined as clinical blood pressure ≥140/90 mmHg and daytime blood pressure <135/85 mmHg and/or 24-h ambulatory BP (ABP) mean value of <130/80 mmHg on ambulatory BP monitoring (ABPM). Weight, waist circumference (WC), body mass index (BMI), waist to height ratio (WHtR), fasting blood glucose, glycosylated hemoglobin level and circadian BP patterns were also measured to find clinical features predictive of WCH in T2DM. The prevalence of WCH was 7.36% (63/856) in the overall population, 6.13% (29/473) in male and 8.88% (34/383) in female (p < 0.05). WCH accounted for 14.03% (63/449) of diagnosed hypertension. Age, course of T2DM, male WC were independent protective factors, whereas female sex, smoking and alcohol consumption were independent risk factors for WCH in T2DM. Non-dippers and reverse dippers made up larger proportion of the WCH group (p < 0.01). WCH is relatively common among T2DM patients, it is a unique condition distinct from essential hypertension (EH), and WCH patients also exhibit significant differences in clinical parameters.

A rare case of atypical pleomorphic adenoma arising from periocular ectopic lacrimal gland.

PubMed

Wajda, Brynn N; Mancini, Ronald; Evers, Bret; Nick Hogan, R

2018-06-23

To describe features of atypical pleomorphic adenoma, a rare clinical entity, particularly when found in ectopic periocular lacrimal gland tissue. Case report of biopsy-confirmed periocular atypical pleomorphic adenoma. A 35-year-old female presented with a unique orbital lesion found to be ectopic lacrimal gland demonstrating atypical pleomorphic adenoma on formal histopathologic review. Pleomorphic adenoma is pathologically characterized as an epithelial lesion intermixed with mesenchymal elements. It is further classified as atypical with the presence of features such as hypercellularity, regions of necrosis or hyalinization, cellular dysplasia, capsular violation, and malignant characteristics without frank local extension or distant metastases. Due to its rarity, the natural history and prognosis of atypical pleomorphic adenoma is unclear. Physicians need to recognize this entity, and complete surgical excision with strict follow-up regimens are likely warranted.

Atopic dermatitis in diverse racial and ethnic groups-Variations in epidemiology, genetics, clinical presentation and treatment.

PubMed

Kaufman, Bridget P; Guttman-Yassky, Emma; Alexis, Andrew F

2018-04-01

Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects diverse ethnic groups with varying prevalence. Despite a predominance of studies in individuals of European ancestry, AD has been found to occur more frequently in Asian and Black individuals than Whites. Therefore, an understanding of the unique clinical features of AD in diverse ethnic groups, as well as the differences in genetic polymorphisms that influence susceptibility to AD and response to current therapies, is paramount for management of an increasingly diverse patient population. In this article, we review key nuances in the epidemiology, pathophysiology, clinical presentation and treatment of AD in non-White ethnic groups, which are largely underappreciated in the literature. We highlight the need for studies evaluating the tissue molecular and cellular phenotypes of AD in non-White patients, as well as greater inclusion of minority groups in clinical trials, to develop targeted treatments for a multi-ethnic population. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Clinical characteristics of ocular toxocariasis in Eastern China.

PubMed

Zhou, Min; Chang, Qing; Gonzales, John A; Chen, Qian; Zhang, Yanqiong; Huang, Xin; Xu, Gezhi; Wang, Wenji; Jiang, Rui

2012-09-01

To explore the clinical characteristics of patients with ocular toxocariasis in eastern China. The medical records of 35 cases of ocular toxocariasis in Fudan University Eye & ENT Hospital between May 2009 and April 2011 were retrospectively reviewed and analyzed. UBM, RetCam or fundus imaging, and high-frequency or conventional ultrasonography were performed in these patients. The mean patient age in our series of ocular toxocariasis was 11.86 ± 8.80 years. There were 28 children and seven adults, the majority residing in a rural area (88.57%). All cases were classified into three clinical subtypes: granuloma in the peripheral retina (60% of cases); granuloma in the posterior pole (28.57% of cases); and vitreous inflammation mimicking chronic endophthalmitis (5.71% of cases). We also identified an additional subtype with unique clinical features that we termed "combined type" presenting in 5.71% of our patients. This subtype exhibited granulomas in both the posterior pole and peripheral retina. RetCam fundus imaging was able to identify granulomas in the posterior and peripheral subtypes, 100% and 80.95% of cases respectively. Moreover, UBM combined with conventional ultrasonography identified granulomas in 95% of the peripheral subtype cases and in 100% of the posterior pole subtype cases. This is the first ocular toxocariasis series described in Chinese patients. Compared with reports from developed countries, the ocular features in our series were more severe and complicated, presenting with poorer visual acuity and a high rate of retinal detachment (45.7%). The application of RetCam and UBM during examination in ocular toxocariasis can provide valuable information in determining the severity of disease and features important in considering surgical procedures in such patients.

Histology, Fusion Status, and Outcome in Alveolar Rhabdomyosarcoma With Low-Risk Clinical Features: A Report From the Children's Oncology Group.

PubMed

Arnold, Michael A; Anderson, James R; Gastier-Foster, Julie M; Barr, Frederic G; Skapek, Stephen X; Hawkins, Douglas S; Raney, R Beverly; Parham, David M; Teot, Lisa A; Rudzinski, Erin R; Walterhouse, David O

2016-04-01

Distinguishing alveolar rhabdomyosarcoma (ARMS) from embryonal rhabdomyosarcoma (ERMS) is of prognostic and therapeutic importance. Criteria for classifying these entities evolved significantly from 1995 to 2013. ARMS is associated with inferior outcome; therefore, patients with alveolar histology have generally been excluded from low-risk therapy. However, patients with ARMS and low-risk stage and group (Stage 1, Group I/II/orbit III; or Stage 2/3, Group I/II) were eligible for the Children's Oncology Group (COG) low-risk rhabdomyosarcoma (RMS) study D9602 from 1997 to 1999. The characteristics and outcomes of these patients have not been previously reported, and the histology of these cases has not been reviewed using current criteria. We re-reviewed cases that were classified as ARMS on D9602 using current histologic criteria, determined PAX3/PAX7-FOXO1 fusion status, and compared these data with outcome for this unique group of patients. Thirty-eight patients with ARMS were enrolled onto D9602. Only one-third of cases with slides available for re-review (11/33) remained classified as ARMS by current histologic criteria. Most cases were reclassified as ERMS (17/33, 51.5%). Cases that remained classified as ARMS were typically fusion-positive (8/11, 73%), therefore current classification results in a similar rate of fusion-positive ARMS for all clinical risk groups. In conjunction with data from COG intermediate-risk treatment protocol D9803, our data demonstrate excellent outcomes for fusion-negative ARMS with otherwise low-risk clinical features. Patients with fusion-positive RMS with low-risk clinical features should be classified and treated as intermediate risk, while patients with fusion-negative ARMS could be appropriately treated with reduced intensity therapy. © 2016 Wiley Periodicals, Inc.

Evaluation of cystoid change phenotypes in ocular toxoplasmosis using optical coherence tomography.

PubMed

Ouyang, Yanling; Pleyer, Uwe; Shao, Qing; Keane, Pearse A; Stübiger, Nicole; Joussen, Antonia M; Sadda, Srinivas R; Heussen, Florian M

2014-01-01

To present unique cystoid changes occurring in patients with ocular toxoplasmosis observed in spectral domain optical coherence tomography (OCT). Forty-six patients (80 eyes) with a diagnosis of ocular toxoplasmosis, who underwent volume OCT examination between January 2005 and October 2012, were retrospectively collected. Review of clinical examination findings, fundus photographs, fluorescein angiograms (FA) and OCT image sets obtained at initial visits and follow-up. Qualitative and quantitative analyses of cystoid space phenotypes visualized using OCT. Of the 80 eyes included, 17 eyes (15 patients) demonstrated cystoid changes in the macula on OCT. Six eyes (7.5%) had cystoid macular edema (CME), 2 eyes (2.5%) had huge outer retinal cystoid space (HORC), 12 eyes (15%) had cystoid degeneration and additional 3 eyes (3.75%) had outer retinal tubulation due to age related macular degeneration. In one eye with HORC, the lesion was seen in the photoreceptor outer segment, accompanied by photoreceptor elongation and splitting. Three eyes presented with paravascular cystoid degeneration in the inner retina without other macular OCT abnormality. In this study, different phenotypes of cystoid spaces seen in eyes with ocular toxoplasmosis using spectral domain OCT (SD-OCT) were demonstrated. CME presented as an uncommon feature, consistently with previous findings. Identification of rare morphological cystoid features (HORC with/without photoreceptor enlongation or splitting) on clinical examination had provided evidence to previous experimental models, which may also expand the clinical spectrum of the disease. Cystoid degeneration in the inner retina next to the retinal vessels in otherwise "normal" looking macula was observed, which may suggest more often clinical evaluation for those patients. Further studies are needed to verify the relevance of cystoid features seen on SD-OCT in assisting with the diagnosis and management of ocular toxoplasmosis.

Evaluation of Cystoid Change Phenotypes in Ocular Toxoplasmosis Using Optical Coherence Tomography

PubMed Central

Shao, Qing; Keane, Pearse A.; Stübiger, Nicole; Joussen, Antonia M.; Sadda, Srinivas R.; Heussen, Florian M.

2014-01-01

Purpose To present unique cystoid changes occurring in patients with ocular toxoplasmosis observed in spectral domain optical coherence tomography (OCT). Methods Forty-six patients (80 eyes) with a diagnosis of ocular toxoplasmosis, who underwent volume OCT examination between January 2005 and October 2012, were retrospectively collected. Review of clinical examination findings, fundus photographs, fluorescein angiograms (FA) and OCT image sets obtained at initial visits and follow-up. Qualitative and quantitative analyses of cystoid space phenotypes visualized using OCT. Results Of the 80 eyes included, 17 eyes (15 patients) demonstrated cystoid changes in the macula on OCT. Six eyes (7.5%) had cystoid macular edema (CME), 2 eyes (2.5%) had huge outer retinal cystoid space (HORC), 12 eyes (15%) had cystoid degeneration and additional 3 eyes (3.75%) had outer retinal tubulation due to age related macular degeneration. In one eye with HORC, the lesion was seen in the photoreceptor outer segment, accompanied by photoreceptor elongation and splitting. Three eyes presented with paravascular cystoid degeneration in the inner retina without other macular OCT abnormality. Conclusions In this study, different phenotypes of cystoid spaces seen in eyes with ocular toxoplasmosis using spectral domain OCT (SD-OCT) were demonstrated. CME presented as an uncommon feature, consistently with previous findings. Identification of rare morphological cystoid features (HORC with/without photoreceptor enlongation or splitting) on clinical examination had provided evidence to previous experimental models, which may also expand the clinical spectrum of the disease. Cystoid degeneration in the inner retina next to the retinal vessels in otherwise “normal” looking macula was observed, which may suggest more often clinical evaluation for those patients. Further studies are needed to verify the relevance of cystoid features seen on SD-OCT in assisting with the diagnosis and management of ocular toxoplasmosis. PMID:24505261

FFDM image quality assessment using computerized image texture analysis

NASA Astrophysics Data System (ADS)

Berger, Rachelle; Carton, Ann-Katherine; Maidment, Andrew D. A.; Kontos, Despina

2010-04-01

Quantitative measures of image quality (IQ) are routinely obtained during the evaluation of imaging systems. These measures, however, do not necessarily correlate with the IQ of the actual clinical images, which can also be affected by factors such as patient positioning. No quantitative method currently exists to evaluate clinical IQ. Therefore, we investigated the potential of using computerized image texture analysis to quantitatively assess IQ. Our hypothesis is that image texture features can be used to assess IQ as a measure of the image signal-to-noise ratio (SNR). To test feasibility, the "Rachel" anthropomorphic breast phantom (Model 169, Gammex RMI) was imaged with a Senographe 2000D FFDM system (GE Healthcare) using 220 unique exposure settings (target/filter, kVs, and mAs combinations). The mAs were varied from 10%-300% of that required for an average glandular dose (AGD) of 1.8 mGy. A 2.5cm2 retroareolar region of interest (ROI) was segmented from each image. The SNR was computed from the ROIs segmented from images linear with dose (i.e., raw images) after flat-field and off-set correction. Image texture features of skewness, coarseness, contrast, energy, homogeneity, and fractal dimension were computed from the Premium ViewTM postprocessed image ROIs. Multiple linear regression demonstrated a strong association between the computed image texture features and SNR (R2=0.92, p<=0.001). When including kV, target and filter as additional predictor variables, a stronger association with SNR was observed (R2=0.95, p<=0.001). The strong associations indicate that computerized image texture analysis can be used to measure image SNR and potentially aid in automating IQ assessment as a component of the clinical workflow. Further work is underway to validate our findings in larger clinical datasets.

No significant difference between chiari malformation type 1.5 and type I.

PubMed

Liu, Wei; Wu, Hongxing; Aikebaier, Yalikun; Wulabieke, Maoliti; Paerhati, Rexiti; Yang, Xiaopeng

2017-06-01

Chiari malformation Type 1.5 (CM 1.5) was defined as the association of Chiari malformation Type I (CM I) and brainstem herniation. The objective was to demonstrate the difference of clinical features and surgical outcomes between CM 1.5 and CM I. All CM 1.5 and CM I adult patients who underwent posterior fossa decompression with duraplasty at our institution between 2006 and 2010 were retrospectively reviewed. Clinical characteristics, imaging features, and long-term outcomes were compared between CM 1.5 and CM I patients. A total of 142 adult patients were enrolled, including 27 CM 1.5 and 115 CM I patients. The average follow-up period was 102 months. Age at diagnosis was significantly younger in CM 1.5 group than CM I group (p=0.039). And the degree of tonsillar herniation was significantly more severe in CM 1.5 group than CM I group (p<0.001). There was no significant difference in other clinical and imaging characteristics. Moreover, improvement of symptoms was observed in 21 CM 1.5 patients (77.8%) and 94 CM I patients (81.7%), and no significant difference was detected (p=0.637). There was no significant difference in the resolution of syringomyelia between CM 1.5 (72.7%) and CM I (76.5%) patients, either (p=0. 710). Although CM 1.5 patients presented with brainstem herniation and more severe tonsillar herniation, other clinical and imaging features and surgical outcomes were similar with CM I patients. We think CM 1.5 is just a subtype of CM I, rather than a unique type of Chiari malformations. Copyright © 2017 Elsevier B.V. All rights reserved.

Modeling the shape and composition of the human body using dual energy X-ray absorptiometry images

PubMed Central

Shepherd, John A.; Fan, Bo; Schwartz, Ann V.; Cawthon, Peggy; Cummings, Steven R.; Kritchevsky, Stephen; Nevitt, Michael; Santanasto, Adam; Cootes, Timothy F.

2017-01-01

There is growing evidence that body shape and regional body composition are strong indicators of metabolic health. The purpose of this study was to develop statistical models that accurately describe holistic body shape, thickness, and leanness. We hypothesized that there are unique body shape features that are predictive of mortality beyond standard clinical measures. We developed algorithms to process whole-body dual-energy X-ray absorptiometry (DXA) scans into body thickness and leanness images. We performed statistical appearance modeling (SAM) and principal component analysis (PCA) to efficiently encode the variance of body shape, leanness, and thickness across sample of 400 older Americans from the Health ABC study. The sample included 200 cases and 200 controls based on 6-year mortality status, matched on sex, race and BMI. The final model contained 52 points outlining the torso, upper arms, thighs, and bony landmarks. Correlation analyses were performed on the PCA parameters to identify body shape features that vary across groups and with metabolic risk. Stepwise logistic regression was performed to identify sex and race, and predict mortality risk as a function of body shape parameters. These parameters are novel body composition features that uniquely identify body phenotypes of different groups and predict mortality risk. Three parameters from a SAM of body leanness and thickness accurately identified sex (training AUC = 0.99) and six accurately identified race (training AUC = 0.91) in the sample dataset. Three parameters from a SAM of only body thickness predicted mortality (training AUC = 0.66, validation AUC = 0.62). Further study is warranted to identify specific shape/composition features that predict other health outcomes. PMID:28423041

Distinguishing early and late brain aging from the Alzheimer's disease spectrum: consistent morphological patterns across independent samples.

PubMed

Doan, Nhat Trung; Engvig, Andreas; Zaske, Krystal; Persson, Karin; Lund, Martina Jonette; Kaufmann, Tobias; Cordova-Palomera, Aldo; Alnæs, Dag; Moberget, Torgeir; Brækhus, Anne; Barca, Maria Lage; Nordvik, Jan Egil; Engedal, Knut; Agartz, Ingrid; Selbæk, Geir; Andreassen, Ole A; Westlye, Lars T

2017-09-01

Alzheimer's disease (AD) is a debilitating age-related neurodegenerative disorder. Accurate identification of individuals at risk is complicated as AD shares cognitive and brain features with aging. We applied linked independent component analysis (LICA) on three complementary measures of gray matter structure: cortical thickness, area and gray matter density of 137 AD, 78 mild (MCI) and 38 subjective cognitive impairment patients, and 355 healthy adults aged 18-78 years to identify dissociable multivariate morphological patterns sensitive to age and diagnosis. Using the lasso classifier, we performed group classification and prediction of cognition and age at different age ranges to assess the sensitivity and diagnostic accuracy of the LICA patterns in relation to AD, as well as early and late healthy aging. Three components showed high sensitivity to the diagnosis and cognitive status of AD, with different relationships with age: one reflected an anterior-posterior gradient in thickness and gray matter density and was uniquely related to diagnosis, whereas the other two, reflecting widespread cortical thickness and medial temporal lobe volume, respectively, also correlated significantly with age. Repeating the LICA decomposition and between-subject analysis on ADNI data, including 186 AD, 395 MCI and 220 age-matched healthy controls, revealed largely consistent brain patterns and clinical associations across samples. Classification results showed that multivariate LICA-derived brain characteristics could be used to predict AD and age with high accuracy (area under ROC curve up to 0.93 for classification of AD from controls). Comparison between classifiers based on feature ranking and feature selection suggests both common and unique feature sets implicated in AD and aging, and provides evidence of distinct age-related differences in early compared to late aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Cholesteatoma in the Sellar Region Presenting as Hypopituitarism and Diabetes Insipidus

PubMed Central

Kong, Xiangyi; Wu, Huanwen; Ma, Wenbin; Li, Yongning; Xing, Bing; Kong, Yanguo; Wang, Renzhi

2016-01-01

Abstract Clinically significant sellar cysts unrelated to pituitary adenomas are uncommon. Intracranial cholesteatomas are also rare and are most common in the middle ear and mastoid region. We report an even rarer case of cholesteatoma in the sellar region—a challenging diagnosis guided by clinical presentations, radiological signs, and biopsy, aiming at emphasize the importance of considering cholesteatoma when making differential diagnoses of sellar lesions. We present a case of cholesteatoma in the sellar region in a 56-year-old man with hypopituitarism, diabetes insipidus, and cystic imaging findings. It was difficult to make an accurate diagnosis before surgery. We present detailed analysis of the patient's disease course and review pertinent literature. The patient underwent a surgical exploration and tumor resection through a transsphenoidal approach. Pathologic results revealed a cholesteatoma. The patient's symptoms improved a lot after surgery, and the postoperative period was uneventful. Taken together, the lesion's imaging appearance, pathological characteristics, and clinical features were all unique features that lead to a diagnosis of cholesteatoma. As we did not see such reports by Pubmed and EMBASE, we believe this is the first reported case of sellar cholesteatoma presenting in this manner. This article emphasized that cholesteatomas, although rare, should be considered part of the differential diagnosis of sellar lesions. PMID:26962793

Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes: basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome.

PubMed

Sproule, Douglas M; Kaufmann, Petra

2008-10-01

Since the initial description almost 25 years ago, the syndrome of mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) has been a useful model to study the complex interplay of factors that define mitochondrial disease. This syndrome, most commonly caused by an A-to-G transition mutation at position 3243 of the mitochondrial genome, is typified by characteristic neurological manifestations including seizures, encephalopathy, and strokelike episodes, as well as other frequent secondary manifestations including short stature, cognitive impairment, migraines, depression, cardiomyopathy, cardiac conduction defects, and diabetes mellitus. In this review, we discuss the history, pathogenesis, clinical features, and diagnostic and management strategies of mitochondrial disease in general and of MELAS in particular. We explore features of mitochondrial genetics, including the concepts of heteroplasmy, mitotic segregation, and threshold effect, as a basis for understanding the variability and complicated inheritance patterns seen with this group of diseases. We also describe systemic manifestations of MELAS-associated mutations, including cardiac, renal, endocrine, gastrointestinal, and endothelial abnormalities and pathology, as well as the hypothetical role of derangements to COX enzymatic function in driving the unique pathology and clinical manifestations of MELAS. Although therapeutic options for MELAS and other mitochondrial diseases remain limited, and recent trials have been disappointing, we also consider current and potential therapeutic modalities.

Inflamed juvenile conjunctival naevus: clinicopathological characterisation

PubMed Central

Zamir, Ehud; Mechoulam, Hadas; Micera, Alessandra; Levi-Schaffer, Francesca; Pe'er, Jacob

2002-01-01

Aim: Inflamed juvenile conjunctival naevi (IJCN) are often erroneously suspected to be malignant because of rapid growth. Their clinical and histopathological features have not been characterised in series of patients. The aim of the study is to characterise IJCN clinically and histopathologically. Methods: This is a retrospective non-randomised clinicopathological study. All patients younger than 20 years with conjunctival naevi which were excised between 1990 and 2000 were included. The clinical signs of the affected patients and the histopathological findings of the excised lesions were characterised. Results: A total of 63 conjunctival naevi were resected. 25% of the patients had simple compound conjunctival naevi and 75% had compound naevi with prominent inflammatory histological features (discrete lymphocyte aggregates, plasma cells, and eosinophils). Epithelial cysts and solid epithelial islands were common in the IJCN. The IJCN were all located at or near the limbus, and characterised by recurrent periods of congestion and growth. 75% of the IJCN patients with complete medical records had a history of allergic disease. Marked conjunctival papillary reaction was present in all of the patients, indicating a possible conjunctival allergy. Conclusions: IJCN is a unique entity, different from simple compound conjunctival naevus. Its association with allergic conjunctivitis is suggestive, and despite periods of alarmingly rapid growth, is histologically benign. PMID:11801498

Genetic syndromes associated with overgrowth in childhood

PubMed Central

2013-01-01

Overgrowth syndromes comprise a diverse group of conditions with unique clinical, behavioral and molecular genetic features. While considerable overlap in presentation sometimes exists, advances in identification of the precise etiology of specific overgrowth disorders continue to improve clinicians' ability to make an accurate diagnosis. Among them, this paper introduces two classic genetic overgrowth syndromes: Sotos syndrome and Beckwith-Wiedemann syndrome. Historically, the diagnosis was based entirely on clinical findings. However, it is now understood that Sotos syndrome is caused by a variety of molecular genetic alterations resulting in haploinsufficiency of the NSD1 gene at chromosome 5q35 and that Beckwith-Wiedemann syndrome is caused by heterogeneous abnormalities in the imprinting of a number of growth regulatory genes within chromosome 11p15 in the majority of cases. Interestingly, the 11p15 imprinting region is also associated with Russell-Silver syndrome which is a typical growth retardation syndrome. Opposite epigenetic alterations in 11p15 result in opposite clinical features shown in Beckwith-Wiedemann syndrome and Russell-Silver syndrome. Although the exact functions of the causing genes have not yet been completely understood, these overgrowth syndromes can be good models to clarify the complex basis of human growth and help to develop better-directed therapies in the future. PMID:24904861

IDGenerator: unique identifier generator for epidemiologic or clinical studies.

PubMed

Olden, Matthias; Holle, Rolf; Heid, Iris M; Stark, Klaus

2016-09-15

Creating study identifiers and assigning them to study participants is an important feature in epidemiologic studies, ensuring the consistency and privacy of the study data. The numbering system for identifiers needs to be random within certain number constraints, to carry extensions coding for organizational information, or to contain multiple layers of numbers per participant to diversify data access. Available software can generate globally-unique identifiers, but identifier-creating tools meeting the special needs of epidemiological studies are lacking. We have thus set out to develop a software program to generate IDs for epidemiological or clinical studies. Our software IDGenerator creates unique identifiers that not only carry a random identifier for a study participant, but also support the creation of structured IDs, where organizational information is coded into the ID directly. This may include study center (for multicenter-studies), study track (for studies with diversified study programs), or study visit (baseline, follow-up, regularly repeated visits). Our software can be used to add a check digit to the ID to minimize data entry errors. It facilitates the generation of IDs in batches and the creation of layered IDs (personal data ID, study data ID, temporary ID, external data ID) to ensure a high standard of data privacy. The software is supported by a user-friendly graphic interface that enables the generation of IDs in both standard text and barcode 128B format. Our software IDGenerator can create identifiers meeting the specific needs for epidemiologic or clinical studies to facilitate study organization and data privacy. IDGenerator is freeware under the GNU General Public License version 3; a Windows port and the source code can be downloaded at the Open Science Framework website: https://osf.io/urs2g/ .

Legionella spp. and Legionnaires' disease.

PubMed

Diederen, B M W

2008-01-01

Infection with Legionella spp. is an important cause of community- and hospital-acquired pneumonia, occurring both sporadically and in outbreaks. Infection with Legionella spp. ranks among the three most common causes of severe pneumonia in the community setting, and is isolated in 1-40% of cases of hospital-acquired pneumonia. There are no clinical features unique to Legionnaires' disease. Macrolides and fluoroquinolones are the most widely used drugs in treatment. The availability of a good diagnostic repertoire, suitable for accurately diagnosing LD, constitutes the basis for the early recognition and treatment of the individual patient as well as for effective measures for prevention and control. This review summarizes the available information regarding the microbiology, clinical presentation, diagnosis and treatment of LD, with an emphasis on the laboratory diagnosis of infection with Legionella spp.

[Malignant vascular tumors of the vulva].

PubMed

Chokoeva, A; Tchernev, G

2015-01-01

Due to the increased vascularity as well as the unique anatomical structure, vascular lesions, which occur in the female reproductive system are common observed and diverse by their morphology. The majority of them are benign, including vascular malformations, lesions due to vascular hyperplasia, tumors with significant vascular component and others. Malignant vascular tumors are rare in the area of the vulva accounting about 1% of all vulvar lesions with vascular origin. Kaposi sarcoma, epithelioid hemangioepithelioma and epithelioid angiosarcoma have been reported with vulvar localization. With a view to their rare incidence, nonspecific clinical manifestation and aggressive behavior associated with high mortality, we present the most common malignant tumors of vascular origin arising in the vulva, as we emphasize on their epidemiology and clinical features, differential diagnosis and therapeutic algorithms for this rare type of malignancies.

Challenges of Pre- and Post-Test Counseling for Orthodox Jewish Individuals in the Premarital Phase.

PubMed

Rose, E; Schreiber-Agus, N; Bajaj, K; Klugman, S; Goldwaser, T

2016-02-01

The Jewish community has traditionally taken ownership of its health, and has taken great strides to raise awareness about genetic issues that affect the community, such as Tay-Sachs disease and Hereditary Breast and Ovarian Cancer syndrome. Thanks in part to these heightened awareness efforts, many Orthodox Jewish individuals are now using genetics services as they begin to plan their families. Due to unique cultural and religious beliefs and perceptions, the Orthodox Jewish patients who seek genetic counseling face many barriers to a successful counseling session, and often seek the guidance of programs such as the Program for Jewish Genetic Health (PJGH). In this article, we present clinical vignettes from the PJGH's clinical affiliate, the Reproductive Genetics practice at the Montefiore Medical Center. These cases highlight unique features of contemporary premarital counseling and screening within the Orthodox Jewish Community, including concerns surrounding stigma, disclosure, "marriageability," the use of reproductive technologies, and the desire to include a third party in decision making. Our vignettes demonstrate the importance of culturally-sensitive counseling. We provide strategies and points to consider when addressing the challenges of pre- and post-test counseling as it relates to genetic testing in this population.

Implant bone integration importance in forensic identification.

PubMed

De Angelis, Danilo; Cattaneo, Cristina

2015-03-01

Odontological identification consists of the comparison of antemortem dental information regarding a missing person with postmortem data from an unidentified corpse or human remains. Usually, the comparison concerns morphologic features that the operator chooses among all the visible characteristics because of inter-individual uniqueness; for this reason, implants can be of enormous assistance. A case concerning the recovery of a burnt oral implant, connected to a bone fragment, among 2780 charred bone fragments, suspected to have belonged to a victim of homicide, is presented to demonstrate that dental implants and their site of bone integration represent a very precious element for personal forensic identification. Because of their morphological invariability in time and because of their morphologic uniqueness, they were used as evidence to associate unidentified human charred remains to a missing person where DNA analysis failed to do so. The case illustrates the fundamental contribution, not yet described in literature, given by the clinical aspects of tooth replacement with dental implants to a forensic discipline. Clinical practitioners should therefore be aware of the great importance of their work and of dental records in a forensic identification scenario. © 2014 American Academy of Forensic Sciences.

Integrating the glioblastoma microenvironment into engineered experimental models

PubMed Central

Xiao, Weikun; Sohrabi, Alireza; Seidlits, Stephanie K

2017-01-01

Glioblastoma (GBM) is the most lethal cancer originating in the brain. Its high mortality rate has been attributed to therapeutic resistance and rapid, diffuse invasion – both of which are strongly influenced by the unique microenvironment. Thus, there is a need to develop new models that mimic individual microenvironmental features and are able to provide clinically relevant data. Current understanding of the effects of the microenvironment on GBM progression, established experimental models of GBM and recent developments using bioengineered microenvironments as ex vivo experimental platforms that mimic the biochemical and physical properties of GBM tumors are discussed. PMID:28883992

Magnetic nanoparticles based cancer therapy: current status and applications.

PubMed

Zhang, Huan; Liu, Xiao Li; Zhang, Yi Fan; Gao, Fei; Li, Ga Long; He, Yuan; Peng, Ming Li; Fan, Hai Ming

2018-04-01

Nanotechnology holds a promising potential for developing biomedical nanoplatforms in cancer therapy. The magnetic nanoparticles, which integrate uniquely appealing features of magnetic manipulation, nanoscale heat generator, localized magnetic field and enzyme-mimics, prompt the development and application of magnetic nanoparticles-based cancer medicine. Considerable success has been achieved in improving the magnetic resonance imaging (MRI) sensitivity, and the therapeutic function of the magnetic nanoparticles should be given adequate attention. This work reviews the current status and applications of magnetic nanoparticles based cancer therapy. The advantages of magnetic nanoparticles that may contribute to improved therapeutics efficacy of clinic cancer treatment are highlighted here.

Atypical Intracranial Epidermoid Cysts: Rare Anomalies with Unique Radiological Features

PubMed Central

Law, Eric K. C.; Lee, Ryan K. L.; Ng, Alex W. H.; Siu, Deyond Y. W.; Ng, Ho-Keung

2015-01-01

Epidermoid cysts are benign slow growing extra-axial tumours that insinuate between brain structures, while their occurrences in intra-axial or intradiploic locations are exceptionally rare. We present the clinical, imaging, and pathological findings in two patients with atypical epidermoid cysts. CT and MRI findings for the first case revealed an intraparenchymal epidermoid cyst that demonstrated no restricted diffusion. The second case demonstrated an aggressive epidermoid cyst that invaded into the intradiploic spaces, transverse sinus, and the calvarium. The timing of ectodermal tissue sequestration during fetal development may account for the occurrence of atypical epidermoid cysts. PMID:25667778

Borderline personality features in depressed or anxious patients.

PubMed

Distel, Marijn A; Smit, Johannes H; Spinhoven, Philip; Penninx, Brenda W J H

2016-07-30

Anxiety and depression frequently co-occur with borderline personality disorder. Relatively little research examined the presence of borderline personality features and its main domains (affective instability, identity problems, negative relationships and self-harm) in individuals with remitted and current anxiety and depression. Participants with current (n=597) or remitted (n=1115) anxiety and/or depression and healthy controls (n=431) were selected from the Netherlands Study of Depression and Anxiety. Assessments included the Personality Assessment Inventory - Borderline Features Scale and several clinical characteristics of anxiety and depression. Borderline personality features were more common in depression than in anxiety. Current comorbid anxiety and depression was associated with most borderline personality features. Anxiety and depression status explained 29.7% of the variance in borderline personality features and 3.8% (self-harm) to 31% (identity problems) of the variance in the four domains. A large part of the variance was shared between anxiety and depression but both disorders also explained a significant amount of unique variance. The severity of anxiety and depression and the level of daily dysfunctioning was positively associated with borderline personality features. Individuals with a longer duration of anxiety and depression showed more affective instability and identity problems. These findings suggest that patients with anxiety and depression may benefit from an assessment of personality pathology as it may have implications for psychological and pharmacological treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A missing piece: the spiny mouse and the puzzle of menstruating species.

PubMed

Bellofiore, Nadia; Cousins, Fiona; Temple-Smith, Peter; Dickinson, Hayley; Evans, Jemma

2018-07-01

We recently discovered the first known menstruating rodent. With the exception of four bats and the elephant shrew, the common spiny mouse ( Acomys cahirinus ) is the only species outside the primate order to exhibit menses. There are few widely accepted theories on why menstruation developed as the preferred reproductive strategy of these select mammals, all of which reference the evolution of spontaneous decidualisation prior to menstrual shedding. Though menstruating species share several reproductive traits, there has been no identifiable feature unique to menstruating species. Such a feature might suggest why spontaneous decidualisation, and thus menstruation, evolved in these species. We propose that a ≥3-fold increase in progesterone during the luteal phase of the reproductive cycle is a unique characteristic linking menstruating species. We discuss spontaneous decidualisation as a consequence of high progesterone, and the potential role of prolactin in screening for defective embryos in these species to aid in minimising implantation of abnormal embryos. We further explore the possible impact of nutrition in selecting species to undergo spontaneous decidualisation and subsequent menstruation. We summarise the current knowledge of menstruation, discuss current pre-clinical models of menstruation and how the spiny mouse may benefit advancing our understanding of this rare biological phenomenon. © 2018 Society for Endocrinology.

The genome sequence of Leishmania (Leishmania) amazonensis: functional annotation and extended analysis of gene models.

PubMed

Real, Fernando; Vidal, Ramon Oliveira; Carazzolle, Marcelo Falsarella; Mondego, Jorge Maurício Costa; Costa, Gustavo Gilson Lacerda; Herai, Roberto Hirochi; Würtele, Martin; de Carvalho, Lucas Miguel; Carmona e Ferreira, Renata; Mortara, Renato Arruda; Barbiéri, Clara Lucia; Mieczkowski, Piotr; da Silveira, José Franco; Briones, Marcelo Ribeiro da Silva; Pereira, Gonçalo Amarante Guimarães; Bahia, Diana

2013-12-01

We present the sequencing and annotation of the Leishmania (Leishmania) amazonensis genome, an etiological agent of human cutaneous leishmaniasis in the Amazon region of Brazil. L. (L.) amazonensis shares features with Leishmania (L.) mexicana but also exhibits unique characteristics regarding geographical distribution and clinical manifestations of cutaneous lesions (e.g. borderline disseminated cutaneous leishmaniasis). Predicted genes were scored for orthologous gene families and conserved domains in comparison with other human pathogenic Leishmania spp. Carboxypeptidase, aminotransferase, and 3'-nucleotidase genes and ATPase, thioredoxin, and chaperone-related domains were represented more abundantly in L. (L.) amazonensis and L. (L.) mexicana species. Phylogenetic analysis revealed that these two species share groups of amastin surface proteins unique to the genus that could be related to specific features of disease outcomes and host cell interactions. Additionally, we describe a hypothetical hybrid interactome of potentially secreted L. (L.) amazonensis proteins and host proteins under the assumption that parasite factors mimic their mammalian counterparts. The model predicts an interaction between an L. (L.) amazonensis heat-shock protein and mammalian Toll-like receptor 9, which is implicated in important immune responses such as cytokine and nitric oxide production. The analysis presented here represents valuable information for future studies of leishmaniasis pathogenicity and treatment.

The Genome Sequence of Leishmania (Leishmania) amazonensis: Functional Annotation and Extended Analysis of Gene Models

PubMed Central

Real, Fernando; Vidal, Ramon Oliveira; Carazzolle, Marcelo Falsarella; Mondego, Jorge Maurício Costa; Costa, Gustavo Gilson Lacerda; Herai, Roberto Hirochi; Würtele, Martin; de Carvalho, Lucas Miguel; e Ferreira, Renata Carmona; Mortara, Renato Arruda; Barbiéri, Clara Lucia; Mieczkowski, Piotr; da Silveira, José Franco; Briones, Marcelo Ribeiro da Silva; Pereira, Gonçalo Amarante Guimarães; Bahia, Diana

2013-01-01

We present the sequencing and annotation of the Leishmania (Leishmania) amazonensis genome, an etiological agent of human cutaneous leishmaniasis in the Amazon region of Brazil. L. (L.) amazonensis shares features with Leishmania (L.) mexicana but also exhibits unique characteristics regarding geographical distribution and clinical manifestations of cutaneous lesions (e.g. borderline disseminated cutaneous leishmaniasis). Predicted genes were scored for orthologous gene families and conserved domains in comparison with other human pathogenic Leishmania spp. Carboxypeptidase, aminotransferase, and 3′-nucleotidase genes and ATPase, thioredoxin, and chaperone-related domains were represented more abundantly in L. (L.) amazonensis and L. (L.) mexicana species. Phylogenetic analysis revealed that these two species share groups of amastin surface proteins unique to the genus that could be related to specific features of disease outcomes and host cell interactions. Additionally, we describe a hypothetical hybrid interactome of potentially secreted L. (L.) amazonensis proteins and host proteins under the assumption that parasite factors mimic their mammalian counterparts. The model predicts an interaction between an L. (L.) amazonensis heat-shock protein and mammalian Toll-like receptor 9, which is implicated in important immune responses such as cytokine and nitric oxide production. The analysis presented here represents valuable information for future studies of leishmaniasis pathogenicity and treatment. PMID:23857904

Jiko-shisen-kyofu (fear of one's own glance), but not taijin-kyofusho (fear of interpersonal relations), is an east Asian culture-related specific syndrome.

PubMed

Iwata, Yasuhide; Suzuki, Katsuaki; Takei, Nori; Toulopoulou, Timothea; Tsuchiya, Kenji J; Matsumoto, Kaori; Takagai, Shu; Oshiro, Masaya; Nakamura, Kazuhiko; Mori, Norio

2011-02-01

According to the DSM-IV-TR, the concept of taijin-kyofusho (fear of interpersonal relations) is both unique to East Asia and a culture-bound syndrome. In the indigenous diagnostic classification system in Japan, taijin-kyofusho consists of four subtypes, i.e. sekimen-kyofu (phobia of blushing), shubo-kyofu (phobia of a deformed face/body), jiko-shu-kyofu (phobia of one's own foul body odour), and jiko-shisen-kyofu (phobia of one's own glance). Each subtype except for phobia of one's own glance can be adequately assigned to a respective existing category in the DSM-IV-TR. The aim of the study was to introduce clinical features of phobia of one's own glance to western psychiatrists. Description of a series of cases with jiko-shisen-kyofu (phobia of one's own glance). All of our cases shared the unique feature that they suffered from the preoccupation that their own glance was offensive to others, and as a result were socially withdrawn themselves. To our best knowledge, no cases with a clear picture of phobia of one's own glance have been reported in the West to date. The controversial issue of the classification of phobia of one's own glance as an east Asian culture-related specific syndrome was addressed.

Mucopolysaccharidosis IVA and glycosaminoglycans

PubMed Central

Khan, Shaukat; Alméciga-Díaz, Carlos J.; Sawamoto, Kazuki; Mackenzie, William G.; Theroux, Mary C; Pizarro, Christian; Mason, Robert W.; Orii, Tadao; Tomatsu, Shunji

2016-01-01

Mucopolysaccharidosis IVA (MPS IVA; Morquio A: OMIM 253000) is a lysosomal storage disease with an autosomal recessive trait caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to accumulation of specific glycosaminoglycans (GAGs): chondroitin-6-sulfate (C6S) and keratan sulfate (KS). C6S and KS are mainly produced in the cartilage. Therefore, the undegraded substrates are stored primarily in cartilage and in its extracellular matrix (ECM), leading to a direct impact on cartilage and bone development, and successive systemic skeletal dysplasia. Chondrogenesis, the earliest phase of skeletal formation, is maintained by cellular interactions with the ECM, growth and differentiation factors, signaling pathways, and transcription factors in a temporal-spatial manner. In patients with MPS IVA, the cartilage is disrupted at birth as a consequence of abnormal chondrogenesis and/or endochondral ossification. The unique skeletal features are distinguished by a disproportional short stature, odontoid hypoplasia, spinal cord compression, tracheal obstruction, pectus carinatum, kyphoscoliosis, platyspondyly, coxa valga, genu valgum, waddling gait, and laxity of joints. In spite of many descriptions of these unique clinical features, delay of diagnosis still happens. The pathogenesis and treatment of systemic skeletal dysplasia in MPS IVA remains an unmet challenge. In this review article, we comprehensively describe historical aspect, property of GAGs, diagnosis, screening, pathogenesis, and current and future therapies of MPS IVA. PMID:27979613

Multi-Disciplinary Management of Athletes with Post-Concussion Syndrome: An Evolving Pathophysiological Approach.

PubMed

Ellis, Michael J; Leddy, John; Willer, Barry

2016-01-01

Historically, patients with sports-related concussion (SRC) have been managed in a uniform fashion consisting mostly of prescribed physical and cognitive rest with the expectation that all symptoms will spontaneously resolve with time. Although this approach will result in successful return to school and sports activities in the majority of athletes, an important proportion will develop persistent concussion symptoms characteristic of post-concussion syndrome (PCS). Recent advances in exercise science, neuroimaging, and clinical research suggest that the clinical manifestations of PCS are mediated by unique pathophysiological processes that can be identified by features of the clinical history and physical examination as well as the use of graded aerobic treadmill testing. Athletes who develop PCS represent a unique population whose care must be individualized and must incorporate a rehabilitative strategy that promotes enhanced recovery of concussion-related symptoms while preventing physical deconditioning. In this review, we present our evolving evidence-based approach to evaluation and management of athletes with PCS that aims to identify the pathophysiological mechanisms mediating persistent concussion symptoms and guides the initiation of individually tailored rehabilitation programs that target these processes. In addition, we outline the important qualified roles that multi-disciplinary healthcare professionals can play in the management of this patient population, and discuss where future research efforts must be focused to further evaluate this evolving pathophysiological approach.

Cryptococcus gattii as an important fungal pathogen of western North America

PubMed Central

Marr, Kieren A

2012-01-01

Cryptococcus gattii, a pathogenic fungus historically appreciated to be endemic to tropical regions, was recognized to emerge in a more temperate zone of North America in the 1990s. Early reports focused on an outbreak that was first apparent on Vancouver Island (BC, Canada), involving both the veterinary and human population. More recently, it has been recognized that this organism is endemic to a wider geography in western North America, with recognized disease caused by unique molecular subtypes in both healthy and immunosuppressed human hosts and a variety of domestic and wild animals. A number of cases of disease caused by C. gattii isolates that are unrelated to the Vancouver Island–Pacific Northwest outbreak strains have also been recognized in different parts of the USA. As microbiology laboratories have historically not identified these organisms to the species level, our current understanding of the scope of this infection is probably an underestimate. Ongoing public health epidemiologic efforts will be facilitated by increased attention towards culture-confirmed diagnosis and species identification in clinical microbiology laboratories. Early experience presents a strong rationale for increasing diagnostic attention, with multiple clinical features that are unique to this infection, including variability in antifungal susceptibilities and a heightened need for aggressive management of inflammatory responses. Larger prospective studies to evaluate and optimize clinical management are needed. PMID:22734955

Multi-Disciplinary Management of Athletes with Post-Concussion Syndrome: An Evolving Pathophysiological Approach

PubMed Central

Ellis, Michael J.; Leddy, John; Willer, Barry

2016-01-01

Historically, patients with sports-related concussion (SRC) have been managed in a uniform fashion consisting mostly of prescribed physical and cognitive rest with the expectation that all symptoms will spontaneously resolve with time. Although this approach will result in successful return to school and sports activities in the majority of athletes, an important proportion will develop persistent concussion symptoms characteristic of post-concussion syndrome (PCS). Recent advances in exercise science, neuroimaging, and clinical research suggest that the clinical manifestations of PCS are mediated by unique pathophysiological processes that can be identified by features of the clinical history and physical examination as well as the use of graded aerobic treadmill testing. Athletes who develop PCS represent a unique population whose care must be individualized and must incorporate a rehabilitative strategy that promotes enhanced recovery of concussion-related symptoms while preventing physical deconditioning. In this review, we present our evolving evidence-based approach to evaluation and management of athletes with PCS that aims to identify the pathophysiological mechanisms mediating persistent concussion symptoms and guides the initiation of individually tailored rehabilitation programs that target these processes. In addition, we outline the important qualified roles that multi-disciplinary healthcare professionals can play in the management of this patient population, and discuss where future research efforts must be focused to further evaluate this evolving pathophysiological approach. PMID:27605923

Medical returns: seeking health care in Mexico.

PubMed

Horton, Sarah; Cole, Stephanie

2011-06-01

Despite the growing prevalence of transnational medical travel among immigrant groups in industrialized nations, relatively little scholarship has explored the diverse reasons immigrants return home for care. To date, most research suggests that cost, lack of insurance and convenience propel US Latinos to seek health care along the Mexican border. Yet medical returns are common even among Latinos who do have health insurance and even among those not residing close to the border. This suggests that the distinct culture of medicine as practiced in the border clinics Latinos visit may be as important a factor in influencing medical returns as convenience and cost. Drawing upon qualitative interviews, this article presents an emic account of Latinos' perceptions of the features of medical practice in Mexico that make medical returns attractive. Between November 15, 2009 and January 15, 2010, we conducted qualitative interviews with 15 Mexican immigrants and nine Mexican Americans who sought care at Border Hospital, a private clinic in Tijuana. Sixteen were uninsured and eight had insurance. Yet of the 16 uninsured, six had purposefully dropped their insurance to make this clinic their permanent "medical home." Moreover, those who substituted receiving care at Border Hospital for their US health insurance plan did so not only because of cost, but also because of what they perceived as the distinctive style of medical practice at Border Hospital. Interviewees mentioned the rapidity of services, personal attention, effective medications, and emphasis on clinical discretion as features distinguishing "Mexican medical practice," opposing these features to the frequent referrals and tests, impersonal doctor-patient relationships, uniform treatment protocols and reliance on surgeries they experienced in the US health care system. While interviewees portrayed these features as characterizing a uniform "Mexican medical culture," we suggest that they are best described as unique to the private clinics and hospitals returning migrants visit. In short, we suggest that the perceived contrast in cultures of medicine derives from the difference in organization of health care services on each side of the border. Copyright © 2011 Elsevier Ltd. All rights reserved.

Ethical issues with informed consent from potential living kidney donors.

PubMed

Petrini, C

2010-05-01

Living organ donation and participation in clinical research trials have several features in common from an ethical perspective. The primary similarity is risk justification: the risk of harm to living organ donors and clinical research participants is justified by a resulting benefit to one or more other individuals. Some authors hold that organ donation and clinical trial participation are full-fledged duties. Such an implicit likening of the two leads to several considerations regarding informed consent in each situation. Informed consent raises ethical concerns in every medical context, and some of those concerns, such as competence, understanding, autonomy, and free or voluntary choice, are uniquely relevant to living organ donation and clinical trial participation. Most countries regulate informed consent procedures for living organ donation in great detail, and although informed consent procedures for clinical trial participation are somewhat less detailed, their rules are subject to review by ethics committees. It would be constructive for research participation informed consent procedures and living organ donation informed consent procedures to learn from one another. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Bioreducible Fluorinated Peptide Dendrimers Capable of Circumventing Various Physiological Barriers for Highly Efficient and Safe Gene Delivery.

PubMed

Cai, Xiaojun; Jin, Rongrong; Wang, Jiali; Yue, Dong; Jiang, Qian; Wu, Yao; Gu, Zhongwei

2016-03-09

Polymeric vectors have shown great promise in the development of safe and efficient gene delivery systems; however, only a few have been developed in clinical settings due to poor transport across multiple physiological barriers. To address this issue and promote clinical translocation of polymeric vectors, a new type of polymeric vector, bioreducible fluorinated peptide dendrimers (BFPDs), was designed and synthesized by reversible cross-linking of fluorinated low generation peptide dendrimers. Through masterly integration all of the features of reversible cross-linking, fluorination, and polyhedral oligomeric silsesquioxane (POSS) core-based peptide dendrimers, this novel vector exhibited lots of unique features, including (i) inactive surface to resist protein interactions; (ii) virus-mimicking surface topography to augment cellular uptake; (iii) fluorination-mediated efficient cellular uptake, endosome escape, cytoplasm trafficking, and nuclear entry, and (iv) disulfide-cleavage-mediated polyplex disassembly and DNA release that allows efficient DNA transcription. Noteworthy, all of these features are functionally important and can synergistically facilitate DNA transport from solution to the nucleus. As a consequences, BFPDs showed excellent gene transfection efficiency in several cell lines (∼95% in HEK293 cells) and superior biocompatibility compared with polyethylenimine (PEI). Meanwhile BFPDs provided excellent serum resistance in gene delivery. More importantly, BFPDs offer considerable in vivo gene transfection efficiency (in muscular tissues and in HepG2 tumor xenografts), which was approximately 77-fold higher than that of PEI in luciferase activity. These results suggest bioreducible fluorinated peptide dendrimers are a new class of highly efficient and safe gene delivery vectors and should be used in clinical settings.

A Systematic Review of the Huntington Disease-Like 2 Phenotype.

PubMed

Anderson, David G; Walker, Ruth H; Connor, Myles; Carr, Jonathan; Margolis, Russell L; Krause, Amanda

2017-01-01

Huntington Disease-like 2 (HDL2) is a neurodegenerative disorder similar to Huntington Disease (HD) in its clinical phenotype, genetic characteristics, neuropathology and longitudinal progression. Proposed specific differences include an exclusive African ancestry, lack of eye movement abnormalities, increased Parkinsonism, and acanthocytes in HDL2. The objective was to determine the similarities and differences between HD and HDL2 by establishing the clinical phenotype of HDL2 with the published cases. A literature review of all clinically described cases of HDL2 until the end of 2016 was performed and a descriptive analysis was carried out. Sixty-nine new cases were described between 2001 and 2016. All cases had likely African ancestry, and most were found in South Africa and the USA. Many features were found to be similar to HD, including a strong negative correlation between repeat length and age of onset. Chorea was noted in 48/57 cases (84%). Dementia was reported in 74% patients, and Parkinsonism in 37%. Psychiatric features were reported in 44 out of 47 cases. Patients with chorea had lower expanded repeat lengths compared to patients without chorea. Eye movements were described in 19 cases, 8 were abnormal. Acanthocytes were detected in 4 of the 13 patients tested. Nineteen out of 20 MRIs were reported as abnormal with findings similar to HD. This review clarifies some aspects of the HDL2 phenotype and highlights others which require further investigation. Features that are unique to HDL2 have been documented in a minority of subjects and require prospective validation.

Radiogenomics analysis identifies correlations of digital mammography with clinical molecular signatures in breast cancer.

PubMed

Tamez-Peña, Jose-Gerardo; Rodriguez-Rojas, Juan-Andrés; Gomez-Rueda, Hugo; Celaya-Padilla, Jose-Maria; Rivera-Prieto, Roxana-Alicia; Palacios-Corona, Rebeca; Garza-Montemayor, Margarita; Cardona-Huerta, Servando; Treviño, Victor

2018-01-01

In breast cancer, well-known gene expression subtypes have been related to a specific clinical outcome. However, their impact on the breast tissue phenotype has been poorly studied. Here, we investigate the association of imaging data of tumors to gene expression signatures from 71 patients with breast cancer that underwent pre-treatment digital mammograms and tumor biopsies. From digital mammograms, a semi-automated radiogenomics analysis generated 1,078 features describing the shape, signal distribution, and texture of tumors along their contralateral image used as control. From tumor biopsy, we estimated the OncotypeDX and PAM50 recurrence scores using gene expression microarrays. Then, we used multivariate analysis under stringent cross-validation to train models predicting recurrence scores. Few univariate features reached Spearman correlation coefficients above 0.4. Nevertheless, multivariate analysis yielded significantly correlated models for both signatures (correlation of OncotypeDX = 0.49 ± 0.07 and PAM50 = 0.32 ± 0.10 in stringent cross-validation and OncotypeDX = 0.83 and PAM50 = 0.78 for a unique model). Equivalent models trained from the unaffected contralateral breast were not correlated suggesting that the image signatures were tumor-specific and that overfitting was not a considerable issue. We also noted that models were improved by combining clinical information (triple negative status and progesterone receptor). The models used mostly wavelets and fractal features suggesting their importance to capture tumor information. Our results suggest that molecular-based recurrence risk and breast cancer subtypes have observable radiographic phenotypes. To our knowledge, this is the first study associating mammographic information to gene expression recurrence signatures.

Towards a clinically informed, data-driven definition of elderly onset epilepsy.

PubMed

Josephson, Colin B; Engbers, Jordan D T; Sajobi, Tolulope T; Jette, Nathalie; Agha-Khani, Yahya; Federico, Paolo; Murphy, William; Pillay, Neelan; Wiebe, Samuel

2016-02-01

Elderly onset epilepsy represents a distinct subpopulation that has received considerable attention due to the unique features of the disease in this age group. Research into this particular patient group has been limited by a lack of a standardized definition and understanding of the attributes associated with elderly onset epilepsy. We used a prospective cohort database to examine differences in patients stratified according to age of onset. Linear support vector machine learning incorporating all significant variables was used to predict age of onset according to prespecified thresholds. Sensitivity and specificity were calculated and plotted in receiver-operating characteristic (ROC) space. Feature coefficients achieving an absolute value of 0.25 or greater were graphed by age of onset to define how they vary with time. We identified 2,449 patients, of whom 149 (6%) had an age of seizure onset of 65 or older. Fourteen clinical variables had an absolute predictive value of at least 0.25 at some point over the age of epilepsy-onset spectrum. Area under the curve in ROC space was maximized between ages of onset of 65 and 70. Features identified through machine learning were frequently threshold specific and were similar, but not identical, to those revealed through simple univariable and multivariable comparisons. This study provides an empirical, clinically informed definition of "elderly onset epilepsy." If validated, an age threshold of 65-70 years can be used for future studies of elderly onset epilepsy and permits targeted interventions according to the patient's age of onset. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Radiogenomics analysis identifies correlations of digital mammography with clinical molecular signatures in breast cancer

PubMed Central

Tamez-Peña, Jose-Gerardo; Rodriguez-Rojas, Juan-Andrés; Gomez-Rueda, Hugo; Celaya-Padilla, Jose-Maria; Rivera-Prieto, Roxana-Alicia; Palacios-Corona, Rebeca; Garza-Montemayor, Margarita; Cardona-Huerta, Servando

2018-01-01

In breast cancer, well-known gene expression subtypes have been related to a specific clinical outcome. However, their impact on the breast tissue phenotype has been poorly studied. Here, we investigate the association of imaging data of tumors to gene expression signatures from 71 patients with breast cancer that underwent pre-treatment digital mammograms and tumor biopsies. From digital mammograms, a semi-automated radiogenomics analysis generated 1,078 features describing the shape, signal distribution, and texture of tumors along their contralateral image used as control. From tumor biopsy, we estimated the OncotypeDX and PAM50 recurrence scores using gene expression microarrays. Then, we used multivariate analysis under stringent cross-validation to train models predicting recurrence scores. Few univariate features reached Spearman correlation coefficients above 0.4. Nevertheless, multivariate analysis yielded significantly correlated models for both signatures (correlation of OncotypeDX = 0.49 ± 0.07 and PAM50 = 0.32 ± 0.10 in stringent cross-validation and OncotypeDX = 0.83 and PAM50 = 0.78 for a unique model). Equivalent models trained from the unaffected contralateral breast were not correlated suggesting that the image signatures were tumor-specific and that overfitting was not a considerable issue. We also noted that models were improved by combining clinical information (triple negative status and progesterone receptor). The models used mostly wavelets and fractal features suggesting their importance to capture tumor information. Our results suggest that molecular-based recurrence risk and breast cancer subtypes have observable radiographic phenotypes. To our knowledge, this is the first study associating mammographic information to gene expression recurrence signatures. PMID:29596496

Steel syndrome: dislocated hips and radial heads, carpal coalition, scoliosis, short stature, and characteristic facial features.

PubMed

Flynn, John M; Ramirez, Norman; Betz, Randal; Mulcahey, Mary Jane; Pino, Franz; Herrera-Soto, Jose A; Carlo, Simon; Cornier, Alberto S

2010-01-01

A syndrome of children with short stature, bilateral hip dislocations, radial head dislocations, carpal coalitions, scoliosis, and cavus feet in Puerto Rican children, was reported by Steel et al in 1993. The syndrome was described as a unique entity with dismal results after conventional treatment of dislocated hips. The purpose of this study is to reevaluate this patient population with a longer follow-up and delineate the clinical and radiologic features, treatment outcomes, and the genetic characteristics. This is a retrospective cohort study of 32 patients in whom we evaluated the clinical, imaging data, and genetic characteristics. We compare the findings and quality of life in patients with this syndrome who have had attempts at reduction of the hips versus those who did not have the treatment. Congenital hip dislocations were present in 100% of the patients. There was no attempt at reduction in 39% (25/64) of the hips. In the remaining 61% (39/64), the hips were treated with a variety of modalities fraught with complications. Of those treated, 85% (33/39) remain dislocated, the rest of the hips continue subluxated with acetabular dysplasia and pain. The group of hips that were not treated reported fewer complaints and limitation in daily activities compared with the hips that had attempts at reduction. Steel syndrome is a distinct clinical entity characterized by short stature, bilateral hip and radial head dislocation, carpal coalition, scoliosis, cavus feet, and characteristic facial features with dismal results for attempts at reduction of the hips. Prognostic Study Level II.

Practice of clinical forensic medicine in Sri Lanka: does it need a new era?

PubMed

Kodikara, Sarathchandra

2012-07-01

Clinical forensic medicine is a sub-specialty of forensic medicine and is intimately associated with the justice system of a country. Practice of clinical forensic medicine is evolving, but deviates from one jurisdiction to another. Most English-speaking countries practice clinical forensic medicine and forensic pathology separately while most non-English-speaking countries practice forensic medicine which includes clinical forensic medicine and forensic pathology. Unlike the practice of forensic pathology, several countries have informal arrangements to deal with forensic patients and there are no international standards of practice or training in this discipline. Besides, this is rarely a topic of discussion. In the adversarial justice system in Sri Lanka, the designated Government Medical Officers practice both clinical forensic medicine and forensic pathology. Practice of clinical forensic medicine, and its teaching and training in Sri Lanka depicts unique features. However, this system has not undergone a significant revision for many decades. In this communication, the existing legal framework, current procedure of practice, examination for drunkenness, investigations, structure of referrals, reports, subsequent legal procedures, undergraduate, in-service, and postgraduate training are discussed with suggestions for reforms. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

T cell lymphomatoid contact dermatitis: a challenging case and review of the literature.

PubMed

Knackstedt, Thomas J; Zug, Kathryn A

2015-02-01

Lymphomatoid contact dermatitis is a pseudolymphoma with clinical and histological features of allergic contact dermatitis and cutaneous T cell lymphoma. Incorrect diagnosis may lead to unnecessary testing, unnecessary treatment, or patient harm. The objective of this study is to present a case to demonstrate the diagnostic challenge and overlap between allergic contact dermatitis and cutaneous T cell lymphoma in a patient with lymphomatoid contact dermatitis caused by methylchoroisothiazolinone/methylisothiazolinone and paraben mix, and to review the existing literature in order to summarize the demographics, clinical features, allergens and treatments reported for lymphomatoid contact dermatitis. A search of major scientific databases was conducted for English-language articles reporting cases of lymphomatoid contact dermatitis or additional synonymous search headings. Nineteen articles with a total of 23 patients were analysed. Lymphomatoid contact dermatitis was more common in men, with an average age of 58.5 years. Fourteen unique allergens were identified and confirmed by patch testing. However, no single test or study was diagnostic of lymphomatoid contact dermatitis. Allergen avoidance was the most useful management tool, but selected patients required topical or systemic immunosuppression. In conclusion, without specific diagnostic features, evaluation for lymphomatoid contact dermatitis should include a thorough history and examination, patch testing, and biopsy with immunohistochemistry and clonality studies. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dominant de novo DSP mutations cause erythrokeratodermia-cardiomyopathy syndrome.

PubMed

Boyden, Lynn M; Kam, Chen Y; Hernández-Martín, Angela; Zhou, Jing; Craiglow, Brittany G; Sidbury, Robert; Mathes, Erin F; Maguiness, Sheilagh M; Crumrine, Debra A; Williams, Mary L; Hu, Ronghua; Lifton, Richard P; Elias, Peter M; Green, Kathleen J; Choate, Keith A

2016-01-15

Disorders of keratinization (DOK) show marked genotypic and phenotypic heterogeneity. In most cases, disease is primarily cutaneous, and further clinical evaluation is therefore rarely pursued. We have identified subjects with a novel DOK featuring erythrokeratodermia and initially-asymptomatic, progressive, potentially fatal cardiomyopathy, a finding not previously associated with erythrokeratodermia. We show that de novo missense mutations clustered tightly within a single spectrin repeat of DSP cause this novel cardio-cutaneous disorder, which we term erythrokeratodermia-cardiomyopathy (EKC) syndrome. We demonstrate that DSP mutations in our EKC syndrome subjects affect localization of desmosomal proteins and connexin 43 in the skin, and result in desmosome aggregation, widening of intercellular spaces, and lipid secretory defects. DSP encodes desmoplakin, a primary component of desmosomes, intercellular adhesion junctions most abundant in the epidermis and heart. Though mutations in DSP are known to cause other disorders, our cohort features the unique clinical finding of severe whole-body erythrokeratodermia, with distinct effects on localization of desmosomal proteins and connexin 43. These findings add a severe, previously undescribed syndrome featuring erythrokeratodermia and cardiomyopathy to the spectrum of disease caused by mutation in DSP, and identify a specific region of the protein critical to the pathobiology of EKC syndrome and to DSP function in the heart and skin. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Redefining cerebral malaria by including malaria retinopathy.

PubMed

Beare, Nicholas A V; Lewallen, Susan; Taylor, Terrie E; Molyneux, Malcolm E

2011-03-01

Accurate diagnosis of cerebral malaria (CM) is important for patient management, epidemiological and end point surveillance, and enrolling patients with CM in studies of pathogenesis or therapeutic trials. In malaria-endemic areas, where asymptomatic Plasmodium falciparum parasitemia is common, a positive blood film in a comatose individual does not prove that the coma is due to malaria. A retinopathy consisting of two unique features - patchy retinal whitening and focal changes of vessel color - is highly specific for encephalopathy of malarial etiology. White-centered retinal hemorrhages are a common but less specific feature. Either indirect or direct ophthalmoscopy can be used to identify the changes, and both procedures can be learned and practiced by nonspecialist clinicians. In view of its important contributions to both clinical care and research, examination of the retina should become a routine component of the assessment of a comatose child or adult when CM is a possible diagnosis.

Redefining cerebral malaria by including malaria retinopathy

PubMed Central

Beare, Nicholas AV; Lewallen, Susan; Taylor, Terrie E; Molyneux, Malcolm E

2011-01-01

Accurate diagnosis of cerebral malaria (CM) is important for patient management, epidemiological and end point surveillance, and enrolling patients with CM in studies of pathogenesis or therapeutic trials. In malaria-endemic areas, where asymptomatic Plasmodium falciparum parasitemia is common, a positive blood film in a comatose individual does not prove that the coma is due to malaria. A retinopathy consisting of two unique features – patchy retinal whitening and focal changes of vessel color – is highly specific for encephalopathy of malarial etiology. White-centered retinal hemorrhages are a common but less specific feature. Either indirect or direct ophthalmoscopy can be used to identify the changes, and both procedures can be learned and practiced by nonspecialist clinicians. In view of its important contributions to both clinical care and research, examination of the retina should become a routine component of the assessment of a comatose child or adult when CM is a possible diagnosis. PMID:21449844

Perforated peptic ulcer in an adolescent girl.

PubMed

Schwartz, Shepard; Edden, Yair; Orkin, Boris; Erlichman, Matityahu

2012-07-01

A perforated peptic ulcer in a child is a rare entity. Severe abdominal pain in an ill-appearing child with a rigid abdomen and possibly with signs of shock is the typical presenting feature of this life-threatening complication of peptic ulcer disease. We present a case of a 14.5-year-old adolescent girl who developed abdominal and shoulder pain that resolved after 1 day. She was then completely well for 2 days until the abdominal and shoulder pain recurred. On examination, she appeared well, but in pain. A chest radiograph revealed a large pneumoperitoneum. She underwent emergent laparoscopic omental patch repair of a perforated ulcer on the anterior wall of her stomach. Result of a urea breath test to detect Helicobacter pylori was negative. The differential diagnosis of pneumoperitoneum in children is discussed, as are childhood perforated peptic ulcer in general, and the unique clinical features present in this case in particular.

Benzimidazole-core as an antimycobacterial agent.

PubMed

Keri, Rangappa S; Rajappa, Chethana Kolambae; Patil, Siddappa A; Nagaraja, Bhari Mallanna

2016-12-01

Mycobacterium tuberculosis (Mtb) is considered as one of the precarious bacterial infections around the world. Through a projected 8.7 million new tuberculosis (TB) cases and 1.4 million mortalities per annum, this deadly infection resulted insubstantial amount of human deaths than any other single organism bacterial infections. TB is one of India's most threatening human health problems and it accounts for approximately 33% of the global health issues. Subsequently, for TB there is an imperative need for the improvement of existing drug candidates with newer targets and specified mechanism of action. Within the wide spectra of heterocycles, benzimidazole and its substituted analogues were evidenced promising biological efficacies enabling them to perform as new drug or prodrug candidates. Exceptional structural features of this class of heterocycle and versatile biological applications made it a privileged structural backbone in new drug design and discovery. Majorly, 2,5- and 2,6-disubstituted benzimidazole derivatives shown to induce significant antiTB potential. To seek more insights on this unique feature of benzimidazole candidates, there is an urgency to assemble the recent advances in this promising area. This review presents an overview of the recent advancements and focuses on the structural features responsible for unique antiTB applications and compiled published reports on benzimidazole derivatives emphasizing on different approaches employed for their syntheses in order to help medicinal and clinical chemists in designing next generation, yet effective and safer antiTB candidates. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Novel autosomal dominant mandibulofacial dysostosis with ptosis: clinical description and exclusion of TCOF1.

PubMed

Hedera, P; Toriello, H V; Petty, E M

2002-07-01

Treacher Collins syndrome (TCS), the most common type of mandibulofacial dysostosis (MFD), is genetically homogeneous. Other types of MFD are less common and, of these, only the Bauru type of MFD has an autosomal dominant (AD) mode of inheritance established. Here we report clinical features of a kindred with a unique AD MFD with the exclusion of linkage to the TCS locus (TCOF1) on chromosome 5q31-q32. Six affected family members underwent a complete medical genetics physical examination and two affected subjects had skeletal survey. All available medical records were reviewed. Linkage analysis using the markers spanning the TCOF1 locus was performed. One typically affected family member had a high resolution karyotype. Affected subjects had significant craniofacial abnormalities without any significant acral changes and thus had a phenotype consistent with a MFD variant. Distinctive features included hypoplasia of the zygomatic complex, micrognathia with malocclusion, auricular abnormalities with conductive hearing loss, and ptosis. Significantly negative two point lod scores were obtained for markers spanning the TCOF1 locus, excluding the possibility that the disease in our kindred is allelic with TCS. High resolution karyotype was normal. We report a kindred with a novel type of MFD that is not linked to the TCOF1 locus and is also clinically distinct from other types of AD MFD. Identification of additional families will facilitate identification of the gene causing this type of AD MFD and further characterisation of the clinical phenotype.

A relativity concept in mesenchymal stromal cell manufacturing.

PubMed

Martin, Ivan; De Boer, Jan; Sensebe, Luc

2016-05-01

Mesenchymal stromal cells (MSCs) are being experimentally tested in several biological systems and clinical settings with the aim of verifying possible therapeutic effects for a variety of indications. MSCs are also known to be heterogeneous populations, with phenotypic and functional features that depend heavily on the individual donor, the harvest site, and the culture conditions. In the context of this multidimensional complexity, a recurrent question is whether it is feasible to produce MSC batches as "standard" therapeutics, possibly within scalable manufacturing systems. Here, we provide a short overview of the literature on different culture methods for MSCs, including those employing innovative technologies, and of some typically assessed functional features (e.g., growth, senescence, genomic stability, clonogenicity, etc.). We then offer our perspective of a roadmap on how to identify and refine manufacturing systems for MSCs intended for specific clinical indications. We submit that the vision of producing MSCs according to a unique standard, although commercially attractive, cannot yet be scientifically substantiated. Instead, efforts should be concentrated on standardizing methods for characterization of MSCs generated by different groups, possibly covering a vast gamut of functionalities. Such assessments, combined with hypotheses on the therapeutic mode of action and associated clinical data, should ultimately allow definition of in-process controls and measurable release criteria for MSC manufacturing. These will have to be validated as predictive of potency in suitable pre-clinical models and of therapeutic efficacy in patients. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Bloodstream Infections and Clinical Significance of Healthcare-associated Bacteremia: A Multicenter Surveillance Study in Korean Hospitals

PubMed Central

Son, Jun Seong; Ko, Kwan Soo; Yeom, Joon Sup; Ki, Hyun Kyun; Kim, Shin-Woo; Chang, Hyun-Ha; Ryu, Seong Yeol; Kim, Yeon-Sook; Jung, Sook-In; Shin, Sang Yop; Oh, Hee Bok; Lee, Yeong Seon; Chung, Doo Ryeon; Lee, Nam Yong; Peck, Kyong Ran

2010-01-01

Recent changes in healthcare systems have changed the epidemiologic paradigms in many infectious fields including bloodstream infection (BSI). We compared clinical characteristics of community-acquired (CA), hospital-acquired (HA), and healthcare-associated (HCA) BSI. We performed a prospective nationwide multicenter surveillance study from 9 university hospitals in Korea. Total 1,605 blood isolates were collected from 2006 to 2007, and 1,144 isolates were considered true pathogens. HA-BSI accounted for 48.8%, CA-BSI for 33.2%, and HCA-BSI for 18.0%. HA-BSI and HCA-BSI were more likely to have severe comorbidities. Escherichia coli was the most common isolate in CA-BSI (47.1%) and HCA-BSI (27.2%). In contrast, Staphylococcus aureus (15.2%), coagulase-negative Staphylococcus (15.1%) were the common isolates in HA-BSI. The rate of appropriate empiric antimicrobial therapy was the highest in CA-BSI (89.0%) followed by HCA-BSI (76.4%), and HA-BSI (75.0%). The 30-day mortality rate was the highest in HA-BSI (23.0%) followed by HCA-BSI (18.4%), and CA-BSI (10.2%). High Pitt score and inappropriate empirical antibiotic therapy were the independent risk factors for mortality by multivariate analysis. In conclusion, the present data suggest that clinical features, outcome, and microbiologic features of causative pathogens vary by origin of BSI. Especially, HCA-BSI shows unique clinical characteristics, which should be considered a distinct category for more appropriate antibiotic treatment. PMID:20592888

Containerless protein crystal growth method

NASA Technical Reports Server (NTRS)

Rhim, Won-Kyu; Chung, Sang K.

1991-01-01

A method of growing protein crystals from levitated drops is introduced and unique features of containerless approach in 1-g and micro-G laboratories are discussed. Electrostatic multidrop levitation system which is capable of simultaneous four drop levitation is described. A method of controlling protein saturation level in a programmed way is introduced and discussed. Finally, some of the unique features of containerless approach of protein crystal growth in space are discussed and summarized.

The clinical impact of serrated colorectal polyps

PubMed Central

O’Connell, Brendon M; Crockett, Seth D

2017-01-01

Serrated polyps (SPs) of the colorectum pose a novel challenge to practicing gastroenterologists. Previously thought benign and unimportant, there is now compelling evidence that SPs are responsible for a significant percentage of incident colorectal cancer worldwide. In contrast to conventional adenomas, which tend to be slow growing and polypoid, SPs have unique features that undermine current screening and surveillance practices. For example, sessile serrated polyps (SSPs) are flat, predominately right-sided, and thought to have the potential for rapid growth. Moreover, SSPs are subject to wide variations in endoscopic detection and pathologic interpretation. Unfortunately, little is known about the natural history of SPs, and current guidelines are based largely on expert opinion. In this review, we outline the current taxonomy, epidemiology, and management of SPs with an emphasis on the clinical and public health impact of these lesions. PMID:28260946

Migraine with Aura or Sports-Related Concussion: Case Report, Pathophysiology, and Multidisciplinary Approach to Management.

PubMed

Ellis, Michael J; Cordingley, Dean; Girardin, Richard; Ritchie, Lesley; Johnston, Janine

The evaluation and management of athletes presenting with clinical features of migraine headache with aura in the setting of sports-related head trauma is challenging. We present a case report of a 15-yr-old boy with a history of migraine with visual aura that developed acute visual disturbance and headache after a head injury during an ice hockey game. The patient underwent comprehensive assessment at a multidisciplinary concussion program, including neuro-ophthalmological examination, neurocognitive testing, and graded aerobic treadmill testing. Clinical history and multidisciplinary assessment was consistent with the diagnosis of coexisting sports-related concussion and migraine with brainstem aura. The authors discuss the pearls and pitfalls of managing patients who develop migraine headache with visual aura after sports-related head injury and the value of a comprehensive multidisciplinary approach to this unique patient population.

Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy and lysosome-autophagosome dysfunction

PubMed Central

Akizu, Naiara; Cantagrel, Vincent; Zaki, Maha S.; Al-Gazali, Lihadh; Wang, Xin; Rosti, Rasim Ozgur; Dikoglu, Esra; Gelot, Antoinette Bernabe; Rosti, Basak; Vaux, Keith K.; Scott, Eric M.; Silhavy, Jennifer L.; Schroth, Jana; Copeland, Brett; Schaffer, Ashleigh E.; Gordts, Philip; Esko, Jeffrey D.; Buschman, Matthew D.; Fields, Seth J.; Napolitano, Gennaro; Ozgul, R. Koksal; Sagiroglu, Mahmut Samil; Azam, Matloob; Ismail, Samira; Aglan, Mona; Selim, Laila; Gamal, Iman; Hadi, Sawsan Abdel; El Badawy, Amera; Sadek, Abdelrahim A.; Mojahedi, Faezeh; Kayserili, Hulya; Masri, Amira; Bastaki, Laila; Temtamy, Samia; Müller, Ulrich; Desguerre, Isabelle; Casanova, Jean-Laurent; Dursun, Ali; Gunel, Murat; Gabriel, Stacey B.; de Lonlay, Pascale; Gleeson, Joseph G.

2015-01-01

Pediatric-onset ataxias often present clinically with developmental delay and intellectual disability, with prominent cerebellar atrophy as a key neuroradiographic finding. Here we describe a novel clinically distinguishable recessive syndrome in 12 families with cerebellar atrophy together with ataxia, coarsened facial features and intellectual disability, due to truncating mutations in sorting nexin 14 (SNX14), encoding a ubiquitously expressed modular PX-domain-containing sorting factor. We found SNX14 localized to lysosomes, and associated with phosphatidyl-inositol (3,5)P2, a key component of late endosomes/lysosomes. Patient cells showed engorged lysosomes and slower autophagosome clearance rate upon starvation induction. Zebrafish morphants showed dramatic loss of cerebellar parenchyma, accumulated autophagosomes, and activation of apoptosis. Our results suggest a unique ataxia syndrome due to biallelic SNX14 mutations, leading to lysosome-autophagosome dysfunction. PMID:25848753

Expression Analysis of Macrodactyly Identifies Pleiotrophin Upregulation

PubMed Central

Lau, Frank H.; Xia, Fang; Kaplan, Adam; Cerrato, Felecia; Greene, Arin K.; Taghinia, Amir; Cowan, Chad A.; Labow, Brian I.

2012-01-01

Macrodactyly is a rare family of congenital disorders characterized by the diffuse enlargement of 1 or more digits. Multiple tissue types within the affected digits are involved, but skeletal patterning and gross morphological features are preserved. Not all tissues are equally involved and there is marked heterogeneity with respect to clinical phenotype. The molecular mechanisms responsible for these growth disturbances offer unique insight into normal limb growth and development, in general. To date, no genes or loci have been implicated in the development of macrodactyly. In this study, we performed the first transcriptional profiling of macrodactyly tissue. We found that pleiotrophin (PTN) was significantly overexpressed across all our macrodactyly samples. The mitogenic functions of PTN correlate closely with the clinical characteristics of macrodactyly. PTN thus represents a promising target for further investigation into the etiology of overgrowth phenotypes. PMID:22848377

Post-SELEX optimization of aptamers.

PubMed

Gao, Shunxiang; Zheng, Xin; Jiao, Binghua; Wang, Lianghua

2016-07-01

Aptamers are functional single-stranded DNA or RNA oligonucleotides, selected in vitro by SELEX (Systematic Evolution of Ligands by Exponential Enrichment), which can fold into stable unique three-dimensional structures that bind their target ligands with high affinity and specificity. Although aptamers show a number of favorable advantages such as better stability and easier modification when compared with the properties of antibodies, only a handful of aptamers have entered clinical trials and only one, pegaptanib, has received US Food and Drug Administration approval for clinical use. The main reasons that limit the practical application of aptamers are insufficient nuclease stability, bioavailability, thermal stability, or even affinity. Some aptamers obtained from modified libraries show better properties; however, polymerase amplification of nucleic acids containing non-natural bases is currently a primary drawback of the SELEX process. This review focuses on several post-SELEX optimization strategies of aptamers identified in recent years. We describe four common methods in detail: truncation, chemical modification, bivalent or multivalent aptamer construction, and mutagenesis. We believe that these optimization strategies should improve one or more specific properties of aptamers, and the type of feature(s) selected for improvement will be dependent on the application purpose.

An examination of the relationship between childhood emotional abuse and borderline personality disorder features: the role of difficulties with emotion regulation.

PubMed

Kuo, Janice R; Khoury, Jennifer E; Metcalfe, Rebecca; Fitzpatrick, Skye; Goodwill, Alasdair

2015-01-01

Childhood abuse has been consistently linked with borderline personality disorder (BPD) and recent studies suggest that some forms of childhood abuse might be uniquely related to both BPD and BPD features. In addition, difficulties with emotion regulation have been found to be associated with childhood abuse, BPD, as well as BPD features. The present study examined (1) whether frequency of childhood emotional abuse is uniquely associated with BPD feature severity when controlling for other forms of childhood abuse and (2) whether difficulties with emotion regulation accounts for the relationship between childhood emotional abuse and BPD feature severity. A sample of undergraduates (n=243) completed the Childhood Trauma Questionnaire - Short Form, Difficulties in Emotion Regulation Scale, and Borderline Symptom List-23. Multiple regression analyses and Structural Equation Modeling were conducted. Results indicated that frequency of childhood emotional abuse (and not sexual or physical abuse) was uniquely associated with BPD feature severity. In addition, while there was no direct path between childhood emotional abuse, childhood physical abuse, or childhood sexual abuse and BPD features, there was an indirect relationship between childhood emotional abuse and BPD features through difficulties with emotion regulation. These findings suggest that, of the different forms of childhood abuse, emotional abuse specifically, may have a developmental role in BPD pathology. Prevention and treatment of BPD pathology might benefit from the provision of emotion regulation strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Engineering Biomaterial Properties for Central Nervous System Applications

NASA Astrophysics Data System (ADS)

Rivet, Christopher John

Biomaterials offer unique properties that are intrinsic to the chemistry of the material itself or occur as a result of the fabrication process; iron oxide nanoparticles are superparamagnetic, which enables controlled heating in the presence of an alternating magnetic field, and a hydrogel and electrospun fiber hybrid material provides minimally invasive placement of a fibrous, artificial extracellular matrix for tissue regeneration. Utilization of these unique properties towards central nervous system disease and dysfunction requires a thorough definition of the properties in concert with full biological assessment. This enables development of material-specific features to elicit unique cellular responses. Iron oxide nanoparticles are first investigated for material-dependent, cortical neuron cytotoxicity in vitro and subsequently evaluated for alternating magnetic field stimulation induced hyperthermia, emulating the clinical application for enhanced chemotherapy efficacy in glioblastoma treatment. A hydrogel and electrospun fiber hybrid material is first applied to a rat brain to evaluate biomaterial interface astrocyte accumulation as a function of hybrid material composition. The hybrid material is then utilized towards increasing functional engraftment of dopaminergic progenitor neural stem cells in a mouse model of Parkinson's disease. Taken together, these two scenarios display the role of material property characterization in development of biomaterial strategies for central nervous system repair and regeneration.

A patient with a unique frameshift mutation in GPC3, causing Simpson-Golabi-Behmel syndrome, presenting with craniosynostosis, penoscrotal hypospadias, and a large prostatic utricle.

PubMed

Villarreal, Diana D; Villarreal, Humberto; Paez, Ana Maria; Peppas, Dennis; Lynch, Jane; Roeder, Elizabeth; Powers, George C

2013-12-01

We present a Hispanic male with the clinical and molecular diagnosis of Simpson-Golabi-Behmel syndrome (SGBS). The patient was born with multiple anomalies not entirely typical of SGBS patients, including penoscrotal hypospadias, a large prostatic utricle, and left coronal craniosynostosis. In addition, he demonstrated endocrine anomalies including a low random cortisol level suspicious for adrenal insufficiency and low testosterone level. To our knowledge, this is the first report of a prostatic utricle in SGBS and the second report of craniosynostosis. The unique disease-causing mutation likely arose de novo in the mother. It is a deletion-insertion that leads to a frameshift at the p.p. S359 [corrected] residue of GPC3 and a premature stop codon after five more amino acids. p. S359 [corrected] is the same residue that is normally cleaved by the Furin convertase, although the significance of this novel mutation with respect to the patient's multiple anomalies is unknown. We present this case as the perinatal course of a patient with unique features of SGBS and a confirmed molecular diagnosis. © 2013 Wiley Periodicals, Inc.

Unique Trichomonas vaginalis gene sequences identified in multinational regions of Northwest China.

PubMed

Liu, Jun; Feng, Meng; Wang, Xiaolan; Fu, Yongfeng; Ma, Cailing; Cheng, Xunjia

2017-07-24

Trichomonas vaginalis (T. vaginalis) is a flagellated protozoan parasite that infects humans worldwide. This study determined the sequence of the 18S ribosomal RNA gene of T. vaginalis infecting both females and males in Xinjiang, China. Samples from 73 females and 28 males were collected and confirmed for infection with T. vaginalis, a total of 110 sequences were identified when the T. vaginalis 18S ribosomal RNA gene was sequenced. These sequences were used to prepare a phylogenetic network. The rooted network comprised three large clades and several independent branches. Most of the Xinjiang sequences were in one group. Preliminary results suggest that Xinjiang T. vaginalis isolates might be genetically unique, as indicated by the sequence of their 18S ribosomal RNA gene. Low migration rate of local people in this province may contribute to a genetic conservativeness of T. vaginalis. The unique genetic feature of our isolates may suggest a different clinical presentation of trichomoniasis, including metronidazole susceptibility, T. vaginalis virus or Mycoplasma co-infection characteristics. The transmission and evolution of Xinjiang T. vaginalis is of interest and should be studied further. More attention should be given to T. vaginalis infection in both females and males in Xinjiang.

Prospective Associations Between Features of Borderline Personality Disorder, Emotion Dysregulation, and Aggression

PubMed Central

Scott, Lori N.; Stepp, Stephanie D.; Pilkonis, Paul A.

2014-01-01

Difficulties with emotion regulation and behavioral instability, including impulsive aggression, are seen as core dimensions underlying borderline personality disorder (BPD). Although both BPD and antisocial personality disorder (ASPD) are associated with impulsivity and aggressive behavior, difficulties regulating emotions may be associated uniquely with BPD and may explain distinctive associations between BPD and aggression. This study was designed to examine the unique prospective associations between BPD symptoms at baseline, difficulties with emotion regulation and trait impulsivity, and psychological and physical aggression (both perpetration and victimization) over the course of a year after controlling for ASPD symptoms in a mixed clinical and community sample of adults (N = 150). Results of a multivariate path analysis demonstrated that associations between BPD symptoms at baseline and later psychological and physical aggression were fully mediated by difficulties with emotion regulation. Although BPD symptoms also predicted trait impulsivity, impulsivity did not predict aggression after controlling for emotion dysregulation. ASPD symptoms were directly associated with physical assault perpetration and victimization but were not associated with emotion dysregulation, impulsivity, or psychological aggression. These findings suggest that although both BPD and ASPD are associated with aggressive behaviors, associations between BPD symptoms and aggression are mediated uniquely by difficulties regulating emotions. PMID:24635753

Dynamic feature analysis of vector-based images for neuropsychological testing

NASA Astrophysics Data System (ADS)

Smith, Stephen L.; Cervantes, Basilio R.

1998-07-01

The dynamic properties of human motor activities, such as those observed in the course of drawing simple geometric shapes, are considerably more complex and often more informative than the goal to be achieved; in this case a static line drawing. This paper demonstrates how these dynamic properties may be used to provide a means of assessing a patient's visuo-spatial ability -- an important component of neuropsychological testing. The work described here provides a quantitative assessment of visuo-spatial ability, whilst preserving the conventional test environment. Results will be presented for a clinical population of long-term haemodialysis patients and test population comprises three groups of children (1) 7-8 years, (2) 9-10 years and (3) 11-12 years, all of which have no known neurological dysfunction. Ten new dynamic measurements extracted from patient responses in conjunction with one static feature deduced from earlier work describe a patient's visuo-spatial ability in a quantitative manner with sensitivity not previously attainable. The dynamic feature measurements in isolation provide a unique means of tracking a patient's approach to motor activities and could prove useful in monitoring a child' visuo-motor development.

Protein Interactome of Muscle Invasive Bladder Cancer

PubMed Central

Bhat, Akshay; Heinzel, Andreas; Mayer, Bernd; Perco, Paul; Mühlberger, Irmgard; Husi, Holger; Merseburger, Axel S.; Zoidakis, Jerome; Vlahou, Antonia; Schanstra, Joost P.; Mischak, Harald; Jankowski, Vera

2015-01-01

Muscle invasive bladder carcinoma is a complex, multifactorial disease caused by disruptions and alterations of several molecular pathways that result in heterogeneous phenotypes and variable disease outcome. Combining this disparate knowledge may offer insights for deciphering relevant molecular processes regarding targeted therapeutic approaches guided by molecular signatures allowing improved phenotype profiling. The aim of the study is to characterize muscle invasive bladder carcinoma on a molecular level by incorporating scientific literature screening and signatures from omics profiling. Public domain omics signatures together with molecular features associated with muscle invasive bladder cancer were derived from literature mining to provide 286 unique protein-coding genes. These were integrated in a protein-interaction network to obtain a molecular functional map of the phenotype. This feature map educated on three novel disease-associated pathways with plausible involvement in bladder cancer, namely Regulation of actin cytoskeleton, Neurotrophin signalling pathway and Endocytosis. Systematic integration approaches allow to study the molecular context of individual features reported as associated with a clinical phenotype and could potentially help to improve the molecular mechanistic description of the disorder. PMID:25569276

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

PubMed

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

2014-10-01

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

Clinical course of sly syndrome (mucopolysaccharidosis type VII)

PubMed Central

Montaño, Adriana M; Lock-Hock, Ngu; Steiner, Robert D; Graham, Brett H; Szlago, Marina; Greenstein, Robert; Pineda, Mercedes; Gonzalez-Meneses, Antonio; Çoker, Mahmut; Bartholomew, Dennis; Sands, Mark S; Wang, Raymond; Giugliani, Roberto; Macaya, Alfons; Pastores, Gregory; Ketko, Anastasia K; Ezgü, Fatih; Tanaka, Akemi; Arash, Laila; Beck, Michael; Falk, Rena E; Bhattacharya, Kaustuv; Franco, José; White, Klane K; Mitchell, Grant A; Cimbalistiene, Loreta; Holtz, Max; Sly, William S

2016-01-01

Background Mucopolysaccharidosis VII (MPS VII) is an ultra-rare disease characterised by the deficiency of β-glucuronidase (GUS). Patients’ phenotypes vary from severe forms with hydrops fetalis, skeletal dysplasia and mental retardation to milder forms with fewer manifestations and mild skeletal abnormalities. Accurate assessments on the frequency and clinical characteristics of the disease have been scarce. The aim of this study was to collect such data. Methods We have conducted a survey of physicians to document the medical history of patients with MPS VII. The survey included anonymous information on patient demographics, family history, mode of diagnosis, age of onset, signs and symptoms, severity, management, clinical features and natural progression of the disease. Results We collected information on 56 patients from 11 countries. Patients with MPS VII were classified based on their phenotype into three different groups: (1) neonatal non-immune hydrops fetalis (NIHF) (n=10), (2) Infantile or adolescent form with history of hydrops fetalis (n=13) and (3) Infantile or adolescent form without known hydrops fetalis (n=33). Thirteen patients with MPS VII who had the infantile form with history of hydrops fetalis and survived childhood, had a wide range of clinical manifestations from mild to severe. Five patients underwent bone marrow transplantation and one patient underwent enzyme replacement therapy with recombinant human GUS. Conclusions MPS VII is a pan-ethnic inherited lysosomal storage disease with considerable phenotypical heterogeneity. Most patients have short stature, skeletal dysplasia, hepatosplenomegaly, hernias, cardiac involvement, pulmonary insufficiency and cognitive impairment. In these respects it resembles MPS I and MPS II. In MPS VII, however, one unique and distinguishing clinical feature is the unexpectedly high proportion of patients (41%) that had a history of NIHF. Presence of NIHF does not, by itself, predict the eventual severity of the clinical course, if the patient survives infancy. PMID:26908836

The Osborne 1.

ERIC Educational Resources Information Center

McWilliams, Peter

1982-01-01

Describes the unique features, available software, performance capabilities, system options, costs, advantages, disadvantages, and eccentricities of the Osborne 1 microcomputer. A table summarizes specifications, features, and costs. (JL)

Malignancy in Children with Trisomy 21

PubMed Central

Rabin, Karen R.; Whitlock, James A.

2009-01-01

Patients with Down syndrome (DS) display a unique spectrum of malignancies, with a 10 to 20-fold increased risk of acute leukemias, and a markedly decreased incidence of solid tumors. This review discusses current understanding of the basis for this distinctive pattern of cancer incidence, and the clinical and biologic features of the malignant disorders most frequent in DS: transient myeloproliferative disease, acute megakaryoblastic leukemia, and acute lymphoblastic leukemia. We also review distinctive pharmacogenetic issues, highlighting the differential chemosensitivity and toxicity profiles of DS patients compared to the general population; and epidemiologic studies of protective and adverse environmental risk factors for development of leukemia. PMID:19176633

Sporadic Jakob-Creutzfeldt Disease Presenting as Primary Progressive Aphasia

PubMed Central

Johnson, David Y.; Dunkelberger, Diana L.; Henry, Maya; Haman, Aissatou; Greicius, Michael D.; Wong, Katherine; DeArmond, Stephen J.; Miller, Bruce L.; Gorno-Tempini, Maria Luisa; Geschwind, Michael D.

2015-01-01

Objective To report the clinical, neuropsychological, linguistic, imaging, and neuropathological features of a unique case of sporadic Jakob-Creutzfeldt disease in which the patient presented with a logopenic variant of primary progressive aphasia. Design Case report. Setting Large referral center for atypical memory and aging disorders, particularly Jakob-Creutzfeldt disease. Patient Patient presenting with logopenic variant primary progressive aphasia initially thought to be due to Alzheimer disease. Results Despite the long, slow 3.5-year course, the patient was shown to have pathology-proven sporadic Jakob-Creutzfeldt disease. Conclusions These findings expand the differential of primary progressive aphasia to include prion disease. PMID:23400721

Insulin dependent diabetes mellitus (IDDM) and autoimmune thyroiditis in a boy with a ring chromosome 18: additional evidence of autoimmunity or IDDM gene(s) on chromosome 18.

PubMed

Dacou-Voutetakis, C; Sertedaki, A; Maniatis-Christidis, M; Sarri, C; Karadima, G; Petersen, M B; Xaidara, A; Kanariou, M; Nicolaidou, P

1999-02-01

A 4 year 3 month old boy with insulin dependent diabetes mellitus (IDDM), autoimmune thyroiditis, slight mental retardation, facial dysmorphism, and a de novo ring chromosome 18 (deletion 18q22.3-18qter) is described. This unique association of defects could represent a chance association. Alternatively, the clinical features could be the result of the chromosomal aberration. If so, one could speculate that a gene or genes on chromosome 18 might act as a suppressor or activator of the autoimmune process by itself or in concert with other IDDM loci.

Ureaplasma--Are you sitting comfortably?

PubMed

Gwee, Amanda; Curtis, Nigel

2014-01-01

The role of Ureaplasma spp. in human disease has been controversial, as these bacteria are commonly isolated as part of the normal genital tract flora. Ureaplasma has been shown to have a causal role in urogenital infections and is associated with significant foetal and neonatal morbidity and mortality when infection occurs during the perinatal period. Although rare, invasive Ureaplasma infection (meningitis, renal abscess, mediastinitis and arthritis) has also been reported in both adults and children. This review outlines the unique microbiological features and various clinical presentations of Ureaplasma infection. It also discusses the treatment options, which in the neonatal period can be particularly challenging. Copyright © 2013. Published by Elsevier Ltd.

Impact of Genetics on the Diagnosis and Treatment of Renal Cancer

PubMed Central

Singer, Eric A.; Bratslavsky, Gennady; Middelton, Lindsay; Srinivasan, Ramaprasad; Linehan, W. Marston

2011-01-01

Kidney cancer is a heterogeneous disease comprised of a number of histologic subtypes, each associated with unique genetic mutations, clinical features, and sensitivity to treatment. By examining families affected with the hereditary kidney cancer syndromes von Hippel-Lindau, hereditary papillary renal cell carcinoma, hereditary leiomyomatosis and renal cell carcinoma, and Birt-Hogg-Dube', researchers have been able to identify the genes responsible for these syndromes. This work has revealed that kidney cancer is fundamentally a metabolic disorder, and as such, novel targeted therapies specific to their molecular biology have been developed and employed in both the hereditary and sporadic forms of renal cell carcinoma. PMID:21128028

A clinical evaluation of renal amyloidosis in the Japan renal biopsy registry: a cross-sectional study.

PubMed

Nishi, Shinichi; Muso, Eri; Shimizu, Akira; Sugiyama, Hitoshi; Yokoyama, Hitoshi; Ando, Yukio; Goto, Shunsuke; Fujii, Hideki

2017-08-01

The available clinical data are limited in a rare glomerular disease, renal amyloidosis. We aimed to clarify the clinical features of renal amyloidosis from database of the Japan Renal Biopsy Registry (J-RBR). We performed a cross-sectional study with database of the J-RBR of the Japanese Society of Nephrology. We identified 281 cases of renal amyloidosis from 20,997 cases enrolled into the J-RBR from 2007 to 2014. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were compared among the levels of ages, amount of urine protein excretion (AUPE) or CKD G stages. The prevalence of renal amyloidosis was 1.3 % (281/20,997). DBP significantly decreased in higher age quartiles (P = 0.034). SBP and DBP did not increase in the progression of AUPE levels and CKD G stages. In multiple regression analysis, eGFR was a significant independent factor for SBP in all cases and a subgroup without hypertensive agents. There was a reverse significant relationship between SBP and eGFR. Blood pressure did not significantly increase in elderly and much proteinuric condition in renal amyloidosis. The progression of CKD and decrease of eGFR did not produce the higher SBP. The mechanism underlying these results remains unclear; however, they are unique features of renal amyloidosis. The couple of hypotensive and hypertensive conditions might produce no relationship between blood pressure and CKD stages.

Phosphodiesterase type 5 and cancers: progress and challenges

PubMed Central

Barone, Ines; Giordano, Cinzia; Bonofiglio, Daniela; Andò, Sebastiano; Catalano, Stefania

2017-01-01

Cancers are an extraordinarily heterogeneous collection of diseases with distinct genetic profiles and biological features that directly influence response patterns to various treatment strategies as well as clinical outcomes. Nevertheless, our growing understanding of cancer cell biology and tumor progression is gradually leading towards rational, tailored medical treatments designed to destroy cancer cells by exploiting the unique cellular pathways that distinguish them from normal healthy counterparts. Recently, inhibition of the activity of phosphodiesterase type 5 (PDE5) is emerging as a promising approach to restore normal intracellular cyclic guanosine monophosphate (cGMP) signalling, and thereby resulting into the activation of various downstream molecules to inhibit proliferation, motility and invasion of certain cancer cells. In this review, we present an overview of the experimental and clinical evidences highlighting the role of PDE5 in the pathogenesis and prevention of various malignancies. Current data are still not sufficient to draw conclusive statements for cancer patient management, but could provide further rational for testing PDE5-targeting drugs as anticancer agents in clinical settings. PMID:29228762

Characterization of Change and Significance for Clinical Findings in Radiology Reports Through Natural Language Processing.

PubMed

Hassanpour, Saeed; Bay, Graham; Langlotz, Curtis P

2017-06-01

We built a natural language processing (NLP) method to automatically extract clinical findings in radiology reports and characterize their level of change and significance according to a radiology-specific information model. We utilized a combination of machine learning and rule-based approaches for this purpose. Our method is unique in capturing different features and levels of abstractions at surface, entity, and discourse levels in text analysis. This combination has enabled us to recognize the underlying semantics of radiology report narratives for this task. We evaluated our method on radiology reports from four major healthcare organizations. Our evaluation showed the efficacy of our method in highlighting important changes (accuracy 99.2%, precision 96.3%, recall 93.5%, and F1 score 94.7%) and identifying significant observations (accuracy 75.8%, precision 75.2%, recall 75.7%, and F1 score 75.3%) to characterize radiology reports. This method can help clinicians quickly understand the key observations in radiology reports and facilitate clinical decision support, review prioritization, and disease surveillance.

Improving the Clinical Pharmacologic Assessment of Abuse Potential: Part 1: Regulatory Context and Risk Management.

PubMed

Sellers, Edward M

2018-02-01

This article brings to the attention of drug developers the Food and Drug Administration's (FDA's) recent final Guidance to Industry on Assessment of Abuse Potential and provides practical suggestions about compliance with the Guidance. The Guidance areas are reviewed, analyzed, and placed in the context of current scientific knowledge and best practices to mitigate regulatory risk. The Guidance provides substantial new detail on what needs to be done at all stages of drug development for central nervous system-active drugs. However, because many psychopharmacologic agents have unique preclinical and clinical features, the plan for each agent needs to be not only carefully prepared but also reviewed and approved by the FDA. Examples are provided where assumptions about interpretation of the Guidance can delay development. If the expertise and experience needed for assessing abuse potential during drug development do not exist within a company, external preclinical and clinical expert should be involved. Consultation with the FDA is encouraged and important because the specific requirements for each drug will vary.

Biology and management of transient abnormal myelopoiesis (TAM) in children with Down syndrome.

PubMed

Roy, Anindita; Roberts, Irene; Vyas, Paresh

2012-08-01

Children with Down syndrome (DS) have an increased risk of Acute Myeloid Leukaemia (ML-DS), particularly megakaryoblastic leukaemia, which is clonally -related to the neonatal myeloproliferative syndrome, Transient Abnormal Myelopoiesis (TAM) unique to infants with DS. Molecular, biological, and clinical data indicate that TAM is initiated before birth when fetal liver haematopoietic cells trisomic for chromosome 21 acquire mutations in GATA1. TAM usually resolves spontaneously by 6 months; however 20-30% subsequently develop ML-DS harbouring the same GATA1 mutation(s). This review focuses on recent studies describing haematological, clinical and biological features of TAM and discusses approaches to diagnose, treat and monitor minimal residual disease in TAM. An important unanswered question is whether ML-DS is always preceded by TAM as it may be clinically and possibly haematologically 'silent'. We have briefly discussed the role of population-based screening for TAM and development of treatment strategies to eliminate the preleukaemic TAM clone, thereby preventing ML-DS. Copyright © 2012 Elsevier Ltd. All rights reserved.

Feature Acquisition with Imbalanced Training Data

NASA Technical Reports Server (NTRS)

Thompson, David R.; Wagstaff, Kiri L.; Majid, Walid A.; Jones, Dayton L.

2011-01-01

This work considers cost-sensitive feature acquisition that attempts to classify a candidate datapoint from incomplete information. In this task, an agent acquires features of the datapoint using one or more costly diagnostic tests, and eventually ascribes a classification label. A cost function describes both the penalties for feature acquisition, as well as misclassification errors. A common solution is a Cost Sensitive Decision Tree (CSDT), a branching sequence of tests with features acquired at interior decision points and class assignment at the leaves. CSDT's can incorporate a wide range of diagnostic tests and can reflect arbitrary cost structures. They are particularly useful for online applications due to their low computational overhead. In this innovation, CSDT's are applied to cost-sensitive feature acquisition where the goal is to recognize very rare or unique phenomena in real time. Example applications from this domain include four areas. In stream processing, one seeks unique events in a real time data stream that is too large to store. In fault protection, a system must adapt quickly to react to anticipated errors by triggering repair activities or follow- up diagnostics. With real-time sensor networks, one seeks to classify unique, new events as they occur. With observational sciences, a new generation of instrumentation seeks unique events through online analysis of large observational datasets. This work presents a solution based on transfer learning principles that permits principled CSDT learning while exploiting any prior knowledge of the designer to correct both between-class and withinclass imbalance. Training examples are adaptively reweighted based on a decomposition of the data attributes. The result is a new, nonparametric representation that matches the anticipated attribute distribution for the target events.

A case of infantile osteopetrosis: The radioclinical features with literature update.

PubMed

El-Sobky, Tamer Ahmed; Elsobky, Ezzat; Sadek, Ismaiel; Elsayed, Solaf M; Khattab, Mohamed Fawzy

2016-06-01

Osteopetrosis is a rare hereditary metabolic bone disorder characterized by generalized skeletal sclerosis caused by a defect in bone resorption and remodelling. Infantile autosomal recessive osteopetrosis is one of three subtypes of osteopetrosis and the most severe form. The correct and early diagnosis of infantile osteopetrosis is important for management of complications and for future genetic counselling. Diagnosis is largely based on clinical and radiographic evaluation, confirmed by gene testing where applicable. Therefore, in this case study the classical clinical and radiological signs of a boy with infantile osteopetrosis will be presented with a comprehensive literature update. The differentiating signs from other causes of hereditary osteosclerosing dysplasias are discussed. This case study and review of available literature show that there tends to be a highly unique clinical and skeletal radiographic pattern of affection in infantile osteopetrosis. Although tremendous advances have been made in the elucidation of the genetic defect of osteopetrosis over the past years, the role of accurate clinical and radiological assessment remains an important contributor to the diagnosis of infantile osteopetrosis.

Depression, anxiety and somatization in primary care: syndrome overlap and functional impairment.

PubMed

Löwe, Bernd; Spitzer, Robert L; Williams, Janet B W; Mussell, Monika; Schellberg, Dieter; Kroenke, Kurt

2008-01-01

To determine diagnostic overlap of depression, anxiety and somatization as well as their unique and overlapping contribution to functional impairment. Two thousand ninety-one consecutive primary care clinic patients participated in a multicenter cross-sectional survey in 15 primary care clinics in the United States (participation rate, 92%). Depression, anxiety, somatization and functional impairment were assessed using validated scales from the Patient Health Questionnaire (PHQ) (PHQ-8, eight-item depression module; GAD-7, seven-item Generalized Anxiety Disorder Scale; and PHQ-15, 15-item somatic symptom scale) and the Short-Form General Health Survey (SF-20). Multiple linear regression analyses were used to investigate unique and overlapping associations of depression, anxiety and somatization with functional impairment. In over 50% of cases, comorbidities existed between depression, anxiety and somatization. The contribution of the commonalities of depression, anxiety and somatization to functional impairment substantially exceeded the contribution of their independent parts. Nevertheless, depression, anxiety and somatization did have important and individual effects (i.e., separate from their overlap effect) on certain areas of functional impairment. Given the large syndrome overlap, a potential consideration for future diagnostic classification would be to describe basic diagnostic criteria for a single overarching disorder and to optionally code additional diagnostic features that allow a more detailed classification into specific depressive, anxiety and somatoform subtypes.

Genetic Characterization of Feline Leukemia Virus from Florida Panthers

PubMed Central

Brown, Meredith A.; Cunningham, Mark W.; Roca, Alfred L.; Troyer, Jennifer L.; Johnson, Warren E.

2008-01-01

From 2002 through 2005, an outbreak of feline leukemia virus (FeLV) occurred in Florida panthers (Puma concolor coryi). Clinical signs included lymphadenopathy, anemia, septicemia, and weight loss; 5 panthers died. Not associated with FeLV outcome were the genetic heritage of the panthers (pure Florida vs. Texas/Florida crosses) and co-infection with feline immunodeficiency virus. Genetic analysis of panther FeLV, designated FeLV-Pco, determined that the outbreak likely came from 1 cross-species transmission from a domestic cat. The FeLV-Pco virus was closely related to the domestic cat exogenous FeLV-A subgroup in lacking recombinant segments derived from endogenous FeLV. FeLV-Pco sequences were most similar to the well-characterized FeLV-945 strain, which is highly virulent and strongly pathogenic in domestic cats because of unique long terminal repeat and envelope sequences. These unique features may also account for the severity of the outbreak after cross-species transmission to the panther. PMID:18258118

Genetic characterization of feline leukemia virus from Florida panthers.

PubMed

Brown, Meredith A; Cunningham, Mark W; Roca, Alfred L; Troyer, Jennifer L; Johnson, Warren E; O'Brien, Stephen J

2008-02-01

From 2002 through 2005, an outbreak of feline leukemia virus (FeLV) occurred in Florida panthers (Puma concolor coryi). Clinical signs included lymphadenopathy, anemia, septicemia, and weight loss; 5 panthers died. Not associated with FeLV outcome were the genetic heritage of the panthers (pure Florida vs. Texas/Florida crosses) and co-infection with feline immunodeficiency virus. Genetic analysis of panther FeLV, designated FeLV-Pco, determined that the outbreak likely came from 1 cross-species transmission from a domestic cat. The FeLV-Pco virus was closely related to the domestic cat exogenous FeLV-A subgroup in lacking recombinant segments derived from endogenous FeLV. FeLV-Pco sequences were most similar to the well-characterized FeLV-945 strain, which is highly virulent and strongly pathogenic in domestic cats because of unique long terminal repeat and envelope sequences. These unique features may also account for the severity of the outbreak after cross-species transmission to the panther.

HIV is Now a Manageable Long-Term Condition, But What Makes it Unique? A Qualitative Study Exploring Views About Distinguishing Features from Multi-Professional HIV Specialists in North West England.

PubMed

Jelliman, Pauline; Porcellato, Lorna

HIV is evolving from a life-threatening infection to a long-term, manageable condition because of medical advances, radical changes in health and social care policy, and the impact of an aging population. However, HIV remains complex, presenting unique characteristics distinguishing it from other long-term conditions (LTCs). Our aim in this qualitative descriptive study was to identify and explore these features in the context of LTCs. A focus group (FG) method was used to gather the views and experiences of multi-professional HIV specialists who worked in North West England. Twenty-four staff participated in FGs (n = 3), which were audio recorded, manually transcribed, and thematically analyzed. We found four main themes: (a) stigma, (b) challenges faced by HIV specialists, (c) lack HIV-related knowledge, and (d) unique features, termed "stand alone." We concluded that these distinguishing features hindered full recognition and acceptance of HIV as an LTC. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Gastric Cancer in Asia: Unique Features and Management.

PubMed

Irino, Tomoyuki; Takeuchi, Hiroya; Terashima, Masanori; Wakai, Toshifumi; Kitagawa, Yuko

2017-01-01

Gastric cancer (GC) poses a burden to patients across the globe as the third leading cause of cancer deaths worldwide. Incidence of GC is particularly high in Asian countries, which is attributed to the prevalence of Helicobacter pylori (H. pylori) infection and has prompted the establishment of unique treatment strategies. D2 gastrectomy, which was established in the 1950s in Japan, has served as a gold standard for locally advanced GC for over half a century. Since the beginning of the 21st century, endoscopic resection (ER) techniques and minimally invasive laparoscopic surgery have greatly changed the treatment of patients with early GC. S-1, which showed a striking survival benefit in a large randomized trial in Japan, has been used as adjuvant therapy for the last decade. Likewise, S-1-based chemotherapy regimens are currently the standard of care for the treatment of unresectable/metastatic GC in Asia. Along with the development of standardized therapy, novel techniques and new drugs have been rapidly brought into clinical practice. State-of-the-art sentinel node (SN) navigation surgery enables clinicians to perform truly minimally invasive surgery for early GC, and appropriate chemotherapy regimens are now determined by a tumor's molecular expression. New classifications based on gene signatures are proposed and may replace conventional clinical classifications. Such highly individualized treatment has the potential to alter our clinical practice in GC in the near future. The best practice in each geographic region should be shared and integrated, resulting in the best practice without borders.

[Multidrug-Resistant Tuberculosis by Strains of Beijing Family, in Patients from Lisbon, Portugal: Preliminary Report].

PubMed

Maltez, Fernando; Martins, Teresa; Póvoas, Diana; Cabo, João; Peres, Helena; Antunes, Francisco; Perdigão, João; Portugal, Isabel

2017-03-31

Beijing family strains of Mycobacterium tuberculosis are associated with multidrug-resistance. Although strains of the Lisboa family are the most common among multidrug-resistant and extensively drug-resistant patients in the region, several studies have reported the presence of the Beijing family. However, the features of patients from whom they were isolated, are not yet known. Retrospective study involving 104 multidrug-resistant and extensively drug-resistant strains of Mycobacterium tuberculosis, from the same number of patients, isolated and genotyped between 1993 and 2015 in Lisbon. We assessed the prevalence of strains of both families and the epidemiologic and clinical features of those infected with Beijing family strains. Seventy-four strains (71.2%) belonged to the Lisboa family, 25 (24.0%) showed a unique genotypic pattern and five (4.8%) belonged to the Beijing family, the latter identified after 2009. Those infected with Beijing family strains were angolan (n = 1), ukrainian (n = 2) and portuguese (n = 2), mainly young-aged and, four of five immunocompetent and with no past history of tuberculosis. All had multidrug-resistant tuberculosis. We did not find any distinctive clinical or radiological features, neither a predominant resistance pattern. Cure rate was high (four patients). Although the number of infected patients with Beijing strains was small, it suggests an important proportion of primary tuberculosis, a potential for transmission in the community but also a better clinical outcome when compared to other reported strains, such as W-Beijing and Lisboa. Although Lisboa family strains account for most of the multidrug and extensively drug-resistant tuberculosis cases in Lisbon area, Beijing strains are transmitted in the city and might change the local characteristics of the epidemics.

The Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels: from Biophysics to Pharmacology of a Unique Family of Ion Channels.

PubMed

Sartiani, Laura; Mannaioni, Guido; Masi, Alessio; Novella Romanelli, Maria; Cerbai, Elisabetta

2017-10-01

Hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels are important members of the voltage-gated pore loop channels family. They show unique features: they open at hyperpolarizing potential, carry a mixed Na/K current, and are regulated by cyclic nucleotides. Four different isoforms have been cloned (HCN1-4) that can assemble to form homo- or heterotetramers, characterized by different biophysical properties. These proteins are widely distributed throughout the body and involved in different physiologic processes, the most important being the generation of spontaneous electrical activity in the heart and the regulation of synaptic transmission in the brain. Their role in heart rate, neuronal pacemaking, dendritic integration, learning and memory, and visual and pain perceptions has been extensively studied; these channels have been found also in some peripheral tissues, where their functions still need to be fully elucidated. Genetic defects and altered expression of HCN channels are linked to several pathologies, which makes these proteins attractive targets for translational research; at the moment only one drug (ivabradine), which specifically blocks the hyperpolarization-activated current, is clinically available. This review discusses current knowledge about HCN channels, starting from their biophysical properties, origin, and developmental features, to (patho)physiologic role in different tissues and pharmacological modulation, ending with their present and future relevance as drug targets. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Mucopolysaccharidosis IVA and glycosaminoglycans.

PubMed

Khan, Shaukat; Alméciga-Díaz, Carlos J; Sawamoto, Kazuki; Mackenzie, William G; Theroux, Mary C; Pizarro, Christian; Mason, Robert W; Orii, Tadao; Tomatsu, Shunji

Mucopolysaccharidosis IVA (MPS IVA; Morquio A: OMIM 253000) is a lysosomal storage disease with an autosomal recessive trait caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to accumulation of specific glycosaminoglycans (GAGs): chondroitin-6-sulfate (C6S) and keratan sulfate (KS). C6S and KS are mainly produced in the cartilage. Therefore, the undegraded substrates are stored primarily in cartilage and in its extracellular matrix (ECM), leading to a direct impact on cartilage and bone development, and successive systemic skeletal dysplasia. Chondrogenesis, the earliest phase of skeletal formation, is maintained by cellular interactions with the ECM, growth and differentiation factors, signaling pathways, and transcription factors in a temporal-spatial manner. In patients with MPS IVA, the cartilage is disrupted at birth as a consequence of abnormal chondrogenesis and/or endochondral ossification. The unique skeletal features are distinguished by a disproportional short stature, odontoid hypoplasia, spinal cord compression, tracheal obstruction, pectus carinatum, kyphoscoliosis, platyspondyly, coxa valga, genu valgum, waddling gait, and laxity of joints. In spite of many descriptions of these unique clinical features, delay of diagnosis still happens. The pathogenesis and treatment of systemic skeletal dysplasia in MPS IVA remains an unmet challenge. In this review article, we comprehensively describe historical aspect, property of GAGs, diagnosis, screening, pathogenesis, and current and future therapies of MPS IVA. Copyright © 2016 Elsevier Inc. All rights reserved.

Ambient response of a unique performance-based design building with dynamic response modification features

USGS Publications Warehouse

Çelebi, Mehmet; Huang, Moh; Shakal, Antony; Hooper, John; Klemencic, Ron

2012-01-01

A 64-story, performance-based design building with reinforced concrete core shear-walls and unique dynamic response modification features (tuned liquid sloshing dampers and buckling-restrained braces) has been instrumented with a monitoring array of 72 channels of accelerometers. Ambient vibration data recorded are analyzed to identify modes and associated frequencies and damping. The low-amplitude dynamic characteristics are considerably different than those computed from design analyses, but serve as a baseline against which to compare with future strong shaking responses. Such studies help to improve our understanding of the effectiveness of the added features to the building and help improve designs in the future.

Support and Development of Workflow Protocols for High Throughput Single-Lap-Joint Testing-Experimental

DTIC Science & Technology

2013-04-01

preparation, and presence of an overflow fillet for a high strength epoxy and ductile methacylate adhesive. A unique feature of this study was the...of expanding adhesive joint test configurations as part of the GEMS program. 15. SUBJECT TERMS single lap joint, adhesion, aluminum, epoxy ... epoxy and ductile methacylate adhesive. A unique feature of this study was the use of untrained GEMS (Gains in the Education of Mathematics and Sci

A computer vision framework for finger-tapping evaluation in Parkinson's disease.

PubMed

Khan, Taha; Nyholm, Dag; Westin, Jerker; Dougherty, Mark

2014-01-01

The rapid finger-tapping test (RFT) is an important method for clinical evaluation of movement disorders, including Parkinson's disease (PD). In clinical practice, the naked-eye evaluation of RFT results in a coarse judgment of symptom scores. We introduce a novel computer-vision (CV) method for quantification of tapping symptoms through motion analysis of index-fingers. The method is unique as it utilizes facial features to calibrate tapping amplitude for normalization of distance variation between the camera and subject. The study involved 387 video footages of RFT recorded from 13 patients diagnosed with advanced PD. Tapping performance in these videos was rated by two clinicians between the symptom severity levels ('0: normal' to '3: severe') using the unified Parkinson's disease rating scale motor examination of finger-tapping (UPDRS-FT). Another set of recordings in this study consisted of 84 videos of RFT recorded from 6 healthy controls. These videos were processed by a CV algorithm that tracks the index-finger motion between the video-frames to produce a tapping time-series. Different features were computed from this time series to estimate speed, amplitude, rhythm and fatigue in tapping. The features were trained in a support vector machine (1) to categorize the patient group between UPDRS-FT symptom severity levels, and (2) to discriminate between PD patients and healthy controls. A new representative feature of tapping rhythm, 'cross-correlation between the normalized peaks' showed strong Guttman correlation (μ2=-0.80) with the clinical ratings. The classification of tapping features using the support vector machine classifier and 10-fold cross validation categorized the patient samples between UPDRS-FT levels with an accuracy of 88%. The same classification scheme discriminated between RFT samples of healthy controls and PD patients with an accuracy of 95%. The work supports the feasibility of the approach, which is presumed suitable for PD monitoring in the home environment. The system offers advantages over other technologies (e.g. magnetic sensors, accelerometers, etc.) previously developed for objective assessment of tapping symptoms. Copyright © 2013 Elsevier B.V. All rights reserved.

A unique phenotype in a patient with a rare triplication of the 22q11.2 region and new clinical insights of the 22q11.2 microduplication syndrome: a report of two cases.

PubMed

Vaz, Sara O; Pires, Renato; Pires, Luís M; Carreira, Isabel M; Anjos, Rui; Maciel, Paula; Mota-Vieira, Luisa

2015-08-22

The rearrangements of the 22q11.2 chromosomal region, most frequently deletions and duplications, have been known to be responsible for multiple congenital anomaly disorders. These rearrangements are implicated in syndromes that have some phenotypic resemblances. While the 22q11.2 deletion, also known as DiGeorge/Velocardiofacial syndrome, has common features that include cardiac abnormalities, thymic hypoplasia, characteristic face, hypocalcemia, cognitive delay, palatal defects, velopharyngeal insufficiency, and other malformations, the microduplication syndrome is largely undetected. This is mainly because phenotypic appearance is variable, milder, less characteristic and unpredictable. In this paper, we report the clinical evaluation and follow-up of two patients affected by 22q11.2 rearrangements, emphasizing new phenotypic features associated with duplication and triplication of this genomic region. Patient 1 is a 24 year-old female with 22q11.2 duplication who has a heart defect (ostium secundum atrial septal defect) and supernumerary teeth (hyperdontia), a feature previously not reported in patients with 22q11.2 microduplication syndrome. Her monozygotic twin sister, who died at the age of one month, had a different heart defect (truncus arteriousus). Patient 2 is a 20 year-old female with a 22q11.2 triplication who had a father with 22q11.2 duplication. In comparison to the first case reported in the literature, she has an aggravated phenotype characterized by heart defects (restrictive VSD and membranous subaortic stenosis), and presented other facial dysmorphisms and urogenital malformations (ovarian cyst). Additionally, she has a hemangioma planum on the right side of her face, a feature of Sturge-Weber syndrome. In this report, we described hyperdontia as a new feature of 22q11.2 microdeletion syndrome. Moreover, this syndrome was diagnosed in a patient who had a deceased monozygotic twin affected with a different heart defect, which corresponds to a phenotypic discordance never reported in the literature. Case 2 is the second clinical report of 22q11.2 triplication and presents an aggravated phenotype in contrast to the patient previously reported.

Management of schizophrenia: clinical experience with asenapine.

PubMed

Cortese, Leonardo; Bressan, Rodrigo A; Castle, David J; Mosolov, Sergey N

2013-04-01

Schizophrenia is a chronic brain disorder comprising a range of clinical features, including positive and negative symptoms, cognitive dysfunction and mood symptoms (particularly depression and anxiety). The management of schizophrenia requires effective short- and long-term treatment with antipsychotic medication that is effective across these symptom domains, while being well tolerated over the long term. Asenapine is the first tetracyclic atypical antipsychotic to be licensed in the USA and several other countries outside Europe for the acute and maintenance treatment of schizophrenia in adults. It has a unique receptor-binding profile and a broad range of therapeutic effects. Since clinical trials are conducted under strict conditions in tightly defined patient populations, evidence of an agent's efficacy and tolerability under 'real-world' clinical practice conditions is also required. As in clinical trials, real-life case reports demonstrate that asenapine is effective in treating the positive symptoms of schizophrenia, both in the acute setting and for relapse prevention. It is also effective in treating negative symptoms and shows promise in the treatment of depressive symptoms associated with schizophrenia. Asenapine has a favourable tolerability profile, having a minimal impact on weight and metabolic parameters. As such, asenapine is valuable option for the treatment of schizophrenia in adults.

Multi-Modal Ultra-Widefield Imaging Features in Waardenburg Syndrome

PubMed Central

Choudhry, Netan; Rao, Rajesh C.

2015-01-01

Background Waardenburg syndrome is characterized by a group of features including; telecanthus, a broad nasal root, synophrys of the eyebrows, piedbaldism, heterochromia irides, and deaf-mutism. Hypopigmentation of the choroid is a unique feature of this condition examined with multi-modal Ultra-Widefield Imaging in this report. Material/Methods Report of a single case. Results Bilateral symmetric choroidal hypopigmentation was observed with hypoautofluorescence in the region of hypopigmentation. Fluorescein angiography revealed a normal vasculature, however a thickened choroid was seen on Enhanced-Depth Imaging Spectral-Domain OCT (EDI SD-OCT). Conclusion(s) Choroidal hypopigmentation is a unique feature of Waardenburg syndrome, which can be visualized with ultra-widefield fundus autofluorescence. The choroid may also be thickened in this condition and its thickness measured with EDI SD-OCT. PMID:26114849

Bronchioloalveolar carcinoma.

PubMed

Arenberg, Douglas

2011-02-01

This review focuses on aspects of bronchioloalveolar carcinoma (BAC) in which it differs importantly from other forms of non-small-cell lung cancer. BAC is a form of adenocarcinoma with unique clinical, radiological, and epidemiological features. With the notable exception of a lower likelihood of a positive positron-emission tomographic (PET) scan in BAC, staging, diagnosis, and treatment are largely the same as for other histological subtypes of lung cancer. However, additional treatment options exist that are equivalent, if not more effective, for many patients with BAC. The diagnosis of BAC should be reserved for those tumors meeting the 1999/2004 criteria set forth by the World Health Organization. Revised nomenclature proposed by an expert consensus panel may change how this disease is viewed. Additional clinical trials are needed on patients with BAC, employing strict definitions and enrollment criteria to allow the results to be applied to appropriate patient populations. © Thieme Medical Publishers.

Parkinsonism in Spinocerebellar Ataxia

PubMed Central

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

2015-01-01

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

Serrated pathway: Alternative route to colorectal cancer

PubMed Central

Patai, Árpád V; Molnár, Béla; Tulassay, Zsolt; Sipos, Ferenc

2013-01-01

Serrated polyps have been an area of intense focus for gastroenterologists over the past several years. Contrary to what was thought before, a growing body of literature indicates that these polyps can be precursors of colorectal cancer (CRC). Most of these lesions, particularly those in the proximal colon, have so far been under-recognized and missed during colonoscopy, qualifying these lesions to be the main cause of interval cancers. It is estimated that 10%-20% of CRCs evolve through this alternative, serrated pathway, with a distinct genetic and epigenetic profile. Aberrant DNA methylation plays a central role in the development of this CRC subtype. This characteristic molecular background is reflected in a unique pathological and clinical manifestation different from cancers arising via the traditional pathway. In this review we would like to highlight morphological, molecular and clinical features of this emerging pathway that are essential for gastroenterologists and may influence their everyday practice. PMID:23431044

An exploratory survey on the views of European tissue engineers concerning the ethical issues of tissue engineering research.

PubMed

Trommelmans, Leen; Selling, Joseph; Dierickx, Kris

2009-09-01

We present the first exploratory survey about the views of tissue engineers on the ethical issues of tissue engineering (TE), conducted among participants of a large European TE consortium. We analyzed the topics for which ethical guidance is necessary and the preferred dissemination channels, which are relevant issues and goals of clinical trials with human tissue-engineered products, and which information is to be given to trial participants. The need for comprehensive, specific ethical guidance of TE is a first key finding of this survey. Second, it becomes clear that little clarity exists on some crucial issues in the setup and conduct of clinical trials in TE. Identifying the unique features of TE and their repercussions for the ethical conduct of TE research and therapy is necessary. Third, prospective trial participants are to be informed about a wide variety of issues before taking part in the trial.

PalmCIS: A Wireless Handheld Application for Satisfying Clinician Information Needs

PubMed Central

Chen, Elizabeth S.; Mendonça, Eneida A.; McKnight, Lawrence K.; Stetson, Peter D.; Lei, Jianbo; Cimino, James J.

2004-01-01

Wireless handheld technology provides new ways to deliver and present information. As with any technology, its unique features must be taken into consideration and its applications designed accordingly. In the clinical setting, availability of needed information can be crucial during the decision-making process. Preliminary studies performed at New York Presbyterian Hospital (NYPH) determined that there are inadequate access to information and ineffective communication among clinicians (potential proximal causes of medical errors). In response to these findings, the authors have been developing extensions to their Web-based clinical information system including PalmCIS, an application that provides access to needed patient information via a wireless personal digital assistant (PDA). The focus was on achieving end-to-end security and developing a highly usable system. This report discusses the motivation behind PalmCIS, design and development of the system, and future directions. PMID:14527976

Cutaneous Collagenous Vasculopathy

PubMed Central

Ortleb, Melanie; Boyd, Alan S.; Powers, Jennifer

2015-01-01

Cutaneous collagenous vasculopathy is a rare microangiopathy of dermal blood vessels. Clinically indistinguishable from generalized essential telangiectasia, this condition is diagnosed by its unique histological appearance. In contrast to other primary telangiectatic processes, cutaneous collagenous vasculopathy has dilated vascular structures that contain deposits of eosinophilic hyaline material within the vessel walls. To date, cutaneous collagenous vasculopathy has been described in a total of 19 cases in the medical literature. The first several cases were described exclusively in middle-aged to elderly men. Though it has now been described in both men and women, cutaneous collagenous vasculopathy is still most often described in middle-aged to older adults. No particular disease or medication has been linked to the development of cutaneous collagenous vasculopathy, and the etiology remains unknown. In this case series, the authors present three additional patients diagnosed with cutaneous collagenous vasculopathy and discuss their clinical and histopathologic features. PMID:26705441

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

Treatment of ALK-rearranged non-small cell lung cancer: A review of the landscape and approach to emerging patterns of treatment resistance in the Australian context.

PubMed

Itchins, M; Chia, P L; Hayes, S A; Howell, V M; Gill, A J; Cooper, W A; John, T; Mitchell, P; Millward, M; Clarke, S J; Solomon, B; Pavlakis, N

2017-08-01

Since the identification of anaplastic lymphoma kinase (ALK) gene rearrangements in non-small cell lung cancer (NSCLC) in 2005, the treatment of ALK-rearranged NSCLC (ALK+ NSCLC) has evolved at a rapid pace. This molecularly distinct subset of NSCLC has uniquely important biology, clinicopathologic features and mechanisms of drug resistance which impact on the choice of treatment for a patient with this disease. There are multiple ALK tyrosine kinase inhibitors now available in clinical practice with efficacy data continuing to emerge and guide the optimal treatment algorithm. A detailed search of medical databases and clinical trial registries was conducted to capture all relevant articles on this topic enabling an updated detailed overview of the landscape of management of ALK-rearranged NSCLC. © 2017 John Wiley & Sons Australia, Ltd.

Outcome prediction in patients with glioblastoma by using imaging, clinical, and genomic biomarkers: focus on the nonenhancing component of the tumor.

PubMed

Jain, Rajan; Poisson, Laila M; Gutman, David; Scarpace, Lisa; Hwang, Scott N; Holder, Chad A; Wintermark, Max; Rao, Arvind; Colen, Rivka R; Kirby, Justin; Freymann, John; Jaffe, C Carl; Mikkelsen, Tom; Flanders, Adam

2014-08-01

To correlate patient survival with morphologic imaging features and hemodynamic parameters obtained from the nonenhancing region (NER) of glioblastoma (GBM), along with clinical and genomic markers. An institutional review board waiver was obtained for this HIPAA-compliant retrospective study. Forty-five patients with GBM underwent baseline imaging with contrast material-enhanced magnetic resonance (MR) imaging and dynamic susceptibility contrast-enhanced T2*-weighted perfusion MR imaging. Molecular and clinical predictors of survival were obtained. Single and multivariable models of overall survival (OS) and progression-free survival (PFS) were explored with Kaplan-Meier estimates, Cox regression, and random survival forests. Worsening OS (log-rank test, P = .0103) and PFS (log-rank test, P = .0223) were associated with increasing relative cerebral blood volume of NER (rCBVNER), which was higher with deep white matter involvement (t test, P = .0482) and poor NER margin definition (t test, P = .0147). NER crossing the midline was the only morphologic feature of NER associated with poor survival (log-rank test, P = .0125). Preoperative Karnofsky performance score (KPS) and resection extent (n = 30) were clinically significant OS predictors (log-rank test, P = .0176 and P = .0038, respectively). No genomic alterations were associated with survival, except patients with high rCBVNER and wild-type epidermal growth factor receptor (EGFR) mutation had significantly poor survival (log-rank test, P = .0306; area under the receiver operating characteristic curve = 0.62). Combining resection extent with rCBVNER marginally improved prognostic ability (permutation, P = .084). Random forest models of presurgical predictors indicated rCBVNER as the top predictor; also important were KPS, age at diagnosis, and NER crossing the midline. A multivariable model containing rCBVNER, age at diagnosis, and KPS can be used to group patients with more than 1 year of difference in observed median survival (0.49-1.79 years). Patients with high rCBVNER and NER crossing the midline and those with high rCBVNER and wild-type EGFR mutation showed poor survival. In multivariable survival models, however, rCBVNER provided unique prognostic information that went above and beyond the assessment of all NER imaging features, as well as clinical and genomic features.

Outcome Prediction in Patients with Glioblastoma by Using Imaging, Clinical, and Genomic Biomarkers: Focus on the Nonenhancing Component of the Tumor

PubMed Central

Poisson, Laila M.; Gutman, David; Scarpace, Lisa; Hwang, Scott N.; Holder, Chad A.; Wintermark, Max; Rao, Arvind; Colen, Rivka R.; Kirby, Justin; Freymann, John; Jaffe, C. Carl; Mikkelsen, Tom; Flanders, Adam

2014-01-01

Purpose To correlate patient survival with morphologic imaging features and hemodynamic parameters obtained from the nonenhancing region (NER) of glioblastoma (GBM), along with clinical and genomic markers. Materials and Methods An institutional review board waiver was obtained for this HIPAA-compliant retrospective study. Forty-five patients with GBM underwent baseline imaging with contrast material–enhanced magnetic resonance (MR) imaging and dynamic susceptibility contrast-enhanced T2*-weighted perfusion MR imaging. Molecular and clinical predictors of survival were obtained. Single and multivariable models of overall survival (OS) and progression-free survival (PFS) were explored with Kaplan-Meier estimates, Cox regression, and random survival forests. Results Worsening OS (log-rank test, P = .0103) and PFS (log-rank test, P = .0223) were associated with increasing relative cerebral blood volume of NER (rCBVNER), which was higher with deep white matter involvement (t test, P = .0482) and poor NER margin definition (t test, P = .0147). NER crossing the midline was the only morphologic feature of NER associated with poor survival (log-rank test, P = .0125). Preoperative Karnofsky performance score (KPS) and resection extent (n = 30) were clinically significant OS predictors (log-rank test, P = .0176 and P = .0038, respectively). No genomic alterations were associated with survival, except patients with high rCBVNER and wild-type epidermal growth factor receptor (EGFR) mutation had significantly poor survival (log-rank test, P = .0306; area under the receiver operating characteristic curve = 0.62). Combining resection extent with rCBVNER marginally improved prognostic ability (permutation, P = .084). Random forest models of presurgical predictors indicated rCBVNER as the top predictor; also important were KPS, age at diagnosis, and NER crossing the midline. A multivariable model containing rCBVNER, age at diagnosis, and KPS can be used to group patients with more than 1 year of difference in observed median survival (0.49–1.79 years). Conclusion Patients with high rCBVNER and NER crossing the midline and those with high rCBVNER and wild-type EGFR mutation showed poor survival. In multivariable survival models, however, rCBVNER provided unique prognostic information that went above and beyond the assessment of all NER imaging features, as well as clinical and genomic features. © RSNA, 2014 Online supplemental material is available for this article. PMID:24646147

AP1000{sup R} severe accident features and post-Fukushima considerations

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

Scobel, J. H.; Schulz, T. L.; Williams, M. G.

2012-07-01

The AP1000{sup R} passive nuclear power plant is uniquely equipped to withstand an extended station blackout scenario such as the events following the earthquake and tsunami at Fukushima without compromising core and containment integrity. The AP1000 plant shuts down the reactor, cools the core, containment and spent fuel pool for more than 3 days using passive systems that do not require AC or DC power or operator actions. Following this passive coping period, minimal operator actions are needed to extend the operation of the passive features to 7 days using installed equipment. To provide defense-in-depth for design extension conditions, themore » AP1000 plant has engineered features that mitigate the effects of core damage. Engineered features retain damaged core debris within the reactor vessel as a key feature. Other aspects of the design protect containment integrity during severe accidents, including unique features of the AP1000 design relative to passive containment cooling with water and air, and hydrogen management. (authors)« less

On subclasses of opioid analgesics.

PubMed

Raffa, Robert B

2014-12-01

The history of discovery of analgesic drugs has followed a trajectory from original serendipitous discovery of plant-derived substances to laboratory creation of customized molecules that are intentionally designed to interact with specific receptors of neurotransmitters involved in either the transmission of the pain signal or the attenuation of such a signal. The drugs most recently developed have been designed to provide incremental greater separation between pain relief and adverse effects. The result has been drugs that have individualized pharmacodynamic and pharmacokinetic characteristics that represent specific advances in basic science and translate into unique clinical profiles. Several of the drugs include non-opioid components. They retain some of the features of opioids, but have distinct clinical characteristics that differentiate them from traditional opioids. Thus they defy simple classification as opioids. A summary is provided of the development of the modern view of multi-mechanistic pain and its treatment using analgesics that have multi-mechanisms of action (consisting of both opioid and non-opioid components). Descriptions of examples of such current analgesics and of those that have pharmacokinetic characteristics that result in atypical opioid clinical profiles are given. By serendipity or design, several current strong analgesics have opioid components of action, but have an additional non-opioid mechanism of action or some pharmacokinetic feature that gives them an atypical opioid clinical profile and renders them not easily classified as classical opioids. An appreciation that there are now opioid analgesics that differentiate from classical opioids in ways that defy their simplistic classification as opioids suggests that recognition of subclasses of opioid analgesics would be more accurate scientifically and would be more informative for healthcare providers and regulators. This would likely lead to positive outcomes for the clinical use and regulatory control of the current drugs, and provide direction/strategy for the discovery of new drugs.

Clinical characteristics of patients with chronic obstructive pulmonary disease overlapped with bronchial asthma.

PubMed

Liang, Jing-Bo; Liu, Li-Jin; Fang, Qiu-Hong

2017-05-01

The clinical characteristics of patients with chronic obstructive pulmonary disease overlapped with bronchial asthma (COPD-BA) have not been discussed thoroughly. To reveal the clinical features of patients with COPD-BA, to evaluate the risk factors of COPD-BA, and to provide suggestions for COPD individualized therapy. A retrospective observational study was performed. A total of 182 patients with COPD (90 with COPD-BA and 92 with pure COPD) were recruited in the study. Information on the following items was collected: demographics, clinical manifestations, complications, laboratory findings, other histories, and inpatient treatments during exacerbation. A total of 182 patients were diagnosed with COPD, with 90 (49.45%) being classified as having COPD-BA. Patients with COPD-BA were more likely to be female (P = .004) and experienced more severe respiratory exacerbations (P = .04) despite being younger (P = .008). Those patients at onset of recurrent cough and sputum production were younger (P = .001). Significantly, a positive asthmatic family history (P = .03) was observed. Patients with COPD-BA usually had higher level of total serum IgE (although no differences were observed), had higher positive rates of the serum specific IgE (P = .004), and were more like to have an allergic history (P = .003). Allergic factor was the risk factor of COPD-BA (odds ratio, 4.477). During hospitalization, patients with COPD-BA tended to be treated with systemic corticosteroids (P = .008). Patients with COPD-BA were characterized by persistent airflow limitation with unique clinical features. Allergic factor was associated with the presence of asthmatic characteristics in patients with COPD. When hospitalized for exacerbation, the individualized therapy for COPD-BA might include the use of corticosteroids systemically. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

A detailed clinical analysis of 13 patients with AUTS2 syndrome further delineates the phenotypic spectrum and underscores the behavioural phenotype.

PubMed

Beunders, Gea; van de Kamp, Jiddeke; Vasudevan, Pradeep; Morton, Jenny; Smets, Katrien; Kleefstra, Tjitske; de Munnik, Sonja A; Schuurs-Hoeijmakers, Janneke; Ceulemans, Berten; Zollino, Marcella; Hoffjan, Sabine; Wieczorek, Stefan; So, Joyce; Mercer, Leanne; Walker, Tanya; Velsher, Lea; Parker, Michael J; Magee, Alex C; Elffers, Bart; Kooy, R Frank; Yntema, Helger G; Meijers-Heijboer, Elizabeth J; Sistermans, Erik A

2016-08-01

AUTS2 syndrome is an 'intellectual disability (ID) syndrome' caused by genomic rearrangements, deletions, intragenic duplications or mutations disrupting AUTS2. So far, 50 patients with AUTS2 syndrome have been described, but clinical data are limited and almost all cases involved young children. We present a detailed clinical description of 13 patients (including six adults) with AUTS2 syndrome who have a pathogenic mutation or deletion in AUTS2. All patients were systematically evaluated by the same clinical geneticist. All patients have borderline to severe ID/developmental delay, 83-100% have microcephaly and feeding difficulties. Congenital malformations are rare, but mild heart defects, contractures and genital malformations do occur. There are no major health issues in the adults; the oldest of whom is now 59 years of age. Behaviour is marked by it is a friendly outgoing social interaction. Specific features of autism (like obsessive behaviour) are seen frequently (83%), but classical autism was not diagnosed in any. A mild clinical phenotype is associated with a small in-frame 5' deletions, which are often inherited. Deletions and other mutations causing haploinsufficiency of the full-length AUTS2 transcript give a more severe phenotype and occur de novo. The 13 patients with AUTS2 syndrome with unique pathogenic deletions scattered around the AUTS2 locus confirm a phenotype-genotype correlation. Despite individual variations, AUTS2 syndrome emerges as a specific ID syndrome with microcephaly, feeding difficulties, dysmorphic features and a specific behavioural phenotype. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The Role of Visual Working Memory in Attentive Tracking of Unique Objects

ERIC Educational Resources Information Center

Makovski, Tal; Jiang, Yuhong V.

2009-01-01

When tracking moving objects in space humans usually attend to the objects' spatial locations and update this information over time. To what extent do surface features assist attentive tracking? In this study we asked participants to track identical or uniquely colored objects. Tracking was enhanced when objects were unique in color. The benefit…

Genomic DNA Methylation Signatures Enable Concurrent Diagnosis and Clinical Genetic Variant Classification in Neurodevelopmental Syndromes.

PubMed

Aref-Eshghi, Erfan; Rodenhiser, David I; Schenkel, Laila C; Lin, Hanxin; Skinner, Cindy; Ainsworth, Peter; Paré, Guillaume; Hood, Rebecca L; Bulman, Dennis E; Kernohan, Kristin D; Boycott, Kym M; Campeau, Philippe M; Schwartz, Charles; Sadikovic, Bekim

2018-01-04

Pediatric developmental syndromes present with systemic, complex, and often overlapping clinical features that are not infrequently a consequence of Mendelian inheritance of mutations in genes involved in DNA methylation, establishment of histone modifications, and chromatin remodeling (the "epigenetic machinery"). The mechanistic cross-talk between histone modification and DNA methylation suggests that these syndromes might be expected to display specific DNA methylation signatures that are a reflection of those primary errors associated with chromatin dysregulation. Given the interrelated functions of these chromatin regulatory proteins, we sought to identify DNA methylation epi-signatures that could provide syndrome-specific biomarkers to complement standard clinical diagnostics. In the present study, we examined peripheral blood samples from a large cohort of individuals encompassing 14 Mendelian disorders displaying mutations in the genes encoding proteins of the epigenetic machinery. We demonstrated that specific but partially overlapping DNA methylation signatures are associated with many of these conditions. The degree of overlap among these epi-signatures is minimal, further suggesting that, consistent with the initial event, the downstream changes are unique to every syndrome. In addition, by combining these epi-signatures, we have demonstrated that a machine learning tool can be built to concurrently screen for multiple syndromes with high sensitivity and specificity, and we highlight the utility of this tool in solving ambiguous case subjects presenting with variants of unknown significance, along with its ability to generate accurate predictions for subjects presenting with the overlapping clinical and molecular features associated with the disruption of the epigenetic machinery. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Glucocerebrosidase Mutations in Parkinson Disease.

PubMed

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

2017-01-01

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

Biomarker-driven phenotyping in Parkinson disease: a translational missing link in disease-modifying clinical trials

PubMed Central

Espay, Alberto J.; Schwarzschild, Michael A.; Tanner, Caroline M.; Fernandez, Hubert H; Simon, David K.; Leverenz, James B.; Merola, Aristide; Chen-Plotkin, Alice; Brundin, Patrik; Kauffman, Marcelo A.; Erro, Roberto; Kieburtz, Karl; Woo, Daniel; Macklin, Eric A.; Standaert, David G.; Lang, Anthony E.

2016-01-01

Past clinical trials of putative neuroprotective therapies have targeted Parkinson disease (PD) as a single pathogenic disease entity. From an Oslerian clinico-pathologic perspective, the wide complexity of PD converges into Lewy bodies and justifies a reductionist approach to PD: a single-mechanism therapy can affect most of those sharing the classic pathologic hallmark. From a systems-biology perspective, PD is a group of disorders that, while related by sharing the feature of nigral dopamine-neuron degeneration, exhibit unique genetic, biological and molecular abnormalities, which probably respond differentially to a given therapeutic approach, particularly for strategies aimed at neuroprotection. Under this model, only biomarker-defined, homogenous subtypes of PD are likely to respond optimally to therapies proven to affect the biological processes within each subtype. Therefore, we suggest that precision medicine applied to PD requires a reevaluation of the biomarker-discovery effort. This effort is currently centered on correlating biological measures to clinical features of PD and on identifying factors that predict whether various prodromal states will convert into the classical movement disorder. We suggest, instead, that subtyping of PD requires the reverse view, where abnormal biological signals (i.e., biomarkers) rather than clinical definitions are used to define disease phenotypes. Successful development of disease-modifying strategies will depend on how relevant the specific biological processes addressed by an intervention are to the pathogenetic mechanisms in the subgroup of targeted patients. This precision-medicine approach will likely yield smaller but well-defined subsets of PD amenable to successful neuroprotection. PMID:28233927

SPECT and PET radiopharmaceuticals for molecular imaging of apoptosis: from bench to clinic

PubMed Central

Wang, Xiaobo; Feng, Han; Zhao, Shichao; Xu, Junling; Wu, Xinyu; Cui, Jing; Zhang, Ying; Qin, Yuhua; Liu, Zhiguo; Gao, Tang; Gao, Yongju; Zeng, Wenbin

2017-01-01

Owing to the central role of apoptosis in many human diseases and the wide-spread application of apoptosis-based therapeutics, molecular imaging of apoptosis in clinical practice is of great interest for clinicians, and holds great promises. Based on the well-defined biochemical changes for apoptosis, a rich assortment of probes and approaches have been developed for molecular imaging of apoptosis with various imaging modalities. Among these imaging techniques, nuclear imaging (including single photon emission computed tomography and positron emission tomography) remains the premier clinical method owing to their high specificity and sensitivity. Therefore, the corresponding radiopharmaceuticals have been a major focus, and some of them like 99mTc-Annexin V, 18F-ML-10, 18F-CP18, and 18F-ICMT-11 are currently under clinical investigations in Phase I/II or Phase II/III clinical trials on a wide scope of diseases. In this review, we summarize these radiopharmaceuticals that have been widely used in clinical trials and elaborate them in terms of radiosynthesis, pharmacokinetics and dosimetry, and their applications in different clinical stages. We also explore the unique features required to qualify a desirable radiopharmaceutical for imaging apoptosis in clinical practice. Particularly, a perspective of the impact of these clinical efforts, namely, apoptosis imaging as predictive and prognostic markers, early-response indicators and surrogate endpoints, is also the highlight of this review. PMID:28108738

Giraffe genome sequence reveals clues to its unique morphology and physiology

PubMed Central

Agaba, Morris; Ishengoma, Edson; Miller, Webb C.; McGrath, Barbara C.; Hudson, Chelsea N.; Bedoya Reina, Oscar C.; Ratan, Aakrosh; Burhans, Rico; Chikhi, Rayan; Medvedev, Paul; Praul, Craig A.; Wu-Cavener, Lan; Wood, Brendan; Robertson, Heather; Penfold, Linda; Cavener, Douglas R.

2016-01-01

The origins of giraffe's imposing stature and associated cardiovascular adaptations are unknown. Okapi, which lacks these unique features, is giraffe's closest relative and provides a useful comparison, to identify genetic variation underlying giraffe's long neck and cardiovascular system. The genomes of giraffe and okapi were sequenced, and through comparative analyses genes and pathways were identified that exhibit unique genetic changes and likely contribute to giraffe's unique features. Some of these genes are in the HOX, NOTCH and FGF signalling pathways, which regulate both skeletal and cardiovascular development, suggesting that giraffe's stature and cardiovascular adaptations evolved in parallel through changes in a small number of genes. Mitochondrial metabolism and volatile fatty acids transport genes are also evolutionarily diverged in giraffe and may be related to its unusual diet that includes toxic plants. Unexpectedly, substantial evolutionary changes have occurred in giraffe and okapi in double-strand break repair and centrosome functions. PMID:27187213

Recurrent seminomas: Clinical features and biologic implications

PubMed Central

Som, Avik; Zhu, Rui; Guo, Charles C.; Efstathiou, Eleni; Xiao, Li; Pisters, Louis L.; Matin, Angabin; Tu, Shi-Ming

2013-01-01

Objectives Certain patients with seminoma and clinically atypical phenotypes—visceral metastases, elevated levels of βhuman chorionic gonadotropin (βHCG), and/or recurrent disease— have a poor prognosis. The primary goal of this pilot study was to characterize the clinical characteristics and treatment profile of these rare patients. We also wished to test whether these tumors expressed any specific biomarkers that might distinguish them as a unique subtype of seminoma. Materials and methods We retrospectively identified 25 patients with a history of seminoma plus visceral metastases, βHCG levels >200 mU/ml, and/or recurrent disease. We reviewed these patients’ histories for treatment efficacy and clinical outcome. Tissue samples were available from 6 of those patients, and we studied them for expression of the markers OCT 3/4, PLAP, CD30, TRA-1-60, c-kit, and gp200. We compared our results with the expression of those markers in tissue samples from mixed seminoma/embryonal carcinomas and classic seminomas. Results Our analysis suggested that certain chemotherapeutic regimens (such as ifosfamide, paclitaxel, and cisplatin) are efficacious for the treatment of patients with these atypical seminomas. Further, specimens from the atypical seminomas generally had staining profiles that resembled those of classic seminomas and the seminoma components in mixed germ-cell tumors, but the profiles differed from those of the embryonal carcinoma components in the same mixed germ-cell tumors. Conclusions Although these atypical seminomas tend to be resistant to chemotherapy, they may still respond to certain chemotherapeutic regimens. Our pilot immunohistochemical study also suggested that the unique phenotypes associated with these atypical seminomas do not result from any relationship with embryonal carcinomas. More study is needed to confirm these initial findings. PMID:20822932

10 CFR 100.10 - Factors to be considered when evaluating sites.

Code of Federal Regulations, 2013 CFR

2013-01-01

... reactor incorporates unique or unusual features having a significant bearing on the probability or consequences of accidental release of radioactive materials; (4) The safety features that are to be engineered... radioactive fission products. In addition, the site location and the engineered features included as...

10 CFR 100.10 - Factors to be considered when evaluating sites.

Code of Federal Regulations, 2012 CFR

2012-01-01

... reactor incorporates unique or unusual features having a significant bearing on the probability or consequences of accidental release of radioactive materials; (4) The safety features that are to be engineered... radioactive fission products. In addition, the site location and the engineered features included as...

10 CFR 100.10 - Factors to be considered when evaluating sites.

Code of Federal Regulations, 2014 CFR

2014-01-01

... reactor incorporates unique or unusual features having a significant bearing on the probability or consequences of accidental release of radioactive materials; (4) The safety features that are to be engineered... radioactive fission products. In addition, the site location and the engineered features included as...

Evaluation of feature selection algorithms for classification in temporal lobe epilepsy based on MR images

NASA Astrophysics Data System (ADS)

Lai, Chunren; Guo, Shengwen; Cheng, Lina; Wang, Wensheng; Wu, Kai

2017-02-01

It's very important to differentiate the temporal lobe epilepsy (TLE) patients from healthy people and localize the abnormal brain regions of the TLE patients. The cortical features and changes can reveal the unique anatomical patterns of brain regions from the structural MR images. In this study, structural MR images from 28 normal controls (NC), 18 left TLE (LTLE), and 21 right TLE (RTLE) were acquired, and four types of cortical feature, namely cortical thickness (CTh), cortical surface area (CSA), gray matter volume (GMV), and mean curvature (MCu), were explored for discriminative analysis. Three feature selection methods, the independent sample t-test filtering, the sparse-constrained dimensionality reduction model (SCDRM), and the support vector machine-recursive feature elimination (SVM-RFE), were investigated to extract dominant regions with significant differences among the compared groups for classification using the SVM classifier. The results showed that the SVM-REF achieved the highest performance (most classifications with more than 92% accuracy), followed by the SCDRM, and the t-test. Especially, the surface area and gray volume matter exhibited prominent discriminative ability, and the performance of the SVM was improved significantly when the four cortical features were combined. Additionally, the dominant regions with higher classification weights were mainly located in temporal and frontal lobe, including the inferior temporal, entorhinal cortex, fusiform, parahippocampal cortex, middle frontal and frontal pole. It was demonstrated that the cortical features provided effective information to determine the abnormal anatomical pattern and the proposed method has the potential to improve the clinical diagnosis of the TLE.

Rare k-mer DNA: Identification of sequence motifs and prediction of CpG island and promoter.

PubMed

Mohamed Hashim, Ezzeddin Kamil; Abdullah, Rosni

2015-12-21

Empirical analysis on k-mer DNA has been proven as an effective tool in finding unique patterns in DNA sequences which can lead to the discovery of potential sequence motifs. In an extensive study of empirical k-mer DNA on hundreds of organisms, the researchers found unique multi-modal k-mer spectra occur in the genomes of organisms from the tetrapod clade only which includes all mammals. The multi-modality is caused by the formation of the two lowest modes where k-mers under them are referred as the rare k-mers. The suppression of the two lowest modes (or the rare k-mers) can be attributed to the CG dinucleotide inclusions in them. Apart from that, the rare k-mers are selectively distributed in certain genomic features of CpG Island (CGI), promoter, 5' UTR, and exon. We correlated the rare k-mers with hundreds of annotated features using several bioinformatic tools, performed further intrinsic rare k-mer analyses within the correlated features, and modeled the elucidated rare k-mer clustering feature into a classifier to predict the correlated CGI and promoter features. Our correlation results show that rare k-mers are highly associated with several annotated features of CGI, promoter, 5' UTR, and open chromatin regions. Our intrinsic results show that rare k-mers have several unique topological, compositional, and clustering properties in CGI and promoter features. Finally, the performances of our RWC (rare-word clustering) method in predicting the CGI and promoter features are ranked among the top three, in eight of the CGI and promoter evaluations, among eight of the benchmarked datasets. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Virus activated artificial ECM induces the osteoblastic differentiation of mesenchymal stem cells without osteogenic supplements

PubMed Central

Wang, Jianglin; Wang, Lin; Li, Xin; Mao, Chuanbin

2013-01-01

Biochemical and topographical features of an artificial extracellular matrix (aECM) can direct stem cell fate. However, it is difficult to vary only the biochemical cues without changing nanotopography to study their unique role. We took advantage of two unique features of M13 phage, a non-toxic nanofiber-like virus, to generate a virus-activated aECM with constant ordered ridge/groove nanotopography but displaying different fibronectin-derived peptides (RGD, its synergy site PHSRN, and a combination of RGD and PHSRN). One feature is the self-assembly of phage into a ridge/groove structure, another is the ease of genetically surface-displaying a peptide. We found that the unique ridge/groove nanotopography and the display of RGD and PHSRN could induce the osteoblastic differentiation of mesenchymal stem cells (MSCs) without any osteogenic supplements. The aECM formed through self-assembly and genetic engineering of phage can be used to understand the role of peptide cues in directing stem cell behavior while keeping nanotopography constant. PMID:23393624

Unique sudden onsets capture attention even when observers are in feature-search mode.

PubMed

Spalek, Thomas M; Yanko, Matthew R; Poiese, Paola; Lagroix, Hayley E P

2012-01-01

Two sources of attentional capture have been proposed: stimulus-driven (exogenous) and goal-oriented (endogenous). A resolution between these modes of capture has not been straightforward. Even such a clearly exogenous event as the sudden onset of a stimulus can be said to capture attention endogenously if observers operate in singleton-detection mode rather than feature-search mode. In four experiments we show that a unique sudden onset captures attention even when observers are in feature-search mode. The displays were rapid serial visual presentation (RSVP) streams of differently coloured letters with the target letter defined by a specific colour. Distractors were four #s, one of the target colour, surrounding one of the non-target letters. Capture was substantially reduced when the onset of the distractor array was not unique because it was preceded by other sets of four grey # arrays in the RSVP stream. This provides unambiguous evidence that attention can be captured both exogenously and endogenously within a single task.

Features and selection of vascular access devices.

PubMed

Sansivero, Gail Egan

2010-05-01

To review venous anatomy and physiology, discuss assessment parameters before vascular access device (VAD) placement, and review VAD options. Journal articles, personal experience. A number of VAD options are available in clinical practice. Access planning should include comprehensive assessment, with attention to patient participation in the planning and selection process. Careful consideration should be given to long-term access needs and preservation of access sites. Oncology nurses are uniquely suited to perform a key role in VAD planning and placement. With knowledge of infusion therapy, anatomy and physiology, device options, and community resources, nurses can be key leaders in preserving vascular access and improving the safety and comfort of infusion therapy. Copyright 2010 Elsevier Inc. All rights reserved.

Severe acute haemorrhagic liver failure in a neonate with a favourable spontaneous outcome.

PubMed

Cavet, Madeleine; Balu, Marie; Garel, Catherine; Mitanchez, Delphine; Renolleau, Sylvain; Alexandre, Marie; Pariente, Danièle; Ducou le Pointe, Hubert

2008-10-01

Acute liver failure in neonates is rare and is frequently associated with an unfavourable outcome. There is no curative treatment other than liver transplantation. Screening for viral, metabolic, toxic or vascular disease is essential to assess the prognosis and to guide specific treatment. Hepatic haemorrhage in neonates is often associated with bacterial infection, trauma and coagulopathies. We present a unique case of neonatal acute liver failure and multifocal massive haemorrhagic intrahepatic lesions of traumatic origin, documented by US and MRI. The patient made a spontaneous recovery. Clinical, biological and imaging outcome was excellent despite the apparent severity of the initial features. The only possible aetiology was a difficult caesarean delivery for mild fetal macrosomia.

Structure and Dynamic Regulation of Abl Kinases*

PubMed Central

Panjarian, Shoghag; Iacob, Roxana E.; Chen, Shugui; Engen, John R.; Smithgall, Thomas E.

2013-01-01

The c-abl proto-oncogene encodes a unique protein-tyrosine kinase (Abl) distinct from c-Src, c-Fes, and other cytoplasmic tyrosine kinases. In normal cells, Abl plays prominent roles in cellular responses to genotoxic stress as well as in the regulation of the actin cytoskeleton. Abl is also well known in the context of Bcr-Abl, the oncogenic fusion protein characteristic of chronic myelogenous leukemia. Selective inhibitors of Bcr-Abl, of which imatinib is the prototype, have had a tremendous impact on clinical outcomes in chronic myelogenous leukemia and revolutionized the field of targeted cancer therapy. In this minireview, we focus on the structural organization and dynamics of Abl kinases and how these features influence inhibitor sensitivity. PMID:23316053

Cystic lung disease in birt-hogg-dubé syndrome: a case series of three patients.

PubMed

Kilincer, Abidin; Ariyurek, Orhan Macit; Karabulut, Nevzat

2014-06-01

Birt-Hogg-Dubé syndrome is characterized by clinical manifestations such as hamartomas of the skin, renal tumors and lung cysts with spontaneous pneumothoraces. Patients with Birt-Hogg-Dubé syndrome may present with only multiple lung cysts. We report the chest computerized tomography (CT) features of three patients with Birt-Hogg-Dubé syndrome. Each patient had multiple lung cysts of various sizes according to chest CT evaluation, most of which were located in lower lobes and related to pleura. The identification of unique characteristics in the chest CT of patients with Birt-Hogg-Dubé syndrome may provide an efficient mechanism for diagnosis.

Complications of Lung Transplantation: A Roentgenographic Perspective.

PubMed

Tejwani, Vickram; Panchabhai, Tanmay S; Kotloff, Robert M; Mehta, Atul C

2016-06-01

Lung transplantation is now an established treatment for a broad spectrum of end-stage pulmonary diseases. According to the International Society for Heart and Lung Transplantation Registry, more than 50,000 lung transplants have been performed worldwide, with nearly 11,000 lung transplant recipients alive in the United States. With the increasing application of lung transplantation, pulmonologists must be cognizant of common complications unique to the postlung transplant period and the associated radiologic findings. The aim of this review is to describe clinical manifestations and prototypical radiographic features of both common and rare complications encountered in lung transplant recipients. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Activity-based funding model provides foundation for province-wide best practices in renal care.

PubMed

Levin, Adeera; Lo, Clifford; Noel, Kevin; Djurdjev, Ogjnenka; Amano, Erlyn C

2013-01-01

British Columbia has a unique funding model for renal care in Canada. Patient care is delivered through six health authorities, while funding is administered by the Provincial Renal Agency using an activity-based funding model. The model allocates funding based on a schedule of costs for every element of renal care, excluding physician fees. Accountability, transparency of allocation and tracking of outcomes are key features that ensure successful implementation. The model supports province-wide best practices and equitable care and fosters innovation. Since its introduction, the outpatient renal services budget has grown less than the population, while maintaining or improving clinical outcomes. Copyright © 2013 Longwoods Publishing.

A Rare Bilateral Presentation of Multiple Dens Invaginatus, Shovel-Shaped Incisor and Talon Cusp With Mesiodens.

PubMed

Hegde, S; Jain, M; Shubha, A B

2014-01-01

The aim of this paper is to describe a unique and unusual case of concomitant appearance of morphological dental anomalies in the maxillary anterior region, along with its management in a patient with no systemic abnormality. This case report describes the clinical and radiographic features of talon cusp, dens invaginatus, shovel-shaped incisors and a supernumerary tooth occurring in a single patient, which is a rare presentation. All 4 permanent maxillary incisors had dens invaginatus, the permanent maxillary canines showed the presence of talon cusps, the permanent maxillary central incisors were shovel-shaped and an erupted mesiodens was also observed. Treatment included restorative, surgical and orthodontic approaches.

Infrastructure Requirements for an Urgent-Start Peritoneal Dialysis Program

PubMed Central

Ghaffari, Arshia; Kumar, Vijay; Guest, Steven

2013-01-01

Patients with advanced chronic kidney disease nearing dialysis but without pre-established access almost uniformly initiate dialysis with a temporary central venous catheter. These catheters are associated with high rates of infection and flow disturbances, requiring removal and subsequent replacement. Many of these patients might be candidates for peritoneal dialysis (PD), but because of the absence of prior catheter placement, the default initial modality is hemodialysis. Recent reports, however, have demonstrated the feasibility of initiating PD urgently despite the late referral for access placement. Urgent-start PD clinical pathways require a unique infrastructure and treatment approach. This article reviews the salient features required to establish an urgent-start PD program. PMID:24335123

Lichenoid Dermatitis of the Vulva: Diagnosis and Differential Diagnosis for the Gynecologic Pathologist.

PubMed

Lewin, Marc R; Hick, Ryan W; Selim, Maria A

2017-09-01

Inflammatory processes affecting the vulva may present a unique challenge due to location specific changes. Different factors are behind the intricacy in the presentation of vulvar dermatoses. First, the vulva is lined by different epithelia (hair-bearing keratinized epithelium, modified mucosa, and mucosa). Furthermore, among other factors, this organ is exposed to friction, occlusion, and trauma. Lastly, as there is a tendency to look for health care advice at an advanced stage of the disease, the lesion may be modified by secondary changes due to self-treatment. This article describes the clinical presentation and pathologic features of vulvar dermatoses with a lichenoid pattern and highlights practical points for their diagnoses.

Kanamycin and its derivative, arbekacin: significance and impact.

PubMed

Hotta, Kunimoto; Kondo, Shinichi

2018-03-01

On the occasion of the 60th anniversary of the discovery (1957) of kanamycin (KM), a series of research achievements on KM and its semisynthetic derivative Arbekacin (ABK) are outlined. KM was first used clinically in 1958 and was appreciated for its remarkable curing effect on various bacterial infections, especially tuberculosis. ABK is a KM derivative rationally semisynthesized to overcome KM resistance due to enzymatic phosphorylation and acetylation. Since its approval in 1990 as an anti-MRSA drug, ABK has been and still is effectively used in chemotherapy because MRSA rarely develops high ABK-resistance. Research that illuminated the unique features of ABK enabling it to resist the development of resistance by MRSA are also described.

Biosynthesis of enediyne antitumor antibiotics.

PubMed

Van Lanen, Steven G; Shen, Ben

2008-01-01

The enediyne polyketides are secondary metabolites isolated from a variety of Actinomycetes. All members share very potent anticancer and antibiotic activity, and prospects for the clinical application of the enediynes has been validated with the recent marketing of two enediyne derivatives as anticancer agents. The biosynthesis of these compounds is of interest because of the numerous structural features that are unique to the enediyne family. The gene cluster for five enediynes has now been cloned and sequenced, providing the foundation to understand natures' means to biosynthesize such complex, exotic molecules. Presented here is a review of the current progress in delineating the biosynthesis of the enediynes with an emphasis on the model enediyne, C-1027.

Dynamic biophotonics: female squid exhibit sexually dimorphic tunable leucophores and iridocytes.

PubMed

DeMartini, Daniel G; Ghoshal, Amitabh; Pandolfi, Erica; Weaver, Aaron T; Baum, Mary; Morse, Daniel E

2013-10-01

Loliginid squid use tunable multilayer reflectors to modulate the optical properties of their skin for camouflage and communication. Contained inside specialized cells called iridocytes, these photonic structures have been a model for investigations into bio-inspired adaptive optics. Here, we describe two distinct sexually dimorphic tunable biophotonic features in the commercially important species Doryteuthis opalescens: bright stripes of rainbow iridescence on the mantle just beneath each fin attachment and a bright white stripe centered on the dorsal surface of the mantle between the fins. Both of these cellular features are unique to the female; positioned in the same location as the conspicuously bright white testis in the male, they are completely switchable, transitioning between transparency and high reflectivity. The sexual dimorphism, location and tunability of these features suggest that they may function in mating or reproduction. These features provide advantageous new models for investigation of adaptive biophotonics. The intensely reflective cells of the iridescent stripes provide a greater signal-to-noise ratio than the adaptive iridocytes studied thus far, while the cells constituting the white stripe are adaptive leucophores--unique biological tunable broadband scatterers containing Mie-scattering organelles activated by acetylcholine, and a unique complement of reflectin proteins.

Proteins without unique 3D structures: biotechnological applications of intrinsically unstable/disordered proteins.

PubMed

Uversky, Vladimir N

2015-03-01

Intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs) are functional proteins or regions that do not have unique 3D structures under functional conditions. Therefore, from the viewpoint of their lack of stable 3D structure, IDPs/IDPRs are inherently unstable. As much as structure and function of normal ordered globular proteins are determined by their amino acid sequences, the lack of unique 3D structure in IDPs/IDPRs and their disorder-based functionality are also encoded in the amino acid sequences. Because of their specific sequence features and distinctive conformational behavior, these intrinsically unstable proteins or regions have several applications in biotechnology. This review introduces some of the most characteristic features of IDPs/IDPRs (such as peculiarities of amino acid sequences of these proteins and regions, their major structural features, and peculiar responses to changes in their environment) and describes how these features can be used in the biotechnology, for example for the proteome-wide analysis of the abundance of extended IDPs, for recombinant protein isolation and purification, as polypeptide nanoparticles for drug delivery, as solubilization tools, and as thermally sensitive carriers of active peptides and proteins. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Innate and adaptive immune responses in male and female reproductive tracts in homeostasis and following HIV infection

PubMed Central

Nguyen, Philip V; Kafka, Jessica K; Ferreira, Victor H; Roth, Kristy; Kaushic, Charu

2014-01-01

The male and female reproductive tracts are complex microenvironments that have diverse functional demands. The immune system in the reproductive tract has the demanding task of providing a protective environment for a fetal allograft while simultaneously conferring protection against potential pathogens. As such, it has evolved a unique set of adaptations, primarily under the influence of sex hormones, which make it distinct from other mucosal sites. Here, we discuss the various components of the immune system that are present in both the male and female reproductive tracts, including innate soluble factors and cells and humoral and cell-mediated adaptive immunity under homeostatic conditions. We review the evidence showing unique phenotypic and functional characteristics of immune cells and responses in the male and female reproductive tracts that exhibit compartmentalization from systemic immunity and discuss how these features are influenced by sex hormones. We also examine the interactions among the reproductive tract, sex hormones and immune responses following HIV-1 infection. An improved understanding of the unique characteristics of the male and female reproductive tracts will provide insights into improving clinical treatments of the immunological causes of infertility and the design of prophylactic interventions for the prevention of sexually transmitted infections. PMID:24976268

Surface display of a massively variable lipoprotein by a Legionella diversity-generating retroelement.

PubMed

Arambula, Diego; Wong, Wenge; Medhekar, Bob A; Guo, Huatao; Gingery, Mari; Czornyj, Elizabeth; Liu, Minghsun; Dey, Sanghamitra; Ghosh, Partho; Miller, Jeff F

2013-05-14

Diversity-generating retroelements (DGRs) are a unique family of retroelements that confer selective advantages to their hosts by facilitating localized DNA sequence evolution through a specialized error-prone reverse transcription process. We characterized a DGR in Legionella pneumophila, an opportunistic human pathogen that causes Legionnaires disease. The L. pneumophila DGR is found within a horizontally acquired genomic island, and it can theoretically generate 10(26) unique nucleotide sequences in its target gene, legionella determinent target A (ldtA), creating a repertoire of 10(19) distinct proteins. Expression of the L. pneumophila DGR resulted in transfer of DNA sequence information from a template repeat to a variable repeat (VR) accompanied by adenine-specific mutagenesis of progeny VRs at the 3'end of ldtA. ldtA encodes a twin-arginine translocated lipoprotein that is anchored in the outer leaflet of the outer membrane, with its C-terminal variable region surface exposed. Related DGRs were identified in L. pneumophila clinical isolates that encode unique target proteins with homologous VRs, demonstrating the adaptability of DGR components. This work characterizes a DGR that diversifies a bacterial protein and confirms the hypothesis that DGR-mediated mutagenic homing occurs through a conserved mechanism. Comparative bioinformatics predicts that surface display of massively variable proteins is a defining feature of a subset of bacterial DGRs.

Chromosome 3p loss of heterozygosity is associated with a unique metabolic network in clear cell renal carcinoma

PubMed Central

Gatto, Francesco; Nookaew, Intawat; Nielsen, Jens

2014-01-01

Several common oncogenic pathways have been implicated in the emergence of renowned metabolic features in cancer, which in turn are deemed essential for cancer proliferation and survival. However, the extent to which different cancers coordinate their metabolism to meet these requirements is largely unexplored. Here we show that even in the heterogeneity of metabolic regulation a distinct signature encompassed most cancers. On the other hand, clear cell renal cell carcinoma (ccRCC) strongly deviated in terms of metabolic gene expression changes, showing widespread down-regulation. We observed a metabolic shift that associates differential regulation of enzymes in one-carbon metabolism with high tumor stage and poor clinical outcome. A significant yet limited set of metabolic genes that explained the partial divergence of ccRCC metabolism correlated with loss of von Hippel-Lindau tumor suppressor (VHL) and a potential activation of signal transducer and activator of transcription 1. Further network-dependent analyses revealed unique defects in nucleotide, one-carbon, and glycerophospholipid metabolism at the transcript and protein level, which contrasts findings in other tumors. Notably, this behavior is recapitulated by recurrent loss of heterozygosity in multiple metabolic genes adjacent to VHL. This study therefore shows how loss of heterozygosity, hallmarked by VHL deletion in ccRCC, may uniquely shape tumor metabolism. PMID:24550497

Clinical and Molecular Features of Laron Syndrome, A Genetic Disorder Protecting from Cancer.

PubMed

Janecka, Anna; Kołodziej-Rzepa, Marta; Biesaga, Beata

2016-01-01

Laron syndrome (LS) is a rare, genetic disorder inherited in an autosomal recessive manner. The disease is caused by mutations of the growth hormone (GH) gene, leading to GH/insulin-like growth factor type 1 (IGF1) signalling pathway defect. Patients with LS have characteristic biochemical features, such as a high serum level of GH and low IGF1 concentration. Laron syndrome was first described by the Israeli physician Zvi Laron in 1966. Globally, around 350 people are affected by this syndrome and there are two large groups living in separate geographic regions: Israel (69 individuals) and Ecuador (90 individuals). They are all characterized by typical appearance such as dwarfism, facial phenotype, obesity and hypogenitalism. Additionally, they suffer from hypoglycemia, hypercholesterolemia and sleep disorders, but surprisingly have a very low cancer risk. Therefore, studies on LS offer a unique opportunity to better understand carcinogenesis and develop new strategies of cancer treatment. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Overlap between autistic and schizotypal personality traits is not accounted for by anxiety and depression.

PubMed

Mealey, Alex; Abbott, Gavin; Byrne, Linda K; McGillivray, Jane

2014-10-30

Autism spectrum and schizophrenia spectrum disorders are classified separately in the DSM-5, yet research indicates that these two disorders share overlapping features. The aim of the present study was to examine the overlap between autistic and schizotypal personality traits and whether anxiety and depression act as confounding variables in this relationship within a non-clinical population. One hundred and forty-four adults completed the Autism Spectrum Quotient and the Schizotypal Personality Questionnaire and the Depression Anxiety Stress Scales-21. A number of associations were seen between autistic and schizotypal personality traits. However, negative traits were the only schizotypal feature to uniquely predict global autistic traits, thus highlighting the importance of interpersonal qualities in the overlap of autistic and schizotypal characteristics. The inclusion of anxiety and depression did not alter relationships between autistic and schizotypal traits, indicating that anxiety and depression are not confounders of this relationship. These findings have important implications for the conceptualisation of both disorders. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Current consensus and guidelines of contrast enhanced ultrasound for the characterization of focal liver lesions

PubMed Central

Jang, Jae Young; Kim, Moon Young; Jeong, Soung Won; Kim, Tae Yeob; Kim, Seung Up; Lee, Sae Hwan; Suk, Ki Tae; Park, Soo Young; Woo, Hyun Young; Kim, Sang Gyune; Heo, Jeong; Baik, Soon Koo; Kim, Hong Soo

2013-01-01

The application of ultrasound contrast agents (UCAs) is considered essential when evaluating focal liver lesions (FLLs) using ultrasonography (US). Microbubble UCAs are easy to use and robust; their use poses no risk of nephrotoxicity and requires no ionizing radiation. The unique features of contrast enhanced US (CEUS) are not only noninvasiveness but also real-time assessing of liver perfusion throughout the vascular phases. The later feature has led to dramatic improvement in the diagnostic accuracy of US for detection and characterization of FLLs as well as the guidance to therapeutic procedures and evaluation of response to treatment. This article describes the current consensus and guidelines for the use of UCAs for the FLLs that are commonly encountered in US. After a brief description of the bases of different CEUS techniques, contrast-enhancement patterns of different types of benign and malignant FLLs and other clinical applications are described and discussed on the basis of our experience and the literature data. PMID:23593604

Fundamentals of rapid injection molding for microfluidic cell-based assays.

PubMed

Lee, Ulri N; Su, Xiaojing; Guckenberger, David J; Dostie, Ashley M; Zhang, Tianzi; Berthier, Erwin; Theberge, Ashleigh B

2018-01-30

Microscale cell-based assays have demonstrated unique capabilities in reproducing important cellular behaviors for diagnostics and basic biological research. As these assays move beyond the prototyping stage and into biological and clinical research environments, there is a need to produce microscale culture platforms more rapidly, cost-effectively, and reproducibly. 'Rapid' injection molding is poised to meet this need as it enables some of the benefits of traditional high volume injection molding at a fraction of the cost. However, rapid injection molding has limitations due to the material and methods used for mold fabrication. Here, we characterize advantages and limitations of rapid injection molding for microfluidic device fabrication through measurement of key features for cell culture applications including channel geometry, feature consistency, floor thickness, and surface polishing. We demonstrate phase contrast and fluorescence imaging of cells grown in rapid injection molded devices and provide design recommendations to successfully utilize rapid injection molding methods for microscale cell-based assay development in academic laboratory settings.

Metastatic breast cancer to the rectum: A case report with emphasis on MRI features.

PubMed

Lau, Li Ching; Wee, Bernard; Wang, Shi; Thian, Yee Liang

2017-04-01

Less than 1% of breast carcinomas metastasize to the gastrointestinal tract. The diagnosis is frequently not recognized especially when the history of breast carcinoma is remote. A 61-year-old female with a remote history of breast carcinoma presented with a 3-month history of change in bowel habits. Colonoscopy showed a circumferential rectal mass with initial impression of primary rectal cancer. MRI of the rectum showed findings that are atypical for primary rectal cancer. Deep biopsy of the rectal mass confirmed lobular breast carcinoma metastasis to the rectum. The patient was treated with radiotherapy and hormonal therapy. She is symptomatically well 2 years after presentation and remains on hormonal therapy. Lobular breast cancer which metastasizes to the rectum can mimic primary rectal cancer clinically. The unique MRI features described in our case when present with a concordant history of lobular breast carcinoma should alert the radiologist to the possibility of this diagnosis which has important treatment implications.

Overlapping gene expression profiles indicative of antigen processing and the interferon pathway characterize inflammatory fibrotic skin diseases.

PubMed

Limpers, Annelies; van Royen-Kerkhof, Annet; van Roon, Joel A G; Radstake, Timothy R D J; Broen, Jasper C A

2014-02-01

Inflammatory fibrotic disorders have been of high interest both for dermatologists and rheumatologists. Although the phenotypic end stage of this group of diseases is ultimately the same, namely fibrosis, patients present with different clinical features and are often treated with distinct therapeutic modalities. This review addresses whether there is evidence for different underlying molecular pathways in the various inflammatory fibrotic diseases such as localized scleroderma, pediatric lichen sclerosus, adult lichen sclerosus, eosinophilic fasciitis and systemic sclerosis. To investigate this, a large number of gene expression microarray studies performed on skin or fibroblasts from patients with these aforementioned diseases were described, (re-)analysed, and compared. As suspected by the heterogeneous phenotype, most diseases showed unique gene expression features. Intriguingly, a clear overlap was observed between adult and pediatric lichen sclerosus and localized scleroderma, in antigen processing and the interferon pathway. Delineating the cause and consequence of these pathways may generate novel tools to better characterize and more effectively treat these patients.

Feeding difficulties, a key feature of the Drosophila NDUFS4 mitochondrial disease model

PubMed Central

Foriel, Sarah; Eidhof, Ilse

2018-01-01

ABSTRACT Mitochondrial diseases are associated with a wide variety of clinical symptoms and variable degrees of severity. Patients with such diseases generally have a poor prognosis and often an early fatal disease outcome. With an incidence of 1 in 5000 live births and no curative treatments available, relevant animal models to evaluate new therapeutic regimes for mitochondrial diseases are urgently needed. By knocking down ND-18, the unique Drosophila ortholog of NDUFS4, an accessory subunit of the NADH:ubiquinone oxidoreductase (Complex I), we developed and characterized several dNDUFS4 models that recapitulate key features of mitochondrial disease. Like in humans, the dNDUFS4 KD flies display severe feeding difficulties, an aspect of mitochondrial disorders that has so far been largely ignored in animal models. The impact of this finding, and an approach to overcome it, will be discussed in the context of interpreting disease model characterization and intervention studies. This article has an associated First Person interview with the first author of the paper. PMID:29590638

World Gastroenterology Organization Practice Guidelines for the diagnosis and management of IBD in 2010.

PubMed

Bernstein, Charles N; Fried, Michael; Krabshuis, J H; Cohen, Henry; Eliakim, R; Fedail, Suleiman; Gearry, Richard; Goh, K L; Hamid, Saheed; Khan, Aamir Ghafor; LeMair, A W; Malfertheiner; Ouyang, Qin; Rey, J F; Sood, Ajit; Steinwurz, Flavio; Thomsen, Ole O; Thomson, Alan; Watermeyer, Gillian

2010-01-01

Inflammatory bowel disease (IBD) represents a group of idiopathic, chronic, inflammatory intestinal conditions. Its two main disease categories are: Crohn's disease (CD) and ulcerative colitis (UC), which feature both overlapping and distinct clinical and pathological features. While these diseases have, in the past, been most evident in the developed world, their prevalence in the developing world has been gradually increasing in recent decades. This poses unique issues in diagnosis and management which have been scarcely addressed in the literature or in extant guidelines. Depending on the nature of the complaints, investigations to diagnose either form of IBD or to assess disease activity will vary and will also be influenced by geographic variations in other conditions that might mimic IBD. Similarly, therapy varies depending on the phenotype of the disease being treated and available resources. The World Gastroenterology Organization has, accordingly, developed guidelines for diagnosing and treating IBD using a cascade approach to account for variability in resources in countries around the world.

Cognitive-Behavioral Therapy for Youth with Body Dysmorphic Disorder: Current Status and Future Directions

PubMed Central

Phillips, Katharine A.; Rogers, Jamison

2011-01-01

SYNOPSIS Body dysmorphic disorder (BDD), a distressing or impairing preoccupation with nonexistent or slight defect(s) in appearance, usually begins during early adolescence and appears to be common in youth. BDD is characterized by substantial impairment in psychosocial functioning and markedly high rates of suicidality. Cognitive-behavioral therapy (CBT) tailored to BDD’s unique features is the best tested and most promising psychosocial treatment for adults with BDD. CBT has been used for youth with BDD, but it has not been systematically developed for or tested in this age group, and there is a pressing need for this work to be done. This article focuses on CBT for BDD in adults and youth, possible adaptations for youth, and the need for treatment research in youth. We also discuss BDD’s prevalence, clinical features, how to diagnose BDD in youth, recommended pharmacotherapy for BDD (serotonin-reuptake inhibitors), and treatments that are not recommended (surgery and other cosmetic treatments). PMID:21440856

Differences in manifestations of Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome.

PubMed

Meester, Josephina A N; Verstraeten, Aline; Schepers, Dorien; Alaerts, Maaike; Van Laer, Lut; Loeys, Bart L

2017-11-01

Many different heritable connective tissue disorders (HCTD) have been described over the past decades. These syndromes often affect the connective tissue of various organ systems, including heart, blood vessels, skin, joints, bone, eyes, and lungs. The discovery of these HCTD was followed by the identification of mutations in a wide range of genes encoding structural proteins, modifying enzymes, or components of the TGFβ-signaling pathway. Three typical examples of HCTD are Marfan syndrome (MFS), Ehlers-Danlos syndrome (EDS), and Loeys-Dietz syndrome (LDS). These syndromes show some degree of phenotypical overlap of cardiovascular, skeletal, and cutaneous features. MFS is typically characterized by cardiovascular, ocular, and skeletal manifestations and is caused by heterozygous mutations in FBN1 , coding for the extracellular matrix (ECM) protein fibrillin-1. The most common cardiovascular phenotype involves aortic aneurysm and dissection at the sinuses of Valsalva. LDS is caused by mutations in TGBR1/2 , SMAD2/3 , or TGFB2/3 , all coding for components of the TGFβ-signaling pathway. LDS can be distinguished from MFS by the unique presence of hypertelorism, bifid uvula or cleft palate, and widespread aortic and arterial aneurysm and tortuosity. Compared to MFS, LDS cardiovascular manifestations tend to be more severe. In contrast, no association is reported between LDS and the presence of ectopia lentis, a key distinguishing feature of MFS. Overlapping features between MFS and LDS include scoliosis, pes planus, anterior chest deformity, spontaneous pneumothorax, and dural ectasia. EDS refers to a group of clinically and genetically heterogeneous connective tissue disorders and all subtypes are characterized by variable abnormalities of skin, ligaments and joints, blood vessels, and internal organs. Typical presenting features include joint hypermobility, skin hyperextensibility, and tissue fragility. Up to one quarter of the EDS patients show aortic aneurysmal disease. The latest EDS nosology distinguishes 13 subtypes. Many phenotypic features show overlap between the different subtypes, which makes the clinical diagnosis rather difficult and highlights the importance of molecular diagnostic confirmation.

Differences in manifestations of Marfan syndrome, Ehlers-Danlos syndrome, and Loeys-Dietz syndrome

PubMed Central

Meester, Josephina A. N.; Verstraeten, Aline; Schepers, Dorien; Alaerts, Maaike; Van Laer, Lut

2017-01-01

Many different heritable connective tissue disorders (HCTD) have been described over the past decades. These syndromes often affect the connective tissue of various organ systems, including heart, blood vessels, skin, joints, bone, eyes, and lungs. The discovery of these HCTD was followed by the identification of mutations in a wide range of genes encoding structural proteins, modifying enzymes, or components of the TGFβ-signaling pathway. Three typical examples of HCTD are Marfan syndrome (MFS), Ehlers-Danlos syndrome (EDS), and Loeys-Dietz syndrome (LDS). These syndromes show some degree of phenotypical overlap of cardiovascular, skeletal, and cutaneous features. MFS is typically characterized by cardiovascular, ocular, and skeletal manifestations and is caused by heterozygous mutations in FBN1, coding for the extracellular matrix (ECM) protein fibrillin-1. The most common cardiovascular phenotype involves aortic aneurysm and dissection at the sinuses of Valsalva. LDS is caused by mutations in TGBR1/2, SMAD2/3, or TGFB2/3, all coding for components of the TGFβ-signaling pathway. LDS can be distinguished from MFS by the unique presence of hypertelorism, bifid uvula or cleft palate, and widespread aortic and arterial aneurysm and tortuosity. Compared to MFS, LDS cardiovascular manifestations tend to be more severe. In contrast, no association is reported between LDS and the presence of ectopia lentis, a key distinguishing feature of MFS. Overlapping features between MFS and LDS include scoliosis, pes planus, anterior chest deformity, spontaneous pneumothorax, and dural ectasia. EDS refers to a group of clinically and genetically heterogeneous connective tissue disorders and all subtypes are characterized by variable abnormalities of skin, ligaments and joints, blood vessels, and internal organs. Typical presenting features include joint hypermobility, skin hyperextensibility, and tissue fragility. Up to one quarter of the EDS patients show aortic aneurysmal disease. The latest EDS nosology distinguishes 13 subtypes. Many phenotypic features show overlap between the different subtypes, which makes the clinical diagnosis rather difficult and highlights the importance of molecular diagnostic confirmation. PMID:29270370

High-efficiency wind turbine

NASA Technical Reports Server (NTRS)

Hein, L. A.; Myers, W. N.

1980-01-01

Vertical axis wind turbine incorporates several unique features to extract more energy from wind increasing efficiency 20% over conventional propeller driven units. System also features devices that utilize solar energy or chimney effluents during periods of no wind.

Unique core genomes of the bacterial family vibrionaceae: insights into niche adaptation and speciation.

PubMed

Kahlke, Tim; Goesmann, Alexander; Hjerde, Erik; Willassen, Nils Peder; Haugen, Peik

2012-05-10

The criteria for defining bacterial species and even the concept of bacterial species itself are under debate, and the discussion is apparently intensifying as more genome sequence data is becoming available. However, it is still unclear how the new advances in genomics should be used most efficiently to address this question. In this study we identify genes that are common to any group of genomes in our dataset, to determine whether genes specific to a particular taxon exist and to investigate their potential role in adaptation of bacteria to their specific niche. These genes were named unique core genes. Additionally, we investigate the existence and importance of unique core genes that are found in isolates of phylogenetically non-coherent groups. These groups of isolates, that share a genetic feature without sharing a closest common ancestor, are termed genophyletic groups. The bacterial family Vibrionaceae was used as the model, and we compiled and compared genome sequences of 64 different isolates. Using the software orthoMCL we determined clusters of homologous genes among the investigated genome sequences. We used multilocus sequence analysis to build a host phylogeny and mapped the numbers of unique core genes of all distinct groups of isolates onto the tree. The results show that unique core genes are more likely to be found in monophyletic groups of isolates. Genophyletic groups of isolates, in contrast, are less common especially for large groups of isolate. The subsequent annotation of unique core genes that are present in genophyletic groups indicate a high degree of horizontally transferred genes. Finally, the annotation of the unique core genes of Vibrio cholerae revealed genes involved in aerotaxis and biosynthesis of the iron-chelator vibriobactin. The presented work indicates that genes specific for any taxon inside the bacterial family Vibrionaceae exist. These unique core genes encode conserved metabolic functions that can shed light on the adaptation of a species to its ecological niche. Additionally, our study suggests that unique core genes can be used to aid classification of bacteria and contribute to a bacterial species definition on a genomic level. Furthermore, these genes may be of importance in clinical diagnostics and drug development.

Phenotype and Clinical Course of Inflammatory Bowel Disease with Co-Existent Celiac Disease.

PubMed

Tse, Chung Sang; Deepak, Parakkal; De La Fuente, Jaime; Bledsoe, Adam C; Larson, Joseph J; Murray, Joseph A; Papadakis, Konstantinos A

2018-05-07

Inflammatory bowel diseases, principally Crohn's disease and ulcerative colitis, and celiac disease are among the most common immune-mediated gastrointestinal diseases. We aim to elucidate the clinical course and outcomes of patients with concomitant inflammatory bowel disease and celiac disease, a unique population that remains scarcely studied to date. A retrospective matched case-control study of adults with coexistent inflammatory bowel disease and celiac disease was performed at a tertiary referral institution in North America. Logistic regression and Kaplan-Meier curves compared disease characteristics and clinical outcomes of the two groups. A total of 342 inflammatory bowel disease patients were included in this study, of which 114 had coexistent celiac disease and 228 did not. Patients with coexistent inflammatory bowel disease and celiac disease had higher rates of primary sclerosing cholangitis (19.3% vs 5.7%; odds ratio, 4.4; 95% confidence interval, 2.1-9.4; p<0.001), extensive ulcerative colitis (78.1% vs 59.0%; odds ratio, 2.8; 95% confidence interval 1.5-5.5, p=0.002), and family history of celiac disease (10.5% vs 3.5%; odds ratio 3.2; 95% confidence interval 1.3-8.2; p=0.01), compared to patients without concomitant celiac disease. Patients with inflammatory bowel disease with concomitant celiac disease have unique phenotypic features compared to non-celiac inflammatory bowel disease, with higher risks for colitis-related hospitalizations, extensive colitis, and primary sclerosing cholangitis. Increased recognition of coexistent IBD and celiac disease can prompt clinicians to investigate for concomitant disease sooner, particularly in patients with seemingly refractory disease.

Autoantibodies Against the Node of Ranvier in Seropositive Chronic Inflammatory Demyelinating Polyneuropathy: Diagnostic, Pathogenic, and Therapeutic Relevance

PubMed Central

Vural, Atay; Doppler, Kathrin; Meinl, Edgar

2018-01-01

Discovery of disease-associated autoantibodies has transformed the clinical management of a variety of neurological disorders. Detection of autoantibodies aids diagnosis and allows patient stratification resulting in treatment optimization. In the last years, a set of autoantibodies against proteins located at the node of Ranvier has been identified in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). These antibodies target neurofascin, contactin1, or contactin-associated protein 1, and we propose to name CIDP patients with these antibodies collectively as seropositive. They have unique clinical characteristics that differ from seronegative CIDP. Moreover, there is compelling evidence that autoantibodies are relevant for the pathogenesis. In this article, we review the current knowledge on the characteristics of autoantibodies against the node of Ranvier proteins and their clinical relevance in CIDP. We start with a description of the structure of the node of Ranvier followed by a summary of assays used to identify seropositive patients; and then, we describe clinical features and characteristics linked to seropositivity. We review knowledge on the role of these autoantibodies for the pathogenesis with relevance for the emerging concept of nodopathy/paranodopathy and summarize the treatment implications. PMID:29867996

Autoantibodies Against the Node of Ranvier in Seropositive Chronic Inflammatory Demyelinating Polyneuropathy: Diagnostic, Pathogenic, and Therapeutic Relevance.

PubMed

Vural, Atay; Doppler, Kathrin; Meinl, Edgar

2018-01-01

Discovery of disease-associated autoantibodies has transformed the clinical management of a variety of neurological disorders. Detection of autoantibodies aids diagnosis and allows patient stratification resulting in treatment optimization. In the last years, a set of autoantibodies against proteins located at the node of Ranvier has been identified in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). These antibodies target neurofascin, contactin1, or contactin-associated protein 1, and we propose to name CIDP patients with these antibodies collectively as seropositive. They have unique clinical characteristics that differ from seronegative CIDP. Moreover, there is compelling evidence that autoantibodies are relevant for the pathogenesis. In this article, we review the current knowledge on the characteristics of autoantibodies against the node of Ranvier proteins and their clinical relevance in CIDP. We start with a description of the structure of the node of Ranvier followed by a summary of assays used to identify seropositive patients; and then, we describe clinical features and characteristics linked to seropositivity. We review knowledge on the role of these autoantibodies for the pathogenesis with relevance for the emerging concept of nodopathy/paranodopathy and summarize the treatment implications.

Nocardia yamanashiensis in an immunocompromised patient presenting as an indurated nodule on the dorsal hand.

PubMed

Anzalone, C Lane; Cohen, Philip R; Tarrand, Jeffrey J; Diwan, Abdul H; Prieto, Victor G

2013-01-01

Nocardia are ubiquitous, aerobic, gram-positive actinomycetes. Nocardiosis typically occurs in immunocompromised patients, although immunocompetent individuals can also be affected. The purpose of this case study is to review the clinical characteristics and treatments of a unique form of cutaneous nocardiosis. We retrospectively reviewed the medical literature using PubMed, searching the terms cutaneous, host, immunocompromised, Nocardia, primary, yamanashiensis. Patient reports and previous reviews of the subject were critically assessed and the salient features are presented. Cutaneous nocardiosis typically presents as pustular nodules and the lesions may progress to become abscesses, cellulitis, granulomas or keloid-like tumors. N. brasiliensis is the predominant species involved in primary cutaneous nocardiosis; other common Nocardia species involved in human disease are N. farcinica, N. abscessus, N. cyriacigeorgica, and N. nova. Only two individuals (including the patient presented here) with primary cutaneous infection by N. yamanashiensis have been described in the literature; a third clinical isolate was recovered from a lung biopsy. Nocardia yamanashiensis is a rare clinical form of primary cutaneous nocardiosis. 16S ribosomal gene sequencing, as well as Gram stain and modified Fite acid-fast stain, play a vital role in identifying this clinical variant.

The Munroe-Meyer Approach: Continuous Integration of Didactic Instruction, Research, and Clinical Practice.

PubMed

Zangrillo, Amanda N; Warzak, William J; Volkert, Valerie M; Valleley, Rachel J; Shriver, Mark D; Rodriguez, Nicole M; Roberts, Holly J; Piazza, Cathleen C; Peterson, Kathryn M; Milnes, Suzanne M; Menousek, Kathryn M; Mathews, Terri L; Luczynski, Kevin C; Kupzyk, Sara S; Kuhn, Brett R; Higgins, William J; Grennan, Allison O; Greer, Brian D; Fisher, Wayne W; Evans, Joseph H; Allen, Keith D

2016-05-01

Increased demand for applied behavior analysis (ABA) services has increased the need for additional masters-level practitioners and doctoral-level academicians and clinical directors. Based on these needs, the University of Nebraska Medical Center's (UNMC) Munroe-Meyer Institute has developed a PhD program. The academic structure at UNMC allowed us to create our PhD program in a relatively quick and efficient manner. Our PhD program has many unique features, including (a) close integration of didactic instruction with clinical and research training provided by leading experts in ABA in which students immediately apply concepts introduced in the classroom during coordinated clinical and research practica; (b) structured grant writing training in which students learn to write and submit an NIH-level grant; (c) financial support in the form of a stipend of $23,400 per year, free health benefits, and a full-tuition waiver for up to 12 credits per semester for UNMC courses (a benefits package worth approximately $50,000 per year for an out-of-state student); and (d) encouragement and financial support to present papers at local, regional, and national behavior analysis conferences.

Thinking and practice of accelerating transformation of traditional Chinese medicine from experience medicine to evidence-based medicine.

PubMed

Liu, Baoyan; Zhang, Yanhong; Hu, Jingqing; He, Liyun; Zhou, Xuezhong

2011-06-01

The gradual development of Chinese medicine is based on constant accumulation and summary of experience in clinical practice, but without the benefit of undergoing the experimental medicine stage. Although Chinese medicine has formed a systematic and unique theory system through thousands of years, with the development of evidence-based medicine, the bondage of the research methods of experience medicine to Chinese medicine is appearing. The rapid transition and transformation from experience medicine to evidence-based medicine have become important content in the development of Chinese medicine. According to the features of Chinese medicine, we propose the research idea of "taking two ways simultaneously," which is the study both in the ideal condition and in the real world. Analyzing and constructing the theoretical basis and methodology of clinical research in the real world, and building the stage for research technique is key to the effective clinical research of Chinese medicine. Only by gradually maturing and completing the clinical research methods of the real world could we realize "taking two ways simultaneously" and complementing each other, continuously produce scientific and reliable evidence of Chinese medicine, as well as transform and develop Chinese medicine from experience medicine to evidence-based medicine.

Full-Text Searching on Major Supermarket Systems: Dialog, Data-Star, and Nexis.

ERIC Educational Resources Information Center

Tenopir, Carol; Berglund, Sharon

1993-01-01

Examines the similarities, differences, and full-text features of the three most-used online systems for full-text searching in general libraries: DIALOG, Data-Star, and NEXIS. Overlapping databases, unique sources, search features, proximity operators, set building, language enhancement and word equivalencies, and display features are discussed.…

Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase.

PubMed

Huang, Wei-Sheng; Liu, Shuangying; Zou, Dong; Thomas, Mathew; Wang, Yihan; Zhou, Tianjun; Romero, Jan; Kohlmann, Anna; Li, Feng; Qi, Jiwei; Cai, Lisi; Dwight, Timothy A; Xu, Yongjin; Xu, Rongsong; Dodd, Rory; Toms, Angela; Parillon, Lois; Lu, Xiaohui; Anjum, Rana; Zhang, Sen; Wang, Frank; Keats, Jeffrey; Wardwell, Scott D; Ning, Yaoyu; Xu, Qihong; Moran, Lauren E; Mohemmad, Qurish K; Jang, Hyun Gyung; Clackson, Tim; Narasimhan, Narayana I; Rivera, Victor M; Zhu, Xiaotian; Dalgarno, David; Shakespeare, William C

2016-05-26

In the treatment of echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase positive (ALK+) non-small-cell lung cancer (NSCLC), secondary mutations within the ALK kinase domain have emerged as a major resistance mechanism to both first- and second-generation ALK inhibitors. This report describes the design and synthesis of a series of 2,4-diarylaminopyrimidine-based potent and selective ALK inhibitors culminating in identification of the investigational clinical candidate brigatinib. A unique structural feature of brigatinib is a phosphine oxide, an overlooked but novel hydrogen-bond acceptor that drives potency and selectivity in addition to favorable ADME properties. Brigatinib displayed low nanomolar IC50s against native ALK and all tested clinically relevant ALK mutants in both enzyme-based biochemical and cell-based viability assays and demonstrated efficacy in multiple ALK+ xenografts in mice, including Karpas-299 (anaplastic large-cell lymphomas [ALCL]) and H3122 (NSCLC). Brigatinib represents the most clinically advanced phosphine oxide-containing drug candidate to date and is currently being evaluated in a global phase 2 registration trial.

Photonanomedicine: a convergence of photodynamic therapy and nanotechnology

NASA Astrophysics Data System (ADS)

Obaid, Girgis; Broekgaarden, Mans; Bulin, Anne-Laure; Huang, Huang-Chiao; Kuriakose, Jerrin; Liu, Joyce; Hasan, Tayyaba

2016-06-01

As clinical nanomedicine has emerged over the past two decades, phototherapeutic advancements using nanotechnology have also evolved and impacted disease management. Because of unique features attributable to the light activation process of molecules, photonanomedicine (PNM) holds significant promise as a personalized, image-guided therapeutic approach for cancer and non-cancer pathologies. The convergence of advanced photochemical therapies such as photodynamic therapy (PDT) and imaging modalities with sophisticated nanotechnologies is enabling the ongoing evolution of fundamental PNM formulations, such as Visudyne®, into progressive forward-looking platforms that integrate theranostics (therapeutics and diagnostics), molecular selectivity, the spatiotemporally controlled release of synergistic therapeutics, along with regulated, sustained drug dosing. Considering that the envisioned goal of these integrated platforms is proving to be realistic, this review will discuss how PNM has evolved over the years as a preclinical and clinical amalgamation of nanotechnology with PDT. The encouraging investigations that emphasize the potent synergy between photochemistry and nanotherapeutics, in addition to the growing realization of the value of these multi-faceted theranostic nanoplatforms, will assist in driving PNM formulations into mainstream oncological clinical practice as a necessary tool in the medical armamentarium.

The somatic POLE P286R mutation defines a unique subclass of colorectal cancer featuring hypermutation, representing a potential genomic biomarker for immunotherapy

PubMed Central

Kim, Jihun; Kim, Deokhoon; Chun, Sung-Min; Kim, Jiyun; Kim, Tae Won; Park, Inja; Yu, Chang-Sik; Jang, Se Jin

2016-01-01

Early-onset colorectal cancers (EOCRCs) may have biological or genomic features distinct from late-onset CRCs (LOCRCs). Previous studies have mostly focused on the germline predisposition conditions of EOCRCs, but we hypothesized that EOCRCs may have distinct somatic aberrations that accelerate cancer development. To identify the somatic aberrations that accelerate cancer development at an early age, we conducted whole exome sequencing for 28 polyposis-unrelated, microsatellite stable (MSS) EOCRCs with no known germline predisposition conditions. Surprisingly, we found two distinct groups in the context of mutational burden: 6 hypermutated cases with 2325 to 10973 mutations and 22 nonhypermutated cases with 47 to 154 mutations. Further analysis revealed that four of the six hypermutated cases had the same POLE P286R mutation. We validated this finding in 83 MSS EOCRCs and 27 MSS LOCRCs, which revealed that 7.2% of EOCRCs (6/83) had the POLE P286R mutation, which was not found in LOCRCs. Clinicopathologically, EOCRCs with POLE mutations occurred far more frequently in the right colon than in the left colon, affecting men more frequently than women. In summary, we have identified a unique subclass of colon cancer characterized by a hypermutation associated with the POLE mutation. The acquisition of the POLE mutation leading to hypermutation can accelerate cancer development. Clinically, this subset with hypermutation may be susceptible to immune checkpoint blockade. PMID:27612425

Iconography in Bradshaw rock art: breaking the circularity.

PubMed

Pettigrew, Jack

2011-09-01

Interpreting the symbols found in the rock art of an extinct culture is hampered by the fact that such symbols are culturally determined. How does one break the circularity inherent in the fact that the knowledge of both the symbols and the culture comes from the same source? In this study, the circularity is broken for the Bradshaw rock art of the Kimberley by seeking anchors from outside the culture. Bradshaw rock art in the Kimberley region of Australia and Sandawe rock art in the Kolo region of Eastern Tanzania were surveyed in six visits on foot, by vehicle, by helicopter and from published or shared images, as well as from the published and online images of Khoisan rock art. Uniquely shared images between Bradshaw and Sandawe art, such as the 'mushroom head' symbol of psilocybin use, link the two cultures and indicate that they were shamanistic. Therefore, many mysterious features in the art can be understood in terms of trance visualisations. A number of other features uniquely link Bradshaw and Sandawe cultures, such as a special affinity for small mammals. There are also many references to baobabs in early Bradshaw art but not later. This can be explained in the context of the Toba super-volcano, the likely human transport of baobabs to the Kimberley and the extraordinary utility of the baobab. Many more mysterious symbols in Bradshaw rock art might await interpretation using the approaches adopted here. © 2011 The Author. Clinical and Experimental Optometry © 2011 Optometrists Association Australia.

Searching CINAHL did not add value to clinical questions posed in NICE guidelines.

PubMed

Beckles, Zosia; Glover, Sarah; Ashe, Joanna; Stockton, Sarah; Boynton, Janette; Lai, Rosalind; Alderson, Philip

2013-09-01

This study aims to quantify the unique useful yield from the Cumulative Index to Nursing and Allied Health Literature (CINAHL) database to National Institute for Health and Clinical Excellence (NICE) clinical guidelines. A secondary objective is to investigate the relationship between this yield and different clinical question types. It is hypothesized that the unique useful yield from CINAHL is low, and this database can therefore be relegated to selective rather than routine searching. A retrospective sample of 15 NICE guidelines published between 2005 and 2009 was taken. Information on clinical review question type, number of references, and reference source was extracted. Only 0.33% (95% confidence interval: 0.01-0.64%) of references per guideline were unique to CINAHL. Nursing- or allied health (AH)-related questions were nearly three times as likely to have references unique to CINAHL as non-nursing- or AH-related questions (14.89% vs. 5.11%), and this relationship was found to be significant (P<0.05). No significant relationship was found between question type and unique CINAHL yield for drug-related questions. The very low proportion of references unique to CINAHL strongly suggests that this database can be safely relegated to selective rather than routine searching. Nursing- and AH-related questions would benefit from selective searching of CINAHL. Copyright © 2013 Elsevier Inc. All rights reserved.

Dementia in the Oldest Old

PubMed Central

Bullain, Szófia S.; Corrada, María M.

2013-01-01

Purpose of Review: This article discusses some of the unique features of dementia in the oldest old, including some of the most common diagnostic challenges, and potential strategies to overcome them. Recent Findings: Advances include new insight into the role of common risk factors and the effects of multiple underlying neuropathologic features for dementia in the oldest old. In addition, this article contains the latest age-specific normative data for commonly used neuropsychological tests for the oldest old. Summary: The oldest old—people aged 90 years and older—are the fastest-growing segment of society and have the highest rates of dementia in the population. The risk factors, diagnostic challenges, and underlying neuropathologic features of dementia are strikingly different in the 90-years-and-older population compared to younger elderly. Special consideration of these unique features of dementia is necessary when evaluating oldest-old subjects with cognitive impairment. PMID:23558489

Radiation biology of HZE particles

NASA Technical Reports Server (NTRS)

Nelson, Gregory A.

1990-01-01

The biological effects of heavy charged particle (HZE) radiation are of particular interest to travellers and planners for long duration space flights where exposure levels represent a potential health hazard. The unique feature of HZE radiation is the structured pattern of its energy deposition in targets which may be related to charge, velocity, or rate of energy loss. There are many consequences of this feature to biological endpoints when compared to effects of ionizing photons. Dose vs response and dose rate kinetics are modified, DNA and cellular repair systems are altered in their abilities to cope with damage and, the qualitative features of damage are unique for different ions. These features must be incorporated into any risk assessment system for radiation health management. HZE induced mutation, cell inactivation and altered organogenesis will be discussed emphasizing studies with the nematode Caenorhabditis elegans and cultured cells. Observations from radiobiology experiments in space will also be reviewed along with plans for future space-based studies.

[Bdellovibrio and like organisms: outstanding predators!

PubMed

Jurkevitch, Édouard; Jacquet, Stéphan

2017-05-01

Obligate predatory bacteria, i.e. bacteria requiring a Gram negative prey cell in order to complete their cell cycle, belong to the polyphyletic group referred to as the Bdellovibrio And Like Organisms (BALO). Predatory interactions between bacteria are complex, yet their dynamics and impact on bacterial communities in the environment are becoming better understood. BALO have unique life cycles: they grow epibiotically with the predator remaining attached to the prey's envelope, dividing in a binary manner or periplasmically, i.e. by penetrating the prey's periplasm to generate a number of progeny cells. The periplasmic life cycle includes unique gene and protein patterns and unique signaling features. These ecological and cellular features, along with applications of the BALO in the medical, agricultural and environmental fields are surveyed. © 2017 médecine/sciences – Inserm.

Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images.

PubMed

Guo, Shengwen; Lai, Chunren; Wu, Congling; Cen, Guiyin

2017-01-01

Neuroimaging measurements derived from magnetic resonance imaging provide important information required for detecting changes related to the progression of mild cognitive impairment (MCI). Cortical features and changes play a crucial role in revealing unique anatomical patterns of brain regions, and further differentiate MCI patients from normal states. Four cortical features, namely, gray matter volume, cortical thickness, surface area, and mean curvature, were explored for discriminative analysis among three groups including the stable MCI (sMCI), the converted MCI (cMCI), and the normal control (NC) groups. In this study, 158 subjects (72 NC, 46 sMCI, and 40 cMCI) were selected from the Alzheimer's Disease Neuroimaging Initiative. A sparse-constrained regression model based on the l2-1-norm was introduced to reduce the feature dimensionality and retrieve essential features for the discrimination of the three groups by using a support vector machine (SVM). An optimized strategy of feature addition based on the weight of each feature was adopted for the SVM classifier in order to achieve the best classification performance. The baseline cortical features combined with the longitudinal measurements for 2 years of follow-up data yielded prominent classification results. In particular, the cortical thickness produced a classification with 98.84% accuracy, 97.5% sensitivity, and 100% specificity for the sMCI-cMCI comparison; 92.37% accuracy, 84.78% sensitivity, and 97.22% specificity for the cMCI-NC comparison; and 93.75% accuracy, 92.5% sensitivity, and 94.44% specificity for the sMCI-NC comparison. The best performances obtained by the SVM classifier using the essential features were 5-40% more than those using all of the retained features. The feasibility of the cortical features for the recognition of anatomical patterns was certified; thus, the proposed method has the potential to improve the clinical diagnosis of sub-types of MCI and predict the risk of its conversion to Alzheimer's disease.

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.

Clinical implications of chromosomal abnormalities in gastric adenocarcinomas

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

Wu, Chew-Wun; Chen, Gen-Der; Fann, Cathy S.-J.

2003-06-23

Gastric carcinoma (GC) is one of the most common malignancies worldwide and has a very poor prognosis. Genetic imbalances in 62 primary gastric adenocarcinomas of various histopathologic types and pathologic stages and six gastric cancer-derived cell lines were analyzed by comparative genomic hybridization, and the relationship of genomic abnormalities to clinical features in primary GC was evaluated at a genome-wide level. Eighty-four percent of the tumors and all six cell lines showed DNA copy number changes. The recurrent chromosomal abnormalities including gains at 15 regions and losses at 8 regions were identified. Statistical analyses revealed that gains at 17q24-qter (53more » percent), 20q13-qter (48 percent), 1p32-p36 (42 percent), 22q12-qter (27 percent), 17p13-pter (24 percent), 16p13-pter (21 percent), 6p21-pter (19 percent), 20p12-pter (19 percent), 7p21-pter (18 percent), 3q28-qter (8 percent), and 13q13-q14 (8 percent), and losses at 18q12-qter (11 percent), 3p12 (8 percent), 3p25-pter (8 percent), 5q14-q23 (8 percent), and 9p21-p23 (5 percent), are associated with unique patient or tumor-related features. GCs of differing histopathologic features were shown to be associated with distinct patterns of genetic alterations, supporting the notion that they evolve through distinct genetic pathways. Metastatic tumors were also associated with specific genetic changes. These regions may harbor candidate genes involved in the pathogenesis of this malignancy.« less

Gut microbial profile analysis by MiSeq sequencing of pancreatic carcinoma patients in China

PubMed Central

Xie, Haiyang; Li, Ang; Lu, Haifeng; Xu, Shaoyan; Zhou, Lin; Zhang, Hua; Cui, Guangying; Chen, Xinhua; Liu, Yuanxing; Wu, Liming; Qin, Nan; Sun, Ranran; Wang, Wei; Li, Lanjuan; Wang, Weilin; Zheng, Shusen

2017-01-01

Pancreatic carcinoma (PC) is a lethal cancer. Gut microbiota is associated with some risk factors of PC, e.g. obesity and types II diabetes. However, the specific gut microbial profile in clinical PC in China has never been reported. This prospective study collected 85 PC and 57 matched healthy controls (HC) to analyze microbial characteristics by MiSeq sequencing. The results showed that gut microbial diversity was decreased in PC with an unique microbial profile, which partly attributed to its decrease of alpha diversity. Microbial alterations in PC featured by the increase of certain pathogens and lipopolysaccharides-producing bacteria, and the decrease of probiotics and butyrate-producing bacteria. Microbial community in obstruction cases was separated from the un-obstructed cases. Streptococcus was associated with the bile. Furthermore, 23 microbial functions e.g. Leucine and LPS biosynthesis were enriched, while 13 functions were reduced in PC. Importantly, based on 40 genera associated with PC, microbial markers achieves a high classification power with AUC of 0.842. In conclusion, gut microbial profile was unique in PC, providing a microbial marker for non-invasive PC diagnosis. PMID:29221120

Urogenital tuberculosis: definition and classification.

PubMed

Kulchavenya, Ekaterina

2014-10-01

To improve the approach to the diagnosis and management of urogenital tuberculosis (UGTB), we need clear and unique classification. UGTB remains an important problem, especially in developing countries, but it is often an overlooked disease. As with any other infection, UGTB should be cured by antibacterial therapy, but because of late diagnosis it may often require surgery. Scientific literature dedicated to this problem was critically analyzed and juxtaposed with the author's own more than 30 years' experience in tuberculosis urology. The conception, terms and definition were consolidated into one system; classification stage by stage as well as complications are presented. Classification of any disease includes dispersion on forms and stages and exact definitions for each stage. Clinical features and symptoms significantly vary between different forms and stages of UGTB. A simple diagnostic algorithm was constructed. UGTB is multivariant disease and a standard unified approach to it is impossible. Clear definition as well as unique classification are necessary for real estimation of epidemiology and the optimization of therapy. The term 'UGTB' has insufficient information in order to estimate therapy, surgery and prognosis, or to evaluate the epidemiology.

Pancreatic Lipomatous Hamartoma: A Hitherto Unrecognized Variant.

PubMed

Tanaka, Mariko; Ushiku, Tetsuo; Ikemura, Masako; Takazawa, Yutaka; Igari, Toru; Shimizu, Michio; Yamaguchi, Hiroshi; Fukushima, Noriyoshi; Sakuma, Kei; Arita, Junichi; Sakamoto, Yoshihiro; Hasegawa, Kiyoshi; Watadani, Takeyuki; Nakai, Yousuke; Koike, Kazuhiko; Fukayama, Masashi

2018-05-04

Pancreatic masses consisting of lipomatous components clinically include lipoma, liposarcoma, lipomatous pseudohypertrophy of the pancreas, fat-containing neoplasms such as perivascular epithelioid cell tumor, and malignant neoplasm with lipoid degeneration. We present pancreatic lipomatous hamartoma, which has not been reported hitherto. A solid pancreatic mass was detected from a computed tomographic scan check-up in each of 3 cases of Japanese men. Macroscopically, well-demarcated solid lipomatous masses were detected at the uncus, body, and tail of the pancreas, respectively. Microscopically, the masses predominantly consisted of mature adipocytes with no atypia, but contained characteristics components of pancreatic hamartoma, such as small ducts, a well-preserved acinar structure, and/or fibrous stroma. On the basis of the unique features, lack of islets and absence of periductal elastic fibers, these tumors are a distinct variant of pancreatic hamartoma. Furthermore, high-mobility group AT-hook 2 expression in the fibro-adipocytes of this tumor indicated that these cells are an integral component of the pancreatic lipomatous hamartoma. Consequently, the unique tumors described herein are pancreatic lipomatous hamartoma, which must be discriminated from other lipomatous lesions of the pancreas.

Trauma Associated Sleep Disorder: A Proposed Parasomnia Encompassing Disruptive Nocturnal Behaviors, Nightmares, and REM without Atonia in Trauma Survivors

PubMed Central

Mysliwiec, Vincent; O'Reilly, Brian; Polchinski, Jason; Kwon, Herbert P.; Germain, Anne; Roth, Bernard J.

2014-01-01

Study Objectives: To characterize the clinical, polysomnographic and treatment responses of patients with disruptive nocturnal behaviors (DNB) and nightmares following traumatic experiences. Methods: A case series of four young male, active duty U.S. Army Soldiers who presented with DNB and trauma related nightmares. Patients underwent a clinical evaluation in a sleep medicine clinic, attended overnight polysomnogram (PSG) and received treatment. We report pertinent clinical and PSG findings from our patients and review prior literature on sleep disturbances in trauma survivors. Results: DNB ranged from vocalizations, somnambulism to combative behaviors that injured bed partners. Nightmares were replays of the patient's traumatic experiences. All patients had REM without atonia during polysomnography; one patient had DNB and a nightmare captured during REM sleep. Prazosin improved DNB and nightmares in all patients. Conclusions: We propose Trauma associated Sleep Disorder (TSD) as a unique sleep disorder encompassing the clinical features, PSG findings, and treatment responses of patients with DNB, nightmares, and REM without atonia after trauma. Citation: Mysliwiec V, O'Reilly B, Polchinski J, Kwon HP, Germain A, Roth BJ. Trauma associated sleep disorder: a proposed parasomnia encompassing disruptive nocturnal behaviors, nightmares, and REM without atonia in trauma survivors. J Clin Sleep Med 2014;10(10):1143-1148. PMID:25317096

Moving oncolytic viruses into the clinic: clinical-grade production, purification, and characterization of diverse oncolytic viruses.

PubMed

Ungerechts, Guy; Bossow, Sascha; Leuchs, Barbara; Holm, Per S; Rommelaere, Jean; Coffey, Matt; Coffin, Rob; Bell, John; Nettelbeck, Dirk M

2016-01-01

Oncolytic viruses (OVs) are unique anticancer agents based on their pleotropic modes of action, which include, besides viral tumor cell lysis, activation of antitumor immunity. A panel of diverse viruses, often genetically engineered, has advanced to clinical investigation, including phase 3 studies. This diversity of virotherapeutics not only offers interesting opportunities for the implementation of different therapeutic regimens but also poses challenges for clinical translation. Thus, manufacturing processes and regulatory approval paths need to be established for each OV individually. This review provides an overview of clinical-grade manufacturing procedures for OVs using six virus families as examples, and key challenges are discussed individually. For example, different virus features with respect to particle size, presence/absence of an envelope, and host species imply specific requirements for measures to ensure sterility, for handling, and for determination of appropriate animal models for toxicity testing, respectively. On the other hand, optimization of serum-free culture conditions, increasing virus yields, development of scalable purification strategies, and formulations guaranteeing long-term stability are challenges common to several if not all OVs. In light of the recent marketing approval of the first OV in the Western world, strategies for further upscaling OV manufacturing and optimizing product characterization will receive increasing attention.

Moving oncolytic viruses into the clinic: clinical-grade production, purification, and characterization of diverse oncolytic viruses

PubMed Central

Ungerechts, Guy; Bossow, Sascha; Leuchs, Barbara; Holm, Per S; Rommelaere, Jean; Coffey, Matt; Coffin, Rob; Bell, John; Nettelbeck, Dirk M

2016-01-01

Oncolytic viruses (OVs) are unique anticancer agents based on their pleotropic modes of action, which include, besides viral tumor cell lysis, activation of antitumor immunity. A panel of diverse viruses, often genetically engineered, has advanced to clinical investigation, including phase 3 studies. This diversity of virotherapeutics not only offers interesting opportunities for the implementation of different therapeutic regimens but also poses challenges for clinical translation. Thus, manufacturing processes and regulatory approval paths need to be established for each OV individually. This review provides an overview of clinical-grade manufacturing procedures for OVs using six virus families as examples, and key challenges are discussed individually. For example, different virus features with respect to particle size, presence/absence of an envelope, and host species imply specific requirements for measures to ensure sterility, for handling, and for determination of appropriate animal models for toxicity testing, respectively. On the other hand, optimization of serum-free culture conditions, increasing virus yields, development of scalable purification strategies, and formulations guaranteeing long-term stability are challenges common to several if not all OVs. In light of the recent marketing approval of the first OV in the Western world, strategies for further upscaling OV manufacturing and optimizing product characterization will receive increasing attention. PMID:27088104

Managing and Communicating Operational Workflow: Designing and Implementing an Electronic Outpatient Whiteboard.

PubMed

Steitz, Bryan D; Weinberg, Stuart T; Danciu, Ioana; Unertl, Kim M

2016-01-01

Healthcare team members in emergency department contexts have used electronic whiteboard solutions to help manage operational workflow for many years. Ambulatory clinic settings have highly complex operational workflow, but are still limited in electronic assistance to communicate and coordinate work activities. To describe and discuss the design, implementation, use, and ongoing evolution of a coordination and collaboration tool supporting ambulatory clinic operational workflow at Vanderbilt University Medical Center (VUMC). The outpatient whiteboard tool was initially designed to support healthcare work related to an electronic chemotherapy order-entry application. After a highly successful initial implementation in an oncology context, a high demand emerged across the organization for the outpatient whiteboard implementation. Over the past 10 years, developers have followed an iterative user-centered design process to evolve the tool. The electronic outpatient whiteboard system supports 194 separate whiteboards and is accessed by over 2800 distinct users on a typical day. Clinics can configure their whiteboards to support unique workflow elements. Since initial release, features such as immunization clinical decision support have been integrated into the system, based on requests from end users. The success of the electronic outpatient whiteboard demonstrates the usefulness of an operational workflow tool within the ambulatory clinic setting. Operational workflow tools can play a significant role in supporting coordination, collaboration, and teamwork in ambulatory healthcare settings.

Seafloor massive sulfide deposits support unique megafaunal assemblages: Implications for seabed mining and conservation.

PubMed

Boschen, Rachel E; Rowden, Ashley A; Clark, Malcolm R; Pallentin, Arne; Gardner, Jonathan P A

2016-04-01

Mining of seafloor massive sulfides (SMS) is imminent, but the ecology of assemblages at SMS deposits is poorly known. Proposed conservation strategies include protected areas to preserve biodiversity at risk from mining impacts. Determining site suitability requires biological characterisation of the mine site and protected area(s). Video survey of a proposed mine site and protected area off New Zealand revealed unique megafaunal assemblages at the mine site. Significant relationships were identified between assemblage structure and environmental conditions, including hydrothermal features. Unique assemblages occurred at both active and inactive chimneys and are particularly at risk from mining-related impacts. The occurrence of unique assemblages at the mine site suggests that the proposed protected area is insufficient alone and should instead form part of a network. These results provide support for including hydrothermally active and inactive features within networks of protected areas and emphasise the need for quantitative survey data of proposed sites. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Indocyanine Green Fluorescence for Free-Flap Perfusion Imaging Revisited: Advanced Decision Making by Virtual Perfusion Reality in Visionsense Fusion Imaging Angiography.

PubMed

Bigdeli, Amir Khosrow; Gazyakan, Emre; Schmidt, Volker Juergen; Hernekamp, Frederick Jochen; Harhaus, Leila; Henzler, Thomas; Kremer, Thomas; Kneser, Ulrich; Hirche, Christoph

2016-06-01

Near-infrared indocyanine green video angiography (ICG-NIR-VA) has been introduced for free-flap surgery and may provide intraoperative flap designing as well as postoperative monitoring. Nevertheless, the technique has not been established in clinical routine because of controversy over benefits. Improved technical features of the novel Visionsense ICG-NIR-VA surgery system are promising to revisit the field of application. It features a unique real-time fusion image of simultaneous NIR and white light visualization, with highlighted perfusion, including a color-coded perfusion flow scale for optimized anatomical understanding. In a feasibility study, the Visionsense ICG-NIR-VA system was applied during 10 free-flap surgeries in 8 patients at our center. Indications included anterior lateral thigh (ALT) flap (n = 4), latissimus dorsi muscle flap (n = 1), tensor fascia latae flap (n = 1), and two bilateral deep inferior epigastric artery perforator flaps (n = 4). The system was used intraoperatively and postoperatively to investigate its impact on surgical decision making and to observe perfusion patterns correlated to clinical monitoring. Visionsense ICG-NIR-VA aided assessing free-flap design and perfusion patterns in all cases and correlated with clinical observations. Additional interventions were performed in 2 cases (22%). One venous anastomosis was revised, and 1 flap was redesigned. Indicated by ICG-NIR-VA, 1 ALT flap developed partial flap necrosis (11%). The Visionsense ICG-NIR-VA system allowed a virtual view of flap perfusion anatomy by fusion imaging in real-time. The system improved decision making for flap design and surgical decisions. Clinical and ICG-NIR-VA parameters correlated. Its future implementation may aid in improving outcomes for free-flap surgery, but additional experience is needed to define its final role. © The Author(s) 2015.

Development of a diabetes care management curriculum in a family practice residency program.

PubMed

Nuovo, Jim; Balsbaugh, Thomas; Barton, Sue; Davidson, Ellen; Fox-Garcia, Jane; Gandolfo, Angela; Levich, Bridget; Seibles, Joann

2004-01-01

Improving the quality of care for patients with chronic illness has become a high priority. Implementing training programs in disease management (DM) so the next generation of physicians can manage chronic illness more effectively is challenging. Residency training programs have no specific mandate to implement DM training. Additional barriers at the training facility include: 1) lack of a population-based perspective for service delivery; 2) weak support for self-management of illness; 3) incomplete implementation due to physician resistance or inertia; and 4) few incentives to change practices and behaviors. In order to overcome these barriers, training programs must take the initiative to implement DM training that addresses each of these issues. We report the implementation of a chronic illness management curriculum based on the Improving Chronic Illness Care (ICIC) Model. Features of this process included both patient care and learner objectives. These were: development of a multidisciplinary diabetes DM team; development of a patient registry; development of diabetes teaching clinics in the family practice center (nutrition, general management classes, and one-on-one teaching); development of a group visit model; and training the residents in the elements of the ICIC Model, ie, the community, the health system, self-management support, delivery system design, decision support, and clinical information systems. Barriers to implementing these curricular changes were: the development of a patient registry; buy-in from faculty, residents, clinic leadership, staff, and patients for the chronic care model; the ability to bill for services and maintain clinical productivity; and support from the health system key stakeholders for sustainability. Unique features of each training site will dictate differences in emphasis and structure; however, the core principles of the ICIC Model in enhancing self-management may be generalized to all sites.

What is "grazing"? Reviewing its definition, frequency, clinical characteristics, and impact on bariatric surgery outcomes, and proposing a standardized definition.

PubMed

Conceição, Eva M; Mitchell, James E; Engel, Scott G; Machado, Paulo P P; Lancaster, Kathryn; Wonderlich, Stephen A

2014-01-01

Grazing, characterized by a repetitive eating pattern, has received increased attention among bariatric surgery patients. However, different definitions and terminology have been used, preventing the accurate measurement of this phenomenon and comparison of data across studies. To review existing definitions and associated clinical features of grazing among different samples and to propose a standardized definition that will allow for consistency in future work. University and Clinical Research Institute. Of the 39 studies found, 9 provided an original definition and 12 provided data of its association with weight outcomes. Six were studies of nonbariatric surgery populations. Based on this literature review, the most common criteria used in previous studies to define grazing were included in a survey that was sent to 24 individuals who have published work in the field. These experts were asked to provide their opinion on what should constitute grazing. Grazing is a frequent behavior in the bariatric surgery population as well as in eating disordered and community samples. Its association with psychopathology is not clear, but its negative impact on weight outcomes after bariatric surgery generally has been supported. Survey data provided a consensus regarding the definition of grazing as an eating behavior characterized by the repetitive eating (more than twice) of small/modest amounts of food in an unplanned manner, with what we characterize as compulsive and noncompulsive subtypes. Given the clinical relevance of grazing among bariatric surgery patients, a unique definition is crucial to better study its associated features and impact on different populations. Copyright © 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved.

Feature Analysis of ToxCast Compounds

EPA Science Inventory

ToxCast was initiated by the US Environmental Protection Agency (EPA) to prioritize environmental chemicals for toxicity testing. Phase I generated data for 309 unique chemicals, mostly pesticide actives, that span diverse chemical feature/property space, as determined by quantu...

Gynecomastia Classification for Surgical Management: A Systematic Review and Novel Classification System.

PubMed

Waltho, Daniel; Hatchell, Alexandra; Thoma, Achilleas

2017-03-01

Gynecomastia is a common deformity of the male breast, where certain cases warrant surgical management. There are several surgical options, which vary depending on the breast characteristics. To guide surgical management, several classification systems for gynecomastia have been proposed. A systematic review was performed to (1) identify all classification systems for the surgical management of gynecomastia, and (2) determine the adequacy of these classification systems to appropriately categorize the condition for surgical decision-making. The search yielded 1012 articles, and 11 articles were included in the review. Eleven classification systems in total were ascertained, and a total of 10 unique features were identified: (1) breast size, (2) skin redundancy, (3) breast ptosis, (4) tissue predominance, (5) upper abdominal laxity, (6) breast tuberosity, (7) nipple malposition, (8) chest shape, (9) absence of sternal notch, and (10) breast skin elasticity. On average, classification systems included two or three of these features. Breast size and ptosis were the most commonly included features. Based on their review of the current classification systems, the authors believe the ideal classification system should be universal and cater to all causes of gynecomastia; be surgically useful and easy to use; and should include a comprehensive set of clinically appropriate patient-related features, such as breast size, breast ptosis, tissue predominance, and skin redundancy. None of the current classification systems appears to fulfill these criteria.

Gas Turbine Engine with Air/Fuel Heat Exchanger

NASA Technical Reports Server (NTRS)

Krautheim, Michael Stephen (Inventor); Chouinard, Donald G. (Inventor); Donovan, Eric Sean (Inventor); Karam, Michael Abraham (Inventor); Vetters, Daniel Kent (Inventor)

2017-01-01

One embodiment of the present invention is a unique aircraft propulsion gas turbine engine. Another embodiment is a unique gas turbine engine. Another embodiment is a unique gas turbine engine. Other embodiments include apparatuses, systems, devices, hardware, methods, and combinations for gas turbine engines with heat exchange systems. Further embodiments, forms, features, aspects, benefits, and advantages of the present application will become apparent from the description and figures provided herewith.

Classification of brain tumors using texture based analysis of T1-post contrast MR scans in a preclinical model

NASA Astrophysics Data System (ADS)

Tang, Tien T.; Zawaski, Janice A.; Francis, Kathleen N.; Qutub, Amina A.; Gaber, M. Waleed

2018-02-01

Accurate diagnosis of tumor type is vital for effective treatment planning. Diagnosis relies heavily on tumor biopsies and other clinical factors. However, biopsies do not fully capture the tumor's heterogeneity due to sampling bias and are only performed if the tumor is accessible. An alternative approach is to use features derived from routine diagnostic imaging such as magnetic resonance (MR) imaging. In this study we aim to establish the use of quantitative image features to classify brain tumors and extend the use of MR images beyond tumor detection and localization. To control for interscanner, acquisition and reconstruction protocol variations, the established workflow was performed in a preclinical model. Using glioma (U87 and GL261) and medulloblastoma (Daoy) models, T1-weighted post contrast scans were acquired at different time points post-implant. The tumor regions at the center, middle, and peripheral were analyzed using in-house software to extract 32 different image features consisting of first and second order features. The extracted features were used to construct a decision tree, which could predict tumor type with 10-fold cross-validation. Results from the final classification model demonstrated that middle tumor region had the highest overall accuracy at 79%, while the AUC accuracy was over 90% for GL261 and U87 tumors. Our analysis further identified image features that were unique to certain tumor region, although GL261 tumors were more homogenous with no significant differences between the central and peripheral tumor regions. In conclusion our study shows that texture features derived from MR scans can be used to classify tumor type with high success rates. Furthermore, the algorithm we have developed can be implemented with any imaging datasets and may be applicable to multiple tumor types to determine diagnosis.

Profiling of Intracellular Metabolites: An Approach to Understanding the Characteristic Physiology of Mycobacterium leprae

PubMed Central

Miyamoto, Yuji; Mukai, Tetsu; Matsuoka, Masanori; Kai, Masanori; Maeda, Yumi; Makino, Masahiko

2016-01-01

Mycobacterium leprae is the causative agent of leprosy and also known to possess unique features such as inability to proliferate in vitro. Among the cellular components of M. leprae, various glycolipids present on the cell envelope are well characterized and some of them are identified to be pathogenic factors responsible for intracellular survival in host cells, while other intracellular metabolites, assumed to be associated with basic physiological feature, remain largely unknown. In the present study, to elucidate the comprehensive profile of intracellular metabolites, we performed the capillary electrophoresis-mass spectrometry (CE-MS) analysis on M. leprae and compared to that of M. bovis BCG. Interestingly, comparison of these two profiles showed that, in M. leprae, amino acids and their derivatives are significantly accumulated, but most of intermediates related to central carbon metabolism markedly decreased, implying that M. leprae possess unique metabolic features. The present study is the first report demonstrating the unique profiles of M. leprae metabolites and these insights might contribute to understanding undefined metabolism of M. leprae as well as pathogenic characteristics related to the manifestation of the disease. PMID:27479467

Profiling of Intracellular Metabolites: An Approach to Understanding the Characteristic Physiology of Mycobacterium leprae.

PubMed

Miyamoto, Yuji; Mukai, Tetsu; Matsuoka, Masanori; Kai, Masanori; Maeda, Yumi; Makino, Masahiko

2016-08-01

Mycobacterium leprae is the causative agent of leprosy and also known to possess unique features such as inability to proliferate in vitro. Among the cellular components of M. leprae, various glycolipids present on the cell envelope are well characterized and some of them are identified to be pathogenic factors responsible for intracellular survival in host cells, while other intracellular metabolites, assumed to be associated with basic physiological feature, remain largely unknown. In the present study, to elucidate the comprehensive profile of intracellular metabolites, we performed the capillary electrophoresis-mass spectrometry (CE-MS) analysis on M. leprae and compared to that of M. bovis BCG. Interestingly, comparison of these two profiles showed that, in M. leprae, amino acids and their derivatives are significantly accumulated, but most of intermediates related to central carbon metabolism markedly decreased, implying that M. leprae possess unique metabolic features. The present study is the first report demonstrating the unique profiles of M. leprae metabolites and these insights might contribute to understanding undefined metabolism of M. leprae as well as pathogenic characteristics related to the manifestation of the disease.

Feasibility of feature-based indexing, clustering, and search of clinical trials: A case study of breast cancer trials from ClinicalTrials.gov

PubMed Central

Boland, Mary Regina; Miotto, Riccardo; Gao, Junfeng; Weng, Chunhua

2013-01-01

Summary Background When standard therapies fail, clinical trials provide experimental treatment opportunities for patients with drug-resistant illnesses or terminal diseases. Clinical Trials can also provide free treatment and education for individuals who otherwise may not have access to such care. To find relevant clinical trials, patients often search online; however, they often encounter a significant barrier due to the large number of trials and in-effective indexing methods for reducing the trial search space. Objectives This study explores the feasibility of feature-based indexing, clustering, and search of clinical trials and informs designs to automate these processes. Methods We decomposed 80 randomly selected stage III breast cancer clinical trials into a vector of eligibility features, which were organized into a hierarchy. We clustered trials based on their eligibility feature similarities. In a simulated search process, manually selected features were used to generate specific eligibility questions to filter trials iteratively. Results We extracted 1,437 distinct eligibility features and achieved an inter-rater agreement of 0.73 for feature extraction for 37 frequent features occurring in more than 20 trials. Using all the 1,437 features we stratified the 80 trials into six clusters containing trials recruiting similar patients by patient-characteristic features, five clusters by disease-characteristic features, and two clusters by mixed features. Most of the features were mapped to one or more Unified Medical Language System (UMLS) concepts, demonstrating the utility of named entity recognition prior to mapping with the UMLS for automatic feature extraction. Conclusions It is feasible to develop feature-based indexing and clustering methods for clinical trials to identify trials with similar target populations and to improve trial search efficiency. PMID:23666475

Feasibility of feature-based indexing, clustering, and search of clinical trials. A case study of breast cancer trials from ClinicalTrials.gov.

PubMed

Boland, M R; Miotto, R; Gao, J; Weng, C

2013-01-01

When standard therapies fail, clinical trials provide experimental treatment opportunities for patients with drug-resistant illnesses or terminal diseases. Clinical Trials can also provide free treatment and education for individuals who otherwise may not have access to such care. To find relevant clinical trials, patients often search online; however, they often encounter a significant barrier due to the large number of trials and in-effective indexing methods for reducing the trial search space. This study explores the feasibility of feature-based indexing, clustering, and search of clinical trials and informs designs to automate these processes. We decomposed 80 randomly selected stage III breast cancer clinical trials into a vector of eligibility features, which were organized into a hierarchy. We clustered trials based on their eligibility feature similarities. In a simulated search process, manually selected features were used to generate specific eligibility questions to filter trials iteratively. We extracted 1,437 distinct eligibility features and achieved an inter-rater agreement of 0.73 for feature extraction for 37 frequent features occurring in more than 20 trials. Using all the 1,437 features we stratified the 80 trials into six clusters containing trials recruiting similar patients by patient-characteristic features, five clusters by disease-characteristic features, and two clusters by mixed features. Most of the features were mapped to one or more Unified Medical Language System (UMLS) concepts, demonstrating the utility of named entity recognition prior to mapping with the UMLS for automatic feature extraction. It is feasible to develop feature-based indexing and clustering methods for clinical trials to identify trials with similar target populations and to improve trial search efficiency.

Some Common and Unique Features of Special Education in the Nordic Countries.

ERIC Educational Resources Information Center

Juul, Kristen D.

1989-01-01

Similarities in special education services in the five Scandinavian countries include their normalization philosophy and cooperative policy development. Among unique Scandinavian innovations are camp schools, folk high schools, toy libraries (lekoteks), therapeutic communities or collectives for young substance abuses, and measures to combat…

[The essence of Professor Wu Lian-Zhong's acupuncture manipulation].

PubMed

Liu, Jing; Guo, Yi; Wu, Lian-Zhong

2014-05-01

The painless needle insertion technique, summarized by Professor WU Lian-zhong during his decades of acupuncture clinical practice is introduced in this article, which is characterized as soft, flexible, fast, plucking and activating antipathogenic qi. The Sancai (three layers) lifting and thrusting manipulation technique is adopted by Professor WU for getting the qi sensation. And features of 10 kinds of needling sensation such as soreness, numbness, heaviness, distension, pain, cold, hot, radiation, jumping and contracture are summarized. Finger force, amplitude, speed and time length are also taken as the basis of reinforcing and reducing manipulations. Moreover, examples are also given to explain the needling technique on some specific points which further embodies Professor WU's unique experiences and understandings on acupuncture.

Ductal Breast Carcinoma Metastatic to the Stomach Resembling Primary Linitis Plastica in a Male Patient.

PubMed

Ricciuti, Biagio; Leonardi, Giulia Costanza; Ravaioli, Noemi; De Giglio, Andrea; Brambilla, Marta; Prosperi, Enrico; Ribacchi, Franca; Meacci, Marialuisa; Crinò, Lucio; Maiettini, Daniele; Chiari, Rita; Metro, Giulio

2016-09-01

Breast cancer metastases to the gastrointestinal tract are very rare occurrences. Among the histological subtypes of breast cancer, invasive lobular carcinomas have a high capacity of metastasis to uncommon sites including the stomach. Conversely, there has not been sufficient evidence supporting the gastric metastasis of invasive ductal carcinoma. Herein, we report a unique case of metastatic ductal breast carcinoma mimicking primary linitis plastica in a male patient, particularly focusing on the clinical and pathological features of presentation. Moreover, we propose a immunohistochemical panel of selected antibodies including those for cytokeratin 20, cytokeratin 7, estrogen receptor, progesterone receptor, E-cadherin, gross cystic disease fluid protein 15, and GATA binding protein 3 for an accurate differential diagnosis.

Recurring ventriculitis due to Citrobacter diversus: clinical and bacteriologic analysis.

PubMed

Eppes, S C; Woods, C R; Mayer, A S; Klein, J D

1993-09-01

Neonatal meningitis due to Citrobacter diversus is usually accompanied by the development of brain abscesses and tends to have high rates of morbidity and mortality. We report a case of a newborn with C. diversus meningitis and brain abscesses who relapsed after initial antibiotic therapy and from whom C. diversus was recovered from cerebrospinal fluid 4 years later during a neurosurgical procedure. Genetic differences in the early and late isolates were discovered, and explanations for this phenomenon are suggested. Possible mechanisms for prolonged persistence in the central nervous system are explored. This unusual case and the analysis of the organisms illustrate the unique features of C. diversus as a pathogen and underscore the need for developing optimal therapeutic strategies.

Inflammation in renal atherosclerotic disease.

PubMed

Udani, Suneel M; Dieter, Robert S

2008-07-01

The study of renal atherosclerotic disease has conventionally focused on the diagnosis and management of renal artery stenosis. With the increased understanding of atherosclerosis as a systemic inflammatory process, there has been increased interest in vascular biology at the microvasculature level. While different organ beds share some features, the inflammation and injury in the microvasculature of the kidney has unique elements as well. Understanding of the pathogenesis yields a better understanding of the clinical manifestations of renal atherosclerotic disease, which can be very subtle. Furthermore, identifying the molecular mechanisms responsible for the progression of kidney damage can also direct clinicians and scientists toward targeted therapies. Existing therapies used to treat atherosclerotic disease in other vascular beds may also play a role in the treatment of renal atherosclerotic disease.

Multidimensional nanomaterials for the control of stem cell fate

NASA Astrophysics Data System (ADS)

Chueng, Sy-Tsong Dean; Yang, Letao; Zhang, Yixiao; Lee, Ki-Bum

2016-09-01

Current stem cell therapy suffers low efficiency in giving rise to differentiated cell lineages, which can replace the original damaged cells. Nanomaterials, on the other hand, provide unique physical size, surface chemistry, conductivity, and topographical microenvironment to regulate stem cell differentiation through multidimensional approaches to facilitate gene delivery, cell-cell, and cell-ECM interactions. In this review, nanomaterials are demonstrated to work both alone and synergistically to guide selective stem cell differentiation. From three different nanotechnology families, three approaches are shown: (1) soluble microenvironmental factors; (2) insoluble physical microenvironment; and (3) nano-topographical features. As regenerative medicine is heavily invested in effective stem cell therapy, this review is inspired to generate discussions in the potential clinical applications of multi-dimensional nanomaterials.

Improving care by understanding the way we work: human factors and behavioural science in the context of intensive care

PubMed Central

Sevdalis, Nick; Brett, Stephen J

2009-01-01

Effectiveness and efficiency of care of the critically ill patient are subject to a number of systemic influences, including skills of individual physicians/nurses (technical and non-technical), team-working in the intensive care unit (ICU), and the ICU environment. We first discuss the paper of Fackler and colleagues as a contribution to the systems approach to clinical performance in the context of intensive care. We then highlight features of care delivery that are unique to intensive care and discuss the need for better understanding of human and non-human elements of the system of care of the critically ill patient as a driver for improvement of care delivery. PMID:19439048

International electives in the final year of German medical school education--a student's perspective.

PubMed

Ebrahimi-Fakhari, Darius; Agrawal, Mridul; Wahlster, Lara

2014-01-01

The final year of medical school has a unique role for introducing students to their future responsibilities and challenges. At many medical schools, electives at an accredited institution abroad are a common part of the student's final year experience. International electives provide an opportunity for a personal and academic experience that will often create new perspectives on clinical medicine and research, medical education and healthcare policy. In this article the authors reflect on their experience as elective students abroad and discuss the contribution of international electives to the constant development and progress of local final year rotations. They identify key areas for improving final year electives and outline essential features for a valuable and successful final year elective.

A Case of Desmoplastic Small Round Cell Tumor.

PubMed

Reisner, David; Brahee, Deborah; Patel, Shweta; Hartman, Matthew

2015-08-01

Desmoplastic small round cell tumor is a rare, aggressive tumor primarily affecting young males. It is considered a childhood cancer, and is characterized by a unique chromosomal translocation which leads to failure to suppress tumor growth. It is classified as a soft tissue sarcoma, sharing some features with other small round cell tumors such as Ewing's Sarcoma and primitive neuroectodermal tumor. Typical imaging findings include multiple heterogeneous, lobular abdominal masses, which can grow very large. Often there is a dominant mass with additional peritoneal, omental, retroperitoneal and retrovesical masses. Prognosis is relatively poor with a 3 year survival rate of 50% in those treated aggressively with surgical resection, chemotherapy, and radiation therapy. The clinical presentation, imaging characteristics and pathology are discussed in regards to a recent case.

TH-E-BRF-04: Characterizing the Response of Texture-Based CT Image Features for Quantification of Radiation-Induced Normal Lung Damage

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

Krafft, S; Court, L; Briere, T

2014-06-15

Purpose: Radiation induced lung damage (RILD) is an important dose-limiting toxicity for patients treated with radiation therapy. Scoring systems for RILD are subjective and limit our ability to find robust predictors of toxicity. We investigate the dose and time-related response for texture-based lung CT image features that serve as potential quantitative measures of RILD. Methods: Pre- and post-RT diagnostic imaging studies were collected for retrospective analysis of 21 patients treated with photon or proton radiotherapy for NSCLC. Total lung and selected isodose contours (0–5, 5–15, 15–25Gy, etc.) were deformably registered from the treatment planning scan to the pre-RT and availablemore » follow-up CT studies for each patient. A CT image analysis framework was utilized to extract 3698 unique texture-based features (including co-occurrence and run length matrices) for each region of interest defined by the isodose contours and the total lung volume. Linear mixed models were fit to determine the relationship between feature change (relative to pre-RT), planned dose and time post-RT. Results: Seventy-three follow-up CT scans from 21 patients (median: 3 scans/patient) were analyzed to describe CT image feature change. At the p=0.05 level, dose affected feature change in 2706 (73.1%) of the available features. Similarly, time affected feature change in 408 (11.0%) of the available features. Both dose and time were significant predictors of feature change in a total of 231 (6.2%) of the extracted image features. Conclusion: Characterizing the dose and time-related response of a large number of texture-based CT image features is the first step toward identifying objective measures of lung toxicity necessary for assessment and prediction of RILD. There is evidence that numerous features are sensitive to both the radiation dose and time after RT. Beyond characterizing feature response, further investigation is warranted to determine the utility of these features as surrogates of clinically significant lung injury.« less

Can theories of animal discrimination explain perceptual learning in humans?

PubMed

Mitchell, Chris; Hall, Geoffrey

2014-01-01

We present a review of recent studies of perceptual learning conducted with nonhuman animals. The focus of this research has been to elucidate the mechanisms by which mere exposure to a pair of similar stimuli can increase the ease with which those stimuli are discriminated. These studies establish an important role for 2 mechanisms, one involving inhibitory associations between the unique features of the stimuli, the other involving a long-term habituation process that enhances the relative salience of these features. We then examine recent work investigating equivalent perceptual learning procedures with human participants. Our aim is to determine the extent to which the phenomena exhibited by people are susceptible to explanation in terms of the mechanisms revealed by the animal studies. Although we find no evidence that associative inhibition contributes to the perceptual learning effect in humans, initial detection of unique features (those that allow discrimination between 2 similar stimuli) appears to depend on an habituation process. Once the unique features have been detected, a tendency to attend to those features and to learn about their properties enhances subsequent discrimination. We conclude that the effects obtained with humans engage mechanisms additional to those seen in animals but argue that, for the most part, these have their basis in learning processes that are common to animals and people. In a final section, we discuss some implications of this analysis of perceptual learning for other aspects of experimental psychology and consider some potential applications. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

An Archetype Semi-Ring Fabry-Perot (SRFP) Resonator

NASA Technical Reports Server (NTRS)

Taghavi-Larigani, Shervin; VanZyl, Jakob

2009-01-01

We introduce and demonstrate the generation of a novel resonator, termed Semi-Ring Fabry-Perot (SRFP), that exhibits unique features, such as, its use of one plane mirror, allowing the SRFP to be easily fabricated as a symmetrical device. In addition to its unique features, it exhibits advantages of ring and Fabry-Perot resonators: 1) compared to a ring resonator that only allows a transmitted intensity, the Semi-Ring Fabry-Perot (SRFP) supports standing waves, allowing both a reflected and transmitted intensity; 2) the reflected light spectrum of the SRFP resonator is much narrower than similar Fabry-Perot, implying higher finesse.

Analysis of the antigen recognition sites of anti-methamphetamine monoclonal antibodies (II): unique feature of MA-3 antibody.

PubMed

Ishimaru, M; Morikawa, K; Hifumi, E; Itoh, T; Uda, T

2000-01-01

A monoclonal antibody against methamphetamine (MA-3 mAb) was found to be strongly bound to ephedrine. This feature was quite different from that of other fourteen mAbs against MA. Analyses of cDNA sequence and steric conformation by molecular modeling revealed that one hydrophilic pocket was generated in the heavy chain of MA-3 mAb involving CDRH-1 and CDRH-2. Asn33, Asn35, Asn50 and Asp52 were the main components of the unique pocket capable of binding to the hydroxyl group of ephedrine.

Analysis of geometric moments as features for firearm identification.

PubMed

Md Ghani, Nor Azura; Liong, Choong-Yeun; Jemain, Abdul Aziz

2010-05-20

The task of identifying firearms from forensic ballistics specimens is exacting in crime investigation since the last two decades. Every firearm, regardless of its size, make and model, has its own unique 'fingerprint'. These fingerprints transfer when a firearm is fired to the fired bullet and cartridge case. The components that are involved in producing these unique characteristics are the firing chamber, breech face, firing pin, ejector, extractor and the rifling of the barrel. These unique characteristics are the critical features in identifying firearms. It allows investigators to decide on which particular firearm that has fired the bullet. Traditionally the comparison of ballistic evidence has been a tedious and time-consuming process requiring highly skilled examiners. Therefore, the main objective of this study is the extraction and identification of suitable features from firing pin impression of cartridge case images for firearm recognition. Some previous studies have shown that firing pin impression of cartridge case is one of the most important characteristics used for identifying an individual firearm. In this study, data are gathered using 747 cartridge case images captured from five different pistols of type 9mm Parabellum Vektor SP1, made in South Africa. All the images of the cartridge cases are then segmented into three regions, forming three different set of images, i.e. firing pin impression image, centre of firing pin impression image and ring of firing pin impression image. Then geometric moments up to the sixth order were generated from each part of the images to form a set of numerical features. These 48 features were found to be significantly different using the MANOVA test. This high dimension of features is then reduced into only 11 significant features using correlation analysis. Classification results using cross-validation under discriminant analysis show that 96.7% of the images were classified correctly. These results demonstrate the value of geometric moments technique for producing a set of numerical features, based on which the identification of firearms are made.

Role of epidermal growth factor receptor tyrosine kinase inhibitors in the treatment of bronchoalveolar carcinoma.

PubMed

Patel, Jyoti D

2004-12-01

Bronchoalveolar carcinoma (BAC) is a previously uncommon subset of non-small-cell lung cancer (NSCLC) with unique epidemiology, pathology, clinical features, and natural history compared with other NSCLC subtypes. Recent data indicate that the incidence of BAC is increasing. Although many studies have reported that patients with BAC have prolonged survival, advanced BAC remains incurable, with most patients eventually dying of respiratory failure from progressive pulmonary involvement or intercurrent illness. Previous limited data suggest that chemotherapy for BAC provides modest benefit; however, anecdotal reports of swift and durable responses after treatment with tyrosine kinase (TK) inhibitors of the epidermal growth factor receptor (EGFR) in patients with BAC have prompted further investigation in this subset of patients. Two trials using the EGFR TK inhibitors gefitinib and/or erlotinib have demonstrated encouraging results, and have prompted further enthusiasm for this approach. Furthermore, recent insights into mechanisms of drug sensitivity should impact future clinical trial design.

Auditory and communicative abilities in the auditory neuropathy spectrum disorder and mutation in the Otoferlin gene: clinical cases study.

PubMed

Costa, Nayara Thais de Oliveira; Martinho-Carvalho, Ana Claudia; Cunha, Maria Claudia; Lewis, Doris Ruthi

2012-01-01

This study had the aim to investigate the auditory and communicative abilities of children diagnosed with Auditory Neuropathy Spectrum Disorder due to mutation in the Otoferlin gene. It is a descriptive and qualitative study in which two siblings with this diagnosis were assessed. The procedures conducted were: speech perception tests for children with profound hearing loss, and assessment of communication abilities using the Behavioral Observation Protocol. Because they were siblings, the subjects in the study shared family and communicative context. However, they developed different communication abilities, especially regarding the use of oral language. The study showed that the Auditory Neuropathy Spectrum Disorder is a heterogeneous condition in all its aspects, and it is not possible to make generalizations or assume that cases with similar clinical features will develop similar auditory and communicative abilities, even when they are siblings. It is concluded that the acquisition of communicative abilities involves subjective factors, which should be investigated based on the uniqueness of each case.

Designing multifunctional quantum dots for bioimaging, detection, and drug delivery

PubMed Central

Zrazhevskiy, Pavel; Sena, Mark; Gao, Xiaohu

2011-01-01

The emerging field of bionanotechnology aims at revolutionizing biomedical research and clinical practice via introduction of nanoparticle-based tools, expanding capabilities of existing investigative, diagnostic, and therapeutic techniques as well as creating novel instruments and approaches for addressing challenges faced by medicine. Quantum dots (QDs), semiconductor nanoparticles with unique photo-physical properties, have become one of the dominant classes of imaging probes as well as universal platforms for engineering of multifunctional nanodevices. Possessing versatile surface chemistry and superior optical features, QDs have found initial use in a variety of in vitro and in vivo applications. However, careful engineering of QD probes guided by application-specific design criteria is becoming increasingly important for successful transition of this technology from proof-of-concept studies towards real-life clinical applications. This review outlines the major design principles and criteria, from general ones to application-specific, governing the engineering of novel QD probes satisfying the increasing demands and requirements of nanomedicine and discusses the future directions of QD-focused bionanotechnology research (critical review, 201 references). PMID:20697629

HPV-Associated Head and Neck Cancer: Unique Features of Epidemiology and Clinical Management

PubMed Central

Maxwell, Jessica H.; Grandis, Jennifer R.; Ferris, Robert L.

2017-01-01

Human papillomavirus (HPV) is a recently identified causative agent for a subset of head and neck cancers, primarily in the oropharynx, and is largely responsible for the rising worldwide incidence of oropharyngeal cancer (OPC). Patients with HPV-positive OPC have distinct risk factor profiles and generally have a better prognosis than patients with traditional, HPV-negative, head and neck cancer. Concurrent chemotherapy and radiation is a widely accepted primary treatment modality for many patients with HPV-positive OPC. However, recent advances in surgical modalities, including transoral laser and robotic surgery, have led to the reemergence of primary surgical treatment for HPV-positive patients. Clinical trials are under way to determine optimal treatment strategies for the growing subset of patients with HPV-positive OPC. Similarly, identifying those patients with HPV-positive cancer who are at risk for recurrence and poor survival is critical in order to tailor individual treatment regimens and avoid potential undertreatment. PMID:26332002

Understanding refraction contrast using a comparison of absorption and refraction computed tomographic techniques

NASA Astrophysics Data System (ADS)

Wiebe, S.; Rhoades, G.; Wei, Z.; Rosenberg, A.; Belev, G.; Chapman, D.

2013-05-01

Refraction x-ray contrast is an imaging modality used primarily in a research setting at synchrotron facilities, which have a biomedical imaging research program. The most common method for exploiting refraction contrast is by using a technique called Diffraction Enhanced Imaging (DEI). The DEI apparatus allows the detection of refraction between two materials and produces a unique ''edge enhanced'' contrast appearance, very different from the traditional absorption x-ray imaging used in clinical radiology. In this paper we aim to explain the features of x-ray refraction contrast as a typical clinical radiologist would understand. Then a discussion regarding what needs to be considered in the interpretation of the refraction image takes place. Finally we present a discussion about the limitations of planar refraction imaging and the potential of DEI Computed Tomography. This is an original work that has not been submitted to any other source for publication. The authors have no commercial interests or conflicts of interest to disclose.

Advanced Ultrasound Technologies for Diagnosis and Therapy.

PubMed

Rix, Anne; Lederle, Wiltrud; Theek, Benjamin; Lammers, Twan; Moonen, Chrit; Schmitz, Georg; Kiessling, Fabian

2018-05-01

Ultrasound is among the most rapidly advancing imaging techniques. Functional methods such as elastography have been clinically introduced, and tissue characterization is improved by contrast-enhanced scans. Here, novel superresolution techniques provide unique morphologic and functional insights into tissue vascularization. Functional analyses are complemented by molecular ultrasound imaging, to visualize markers of inflammation and angiogenesis. The full potential of diagnostic ultrasound may become apparent by integrating these multiple imaging features in radiomics approaches. Emerging interest in ultrasound also results from its therapeutic potential. Various applications of tumor ablation with high-intensity focused ultrasound are being clinically evaluated, and its performance strongly benefits from the integration into MRI. Additionally, oscillating microbubbles mediate sonoporation to open biologic barriers, thus improving the delivery of drugs or nucleic acids that are coadministered or coformulated with microbubbles. This article provides an overview of recent developments in diagnostic and therapeutic ultrasound, highlighting multiple innovation tracks and their translational potential. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Some contributions of the Department of Veterans Affairs to the epidemiology of multiple sclerosis.

PubMed

Kurtzke, J F

2008-09-01

The first class 1 treatment trial ever conducted in multiple sclerosis (MS) was a Veterans Administration Cooperative Study. This led us to explore MS in the military-veteran populations of the United States in three main series: Army men hospitalized with final diagnoses of MS in World War II, all veterans of World War II and the Korean Conflict, and veterans of later service up to 1994. In each series, all cases had been matched with pre-illness military peers. These series provide major information on its clinical features, course and prognosis, including survival, by sex and race (white men and women; black men), as well as risk factors for occurrence, course, and survival. They comprise the only available nationwide morbidity distributions of MS in the United States. Veterans who are service-connected for MS by the Department of Veterans Affairs and matched with their military peers remain a unique and currently available resource for further clinical and epidemiological study of this disease.

Canine prostate models in preclinical studies of minimally invasive interventions: part II, benign prostatic hyperplasia models

PubMed Central

Báez-Díaz, Claudia; Sánchez-Margallo, Francisco Miguel

2017-01-01

Canine prostate is widely used as animal model in the preclinical evaluation of emerging therapeutic interventions. Spontaneous benign prostatic hyperplasia (BPH) is common in adult intact male dogs with two distinct pathological types: glandular and complex form of prostatic hyperplasia. The complex form of prostatic hyperplasia, usually occurring in older dogs, represents an ideal model because of its unique pathologic feature, including not only glandular hyperplasia but also an increase in prostate stromal components. The limited commercial availability of adult dogs with spontaneous BPH motivates experimentally induced BPH in young dogs. Hormone-induced canine BPH model has been well established with various hormonal treatment regimens and administration approaches. The goal of this review is to provide the veterinary background in spontaneous BPH in dogs, summarize the techniques in hormonal induction of canine BPH, and highlight the pathological and clinical limitations of the canine models that may lead to distinct therapeutic responses compared to clinical trials in humans. PMID:28725598

The biological significance and clinical applications of exosomes in ovarian cancer

PubMed Central

Dorayappan, Kalpana Deepa Priya; Wallbillich, John J.; Cohn, David E.; Selvendiran, Karuppaiyah

2016-01-01

Exosomes are nano-sized (20–100 nm) vesicles released by a variety of cells and are generated within the endosomal system or at the plasma membrane. There is emerging evidence that exosomes play a key role in intercellular communication in ovarian and other cancers. The protein and microRNA content of exosomes has been implicated in various intracellular processes that mediate oncogenesis, tumor spread, and drug resistance. Exosomes may prime distant tissue sites for reception of future metastases and their release can be mediated by the tumor microenvironment (e.g., hypoxia). Ovarian cancer-derived exosomes have unique features that could be leveraged for use as biomarkers to facilitate improved detection and treatment of the disease. Further, exosomes have the potential to serve as targets and/or drug delivery vehicles in the treatment of ovarian cancer. In this review we discuss the biological and clinical significance of exosomes relevant to the progression, detection, and treatment of ovarian cancer. PMID:27058839

The biological significance and clinical applications of exosomes in ovarian cancer.

PubMed

Dorayappan, Kalpana Deepa Priya; Wallbillich, John J; Cohn, David E; Selvendiran, Karuppaiyah

2016-07-01

Exosomes are nano-sized (20-100nm) vesicles released by a variety of cells and are generated within the endosomal system or at the plasma membrane. There is emerging evidence that exosomes play a key role in intercellular communication in ovarian and other cancers. The protein and microRNA content of exosomes has been implicated in various intracellular processes that mediate oncogenesis, tumor spread, and drug resistance. Exosomes may prime distant tissue sites for reception of future metastases and their release can be mediated by the tumor microenvironment (e.g., hypoxia). Ovarian cancer-derived exosomes have unique features that could be leveraged for use as biomarkers to facilitate improved detection and treatment of the disease. Further, exosomes have the potential to serve as targets and/or drug delivery vehicles in the treatment of ovarian cancer. In this review we discuss the biological and clinical significance of exosomes relevant to the progression, detection, and treatment of ovarian cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

One-dimensional model for the intracranial pulse morphological analysis during hyperventilation and CO2 inhalation tests

NASA Astrophysics Data System (ADS)

Ryu, Jaiyoung; Hu, Xiao; Shadden, Shawn C.

2015-11-01

The brain's CO2 reactivity mechanism is coupled with cerebral autoregulation and other unique features of cerebral hemodynamics. We developed a one-dimensional nonlinear model of blood flow in the cerebral arteries coupled to lumped parameter (LP) networks. The LP networks incorporate cerebral autoregulation, CO2 reactivity, intracranial pressure, cerebrospinal fluid, and cortical collateral blood flow models. The model was used to evaluate hemodynamic variables (arterial deformation, blood velocity and pressure) in the cerebral vasculature during hyperventilation and CO2 inhalation test. Tests were performed for various arterial blood pressure (ABP) representing normal and hypotensive conditions. The increase of the cerebral blood flow rates agreed well with the published measurements for various ABP measurements taken during clinical CO2 reactivity tests. The changes in distal vasculature affected the reflected pulse wave energy, which caused the waveform morphological changes at the middle cerebral, common and internal carotid arteries. The pulse morphological analysis demonstrated agreement with previous clinical measurements for cerebral vasoconstriction and vasodilation.

A 725 kb deletion at 22q13.1 chromosomal region including SOX10 gene in a boy with a neurologic variant of Waardenburg syndrome type 2.

PubMed

Siomou, Elisavet; Manolakos, Emmanouil; Petersen, Michael; Thomaidis, Loretta; Gyftodimou, Yolanda; Orru, Sandro; Papoulidis, Ioannis

2012-11-01

Waardenburg syndrome (WS) is a rare (1/40,000) autosomal dominant disorder resulting from melanocyte defects, with varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair, skin, and inner ear. WS is classified into four clinical subtypes (WS1-S4). Six genes have been identified to be associated with the different subtypes of WS, among which SOX10, which is localized within the region 22q13.1. Lately it has been suggested that whole SOX10 gene deletions can be encountered when testing for WS. In this study we report a case of a 13-year-old boy with a unique de novo 725 kb deletion within the 22q13.1 chromosomal region, including the SOX10 gene and presenting clinical features of a neurologic variant of WS2. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Genetic and Clinical Features of Progranulin-Associated Frontotemporal Lobar Degeneration

PubMed Central

Chen-Plotkin, Alice S.; Martinez-Lage, Maria; Sleiman, Patrick M. A.; Hu, William; Greene, Robert; Wood, Elisabeth McCarty; Bing, Shaoxu; Grossman, Murray; Schellenberg, Gerard D.; Hatanpaa, Kimmo J.; Weiner, Myron F.; White, Charles L.; Brooks, William S.; Halliday, Glenda M.; Kril, Jillian J.; Gearing, Marla; Beach, Thomas G.; Graff-Radford, Neill R.; Dickson, Dennis W.; Rademakers, Rosa; Boeve, Bradley F.; Pickering-Brown, Stuart M.; Snowden, Julie; van Swieten, John C.; Heutink, Peter; Seelaar, Harro; Murrell, Jill R.; Ghetti, Bernardino; Spina, Salvatore; Grafman, Jordan; Kaye, Jeffrey A.; Woltjer, Randall L.; Mesulam, Marsel; Bigio, Eileen; Lladó, Albert; Miller, Bruce L.; Alzualde, Ainhoa; Moreno, Fermin; Rohrer, Jonathan D.; Mackenzie, Ian R. A.; Feldman, Howard H.; Hamilton, Ronald L.; Cruts, Marc; Engelborghs, Sebastiaan; De Deyn, Peter P.; Van Broeckhoven, Christine; Bird, Thomas D.; Cairns, Nigel J.; Goate, Allison; Frosch, Matthew P.; Riederer, Peter F.; Bogdanovic, Nenad; Lee, Virginia M. Y.; Trojanowski, John Q.; Van Deerlin, Vivianna M.

2011-01-01

Objective To assess the relative frequency of unique mutations and their associated characteristics in 97 individuals with mutations in progranulin (GRN), an important cause of frontotemporal lobar degeneration (FTLD). Participants and Design A 46-site International Frontotemporal Lobar Degeneration Collaboration was formed to collect cases of FTLD with TAR DNA-binding protein of 43-kDa (TDP-43)–positive inclusions (FTLD-TDP). We identified 97 individuals with FTLD-TDP with pathogenic GRN mutations (GRN+ FTLD-TDP), assessed their genetic and clinical characteristics, and compared them with 453 patients with FTLD-TDP in which GRN mutations were excluded (GRN− FTLD-TDP). No patients were known to be related. Neuropathologic characteristics were confirmed as FTLD-TDP in 79 of the 97 GRN+ FTLDTDP cases and all of the GRN− FTLD-TDP cases. Results Age at onset of FTLD was younger in patients with GRN+ FTLD-TDP vs GRN− FTLD-TDP (median, 58.0 vs 61.0 years; P<.001), as was age at death (median, 65.5 vs 69.0 years; P<.001). Concomitant motor neuron disease was much less common in GRN+ FTLDTDP vs GRN− FTLD-TDP (5.4% vs 26.3%; P<.001). Fifty different GRN mutations were observed, including 2 novel mutations: c.139delG (p.D47TfsX7) and c.378C>A (p.C126X). The 2 most common GRN mutations were c.1477C>T (p.R493X, found in 18 patients, representing 18.6% of GRN cases) and c.26C>A (p.A9D, found in 6 patients, representing 6.2% of cases). Patients with the c.1477C>T mutation shared a haplotype on chromosome 17; clinically, they resembled patients with other GRN mutations. Patients with the c.26C>A mutation appeared to have a younger age at onset of FTLD and at death and more parkinsonian features than those with other GRN mutations. Conclusion GRN+ FTLD-TDP differs in key features from GRN− FTLD-TDP. PMID:21482928

A novel, privacy-preserving cryptographic approach for sharing sequencing data

PubMed Central

Cassa, Christopher A; Miller, Rachel A; Mandl, Kenneth D

2013-01-01

Objective DNA samples are often processed and sequenced in facilities external to the point of collection. These samples are routinely labeled with patient identifiers or pseudonyms, allowing for potential linkage to identity and private clinical information if intercepted during transmission. We present a cryptographic scheme to securely transmit externally generated sequence data which does not require any patient identifiers, public key infrastructure, or the transmission of passwords. Materials and methods This novel encryption scheme cryptographically protects participant sequence data using a shared secret key that is derived from a unique subset of an individual’s genetic sequence. This scheme requires access to a subset of an individual’s genetic sequence to acquire full access to the transmitted sequence data, which helps to prevent sample mismatch. Results We validate that the proposed encryption scheme is robust to sequencing errors, population uniqueness, and sibling disambiguation, and provides sufficient cryptographic key space. Discussion Access to a set of an individual’s genotypes and a mutually agreed cryptographic seed is needed to unlock the full sequence, which provides additional sample authentication and authorization security. We present modest fixed and marginal costs to implement this transmission architecture. Conclusions It is possible for genomics researchers who sequence participant samples externally to protect the transmission of sequence data using unique features of an individual’s genetic sequence. PMID:23125421

Twenty-First Century Diseases: Commonly Rare and Rarely Common?

PubMed

Daunert, Sylvia; Sittampalam, Gurusingham Sitta; Goldschmidt-Clermont, Pascal J

2017-09-20

Alzheimer's drugs are failing at a rate of 99.6%, and success rate for drugs designed to help patients with this form of dementia is 47 times less than for drugs designed to help patients with cancers ( www.scientificamerican.com/article/why-alzheimer-s-drugs-keep-failing/2014 ). How can it be so difficult to produce a valuable drug for Alzheimer's disease? Each human has a unique genetic and epigenetic makeup, thus endowing individuals with a highly unique complement of genes, polymorphisms, mutations, RNAs, proteins, lipids, and complex sugars, resulting in distinct genome, proteome, metabolome, and also microbiome identity. This editorial is taking into account the uniqueness of each individual and surrounding environment, and stresses the point that a more accurate definition of a "common" disorder could be simply the amalgamation of a myriad of "rare" diseases. These rare diseases are being grouped together because they share a rather constant complement of common features and, indeed, generally respond to empirically developed treatments, leading to a positive outcome consistently. We make the case that it is highly unlikely that such treatments, despite their statistical success measured with large cohorts using standardized clinical research, will be effective on all patients until we increase the depth and fidelity of our understanding of the individual "rare" diseases that are grouped together in the "buckets" of common illnesses. Antioxid. Redox Signal. 27, 511-516.

Clinical Significance of Component Allergens in Fagales Pollen-Sensitized Peanut Allergy in Korea

PubMed Central

Park, Kyung Hee; Son, Young Woong; Lee, Sang Chul; Jeong, Kyunguk; Sim, Da Woon; Park, Hye Jung; Lee, Sooyoung; Lee, Jae-Hyun

2016-01-01

Purpose Clinical features of peanut allergy can range from localized to systemic reactions. Because peanut and birch pollen have cross-reactivity, peanut can lead to localized allergic reaction in Fagales pollen-sensitized oral allergy syndrome (OAS) patients without peanut sensitization per se. The purpose of this study was to discriminate true peanut food allergy from cross-reactive hypersensitivity in birch-sensitized peanut allergy. Methods Birch-sensitized (n=81) and peanut anaphylaxis patients (n=12) were enrolled. Peanut-related allergic reactions and sensitization profiles were examined. Specific IgE to Fagales tree pollens (birch, oak), peanut, and their component allergens (Bet v 1, Bet v 2, Ara h 1, Ara h 2, Ara h 3, Ara h 8, and Ara h 9) were evaluated. Based on these specific IgEs and clinical features, the patients were classified into 4 groups: group 1 (Fagales pollen allergy without OAS), group 2 (Fagales pollen allergy with OAS), group 3 (OAS with peanut anaphylaxis), and group 4 (peanut anaphylaxis). Results After peanut consumption, one-third of OAS patients experienced oral symptoms not associated with peanut sensitization. Ara h 1 or Ara h 2 was positive in peanut anaphylaxis patients, whereas Ara h 8 was positive in OAS patients. There were 4 patients with both peanut anaphylaxis and OAS (group 3). Both Ara h 2 and Ara h 8 were positive in these patients. Foods associated with OAS in Korea showed unique patterns compared to Westernized countries. Conclusions Ara h 2 and Ara h 8 may be important component allergens for discriminating peanut allergy. PMID:27582401

Optimizing Parkinson's disease diagnosis: the role of a dual nuclear imaging algorithm.

PubMed

Langston, J William; Wiley, Jesse C; Tagliati, Michele

2018-01-01

The diagnosis of Parkinson's disease (PD) currently relies almost exclusively on the clinical judgment of an experienced neurologist, ideally a specialist in movement disorders. However, such clinical diagnosis is often incorrect in a large percentage of patients, particularly in the early stages of the disease. A commercially available, objective and quantitative marker of nigrostriatal neurodegeneration was recently provided by 123-iodine 123 I-ioflupane SPECT imaging, which is however unable to differentiate PD from a variety of other parkinsonian syndromes associated with striatal dopamine deficiency. There is evidence to support an algorithm utilizing a dual neuroimaging strategy combining 123 I-ioflupane SPECT and the noradrenergic receptor ligand 123 I-metaiodobenzylguanidine (MIBG), which assesses the post-ganglion peripheral autonomic nervous system. Evolving concepts regarding the synucleinopathy affecting the central and peripheral autonomic nervous systems as part of a multisystem disease are reviewed to sustain such strategy. Data are presented to show how MIBG deficits are a common feature of multisystem Lewy body disease and can be used as a unique feature to distinguish PD from atypical parkinsonisms. We propose that the combination of cardiac (MIBG) and cerebral 123 I-ioflupane SPECT could satisfy one of the most significant unmet needs of current PD diagnosis and management, namely the early and accurate diagnosis of patients with typical Lewy body PD. Exemplary case scenarios will be described, highlighting how dual neuroimaging strategy can maximize diagnostic accuracy for patient care, clinical trials, pre-symptomatic PD screening, and special cases provided by specific genetic mutations associated with PD.

Reproductive Physiology of Marsupials

ERIC Educational Resources Information Center

Sharman, G. B.

1970-01-01

Describes some unique features of marsupial reproduction which include (1) chromosomal sex determination, (2) reproductive system, (3) birth, (4) location, and (5) embryonic diapause. These features suggest that viviparity evolved separately in eutherian and marsupial stocks after their derivation from a common oviparous ancestor. Bibliography.…

Single trial decoding of belief decision making from EEG and fMRI data using independent components features

PubMed Central

Douglas, Pamela K.; Lau, Edward; Anderson, Ariana; Head, Austin; Kerr, Wesley; Wollner, Margalit; Moyer, Daniel; Li, Wei; Durnhofer, Mike; Bramen, Jennifer; Cohen, Mark S.

2013-01-01

The complex task of assessing the veracity of a statement is thought to activate uniquely distributed brain regions based on whether a subject believes or disbelieves a given assertion. In the current work, we present parallel machine learning methods for predicting a subject's decision response to a given propositional statement based on independent component (IC) features derived from EEG and fMRI data. Our results demonstrate that IC features outperformed features derived from event related spectral perturbations derived from any single spectral band, yet were similar to accuracy across all spectral bands combined. We compared our diagnostic IC spatial maps with our conventional general linear model (GLM) results, and found that informative ICs had significant spatial overlap with our GLM results, yet also revealed unique regions like amygdala that were not statistically significant in GLM analyses. Overall, these results suggest that ICs may yield a parsimonious feature set that can be used along with a decision tree structure for interpretation of features used in classifying complex cognitive processes such as belief and disbelief across both fMRI and EEG neuroimaging modalities. PMID:23914164

Which ante mortem clinical features predict progressive supranuclear palsy pathology?

PubMed

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

2017-07-01

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

Understanding the molecular pathogenesis of acute promyelocytic leukemia.

PubMed

Lo-Coco, Francesco; Hasan, Syed Khizer

2014-03-01

Acute promyelocytic leukemia (APL) is a distinct subset of acute myeloid leukemia (AML) associated with peculiar biologic and clinical features and requiring specific management. At the genetic level, APL is featured by a unique chromosome translocation t(15;17) which results in the PML-RARα gene fusion and chimeric protein. APL is the first example of differentiation therapy targeted to a defined genetic target i.e. PML-RARα. PML-RARα behaves as an altered retinoic acid receptor with an ability of transmitting oncogenic signaling leading to accumulation of undifferentiated promyelocytes. All-trans-retinoic acid (ATRA) induces disease remission in APL patients by triggering terminal differentiation of leukemic promyelocytes. More recently, arsenic trioxide (ATO) has been shown to contribute degradation of the PML-RARα oncoprotein through bonding the PML moiety and has shown excellent synergism with ATRA in clinical trials. Elucidating the oncogenic signaling of PML-RARα through various transcription factors and the study of APL mouse models have greatly helped to understand the molecular pathogenesis of APL. However, the precise molecular mechanism by which t(15;17) is formed and initiates leukemia remains unknown. While transforming oncogenic potential of PML-RARα has been described extensively, the mechanistic events important for the formation of t(15;17) have been taken from the model of Therapy-related APL (t-APL). Copyright © 2014 Elsevier Ltd. All rights reserved.

Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo.

PubMed

von Brühl, Marie-Luise; Stark, Konstantin; Steinhart, Alexander; Chandraratne, Sue; Konrad, Ildiko; Lorenz, Michael; Khandoga, Alexander; Tirniceriu, Anca; Coletti, Raffaele; Köllnberger, Maria; Byrne, Robert A; Laitinen, Iina; Walch, Axel; Brill, Alexander; Pfeiler, Susanne; Manukyan, Davit; Braun, Siegmund; Lange, Philipp; Riegger, Julia; Ware, Jerry; Eckart, Annekathrin; Haidari, Selgai; Rudelius, Martina; Schulz, Christian; Echtler, Katrin; Brinkmann, Volker; Schwaiger, Markus; Preissner, Klaus T; Wagner, Denisa D; Mackman, Nigel; Engelmann, Bernd; Massberg, Steffen

2012-04-09

Deep vein thrombosis (DVT) is a major cause of cardiovascular death. The sequence of events that promote DVT remains obscure, largely as a result of the lack of an appropriate rodent model. We describe a novel mouse model of DVT which reproduces a frequent trigger and resembles the time course, histological features, and clinical presentation of DVT in humans. We demonstrate by intravital two-photon and epifluorescence microscopy that blood monocytes and neutrophils crawling along and adhering to the venous endothelium provide the initiating stimulus for DVT development. Using conditional mutants and bone marrow chimeras, we show that intravascular activation of the extrinsic pathway of coagulation via tissue factor (TF) derived from myeloid leukocytes causes the extensive intraluminal fibrin formation characteristic of DVT. We demonstrate that thrombus-resident neutrophils are indispensable for subsequent DVT propagation by binding factor XII (FXII) and by supporting its activation through the release of neutrophil extracellular traps (NETs). Correspondingly, neutropenia, genetic ablation of FXII, or disintegration of NETs each confers protection against DVT amplification. Platelets associate with innate immune cells via glycoprotein Ibα and contribute to DVT progression by promoting leukocyte recruitment and stimulating neutrophil-dependent coagulation. Hence, we identified a cross talk between monocytes, neutrophils, and platelets responsible for the initiation and amplification of DVT and for inducing its unique clinical features.

Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo

PubMed Central

von Brühl, Marie-Luise; Stark, Konstantin; Steinhart, Alexander; Chandraratne, Sue; Konrad, Ildiko; Lorenz, Michael; Khandoga, Alexander; Tirniceriu, Anca; Coletti, Raffaele; Köllnberger, Maria; Byrne, Robert A.; Laitinen, Iina; Walch, Axel; Brill, Alexander; Pfeiler, Susanne; Manukyan, Davit; Braun, Siegmund; Lange, Philipp; Riegger, Julia; Ware, Jerry; Eckart, Annekathrin; Haidari, Selgai; Rudelius, Martina; Schulz, Christian; Echtler, Katrin; Brinkmann, Volker; Schwaiger, Markus; Preissner, Klaus T.; Wagner, Denisa D.; Mackman, Nigel; Engelmann, Bernd

2012-01-01

Deep vein thrombosis (DVT) is a major cause of cardiovascular death. The sequence of events that promote DVT remains obscure, largely as a result of the lack of an appropriate rodent model. We describe a novel mouse model of DVT which reproduces a frequent trigger and resembles the time course, histological features, and clinical presentation of DVT in humans. We demonstrate by intravital two-photon and epifluorescence microscopy that blood monocytes and neutrophils crawling along and adhering to the venous endothelium provide the initiating stimulus for DVT development. Using conditional mutants and bone marrow chimeras, we show that intravascular activation of the extrinsic pathway of coagulation via tissue factor (TF) derived from myeloid leukocytes causes the extensive intraluminal fibrin formation characteristic of DVT. We demonstrate that thrombus-resident neutrophils are indispensable for subsequent DVT propagation by binding factor XII (FXII) and by supporting its activation through the release of neutrophil extracellular traps (NETs). Correspondingly, neutropenia, genetic ablation of FXII, or disintegration of NETs each confers protection against DVT amplification. Platelets associate with innate immune cells via glycoprotein Ibα and contribute to DVT progression by promoting leukocyte recruitment and stimulating neutrophil-dependent coagulation. Hence, we identified a cross talk between monocytes, neutrophils, and platelets responsible for the initiation and amplification of DVT and for inducing its unique clinical features. PMID:22451716

Clinical Features and Associated Likelihood of Primary Ciliary Dyskinesia in Children and Adolescents.

PubMed

Leigh, Margaret W; Ferkol, Thomas W; Davis, Stephanie D; Lee, Hye-Seung; Rosenfeld, Margaret; Dell, Sharon D; Sagel, Scott D; Milla, Carlos; Olivier, Kenneth N; Sullivan, Kelli M; Zariwala, Maimoona A; Pittman, Jessica E; Shapiro, Adam J; Carson, Johnny L; Krischer, Jeffrey; Hazucha, Milan J; Knowles, Michael R

2016-08-01

Primary ciliary dyskinesia (PCD), a genetically heterogeneous, recessive disorder of motile cilia, is associated with distinct clinical features. Diagnostic tests, including ultrastructural analysis of cilia, nasal nitric oxide measurements, and molecular testing for mutations in PCD genes, have inherent limitations. To define a statistically valid combination of systematically defined clinical features that strongly associates with PCD in children and adolescents. Investigators at seven North American sites in the Genetic Disorders of Mucociliary Clearance Consortium prospectively and systematically assessed individuals (aged 0-18 yr) referred due to high suspicion for PCD. The investigators defined specific clinical questions for the clinical report form based on expert opinion. Diagnostic testing was performed using standardized protocols and included nasal nitric oxide measurement, ciliary biopsy for ultrastructural analysis of cilia, and molecular genetic testing for PCD-associated genes. Final diagnoses were assigned as "definite PCD" (hallmark ultrastructural defects and/or two mutations in a PCD-associated gene), "probable/possible PCD" (no ultrastructural defect or genetic diagnosis, but compatible clinical features and nasal nitric oxide level in PCD range), and "other diagnosis or undefined." Criteria were developed to define early childhood clinical features on the basis of responses to multiple specific queries. Each defined feature was tested by logistic regression. Sensitivity and specificity analyses were conducted to define the most robust set of clinical features associated with PCD. From 534 participants 18 years of age and younger, 205 were identified as having "definite PCD" (including 164 with two mutations in a PCD-associated gene), 187 were categorized as "other diagnosis or undefined," and 142 were defined as having "probable/possible PCD." Participants with "definite PCD" were compared with the "other diagnosis or undefined" group. Four criteria-defined clinical features were statistically predictive of PCD: laterality defect; unexplained neonatal respiratory distress; early-onset, year-round nasal congestion; and early-onset, year-round wet cough (adjusted odds ratios of 7.7, 6.6, 3.4, and 3.1, respectively). The sensitivity and specificity based on the number of criteria-defined clinical features were four features, 0.21 and 0.99, respectively; three features, 0.50 and 0.96, respectively; and two features, 0.80 and 0.72, respectively. Systematically defined early clinical features could help identify children, including infants, likely to have PCD. Clinical trial registered with ClinicalTrials.gov (NCT00323167).

Nodular lymphocyte-predominant Hodgkin lymphoma: a unique disease deserving unique management.

PubMed

Eichenauer, Dennis A; Engert, Andreas

2017-12-08

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity with an incidence of 0.1 to 0.2/100 000/y. Compared with the more common subtypes of classical Hodgkin lymphoma, NLPHL is characterized by distinct pathological and clinical features. Histologically, the disease-defining lymphocyte predominant cells consistently express CD20 but lack CD30. Clinically, NLPHL mostly has a rather indolent course, and patients usually are diagnosed in early stages. The prognosis of early-stage NLPHL is excellent, with progression-free survival and overall survival rates exceeding 90% after involved-field radiotherapy (IF-RT) alone (stage IA) or combined modality treatment consisting of a brief chemotherapy with 2 cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy followed by IF-RT (early stages other than stage IA). In contrast, patients with advanced disease at diagnosis tend to relapse either with NLPHL histology or with histological transformation into aggressive B-cell non-Hodgkin lymphoma despite more aggressive first-line treatment with 6 to 8 cycles of multiagent chemotherapy. However, even NLPHL patients with multiple relapses successfully respond to salvage therapy in many cases. Salvage therapies range from single-agent anti-CD20 antibody treatment to high-dose chemotherapy followed by autologous stem cell transplantation. Treatment at disease recurrence should be chosen on the basis of various factors, including histology at relapse, time to relapse, extent of disease at relapse, and prior treatment. Because death among NLPHL patients is more often caused by therapy-related late effects than lymphoma-related complications, optimizing the risk-benefit ratio of treatment by decreasing toxicity whenever possible is the major goal of clinical research in this disease. © 2016 by The American Society of Hematology. All rights reserved.

Lipid-Based Nanoparticles as Pharmaceutical Drug Carriers: From Concepts to Clinic

PubMed Central

Puri, Anu; Loomis, Kristin; Smith, Brandon; Lee, Jae-Ho; Yavlovich, Amichai; Heldman, Eli; Blumenthal, Robert

2010-01-01

In recent years, various nanotechnology platforms in the area of medical biology, including both diagnostics and therapy, have gained remarkable attention. Moreover, research and development of engineered multifunctional nanoparticles as pharmaceutical drug carriers have spurred exponential growth in applications to medicine in the last decade. Design principles of these nanoparticles, including nano-emulsions, dendrimers, nano-gold, liposomes, drug-carrier conjugates, antibody-drug complexes, and magnetic nanoparticles, are primarily based on unique assemblies of synthetic, natural, or biological components, including but not limited to synthetic polymers, metal ions, oils, and lipids as their building blocks. However, the potential success of these particles in the clinic relies on consideration of important parameters such as nanoparticle fabrication strategies, their physical properties, drug loading efficiencies, drug release potential, and, most importantly, minimum toxicity of the carrier itself. Among these, lipid-based nanoparticles bear the advantage of being the least toxic for in vivo applications, and significant progress has been made in the area of DNA/RNA and drug delivery using lipid-based nanoassemblies. In this review, we will primarily focus on the recent advances and updates on lipid-based nanoparticles for their projected applications in drug delivery. We begin with a review of current activities in the field of liposomes (the so-called honorary nanoparticles), and challenging issues of targeting and triggering will be discussed in detail. We will further describe nanoparticles derived from a novel class of amphipathic lipids called bolaamphiphiles with unique lipid assembly features that have been recently examined as drug/DNA delivery vehicles. Finally, an overview of an emerging novel class of particles (based on lipid components other than phospholipids), solid lipid nanoparticles and nanostructured lipid carriers will be presented. We conclude with a few examples of clinically successful formulations of currently available lipid-based nanoparticles. PMID:20402623

Low-dose intrathecal fluorescein for diagnosis of cerebrospinal fluid rhinorrhea using the scanning fiber endoscope in the human nasal cavities

NASA Astrophysics Data System (ADS)

Hou, Vivian W.; Davis, Calvin G.; Davis, Greg E.; Seibel, Eric J.

2016-03-01

Intrathecal fluorescein (ITF) enhances detection of cerebrospinal fluid rhinorrhea (CSFR). Clinically administered doses fall in the range of 0.1ml to 0.5ml of 5% to 10% fluorescein (1.3×10-3M to 1.3×10-2M). Though uncommon, significant morbidities associated with high doses of fluorescein have been reported. High concentrations are necessary for white light visual assessment; in contrast, fluorescent imaging enhances signal contrast and requires lower ITF concentrations for visualization. The ultrathin and flexible, multimodal scanning fiber endoscope (SFE) can visualize nanomolar concentrations of fluorescein as pseudocolor over reflectance, video-rate imaging. The application of the SFE for CSFR detection was assessed in a cadaver study. Briefly, 10μM (1×10-5M) fluorescein, 100X-1000X less than the standard clinical dose, was injected intra-cranially into the epidural space through an orbital roof puncture. The resulting rhinorrhea was assessed with a conventional, rigid ENT scope and second with the SFE in both video reflectance and multimodal fluorescent imaging modes. Neither system could visualize the 10μM ITF during white light imaging however the nanomolar sensitive SFE visualized the rhinorrhea during fluorescent imaging. Despite the low concentration used, a target-to-background ratio of 5.6 +/- 2.7 was achieved. To demonstrate SFE guidance of CSFR detection and repair, de-identified patient computed tomography (CT) scans were used to generate 3D printed phantoms. Cases were selected for unique anatomical features and overall clinical difficulty as determined by an experienced ENT clinician (GED). The sensitivity and minimally invasive nature of the SFE provide a unique platform for enhancing diagnosis and monitoring interventions in surgical endoscopic approaches into the sinuses.

Virulence factors encoded by Legionella longbeachae identified on the basis of the genome sequence analysis of clinical isolate D-4968.

PubMed

Kozak, Natalia A; Buss, Meghan; Lucas, Claressa E; Frace, Michael; Govil, Dhwani; Travis, Tatiana; Olsen-Rasmussen, Melissa; Benson, Robert F; Fields, Barry S

2010-02-01

Legionella longbeachae causes most cases of legionellosis in Australia and may be underreported worldwide due to the lack of L. longbeachae-specific diagnostic tests. L. longbeachae displays distinctive differences in intracellular trafficking, caspase 1 activation, and infection in mouse models compared to Legionella pneumophila, yet these two species have indistinguishable clinical presentations in humans. Unlike other legionellae, which inhabit freshwater systems, L. longbeachae is found predominantly in moist soil. In this study, we sequenced and annotated the genome of an L. longbeachae clinical isolate from Oregon, isolate D-4968, and compared it to the previously published genomes of L. pneumophila. The results revealed that the D-4968 genome is larger than the L. pneumophila genome and has a gene order that is different from that of the L. pneumophila genome. Genes encoding structural components of type II, type IV Lvh, and type IV Icm/Dot secretion systems are conserved. In contrast, only 42/140 homologs of genes encoding L. pneumophila Icm/Dot substrates have been found in the D-4968 genome. L. longbeachae encodes numerous proteins with eukaryotic motifs and eukaryote-like proteins unique to this species, including 16 ankyrin repeat-containing proteins and a novel U-box protein. We predict that these proteins are secreted by the L. longbeachae Icm/Dot secretion system. In contrast to the L. pneumophila genome, the L. longbeachae D-4968 genome does not contain flagellar biosynthesis genes, yet it contains a chemotaxis operon. The lack of a flagellum explains the failure of L. longbeachae to activate caspase 1 and trigger pyroptosis in murine macrophages. These unique features of L. longbeachae may reflect adaptation of this species to life in soil.

A temperature-based feedback control system for electromagnetic phased-array hyperthermia: theory and simulation.

PubMed

Kowalski, M E; Jin, J M

2003-03-07

A hybrid proportional-integral-in-time and cost-minimizing-in-space feedback control system for electromagnetic, deep regional hyperthermia is proposed. The unique features of this controller are that (1) it uses temperature, not specific absorption rate, as the criterion for selecting the relative phases and amplitudes with which to drive the electromagnetic phased-array used for hyperthermia and (2) it requires on-line computations that are all deterministic in duration. The former feature, in addition to optimizing the treatment directly on the basis of a clinically relevant quantity, also allows the controller to sense and react to time- and temperature-dependent changes in local blood perfusion rates and other factors that can significantly impact the temperature distribution quality of the delivered treatment. The latter feature makes it feasible to implement the scheme on-line in a real-time feedback control loop. This is in sharp contrast to other temperature optimization techniques proposed in the literature that generally involve an iterative approximation that cannot be guaranteed to terminate in a fixed amount of computational time. An example of its application is presented to illustrate the properties and demonstrate the capability of the controller to sense and compensate for local, time-dependent changes in blood perfusion rates.

Childhood nodal marginal zone lymphoma with unusual clinicopathologic and cytogenetic features for the pediatric variant: a case report.

PubMed

Aqil, Barina; Merritt, Brian Y; Elghetany, M Tarek; Kamdar, Kala Y; Lu, Xinyan Y; Curry, Choladda V

2015-01-01

Nodal marginal zone lymphoma (NMZL) is a B-cell lymphoma that shares morphologic and immunophenotypic features with extranodal and splenic marginal zone lymphomas but lacks extranodal or splenic involvement at presentation. NMZL occurs mostly in adults with no sex predilection, at advanced stage (III or IV), with frequent relapses and a high incidence of tumoral genetic abnormalities including trisomies 3 and 18 and gain of 7q. Pediatric NMZL, however, is a rare but distinct variant of NMZL with characteristic features including male predominance, asymptomatic and localized (stage I) disease, low relapse rates with excellent outcomes, and a lower incidence of essentially similar genetic aberrations compared to adult NMZL. Here we describe a unique case of childhood NMZL with unusual clinicopathologic features for the pediatric variant including generalized lymphadenopathy, high-stage disease with persistence after therapy, unusual immunophenotype (CD5, CD23, and BCL6 positive), and unique chromosomal abnormalities including monosomy 20 and add(10)(p11.2).

Clinical features and subjective/physiological responses to emotional stimuli in the presence of emotion dysregulation in attention-deficit hyperactivity disorder.

PubMed

Taskiran, Candan; Karaismailoglu, Serkan; Cak Esen, Halime Tuna; Tuzun, Zeynep; Erdem, Aysen; Balkanci, Zeynep Dicle; Dolgun, Anil Barak; Cengel Kultur, Sadriye Ebru

2018-05-01

Emotion dysregulation (ED) has long been recognized in clinical descriptions of attention-deficit hyperactivity disorder (ADHD), but a renewed interest in ED has advanced research on the overlap between the two entities. Autonomic reactivity (AR) is a neurobiological correlate of emotion regulation; however, the association between ADHD and AR remains unclear. Our aim was to explore the clinical differences, AR, and subjective emotional responses to visual emotional stimuli in ADHD children with and without ED. School-aged ADHD children with (n = 28) and without (n = 20) ED, according to the definition of deficiency in emotional self-regulation (DESR), and healthy controls (n = 22) were interviewed by using the Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime version (K-SADS-PL) to screen frequent psychopathologies for these ages. All subjects were evaluated with Child Behavior Checklist 6-18 (CBCL), the Strengths and Difficulties Questionnaire (SDQ), the McMaster Family Assessment Device (FAD), the School-Age Temperament Inventory (SATI), and Conners' Parent Rating Scale (CPRS-48), which were completed by parents. To evaluate emotional responses, the International Affective Picture System (IAPS) and the subjective and physiological responses (electrodermal activity and heart rate reactivity) to selected pictures were examined. Regarding clinically distinctive features, the ADHD+ED group differed from the ADHD-ED and the control groups in terms of having higher temperamental negative reactivity, more oppositional/conduct problems, and lower prosocial behaviors. In the AR measures, children in the ADHD+ED group rated unpleasant stimuli as more negative, but they still had lower heart rate reactivity (HRR) than the ADHD-ED and control groups; moreover, unlike the two other groups, the ADHD+ED group showed no differences in HRR between different emotional stimuli. The presented findings are unique in terms of their ability to clinically and physiologically differentiate between ADHD children with and without ED.

Clinical Characteristics of Patients with Chronic Rhinosinusitis with Nasal Polyps, Asthma, and Aspirin-Exacerbated Respiratory Disease.

PubMed

Stevens, Whitney W; Peters, Anju T; Hirsch, Annemarie G; Nordberg, Cara M; Schwartz, Brian S; Mercer, Dione G; Mahdavinia, Mahboobeh; Grammer, Leslie C; Hulse, Kathryn E; Kern, Robert C; Avila, Pedro; Schleimer, Robert P

Aspirin-exacerbated respiratory disease (AERD) comprises the triad of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and intolerance to inhibitors of the cyclooxygenase-1 (COX-1) enzyme. The prevalence of AERD remains unclear, and few studies have compared the clinical characteristics of patients with AERD to those with CRSwNP alone, asthma alone, or both CRSwNP and asthma. To determine the prevalence of AERD within a tertiary care setting, and to identify unique clinical features that could distinguish these patients from those with both CRSwNP and asthma or with CRSwNP alone. Electronic medical records of patients at Northwestern in Chicago, Illinois, were searched by computer algorithm and then manual chart review to identify 459 patients with CRSwNP alone, 412 with both CRSwNP and asthma, 171 with AERD, and 300 with asthma only. Demographic and clinical features including sex, atopy, and sinus disease severity were characterized. The prevalence of AERD among patients with CRSwNP was 16%. Patients with AERD had undergone 2-fold more sinus surgeries (P < .001) and were significantly younger at the time of their first surgery (40 ± 13 years) than were patients with CRSwNP (43 ± 14 years; P < .05). Atopy was significantly more prevalent in patients with AERD (84%) or asthma (85%) than in patients with CRSwNP (66%, P < .05). More patients with AERD (13%) had corticosteroid-dependent disease than patients with both CRSwNP and asthma (4%, P < .01) or asthma (1%, P < .001). AERD is common among patients with CRSwNP; even though patients with AERD have CRSwNP and asthma, the clinical course of their disease is not the same as of patients who have CRSwNP and asthma but are tolerant to COX-1 inhibitors. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Measuring thought content valence after a breakup: Development of the Positive and Negative Ex-Relationship Thoughts (PANERT) scale.

PubMed

Brenner, Rachel E; Vogel, David L

2015-07-01

The end of a romantic relationship is a common and serious presenting concern among clients at university counseling centers. Researchers have highlighted the need to understand the nature of thoughts about an ex-relationship, because they may lead to unique clinical interventions. One aspect of thought that may be clinically relevant is content valence, or the positive or negative emotions associated with the content of the thought. Unfortunately, content valence has not been addressed in the romantic relationship dissolution literature. To address this omission, we developed the 12-item Positive and Negative Ex-Relationship Thoughts (PANERT) scale across 4 samples. In Sample 1 (n = 475), exploratory factor analyses demonstrated a multidimensional scale with 2 factors: positive content valence and negative content valence. Sample 2 (n = 509) and Sample 3 (n = 291) confirmed the factor structure in college and community samples. Internal consistencies ranged from .88-.94 for positive content valence and from .87-.94 for negative content valence. In Sample 4 (n = 133), construct validity was supported, with the PANERT factors uniquely predicting breakup distress, relationship preoccupation, depression, loss of self-concept, rediscovery of self-concept, negative emotional adjustment, and positive emotional adjustment. Further, the direction of these relationships suggest that positive thought content valence may be consistently maladaptive to recovery from an ex-relationship, and negative thought content valence may have maladaptive and adaptive features. Implications for future research and practice are discussed. (c) 2015 APA, all rights reserved).

Synthesis, chemical reactivity as Michael acceptors, and biological potency of monocyclic cyanoenones, novel and highly potent anti-inflammatory and cytoprotective agents.

PubMed

Zheng, Suqing; Santosh Laxmi, Y R; David, Emilie; Dinkova-Kostova, Albena T; Shiavoni, Katherine H; Ren, Yanqing; Zheng, Ying; Trevino, Isaac; Bumeister, Ronald; Ojima, Iwao; Wigley, W Christian; Bliska, James B; Mierke, Dale F; Honda, Tadashi

2012-05-24

Novel monocyclic cyanoenones examined to date display unique features regarding chemical reactivity as Michael acceptors and biological potency. Remarkably, in some biological assays, the simple structure is more potent than pentacyclic triterpenoids (e.g., CDDO and bardoxolone methyl) and tricycles (e.g., TBE-31). Among monocyclic cyanoenones, 1 is a highly reactive Michael acceptor with thiol nucleophiles. Furthermore, an important feature of 1 is that its Michael addition is reversible. For the inhibition of NO production, 1 shows the highest potency. Notably, its potency is about three times higher than CDDO, whose methyl ester (bardoxolone methyl) is presently in phase III clinical trials. For the induction of NQO1, 1 also demonstrated the highest potency. These results suggest that the reactivity of these Michael acceptors is closely related to their biological potency. Interestingly, in LPS-stimulated macrophages, 1 causes apoptosis and inhibits secretion of TNF-α and IL-1β with potencies that are higher than those of bardoxolone methyl and TBE-31.

Cyberbullying in Children and Youth: Implications for Health and Clinical Practice

PubMed Central

Faris, Robert; Mishna, Faye

2016-01-01

We review the recent literature on cyberbullying and its effects on victimised youth, identifying key points. We conclude that cyberbullying, while following many of the underlying dynamics of more traditional forms of bullying, features some unique qualities that can both magnify the damage caused and make it more difficult to detect. These features include the pervasive, never-ending nature of cyberbullying and the ability to quickly reach large audiences. The potential for anonymity and the related distance afforded by screens and devices compared to in-person interaction allow the cruelty of cyberbullying to go unchecked. Despite the perceived anonymity of cyberbullying, cyberbullying can be perpetrated by friends, who often have intimate knowledge about the victimised youth that can be devastating when made public. Given the difficulty schools face in preventing or even detecting cyberbullying, health care providers are an important ally, due to their knowledge of the youth, the sense of trust they bring to youth, and their independence from the school setting. We conclude by calling for routine screening of bullying by health care providers who deal with paediatric populations. PMID:28562091

Cyberbullying in Children and Youth: Implications for Health and Clinical Practice.

PubMed

Vaillancourt, Tracy; Faris, Robert; Mishna, Faye

2017-06-01

We review the recent literature on cyberbullying and its effects on victimised youth, identifying key points. We conclude that cyberbullying, while following many of the underlying dynamics of more traditional forms of bullying, features some unique qualities that can both magnify the damage caused and make it more difficult to detect. These features include the pervasive, never-ending nature of cyberbullying and the ability to quickly reach large audiences. The potential for anonymity and the related distance afforded by screens and devices compared to in-person interaction allow the cruelty of cyberbullying to go unchecked. Despite the perceived anonymity of cyberbullying, cyberbullying can be perpetrated by friends, who often have intimate knowledge about the victimised youth that can be devastating when made public. Given the difficulty schools face in preventing or even detecting cyberbullying, health care providers are an important ally, due to their knowledge of the youth, the sense of trust they bring to youth, and their independence from the school setting. We conclude by calling for routine screening of bullying by health care providers who deal with paediatric populations.

Comparing Dynamic Treatment Regimes Using Repeated-Measures Outcomes: Modeling Considerations in SMART Studies

PubMed Central

Lu, Xi; Nahum-Shani, Inbal; Kasari, Connie; Lynch, Kevin G.; Oslin, David W.; Pelham, William E.; Fabiano, Gregory; Almirall, Daniel

2016-01-01

A dynamic treatment regime (DTR) is a sequence of decision rules, each of which recommends a treatment based on a patient’s past and current health status. Sequential, multiple assignment, randomized trials (SMARTs) are multi-stage trial designs that yield data specifically for building effective DTRs. Modeling the marginal mean trajectories of a repeated-measures outcome arising from a SMART presents challenges, because traditional longitudinal models used for randomized clinical trials do not take into account the unique design features of SMART. We discuss modeling considerations for various forms of SMART designs, emphasizing the importance of considering the timing of repeated measures in relation to the treatment stages in a SMART. For illustration, we use data from three SMART case studies with increasing level of complexity, in autism, child attention deficit hyperactivity disorder (ADHD), and adult alcoholism. In all three SMARTs we illustrate how to accommodate the design features along with the timing of the repeated measures when comparing DTRs based on mean trajectories of the repeated-measures outcome. PMID:26638988

In their own words? A terminological analysis of e-mail to a cancer information service.

PubMed Central

Smith, Catherine Arnott; Stavri, P. Zoë; Chapman, Wendy Webber

2002-01-01

OBJECTIVE: To better understand the terms used by consumers to describe their health information needs and determine if this "consumer terminology"differs from those used by health care professionals. METHODS: Features and findings identified in 139 e-mail messages to the University of Pittsburgh Cancer Institute's Cancer Information and Referral Service were coded and matched against the 2001 Unified Medical Language System Metathesaurus. RESULTS:504 unique terms were identified. 185 (36%) were exact matches to concepts in the 2001 UMLS Metathesaurus (MTH). 179 (35%) were partial string matches; 119 (24%) were known synonyms for MTH concepts; and 2 (<1%) were lexical variants. Only 19,or 4% of the total terms, were not found to be present in the 2001 MT1H. CONCLUSION: 96% of the clinical findings and features mentioned in e-mail by correspondents who did not self-identify as healthcare professionals were described using terms from controlled healthcare terminologies. The notion of a paradigmatic "consumer" who uses a particular vocabulary specific to her "consumer" status may be ill-founded. PMID:12463914

Comparing dynamic treatment regimes using repeated-measures outcomes: modeling considerations in SMART studies.

PubMed

Lu, Xi; Nahum-Shani, Inbal; Kasari, Connie; Lynch, Kevin G; Oslin, David W; Pelham, William E; Fabiano, Gregory; Almirall, Daniel

2016-05-10

A dynamic treatment regime (DTR) is a sequence of decision rules, each of which recommends a treatment based on a patient's past and current health status. Sequential, multiple assignment, randomized trials (SMARTs) are multi-stage trial designs that yield data specifically for building effective DTRs. Modeling the marginal mean trajectories of a repeated-measures outcome arising from a SMART presents challenges, because traditional longitudinal models used for randomized clinical trials do not take into account the unique design features of SMART. We discuss modeling considerations for various forms of SMART designs, emphasizing the importance of considering the timing of repeated measures in relation to the treatment stages in a SMART. For illustration, we use data from three SMART case studies with increasing level of complexity, in autism, child attention deficit hyperactivity disorder, and adult alcoholism. In all three SMARTs, we illustrate how to accommodate the design features along with the timing of the repeated measures when comparing DTRs based on mean trajectories of the repeated-measures outcome. Copyright © 2015 John Wiley & Sons, Ltd.

Trajectories of Attention Deficit Hyperactivity Disorder and Oppositional Defiant Disorder Symptoms as Precursors of Borderline Personality Disorder Symptoms in Adolescent Girls

PubMed Central

Stepp, Stephanie D.; Burke, Jeffrey D.; Hipwell, Alison E.; Loeber, Rolf

2011-01-01

Little empirical evidence exists regarding the developmental links between childhood psychopathology and borderline personality disorder (BPD) in adolescence. The current study addresses this gap by examining symptoms of attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) as potential precursors. ADHD and BPD share clinical features of impulsivity, poor self-regulation, and executive dysfunction, while ODD and BPD share features of anger and interpersonal turmoil. The study is based on annual, longitudinal data from the two oldest cohorts in the Pittsburgh Girls Study (N = 1233). We used piecewise latent growth curve models of ADHD and ODD scores from age 8–10 and 10–13 years to examine the prospective associations between dual trajectories of ADHD and ODD symptom severity and later BPD symptoms at age 14 in girls. To examine the specificity of these associations, we also included conduct disorder (CD) and depression symptom severity at age 14 as additional outcomes. We found that higher levels of ADHD and ODD scores at age 8 uniquely predicted BPD symptoms at age 14. Additionally, the rate of growth in ADHD scores from age 10–13 and the rate of growth in ODD scores from 8–10 uniquely predicted higher BPD symptoms at age 14. This study adds to the literature on the early development of BPD by providing the first longitudinal study to examine ADHD and ODD symptom trajectories as specific childhood precursors of BPD symptoms in adolescent girls. PMID:21671009

Perfusion characteristics of Moyamoya disease: an anatomically and clinically oriented analysis and comparison.

PubMed

Schubert, Gerrit Alexander; Czabanka, Marcus; Seiz, Marcel; Horn, Peter; Vajkoczy, Peter; Thomé, Claudius

2014-01-01

Moyamoya disease (MMD) is characterized by unique angiographic features of collateralization. However, a detailed quantification as well as comparative analysis with cerebrovascular atherosclerotic disease (CAD) and healthy controls have not been performed to date. We reviewed 67 patients with MMD undergoing Xenon-enhanced computed tomography, as well as 108 patients with CAD and 5 controls. In addition to cortical, central, and infratentorial regions of interest, particular emphasis was put on regions that are typically involved in MMD (pericallosal territory, basal ganglia). Cerebral blood flow (CBF), cerebrovascular reserve capacity (CVRC), and hemodynamic stress distribution were calculated. MMD is characterized by a significant, ubiquitous decrease in CVRC and a cortical but not pericallosal decrease in CBF when compared with controls. Baseline perfusion is maintained within the basal ganglia, and hemodynamic stress distribution confirmed a relative preservation of central regions of interest in MMD, indicative for its characteristic proximal collateralization pattern. In MMD and CAD, cortical and central CBF decreased significantly with age, whereas CVRC and hemodynamic stress distribution are relatively unaffected by age. No difference in CVRC of comparable regions of interest was seen between MMD and CAD, but stress distribution was significantly higher in MMD, illustrating the functionality of the characteristic rete mirabilis. Our data provide quantitative support for a territory-specific perfusion pattern that is unique for MMD, including central preservation of CBF compared with controls and patients with CAD. This correlates well with its characteristic feature of proximal collateralization. CVRC and hemodynamic stress distribution seem to be more robust parameters than CBF alone for assessment of disease severity.

Features of the bronchial bacterial microbiome associated with atopy, asthma, and responsiveness to inhaled corticosteroid treatment.

PubMed

Durack, Juliana; Lynch, Susan V; Nariya, Snehal; Bhakta, Nirav R; Beigelman, Avraham; Castro, Mario; Dyer, Anne-Marie; Israel, Elliot; Kraft, Monica; Martin, Richard J; Mauger, David T; Rosenberg, Sharon R; Sharp-King, Tonya; White, Steven R; Woodruff, Prescott G; Avila, Pedro C; Denlinger, Loren C; Holguin, Fernando; Lazarus, Stephen C; Lugogo, Njira; Moore, Wendy C; Peters, Stephen P; Que, Loretta; Smith, Lewis J; Sorkness, Christine A; Wechsler, Michael E; Wenzel, Sally E; Boushey, Homer A; Huang, Yvonne J

2017-07-01

Compositional differences in the bronchial bacterial microbiota have been associated with asthma, but it remains unclear whether the findings are attributable to asthma, to aeroallergen sensitization, or to inhaled corticosteroid treatment. We sought to compare the bronchial bacterial microbiota in adults with steroid-naive atopic asthma, subjects with atopy but no asthma, and nonatopic healthy control subjects and to determine relationships of the bronchial microbiota to phenotypic features of asthma. Bacterial communities in protected bronchial brushings from 42 atopic asthmatic subjects, 21 subjects with atopy but no asthma, and 21 healthy control subjects were profiled by using 16S rRNA gene sequencing. Bacterial composition and community-level functions inferred from sequence profiles were analyzed for between-group differences. Associations with clinical and inflammatory variables were examined, including markers of type 2-related inflammation and change in airway hyperresponsiveness after 6 weeks of fluticasone treatment. The bronchial microbiome differed significantly among the 3 groups. Asthmatic subjects were uniquely enriched in members of the Haemophilus, Neisseria, Fusobacterium, and Porphyromonas species and the Sphingomonodaceae family and depleted in members of the Mogibacteriaceae family and Lactobacillales order. Asthma-associated differences in predicted bacterial functions included involvement of amino acid and short-chain fatty acid metabolism pathways. Subjects with type 2-high asthma harbored significantly lower bronchial bacterial burden. Distinct changes in specific microbiota members were seen after fluticasone treatment. Steroid responsiveness was linked to differences in baseline compositional and functional features of the bacterial microbiome. Even in subjects with mild steroid-naive asthma, differences in the bronchial microbiome are associated with immunologic and clinical features of the disease. The specific differences identified suggest possible microbiome targets for future approaches to asthma treatment or prevention. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Landscape pattern metrics and regional assessment

Treesearch

Robert V. O' Neill; Kurt H. Riitters; J.D. Wickham; Bruce K. Jones

1999-01-01

The combination of remote imagery data, geographic information systems software, and landscape ecology theory provides a unique basis for monitoring and assessing large-scale ecological systems. The unique feature of the work has been the need to develop interpret quantitative measures of spatial patter-the landscape indices. This article reviews what is known about...

When the Medium Illustrates the Content: Exploiting the Unique Features of Online Communication

ERIC Educational Resources Information Center

Foertsch, Julie; Gernsbacher, Morton Ann

2008-01-01

Julie Foertsch and Morton Ann Gernsbacher present the results of an evaluation of an online undergraduate course in psychology that adheres to the seven widely accepted principles of effective online teaching and suggests an eighth principle: using the unique benefits and constraints of online communication to prompt critical thinking about…

Rethinking the Notion of Technology in Education: Techno-Epistemology as a Feature Inherent to Human Praxis

ERIC Educational Resources Information Center

Van Eijck, Michiel; Claxton, Nicholas Xumthoult

2009-01-01

Educators repeatedly underscore the intimate relationship between science and technology. This is problematic because technology, far from being "applied science," presupposes a unique epistemology (techno-epistemology). A focus on the role of science in technology overshadows this unique way of knowing and hence limits technology…

Preliminary Investigation of the Role of Cellular Immunity in Estrous Cycle Modulation of Post-Resection Breast Cancer Spread

DTIC Science & Technology

2004-08-01

established MTCIL tumor rolls retain this unique biologic feature. -ll suspeniionsw from sth moat vsital porn MTP ntutur arnd injected we inoutlated...rather than linear or continuous process. This biologic growth pattern is not unique nor unprecedented. Growth studies in children using serial height

Radiofrequency Ablation of Hepatocellular Carcinoma with a “Nodule-in-Nodule” Appearance: Long-Term Follow-up and Clinical Implications

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

Kang, Tae Wook; Rhim, Hyunchul, E-mail: rhimhc@skku.edu; Song, Kyoung Doo

PurposeHepatocellular carcinoma (HCC) with a “nodule-in-nodule” (NIN) appearance has unique histological characteristics as an early HCC. We assessed long-term therapeutic outcomes of radiofrequency ablation (RFA) in HCC patients considering this appearance.Materials and MethodsOur Institutional Review Board approved this retrospective study, and the requirement for written informed consent was waived. Between May 2006 and April 2012, a total of 572 patients underwent RFA for single HCC as a first-line treatment. Patients were divided into a NIN HCC group (n = 22) and a non-NIN HCC group (n = 550), according to the NIN feature on pretreatment imaging studies. Local tumor progression (LTP) and disease-free survivalmore » (DFS) were compared. Prognostic factors for LTP and DFS were assessed using a Cox proportional hazards model.ResultsThe cumulative LTP rates were 4.6 and 4.6% at 3 and 5 years, respectively, in the NIN HCC group, and 15.9 and 20.5% in the non-NIN HCC group, with borderline statistical significance (p = 0.085). The corresponding DFS rates were 53.8 and 37.7% in the NIN HCC group and 44.0 and 31.7% in the non-NIN HCC group, with no significant difference (p = 0.318). Although on multivariate analysis only tumor size was a significant prognostic factor for LTP, there was a trend bordering on the significance for the NIN feature [hazard ratio (HR) = 0.19; p = 0.099]. However, it was not a significant factor for DFS (HR = 0.18; p = 0.682).ConclusionsThe NIN appearance, a rare (4%, 22/550) but unique feature of early HCC, may be a favorable prognostic factor for RFA in terms of local tumor control.« less

Evidence for Feature and Location Learning in Human Visual Perceptual Learning

ERIC Educational Resources Information Center

Moreno-Fernández, María Manuela; Salleh, Nurizzati Mohd; Prados, Jose

2015-01-01

In Experiment 1, human participants were pre-exposed to two similar checkerboard grids (AX and X) in alternation, and to a third grid (BX) in a separate block of trials. In a subsequent test, the unique feature A was better detected than the feature B when they were presented in the same location during the pre-exposure and test phases. However,…

Evaluation of a web based informatics system with data mining tools for predicting outcomes with quantitative imaging features in stroke rehabilitation clinical trials

NASA Astrophysics Data System (ADS)

Wang, Ximing; Kim, Bokkyu; Park, Ji Hoon; Wang, Erik; Forsyth, Sydney; Lim, Cody; Ravi, Ragini; Karibyan, Sarkis; Sanchez, Alexander; Liu, Brent

2017-03-01

Quantitative imaging biomarkers are used widely in clinical trials for tracking and evaluation of medical interventions. Previously, we have presented a web based informatics system utilizing quantitative imaging features for predicting outcomes in stroke rehabilitation clinical trials. The system integrates imaging features extraction tools and a web-based statistical analysis tool. The tools include a generalized linear mixed model(GLMM) that can investigate potential significance and correlation based on features extracted from clinical data and quantitative biomarkers. The imaging features extraction tools allow the user to collect imaging features and the GLMM module allows the user to select clinical data and imaging features such as stroke lesion characteristics from the database as regressors and regressands. This paper discusses the application scenario and evaluation results of the system in a stroke rehabilitation clinical trial. The system was utilized to manage clinical data and extract imaging biomarkers including stroke lesion volume, location and ventricle/brain ratio. The GLMM module was validated and the efficiency of data analysis was also evaluated.

Review of fluorescence guided surgery systems: identification of key performance capabilities beyond indocyanine green imaging

PubMed Central

DSouza, Alisha V.; Lin, Huiyun; Henderson, Eric R.; Samkoe, Kimberley S.; Pogue, Brian W.

2016-01-01

Abstract. There is growing interest in using fluorescence imaging instruments to guide surgery, and the leading options for open-field imaging are reviewed here. While the clinical fluorescence-guided surgery (FGS) field has been focused predominantly on indocyanine green (ICG) imaging, there is accelerated development of more specific molecular tracers. These agents should help advance new indications for which FGS presents a paradigm shift in how molecular information is provided for resection decisions. There has been a steady growth in commercially marketed FGS systems, each with their own differentiated performance characteristics and specifications. A set of desirable criteria is presented to guide the evaluation of instruments, including: (i) real-time overlay of white-light and fluorescence images, (ii) operation within ambient room lighting, (iii) nanomolar-level sensitivity, (iv) quantitative capabilities, (v) simultaneous multiple fluorophore imaging, and (vi) ergonomic utility for open surgery. In this review, United States Food and Drug Administration 510(k) cleared commercial systems and some leading premarket FGS research systems were evaluated to illustrate the continual increase in this performance feature base. Generally, the systems designed for ICG-only imaging have sufficient sensitivity to ICG, but a fraction of the other desired features listed above, with both lower sensitivity and dynamic range. In comparison, the emerging research systems targeted for use with molecular agents have unique capabilities that will be essential for successful clinical imaging studies with low-concentration agents or where superior rejection of ambient light is needed. There is no perfect imaging system, but the feature differences among them are important differentiators in their utility, as outlined in the data and tables here. PMID:27533438

Review of fluorescence guided surgery systems: identification of key performance capabilities beyond indocyanine green imaging

NASA Astrophysics Data System (ADS)

DSouza, Alisha V.; Lin, Huiyun; Henderson, Eric R.; Samkoe, Kimberley S.; Pogue, Brian W.

2016-08-01

There is growing interest in using fluorescence imaging instruments to guide surgery, and the leading options for open-field imaging are reviewed here. While the clinical fluorescence-guided surgery (FGS) field has been focused predominantly on indocyanine green (ICG) imaging, there is accelerated development of more specific molecular tracers. These agents should help advance new indications for which FGS presents a paradigm shift in how molecular information is provided for resection decisions. There has been a steady growth in commercially marketed FGS systems, each with their own differentiated performance characteristics and specifications. A set of desirable criteria is presented to guide the evaluation of instruments, including: (i) real-time overlay of white-light and fluorescence images, (ii) operation within ambient room lighting, (iii) nanomolar-level sensitivity, (iv) quantitative capabilities, (v) simultaneous multiple fluorophore imaging, and (vi) ergonomic utility for open surgery. In this review, United States Food and Drug Administration 510(k) cleared commercial systems and some leading premarket FGS research systems were evaluated to illustrate the continual increase in this performance feature base. Generally, the systems designed for ICG-only imaging have sufficient sensitivity to ICG, but a fraction of the other desired features listed above, with both lower sensitivity and dynamic range. In comparison, the emerging research systems targeted for use with molecular agents have unique capabilities that will be essential for successful clinical imaging studies with low-concentration agents or where superior rejection of ambient light is needed. There is no perfect imaging system, but the feature differences among them are important differentiators in their utility, as outlined in the data and tables here.

Concentrating photovoltaic solar panel

DOEpatents

Cashion, Steven A; Bowser, Michael R; Farrelly, Mark B; Hines, Braden E; Holmes, Howard C; Johnson, Jr., Richard L; Russell, Richard J; Turk, Michael F

2014-04-15

The present invention relates to photovoltaic power systems, photovoltaic concentrator modules, and related methods. In particular, the present invention features concentrator modules having interior points of attachment for an articulating mechanism and/or an articulating mechanism that has a unique arrangement of chassis members so as to isolate bending, etc. from being transferred among the chassis members. The present invention also features adjustable solar panel mounting features and/or mounting features with two or more degrees of freedom. The present invention also features a mechanical fastener for secondary optics in a concentrator module.

An optical microfluidic platform for spatiotemporal biofilm treatment monitoring

NASA Astrophysics Data System (ADS)

Kim, Young Wook; Mosteller, Matthew P.; Subramanian, Sowmya; Meyer, Mariana T.; Bentley, William E.; Ghodssi, Reza

2016-01-01

Bacterial biofilms constitute in excess of 65% of clinical microbial infections, with the antibiotic treatment of biofilm infections posing a unique challenge due to their high antibiotic tolerance. Recent studies performed in our group have demonstrated that a bioelectric effect featuring low-intensity electric signals combined with antibiotics can significantly improve the efficacy of biofilm treatment. In this work, we demonstrate the bioelectric effect using sub-micron thick planar electrodes in a microfluidic device. This is critical in efforts to develop microsystems for clinical biofilm infection management, including both in vivo and in vitro applications. Adaptation of the method to the microscale, for example, can enable the development of localized biofilm infection treatment using microfabricated medical devices, while augmenting existing capabilities to perform biofilm management beyond the clinical realm. Furthermore, due to scale-down of the system, the voltage requirement for inducing the electric field is reduced further below the media electrolysis threshold. Enhanced biofilm treatment using the bioelectric effect in the developed microfluidic device elicited a 56% greater reduction in viable cell density and 26% further decrease in biomass growth compared to traditional antibiotic therapy. This biofilm treatment efficacy, demonstrated in a micro-scale device and utilizing biocompatible voltage ranges, encourages the use of this method for future clinical biofilm treatment applications.

Molar incisor hypomineralisation (MIH) training manual for clinical field surveys and practice.

PubMed

Ghanim, A; Silva, M J; Elfrink, M E C; Lygidakis, N A; Mariño, R J; Weerheijm, K L; Manton, D J

2017-08-01

Despite clear assessment criteria, studies of molar incisor hypomineralisation (MIH) and hypomineralised second primary molars (HSPM) are marked by inconsistency in outcome measurements. This has detracted from meaningful comparisons between studies and limited interpretation. To provide a comprehensive manual as a companion to assist researchers in planning epidemiological studies of MIH and HSPM, with particular reference to outcome measurement. This manual begins with a succinct review of the clinical problems and evidence for management of the conditions. The subsequent sections guide researchers through diagnosis of MIH and HSPM and implementation of both the long and short forms of a recently proposed grading system. MIH and HSPM can often be confused with fluorosis, enamel hypoplasia, amelogenesis imperfecta, and white spot lesions but can be distinguished by a number of unique clinical features. Based on the grading system, a standardised protocol is proposed for clinical examinations. Intra and inter-examiner reliability is of key importance when outcome measurement is subjective and should be reported in all epidemiological studies of MIH. The manual concludes with an exercise forum aimed to train examiners in the use of the grading system, with answers provided. The use of a standardised protocol, diagnostic and grading criteria will greatly enhance the quality of epidemiological studies of MIH.

Aspergillus Section Fumigati Typing by PCR-Restriction Fragment Polymorphism▿

PubMed Central

Staab, Janet F.; Balajee, S. Arunmozhi; Marr, Kieren A.

2009-01-01

Recent studies have shown that there are multiple clinically important members of the Aspergillus section Fumigati that are difficult to distinguish on the basis of morphological features (e.g., Aspergillus fumigatus, A. lentulus, and Neosartorya udagawae). Identification of these organisms may be clinically important, as some species vary in their susceptibilities to antifungal agents. In a prior study, we utilized multilocus sequence typing to describe A. lentulus as a species distinct from A. fumigatus. The sequence data show that the gene encoding β-tubulin, benA, has high interspecies variability at intronic regions but is conserved among isolates of the same species. These data were used to develop a PCR-restriction fragment length polymorphism (PCR-RFLP) method that rapidly and accurately distinguishes A. fumigatus, A. lentulus, and N. udagawae, three major species within the section Fumigati that have previously been implicated in disease. Digestion of the benA amplicon with BccI generated unique banding patterns; the results were validated by screening a collection of clinical strains and by in silico analysis of the benA sequences of Aspergillus spp. deposited in the GenBank database. PCR-RFLP of benA is a simple method for the identification of clinically important, similar morphotypes of Aspergillus spp. within the section Fumigati. PMID:19403766

Aspergillus section Fumigati typing by PCR-restriction fragment polymorphism.

PubMed

Staab, Janet F; Balajee, S Arunmozhi; Marr, Kieren A

2009-07-01

Recent studies have shown that there are multiple clinically important members of the Aspergillus section Fumigati that are difficult to distinguish on the basis of morphological features (e.g., Aspergillus fumigatus, A. lentulus, and Neosartorya udagawae). Identification of these organisms may be clinically important, as some species vary in their susceptibilities to antifungal agents. In a prior study, we utilized multilocus sequence typing to describe A. lentulus as a species distinct from A. fumigatus. The sequence data show that the gene encoding beta-tubulin, benA, has high interspecies variability at intronic regions but is conserved among isolates of the same species. These data were used to develop a PCR-restriction fragment length polymorphism (PCR-RFLP) method that rapidly and accurately distinguishes A. fumigatus, A. lentulus, and N. udagawae, three major species within the section Fumigati that have previously been implicated in disease. Digestion of the benA amplicon with BccI generated unique banding patterns; the results were validated by screening a collection of clinical strains and by in silico analysis of the benA sequences of Aspergillus spp. deposited in the GenBank database. PCR-RFLP of benA is a simple method for the identification of clinically important, similar morphotypes of Aspergillus spp. within the section Fumigati.

Suicide by burning: epidemiological and clinical profiles.

PubMed

Theodorou, Panagiotis; Phan, Vu T Q; Weinand, Christian; Maegele, Marc; Maurer, Christoph A; Perbix, Walter; Leitsch, Sebastian; Lefering, Rolf; Spilker, Gerald

2011-04-01

Self-immolation constitutes a rare form of suicide in developed countries, though it accounts for unique injury characteristics in the burn intensive care unit. The aim of this study was to present the epidemiological and clinical features of patients burned during a suicidal attempt seen in a North Rhine-Westphalia burn intensive care unit (BICU). To address this aim, we undertook a 21-year retrospective study involving patients with thermal injuries admitted to the largest burn unit in Germany. A total of 125 suicide-related burn victims were identified in the study period (9.4%). Comparing the self-immolation group with the rest burn patient cohort, suicide victims were more likely to be single and to act under the influence of alcohol. The suicidal group had a larger extent of burns, higher incidence of inhalation injury, required more surgical procedures, catecholamines, blood transfusions, and a longer BICU stay. Their clinical course was complicated by prolonged intubation period, higher rate of multiple drug-resistant bacteria acquisition and sepsis, leading to a higher mortality rate. Although the proportion of self-immolation victims among all burned patients is not high, the markedly higher severity of their burns and their poorer quality of outcomes makes them an important clinical subgroup for further study.

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

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Aircraft Landing Dynamics Facility - A unique facility with new capabilities

NASA Technical Reports Server (NTRS)

Davis, P. A.; Stubbs, S. M.; Tanner, J. A.

1985-01-01

The Aircraft Landing Dynamics Facility (ALDF), formerly called the Landing Loads Track, is described. The paper gives a historical overview of the original NASA Langley Research Center Landing Loads Track and discusses the unique features of this national test facility. Comparisons are made between the original track characteristics and the new capabilities of the Aircraft Landing Dynamics Facility following the recently completed facility update. Details of the new propulsion and arresting gear systems are presented along with the novel features of the new high-speed carriage. The data acquisition system is described and the paper concludes with a review of future test programs.

Clinical Features and Associated Likelihood of Primary Ciliary Dyskinesia in Children and Adolescents

PubMed Central

Ferkol, Thomas W.; Davis, Stephanie D.; Lee, Hye-Seung; Rosenfeld, Margaret; Dell, Sharon D.; Sagel, Scott D.; Milla, Carlos; Olivier, Kenneth N.; Sullivan, Kelli M.; Zariwala, Maimoona A.; Pittman, Jessica E.; Shapiro, Adam J.; Carson, Johnny L.; Krischer, Jeffrey; Hazucha, Milan J.

2016-01-01

Rationale: Primary ciliary dyskinesia (PCD), a genetically heterogeneous, recessive disorder of motile cilia, is associated with distinct clinical features. Diagnostic tests, including ultrastructural analysis of cilia, nasal nitric oxide measurements, and molecular testing for mutations in PCD genes, have inherent limitations. Objectives: To define a statistically valid combination of systematically defined clinical features that strongly associates with PCD in children and adolescents. Methods: Investigators at seven North American sites in the Genetic Disorders of Mucociliary Clearance Consortium prospectively and systematically assessed individuals (aged 0–18 yr) referred due to high suspicion for PCD. The investigators defined specific clinical questions for the clinical report form based on expert opinion. Diagnostic testing was performed using standardized protocols and included nasal nitric oxide measurement, ciliary biopsy for ultrastructural analysis of cilia, and molecular genetic testing for PCD-associated genes. Final diagnoses were assigned as “definite PCD” (hallmark ultrastructural defects and/or two mutations in a PCD-associated gene), “probable/possible PCD” (no ultrastructural defect or genetic diagnosis, but compatible clinical features and nasal nitric oxide level in PCD range), and “other diagnosis or undefined.” Criteria were developed to define early childhood clinical features on the basis of responses to multiple specific queries. Each defined feature was tested by logistic regression. Sensitivity and specificity analyses were conducted to define the most robust set of clinical features associated with PCD. Measurements and Main Results: From 534 participants 18 years of age and younger, 205 were identified as having “definite PCD” (including 164 with two mutations in a PCD-associated gene), 187 were categorized as “other diagnosis or undefined,” and 142 were defined as having “probable/possible PCD.” Participants with “definite PCD” were compared with the “other diagnosis or undefined” group. Four criteria-defined clinical features were statistically predictive of PCD: laterality defect; unexplained neonatal respiratory distress; early-onset, year-round nasal congestion; and early-onset, year-round wet cough (adjusted odds ratios of 7.7, 6.6, 3.4, and 3.1, respectively). The sensitivity and specificity based on the number of criteria-defined clinical features were four features, 0.21 and 0.99, respectively; three features, 0.50 and 0.96, respectively; and two features, 0.80 and 0.72, respectively. Conclusions: Systematically defined early clinical features could help identify children, including infants, likely to have PCD. Clinical trial registered with ClinicalTrials.gov (NCT00323167). PMID:27070726

Cancer immunotherapy: Opportunities and challenges in the rapidly evolving clinical landscape.

PubMed

Emens, Leisha A; Ascierto, Paolo A; Darcy, Phillip K; Demaria, Sandra; Eggermont, Alexander M M; Redmond, William L; Seliger, Barbara; Marincola, Francesco M

2017-08-01

Cancer immunotherapy is now established as a powerful way to treat cancer. The recent clinical success of immune checkpoint blockade (antagonists of CTLA-4, PD-1 and PD-L1) highlights both the universal power of treating the immune system across tumour types and the unique features of cancer immunotherapy. Immune-related adverse events, atypical clinical response patterns, durable responses, and clear overall survival benefit distinguish cancer immunotherapy from cytotoxic cancer therapy. Combination immunotherapies that transform non-responders to responders are under rapid development. Current challenges facing the field include incorporating immunotherapy into adjuvant and neoadjuvant cancer therapy, refining dose, schedule and duration of treatment and developing novel surrogate endpoints that accurately capture overall survival benefit early in treatment. As the field rapidly evolves, we must prioritise the development of biomarkers to guide the use of immunotherapies in the most appropriate patients. Immunotherapy is already transforming cancer from a death sentence to a chronic disease for some patients. By making smart, evidence-based decisions in developing next generation immunotherapies, cancer should become an imminently treatable, curable and even preventable disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Biological Gene Delivery Vehicles: Beyond Viral Vectors

PubMed Central

Seow, Yiqi; Wood, Matthew J

2009-01-01

Gene therapy covers a broad spectrum of applications, from gene replacement and knockdown for genetic or acquired diseases such as cancer, to vaccination, each with different requirements for gene delivery. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications today, but both have limitations and risks, including complexity of production, limited packaging capacity, and unfavorable immunological features, which restrict gene therapy applications and hold back the potential for preventive gene therapy. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents which include bacteria, bacteriophage, virus-like particles (VLPs), erythrocyte ghosts, and exosomes. Exploiting the natural properties of these biological entities for specific gene delivery applications will expand the repertoire of gene therapy vectors available for clinical use. Here, we review the prospects for nonviral biological delivery vehicles as gene therapy agents with focus on their unique evolved biological properties and respective limitations and potential applications. The potential of these nonviral biological entities to act as clinical gene therapy delivery vehicles has already been shown in clinical trials using bacteria-mediated gene transfer and with sufficient development, these entities will complement the established delivery techniques for gene therapy applications. PMID:19277019

Biological gene delivery vehicles: beyond viral vectors.

PubMed

Seow, Yiqi; Wood, Matthew J

2009-05-01

Gene therapy covers a broad spectrum of applications, from gene replacement and knockdown for genetic or acquired diseases such as cancer, to vaccination, each with different requirements for gene delivery. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications today, but both have limitations and risks, including complexity of production, limited packaging capacity, and unfavorable immunological features, which restrict gene therapy applications and hold back the potential for preventive gene therapy. While continuing to improve these vectors, it is important to investigate other options, particularly nonviral biological agents which include bacteria, bacteriophage, virus-like particles (VLPs), erythrocyte ghosts, and exosomes. Exploiting the natural properties of these biological entities for specific gene delivery applications will expand the repertoire of gene therapy vectors available for clinical use. Here, we review the prospects for nonviral biological delivery vehicles as gene therapy agents with focus on their unique evolved biological properties and respective limitations and potential applications. The potential of these nonviral biological entities to act as clinical gene therapy delivery vehicles has already been shown in clinical trials using bacteria-mediated gene transfer and with sufficient development, these entities will complement the established delivery techniques for gene therapy applications.

Cerebral microhemorrhages due to traumatic brain injury and their effects on the aging human brain.

PubMed

Irimia, Andrei; Van Horn, John D; Vespa, Paul M

2018-06-01

Although cerebral microbleeds (CMBs) are frequently associated with traumatic brain injury (TBI), their effects on clinical outcome after TBI remain controversial and poorly understood, particularly in older adults. Here we (1) highlight major challenges and opportunities associated with studying the effects of TBI-mediated CMBs; (2) review the evidence on their potential effects on cognitive and neural outcome as a function of age at injury; and (3) suggest priorities for future research on understanding the clinical implications of CMBs. Although TBI-mediated CMBs are likely distinct from those due to cerebral amyloid angiopathy or other neurodegenerative diseases, the effects of these 2 CMB types on brain function may share common features. Furthermore, in older TBI victims, the incidence of TBI-mediated CMBs may approximate that of cerebral amyloid angiopathy-related CMBs, and thus warrants detailed study. Because the alterations effected by CMBs on brain structure and function are both unique and age-dependent, it seems likely that novel, age-tailored therapeutic approaches are necessary for the adequate clinical interpretation and treatment of these ubiquitous and underappreciated TBI sequelae. Copyright © 2018 Elsevier Inc. All rights reserved.

Hypnosis Training and Education: Distinctive Features of Training Hypnosis Educators.

PubMed

Linden, Julie H; Anbar, Ran

2017-01-01

Much of the field of hypnosis education focuses on what to teach (content) and who to teach (professional identities). A deserving area of focus, and less often addressed, is how to teach basic hypnosis concepts. Worldwide models for teaching hypnosis have mostly included lecture, demonstration, and practice, with little attention paid to the meta-level of educational principles (i.e., what makes an expert trainer). Trainers in hypnosis have been compared to parents: They teach the way they were taught (adults parent the way they were parented). There is a human tendency to repeat what we have experienced. This propensity can be seen while watching the new student use the same induction, in the same way, as his or her first "operator" did when s/he was a subject of his/her first hypnotic experience. Mirroring is a part of all learning, and this article asks what else is needed in faculty education for the trainer to take students beyond mere mimicry to scientifically informed, skilled, and clinically creative uses of hypnosis. This article addresses the unique requirements for teaching hypnosis, reviews a teaching program for clinical hypnosis educators developed by the authors, and looks to future innovations in clinical hypnosis training.

Managing and Communicating Operational Workflow

PubMed Central

Weinberg, Stuart T.; Danciu, Ioana; Unertl, Kim M.

2016-01-01

Summary Background Healthcare team members in emergency department contexts have used electronic whiteboard solutions to help manage operational workflow for many years. Ambulatory clinic settings have highly complex operational workflow, but are still limited in electronic assistance to communicate and coordinate work activities. Objective To describe and discuss the design, implementation, use, and ongoing evolution of a coordination and collaboration tool supporting ambulatory clinic operational workflow at Vanderbilt University Medical Center (VUMC). Methods The outpatient whiteboard tool was initially designed to support healthcare work related to an electronic chemotherapy order-entry application. After a highly successful initial implementation in an oncology context, a high demand emerged across the organization for the outpatient whiteboard implementation. Over the past 10 years, developers have followed an iterative user-centered design process to evolve the tool. Results The electronic outpatient whiteboard system supports 194 separate whiteboards and is accessed by over 2800 distinct users on a typical day. Clinics can configure their whiteboards to support unique workflow elements. Since initial release, features such as immunization clinical decision support have been integrated into the system, based on requests from end users. Conclusions The success of the electronic outpatient whiteboard demonstrates the usefulness of an operational workflow tool within the ambulatory clinic setting. Operational workflow tools can play a significant role in supporting coordination, collaboration, and teamwork in ambulatory healthcare settings. PMID:27081407

Social Media Use, Friendship Quality, and the Moderating Role of Anxiety in Adolescents with Autism Spectrum Disorder.

PubMed

van Schalkwyk, Gerrit I; Marin, Carla E; Ortiz, Mayra; Rolison, Max; Qayyum, Zheala; McPartland, James C; Lebowitz, Eli R; Volkmar, Fred R; Silverman, Wendy K

2017-09-01

Social media holds promise as a technology to facilitate social engagement, but may displace offline social activities. Adolescents with ASD are well suited to capitalize on the unique features of social media, which requires less decoding of complex social information. In this cross-sectional study, we assessed social media use, anxiety and friendship quality in 44 adolescents with ASD, and 56 clinical comparison controls. Social media use was significantly associated with high friendship quality in adolescents with ASD, which was moderated by the adolescents' anxiety levels. No associations were founds between social media use, anxiety and friendship quality in the controls. Social media may be a way for adolescents with ASD without significant anxiety to improve the quality of their friendships.

Insulin dependent diabetes mellitus (IDDM) and autoimmune thyroiditis in a boy with a ring chromosome 18: additional evidence of autoimmunity or IDDM gene(s) on chromosome 18

PubMed Central

Dacou-Voutetakis, C; Sertedaki, A; Maniatis-Christid..., M; Sarri, C; Karadima, G; Petersen, M; Xaidara, A; Kanariou, M; Nicolaidou, P

1999-01-01

A 4 year 3 month old boy with insulin dependent diabetes mellitus (IDDM), autoimmune thyroiditis, slight mental retardation, facial dysmorphism, and a de novo ring chromosome 18 (deletion 18q22.3-18qter) is described. This unique association of defects could represent a chance association. Alternatively, the clinical features could be the result of the chromosomal aberration. If so, one could speculate that a gene or genes on chromosome 18 might act as a suppressor or activator of the autoimmune process by itself or in concert with other IDDM loci.


Keywords: ring chromosome 18; chromosome 18 deletion; IDDM; hypothyroidism PMID:10051018

[A parotitis as primary infection of Lemierre's syndrome].

PubMed

Valleix, B; Floccard, B; Hautin, E; Faure, F; Allaouchiche, B

2011-09-01

Lemierre's syndrome is a classical presentation of human necrobacillosis. It is characterized by a primary infection in the face including a septic thrombophlebitis of the internal jugular vein and disseminated metastatic abcesses. Fusobacterium necrophorum is the main pathogen found in that syndrome. The diagnosis is based on clinical features, then on the microbiology with positive anaerobic blood cultures as key role and finally on the computed tomography. Most of the time a well-chosen antibiotic treatment against anaerobic pathogens and Gram negative bacilli is efficient but surgery can be useful. We report a case of a 73 years old man, which seems to be unique because it is the first case reported of a Lemierre's syndrome characterized by a parotitis infected by F. necrophorum. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Juvenile Spring Eruption: A Variant of Perniosis?

PubMed

Nabatian, Adam S; Rosman, Ilana S; Sturza, Jeffrey; Jacobson, Mark

2015-09-01

Juvenile spring eruption (JSE) is a unique condition that typically affects the helices of the ears of boys and young men. The classical clinical picture of JSE includes the abrupt onset of lesions after spending time outdoors in the early spring. Because of the papulovesicular nature of the rash and the history of sun exposure, JSE is considered a variant of polymorphous light eruption. In addition to the term "juvenile spring eruption," this entity has also been described under other less common terms such as "perniosis juvenilis vernalis aurium" or "spring perniosis," which emphasizes the onset in the spring and the possible pathogenic role of cold weather. We present a case of likely JSE with histopathologic features more consistent with perniosis than polymorphous light eruption and present a review the literature.

Advantages and challenges offered by biofunctional core-shell fiber systems for tissue engineering and drug delivery.

PubMed

Sperling, Laura E; Reis, Karina P; Pranke, Patricia; Wendorff, Joachim H

2016-08-01

Whereas highly porous scaffolds composed of electrospun nanofibers can mimick major features of the extracellular matrix in tissue engineering, they lack the ability to incorporate and release biocompounds (drugs, growth factors) safely in a controlled way. Here, electrospun core-shell fibers (core made from water and aqueous solutions of hydrophilic polymers and the shell from materials with well-defined release mechanisms) offer unique advantages in comparison with those that have helped make porous nanofibrillar scaffolds highly successful in tissue engineering. This review considers the preparation and biofunctionalization of such core-shell fibers as well as applications in various areas, including neural, vascular, cardiac, cartilage and bone tissue engineering, and touches on the topic of clinical trials. Copyright © 2016 Elsevier Ltd. All rights reserved.

GISentinel: a software platform for automatic ulcer detection on capsule endoscopy videos

NASA Astrophysics Data System (ADS)

Yi, Steven; Jiao, Heng; Meng, Fan; Leighton, Jonathon A.; Shabana, Pasha; Rentz, Lauri

2014-03-01

In this paper, we present a novel and clinically valuable software platform for automatic ulcer detection on gastrointestinal (GI) tract from Capsule Endoscopy (CE) videos. Typical CE videos take about 8 hours. They have to be reviewed manually by physicians to detect and locate diseases such as ulcers and bleedings. The process is time consuming. Moreover, because of the long-time manual review, it is easy to lead to miss-finding. Working with our collaborators, we were focusing on developing a software platform called GISentinel, which can fully automated GI tract ulcer detection and classification. This software includes 3 parts: the frequency based Log-Gabor filter regions of interest (ROI) extraction, the unique feature selection and validation method (e.g. illumination invariant feature, color independent features, and symmetrical texture features), and the cascade SVM classification for handling "ulcer vs. non-ulcer" cases. After the experiments, this SW gave descent results. In frame-wise, the ulcer detection rate is 69.65% (319/458). In instance-wise, the ulcer detection rate is 82.35%(28/34).The false alarm rate is 16.43% (34/207). This work is a part of our innovative 2D/3D based GI tract disease detection software platform. The final goal of this SW is to find and classification of major GI tract diseases intelligently, such as bleeding, ulcer, and polyp from the CE videos. This paper will mainly describe the automatic ulcer detection functional module.

Collinearity Impairs Local Element Visual Search

ERIC Educational Resources Information Center

Jingling, Li; Tseng, Chia-Huei

2013-01-01

In visual searches, stimuli following the law of good continuity attract attention to the global structure and receive attentional priority. Also, targets that have unique features are of high feature contrast and capture attention in visual search. We report on a salient global structure combined with a high orientation contrast to the…

Principal Stability and the Rural Divide

ERIC Educational Resources Information Center

Pendola, Andrew; Fuller, Edward J.

2018-01-01

This article examines the unique features of the rural school context and how these features are associated with the stability of principals in these schools. Given the small but growing literature on the characteristics of rural principals, this study presents an exploratory analysis of principal stability across schools located in different…

Ergonomic audit of a specially engineered sonic powered toothbrush with unique sensing and control technologies, the Sonicare Flexcare, and the Oral-B Smart Series 5000.

PubMed

Hunter, Gail; Burns, Laurie; Bone, Brian; Mintel, Thomas; Jimenez, Eduardo

2012-01-01

The presence of ergonomic features can impact the marketplace success of a new product. Metaphase Design Group, Inc., in partnership with the Colgate-Palmolive Company, conducted an ergonomic audit on three electric toothbrushes: a specially engineered sonic powered toothbrush with unique sensing and control technologies, the Sonicare FlexCare, and the Oral-B Smart Series 5000. The ergonomic audit was conducted by Metaphase Design Groups's ergonomic and usability experts. Two experts used the toothbrushes over a one-week period and assessed the performance of each brush against a set of ergonomic principles. The three toothbrushes have some solid ergonomic features. They each have adequate grip zones, provide grip security with elastomeric materials, and provide easy access to the on/off button. The most distinctive feature is the longitudinal shape of the handle of the specially engineered sonic powered toothbrush with unique sensing and control technologies. This handle angles downward at the top end and provides additional advantages through improved grip security and visibility. Yet all three toothbrushes have different opportunities for improvement. The Sonicare Flex Care toothbrush has a cluttered and complicated user interface that is difficult to read. The disadvantages of the Oral-B Smart Series 5000 toothbrush are related to its physical dimensions and audible feedback. The specially engineered sonic powered toothbrush with unique sensing afid control technologies is surprising to use with its changes in speeds, brush movements, and resulting changes in audible feedback.

Robust extrema features for time-series data analysis.

PubMed

Vemulapalli, Pramod K; Monga, Vishal; Brennan, Sean N

2013-06-01

The extraction of robust features for comparing and analyzing time series is a fundamentally important problem. Research efforts in this area encompass dimensionality reduction using popular signal analysis tools such as the discrete Fourier and wavelet transforms, various distance metrics, and the extraction of interest points from time series. Recently, extrema features for analysis of time-series data have assumed increasing significance because of their natural robustness under a variety of practical distortions, their economy of representation, and their computational benefits. Invariably, the process of encoding extrema features is preceded by filtering of the time series with an intuitively motivated filter (e.g., for smoothing), and subsequent thresholding to identify robust extrema. We define the properties of robustness, uniqueness, and cardinality as a means to identify the design choices available in each step of the feature generation process. Unlike existing methods, which utilize filters "inspired" from either domain knowledge or intuition, we explicitly optimize the filter based on training time series to optimize robustness of the extracted extrema features. We demonstrate further that the underlying filter optimization problem reduces to an eigenvalue problem and has a tractable solution. An encoding technique that enhances control over cardinality and uniqueness is also presented. Experimental results obtained for the problem of time series subsequence matching establish the merits of the proposed algorithm.

Is God Coming to Campus Too? Thoughts on the Distinctive Features of Adventist Higher Education

ERIC Educational Resources Information Center

Andreason, Niels-Erik

2005-01-01

In this, the first of a series of short essays which explore the unique ethos embraced and advanced by different Christian denominations in their schools, Andreasen argues the necessity of Christian colleges and universities offering their students a unique, distinctive Christian perspective throughout their learning experience rather than some…

Draft Genome Sequence of the Spore-Forming Probiotic Strain Bacillus coagulans Unique IS-2

PubMed Central

Upadrasta, Aditya; Pitta, Swetha

2016-01-01

Bacillus coagulans Unique IS-2 is a potential spore-forming probiotic that is commercially available on the market. The draft genome sequence presented here provides deep insight into the beneficial features of this strain for its safe use as a probiotic for various human and animal health applications. PMID:27103709

Engine systems and methods of operating an engine

DOEpatents

Scotto, Mark Vincent

2015-08-25

One embodiment of the present invention is a unique method for operating an engine. Another embodiment is a unique engine system. Other embodiments include apparatuses, systems, devices, hardware, methods, and combinations for engines and engine systems. Further embodiments, forms, features, aspects, benefits, and advantages of the present application will become apparent from the description and figures provided herewith.

Engine systems and methods of operating an engine

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

Scotto, Mark Vincent

One embodiment of the present invention is a unique method for operating an engine. Another embodiment is a unique engine system. Other embodiments include apparatuses, systems, devices, hardware, methods, and combinations for engines and engine systems. Further embodiments, forms, features, aspects, benefits, and advantages of the present application will become apparent from the description and figures provided herewith.

Unusual presentation of obscure Meckel diverticulum treated with robot-assisted diverticulectomy: A case report.

PubMed

Pandey, Sagar; Fan, Miao; Xu, Zhe; Yan, Chaogui; Zhu, Junfeng; Li, Xiuhong

2016-10-01

Meckel diverticulum (MD) is the most common congenital abnormality of gastrointestinal tract. Tough believed to occur in 2% of population, most of them remain veiled because majority are clinically asymptomatic and remain obscure in radiological examination. A 26-year-old male with episodic black colored stool since last 10 years. Tough symptomatic, diagnosis of pathological lesion, and the bleeding site could not be established with any of the sophisticated diagnostic technique. After 10 years, it was finally diagnosed as MD with careful observation of bowel loops on computed tomography enterography (CTE) where remnant of vitelline vessel and hyper-enhancing nodule are seen along the wall of diverticular loop. The patient underwent robot assisted laparoscopic surgery with excision of diverticular loop. To the best of our knowledge, this robot-assistant Meckel diverculectomy is probably the first reported surgical procedure in PubMed. Follow-up for 3 month showed no complication or recurrence. Every case is unique and we must be aware and remain alert in tracing the possible morphological variation of the case. Here, we present one unique but rare feature of MD, which helped us in making diagnosis.

Aging Differences in Ethnic Skin

PubMed Central

Buainain De Castro Maymone, Mayra; Kundu, Roopal V.

2016-01-01

Aging is an inevitable and complex process that can be described clinically as features of wrinkles, sunspots, uneven skin color, and sagging skin. These cutaneous effects are influenced by both intrinsic and extrinsic factors and often are varied based on ethnic origin given underlying structural and functional differences. The authors sought to provide updated information on facets of aging and how it relates to ethnic variation given innate differences in skin structure and function. Publications describing structural and functional principles of ethnic and aging skin were primarily found through a PubMed literature search and supplemented with a review of textbook chapters. The most common signs of skin aging despite skin type are dark spots, loss of elasticity, loss of volume, and rhytides. Skin of color has many characteristics that make its aging process unique. Those of Asian, Hispanic, and African American descent have distinct facial structures. Differences in the concentration of epidermal melanin makes darkly pigmented persons more vulnerable to dyspigmentation, while a thicker and more compact dermis makes facial lines less noticeable. Ethnic skin comprises a large portion of the world population. Therefore, it is important to understand the unique structural and functional differences among ethnicities to adequately treat the signs of aging. PMID:26962390

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

PubMed

Kusec, Andrea; Tallon, Kathleen; Koerner, Naomi

2016-06-01

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

Resting State EEG-based biometrics for individual identification using convolutional neural networks.

PubMed

Lan Ma; Minett, James W; Blu, Thierry; Wang, William S-Y

2015-08-01

Biometrics is a growing field, which permits identification of individuals by means of unique physical features. Electroencephalography (EEG)-based biometrics utilizes the small intra-personal differences and large inter-personal differences between individuals' brainwave patterns. In the past, such methods have used features derived from manually-designed procedures for this purpose. Another possibility is to use convolutional neural networks (CNN) to automatically extract an individual's best and most unique neural features and conduct classification, using EEG data derived from both Resting State with Open Eyes (REO) and Resting State with Closed Eyes (REC). Results indicate that this CNN-based joint-optimized EEG-based Biometric System yields a high degree of accuracy of identification (88%) for 10-class classification. Furthermore, rich inter-personal difference can be found using a very low frequency band (0-2Hz). Additionally, results suggest that the temporal portions over which subjects can be individualized is less than 200 ms.

Radiobiological studies with the nematode Caenorhabditis elegans. Genetic and developmental effects of high LET radiation

NASA Technical Reports Server (NTRS)

Nelson, G. A.; Schubert, W. W.; Marshall, T. M.

1992-01-01

The biological effects of heavy charged particle (HZE) radiation are of particular interest to travellers and planners for long-duration space flights where exposure levels represent a potential health hazard. The unique feature of HZE radiation is the structured pattern of its energy deposition in targets. There are many consequences of this feature to biological endpoints when compared with effects of ionizing photons. Dose vs response and dose-rate kinetics may be modified, DNA and cellular repair systems may be altered in their abilities to cope with damage, and the qualitative features of damage may be unique for different ions. The nematode Caenorhabditis elegans is being used to address these and related questions associated with exposure to radiation. HZE-induced mutation, chromosome aberration, cell inactivation and altered organogenesis are discussed along with plans for radiobiological experiments in space.

Context-based automated defect classification system using multiple morphological masks

DOEpatents

Gleason, Shaun S.; Hunt, Martin A.; Sari-Sarraf, Hamed

2002-01-01

Automatic detection of defects during the fabrication of semiconductor wafers is largely automated, but the classification of those defects is still performed manually by technicians. This invention includes novel digital image analysis techniques that generate unique feature vector descriptions of semiconductor defects as well as classifiers that use these descriptions to automatically categorize the defects into one of a set of pre-defined classes. Feature extraction techniques based on multiple-focus images, multiple-defect mask images, and segmented semiconductor wafer images are used to create unique feature-based descriptions of the semiconductor defects. These feature-based defect descriptions are subsequently classified by a defect classifier into categories that depend on defect characteristics and defect contextual information, that is, the semiconductor process layer(s) with which the defect comes in contact. At the heart of the system is a knowledge database that stores and distributes historical semiconductor wafer and defect data to guide the feature extraction and classification processes. In summary, this invention takes as its input a set of images containing semiconductor defect information, and generates as its output a classification for the defect that describes not only the defect itself, but also the location of that defect with respect to the semiconductor process layers.

Catatonia in Psychotic Patients: Clinical Features and Treatment Response

PubMed Central

England, Mary L.; Öngür, Dost; Konopaske, Glenn T.; Karmacharya, Rakesh

2012-01-01

We report clinical features and treatment response in 25 patients with catatonia admitted to an inpatient psychiatric unit specializing in psychotic disorders. ECT, benzodiazepines, and clozapine had beneficial effects on catatonic features, while typical antipsychotics resulted in clinical worsening. PMID:21677256

Clinical and Public Health Considerations in Urine Drug Testing to Identify and Treat Substance Use.

PubMed

Barthwell, Andrea G

2016-05-11

To expand appropriate use of substance use testing, practitioners must increase their knowledge of the appropriate methodology, scope, and frequency. Yet, there is a current lack of accepted guidelines on clinical testing to identify and treat substance use. This article (1) conveys the importance of substance use testing as a clinical and public health response to trends of prescription drug abuse and increased access to medical and commercialized marijuana; (2) summarizes central features of the rapidly evolving science and the practice of patient-centered substance use testing in a clinical setting; and (3) provides recommendations that balance costs and benefits and serve as a starting point for appropriate testing to prevent, identify, and treat substance use disorders. The author conducted a search of peer-reviewed and government-supported articles and books in electronic databases and used her own knowledge and clinical experience. The author makes recommendations for determining the methodology, scope, and frequency of testing in each stage of care based on clinical considerations and methodological factors. Conclusion/Importance: Integrating sensible substance use testing broadly into clinical health care to identify substance use, diagnose substance use disorders, and guide patients into treatment can improve health outcomes and reduce the costs of substance use and addiction. No single testing regimen is suitable for all clinical scenarios; rather, a multitude of options, as discussed herein, can be adapted to meet a patient's unique needs. Ultimately, the practitioner must combine patient-specific information with knowledge of test technologies, capabilities, limitations, and costs.

Clinical and Radiological Profile of Acute Fibrinous and Organizing Pneumonia: A Retrospective Study.

PubMed

Dai, Jing-Hong; Li, Hui; Shen, Wei; Miao, Li-Yun; Xiao, Yong-Long; Huang, Mei; Cao, Meng-Shu; Wang, Yang; Zhu, Bin; Meng, Fan-Qing; Cai, Hou-Rong

2015-10-20

Acute fibrinous and organizing pneumonia (AFOP) is a unique pathological entity with intra-alveolar fibrin in the form of "fibrin balls" and organizing pneumonia. It was divided into rare idiopathic interstitial pneumonia according to the classification notified by American Thoracic Society/European Respiratory Society in 2013. As a rare pathological entity, it is still not well known and recognized by clinicians. We reviewed the clinical features of 20 patients with AFOP diagnosed in a teaching hospital. The medical records of 20 patients with biopsy-proven diagnosis of AFOP were retrospectively reviewed. The patients' symptoms, duration of the disease, comorbidities, clinical laboratory data, pulmonary function testing, radiographic studies, and the response to treatment were extracted and analyzed. Fever was the most common symptom and was manifested in 90% of AFOP patients. For clinical laboratory findings, systematic inflammatory indicators, including C-reactive protein and erythrocyte sedimentation rate, were significantly higher than normal in AFOP patients. In accordance with this increased indicators, injured liver functions were common in AFOP patients. Inversely, AFOP patients had worse clinical conditions including anemia and hypoalbuminemia. For pulmonary function testing, AFOP patients showed the pattern of restrictive mixed with obstructive ventilation dysfunction. For high-resolution computerized tomography (HRCT) findings, the most common pattern for AFOP patients was lobar consolidation which was very similar to pneumonia. However, unlike pneumonia, AFOP patients responded well to glucocorticoids. Patients with AFOP manifest as acute inflammatory-like clinical laboratory parameters and lobar consolidation on HRCT, but respond well to steroid.

Subacute Sclerosing Panencephalitis of the Brainstem as a Clinical Entity

PubMed Central

Yang, Jason; Ciacci, Joseph D.

2017-01-01

Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine. SSPE is a devastating disease with a characteristic clinical course in subcortical white matter; however, atypical presentations of brainstem involvement may be seen in rare cases. This review summarizes reports to date on brainstem involvement in SSPE, including the clinical course of disease, neuroimaging presentations, and guidelines for treatment. A comprehensive literature search was performed for English-language publications with keywords “subacute sclerosing panencephalitis” and “brainstem” using the National Library of Medicine PubMed database (March 1981–September 2017). Eleven articles focusing on SSPE of the brainstem were included. Predominant brainstem involvement remains uncharacteristic of SSPE, which may lead to misdiagnosis and poor outcome. A number of case reports have demonstrated brainstem involvement associated with other intracranial lesions commonly presenting in later SSPE stages (III and IV). However, brainstem lesions can appear in all stages, independent of higher cortical structures. The varied clinical presentations complicate diagnosis from a neuroimaging perspective. SSPE of the brainstem is a rare but important clinical entity. It may present like canonical SSPE or with unique clinical features such as absence seizures and pronounced ataxia. While SSPE generally progresses to the brainstem, it can also begin with a primary focus of infection in the brainstem. Awareness of varied SSPE presentations can aid in early diagnosis as well as guide management and treatment. PMID:29112137

Subacute Sclerosing Panencephalitis of the Brainstem as a Clinical Entity.

PubMed

Upadhyayula, Pavan S; Yang, Jason; Yue, John K; Ciacci, Joseph D

2017-11-07

Subacute sclerosing panencephalitis (SSPE) is a rare progressive neurological disorder of early adolescence caused by persistent infection of the measles virus, which remains prevalent worldwide despite an effective vaccine. SSPE is a devastating disease with a characteristic clinical course in subcortical white matter; however, atypical presentations of brainstem involvement may be seen in rare cases. This review summarizes reports to date on brainstem involvement in SSPE, including the clinical course of disease, neuroimaging presentations, and guidelines for treatment. A comprehensive literature search was performed for English-language publications with keywords "subacute sclerosing panencephalitis" and "brainstem" using the National Library of Medicine PubMed database (March 1981-September 2017). Eleven articles focusing on SSPE of the brainstem were included. Predominant brainstem involvement remains uncharacteristic of SSPE, which may lead to misdiagnosis and poor outcome. A number of case reports have demonstrated brainstem involvement associated with other intracranial lesions commonly presenting in later SSPE stages (III and IV). However, brainstem lesions can appear in all stages, independent of higher cortical structures. The varied clinical presentations complicate diagnosis from a neuroimaging perspective. SSPE of the brainstem is a rare but important clinical entity. It may present like canonical SSPE or with unique clinical features such as absence seizures and pronounced ataxia. While SSPE generally progresses to the brainstem, it can also begin with a primary focus of infection in the brainstem. Awareness of varied SSPE presentations can aid in early diagnosis as well as guide management and treatment.

A neuro-fuzzy architecture for real-time applications

NASA Technical Reports Server (NTRS)

Ramamoorthy, P. A.; Huang, Song

1992-01-01

Neural networks and fuzzy expert systems perform the same task of functional mapping using entirely different approaches. Each approach has certain unique features. The ability to learn specific input-output mappings from large input/output data possibly corrupted by noise and the ability to adapt or continue learning are some important features of neural networks. Fuzzy expert systems are known for their ability to deal with fuzzy information and incomplete/imprecise data in a structured, logical way. Since both of these techniques implement the same task (that of functional mapping--we regard 'inferencing' as one specific category under this class), a fusion of the two concepts that retains their unique features while overcoming their individual drawbacks will have excellent applications in the real world. In this paper, we arrive at a new architecture by fusing the two concepts. The architecture has the trainability/adaptibility (based on input/output observations) property of the neural networks and the architectural features that are unique to fuzzy expert systems. It also does not require specific information such as fuzzy rules, defuzzification procedure used, etc., though any such information can be integrated into the architecture. We show that this architecture can provide better performance than is possible from a single two or three layer feedforward neural network. Further, we show that this new architecture can be used as an efficient vehicle for hardware implementation of complex fuzzy expert systems for real-time applications. A numerical example is provided to show the potential of this approach.

β-Propeller protein-associated neurodegeneration: a new X-linked dominant disorder with brain iron accumulation.

PubMed

Hayflick, Susan J; Kruer, Michael C; Gregory, Allison; Haack, Tobias B; Kurian, Manju A; Houlden, Henry H; Anderson, James; Boddaert, Nathalie; Sanford, Lynn; Harik, Sami I; Dandu, Vasuki H; Nardocci, Nardo; Zorzi, Giovanna; Dunaway, Todd; Tarnopolsky, Mark; Skinner, Steven; Holden, Kenton R; Frucht, Steven; Hanspal, Era; Schrander-Stumpel, Connie; Mignot, Cyril; Héron, Delphine; Saunders, Dawn E; Kaminska, Margaret; Lin, Jean-Pierre; Lascelles, Karine; Cuno, Stephan M; Meyer, Esther; Garavaglia, Barbara; Bhatia, Kailash; de Silva, Rajith; Crisp, Sarah; Lunt, Peter; Carey, Martyn; Hardy, John; Meitinger, Thomas; Prokisch, Holger; Hogarth, Penelope

2013-06-01

Neurodegenerative disorders with high iron in the basal ganglia encompass an expanding collection of single gene disorders collectively known as neurodegeneration with brain iron accumulation. These disorders can largely be distinguished from one another by their associated clinical and neuroimaging features. The aim of this study was to define the phenotype that is associated with mutations in WDR45, a new causative gene for neurodegeneration with brain iron accumulation located on the X chromosome. The study subjects consisted of WDR45 mutation-positive individuals identified after screening a large international cohort of patients with idiopathic neurodegeneration with brain iron accumulation. Their records were reviewed, including longitudinal clinical, laboratory and imaging data. Twenty-three mutation-positive subjects were identified (20 females). The natural history of their disease was remarkably uniform: global developmental delay in childhood and further regression in early adulthood with progressive dystonia, parkinsonism and dementia. Common early comorbidities included seizures, spasticity and disordered sleep. The symptoms of parkinsonism improved with l-DOPA; however, nearly all patients experienced early motor fluctuations that quickly progressed to disabling dyskinesias, warranting discontinuation of l-DOPA. Brain magnetic resonance imaging showed iron in the substantia nigra and globus pallidus, with a 'halo' of T1 hyperintense signal in the substantia nigra. All patients harboured de novo mutations in WDR45, encoding a beta-propeller protein postulated to play a role in autophagy. Beta-propeller protein-associated neurodegeneration, the only X-linked disorder of neurodegeneration with brain iron accumulation, is associated with de novo mutations in WDR45 and is recognizable by a unique combination of clinical, natural history and neuroimaging features.

Does hemiplegic shoulder pain share clinical and sensory characteristics with central neuropathic pain? A comparative study.

PubMed

Zeilig, Gabi; Rivel, Michal; Doron, Dana; Defrin, Ruth

2016-10-01

Hemiplegic shoulder pain (HSP) is a common poststroke complication and is considered to be a chronic pain syndrome. It is negatively correlated with the functional recovery of the affected arm and the quality of life of the individual. It also leads to a longer length of stay in rehabilitation. Today, there is no consensus as to the underlying mechanism causing HSP, making the syndrome difficult to treat. The aim of this study was to compare the clinical and sensory profile of individuals with HSP to that of individuals with established central neuropathic pain (CNP) in order to identify common features and the presence of neuropathic components in HSP. Cross sectional controlled study. Outpatient rehabilitation clinics. Sixteen chronic HSP patients and 18 chronic CNP patients with spinal cord injury (SCI-CNP). The chronic pain characteristics, thresholds of thermal and tactile sensations and presence of pathological sensations were compared between groups, and between painful and pain free body regions within groups. Correlations were calculated between HSP intensity and sensory and musculoskeletal characteristics. Patients with HSP and patients with SCI-CNP had similar decrease of thermal sensibility in the painful compared to intact body regions and both groups presented similar rates of pathological sensations in painful regions. HSP and SCI-CNP differed however, in the quality of pain and aggravating factors. Significant correlations were found between HSP intensity and heat-pain threshold, presence of subluxation and spasticity. The similarities between HSP and SCI-CNP and the altered spinothalamic function and sensitization suggest that HSP has neuropathic components in its mechanism. Nevertheless, the unique features of HSP point towards additional possible mechanisms. The use of specific therapy options for neuropathic pain should be considered when treating patients with HSP.

A combinatorial feature selection approach to describe the QSAR of dual site inhibitors of acetylcholinesterase.

PubMed

Asadabadi, Ebrahim Barzegari; Abdolmaleki, Parviz; Barkooie, Seyyed Mohsen Hosseini; Jahandideh, Samad; Rezaei, Mohammad Ali

2009-12-01

Regarding the great potential of dual binding site inhibitors of acetylcholinesterase as the future potent drugs of Alzheimer's disease, this study was devoted to extraction of the most effective structural features of these inhibitors from among a large number of quantitative descriptors. To do this, we adopted a unique approach in quantitative structure-activity relationships. An efficient feature selection method was emphasized in such an approach, using the confirmative results of different routine and novel feature selection methods. The proposed methods generated quite consistent results ensuring the effectiveness of the selected structural features.

Successful Solutions to SSME/AT Development Turbine Blade Distress

NASA Technical Reports Server (NTRS)

Montgomery, Stuart K.

1999-01-01

As part of the High-Pressure Fuel Turbopump/Alternate Turbopump (HPFTP/AT) turbine blade development program, unique turbine blade design features were implemented to address 2nd stage turbine blade high cycle fatigue distress and improve turbine robustness. Features included the addition of platform featherseal dampers, asymmetric blade tip seal segments, gold plating of the blade attachments, and airfoil tip trailing edge modifications. Development testing shows these features have eliminated turbine blade high cycle fatigue distress and consequently these features are currently planned for incorporation to the flight configuration. Certification testing will begin in 1999. This presentation summarizes these features.

Design, construction and operation features of high-rise structures

NASA Astrophysics Data System (ADS)

Mylnik, Alexey; Mylnik, Vladimir; Zubeeva, Elena; Mukhamedzhanova, Olga

2018-03-01

The article considers design, construction and operation features of high-rise facilities. The analysis of various situations, that come from improper designing, construction and operation of unique facilities, is carried out. The integrated approach is suggested, when the problems of choosing acceptable constructional solutions related to the functional purpose, architectural solutions, methods of manufacturing and installation, operating conditions for unique buildings and structures are being tackled. A number of main causes for the emergency destruction of objects under construction and operation is considered. A number of measures are proposed on the basis of factor classification in order to efficiently prevent the situations, when various negative options of design loads and emergency impacts occur.

Chemical reactions directed Peptide self-assembly.

PubMed

Rasale, Dnyaneshwar B; Das, Apurba K

2015-05-13

Fabrication of self-assembled nanostructures is one of the important aspects in nanoscience and nanotechnology. The study of self-assembled soft materials remains an area of interest due to their potential applications in biomedicine. The versatile properties of soft materials can be tuned using a bottom up approach of small molecules. Peptide based self-assembly has significant impact in biology because of its unique features such as biocompatibility, straight peptide chain and the presence of different side chain functionality. These unique features explore peptides in various self-assembly process. In this review, we briefly introduce chemical reaction-mediated peptide self-assembly. Herein, we have emphasised enzymes, native chemical ligation and photochemical reactions in the exploration of peptide self-assembly.

Chemical Reactions Directed Peptide Self-Assembly

PubMed Central

Rasale, Dnyaneshwar B.; Das, Apurba K.

2015-01-01

Fabrication of self-assembled nanostructures is one of the important aspects in nanoscience and nanotechnology. The study of self-assembled soft materials remains an area of interest due to their potential applications in biomedicine. The versatile properties of soft materials can be tuned using a bottom up approach of small molecules. Peptide based self-assembly has significant impact in biology because of its unique features such as biocompatibility, straight peptide chain and the presence of different side chain functionality. These unique features explore peptides in various self-assembly process. In this review, we briefly introduce chemical reaction-mediated peptide self-assembly. Herein, we have emphasised enzymes, native chemical ligation and photochemical reactions in the exploration of peptide self-assembly. PMID:25984603

Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features

PubMed Central

2010-01-01

Background Bone-destructive disease treatments include bisphosphonates and antibodies against the osteoclast differentiator, RANKL (aRANKL); however, osteonecrosis of the jaw (ONJ) is a frequent side-effect. Current models fail to explain the restriction of bisphosphonate (BP)-related and denosumab (anti-RANKL antibody)-related ONJ to jaws. Msx-1 is exclusively expressed in craniofacial structures and pivotal to cranial neural crest (CNC)-derived periodontal tissue remodeling. We hypothesised that Msx-1 expression might be impaired in bisphosphonate-related ONJ. The study aim was to elucidate Msx-1 and RANKL-associated signal transduction (BMP-2/4, RANKL) in ONJ-altered and healthy periodontal tissue. Methods Twenty ONJ and twenty non-BP exposed periodontal samples were processed for RT-PCR and immunohistochemistry. An automated staining-based alkaline phosphatase-anti-alkaline phosphatase method was used to measure the stained cells:total cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed on ONJ-affected and healthy jaw periodontal samples (n = 20 each) to quantitatively compare Msx-1, BMP-2, RANKL, and GAPDH mRNA levels. Results Semi-quantitative assessment of the ratio of stained cells showed decreased Msx-1 and RANKL and increased BMP-2/4 (all p < 0.05) expression in ONJ-adjacent periodontal tissue. ONJ tissue also exhibited decreased relative gene expression for Msx-1 (p < 0.03) and RANKL (p < 0.03) and increased BMP-2/4 expression (p < 0.02) compared to control. Conclusions These results explain the sclerotic and osteopetrotic changes of periodontal tissue following BP application and substantiate clinical findings of BP-related impaired remodeling specific to periodontal tissue. RANKL suppression substantiated the clinical finding of impaired bone remodelling in BP- and aRANKL-induced ONJ-affected bone structures. Msx-1 suppression in ONJ-adjacent periodontal tissue suggested a bisphosphonate-related impairment in cellular differentiation that occurred exclusively jaw remodelling. Further research on developmental biology-related unique features of jaw bone structures will help to elucidate pathologies restricted to maxillofacial tissue. PMID:20942943

Expression of Msx-1 is suppressed in bisphosphonate associated osteonecrosis related jaw tissue-etiopathology considerations respecting jaw developmental biology-related unique features.

PubMed

Wehrhan, Falk; Hyckel, Peter; Ries, Jutta; Stockmann, Phillip; Nkenke, Emeka; Schlegel, Karl A; Neukam, Friedrich W; Amann, Kerstin

2010-10-13

Bone-destructive disease treatments include bisphosphonates and antibodies against the osteoclast differentiator, RANKL (aRANKL); however, osteonecrosis of the jaw (ONJ) is a frequent side-effect. Current models fail to explain the restriction of bisphosphonate (BP)-related and denosumab (anti-RANKL antibody)-related ONJ to jaws. Msx-1 is exclusively expressed in craniofacial structures and pivotal to cranial neural crest (CNC)-derived periodontal tissue remodeling. We hypothesised that Msx-1 expression might be impaired in bisphosphonate-related ONJ. The study aim was to elucidate Msx-1 and RANKL-associated signal transduction (BMP-2/4, RANKL) in ONJ-altered and healthy periodontal tissue. Twenty ONJ and twenty non-BP exposed periodontal samples were processed for RT-PCR and immunohistochemistry. An automated staining-based alkaline phosphatase-anti-alkaline phosphatase method was used to measure the stained cells:total cell-number ratio (labelling index, Bonferroni adjustment). Real-time RT-PCR was performed on ONJ-affected and healthy jaw periodontal samples (n = 20 each) to quantitatively compare Msx-1, BMP-2, RANKL, and GAPDH mRNA levels. Semi-quantitative assessment of the ratio of stained cells showed decreased Msx-1 and RANKL and increased BMP-2/4 (all p < 0.05) expression in ONJ-adjacent periodontal tissue. ONJ tissue also exhibited decreased relative gene expression for Msx-1 (p < 0.03) and RANKL (p < 0.03) and increased BMP-2/4 expression (p < 0.02) compared to control. These results explain the sclerotic and osteopetrotic changes of periodontal tissue following BP application and substantiate clinical findings of BP-related impaired remodeling specific to periodontal tissue. RANKL suppression substantiated the clinical finding of impaired bone remodelling in BP- and aRANKL-induced ONJ-affected bone structures. Msx-1 suppression in ONJ-adjacent periodontal tissue suggested a bisphosphonate-related impairment in cellular differentiation that occurred exclusively jaw remodelling. Further research on developmental biology-related unique features of jaw bone structures will help to elucidate pathologies restricted to maxillofacial tissue.

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ERIC Educational Resources Information Center

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NASA Technical Reports Server (NTRS)

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ERIC Educational Resources Information Center

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ERIC Educational Resources Information Center

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