News from the Library: Gordon Fraser presents his book, "Quantum Exodus"

CERN Multimedia

CERN Library

2012-01-01

The book "Quantum Exodus" will be presented by the author Gordon Fraser on Thursday 14 June at 4 P.M. in the Library, Building 52-1-052.   "Quantum Exodus" by Gordon Fraser, Oxford University Press, 2012. Here's what the publisher says about the book: "It was no accident that the Holocaust and the Atomic Bomb happened at the same time. (...) Atomic science had attracted a lot of Jewish talent, and as Albert Einstein and other quantum exiles scattered, they realized that they held the key to a weapon of unimaginable power. Convinced that their gentile counterparts in Germany had come to the same conclusion, and having witnessed what the Nazis were prepared to do, the exiles were afraid. They had to get to the Atomic Bomb first. The Nazis meanwhile had acquired a more pressing objective: their persecution of the Jews had evolved into extermination. Two dreadfu...

Civic Fragmentation or Voluntary Association? Habermas, Fraser, and Charter School Segregation

Science.gov (United States)

Wilson, Terri S.

2010-01-01

In this essay, Terri Wilson puts the argument developed by Kathleen Knight Abowitz that charter schools could be considered as counterpublic spaces into interaction with empirical research that explores patterns of voluntary self-segregation in charter schools. Wilson returns to the theoretical tension between Jurgen Habermas and Nancy Fraser over…

Fraser and the Cheerleader: Values and the Boundaries of Student Speech

Science.gov (United States)

Ehrensal, Patricia A. L.

2012-01-01

Student speech has and continues to be a contested issue in schools. The Supreme Court ruled in "Tinker" that students do not shed their rights at the schoolhouse gate; in the "Kuhlmeier" and "Fraser" decisions, however, the Court gave school officials greater latitude in regulating student speech, especially when it…

Gordon Fraser (1943-2013)

CERN Document Server

2013-01-01

We were deeply saddened to learn that Gordon Fraser had passed away on 3 January. During his 25-year career at CERN, until his retirement in 2002, he made many valuable contributions to the Laboratory, in particular as editor of CERN Courier.   Gordon’s life in science began at Imperial College London, where he obtained a PhD with the theory group of the future Nobel laureate Abdus Salam. He then spent time at Tel Aviv University in Yuval Ne’eman’s group and at Brighton University, before changing career to become a journalist, at first for Computer Weekly in London. He moved into scientific editing at the Rutherford Appleton Laboratory in 1975 and it was from there that he was hired to join the publications team at CERN in 1977. By 1982 Gordon had become the editor of the CERN Courier. During his time at the helm, both particle physics and the Courier changed considerably. Under his careful stewardship aspects of publishing were outsourced, leading to a...

Evaluating the Fraser Health Balanced Scorecard--a formative evaluation.

Science.gov (United States)

Barnardo, Catherine; Jivanni, Amin

2009-01-01

Fraser Health (FH), a large, Canadian, integrated health care network, adopted the Balanced Scorecard (BSC) approach to monitor organizational performance in 2006. This paper reports on the results of a formative evaluation, conducted in April, 2008, to assess the usefulness of the BSC as a performance-reporting system and a performance management tool. Results indicated that the BSC has proven to be useful for reporting performance but is not currently used for performance management in a substantial way.

Performance and Size of Fraser & Neave Holdings Bhd (F&N)

OpenAIRE

Othaman, Ridhuan

2017-01-01

The main study is to analyze about the overall of the risk and the performance of the Fraser & Neave Holdings Bhd (F&N). All the is get from annual report that get from the Bursa Malaysia. The measurement of the company is used in variety of ratio such as liquidity risk, operational risk, credit risk and financial risk. These ratio is useful to know well about the company.

Impairment of flow-mediated dilation correlates with aortic dilation in patients with Marfan syndrome.

Science.gov (United States)

Takata, Munenori; Amiya, Eisuke; Watanabe, Masafumi; Omori, Kazuko; Imai, Yasushi; Fujita, Daishi; Nishimura, Hiroshi; Kato, Masayoshi; Morota, Tetsuro; Nawata, Kan; Ozeki, Atsuko; Watanabe, Aya; Kawarasaki, Shuichi; Hosoya, Yumiko; Nakao, Tomoko; Maemura, Koji; Nagai, Ryozo; Hirata, Yasunobu; Komuro, Issei

2014-07-01

Marfan syndrome is an inherited disorder characterized by genetic abnormality of microfibrillar connective tissue proteins. Endothelial dysfunction is thought to cause aortic dilation in subjects with a bicuspid aortic valve; however, the role of endothelial dysfunction and endothelial damaging factors has not been elucidated in Marfan syndrome. Flow-mediated dilation, a noninvasive measurement of endothelial function, was evaluated in 39 patients with Marfan syndrome. Aortic diameter was measured at the aortic annulus, aortic root at the sinus of Valsalva, sinotubular junction and ascending aorta by echocardiography, and adjusted for body surface area (BSA). The mean value of flow-mediated dilation was 6.5 ± 2.4 %. Flow-mediated dilation had a negative correlation with the diameter of the ascending thoracic aorta (AscAd)/BSA (R = -0.39, p = 0.020) and multivariate analysis revealed that flow-mediated dilation was an independent factor predicting AscAd/BSA, whereas other segments of the aorta had no association. Furthermore, Brinkman index had a somewhat greater influence on flow-mediated dilation (R = -0.42, p = 0.008). Although subjects who smoked tended to have a larger AscAd compared with non-smokers (AscA/BSA: 17.3 ± 1.8 versus 15.2 ± 3.0 mm/m(2), p = 0.013), there was no significant change in flow-mediated dilation, suggesting that smoking might affect aortic dilation via an independent pathway. Common atherogenic risks, such as impairment of flow-mediated dilation and smoking status, affected aortic dilation in subjects with Marfan syndrome.

Justicia como redistribución, reconocimiento y representación: las reconciliaciones de Nancy Fraser

Directory of Open Access Journals (Sweden)

Clara Iglesias

2013-01-01

Full Text Available Si nos preguntamos por el desarrollo de la Teoría Crítica y sus marcos conceptuales, es imprescindible tener en cuenta el pensamiento de Nancy Fraser. Con el presente artículo se pretende desglosar el entramado conceptual del que se vale Fraser, tomando para ello principalmente dos de sus obras: ¿Redistribución o reconocimiento? y Escalas de justicia. Con ello el artículo se centra en la consideración de conceptos clave para la elaboración de una teoría crítica capaz de integrar las reivindicaciones actuales presentes en los movimientos sociales, y con ello la puesta de manifiesto de la injusticia y su posible reparación, sin perder de vista en ningún momento el correlato social fáctico de la teoría.

Supporting frail seniors through a family physician and Home Health integrated care model in Fraser Health

Directory of Open Access Journals (Sweden)

Grace Haeson Park

2014-03-01

Full Text Available Background: A major effort is underway to integrate primary and community care in Canada's western province of British Columbia and in Fraser Health, its largest health authority. Integrated care is a critical component of Fraser Health's planning, to meet the challenges of caring for a growing, elderly population that is presenting more complex and chronic medical conditions. Description of integrated practice: An integrated care model partners family physicians with community-based home health case managers to support frail elderly patients who live at home. It is resulting in faster response times to patient needs, more informed assessments of a patient's state of health and pro-active identification of emerging patient issues. Early results: The model is intended to improve the quality of patient care and maintain the patients’ health status, to help them live at home confidently and safely, as long as possible. Preliminary pilot data measuring changes in home care services is showing positive trends when it comes to extending the length of a person's survival/tenure in the community (living in their home vs. admitted to residential care or deceased. Conclusion: Fraser Health's case manager–general practitioner partnership model is showing promising results including higher quality, appropriate, coordinated and efficient care; improved patient, caregiver and physician interactions with the system; improved health and prevention of acute care visits by senior adult patients.

Professor Barry Fraser's contributions to science education research

Science.gov (United States)

Aldridge, Jill M.

2011-09-01

In this article, I endeavour to convey the depth of Barry Fraser's contributions to science education research, including his tireless endeavours to promote and advance research, especially the field of learning environments, the realisation of his vision to create one of the largest doctoral programs in science and mathematics education in the world, his leadership capacity in terms of guiding and leading an internationally renowned centre and large-scale cross-national and cross-cultural studies, his dedication towards human capacity building in Africa, Asia and elsewhere, his capacity as a mentor and editor that have seen the publication of numerous journal articles and books and the ongoing success of science education research journals.

Cocaine/levamisole-associated autoimmune syndrome: a disease of neutrophil-mediated autoimmunity.

Science.gov (United States)

Cascio, Michael J; Jen, Kuang-Yu

2018-01-01

Levamisole was previously used for its immunomodulatory properties to treat rheumatoid arthritis and some cancers. However, because of serious side-effects, it was taken off the market in the United States. Recently, levamisole has reemerged as a popular cocaine adulterant. Some individuals who consume levamisole-adulterated cocaine can develop a life-threatening autoimmune syndrome. In this review, the medical consequences of levamisole exposure and postulated mechanisms by which levamisole induces these adverse effects are discussed. Although agranulocytosis and cutaneous vasculitis are the major findings in patients who develop cocaine/levamisole-associated autoimmune syndrome (CLAAS), more recent experience indicates that other organ systems can be involved as well. Current studies point to neutrophil activation and neutrophil extracellular trap formation with subsequent antineutrophil cytoplasmic antibody-mediated tissue injury as a possible mechanism of CLAAS. In the past decade, the detrimental effects of levamisole have reemerged because of its popularity as a cocaine adulterant. Although infrequent, some individuals develop a systemic autoimmune syndrome characterized by immune-mediated agranulocytosis and antineutrophil cytoplasmic antibody-mediated vasculitis. Mechanistically, neutrophil antigens appear to be a major player in inducing CLAAS. Prompt cessation of levamisole exposure is key to treatment, although relapses are frequent because of the addictive effects of cocaine and the high prevalence of levamisole within the cocaine supply.

2000 emission inventory for the Lower Fraser Valley airshed

International Nuclear Information System (INIS)

2002-10-01

This emissions inventory is a compilation of all emissions in the Lower Fraser Valley International Airshed. Its objective is to harmonize the inventory data of Canada's Greater Vancouver Regional District (GVRD), the Fraser Valley Regional District (FVRD) and Whatcom County in the United States. It provides an idea of the current state of air emissions on both sides of the Canada-United States border. This inventory provides information regarding the types of emissions sources in the region, their location and the amount of air pollution emitted within a given time frame. It is designed to help manage air quality by identifying sectors which need to be more vigilant. The common air pollutants addressed in the inventory include total particulate matter, nitrogen oxides, sulphur oxides, volatile organic compounds, carbon monoxide, and ammonia. The greenhouse gases include carbon dioxide, methane, and nitrous oxide. The inventory distinguishes between point, area, and mobile sources. Carbon monoxide emissions are found to be dominated by cars, trucks and non-road engines. Nitrogen oxide emissions are also dominated by cars, trucks, marine vessels and non-road engines. Natural sources such as trees and vegetation contribute to volatile organic compounds, as do cars, lights trucks and solvent evaporation from industrial, commercial and consumer products. Marine vessels are the largest contributors of sulphur oxide emissions in the region. In addition, the petroleum industry emits 26 per cent of sulphur oxide emissions in the region. Significant amounts of particulate matter come from area sources such as wind erosion in the agricultural sector. Point sources for PM include bulk shipping terminals and the wood products industry. Agriculture contributes the largest amount of ammonia in the region. refs., tabs., figs

Mediators of the association of major depressive syndrome and anxiety syndrome with postpartum smoking relapse.

Science.gov (United States)

Correa-Fernández, Virmarie; Ji, Lingyun; Castro, Yessenia; Heppner, Whitney L; Vidrine, Jennifer Irvin; Costello, Tracy J; Mullen, Patricia Dolan; Cofta-Woerpel, Ludmila; Velasquez, Mary M; Greisinger, Anthony; Cinciripini, Paul M; Wetter, David W

2012-08-01

Based on conceptual models of addiction and affect regulation, this study examined the mechanisms linking current major depressive syndrome (MDS) and anxiety syndrome (AS) to postpartum smoking relapse. Data were collected in a randomized clinical trial from 251 women who quit smoking during pregnancy. Simple and multiple mediation models of the relations of MDS and AS with postpartum relapse were examined using linear regression, continuation ratio logit models, and a bootstrapping procedure to test the indirect effects. Both MDS and AS significantly predicted postpartum smoking relapse. After adjusting for MDS, AS significantly predicted relapse. However, after adjusting for AS, MDS no longer predicted relapse. Situationally based self-efficacy, expectancies of controlling negative affect by means other than smoking, and various dimensions of primary and secondary tobacco dependence individually mediated the effect of both MDS and AS on relapse. In multiple mediation models, self-efficacy in negative/affective situations significantly mediated the effect of MDS and AS on relapse. The findings underscore the negative impact of depression and anxiety on postpartum smoking relapse and suggest that the effects of MDS on postpartum relapse may be largely explained by comorbid AS. The current investigation provided mixed support for affect regulation models of addiction. Cognitive and tobacco dependence-related aspects of negative and positive reinforcement significantly mediated the relationship of depression and anxiety with relapse, whereas affect and stress did not. The findings emphasize the unique role of low agency with respect to abstaining from smoking in negative affective situations as a key predictor of postpartum smoking relapse. © 2012 American Psychological Association

Crustal surface wave velocity structure of the east Albany-Fraser Orogen, Western Australia, from ambient noise recordings

Science.gov (United States)

Sippl, C.; Kennett, B. L. N.; Tkalčić, H.; Gessner, K.; Spaggiari, C. V.

2017-09-01

Group and phase velocity maps in the period range 2-20 s for the Proterozoic east Albany-Fraser Orogen, Western Australia, are extracted from ambient seismic noise recorded with the 70-station ALFREX array. This 2 yr temporary installation provided detailed coverage across the orogen and the edge of the Neoarchean Yilgarn Craton, a region where no passive seismic studies of this scale have occurred to date. The surface wave velocities are rather high overall (>3 km s-1 nearly everywhere), as expected for exposed Proterozoic basement rocks. No clear signature of the transition between Yilgarn Craton and Albany-Fraser Orogen is observed, but several strong anomalies corresponding to more local geological features were obtained. A prominent, NE-elongated high-velocity anomaly in the northern part of the array is coincident with a Bouguer gravity high caused by the upper crustal metamorphic rocks of the Fraser Zone. This feature disappears towards longer periods, which hints at an exclusively upper crustal origin for this anomaly. Further east, the limestones of the Cenozoic Eucla Basin are clearly imaged as a pronounced low-velocity zone at short periods, but the prevalence of low velocities to periods of ≥5 s implies that the uppermost basement in this area is likewise slow. At longer periods, slightly above-average surface wave velocities are imaged below the Eucla Basin.

A homozygous missense variant in VWA2, encoding an interactor of the Fraser-complex, in a patient with vesicoureteral reflux.

Directory of Open Access Journals (Sweden)

Amelie T van der Ven

Full Text Available Congenital anomalies of the kidney and urinary tract (CAKUT are the most common cause (40-50% of chronic kidney disease (CKD in children. About 40 monogenic causes of CAKUT have so far been discovered. To date less than 20% of CAKUT cases can be explained by mutations in these 40 genes. To identify additional monogenic causes of CAKUT, we performed whole exome sequencing (WES and homozygosity mapping (HM in a patient with CAKUT from Indian origin and consanguineous descent. We identified a homozygous missense mutation (c.1336C>T, p.Arg446Cys in the gene Von Willebrand factor A domain containing 2 (VWA2. With immunohistochemistry studies on kidneys of newborn (P1 mice, we show that Vwa2 and Fraser extracellular matrix complex subunit 1 (Fras1 co-localize in the nephrogenic zone of the renal cortex. We identified a pronounced expression of Vwa2 in the basement membrane of the ureteric bud (UB and derivatives of the metanephric mesenchyme (MM. By applying in vitro assays, we demonstrate that the Arg446Cys mutation decreases translocation of monomeric VWA2 protein and increases translocation of aggregated VWA2 protein into the extracellular space. This is potentially due to the additional, unpaired cysteine residue in the mutated protein that is used for intermolecular disulfide bond formation. VWA2 is a known, direct interactor of FRAS1 of the Fraser-Complex (FC. FC-encoding genes and interacting proteins have previously been implicated in the pathogenesis of syndromic and/or isolated CAKUT phenotypes in humans. VWA2 therefore constitutes a very strong candidate in the search for novel CAKUT-causing genes. Our results from in vitro experiments indicate a dose-dependent neomorphic effect of the Arg446Cys homozygous mutation in VWA2.

Mediators of low-grade chronic inflammation in polycystic ovary syndrome (PCOS).

Science.gov (United States)

Ojeda-Ojeda, Miriam; Murri, Mora; Insenser, María; Escobar-Morreale, Héctor F

2013-01-01

Chronic low-grade subclinical inflammation has been increasingly recognized as an interposer in the endocrine, metabolic and reproductive disturbances that characterize the polycystic ovary syndrome (PCOS). Abdominal adiposity and obesity are often present in PCOS. Mounting evidence indicates that adipose tissue is involved in innate and adaptive immune responses. Continuous release of inflammatory mediators such as cytokines, acute phase proteins, and adipokines perpetuates the inflammatory condition associated with obesity in women with PCOS, possibly contributing to insulin resistance and other long-term cardiometabolic risk factors. Genetic variants in the genes encoding inflammation-related mediators underlie the development of PCOS and their interaction with environmental factors may contribute to the heterogeneous clinical phenotype of this syndrome. In the future, strategies ameliorating inflammation may prove useful for the management of PCOS and associated conditions.

Charting shifts and moving forward in abnormal times: An interview with Nancy Fraser

Directory of Open Access Journals (Sweden)

Julia Sichieri Moura

2016-09-01

Full Text Available http://dx.doi.org/10.5007/1677-2954.2016v15n1p1 In this interview Nancy Fraser elucidates important conceptual topics of her theory, she also shares her analysis of the global financial crisis and how it has changed the setting for theorists of justice. Her account reminds us of critical theory’s important role in helping us think - and act – differently in difficult times.

E2F1-mediated human POMC expression in ectopic Cushing's syndrome.

Science.gov (United States)

Araki, Takako; Liu, Ning-Ai; Tone, Yukiko; Cuevas-Ramos, Daniel; Heltsley, Roy; Tone, Masahide; Melmed, Shlomo

2016-11-01

Cushing's syndrome is caused by excessive adrenocorticotropic hormone (ACTH) secretion derived from pituitary corticotroph tumors (Cushing disease) or from non-pituitary tumors (ectopic Cushing's syndrome). Hypercortisolemic features of ectopic Cushing's syndrome are severe, and no definitive treatment for paraneoplastic ACTH excess is available. We aimed to identify subcellular therapeutic targets by elucidating transcriptional regulation of the human ACTH precursor POMC (proopiomelanocortin) and ACTH production in non-pituitary tumor cells and in cell lines derived from patients with ectopic Cushing's syndrome. We show that ectopic hPOMC transcription proceeds independently of pituitary-specific Tpit/Pitx1 and demonstrate a novel E2F1-mediated transcriptional mechanism regulating hPOMC We identify an E2F1 cluster binding to the proximal hPOMC promoter region (-42 to +68), with DNA-binding activity determined by the phosphorylation at Ser-337. hPOMC mRNA expression in cancer cells was upregulated (up to 40-fold) by the co-expression of E2F1 and its heterodimer partner DP1. Direct and indirect inhibitors of E2F1 activity suppressed hPOMC gene expression and ACTH by modifying E2F1 DNA-binding activity in ectopic Cushing's cell lines and primary tumor cells, and also suppressed paraneoplastic ACTH and cortisol levels in xenografted mice. E2F1-mediated hPOMC transcription is a potential target for suppressing ACTH production in ectopic Cushing's syndrome. © 2016 Society for Endocrinology.

Climate change and the Lower Fraser Valley. rev. ed.

International Nuclear Information System (INIS)

Taylor, E.; Langlois, D.

2000-01-01

The climatic changes that are expected to occur in British Columbia's Lower Fraser Valley over the next century were described in this report which included information about the science of climate change and the development of global climate models that provide estimates of global climate for the coming century. The confidence that scientists have in these models was reflected in the fact that most can simulate the important seasonal and geographical large scale features of the global climate, and that many of the large scale changes that are effected by greenhouse gas concentrations can be explained in terms of physical processes which operate around the world. The models also reproduce with reasonable accuracy the variations of climate such as the El Nino phenomena., the cooling due to the Mount Pinatubo eruption in 1991 and the global warming that occurred over the past 100 years. Three climate stations were analyzed in this study to assess the climate change of the Valley. Climatic change is influenced by increased concentrations of greenhouse gases in the atmosphere which in turn cause accelerated global warming. Scientists generally believe that the combustion of fossil fuels and other human activities are a major reason for the increased concentration of carbon dioxide. Plant respiration and the decomposition of organic matter releases 10 times more CO 2 than that released anthropogenically, but these releases are in balance with plant photosynthesis. The rate of warming in the Lower Fraser Valley is uncertain, but climate models suggest it could be about 3 to 4 degrees warming with wetter winters and drier summers by the end of the century. The Valley currently has mild temperatures and high precipitation because of its proximity to the Pacific Oceans and the surrounding mountains. Global warming can have an impact on sea levels along the coast, spring flooding, summer drought, coastal ecosystems, air quality, occurrences of forest fires, and recreation

Immune-mediated animal models of Tourette syndrome

Science.gov (United States)

Hornig, Mady; Lipkin, W. Ian

2014-01-01

An autoimmune diathesis has been proposed in Tourette syndrome (TS) and related neuropsychiatric disorders such as obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism and anorexia nervosa. Environmental triggers including infection and xenobiotics are hypothesized to lead to the production of brain-directed autoantibodies in a subset of genetically susceptible individuals. Although much work has focused on Group A Streptococcus (GAS), the role of this common childhood infection remains controversial. Animal model studies based on immune and autoantibody findings in TS have demonstrated immunoglobulin (Ig) deposits and stereotypic movements and related behavioral disturbances reminiscent of TS following exposure to GAS and other activators of host anti-microbial responses, soluble immune mediators and anti-GAS or anti-neuronal antibodies. Demonstration of the ability to recreate these abnormalities through passive transfer of serum IgG from GAS-immunized mice into naïve mice and abrogation of this activity through depletion of IgG has provided compelling evidence in support of the autoimmune hypothesis. Immunologically-based animal models of TS are a potent tool for dissecting the pathogenesis of this serious neuropsychiatric syndrome. PMID:23313649

Age-class differences in shoot photosynthesis and water relations of Fraser fir (Abies fraseri), southern Appalachian Mountains, USA

Science.gov (United States)

Keith Reinhardt; Daniel M. Johnson; William K. Smith

2009-01-01

Fraser fir (Abies fraseri (Pursh) Poir.) is an endemic tree species found only in refugial mountain-top forests in the southern Appalachian Mountains, USA. Very few studies have investigated the ecophysiology of this species in its natural environment. We measured and compared photosynthetic gas exchange and water relations of understory germinant...

Rebalancing the Simon Fraser University’s Academic Pension Plan’s Balanced Fund: A Case Study

OpenAIRE

Wang, Yingshuo; Ren, Jing

2012-01-01

The purpose of the paper is to investigate the rebalancing strategy for Simon Fraser University’s Academic Pension Plan’s Balanced Fund. First, we examine performances of a “no rebalancing” fund and rebalanced funds with different rebalancing frequencies and thresholds based on the historic data. The results show that the rebalancing frequency and thresholds do not significantly affect the performance of the portfolio. Additionally, the rebalanced portfolios significantly outperform the “no r...

From the Aldine Press to Aldus@SFU: Showcasing Simon Fraser University Library’s Aldines Online

OpenAIRE

Bordini, Alessandra

2017-01-01

This report stems from a joint commemoration in 2015 of the fiftieth anniversary of the opening of Simon Fraser University and the five-hundredth anniversary of the death of pioneering Renaissance publisher and scholar Aldus Manutius. To mark these occasions, Publishing@SFU and SFU Library Special Collections joined forces to create a web-based resource comprising an outstanding selection of Aldines from the Wosk–McDonald collection, one of the largest such in North America. This report detai...

Notes on Cordulegaster Leach, and Neallogaster Cowley, from China, and the identity of Anotogaster annandalei Fraser (Insecta: Odonata: Anisoptera: Cordulegastridae)

NARCIS (Netherlands)

Pelt, van G.J.

1996-01-01

A translation of the Chinese description of a female of Neallogaster annandalei (Fraser, 1923), by Zhou (1988) is given and compared with the original description of Anotogaster annandalei. It is concluded that this species should be included in the genus Cordulegaster. A translation of the original

Impacts of cloud immersion on microclimate, photosynthesis and water relations of fraser fir in a temperate mountain cloud forest

Science.gov (United States)

Keith Reinhardt; William K. Smith

2010-01-01

The red spruce-Fraser fir ecosystem (Picea rubens Sarg.-Abies fraseri [Pursh] Poir.) of the southern Appalachian mountains is a temperate zone cloud forest immersed in clouds for 30 to 40 percent of a typical summer day, and experiencing immersion on about 65 percent of all days annually. We compared the microclimate,...

REVEAL II: Seasonality and spatial variability of particle and visibility conditions in the Fraser Valley

DEFF Research Database (Denmark)

Pryor, S.C.; Barthelmie, R.J.

2000-01-01

This paper presents data collected during a year-long field experiment (REVEAL II) in the Fraser Valley, British Columbia. The data are used to provide information regarding ambient visibility conditions and fine particle concentrations in the valley. Although average fine mass measured during RE...... taken at a number of sites during REVEAL II are used to evaluate a simple method for obtaining (classed) quantitative estimates of visual range from this medium without requiring access to specialized instrumentation. (C) 2000 Elsevier Science B.V. All rights reserved....

Chronic condition as a mediator between metabolic syndrome and cognition among community-dwelling older adults: The moderating role of sex.

Science.gov (United States)

Foong, Hui Foh; Hamid, Tengku Aizan; Ibrahim, Rahimah; Haron, Sharifah Azizah; Shahar, Suzana

2017-11-01

Metabolic syndrome and chronic conditions are significant predictors of cognition; however, few studies have examined how they work together in predicting cognition in old age. Therefore, the present study examines whether a chronic condition mediates the association between metabolic syndrome and cognition. In addition, it discusses the moderating role of sex in the relationships between metabolic syndrome, chronic conditions and cognition. Secondary analysis was carried out of data from the Malaysian national survey that involved 2322 community residents aged 60 years or older in Peninsular Malaysia. Cognition was measured by the digit symbol substitution test. Metabolic syndrome was assessed by five biomarkers: triglyceride, fasting blood sugar, systolic blood pressure, cholesterol ratio and body mass index. Chronic conditions were assessed by self-reported medical history. The structural equation modeling technique was used to analyze the mediation and moderation tests. The number of chronic conditions partially mediated the association between metabolic syndrome and cognition. Men and women did not differ in the relationship between metabolic syndrome and cognition; however, the number of chronic conditions was found to be negatively associated with cognition in older women, but not in men. Metabolic syndrome might increase the likelihood of older adults to suffer from more chronic conditions; these responses might reduce their cognition. To prevent cognitive decline in old age, specific intervention to minimize the number of chronic conditions by reducing their vascular risk factors is warranted, especially among older women. Geriatr Gerontol Int 2017; 17: 1914-1920. © 2017 Japan Geriatrics Society.

Severity of a mountain pine beetle outbreak across a range of stand conditions in Fraser Experimental Forest, Colorado, United States

Science.gov (United States)

Anthony G. Vorster; Paul H. Evangelista; Thomas J. Stohlgren; Sunil Kumar; Charles C. Rhoades; Robert M. Hubbard; Antony S. Cheng; Kelly Elder

2017-01-01

The recent mountain pine beetle (Dendroctonus ponderosae Hopkins) outbreaks had unprecedented effects on lodgepole pine (Pinus contorta var. latifolia) in western North America. We used data from 165 forest inventory plots to analyze stand conditions that regulate lodgepole pine mortality across a wide range of stand structure and species composition at the Fraser...

Mediators of the effects on fatigue of pragmatic rehabilitation for chronic fatigue syndrome.

Science.gov (United States)

Wearden, Alison J; Emsley, Richard

2013-10-01

To examine potential mediators of the effect of pragmatic rehabilitation on improvements in fatigue following a randomized controlled trial for patients with chronic fatigue syndrome (CFS/ME) in primary care (IRCTN 74156610). Patients fulfilled the Oxford criteria for CFS. Ninety-five patients were randomized to pragmatic rehabilitation and 100 to general practitioner (GP) treatment as usual. The outcome was the Chalder fatigue scale score (0123 scoring) at end of treatment (20 weeks) and 1-year follow up (70 weeks). First, the effect of treatment on potential mediators was assessed. Then fatigue was regressed on significant mediators, treatment allocation, and baseline measures of fatigue and significant mediators. Reduction in limiting activities at 20 weeks mediated the positive effect of pragmatic rehabilitation on fatigue at 70 weeks (mediated effect size = -2.64, SE = 0.81, p = .001, proportion of effect mediated = 82.0%). Reduction in catastrophizing at 20 weeks mediated the positive effect of pragmatic rehabilitation on fatigue at 70 weeks (mediated effect size = -1.39, SE = 0.61, p = .023, proportion of effect mediated = 43.2%). Reductions in 70-week measures of fear avoidance, embarrassment avoidance, limiting activities, and all-or-nothing behavior all mediated improvement in fatigue at 70 weeks, although the causal direction of these cross-sectional effects cannot be determined. There were no between-group differences on measures of exercise capacity (a timed step test). Improvements in fatigue following pragmatic rehabilitation are related to changes in behavioral responses to and beliefs about fatigue.

Lectotype designations of new species of hydroids (Cnidaria, Hydrozoa), described by C.M. Fraser, from Allan Hancock Pacific and Caribbean Sea Expeditions

NARCIS (Netherlands)

Calder, D.R.; Vervoort, W.; Hochberg, F.G.

2009-01-01

Hydroids of the Allan Hancock Pacific Expeditions, and those of the Allan Hancock Caribbean Sea Expedition, were examined by Charles McLean Fraser in a series of reports published between 1938 and 1948. A total of 159 new nominal species was described from material collected in the eastern Pacific

Acute Systolic Heart Failure Associated with Complement-Mediated Hemolytic Uremic Syndrome

Directory of Open Access Journals (Sweden)

John L. Vaughn

2015-01-01

Full Text Available Complement-mediated hemolytic uremic syndrome (otherwise known as atypical HUS is a rare disorder of uncontrolled complement activation that may be associated with heart failure. We report the case of a 49-year-old female with no history of heart disease who presented with microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Given her normal ADAMSTS13 activity, evidence of increased complement activation, and renal biopsy showing evidence of thrombotic microangiopathy, she was diagnosed with complement-mediated HUS. She subsequently developed acute hypoxemic respiratory failure secondary to pulmonary edema requiring intubation and mechanical ventilation. A transthoracic echocardiogram showed evidence of a Takotsubo cardiomyopathy with an estimated left ventricular ejection fraction of 20%, though ischemic cardiomyopathy could not be ruled out. Treatment was initiated with eculizumab. After several failed attempts at extubation, she eventually underwent tracheotomy. She also required hemodialysis to improve her uremia and hypervolemia. After seven weeks of hospitalization and five doses of eculizumab, her renal function and respiratory status improved, and she was discharged in stable condition on room air and independent of hemodialysis. Our case illustrates a rare association between acute systolic heart failure and complement-mediated HUS and highlights the potential of eculizumab in stabilizing even the most critically-ill patients with complement-mediated disease.

Two attempts at grounding social critique in „ordinary“ actors’ perspectives: The critical theories of Nancy Fraser and Axel Honneth

Directory of Open Access Journals (Sweden)

Ivković Marjan

2014-01-01

Full Text Available This paper analyzes two contemporary, „third-generation“ perspectives within critical theory - Nancy Fraser’s and Axel Honneth’s - with the aim of examining the degree to which the two authors succeed in grounding the normative criteria of social critique in the perspectives of ’ordinary’ social actors, as opposed to speculative social theory. To that end, the author focuses on the influential debate between Fraser and Honneth Redistribution or Recognition? which concerns the appropriate normative foundations of a „post-metaphysical“ critical theory, and attempts to reconstruct the fundamental 29 disagreements between Fraser and Honneth over the meaning and tasks of critical theory. The author concludes that both critical theorists ultimately secure the normative foundations of critique through substantive theorizations of the social, which frame the two authors’ „reconstructions“ of the normativity of everyday social action, but argues that post-metaphysical critical theory does not have to abandon comprehensive social theory in order to be epistmologically „non-authoritarian“. [Projekat Ministarstva nauke Republike Srbije, br. 43007: Ethics and Politics of Environment: Institutions, Techniques and Norms Facing the Challenge of Environmental Change

Effect of clear cutting on nutrient fluxes in a subalpine forest at Fraser, Colorado

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J. O. Reuss

1997-01-01

Full Text Available Nutrient fluxes were investigated on a forested and a clearcut plot in a mixed conifer high elevation (2900 m forest at the Fraser Experimental Forest in Fraser, Colorado, USA. Plots were located on a coarse loamy mixed Dystric Cryochrept with relatively high base saturation (30-90% and underlain by an impermeable clay subsoil. Following harvest in late 1984, annual mean NO3 concentrations of 195 to 198 μmol l-1 were observed from 1988 through 1990 and concentrations were still above reference levels in 1993. Total nitrogen loss attributable to leaching following harvest was estimated at 48kg ha-1 over 8 years. Over this same period, atmospheric nitrogen inputs exceeded annual outflow of NH4 plus NO3 from the control plots by approximately 11 kg N ha-1. A slight enrichment Of SO4 and Cl was observed from the harvested plot in 1986 but concentrations later fell below control plot levels, apparently due to dilution by the increased discharge from the harvested plot which was three to four times that from the control plot. Elevated Ca, Mg, and Na concentrations followed a similar pattern to NO3 due to exchange reactions, while a depression in alkalinity of about one-third the amount of NO3 found was also observed. Enrichment of K occurred primarily in water collected at less than 1 m depth. Increases in base cation loss due to leaching after harvest were about twice the amount that can be accounted for by the increased flux of NO3, SO4, and Cl anions. The excess reflects the increased water flux and consequent leaching of base cations in association with HCO3 and organic anions.

Fraser Valley System Reinforcement Project: Environmental planning and assessment report

International Nuclear Information System (INIS)

1991-06-01

Transmission facilities in the south central Fraser Valley, British Columbia, need reinforcement in order to meet anticipated growth in power demand. This objective could be met by reinforcing substation facilities (adding 500-kV equipment and connection to transmission line 5L41) at the McLellan Substation in Surrey, at the Clayburn Substation in Matsqui, or at the Atchelitz Substation in Chilliwack. An assessment is provided of the environmental evaluation criteria applied to these potential sites for substation reinforcement and the rationale for selection of the Clayburn site as the environmentally most effective alternative. The Clayburn site is already cleared and managed for a 230-kV substation; environmental, land use, and socioeconomic impacts are considered manageable. The existing right-of-way for the 500-kV loop in to the substation can be utilized. In addition, the results of an environmental assessment and mitigation plan for the Clayburn substation reinforcement are described. The most significant factors that will require possible mitigative measures include fisheries, water quality, floodplain management, visual and recreational aspects, and heritage resources. 16 figs., 5 tabs

Changes in illness perceptions mediated the effect of cognitive behavioural therapy in severe functional somatic syndromes

DEFF Research Database (Denmark)

Christensen, Sara Sletten; Frostholm, Lisbeth; Ørnbøl, Eva

2014-01-01

Objective Although there is substantial evidence that cognitive behavioural therapy alleviates symptoms in functional somatic syndromes, the mechanisms of change are less investigated. This study examined whether changes in illness perceptions mediated the effect of cognitive behavioural therapy....... Methods We analysed additional data from a randomised controlled trial comparing completers of cognitive behavioural group therapy (46 patients) to an enhanced usual care group (66 patients). Proposed mediators (illness perceptions) and primary (physical health) and secondary (somatic symptoms and illness...... worry) outcomes were assessed by means of questionnaires at referral, baseline, end of treatment, and 10 and 16 months after randomisation. Multiple mediation analysis determined whether (1) changes in specific illness perceptions during treatment mediated the effect of cognitive behavioural therapy...

The impact of visual air quality on tourism revenues in Greater Vancouver and the Lower Fraser Valley

Energy Technology Data Exchange (ETDEWEB)

McNeill, R. [Environment Canada, Vancouver, BC (Canada); Roberge, A.

2000-07-01

The Greater Vancouver area has been experiencing common episodes of poor visibility as a result of urban and agricultural sources of emissions. A study was conducted to determine the response of tourists in the Vancouver and Lower Fraser Valley Regions to visible air quality and to estimate the potential losses in tourist revenue due to poor visibility episodes. This was accomplished using an interactive survey of tourists in 1999. The results were statistically analyzed to develop visibility response functions. A simple economic model based on the visibility response function was then created to predict losses in tourist revenue. The group of tourists were shown four photographic slides of the Valley and Vancouver area depicting various stages of degradation in visibility. They were asked to rate each slide as either acceptable or unacceptable (if they would not make a return visit). Unacceptability rates for the four camera locations were statistically analyzed. The effect of clouds and the measurable visibility parameter was examined. The model predicts future tourist revenue losses in the amount of $7.45 million for the Greater Vancouver Area and $1.32 million in the Fraser Valley. It was recommended that further research should be conducted with more camera locations to provide a wider variety of viewpoints for assessment. This study can provide direction in setting policies to improve visibility in the region. 25 refs., 20 tabs., 4 figs., 3 appendices.

2005 nonroad engine fleet characterization in the Canadian Lower Fraser Valley : final report

International Nuclear Information System (INIS)

Mak, J.; Chan, N.; Campbell, K.; Preston, K.; Bolechowsky, K.

2007-12-01

Metro Vancouver conducts an emission inventory for the Lower Fraser Valley on a five year basis. This report presented an estimate of the nonroad engine fleet population and emissions in the Canadian portion of the Lower Fraser Valley (CLFV). The nonroad engine fleet includes internal combustion engines of different fuel types used in mobile equipment such as on-road vehicles, aircraft, locomotives and ocean-going marine vessels. Some examples of nonroad equipment that were estimated included agricultural tractors; airport ground equipment; forklifts; excavators; generator sets; lawn mowers; railroad maintenance equipment; pleasure boats; and off-road motorcycles. The purpose of the study was to assist Metro Vancouver and other levels of government in determining what progress has been made in improving air quality, as well as the effect of policies and regulations on the environment in terms of nonroad vehicles. The report presented the objectives of the nonroad engine fleet characterization project which were to review the current data on nonroad engine populations and associated information, and confirm or improve the data through appropriate means; prepare estimates of 2005 emissions in the CLFV based on the revised engine counts using the United States Environmental Protection Agency's nonroad 2005 model; and prepare backcasts and forecasts of the 2005 nonroad engine emission estimates for 1990 to 2030 in five-year increments. Results were presented and analysed into the following 9 equipment type categories: agricultural, airport ground support, commercial, construction, industrial, lawn and garden, railway maintenance, recreational marine and recreational off-road vehicle. Four fuel types were considered for each type of equipment, notably gasoline, diesel, liquefied petroleum gases and compressed natural gas. The report described the methodologies and sources and presented the equipment population data. Emission results for carbon monoxide, nitrogen oxides

Twenty-Five year (1982-2007) history of lodgepole pine dwarf mistletoe animal vectors and ethephon control on the Fraser Experimental Forest in Colorado

Science.gov (United States)

Thomas. Nicholls

2009-01-01

This is a summary of the 25-year history of studies of mammal and bird vectors of lodgepole pine dwarf mistletoe (Arceuthobium americanum), ethephon control of dwarf mistletoe, and the ecology of the most important dwarf mistletoe vector, the gray jay (Persisoreus canadensis), on the USDA Forest Service, Fraser Experimental Forest...

O Casamento entre Pessoas do Mesmo Sexo na Suprema Corte Norte-Americana: uma reflexão baseada no diálogo entre Honneth-Fraser

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Maria Eugenia Bunchaft

2016-12-01

Full Text Available http://dx.doi.org/10.5007/2177-7055.2016v37n74p233 Este trabalho objetiva analisar a decisão majoritária no julgamento do caso Obergefell v. Hodges à luz dos referenciais teóricos desenvolvidos por Axel Honneth e Nancy Fraser e seus reflexos na interpretação e na crítica de posturas proativas do Poder Judiciário. Sustenta-se que o voto de Justice Kennedy contempla um conjunto de discursos implícitos que não apenas estabelecem a subordinação de status de casais homossexuais não casados - que é tão criticada por Fraser - mas essencializam a identidade gay. Utiliza-se o método de indução analítica e a análise crítica do discurso feminista. Outrossim, o trabalho também emprega a documentação indireta.

Evolutionary history and population genetics of fraser fir and intermediate fir, southern Appalachian endemic conifers imperiled by an exotic pest and climate change

Science.gov (United States)

Kevin M. Potter; John Frampton; Sedley Josserand; C. Dana. Nelson

2010-01-01

Two Abies (true fir) taxa are endemic to high elevations of the Appalachian Mountains, where both are restricted to small populations and are imperiled by the same exotic insect. Fraser fir (Abies fraseri) exists in a handful of island-like populations on mountain ridges in the southern Appalachians of North Carolina, Tennessee and...

On the changing contribution of snow to the hydrology of the Fraser River Basin, Canada

Science.gov (United States)

Dery, S. J.; Kang, D.; Shi, X.; Gao, H.

2013-12-01

This talk will present an application of the Variable Infiltration Capacity (VIC) model to the Fraser River Basin (FRB) of British Columbia (BC), Canada over the latter half of the 20th century. The Fraser River is the longest waterway in BC and supports the world's most abundant Pacific Ocean salmon populations. Previous modeling and observational studies have demonstrated that the FRB is a snow-dominated system but with climate change it may evolve to a pluvial regime. Thus the goal of this study is to evaluate the changing contribution of snow to the hydrology of the watershed over the latter half of the 20th century. To this end, a 0.25° atmospheric forcing dataset is used to drive the VIC model from 1948 to 2006 at a daily time step over a domain covering the entire FRB. A model evaluation is first conducted over 11 major sub-watersheds of the FRB to quantitatively assess the spatial variations of snow water equivalent (SWE) and runoff. The ratio of the spatially averaged maximum SWE to runoff (RSR) is used to quantify the contribution of snow to the runoff in the 11 sub-watersheds of interest. From 1948 to 2006, RSR exhibits a significant decreasing trend in 9 of the 11 sub-watersheds (at a 0.05 of p-value according to the Mann-Kendall Test statistics). Changes in snow accumulation and melt lead to significant advances of the spring freshet throughout the basin. As the climate continues to warm, ecological processes and human usage of natural resources in the FRB may be substantially affected by its transition from a snow to a hybrid (nival/pluvial) and even a rain-dominated watershed.

The Expression of Inflammatory Mediators in Bladder Pain Syndrome.

Science.gov (United States)

Offiah, Ifeoma; Didangelos, Athanasios; Dawes, John; Cartwright, Rufus; Khullar, Vik; Bradbury, Elizabeth J; O'Sullivan, Suzanne; Williams, Dic; Chessell, Iain P; Pallas, Kenny; Graham, Gerry; O'Reilly, Barry A; McMahon, Stephen B

2016-08-01

Bladder pain syndrome (BPS) pathology is poorly understood. Treatment strategies are empirical, with limited efficacy, and affected patients have diminished quality of life. We examined the hypothesis that inflammatory mediators within the bladder contribute to BPS pathology. Fifteen women with BPS and 15 women with stress urinary incontinence without bladder pain were recruited from Cork University Maternity Hospital from October 2011 to October 2012. During cystoscopy, 5-mm bladder biopsies were taken and processed for gene expression analysis. The effect of the identified genes was tested in laboratory animals. We studied the expression of 96 inflammation-related genes in diseased and healthy bladders. We measured the correlation between genes and patient clinical profiles using the Pearson correlation coefficient. Analysis revealed 15 differentially expressed genes, confirmed in a replication study. FGF7 and CCL21 correlated significantly with clinical outcomes. Intravesical CCL21 instillation in rats caused increased bladder excitability and increased c-fos activity in spinal cord neurons. CCL21 atypical receptor knockout mice showed significantly more c-fos upon bladder stimulation with CCL21 than wild-type littermates. There was no change in FGF7-treated animals. The variability in patient samples presented as the main limitation. We used principal component analysis to identify similarities within the patient group. Our study identified two biologically relevant inflammatory mediators in BPS and demonstrated an increase in nociceptive signalling with CCL21. Manipulation of this ligand is a potential new therapeutic strategy for BPS. We compared gene expression in bladder biopsies of patients with bladder pain syndrome (BPS) and controls without pain and identified two genes that were increased in BPS patients and correlated with clinical profiles. We tested the effect of these genes in laboratory animals, confirming their role in bladder pain. Manipulating

Eficiencia de una modificación de la prueba de Fraser para la alternativa de localización en el problema de muestra / Efficiency of a modification the Fraser's test for alternative location on the problem of sample

OpenAIRE

Hidalgo Troya, Arsenio

2009-01-01

Se propone una familia de pruebas de rangos para el problema de localización en una muestra, usando como función de puntajes, la función percentil de la Distribución Lambda Generalizada (DLG), extendiendo la idea de Fraser de la función puntajes normales. Se obtienen las expresiones de las eficacias de las pruebas propuestas como funciones de los parámetros de curtósis de la distribución usada como función de puntajes y de la distribución muestreada. Por medio de un estudio de simulación se m...

Theology and psychology – the interdisciplinary work of Fraser Watts

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Willem J. Smith

2005-10-01

Full Text Available In the preface to his book, Theology and Psychology, Fraser Watts, a lecturer in Theology and Natural Science at the University of Cambridge, states that he approaches “… the interface between theology and psychology by looking at each discipline from the perspective of the other. This includes a religious perspective on several current hot topics in psychology, such as evolution, neuroscience, and computer intelligence. I also consider theological topics like divine action, salvation history and eschatology, in each case using the psychological perspective in a different way”. By taking an interdisciplinary approach, Watts aims at proposing a psychology of religious experience. He considers theology to be the rational reflection on the Christian tradition. When exponents of this tradition are in dialogue with exponents of psychology, the focus falls on human nature. Watts admits that a certain lack of competence in one of the two disciplines can be a problem when working in an interdisciplinary way. However, he is willing to take the risk. Watts worked in psychology for 25 years and was also involved with a medical research council, before taking up a position at the Faculty of Divinity, University of Cambridge.

Sleep duration as a mediator between an alternating day and night shift work schedule and metabolic syndrome among female hospital employees.

Science.gov (United States)

Korsiak, Jill; Tranmer, Joan; Day, Andrew; Aronson, Kristan J

2018-02-01

The main objective was to determine whether sleep duration on work shifts mediates the relationship between a current alternating day and night shift work schedule and metabolic syndrome among female hospital employees. The secondary objective was to assess whether cumulative lifetime shift work exposure was associated with metabolic syndrome. In this cross-sectional study of 294 female hospital employees, sleep duration was measured with the ActiGraph GT3X+. Shift work status was determined through self-report. Investigation of the total, direct and indirect effects between shift work, sleep duration on work shifts and metabolic syndrome was conducted using regression path analysis. Logistic regression was used to determine the association between cumulative shift work exposure and metabolic syndrome. Shift work is strongly associated with metabolic syndrome (OR Total =2.72, 95% CI 1.38 to 5.36), and the relationship is attenuated when work shift sleep duration is added to the model (OR Direct =1.18, 95% CI 0.49 to 2.89). Sleep duration is an important intermediate between shift work and metabolic syndrome (OR Indirect =2.25, 95% CI 1.27 to 4.26). Cumulative shift work exposure is not associated with metabolic syndrome in this population. Sleep duration mediates the association between a current alternating day-night shift work pattern and metabolic syndrome. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Alu-mediated deletion of SOX10 regulatory elements in Waardenburg syndrome type 4.

Science.gov (United States)

Bondurand, Nadége; Fouquet, Virginie; Baral, Viviane; Lecerf, Laure; Loundon, Natalie; Goossens, Michel; Duriez, Benedicte; Labrune, Philippe; Pingault, Veronique

2012-09-01

Waardenburg syndrome type 4 (WS4) is a rare neural crest disorder defined by the combination of Waardenburg syndrome (sensorineural hearing loss and pigmentation defects) and Hirschsprung disease (intestinal aganglionosis). Three genes are known to be involved in this syndrome, that is, EDN3 (endothelin-3), EDNRB (endothelin receptor type B), and SOX10. However, 15-35% of WS4 remains unexplained at the molecular level, suggesting that other genes could be involved and/or that mutations within known genes may have escaped previous screenings. Here, we searched for deletions within recently identified SOX10 regulatory sequences and describe the first characterization of a WS4 patient presenting with a large deletion encompassing three of these enhancers. Analysis of the breakpoint region suggests a complex rearrangement involving three Alu sequences that could be mediated by a FosTes/MMBIR replication mechanism. Taken together with recent reports, our results demonstrate that the disruption of highly conserved non-coding elements located within or at a long distance from the coding sequences of key genes can result in several neurocristopathies. This opens up new routes to the molecular dissection of neural crest disorders.

Síndrome de Fraser: relato de caso nas vias lacrimais

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Silvia Helena Tavares Lorena

2014-04-01

Full Text Available A síndrome de Fraser é uma condição sistêmica caracterizada por criptoftalmo, sindactilia e anomalia da genitália, podendo se associar com alterações dos rins, do ouvido, do nariz, da laringe e do esqueleto. O criptoftalmo pode representar um achado isolado, representado por herança autossômica dominante, associado a outras anomalias congênitas, relatado como herança autossômica recessiva. Criança do sexo feminino, 9 meses, avaliada no ambulatório de vias lacrimais da Universidade Federal de São Paulo. Filha de pais consanguíneos. Ao exame, foram observados criptoftalmo total à esquerda, epífora em olho direito associada à secreção mucopurulenta, nariz em sela, implantação baixa das orelhas, malformação de conduto auditivo, aumento de grandes lábios e sindactilia de mãos e pés. A tomografia de crânio evidenciou braquicefalia ausência de septo pelúcido, proeminência dos ventrículos laterais, importante falha óssea na calota craniana, presença de afilamento do manto tecidual cerebral, fossa posterior pequena, desorganização do segmento anterior, afacia e descolamento total da retina.

Contribution of Large Genomic Rearrangements in Italian Lynch Syndrome Patients: Characterization of a Novel Alu-Mediated Deletion

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Francesca Duraturo

2013-01-01

Full Text Available Lynch syndrome is associated with germ-line mutations in the DNA mismatch repair (MMR genes, mainly MLH1 and MSH2. Most of the mutations reported in these genes to date are point mutations, small deletions, and insertions. Large genomic rearrangements in the MMR genes predisposing to Lynch syndrome also occur, but the frequency varies depending on the population studied on average from 5 to 20%. The aim of this study was to examine the contribution of large rearrangements in the MLH1 and MSH2 genes in a well-characterised series of 63 unrelated Southern Italian Lynch syndrome patients who were negative for pathogenic point mutations in the MLH1, MSH2, and MSH6 genes. We identified a large novel deletion in the MSH2 gene, including exon 6 in one of the patients analysed (1.6% frequency. This deletion was confirmed and localised by long-range PCR. The breakpoints of this rearrangement were characterised by sequencing. Further analysis of the breakpoints revealed that this rearrangement was a product of Alu-mediated recombination. Our findings identified a novel Alu-mediated rearrangement within MSH2 gene and showed that large deletions or duplications in MLH1 and MSH2 genes are low-frequency mutational events in Southern Italian patients with an inherited predisposition to colon cancer.

Modelling the internal boundary layer over the lower fraser valley, British Columbia

Energy Technology Data Exchange (ETDEWEB)

Batchvarova, E. [National Inst. of Meteorology and Hydrology, Sofia (Bulgaria); Steyn, D. [Univ. of British Columbia, Dept. of Geography, Vancouver (Canada); Cai, X. [Univ. of Birmingham, School of Geography, Edgbaston (United Kingdom); Gryning, S.E. [Risoe National Lab., Roskilde (Denmark); Baldi, M. [Inst. for Atmospheric Physics, IFA-CNR, Rome (Italy)

1997-10-01

In this study we use the very extensive data-set on temporal and spatial structure of the internal boundary layer on the Lower Faser Valley, Canada, collected during the so-called Pacific `93 field campaign, to study the ability of the simple applied model by Gryning and Batchvarova (1996) and the CSU-RAMS meso-scale model summarised in Pielke et al. (1992) to describe the development and variability of the internal boundary layer depth during the course of a day. Given the complexity of topography, coastline and land-use in the Lower Fraser Valley region, both models perform remarkably well. The simple applied model performs extremely well, given its simplicity. It is clear that correct specification of spatially resolved surface sensible heat flux and wind field are crucial to the success of this model which can be operated at very fine spatial resolution. The 3D model performs extremely well, though it too must capture the local wind field correctly for complete success. Its limited horizontal resolution results in strongly smoothed internal boundary layer height fields. (LN)

A temática das uniões homoafetivas no Supremo Tribunal Federal à luz do debate Honneth-Fraser The issue of homosexual unions in the Federal Supreme Court in light of the debate Honneth-Fraser

Directory of Open Access Journals (Sweden)

Maria Eugenia Bunchaft

2012-06-01

Full Text Available O debate sobre os direitos das uniões homoafetivas constitui um dos tópicos mais controversos do direito constitucional. Como se sabe, a união homoafetiva não foi reconhecida expressamente no § 3º do artigo 226 da CF, inexistindo norma específica. O presente artigo pretende investigar a posição de ministros do STF em relação ao tema das uniões homoafetivas, em conexão com as filosofias do reconhecimento propostas por Axel Honneth e Nancy Fraser. Nesse sentido, os fundamentos filosóficos das teorias do reconhecimento podem ser um instrumental teórico fundamental para a compreensão de determinadas formas de ativismo judicial que objetivam a proteção de minorias estigmatizadas cujas pretensões normativas são desconsideradas pelo processo político. Pretendemos demonstrar que o paradigma da autorrealização proposto por Honneth é impreciso e incapaz de legitimar formas de ativismo judicial voltadas para a proteção dos direitos das uniões homoafetivas.The homosexual union rights are debated as one of the most controversial topics of Constitutional Law. It is known that the homosexual union was not explicitly recognized by the article 226 § 3º from FC, as there is no specific regulation for this subject. This paper intends to investigate STF ministers' position in relation to homosexual union according to Axel Honneth and Nancy Fraser philosophies of recognition. In this sense, the philosophical basis from recognition theories may be a theoretical instrument to comprehend some forms of judicial activism which aims are to protect stigmatized minorities whose regulatory intentions are disregarded by the political process. We intend to demonstrate that the Honneth's paradigm of achievement is imprecise and can't legitimate forms of judicial activism aimed to protect the rights of homosexual unions.

Coexistence of Cushing syndrome from functional adrenal adenoma and Addison disease from immune-mediated adrenalitis.

Science.gov (United States)

Colucci, Randall; Jimenez, Rafael E; Farrar, William; Malgor, Ramiro; Kohn, Leonard; Schwartz, Frank L

2012-06-01

A 56-year-old woman presented with an incidental adrenal adenoma and physical examination findings that included moderate obesity, a slight cervicothoracic fat pad ("buffalo hump"), increased supraclavicular fat pads, and white abdominal striae. Biochemical workup revealed elevated levels of 24-hour urinary free cortisol but normal serum morning cortisol and suppressed levels of corticotropin, suggestive of adrenal-dependent Cushing syndrome. The resected adrenal gland revealed macronodular cortical hyperplasia with a dominant nodule. Other findings included an absent cortisol response to corticotropin stimulation, presence of serum anti-21-hydroxylase antibodies, and mononuclear cell infiltration--consistent with adrenalitis. The findings represent, to the authors' knowledge, the first known case of a patient with coexistent functional cortisol-secreting macronodular adrenal tumor resulting in Cushing syndrome and immune-mediated adrenalitis resulting in Addison disease.

Implementing information technology to improve workplace health: a web-based information needs assessment of managers in Fraser Health, British Columbia.

Science.gov (United States)

Sandhu, Jag S; Anderson, Keith; Keen, Dave; Yassi, Annalee

2005-01-01

A web-based questionnaire-survey was administered primarily to determine what information is useful to managers in Fraser Health, of British Columbia to support decision-making for workplace health and safety. The results indicated that managers prefer electronic quarterly reports, with targets, goals, and historical trends rated as "very important." Over 85.7% "agree" that if information was readily available in the "most beneficial" format, they would be able to improve workplace health. Recommendations include that managers be presented with clear and concise workplace health reports that facilitate analysis for decision-making.

Non-IgE-mediated food allergies | Terblanche | South African ...

African Journals Online (AJOL)

mediated conditions such as atopic dermatitis and eosinophilic oesophagitis, and pure T-cell-mediated conditions such as food protein-induced enterocolitis syndrome, allergic proctocolitis and enteropathy syndromes. Diagnosing mixed or ...

Selected Food Consumption Mediates the Association between Education Level and Metabolic Syndrome in Korean Adults.

Science.gov (United States)

Kim, Oh Yoen; Kwak, So-Young; Kim, Boeun; Kim, Young-Sun; Kim, Hye Young; Shin, Min-Jeong

2017-01-01

Low socioeconomic status (SES) is linked to higher incidence/mortality of cardiovascular disease, but emerging evidence inconsistently reported that education level, a proxy for SES, is related to cardiovascular risk and metabolic syndrome (MetS) in Koreans. Furthermore, limited information is available on whether dietary components would mediate the relationship between education level and cardiovascular risk. We hypothesized that selected food consumption mediates the association between education level and MetS prevalence. Data from the Korea National Health and Nutritional Examination Survey (2008-2011) were included in cross-sectional analyses (n = 11,029, 30-64 years). The possible mediating effect of selected food groups (fruits, raw vegetables, red meat, milk, and soft drinks) on the association between education level and MetS was tested using a multiple mediation model. Education level was negatively associated with MetS prevalence. The association between lower education level and higher MetS prevalence was partially mediated by selected food consumption (lower intakes of fruit, red meat and milk; higher intakes of vegetable and soft drink) after adjusted for covariates. Gender also modified the association between education level and MetS prevalence that was more prominent in women than in men. Selected food consumption substantially contributes to the association between education level and MetS in Korean adults, especially among women. © 2017 S. Karger AG, Basel.

Designing an Educational Application of Parental-Mediated Intervention and Its Effectiveness to Promote Reading Skills Among Slow-Paced Students with Down Syndrome

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Kosar Bereyhi

2017-02-01

Full Text Available Objectives This study aimed to design an educational application of parental-mediated intervention and its effectiveness to promote reading skills in students with Down syndrome. Methods This applied semi-experimental study is a pre-test- and post-test project, follow-up with the test and control groups which was conducted on twenty slow-paced students with Down syndrome in the range of 5 to 12 years old. Patients were randomly selected and classify into two groups; test and control. Wechsler IQ test, TOLD test and peabody picture vocabulary test (PPVT were performed for students in the pre-test however; TOLD test was conducted as the post-test and a half month at 15-day after follow-up stage. Results results showed α > 0.001 for reading skills between test and control groups; however the difference is remained sustainable in follow-up stage. Conclusions Education with new educational technologies that focused on software may be helpful for children with Down syndrome and should be seriously considered. Family- centered parental-mediated intervention in order to promote reading skills application can be used for teaching children, families and educators.

Dust records in the Pleistocene sediments of Fraser Island: palaeoclimatic reconstruction of wind erosion over the last 600 ka

International Nuclear Information System (INIS)

Longmore, M.E.; McTainsh, G.H.

1997-01-01

Full text: Pleistocene lake sediments from a relic perched freshwater lake on Fraser Island have been found to date back to ca.600 ka using U/Th analysis of the organics. This sequence is one of the three longest terrestrial records of environmental change in Australia and the contained evidence of vegetation, fire and lake level changes (Longmore and Heijnis, 1996) and is an invaluable contribution to palaeoclimatic reconstruction. A younger sequence, dated by conventional radiocarbon analysis, has 6.5 m of continuous organic sedimentation from ca. 30 ka to the present. The last 8.5 ka has been analysed in detail, showing a mid-Holocene 'dry' period (Longmore, 1996). Continental aeolian dust from extreme wind erosional events has been measured in modern atmospheres (McTainsh, 1989; Knight et al., 1995) and deep sea cores (Hesse, 1994), but the terrestrial record of wind erosion during the Pleistocene is sparse. We will report on a pilot project to determine the presence of aeolian dust from extreme wind erosional events in the past in the sediments of Fraser Island lakes. Due to the highly weathered, well-sorted, siliceous nature of the dune sands forming the Island and the highly organic nature of the lake sediments (80-95% LOI), these are some of the few terrestrial sequences that permit separation of aeolian dust from local catchment materials. In the future, oxygen isotope and XRD analysis of the extracted dust will allow the most likely source of the entrained material to be determined and thus provide further evidence as to the wind regime during the last 600ka and 30ka respectively. The separation of dust from these terrestrial sequences is a major achievement and potentially may make a significant contribution to global palaeoclimatic models

Analysis of Seasonal Soil Organic Carbon Content at Bukit Jeriau Forest, Fraser Hill, Pahang

International Nuclear Information System (INIS)

Ahmad Adnan Mohamed; Ahmad Adnan Mohamed; Sahibin Abd Rahim; David Allan Aitman; Mohd Khairul Amri Kamarudin; Mohd Khairul Amri Kamarudin

2016-01-01

Soil carbon is the carbon held within the soil, primarily in association with its organic content. The total soil organic carbon study was determined in a plot at Bukit Jeriau forest in Bukit Fraser, Pahang, Malaysia. The aim of this study is to determine the changing of soil organic carbon between wet season and dry season. Soil organic carbon was fined out using titrimetric determination. The soil organic carbon content in wet season is 223.24 t/ ha while dry season is 217.90 t/ ha. The soil pH range in wet season is between 4.32 to 4.45 and in dry season in 3.95 to 4.08 which is considered acidic. Correlation analysis showed that soil organic carbon value is influenced by pH value and climate. Correlation analysis between clay and soil organic carbon with depth showed positively significant differences and clay are very much influenced soil organic carbon content. Correlation analysis between electrical conductivity and soil organic carbon content showed negative significantly difference on wet season and positively significant different in dry season. (author)

Examining controls on peak annual streamflow and floods in the Fraser River Basin of British Columbia

Science.gov (United States)

Curry, Charles L.; Zwiers, Francis W.

2018-04-01

The Fraser River Basin (FRB) of British Columbia is one of the largest and most important watersheds in western North America, and home to a rich diversity of biological species and economic assets that depend implicitly upon its extensive riverine habitats. The hydrology of the FRB is dominated by snow accumulation and melt processes, leading to a prominent annual peak streamflow invariably occurring in May-July. Nevertheless, while annual peak daily streamflow (APF) during the spring freshet in the FRB is historically well correlated with basin-averaged, 1 April snow water equivalent (SWE), there are numerous occurrences of anomalously large APF in below- or near-normal SWE years, some of which have resulted in damaging floods in the region. An imperfect understanding of which other climatic factors contribute to these anomalously large APFs hinders robust projections of their magnitude and frequency. We employ the Variable Infiltration Capacity (VIC) process-based hydrological model driven by gridded observations to investigate the key controlling factors of anomalous APF events in the FRB and four of its subbasins that contribute nearly 70 % of the annual flow at Fraser-Hope. The relative influence of a set of predictors characterizing the interannual variability of rainfall, snowfall, snowpack (characterized by the annual maximum value, SWEmax), soil moisture and temperature on simulated APF at Hope (the main outlet of the FRB) and at the subbasin outlets is examined within a regression framework. The influence of large-scale climate modes of variability (the Pacific Decadal Oscillation (PDO) and the El Niño-Southern Oscillation - ENSO) on APF magnitude is also assessed, and placed in context with these more localized controls. The results indicate that next to SWEmax (univariate Spearman correlation with APF of ρ ^ = 0.64; 0.70 (observations; VIC simulation)), the snowmelt rate (ρ ^ = 0.43 in VIC), the ENSO and PDO indices (ρ ^ = -0.40; -0.41) and (�

Age-related changes in humoral and cell-mediated immunity in Down syndrome children living at home.

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Lockitch, G; Singh, V K; Puterman, M L; Godolphin, W J; Sheps, S; Tingle, A J; Wong, F; Quigley, G

1987-11-01

Abnormalities of humoral and cell-mediated immunity have been described in Down syndrome but reported findings have been inconsistent. Confounding factors have included age, institutional versus home life, hepatitis B antigenemia, and zinc deficiency. To clarify this problem, we studied 64 children with Down syndrome (DS) compared with an age-matched control group. All children had always lived at home. All the DS children were negative for hepatitis B surface antigen. Serum zinc concentration in the DS group was on average 12 micrograms/dl lower than age-matched control children. They also had significantly lower levels of immunoglobulin M, total lymphocyte count, T and B lymphocytes, and T helper and suppressor cells. In vitro lymphocyte response to phytohemagglutinin and concanavalin A was significantly reduced at all ages in the DS group. Lymphocyte response to pokeweed mitogen increased with age in control children but decreased in the DS children. By 18 yr, the mean response for DS was 60000 cpm lower than controls. The DS group had significantly higher concentrations of immunoglobulins A and G than controls and the difference increased with age. Complement fractions C3 and C4 were also higher in the DS group at all ages. The number of HNK-1 positive cells was higher in the DS group than controls at all ages. When hepatitis and institutionalization are excluded as confounding factors, DS children still differ in both humoral and cell-mediated immunity from an age-matched control group.

Are Pain-Related Fears Mediators for Reducing Disability and Pain in Patients with Complex Regional Pain Syndrome Type 1? An Explorative Analysis on Pain Exposure Physical Therapy

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Barnhoorn, Karlijn J.; Staal, J. Bart; van Dongen, Robert T. M.; Frölke, Jan Paul M.; Klomp, Frank P.; van de Meent, Henk; Samwel, Han; Nijhuis-van der Sanden, Maria W. G.

2015-01-01

Objective To investigate whether pain-related fears are mediators for reducing disability and pain in patients with Complex Regional Pain Syndrome type 1 when treating with Pain Exposure Physical Therapy. Design An explorative secondary analysis of a randomised controlled trial. Participants Fifty-six patients with Complex Regional Pain Syndrome type 1. Interventions The experimental group received Pain Exposure Physical Therapy in a maximum of five treatment sessions; the control group received conventional treatment following the Dutch multidisciplinary guideline. Outcome measures Levels of disability, pain, and pain-related fears (fear-avoidance beliefs, pain catastrophizing, and kinesiophobia) were measured at baseline and after 3, 6, and 9 months follow-up. Results The experimental group had a significantly larger decrease in disability of 7.77 points (95% CI 1.09 to 14.45) and in pain of 1.83 points (95% CI 0.44 to 3.23) over nine months than the control group. The potential mediators pain-related fears decreased significantly in both groups, but there were no significant differences between groups, which indicated that there was no mediation. Conclusion The reduction of pain-related fears was comparable in both groups. We found no indication that pain-related fears mediate the larger reduction of disability and pain in patients with Complex Regional Pain Syndrome type 1 treated with Pain Exposure Physical Therapy compared to conventional treatment. Trial registration International Clinical Trials Registry NCT00817128 PMID:25919011

Phosphorylation of the Usher syndrome 1G protein SANS controls Magi2-mediated endocytosis.

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Bauß, Katharina; Knapp, Barbara; Jores, Pia; Roepman, Ronald; Kremer, Hannie; Wijk, Erwin V; Märker, Tina; Wolfrum, Uwe

2014-08-01

The human Usher syndrome (USH) is a complex ciliopathy with at least 12 chromosomal loci assigned to three clinical subtypes, USH1-3. The heterogeneous USH proteins are organized into protein networks. Here, we identified Magi2 (membrane-associated guanylate kinase inverted-2) as a new component of the USH protein interactome, binding to the multifunctional scaffold protein SANS (USH1G). We showed that the SANS-Magi2 complex assembly is regulated by the phosphorylation of an internal PDZ-binding motif in the sterile alpha motif domain of SANS by the protein kinase CK2. We affirmed Magi2's role in receptor-mediated, clathrin-dependent endocytosis and showed that phosphorylated SANS tightly regulates Magi2-mediated endocytosis. Specific depletions by RNAi revealed that SANS and Magi2-mediated endocytosis regulates aspects of ciliogenesis. Furthermore, we demonstrated the localization of the SANS-Magi2 complex in the periciliary membrane complex facing the ciliary pocket of retinal photoreceptor cells in situ. Our data suggest that endocytotic processes may not only contribute to photoreceptor cell homeostasis but also counterbalance the periciliary membrane delivery accompanying the exocytosis processes for the cargo vesicle delivery. In USH1G patients, mutations in SANS eliminate Magi2 binding and thereby deregulate endocytosis, lead to defective ciliary transport modules and ultimately disrupt photoreceptor cell function inducing retinal degeneration. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Neuroendocrine androgen action is a key extraovarian mediator in the development of polycystic ovary syndrome.

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Caldwell, Aimee S L; Edwards, Melissa C; Desai, Reena; Jimenez, Mark; Gilchrist, Robert B; Handelsman, David J; Walters, Kirsty A

2017-04-18

Polycystic ovary syndrome (PCOS) is a complex hormonal disorder characterized by reproductive, endocrine, and metabolic abnormalities. As the origins of PCOS remain unknown, mechanism-based treatments are not feasible and current management relies on treatment of symptoms. Hyperandrogenism is the most consistent PCOS characteristic; however, it is unclear whether androgen excess, which is treatable, is a cause or a consequence of PCOS. As androgens mediate their actions via the androgen receptor (AR), we combined a mouse model of dihydrotestosterone (DHT)-induced PCOS with global and cell-specific AR-resistant (ARKO) mice to investigate the locus of androgen actions that mediate the development of the PCOS phenotype. Global loss of the AR reveals that AR signaling is required for all DHT-induced features of PCOS. Neuron-specific AR signaling was required for the development of dysfunctional ovulation, classic polycystic ovaries, reduced large antral follicle health, and several metabolic traits including obesity and dyslipidemia. In addition, ovariectomized ARKO hosts with wild-type ovary transplants displayed normal estrous cycles and corpora lutea, despite DHT treatment, implying extraovarian and not intraovarian AR actions are key loci of androgen action in generating the PCOS phenotype. These findings provide strong evidence that neuroendocrine genomic AR signaling is an important extraovarian mediator in the development of PCOS traits. Thus, targeting AR-driven mechanisms that initiate PCOS is a promising strategy for the development of novel treatments for PCOS.

Fiber-Mediated Nourishment of Gut Microbiota Protects against Diet-Induced Obesity by Restoring IL-22-Mediated Colonic Health.

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Zou, Jun; Chassaing, Benoit; Singh, Vishal; Pellizzon, Michael; Ricci, Matthew; Fythe, Michael D; Kumar, Matam Vijay; Gewirtz, Andrew T

2018-01-10

Dietary supplementation with fermentable fiber suppresses adiposity and the associated parameters of metabolic syndrome. Microbiota-generated fiber-derived short-chain fatty acids (SCFAs) and free fatty acid receptors including GPR43 are thought to mediate these effects. We find that while fermentable (inulin), but not insoluble (cellulose), fiber markedly protected mice against high-fat diet (HFD)-induced metabolic syndrome, the effect was not significantly impaired by either inhibiting SCFA production or genetic ablation of GPR43. Rather, HFD decimates gut microbiota, resulting in loss of enterocyte proliferation, leading to microbiota encroachment, low-grade inflammation (LGI), and metabolic syndrome. Enriching HFD with inulin restored microbiota loads, interleukin-22 (IL-22) production, enterocyte proliferation, and antimicrobial gene expression in a microbiota-dependent manner, as assessed by antibiotic and germ-free approaches. Inulin-induced IL-22 expression, which required innate lymphoid cells, prevented microbiota encroachment and protected against LGI and metabolic syndrome. Thus, fermentable fiber protects against metabolic syndrome by nourishing microbiota to restore IL-22-mediated enterocyte function. Copyright © 2017 Elsevier Inc. All rights reserved.

Beliefs about emotions mediate the relationship between emotional suppression and quality of life in irritable bowel syndrome.

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Bowers, Hannah; Wroe, Abigail

2016-01-01

Cross-sectional and experimental research has demonstrated an association between emotional suppression and IBS. However, the relationship is not well understood. To examine the relationships between emotional suppression, we compare the measures of beliefs about emotions and quality of life in irritable bowel syndrome (IBS) with healthy controls. Online questionnaires measured beliefs about emotions, emotional suppression and IBS-related quality of life in participants with (n = 87) and without (n = 37) IBS. Mediation analyses and group comparisons were used to explore the role of emotional suppression and beliefs about emotions in this sample. IBS participants held significantly more beliefs about the unacceptability of emotions compared to healthy controls despite no differences in emotional suppression. The relationship between beliefs about emotions and quality of life was not mediated by emotional suppression. However, the relationship between emotional suppression and quality of life was mediated by beliefs about emotions. The findings suggest a role of beliefs about emotions and emotional suppression in IBS, where emotional suppression may relate to changes in beliefs about emotions and consequently quality of life. This is discussed in relation to the cognitive-behavioural model of medically unexplained symptoms.

Evolution of a short-term study of lodgepole pine dwarf mistletoe vectors that turned into a long-term study of the remarkable gray jay on the Fraser Experimental Forest,Colorado, 1982-2009

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Thomas H. Nicholls

2014-01-01

This is a summary of a 5-year short-term study that evolved into 28 years of long-term research on the US Department of Agriculture, Forest Service's Fraser Experimental Forest in Colorado. The study was begun in 1982 by Forest Service Research Scientists Thomas H. Nicholls and Frank G. Hawksworth to determine the importance of mammal and bird vectors in the long-...

TALEN-mediated single-base-pair editing identification of an intergenic mutation upstream of BUB1B as causative of PCS (MVA) syndrome

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Ochiai, Hiroshi; Miyamoto, Tatsuo; Kanai, Akinori; Hosoba, Kosuke; Sakuma, Tetsushi; Kudo, Yoshiki; Asami, Keiko; Ogawa, Atsushi; Watanabe, Akihiro; Kajii, Tadashi; Yamamoto, Takashi; Matsuura, Shinya

2014-01-01

Cancer-prone syndrome of premature chromatid separation with mosaic variegated aneuploidy [PCS (MVA) syndrome] is a rare autosomal recessive disorder characterized by constitutional aneuploidy and a high risk of childhood cancer. We previously reported monoallelic mutations in the BUB1B gene (encoding BUBR1) in seven Japanese families with the syndrome. No second mutation was found in the opposite allele of any of the families studied, although a conserved BUB1B haplotype and a decreased transcript were identified. To clarify the molecular pathology of the second allele, we extended our mutational search to a candidate region surrounding BUB1B. A unique single nucleotide substitution, G > A at ss802470619, was identified in an intergenic region 44 kb upstream of a BUB1B transcription start site, which cosegregated with the disorder. To examine whether this is the causal mutation, we designed a transcription activator-like effector nuclease–mediated two-step single-base pair editing strategy and biallelically introduced this substitution into cultured human cells. The cell clones showed reduced BUB1B transcripts, increased PCS frequency, and MVA, which are the hallmarks of the syndrome. We also encountered a case of a Japanese infant with PCS (MVA) syndrome carrying a homozygous single nucleotide substitution at ss802470619. These results suggested that the nucleotide substitution identified was the causal mutation of PCS (MVA) syndrome. PMID:24344301

Neuroendocrine androgen action is a key extraovarian mediator in the development of polycystic ovary syndrome

Science.gov (United States)

Caldwell, Aimee S. L.; Edwards, Melissa C.; Desai, Reena; Jimenez, Mark; Gilchrist, Robert B.; Walters, Kirsty A.

2017-01-01

Polycystic ovary syndrome (PCOS) is a complex hormonal disorder characterized by reproductive, endocrine, and metabolic abnormalities. As the origins of PCOS remain unknown, mechanism-based treatments are not feasible and current management relies on treatment of symptoms. Hyperandrogenism is the most consistent PCOS characteristic; however, it is unclear whether androgen excess, which is treatable, is a cause or a consequence of PCOS. As androgens mediate their actions via the androgen receptor (AR), we combined a mouse model of dihydrotestosterone (DHT)-induced PCOS with global and cell-specific AR-resistant (ARKO) mice to investigate the locus of androgen actions that mediate the development of the PCOS phenotype. Global loss of the AR reveals that AR signaling is required for all DHT-induced features of PCOS. Neuron-specific AR signaling was required for the development of dysfunctional ovulation, classic polycystic ovaries, reduced large antral follicle health, and several metabolic traits including obesity and dyslipidemia. In addition, ovariectomized ARKO hosts with wild-type ovary transplants displayed normal estrous cycles and corpora lutea, despite DHT treatment, implying extraovarian and not intraovarian AR actions are key loci of androgen action in generating the PCOS phenotype. These findings provide strong evidence that neuroendocrine genomic AR signaling is an important extraovarian mediator in the development of PCOS traits. Thus, targeting AR-driven mechanisms that initiate PCOS is a promising strategy for the development of novel treatments for PCOS. PMID:28320971

Idiopathic combined, autoantibody-mediated ADAMTS-13/factor H deficiency in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in a 17-year-old woman: a case report

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Patschan Daniel

2011-12-01

Full Text Available Abstract Introduction Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome is a life-threatening condition with various etiopathogeneses. Without therapy approximately 90% of all patients die from the disease. Case presentation We report the case of a 17-year-old Caucasian woman with widespread hematomas and headache. Due to hemolytic anemia, thrombocytopenia, and schistocytosis, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome was suspected and plasma exchange therapy was initiated immediately. Since her thrombocyte level did not increase during the first week of therapy, plasma treatment had to be intensified to a twice-daily schedule. Further diagnostics showed markedly reduced activities of both ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 - also known as von Willebrand factor-cleaving protease and factor H. Test results for antibodies against both proteins were positive. While plasma exchange therapy was continued, rituximab was given once weekly for four consecutive weeks. After the last dose, thrombocytes and activities of ADAMTS-13 and factor H increased into the normal range. Our patient improved and was discharged from the hospital. Conclusions Since no clinical symptoms/laboratory findings indicated a malignant or specific autoimmune-mediated disorder, the diagnosis made was thrombotic thrombocytopenic purpura-hemolytic uremic syndrome due to idiopathic combined, autoantibody-mediated ADAMTS-13/factor H deficiency.

Examining controls on peak annual streamflow and floods in the Fraser River Basin of British Columbia

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C. L. Curry

2018-04-01

Full Text Available The Fraser River Basin (FRB of British Columbia is one of the largest and most important watersheds in western North America, and home to a rich diversity of biological species and economic assets that depend implicitly upon its extensive riverine habitats. The hydrology of the FRB is dominated by snow accumulation and melt processes, leading to a prominent annual peak streamflow invariably occurring in May–July. Nevertheless, while annual peak daily streamflow (APF during the spring freshet in the FRB is historically well correlated with basin-averaged, 1 April snow water equivalent (SWE, there are numerous occurrences of anomalously large APF in below- or near-normal SWE years, some of which have resulted in damaging floods in the region. An imperfect understanding of which other climatic factors contribute to these anomalously large APFs hinders robust projections of their magnitude and frequency. We employ the Variable Infiltration Capacity (VIC process-based hydrological model driven by gridded observations to investigate the key controlling factors of anomalous APF events in the FRB and four of its subbasins that contribute nearly 70 % of the annual flow at Fraser-Hope. The relative influence of a set of predictors characterizing the interannual variability of rainfall, snowfall, snowpack (characterized by the annual maximum value, SWEmax, soil moisture and temperature on simulated APF at Hope (the main outlet of the FRB and at the subbasin outlets is examined within a regression framework. The influence of large-scale climate modes of variability (the Pacific Decadal Oscillation (PDO and the El Niño–Southern Oscillation – ENSO on APF magnitude is also assessed, and placed in context with these more localized controls. The results indicate that next to SWEmax (univariate Spearman correlation with APF of ρ ^   =  0.64; 0.70 (observations; VIC simulation, the snowmelt rate (ρ ^   =  0.43 in VIC, the

Cytokine-mediated inflammation mediates painful neuropathy from metabolic syndrome.

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Can Zhang

Full Text Available Painful neuropathy (PN is a prevalent condition in patients with metabolic syndrome (MetS. However, the pathogenic mechanisms of metabolic syndrome-associated painful neuropathy (MetSPN remain unclear. In the current study, high-fat-fed mice (HF mice were used to study MetSPN. HF mice developed MetS phenotypes, including increased body weight, elevated plasma cholesterol levels, and insulin resistance in comparison with control-fat-fed (CF mice. Subsequently, HF mice developed mechanical allodynia and thermal hyperalgesia in hind paws after 8 wk of diet treatment. These pain behaviors coincided with increased densities of nociceptive epidermal nerve fibers and inflammatory cells such as Langerhans cells and macrophages in hind paw skin. To study the effect of MetS on profiles of cytokine expression in HF mice, we used a multiplex cytokine assay to study the protein expression of 12 pro-inflammatory and anti-inflammatory cytokines in dorsal root ganglion and serum samples. This method detected the elevated levels of proinflammatory cytokines, including tumor necrosis factor (TNF-α, and interleukin (IL-6, IL-1β as well as reduced anti-inflammatory IL-10 in lumbar dorsal root ganglia (LDRG of HF mice. Intraperitoneal administration of IL-10 reduced the upregulation of pro-inflammatory cytokines and alleviated pain behaviors in HF mice without affecting MetS phenotypes. Our findings suggested targeting HF-induced cytokine dysregulation could be an effective strategy for treating MetSPN.

Mediators of the Association of Major Depressive Syndrome and Anxiety Syndrome with Postpartum Smoking Relapse

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Correa-Fernandez, Virmarie; Ji, Lingyun; Castro, Yessenia; Heppner, Whitney L.; Vidrine, Jennifer Irvin; Costello, Tracy J.; Mullen, Patricia Dolan; Cofta-Woerpel, Ludmila; Velasquez, Mary M.; Greisinger, Anthony; Cinciripini, Paul M.; Wetter, David W.

2012-01-01

Objective: Based on conceptual models of addiction and affect regulation, this study examined the mechanisms linking current major depressive syndrome (MDS) and anxiety syndrome (AS) to postpartum smoking relapse. Method: Data were collected in a randomized clinical trial from 251 women who quit smoking during pregnancy. Simple and multiple…

The role of burnout syndrome as a mediator for the effect of psychosocial risk factors on the intensity of musculoskeletal disorders: a structural equation modeling approach.

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Gholami, Tahereh; Pahlavian, Ahmad Heidari; Akbarzadeh, Mahdi; Motamedzade, Majid; Moghaddam, Rashid Heidari

2016-01-01

This study examined the hypothesis that burnout syndrome mediates effects of psychosocial risk factors and intensity of musculoskeletal disorders (MSDs) among hospital nurses. The sample was composed of 415 nurses from various wards across five hospitals of Iran's Hamedan University of Medical Sciences. Data were collected through three questionnaires: job content questionnaire, Maslach burnout inventory and visual analogue scale. Results of structural equation modeling with a mediating effect showed that psychosocial risk factors were significantly related to changes in burnout, which in turn affects intensity of MSDs.

A rare case of Kounis syndrome provoked by mad honey poisoning

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Yakup Alsancak

2016-06-01

Full Text Available Kounis syndrome, resulting in acute coronary syndromes, as a result of allergic or hypersensitivity reaction is triggered by several factors. Vasospasm which is mediated by mediators released after mast cell activation, is the responsible mechanism for comprising of type 2-myocardial infarction. Mad honey containing grayanotoxin is previously shown to be associated with gastrointestinal, neurological and cardiac disorders. In this case report, we presented a Kounis syndrome that has occurred after the mad honey intake and treated successfully, previously not mentioned in the literature.

Autoimmune/inflammatory syndrome induced by adjuvants (Shoenfeld's syndrome) - An update.

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Watad, A; Quaresma, M; Brown, S; Cohen Tervaert, J W; Rodríguez-Pint, I; Cervera, R; Perricone, C; Shoenfeld, Y

2017-06-01

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) has been widely described in many studies conducted thus far. The syndrome incorporates five immune-mediated conditions, all associated with previous exposure to various agents such as vaccines, silicone implants and several others. The emergence of ASIA syndrome is associated with individual genetic predisposition, for instance those carrying HLA-DRB1*01 or HLA-DRB4 and results from exposure to external or endogenous factors triggering autoimmunity. Such factors have been demonstrated as able to induce autoimmunity in both animal models and humans via a variety of proposed mechanisms. In recent years, physicians have become more aware of the existence of ASIA syndrome and the relationship between adjuvants exposure and autoimmunity and more cases are being reported. Accordingly, we have created a registry that includes at present more than 300 ASIA syndrome cases that have been reported by different physicians worldwide, describing various autoimmune conditions induced by diverse adjuvants. In this review, we have summarized the updated literature on ASIA syndrome and the knowledge accumulated since 2013 in order to elucidate the association between the exposure to various adjuvant agents and its possible clinical manifestations. Furthermore, we especially referred to the relationship between ASIA syndrome and systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS).

Susceptibility of Shallow Landslide in Fraser Hill Catchment, Pahang Malaysia

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Wan Nor Azmin Sulaiman

2010-01-01

Full Text Available In tropical areas especially during monsoon seasons intense precipitation is the main caused that trigger the natural shallow landslide phenomena. This phenomenon can be disastrous and widespread in occurrence even in undisturbed forested catchment. In this paper, an attempt has been made to evaluate the susceptibility of natural hill slopes to failure for a popular hill resort area, the Fraser Hill Catchment under different rainfall regimes and soil thickness. A Digital Elevation Model (DEM was prepared for the 8.2 km2 catchment. A GIS based deterministic model was then applied to predict the spatial landslide occurrence within catchment. Model input parameters include bulk density, friction angle, cohesion and hydraulic conductivity were gathered through in situ and lab analysis as well as from previous soil analysis records. Landslides locations were recorded using GPS as well as previous air photos and satellite imagery to establish landslide source areas inventory. The landslide susceptibility map was produced under different precipitation event’s simulation to see the effects of precipitation to stability of the hill slopes of the catchment. The results were categorized into naturally unstable (Defended, Upper Threshold, Lower Threshold, marginal instability (Quasi Stable and stable area (Moderately Stable and Stable. Results of the simulation indicated notable change in precipitation effect on Defended area is between 10mm to 40mm range in a single storm event. However, when storm event is exceeded 120mm, the result on Defended area produced by the model tends to be constant further on. For area categorized as naturally unstable (Factor of Safety, SF<1, with 110 mm of precipitation in a single storm event and soil depth at 2 meters and 4 meters could affect 69.51% and 69.88% respectively of the catchment area fall under that class. In addition, the model was able to detect 4% more of the landslide inventory under shallower soil depth of

Depression in obese patients with primary fibromyalgia: the mediating role of poor sleep and eating disorder features.

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Senna, Mohammed K; Ahmad, Hamada S; Fathi, Warda

2013-03-01

Depression is a prominent feature in fibromyalgia syndrome. Patients with fibromyalgia syndrome who are obese, with poor sleep quality, and those who have recurrent episodes of binge eating are at greater risk to develop depression. The aim of this cross-sectional study was to examine the hypothesis that the relationship between obesity and depression in patients with primary fibromyalgia syndrome is mediated by poor sleep, binge eating disorder (BED), and weight and shape concern. This study included 131 patients with primary fibromyalgia syndrome. Participants completed the following questionnaires: Pittsburgh Sleep Quality Index, Beck Depression Inventory-II, Eating Disorder questionnaire, and Fibromyalgia Impact Questionnaire. Body mass index (BMI) provided the primary indicator of obesity. Sobel test showed that the conditions for complete mediation were satisfied on the weight and shape concern as mediator between BMI and depression because the association between BMI and depression score became insignificant after controlling of weight and shape concern. However, since the association between BMI and depression remained significant after BED and poor sleep score were controlled, thus for both mediators, the conditions for partial mediation on the depression were satisfied. The findings suggest that in patients with primary fibromyalgia syndrome, weight and shape concern, BED, and poor sleep quality are important mediators of the relationship between obesity and depression. We suggest that a greater focus on these mediators in depression treatment may be indicated.

Lumbar dorsal ramus syndrome.

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Bogduk, N

1980-11-15

Low back pain, referred pain in the lower limbs, and spasm of the back, gluteal, and hamstring muscles are clinical features which can be induced in normal volunteers by stimulating structures which are innervated by the lumbar dorsal rami. Conversely, they can be relieved in certain patients by selective interruption of conduction along dorsal rami. These facts permit the definition of a lumbar dorsal ramus syndrome, which can be distinguished from the intervertebral disc syndrome and other forms of low back pain. The distinguishing feature is that, in lumbar dorsal ramus syndrome, all the clinical features are exclusively mediated by dorsal rami and do not arise from nerve-root compression. The pathophysiology, pathology, and treatment of this syndrome are described. Recognition of this syndrome, and its treatment with relatively minor procedures, can obviate the need for major surgery which might otherwise be undertaken.

Prolonged REM sleep restriction induces metabolic syndrome-related changes: Mediation by pro-inflammatory cytokines.

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Venancio, Daniel Paulino; Suchecki, Deborah

2015-07-01

Chronic sleep restriction in human beings results in metabolic abnormalities, including changes in the control of glucose homeostasis, increased body mass and risk of cardiovascular disease. In rats, 96h of REM sleep deprivation increases caloric intake, but retards body weight gain. Moreover, this procedure increases the expression of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), which may be involved with the molecular mechanism proposed to mediate insulin resistance. The goal of the present study was to assess the effects of a chronic protocol of sleep restriction on parameters of energy balance (food intake and body weight), leptin plasma levels and its hypothalamic receptors and mediators of the immune system in the retroperitoneal adipose tissue (RPAT). Thirty-four Wistar rats were distributed in control (CTL) and sleep restriction groups; the latter was kept onto individual narrow platforms immersed in water for 18h/day (from 16:00h to 10:00h), for 21days (SR21). Food intake was assessed daily, after each sleep restriction period and body weight was measured daily, after the animals were taken from the sleep deprivation chambers. At the end of the 21day of sleep restriction, rats were decapitated and RPAT was obtained for morphological and immune functional assays and expression of insulin receptor substrate 1 (IRS-1) was assessed in skeletal muscle. Another subset of animals was used to evaluate blood glucose clearance. The results replicated previous findings on energy balance, e.g., increased food intake and reduced body weight gain. There was a significant reduction of RPAT mass (pmetabolic syndrome-related alterations that may be mediated by inflammation of the RPAT. Copyright © 2014 Elsevier Inc. All rights reserved.

Restless Legs Syndrome and Depression: Effect Mediation by Disturbed Sleep and Periodic Limb Movements.

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Koo, Brian B; Blackwell, Terri; Lee, Hochang B; Stone, Katie L; Louis, Elan D; Redline, Susan

2016-11-01

To investigate an association between restless legs syndrome (RLS) and depression and to what extent sleep disturbance, periodic limb movements during sleep (PLMS), and antidepressant medication mediate this relationship. A cross-sectional analysis was conducted of the Osteoporotic Fractures in Older Men Study data in 982 men assessed for RLS (International RLS Study Group scale [IRLSS]) and depression (Geriatric Depression Scale [GDS]), who underwent actigraphy (for sleep latency/efficiency) and polysomnography (for PLMS). Men were split into three groups: no RLS (N = 815), mild RLS (IRLSS ≤ 12, N = 85), moderate-to-severe RLS (IRLSS > 12, N = 82). Depression was defined as GDS score ≥ 6. Logistic and linear regression assessed associations of RLS and depression or number depressive symptoms, respectively. Models were adjusted for age, site, race, education, body mass index, personal habits, benzodiazepine/dopaminergic medication, physical activity, cardiovascular risk factors, and apnea-hypopnea index. Of 982 men, 167 (17.0%) had RLS. Depression was significantly associated with moderate-to-severe RLS after adjustment (versus no RLS: OR [95% CI] 2.85 [1.23, 6.64]). Further adjustment for potential mediators attenuated effect size modestly, most for sleep efficiency (OR: 2.85-2.55). Compared with no RLS, moderate-to-severe RLS was associated with the number of depressive symptoms after adjustment (adjusted means [95% CI]; no RLS: 1.14 [1.05, 1.24] versus IRLSS > 12: 1.69 [1.32, 2.11]). Further adjustment for potential mediators did not alter effect size. For men with PLMS index at least median, number of depressive symptoms significantly increased as RLS category became more severe. Depression is more common as RLS severity worsens. The RLS-depression relationship is modestly explained by sleep disturbance and PLMS. Published by Elsevier Inc.

Celiac Plexus Block as a Predictor of Surgical Outcome for Sympathetically Mediated Abdominal Pain in a Case of Suspected Median Arcuate Ligament Syndrome: A Case Report.

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Sun, Zhuo; Fritz, David A; Turner, Suzanne; Hardy, David M; Meiler, Steffen E; Martin, Dan C; Dua, Anterpreet

2018-02-14

Median arcuate ligament syndrome (MALS), also known as celiac artery compression syndrome, is an uncommon condition classically characterized by chronic abdominal pain, weight loss, and abdominal bruit. Chronic mesenteric ischemia caused by intermittent compression of the celiac artery by the MAL provokes upper abdominal pain that is sympathetically mediated via the celiac plexus. Because it is a diagnosis of exclusion, diagnosis of MALS in the clinical setting is typically challenging. We present an atypical case which highlights the utility of celiac plexus block as both an assistant diagnostic tool and a predictor of surgical outcomes for suspected MALS.

Use of Hemadsorption in a Case of Pediatric Toxic Shock Syndrome

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Andrea Berkes

2017-01-01

Full Text Available Background. Toxic shock syndrome is a potentially fatal toxin-mediated disease. The role of toxins in this clinical entity made us hypothesize that extracorporeal blood purification with CytoSorb® could play a beneficial role in the clinical management of toxic shock syndrome. This case report describes the successful treatment of toxic shock syndrome using a combination of renal replacement therapy and hemadsorption in a pediatric patient. Case Presentation. A 5-year-old girl with Down’s syndrome presented with an inflamed area surrounding an insect bite, signs of systemic inflammation, and multiple organ failure. As previous attempts of immune modulation therapy were unsuccessful, renal replacement therapy was supplemented by the cytokine absorber CytoSorb. Treatment using this combination was associated with a rapid and significant stabilization in the hemodynamic situation and a decrease in inflammatory mediators within hours after the initiation of therapy. The application of CytoSorb therapy was simple and safe. Conclusion. The use of extracorporeal blood purification with CytoSorb proved potentially beneficial by removing toxins and inflammatory mediators in this case and could therefore play a role in the clinical management of toxic shock syndrome. Whether CytoSorb has the potential to even positively influence mortality in patients with toxic shock syndrome still needs to be confirmed.

SKIV2L Mutations Cause Syndromic Diarrhea, or Trichohepatoenteric Syndrome

Science.gov (United States)

Fabre, Alexandre; Charroux, Bernard; Martinez-Vinson, Christine; Roquelaure, Bertrand; Odul, Egritas; Sayar, Ersin; Smith, Hilary; Colomb, Virginie; Andre, Nicolas; Hugot, Jean-Pierre; Goulet, Olivier; Lacoste, Caroline; Sarles, Jacques; Royet, Julien; Levy, Nicolas; Badens, Catherine

2012-01-01

Syndromic diarrhea (or trichohepatoenteric syndrome) is a rare congenital bowel disorder characterized by intractable diarrhea and woolly hair, and it has recently been associated with mutations in TTC37. Although databases report TTC37 as being the human ortholog of Ski3p, one of the yeast Ski-complex cofactors, this lead was not investigated in initial studies. The Ski complex is a multiprotein complex required for exosome-mediated RNA surveillance, including the regulation of normal mRNA and the decay of nonfunctional mRNA. Considering the fact that TTC37 is homologous to Ski3p, we explored a gene encoding another Ski-complex cofactor, SKIV2L, in six individuals presenting with typical syndromic diarrhea without variation in TTC37. We identified mutations in all six individuals. Our results show that mutations in genes encoding cofactors of the human Ski complex cause syndromic diarrhea, establishing a link between defects of the human exosome complex and a Mendelian disease. PMID:22444670

A case of possible Kounis syndrome as a complication of scombroid syndrome

Directory of Open Access Journals (Sweden)

Stefano Rusconi

2017-11-01

Full Text Available Kounis syndrome is defined as the concurrence of acute coronary syndromes such as coronary spasm or acute myocardial infarction with conditions associated with activation of inflammatory mediators such histamine, arachidonic acid and various cytokines and chemokines. Recently, a variety of unusual etiologies have been reported, including scombroid syndrome. We present a case of a woman without previous history of cardiac diseases or cardiovascular risk factors, who presented to emergency department after the onset of flushing, asthenia, palpitations, burning sensation in the mouth having just eaten tuna. The electrocardiogram revealed a sinus tachycardia with diffuse ST segment depression. After therapy, in a short time symptoms recovered and a second electrocardiogram no longer showed any ST changes. These electrocardiographic changes observed in our case were probably due to transitory coronary vasospasm as described in type I variant of Kounis syndrome.

Cell-mediated immune response of synovial fluid lymphocytes to ureaplasma antigen in Reiter's syndrome

Directory of Open Access Journals (Sweden)

Pavlica Ljiljana

2003-01-01

Full Text Available INTRODUCTION Reiter's syndrome (RS is an seronegative arthritis that occurs after urogenital or enteric infection which in addition with occular and/or mucocutaneous manifestations presents complete form of disease. According to previous understanding arthritis in the RS is the reactive one, which means that it is impossible to isolate its causative agent. However, there are the more and more authors suggesting that arthritis in the urogenital form of disease is caused by the infective agent in the affected joint. This suggestion is based on numerous studies on the presence of Chlmaydia trachomatis and Ureaplasma urealyticum in the inflamed joint by using new diagnostic methods in molecular biology published in the recent literature [1-3]. Besides, numerous studies of the humoral and cell-mediated immune response to "triggering" bacteria in the affected joint have supported previous suggestions [4-7]. Aim of the study was to determine whether synovial fluid T-cells specifically recognize the "triggering" bacteria presumably responsible for the Reiter's syndrome. METHOD The 3H-thymidine uptake procedure for measuring lymphocyte responses was applied to lymphocytes derived concurrently from synovial fluid (SF and from peripheral blood (PB [8]. Ureaplasma antigen and mitogen PHA stimulated lymphocytes in 24 RS patients (24 PB samples, 9 SF samples and the results were compared with those found in 10 patients with rheumatoid arthritis (RA (10 PB samples, 5 SF samples. Preparation of ureaplasma antigen. Ureaplasma was cultured on cell-free liquid medium [9]. Sample of 8 ml was heat-inactivated for 15 minutes at 601C and permanently stirred with magnetic mixer. The sample was centrifuged at 2000 x g for 40 minutes and than deposits carefully carried to other sterile glass tubes (Corex and recentrifuged at 9000 x g for 30 minutes. The deposit was washed 3 times in sterile 0.9% NaCl, and final sediment was resuspended in 1.2 ml sterile 0.9% Na

Reconstructing a sediment pulse: Modeling the effect of placer mining on Fraser River, Canada

Science.gov (United States)

Ferguson, R. I.; Church, M.; Rennie, C. D.; Venditti, J. G.

2015-07-01

Gold mining along 525 km of the Fraser River between 1858 and 1909 added an estimated 1.1 × 108 t of tailings, half gravel and the rest finer, to the river's natural sediment load. We simulate the response using a 1-D multigrain size morphodynamic model. Since premining conditions are unknown and modern data are insufficient for tuning the process representation, we devised a novel modeling strategy which may be useful in other data-poor applications. We start the model from a smoothed version of the modern longitudinal profile with bed grain size distributions optimized to match alternative assumptions about natural sediment supply and compare runs that include mining with control runs that can be used to quantify the effects of deficiencies in process representation and initialization. Simulations with an appropriate choice of natural supply rate closely match the best available test data, which consist of a detailed 1952-1999 gravel budget for the distal part of the model domain. The simulations suggest that the main response to mining was rapid bed fining, which allowed a major increase in bed load transport rate with only slight (~0.1 m) mean aggradation within the mining region and most of the excess sediment exported well beyond the mountain front within the mining period or soon afterward. We compare this pattern of response by a large, powerful river with previous case studies of river adjustment to sediment supply change.

Wolfram syndrome 1 and Wolfram syndrome 2.

Science.gov (United States)

Rigoli, Luciana; Di Bella, Chiara

2012-08-01

Wolfram syndrome 1 (WS1) is an autosomal recessive disorder characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (DI DM OA D syndrome) associated with other variable clinical manifestations. The causative gene for WS1 (WFS1) encoding wolframin maps to chromosome 4p16.1. Wolframin has an important function in maintaining the homeostasis of the endoplasmic reticulum (ER) in pancreatic β cells. Recently, another causative gene, CISD2, has been identified in patients with a type of Wolfram syndrome (WS2) resulting in early optic atrophy, diabetes mellitus, deafness, decreased lifespan, but not diabetes insipidus. The CISD2-encoded protein ERIS (endoplasmic reticulum intermembrane small protein) also localizes to ER, but does not interact directly with wolframin. ERIS maps to chromosome 4q22. Numerous studies have shown an interesting similarity between WFS1 and CISD2 genes. Experimental studies demonstrated that the Cisd2 knockout (Cisd2) mouse shows premature aging and typical symptoms of Wolfram syndrome. These researches provide interesting insight into the relation of neurodegenerative diseases, mitochondrial disorders, and autophagy and are useful for the pathophysiological understanding of both Wolfram syndrome and mitochondrial-mediated premature aging. The knowledge of WS1 and WS2 pathogenesis, and of the interactions between WFS1 and CISD2 genes, is useful for accurate diagnostic classification and for diagnosis of presymptomatic individuals.

Two case reports of anophthalmia and congenital heart disease: Adding a new dimension to this association.

Science.gov (United States)

Wang, Jenny; Steelman, Charlotte K; Vincent, Robert; Richburg, Delene; Chang, Tiffany S; Shehata, Bahig M

2010-01-01

Anophthalmia is the congenital absence of ocular tissue from the orbit. Many syndromes and malformations (e.g., anophthalmia-esophageal-genital syndrome, Matthew-Wood syndrome, CHARGE syndrome, oculo-facial-cardio-dental-syndome, heterotaxy, and Fraser syndrome) have been associated with anophthalmia. However, its relation with congenital heart disease has not been fully elucidated. In this article, we discuss two cases of patients with anophthalmia and congenital heart defects, and we compare these findings with other syndromes with which anophthalmia has been associated. One of our two patients showed complex congenital heart disease with heterotaxia, polysplenia, and normal lung lobation. These findings may reflect a new dimension of anophthalmia, heterotaxia, and congenital heart disease associations.

Prevention of infectious diseases in patients with Good syndrome.

Science.gov (United States)

Multani, Ashrit; Gomez, Carlos A; Montoya, José G

2018-08-01

Good syndrome is a profoundly immunocompromising condition with heterogeneous immune deficits characterized by the presence of thymoma, low-to-absent B-lymphocyte counts, hypogammaglobulinemia, and impaired cell-mediated immunity. Opportunistic infectious diseases associated with Good syndrome represent a diagnostic and therapeutic challenge, given their protean clinical manifestations. Although these infectious complications have been reviewed in prior publications, recommendations regarding their prevention have been lacking. Good syndrome usually occurs in adult patients between the ages of 40 and 70 years. Immunologically, it is characterized by low or absent peripheral blood B lymphocytes, hypogammaglobulinemia, and variable defects in cell-mediated immunity including low CD4 T counts, inverted CD4:CD8 T-lymphocyte ratio, and reduced T-lymphocyte mitogen proliferative responses. Patients with Good syndrome are susceptible to a variety of infectious diseases, of which the most common are recurrent bacterial sinopulmonary infections, mucocutaneous candidiasis, and CMV tissue-invasive disease. Preventive guidelines including targeted antimicrobial prophylaxis and vaccination strategies can mitigate infectious complications in patients with Good syndrome. Immunological deficits and infectious complications in Good syndrome have been described for over 60 years. Further research is needed to elucidate its exact pathogenesis and define the mechanistic relationship between thymoma and hypogammaglobulinemia. However, tailored prophylactic strategies can be recommended for patients with Good syndrome.

Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome.

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Kuo, Lydia E; Kitlinska, Joanna B; Tilan, Jason U; Li, Lijun; Baker, Stephen B; Johnson, Michael D; Lee, Edward W; Burnett, Mary Susan; Fricke, Stanley T; Kvetnansky, Richard; Herzog, Herbert; Zukowska, Zofia

2007-07-01

The relationship between stress and obesity remains elusive. In response to stress, some people lose weight, whereas others gain. Here we report that stress exaggerates diet-induced obesity through a peripheral mechanism in the abdominal white adipose tissue that is mediated by neuropeptide Y (NPY). Stressors such as exposure to cold or aggression lead to the release of NPY from sympathetic nerves, which in turn upregulates NPY and its Y2 receptors (NPY2R) in a glucocorticoid-dependent manner in the abdominal fat. This positive feedback response by NPY leads to the growth of abdominal fat. Release of NPY and activation of NPY2R stimulates fat angiogenesis, macrophage infiltration, and the proliferation and differentiation of new adipocytes, resulting in abdominal obesity and a metabolic syndrome-like condition. NPY, like stress, stimulates mouse and human fat growth, whereas pharmacological inhibition or fat-targeted knockdown of NPY2R is anti-angiogenic and anti-adipogenic, while reducing abdominal obesity and metabolic abnormalities. Thus, manipulations of NPY2R activity within fat tissue offer new ways to remodel fat and treat obesity and metabolic syndrome.

Abnormalities of Gq-mediated cell signaling in Bartter and Gitelman syndromes.

NARCIS (Netherlands)

Calo, L.; Ceolotto, G.; Milani, M.; Pagnin, E.; Heuvel, L.P.W.J. van den; Sartori, M.; Davis, A.P.; Costa, R.; Semplicini, A.

2001-01-01

BACKGROUND: The constitutive endothelial isoform of nitric oxide synthase (ecNOS) and nitric oxide (NO) production are increased in patients with Bartter syndrome (BS) and Gitelman (GS) syndrome and may reduce vascular tone. Moreover, these patients present an abnormal cell signaling [reduced

Psychosocial job conditions, fear avoidance beliefs and expected return to work following acute coronary syndrome: a cross-sectional study of fear-avoidance as a potential mediator.

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Söderberg, Mia; Rosengren, Annika; Gustavsson, Sara; Schiöler, Linus; Härenstam, Annika; Torén, Kjell

2015-12-21

Despite improvements in treatment, acute coronary syndrome remains a substantial cause for prolonged sick absences and premature retirement. Knowledge regarding what benefits return to work is limited, especially the effect of psychological processes and psychosocial work factors. The purposes of this cross-sectional study were two-fold: to examine associations between adverse psychosocial job conditions and fear-avoidance beliefs towards work, and to determine whether such beliefs mediated the relationship between work conditions and expected return to work in acute coronary syndrome survivors. Study inclusion criteria: acute myocardial infarction or unstable angina diagnosis, below 65 years of age, being a resident in the West county of Sweden and currently working. In all, 509 individuals (21.8 % women) accepted study participation and for whom all data of study interest were available for analysis. Psychosocial work variables; job demand-control and effort-reward imbalance, were assessed with standard questionnaire batteries. Linear regression models were used to investigate relationships between psychosocial factors and fear-avoidance, and to evaluate mediator effects for fear-avoidance. Both total sample and gender stratified analyses were calculated. Fear-avoidance beliefs about work were associated to psychosocial job environments characterized by high strain (β 1.4; CI 1.2-1.6), active and passive work and high effort-reward imbalance (β 0.6; CI 0.5-0.7). Further, such beliefs also mediated the relationship between adverse work conditions and expected time for return to work. However, these results were only observed in total sample analyses or among or male participants. For women only high strain was linked to fear-avoidance, and these relationships became non-significant when entering chosen confounders. This cross-sectional study showed that acute coronary syndrome survivors, who laboured under adverse psychosocial work conditions, held fear

Estrogen-mediated Height Control in Girls with Marfan Syndrome.

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Lee, Dong-Yun; Hyun, Hye Sun; Huh, Rimm; Jin, Dong-Kyu; Kim, Duk-Kyung; Yoon, Byung-Koo; Choi, DooSeok

2016-02-01

This study evaluated the efficacy of a stepwise regimen of estradiol valerate for height control in girls with Marfan syndrome. Eight girls with Marfan syndrome who had completed estrogen treatment for height control were included. Estradiol valerate was started at a dose of 2 mg/day, and then was increased. The projected final height was estimated using the initial height percentile (on a disease-specific growth curve for Korean Marfan syndrome [gcPFHt]), and the initial bone age (baPFHt). After the estrogen treatment, the projected final height was compared to the actual final height (FHt). The median baseline chronological and bone age were 10.0 and 10.5 years, respectively. After a median of 36.5 months of treatment, the median FHt (172.6 cm) was shorter than the median gcPFHt (181.0 cm) and baPFHt (175.9 cm). In the six patients who started treatment before the age of 11 years, the median FHt (171.8 cm) was shorter than the median gcPFHt (181.5 cm) and baPFHt (177.4 cm) after treatment. The median differences between the FHt and gcPFHt and baPFHt were 9.2 and 8.3 cm, respectively. In two patients started treatment after the age of 11, the differences between FHt and gcPFHt, and baPFHt after treatment were -4 and 1.4 cm, and -1.2 and 0 cm for each case, respectively. A stepwise increasing regimen of estradiol valerate may be an effective treatment for height control in girls with Marfan syndrome, especially when started under 11 years old.

POSTPARTUM BONDING DIFFICULTIES AND ADULT ATTACHMENT STYLES: THE MEDIATING ROLE OF POSTPARTUM DEPRESSION AND CHILDBIRTH-RELATED PTSD.

Science.gov (United States)

S Hairston, Ilana; E Handelzalts, Jonathan; Assis, Chen; Kovo, Michal

2018-03-01

Despite decades of research demonstrating the role of adult attachment styles and early mother-infant bonding in parenting behaviors and maternal mental health, these constructs have seldom been studied together. The present study aimed to investigate the relationship between attachment styles and specific bonding difficulties of mothers. In addition, as postpartum depression and childbirth-related posttraumatic stress symptoms have been associated with both constructs, we explored their possible mediation effect. One hundred fourteen mothers, 4 to 12 weeks' postpartum, completed a demographic questionnaire, the Adult Attachment Style Questionnaire (M. Mikulincer, V. Florian, & A. Tolmacz, 1990), the Postpartum Bonding Questionnaire (L.F. Brockington, C. Fraser, & D. Wilson, 2006), the Modified Perinatal Posttraumatic Stress Disorder Questionnaire (J.L. Callahan, S.E. Borja, & M.T. Hynan, 2006), and the Edinburgh Postnatal Depression Scale (J.L. Cox, G. Chapman, D. Murray, & P. Jones, 1996), using an online survey system. As predicted, insecure attachment styles were associated with bonding difficulties wherein anxious/ambivalent attachment was associated with greater infant-focused anxiety, mediated by postpartum depression but not childbirth-related PTSD symptoms. In contrast, greater avoidant attachment style was associated with greater rejection and anger, mediated by childbirth-related posttraumatic stress disorder (PTSD), but not depression symptoms. The current study confirmed the association of different attachment styles with bonding as well as the mediating roles of childbirth-related PTSD and postpartum depression symptoms. Future psychological interventions may utilize such evidence to target interventions for bonding disorders in accordance with individual differences. © 2018 Michigan Association for Infant Mental Health.

MODERNISATION ISSUES OF GENDER AND SPACE

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Titien Saraswati

2000-01-01

Full Text Available Jurgen Habermas proposes a theory of modernisation based on the notion of a progressive "uncoupling" or separation of some aspects of everyday life, and their take over or "colonisation" by an expanding state and formal economy. This model is criticised by Nancy Fraser on the basis that it ignores the place of gender in the various roles that the individual plays in society and which mediate between the world of everyday life and the "system world" of the state and the official economy. Habermas's argument is further criticised for ignoring the issue of space (the house, the neighbourhood in that mediation. Further, Habermas and also Fraser arguments however yield to what they call symbolic reproduction and material reproduction, socially integrated action contexts and system integrated action contexts, and also private sphere and public sphere. The above terms will be elaborated more fully in this paper.

Severe antiphospholipid syndrome and cardiac surgery: Perioperative management.

Science.gov (United States)

Mishra, Pankaj Kumar; Khazi, Fayaz Mohammed; Yiu, Patrick; Billing, John Stephen

2016-06-01

Antiphospholipid syndrome is an antiphospholipid antibody-mediated prothrombotic state leading to arterial and venous thrombosis. This condition alters routine in-vitro coagulation tests, making results unreliable. Antiphospholipid syndrome patients requiring cardiac surgery with cardiopulmonary bypass present a unique challenge in perioperative anticoagulation management. We describe 3 patients with antiphospholipid syndrome who had successful heart valve surgery at our institution. We have devised an institutional protocol for antiphospholipid syndrome patients, and all 3 patients were managed according to this protocol. An algorithm-based approach is recommended because it improves team work, optimizes treatment, and improves patient outcome. © The Author(s) 2015.

Debates feministas sobre direito, justiça e reconhecimento: uma reflexão a partir do modelo teórico de Nancy Fraser

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Silvana Mariano

2009-12-01

Full Text Available O feminismo pós-estruturalista é a escolha teórica que, em grande parte, orienta aqui nossa perspectiva. Os debates em torno das noções de “direito”, “justiça” e “reconhecimento” ilustram essa discussão. Propomo-nos a fazer uma reflexão sociológica conceitual, de orientação feminista, de forma a constituir um suporte teórico para análises sobre políticas sociais, com o objetivo de investigar as condições de cidadania das mulheres pobres e apreender os determinantes de gênero presentes nos programas estatais. Ao tratar das categorias apontadas, adotamos o modelo proposto por Nancy Fraser, a qual combina a luta pela justiça redistributiva com a luta por justiça de reconhecimento.

The skin function: a factor of anti-metabolic syndrome

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Zhou Shi-Sheng

2012-04-01

Full Text Available Abstract The body’s total antioxidant capacity represents a sum of the antioxidant capacity of various tissues/organs. A decrease in the body’s antioxidant capacity may induce oxidative stress and subsequent metabolic syndrome, a clustering of risk factors for type 2 diabetes and cardiovascular disease. The skin, the largest organ of the body, is one of the major components of the body’s total antioxidant defense system, primarily through its xenobiotic/drug biotransformation system, reactive oxygen species-scavenging system, and sweat glands- and sebaceous glands-mediated excretion system. Notably, unlike other contributors, the skin contribution is variable, depending on lifestyles and ambient temperature or seasonal variations. Emerging evidence suggests that decreased skin’s antioxidant and excretory functions (e.g., due to sedentary lifestyles and low ambient temperature may increase the risk for metabolic syndrome. This review focuses on the relationship between the variability of skin-mediated detoxification and elimination of exogenous and endogenous toxic substances and the development of metabolic syndrome. The potential role of sebum secretion in lipid and cholesterol homeostasis and its impact on metabolic syndrome, and the association between skin disorders (acanthosis nigricans, acne, and burn and metabolic syndrome are also discussed.

Fraser syndrome: Phenotypic variability and unusual findings in four ...

African Journals Online (AJOL)

Ebtesam M. Abdalla

2015-11-25

Nov 25, 2015 ... a Department of Human Genetics, Medical Research Institute, Alexandria University, Egypt .... centin1 (HMCN1), Furin, and Fibulin 1, that interact in base- ... The first child of this couple [case 2-1], who was born at term and ...

Effect on Insulin-Stimulated Release of D-Chiro-Inositol-Containing Inositolphosphoglycan Mediator during Weight Loss in Obese Women with and without Polycystic Ovary Syndrome

OpenAIRE

Cheang, Kai I.; Sistrun, Sakita N.; Morel, Kelley S.; Nestler, John E.

2016-01-01

Background. A deficiency of D-chiro-inositol-inositolphosphoglycan mediator (DCI-IPG) may contribute to insulin resistance in polycystic ovary syndrome (PCOS). Whether the relationship between impaired DCI-IPG release and insulin resistance is specific to PCOS rather than obesity is unknown. We assessed insulin-released DCI-IPG and its relationship to insulin sensitivity at baseline and after weight loss in obese women with and without PCOS. Methods. Obese PCOS (n = 16) and normal (n = 15) wo...

Marine vessel air emissions in the Lower Fraser Valley for the year 2000

International Nuclear Information System (INIS)

Quan, R.G.; Cheng, K.C.; Trask, T.C.; Meilleur, R.A.

2002-01-01

Emissions inventories are used by government agencies as a tool for policy development and air quality management. Marine vessels have been identified as a major source of anthropogenic pollution in British Columbia. This report presents estimates of emissions from marine vessels in coastal areas of British Columbia's Fraser Valley Regional District (FVRD) for the year 2000. The project includes an update of emission estimates for each marine vessel category and an update of emission estimates for pollutants of interest, including carbon monoxide (CO), nitrogen oxides (NOx), particulate matter (PM), sulphur oxides (SOx), volatile organic compounds (VOCs), as well as inhalable fine particulates (PM10 and PM2.5) and greenhouse gases such as carbon dioxide, methane, nitrous oxide and ammonia. This report presents both spatial and temporal allocation of emissions. Results indicate that ocean-going vessels are the major contributor to emissions of NOx, SOx, PM and greenhouse gases, accounting for 58, 95, 82, and 58 per cent of the total marine vessel emissions respectively. They also contribute 14 per cent to the marine totals for CO and VOCs. Harbour vessels contribute 28 and 27 per cent of NOx and greenhouse gases and 10 per cent or less to all other contaminant totals. Ferries contribute between 2 per cent and 13 per cent for to each contaminant, including 13 per cent of NOx, 12 per cent of greenhouse gases, and 6 per cent of CO. Fishing vessels contribute 1 per cent or less of all contaminants. Although recreational vessels are major contributors for CO and VOC, they contribute less than 10 per cent for all other contaminants. A comparison of 1993 and 2000 marine vessel inventory for British Columbia was presented and recommendations for improvements were presented. refs., tabs., figs

Redefining the MED13L syndrome.

Science.gov (United States)

Adegbola, Abidemi; Musante, Luciana; Callewaert, Bert; Maciel, Patricia; Hu, Hao; Isidor, Bertrand; Picker-Minh, Sylvie; Le Caignec, Cedric; Delle Chiaie, Barbara; Vanakker, Olivier; Menten, Björn; Dheedene, Annelies; Bockaert, Nele; Roelens, Filip; Decaestecker, Karin; Silva, João; Soares, Gabriela; Lopes, Fátima; Najmabadi, Hossein; Kahrizi, Kimia; Cox, Gerald F; Angus, Steven P; Staropoli, John F; Fischer, Ute; Suckow, Vanessa; Bartsch, Oliver; Chess, Andrew; Ropers, Hans-Hilger; Wienker, Thomas F; Hübner, Christoph; Kaindl, Angela M; Kalscheuer, Vera M

2015-10-01

Congenital cardiac and neurodevelopmental deficits have been recently linked to the mediator complex subunit 13-like protein MED13L, a subunit of the CDK8-associated mediator complex that functions in transcriptional regulation through DNA-binding transcription factors and RNA polymerase II. Heterozygous MED13L variants cause transposition of the great arteries and intellectual disability (ID). Here, we report eight patients with predominantly novel MED13L variants who lack such complex congenital heart malformations. Rather, they depict a syndromic form of ID characterized by facial dysmorphism, ID, speech impairment, motor developmental delay with muscular hypotonia and behavioral difficulties. We thereby define a novel syndrome and significantly broaden the clinical spectrum associated with MED13L variants. A prominent feature of the MED13L neurocognitive presentation is profound language impairment, often in combination with articulatory deficits.

Redefining the MED13L syndrome

Science.gov (United States)

Adegbola, Abidemi; Musante, Luciana; Callewaert, Bert; Maciel, Patricia; Hu, Hao; Isidor, Bertrand; Picker-Minh, Sylvie; Le Caignec, Cedric; Delle Chiaie, Barbara; Vanakker, Olivier; Menten, Björn; Dheedene, Annelies; Bockaert, Nele; Roelens, Filip; Decaestecker, Karin; Silva, João; Soares, Gabriela; Lopes, Fátima; Najmabadi, Hossein; Kahrizi, Kimia; Cox, Gerald F; Angus, Steven P; Staropoli, John F; Fischer, Ute; Suckow, Vanessa; Bartsch, Oliver; Chess, Andrew; Ropers, Hans-Hilger; Wienker, Thomas F; Hübner, Christoph; Kaindl, Angela M; Kalscheuer, Vera M

2015-01-01

Congenital cardiac and neurodevelopmental deficits have been recently linked to the mediator complex subunit 13-like protein MED13L, a subunit of the CDK8-associated mediator complex that functions in transcriptional regulation through DNA-binding transcription factors and RNA polymerase II. Heterozygous MED13L variants cause transposition of the great arteries and intellectual disability (ID). Here, we report eight patients with predominantly novel MED13L variants who lack such complex congenital heart malformations. Rather, they depict a syndromic form of ID characterized by facial dysmorphism, ID, speech impairment, motor developmental delay with muscular hypotonia and behavioral difficulties. We thereby define a novel syndrome and significantly broaden the clinical spectrum associated with MED13L variants. A prominent feature of the MED13L neurocognitive presentation is profound language impairment, often in combination with articulatory deficits. PMID:25758992

Gene repair of an Usher syndrome causing mutation by zinc-finger nuclease mediated homologous recombination.

Science.gov (United States)

Overlack, Nora; Goldmann, Tobias; Wolfrum, Uwe; Nagel-Wolfrum, Kerstin

2012-06-26

Human Usher syndrome (USH) is the most frequent cause of inherited deaf-blindness. It is clinically and genetically heterogeneous, assigned to three clinical types of which the most severe type is USH1. No effective treatment for the ophthalmic component of USH exists. Gene augmentation is an attractive strategy for hereditary retinal diseases. However, several USH genes, like USH1C, are expressed in various isoforms, hampering gene augmentation. As an alternative treatment strategy, we applied the zinc-finger nuclease (ZFN) technology for targeted gene repair of an USH1C, causing mutation by homologous recombination. We designed ZFNs customized for the p.R31X nonsense mutation in Ush1c. We evaluated ZFNs for DNA cleavage capability and analyzed ZFNs biocompatibilities by XTT assays. We demonstrated ZFNs mediated gene repair on genomic level by digestion assays and DNA sequencing, and on protein level by indirect immunofluorescence and Western blot analyses. The specifically designed ZFNs did not show cytotoxic effects in a p.R31X cell line. We demonstrated that ZFN induced cleavage of their target sequence. We showed that simultaneous application of ZFN and rescue DNA induced gene repair of the disease-causing mutation on the genomic level, resulting in recovery of protein expression. In our present study, we analyzed for the first time ZFN-activated gene repair of an USH gene. The data highlight the ability of ZFNs to induce targeted homologous recombination and mediate gene repair in USH. We provide further evidence that the ZFN technology holds great potential to recover disease-causing mutations in inherited retinal disorders.

Churg-strauss syndrome

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Subhasish Ghosh

2011-01-01

Full Text Available Churg-Strauss syndrome (CSS is a rare granulomatous necrotizing small vessel vasculitis characterized by the presence of asthma, sinusitis, and hypereosinophilia. The cause of this allergic angiitis and granulomatosis is unknown. Other common manifestations are pulmonary infiltrates, skin, gastrointestinal, and cardiovascular involvement. No data have been reported regarding the role of immune complexes or cell mediated mechanisms in this disease, although autoimmunity is evident with the presence hypergammaglobulinemia, increased levels of IgE and Antineutrophil cytoplasmic antibody (positive in 40%. We report the case of a 27-year-old lady presenting with painful swelling of predominantly lower limbs with extensive vesicles and ecchymotic patches and fever shortly after stopping systemic steroids taken for a prolonged duration (2002--2010. The aim of this case report is to point to the possibility of CSS in patients presenting with extensive skin lesions masquerading as Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Syndrome (SJS/TENS.

Paraneoplastic syndromes and autoimmune encephalitis

Science.gov (United States)

Rosenfeld, Myrna R.; Titulaer, Maarten J.

2012-01-01

Summary We review novel findings in paraneoplastic syndromes including the Lambert-Eaton myasthenic syndrome, and then focus on the novel disorders associated with antibodies against cell surface antigens, discussing the importance and caveats of antibody testing, and providing an algorithm for interpretation of results. In anti-NMDAR encephalitis 2 novel findings include the recognition of a characteristic EEG pattern (“extreme delta brush”) in 30% of patients and the demonstration of a fronto-temporo-occipital gradient of glucose metabolism that correlates with disease activity. In limbic encephalitis, antibodies to GABA(B) receptor are the most frequently detected in patients with small-cell lung cancer who are anti-Hu negative, and antibodies to mGluR5 distinctively associate with Hodgkin lymphoma (Ophelia syndrome). We also address the syndromes associated with “VGKC-complex antibodies,” a problematic term that groups well-characterized immune-mediated disorders (LGI1, Caspr2) with others that lack syndrome specificity, are less responsive to treatment, and for which the target antigens are unknown. PMID:23634368

Canada's Fraser River Basin transitioning from a nival to a hybrid system in the late 20th century

Science.gov (United States)

Kang, D. H.; Gao, H.; Shi, X.; Dery, S. J.

2014-12-01

The Fraser River Basin (FRB) is the largest river draining to the Pacific Ocean in British Columbia (BC), Canada, and it provides the world's most abundant salmon populations. With recent climate change, the shifting hydrologic regime of the FRB is evaluated using hydrological modeling results over the period 1949 to 2006. To quantify the contribution of snowmelt to runoff generation, the ratio RSR, defined as the division of the sum of the snowmelt across the watershed by the integrated runoff over the water year, is employed. Modeled results for RSR at Hope, BC — the furthest downstream hydrometric station of the FRB — show a significant decrease (from 0.80 to 0.65) in the latter part of the 20th century. RSR is found to be mainly suppressed by a decrease of the snowmelt across the FRB with a decline with 107 mm by 26 % along the simulation period. There is also a prominent shift in the timing of streamflow, with the spring freshet at Hope, BC advancing 30 days followed by reduced summer flows for over two months. The timing of the peak spring freshet becomes even earlier when moving upstream of the FRB owing to short periods of time after melting from the snow source to the rivers.

Simultaneous Combined Myositis, Inflammatory Polyneuropathy, and Overlap Myasthenic Syndrome

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Stéphane Mathis

2016-01-01

Full Text Available Immune-mediated neuromuscular disorders include pathologies of the peripheral nervous system, neuromuscular junction, and muscles. If overlap syndromes (or the association of almost two autoimmune disorders are recognized, the simultaneous occurrence of several autoimmune neuromuscular disorders is rare. We describe two patients presenting the simultaneous occurrence of inflammatory neuropathy, myositis, and myasthenia gravis (with positive acetylcholine receptor antibodies. For each patient, we carried out a pathological analysis (nerve and muscle and an electrophysiological study (and follow-up. To our knowledge, this is the first description of such a triple immune-mediated neuromuscular syndrome. We compared our observations with a few other cases of simultaneous diagnosis of two inflammatory neuromuscular disorders.

Diabetes and Neurodegeneration in Wolfram Syndrome

Science.gov (United States)

Rohayem, Julia; Ehlers, Christian; Wiedemann, Bärbel; Holl, Reinhard; Oexle, Konrad; Kordonouri, Olga; Salzano, Giuseppina; Meissner, Thomas; Burger, Walter; Schober, Edith; Huebner, Angela; Lee-Kirsch, Min Ae

2011-01-01

OBJECTIVE To describe the diabetes phenotype in Wolfram syndrome compared with type 1 diabetes, to investigate the effect of glycemic control on the neurodegenerative process, and to assess the genotype-phenotype correlation. RESEARCH DESIGN AND METHODS The clinical data of 50 patients with Wolfram syndrome-related diabetes (WSD) were reviewed and compared with the data of 24,164 patients with type 1 diabetes. Patients with a mean HbA1c during childhood and adolescence of ≤7.5 and >7.5% were compared with respect to the occurrence of additional Wolfram syndrome symptoms. The wolframin (WFS1) gene was screened for mutations in 39 patients. WFS1 genotypes were examined for correlation with age at onset of diabetes. RESULTS WSD was diagnosed earlier than type 1 diabetes (5.4 ± 3.8 vs. 7.9 ± 4.2 years; P diabetes (NS). Severe hypoglycemia occurred in 37 vs. 7.9% (P 7.5% (P = 0.031). Thirteen novel WSF1 mutations were identified. Predicted functional consequence of WFS1 mutations correlated with age at WSD onset (P = 0.028). CONCLUSIONS Endoplasmic reticulum stress–mediated decline of β-cells in WSD occurs earlier in life than autoimmune-mediated β-cell destruction in type 1 diabetes. This study establishes a role for WFS1 in determining the age at onset of diabetes in Wolfram syndrome and identifies glucose toxicity as an accelerating feature in the progression of disease. PMID:21602428

Sedimentology of Fraser River delta peat deposits: a modern analogue for some deltaic coals

Energy Technology Data Exchange (ETDEWEB)

Styan, W B; Bustin, R M

1984-01-01

On the Recent lobe of the Fraser River delta, peat accumulation has actively occurred on the distal lower delta plain, the transition between upper and lower delta plains, and the alluvial plain. Distal lower delta plain peats developed from widespread salt and brackish marshes and were not influenced appreciably by fluvial activity. Lateral development of the marsh facies were controlled by compaction and eustatic sea-level rise. The resulting thin, discontinuous peat network contains numerous silty clay partings and high concentrations of sulphur. Freshwater marsh facies formed but were later in part eroded and altered by transgressing marine waters. Peats overlie a thin, fluvial, fining-upward sequence which in turn overlies a thick, coarsening-upward, prodelta-delta front succession. Lower- upper delta plain peats initially developed from interdistributary brackish marshes and were later fluvially influenced as the delta prograded. Thickest peats occur in areas where distributary channels were abandoned earliest. Sphagnum biofacies replace sedge-grass-dominated communities except along active channel margins, where the sedge-grass facies is intercalated with overbank and splay deposits. Peats are underlain by a relatively thin sequence of fluvial deposits which in turn is underlain by a major coarsening-upward delta front and pro-delta sequence. Alluvial plain peats accumulated in back swamp environments of the flood plain. Earliest sedge-clay and gyttja peats developed over thin fining-upward fluvial cycles or are interlaminated with fine-grained flood deposits. Thickest accumulations occur where peat fills small avulsed flood channels. Overlying sedge-grass and sphagnum biofacies are horizontally stratified and commonly have sharp boundaries with fine-grained flood sediments. At active channel margins, however, sedge-grass peats are intercalated with natural levee deposits consisting of silty clay.

Regulation of PDGFC signalling and extracellular matrix composition by FREM1 in mice

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Fenny Wiradjaja

2013-11-01

Fras1-related extracellular matrix protein 1 (FREM1 is required for epidermal adhesion during embryogenesis, and mice lacking the gene develop fetal skin blisters and a range of other developmental defects. Mutations in members of the FRAS/FREM gene family cause diseases of the Fraser syndrome spectrum. Embryonic epidermal blistering is also observed in mice lacking PdgfC and its receptor, PDGFRα. In this article, we show that FREM1 binds to PDGFC and that this interaction regulates signalling downstream of PDGFRα. Fibroblasts from Frem1-mutant mice respond to PDGFC stimulation, but with a shorter duration and amplitude than do wild-type cells. Significantly, PDGFC-stimulated expression of the metalloproteinase inhibitor Timp1 is reduced in cells with Frem1 mutations, leading to reduced basement membrane collagen I deposition. These results show that the physical interaction of FREM1 with PDGFC can regulate remodelling of the extracellular matrix downstream of PDGFRα. We propose that loss of FREM1 function promotes epidermal blistering in Fraser syndrome as a consequence of reduced PDGFC activity, in addition to its stabilising role in the basement membrane.

Guillain-Barré Syndrome after Thrombolysis with Streptokinase

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Ertugrul Okuyan

2010-01-01

Full Text Available Guillain-Barre syndrome (GBS is an eponym for a heterogeneous group of immune-mediated peripheral neuropathies. We describe a case of GBS in a patient who recieved intravenous streptokinase therapy for acute anterior myocardial infarction. Clinical symptoms are thought to result from streptokinase-antibody complex mediated damage to the local blood-nerve barrier. Patient was treated with 5-days course of intravenous gammaglobulin and his outcome was good.

Malignancy in Noonan syndrome and related disorders.

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Smpokou, P; Zand, D J; Rosenbaum, K N; Summar, M L

2015-12-01

Noonan syndrome (NS) and related disorders, such as NS with multiple lentigines (formerly called LEOPARD syndrome), cardiofaciocutaneous syndrome, and Costello syndrome, constitute an important group of developmental malformation syndromes with variable clinical and molecular features. Their underlying pathophysiologic mechanism involves dysregulation of the Ras/mitogen-activated protein kinase signaling pathway, an essential mediator of developmental and growth processes in the prenatal and postnatal setting. Malignant tumor development is an important complication encountered in other RASopathies, such as neurofibromatosis type 1, but the neoplastic risks and incidence of malignant tumors are less clearly defined in NS and related disorders of the Noonan spectrum. Malignant tumor development remains an important complication variably seen in the RASopathies and, thus, a clear understanding of the underlying risks is essential for appropriate clinical care in this patient population. This review discusses previously published reports of malignancies in individuals with RASopathies of the Noonan spectrum. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Obstetric antiphospholipid syndrome.

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Esteve-Valverde, E; Ferrer-Oliveras, R; Alijotas-Reig, J

2016-04-01

Obstetric antiphospholipid syndrome is an acquired autoimmune disorder that is associated with various obstetric complications and, in the absence of prior history of thrombosis, with the presence of antiphospholipid antibodies directed against other phospholipids, proteins called cofactors or PL-cofactor complexes. Although the obstetric complications have been related to the procoagulant properties of antiphospholipid antibodies, pathological studies of human placenta have shown the proinflammatory capacity of antiphospholipid antibodies via the complement system and proinflammatory cytokines. There is no general agreement on which antiphospholipid antibodies profile (laboratory) confers the greatest obstetric risk, but the best candidates are categories I and IIa. Combined treatment with low doses of aspirin and heparin achieves good obstetric and maternal outcomes. In this study, we also review the therapeutic possibilities in refractory cases, although the likelihood of progressing to other autoimmune diseases is low. We briefly comment on incomplete obstetric antiphospholipid syndrome, also known as antiphospholipid antibody-mediated pregnancy morbidity syndrome. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Development of loop-mediated isothermal amplification method for ...

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A novel assay method to detect the highly virulent Porcine reproductive and respiratory syndrome virus (PRRSV) termed reverse transcriptase loop-mediated isothermal amplification (RT-LAMP), was reported by using hydroxynaphthol blue (HNB) as the LAMP product colorimetric judgment. By the set of special primers, ...

Quantitative sensory testing of temperature, pain, and touch in adults with Down syndrome

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de Knegt, N.C.; Defrin, R.; Schuengel, C.; Lobbezoo, F.; Evenhuis, H.M.; Scherder, E.J.A.

2015-01-01

The spinothalamic pathway mediates sensations of temperature, pain, and touch. These functions seem impaired in children with Down syndrome (DS), but have not been extensively examined in adults. The objective of the present study was to compare the spinothalamic-mediated sensory functions between

Mutations in WNT7A cause a range of limb malformations, including Fuhrmann syndrome and Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome.

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Woods, C G; Stricker, S; Seemann, P; Stern, R; Cox, J; Sherridan, E; Roberts, E; Springell, K; Scott, S; Karbani, G; Sharif, S M; Toomes, C; Bond, J; Kumar, D; Al-Gazali, L; Mundlos, S

2006-08-01

Fuhrmann syndrome and the Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome are considered to be distinct limb-malformation disorders characterized by various degrees of limb aplasia/hypoplasia and joint dysplasia in humans. In families with these syndromes, we found homozygous missense mutations in the dorsoventral-patterning gene WNT7A and confirmed their functional significance in retroviral-mediated transfection of chicken mesenchyme cell cultures and developing limbs. The results suggest that a partial loss of WNT7A function causes Fuhrmann syndrome (and a phenotype similar to mouse Wnt7a knockout), whereas the more-severe limb truncation phenotypes observed in Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome result from null mutations (and cause a phenotype similar to mouse Shh knockout). These findings illustrate the specific and conserved importance of WNT7A in multiple aspects of vertebrate limb development.

The catastrophic antiphospholipid syndrome in children.

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Go, Ellen J L; O'Neil, Kathleen M

2017-09-01

To review the difficult syndrome of catastrophic antiphospholipid syndrome, emphasizing new developments in the diagnosis, pathogenesis and treatment. Few recent publications directly address pediatric catastrophic antiphospholipid syndrome (CAPS). Most articles are case reports or are data from adult and pediatric registries. The major factors contributing to most pediatric catastrophic antiphospholipid syndrome include infection and the presence of antiphospholipid antibodies, but complement activation also is important in creating diffuse thrombosis in the microcirculation. Treatment of the acute emergency requires anticoagulation, suppression of the hyperinflammatory state and elimination of the triggering infection. Inhibition of complement activation appears to improve outcome in limited studies, and suppression of antiphospholipid antibody formation may be important in long-term management. CAPS, an antibody-mediated diffuse thrombotic disease of microvasculature, is rare in childhood but has high mortality (33-50%). It requires prompt recognition and aggressive multimodality treatment, including anticoagulation, anti-inflammatory therapy and elimination of inciting infection and pathogenic autoantibodies.

Systemic inflammatory mediators in post-traumatic complex regional pain syndrome (CRPS I) - longitudinal investigations and differences to control groups.

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Schinkel, Christian; Scherens, A; Köller, M; Roellecke, G; Muhr, G; Maier, C

2009-03-17

The Complex Regional Pain Syndrome I (CRPS I) is a disease that might affect an extremity after trauma or operation. The pathogenesis remains yet unclear. It has clinical signs of severe local inflammation as a result of an exaggerated inflammatory response but neurogenic dysregulation also contributes to it. Some studies investigated the role inflammatory mediators and cytokines; however, few longitudinal studies exist and control groups except healthy controls were not investigated yet. To get further insights into the role of systemic inflammatory mediators in CRPS I, we investigated a variety of pro-, anti-, or neuro-inflammatory mediators such as C-Reactive Protein (CRP), White Blood Cell Count (WBC), Interleukins 4, 6, 8, 10, 11, 12 (p70), Interferon gamma, Tumor-Necrosis-Factor alpha (TNF-a) and its soluble Receptors I/II, soluble Selectins (E,L,P), Substance-P (SP), and Calcitonin Gene-Related Peptide (CGRP) at different time points in venous blood from patients with acute (AC) and chronic (CC) CRPS I, patients with forearm fractures (FR), with neuralgia (NE), and from healthy volunteers (C). No significant changes for serum parameters investigated in CRPS compared to control groups were found except for CC/C (CGRP p = 0.007), FR/C (CGRP p = 0.048) and AC/CC (IL-12 p = 0.02; TNFRI/II p = 0.01; SP p = 0.049). High interindividual variations were observed. No intra- or interindividual correlation of parameters with clinical course (e.g. chronification) or outcome was detectable. Although clinically appearing as inflammation in acute stages, local rather than systemic inflammatory responses seem to be relevant in CRPS. Variable results from different studies might be explained by unpredictable intermittent release of mediators from local inflammatory processes into the blood combined with high interindividual variabilities. A clinically relevant difference to various control groups was not notable in this pilot study. Determination of systemic inflammatory

Systemic inflammatory mediators in post-traumatic Complex Regional Pain Syndrome (CRPS I - longitudinal investigations and differences to control groups

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Schinkel Ch

2009-03-01

Full Text Available Abstract Objectives The Complex Regional Pain Syndrome I (CRPS I is a disease that might affect an extremity after trauma or operation. The pathogenesis remains yet unclear. It has clinical signs of severe local inflammation as a result of an exaggerated inflammatory response but neurogenic dysregulation also contributes to it. Some studies investigated the role inflammatory mediators and cytokines; however, few longitudinal studies exist and control groups except healthy controls were not investigated yet. Methods To get further insights into the role of systemic inflammatory mediators in CRPS I, we investigated a variety of pro-, anti-, or neuro-inflammatory mediators such as C-Reactive Protein (CRP, White Blood Cell Count (WBC, Interleukins 4, 6, 8, 10, 11, 12 (p70, Interferon gamma, Tumor-Necrosis-Factor alpha (TNF-α and its soluble Receptors I/II, soluble Selectins (E, L, P, Substance-P (SP, and Calcitonin Gene-Related Peptide (CGRP at different time points in venous blood from patients with acute (AC and chronic (CC CRPS I, patients with forearm fractures (FR, with neuralgia (NE, and from healthy volunteers (C. Results No significant changes for serum parameters investigated in CRPS compared to control groups were found except for CC/C (CGRP p = 0.007, FR/C (CGRP p = 0.048 and AC/CC (IL-12 p = 0.02; TNFRI/II p = 0.01; SP p = 0.049. High interindividual variations were observed. No intra-or interindividual correlation of parameters with clinical course (e.g. chronification or outcome was detectable. Conclusion Although clinically appearing as inflammation in acute stages, local rather than systemic inflammatory responses seem to be relevant in CRPS. Variable results from different studies might be explained by unpredictable intermittent release of mediators from local inflammatory processes into the blood combined with high interindividual variabilities. A clinically relevant difference to various control groups was not notable in this

Calcineurin-inhibitor pain syndrome.

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Prommer, Eric

2012-07-01

There has been increased recognition of calcineurin, a phosphoprotein serine/threonine phosphatase enzyme, in the regulation of many physiologic systems. Calcineurin mediates activation of lymphocytes, which play a role in immune response. Widely distributed in the central nervous system, calcinuerin also plays an important role in sensory neural function, via its role in the regulation of newly discovered 2-pore potassium channels, which greatly influence neuronal resting membrane potentials. Calcinuerin inhibition is the mechanism of action of immunomodulatory drugs such as cyclosporine and tacrolimus, which are widely used in transplantation medicine to prevent rejection. While important for immunosuppression, the use of calcineurin inhibitors has been associated with the development of a new pain syndrome called the calcineurin pain syndrome, which appears to be an untoward complication of the interruption of the physiologic function of calcineurin. This is a narrative review focusing on the epidemiology, pathophysiology, characterization of a newly recognized pain syndrome associated with the use of calcineurin inhibitors. The use of immunosuppressants however is associated with several well-known toxicities to which the calcineurin pain syndrome can be added. The development of this syndrome most likely involves altered nociceptive processing due to the effect of calcineurin inhibition on neuronal firing, as well as effects of calcineurin on vascular tone. The most striking aspect of the treatment of this syndrome is the response to calcium channel blockers, which suggest that the effects of calcineurin inhibition on vascular tone play an important role in the development of the calcineurin pain syndrome. The calcineurin syndrome is a newly recognized complication associated with the use of calcineurin inhibitors. There is no standard therapy at this time but anecdotal reports suggest the effectiveness of calcium channel blockers.

Receptor Interacting Protein 3-Mediated Necroptosis Promotes Lipopolysaccharide-Induced Inflammation and Acute Respiratory Distress Syndrome in Mice.

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Linlin Wang

Full Text Available Necrosis amplifies inflammation and plays important roles in acute respiratory distress syndrome (ARDS. Necroptosis is a newly identified programmed necrosis that is mediated by receptor interacting protein 3 (RIP3. However, the potential involvement and impact of necroptosis in lipopolysaccharide (LPS-induced ARDS remains unknown. We therefore explored the role and mechanism of RIP3-mediated necroptosis in LPS-induced ARDS. Mice were instilled with increasing doses of LPS intratracheally to induce different degrees of ARDS. Lung tissues were harvested for histological and TUNEL staining and western blot for RIP3, p-RIP3, X-linked inhibitor of apoptosis protein (XIAP, mixed lineage kinase domain-like protein (MLKL, total and cleaved caspases-3/8. Then, wild-type and RIP3 knock-out mice were induced ARDS with 30 mg/kg LPS. Pulmonary cellular necrosis was labeled by the propidium Iodide (PI staining. Levels of TNF-a, Interleukin (IL-1β, IL-6, IL-1α, IL-10 and HMGB1, tissue myeloperoxidase (MPO activity, neutrophil counts and total protein concentration were measured. Results showed that in high dose LPS (30mg/kg and 40mg/kg -induced severe ARDS, RIP3 protein was increased significantly, accompanied by increases of p-RIP3 and MLKL, while in low dose LPS (10mg/kg and 20mg/kg -induced mild ARDS, apoptosis was remarkably increased. In LPS-induced severe ARDS, RIP3 knock-out alleviated the hypothermia symptom, increased survival rate and ameliorated the lung tissue injury RIP3 depletion also attenuated LPS-induced increase in IL-1α/β, IL-6 and HMGB1 release, decreased tissue MPO activity, and reduced neutrophil influx and total protein concentration in BALF in severe ARDS. Further, RIP3 depletion reduced the necrotic cells in the lung and decreased the expression of MLKL, but had no impact on cleaved caspase-3 in LPS-induced ARDS. It is concluded that RIP3-mediated necroptosis is a major mechanism of enhanced inflammation and lung tissue injury in

Re-interventions on the thoracic and thoracoabdominal aorta in patients with Marfan syndrome

OpenAIRE

Schoenhoff, Florian S.; Carrel, Thierry P.

2017-01-01

The advent of multi-gene panel genetic testing and the discovery of new syndromic and non-syndromic forms of connective tissue disorders have established thoracic aortic aneurysms as a genetically mediated disease. Surgical results in patients with Marfan syndrome (MFS) provide an important benchmark for this patient population. Prophylactic aortic root surgery prevents acute dissection and has contributed to the improved survival of MFS patients. In the majority of patients, re-interventions...

Core self-evaluation and burnout among Nurses: the mediating role of coping styles.

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Li, Xiaofei; Guan, Lili; Chang, Hui; Zhang, Bo

2014-01-01

This study aimed to determine the potential association between core self-evaluation and the burnout syndrome among Chinese nurses, and the mediating role of coping styles in this relationship. A cross-sectional survey was conducted in Shenyang, China, from May to July, 2013. A questionnaire which consisted of the Maslach Burnout Inventory-General Survey (MBI-GS), the Core Self-Evaluation Scale (CSE), and the Simplified Coping Style Questionnaire (CSQ), was completed by a total of 1,559 nurses. Hierarchical linear regression analyses and the Sobel test were performed to determine the mediating role of coping styles on the relationship between CSE and burnout. Nurses who had higher self-evaluation characteristics, reported less emotional exhaustion and cynicism, and higher professional efficacy. Coping style had a partial mediating effect on the relationship between CSE and the burnout syndrome among nurses. Core self-evaluation had effects on burnout and coping style was a mediating factor in this relationship among Chinese nurses. Therefore, the improvement of coping strategies may be helpful in the prevention of burnout among nurses, thus enhancing professional performance.

Fcγ receptor-mediated inflammation inhibits axon regeneration.

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Gang Zhang

Full Text Available Anti-glycan/ganglioside antibodies are the most common immune effectors found in patients with Guillain-Barré Syndrome, which is a peripheral autoimmune neuropathy. We previously reported that disease-relevant anti-glycan autoantibodies inhibited axon regeneration, which echo the clinical association of these antibodies and poor recovery in Guillain-Barré Syndrome. However, the specific molecular and cellular elements involved in this antibody-mediated inhibition of axon regeneration are not previously defined. This study examined the role of Fcγ receptors and macrophages in the antibody-mediated inhibition of axon regeneration. A well characterized antibody passive transfer sciatic nerve crush and transplant models were used to study the anti-ganglioside antibody-mediated inhibition of axon regeneration in wild type and various mutant and transgenic mice with altered expression of specific Fcγ receptors and macrophage/microglia populations. Outcome measures included behavior, electrophysiology, morphometry, immunocytochemistry, quantitative real-time PCR, and western blotting. We demonstrate that the presence of autoantibodies, directed against neuronal/axonal cell surface gangliosides, in the injured mammalian peripheral nerves switch the proregenerative inflammatory environment to growth inhibitory milieu by engaging specific activating Fcγ receptors on recruited monocyte-derived macrophages to cause severe inhibition of axon regeneration. Our data demonstrate that the antibody orchestrated Fcγ receptor-mediated switch in inflammation is one mechanism underlying inhibition of axon regeneration. These findings have clinical implications for nerve repair and recovery in antibody-mediated immune neuropathies. Our results add to the complexity of axon regeneration in injured peripheral and central nervous systems as adverse effects of B cells and autoantibodies on neural injury and repair are increasingly recognized.

Immune mediated liver failure.

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Wang, Xiaojing; Ning, Qin

2014-01-01

Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capacity. Direct damage and immune-mediated liver injury are two major factors involved in this process. Increasing evidence has suggested the essential role of immune-mediated liver injury in the pathogenesis of liver failure. Here, we review the evolved concepts concerning the mechanisms of immune-mediated liver injury in liver failure from human and animal studies. Both innate and adaptive immunity, especially the interaction of various immune cells and molecules as well as death receptor signaling system are discussed. In addition, we highlight the concept of "immune coagulation", which has been shown to be related to the disease progression and liver injury exacerbation in HBV related acute-on-chronic liver failure.

Genetic Associations in Acquired Immune-Mediated Bone Marrow Failure Syndromes: Insights in Aplastic Anemia and Chronic Idiopathic Neutropenia

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Mavroudi, Irene; Papadaki, Helen A.

2012-01-01

Increasing interest on the field of autoimmune diseases has unveiled a plethora of genetic factors that predispose to these diseases. However, in immune-mediated bone marrow failure syndromes, such as acquired aplastic anemia and chronic idiopathic neutropenia, in which the pathophysiology results from a myelosuppressive bone marrow microenvironment mainly due to the presence of activated T lymphocytes, leading to the accelerated apoptotic death of the hematopoietic stem and progenitor cells, such genetic associations have been very limited. Various alleles and haplotypes of human leucocyte antigen (HLA) molecules have been implicated in the predisposition of developing the above diseases, as well as polymorphisms of inhibitory cytokines such as interferon-γ, tumor necrosis factor-α, and transforming growth factor-β1 along with polymorphisms on molecules of the immune system including the T-bet transcription factor and signal transducers and activators of transcription. In some cases, specific polymorphisms have been implicated in the outcome of treatment on those patients. PMID:22956967

Emotion Potentiated Startle in Fragile X Syndrome

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Ballinger, Elizabeth C.; Cordeiro, Lisa; Chavez, Alyssa D.; Hagerman, Randi J.; Hessl, David

2014-01-01

Social avoidance and anxiety are prevalent in fragile X syndrome (FXS) and are potentially mediated by the amygdala, a brain region critical for social behavior. Unfortunately, functional brain resonance imaging investigation of the amygdala in FXS is limited by the difficulties experienced by intellectually impaired and anxious participants. We…

Hydrological variability in the Fraser River Basin during the 20th century: A sensitivity study with the VIC model

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Kang, D.; Gao, H.; Dery, S. J.

2012-12-01

The Variable Infiltration Capacity (VIC) model, a macroscale surface hydrology model, was applied to the Fraser River Basin (FRB) of British Columbia, Canada. Previous modeling studies have demonstrated that the FRB is a snow-dominated system but with climate change may evolve to a pluvial regime. The ultimate goal of this model application is to evaluate the changing contribution of snowmelt to streamflow in the FRB both spatially and temporally. To this end, the National Centers for Environmental Prediction (NCEP) reanalysis data combined with meteorological observations over 1953 to 2006 are used to drive the model at a resolution of 0.25°. Model simulations are first validated with daily discharge observations from the Water Survey of Canada (WSC). In addition, the snow water equivalent (SWE) results from VIC are compared with snow pillow observations from the B.C. Ministry of Environment. Then peak SWE values simulated each winter are compared with the annual runoff data to quantify the changing contribution of snowmelt to the hydrology of the FRB. With perturbed model forcings such as precipitation and air temperature, how streamflow and surface energy-mass balance are changed is evaluated. Finally, interactions between the land surface and ambient atmosphere are evaluated by analyzing VIC results such as evaporation, soil moisture, snowmelt and sensible-latent heat flux with corresponding meteorological forcings, i.e. precipitation and air temperature.

Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome.

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Aoki, Yoko; Niihori, Tetsuya; Banjo, Toshihiro; Okamoto, Nobuhiko; Mizuno, Seiji; Kurosawa, Kenji; Ogata, Tsutomu; Takada, Fumio; Yano, Michihiro; Ando, Toru; Hoshika, Tadataka; Barnett, Christopher; Ohashi, Hirofumi; Kawame, Hiroshi; Hasegawa, Tomonobu; Okutani, Takahiro; Nagashima, Tatsuo; Hasegawa, Satoshi; Funayama, Ryo; Nagashima, Takeshi; Nakayama, Keiko; Inoue, Shin-Ichi; Watanabe, Yusuke; Ogura, Toshihiko; Matsubara, Yoichi

2013-07-11

RAS GTPases mediate a wide variety of cellular functions, including cell proliferation, survival, and differentiation. Recent studies have revealed that germline mutations and mosaicism for classical RAS mutations, including those in HRAS, KRAS, and NRAS, cause a wide spectrum of genetic disorders. These include Noonan syndrome and related disorders (RAS/mitogen-activated protein kinase [RAS/MAPK] pathway syndromes, or RASopathies), nevus sebaceous, and Schimmelpenning syndrome. In the present study, we identified a total of nine missense, nonsynonymous mutations in RIT1, encoding a member of the RAS subfamily, in 17 of 180 individuals (9%) with Noonan syndrome or a related condition but with no detectable mutations in known Noonan-related genes. Clinical manifestations in the RIT1-mutation-positive individuals are consistent with those of Noonan syndrome, which is characterized by distinctive facial features, short stature, and congenital heart defects. Seventy percent of mutation-positive individuals presented with hypertrophic cardiomyopathy; this frequency is high relative to the overall 20% incidence in individuals with Noonan syndrome. Luciferase assays in NIH 3T3 cells showed that five RIT1 alterations identified in children with Noonan syndrome enhanced ELK1 transactivation. The introduction of mRNAs of mutant RIT1 into 1-cell-stage zebrafish embryos was found to result in a significant increase of embryos with craniofacial abnormalities, incomplete looping, a hypoplastic chamber in the heart, and an elongated yolk sac. These results demonstrate that gain-of-function mutations in RIT1 cause Noonan syndrome and show a similar biological effect to mutations in other RASopathy-related genes. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Gastrointestinal and Hepatic Disease in Sjogren Syndrome.

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Popov, Yevgeniy; Salomon-Escoto, Karen

2018-02-01

Sjogren syndrome (SS) is a lymphocyte-mediated, infiltrative autoimmune disorder characterized by destruction of exocrine glands leading to secretory dysfunction. The typical manifestations include xerostomia and xerophthalmia; however, extensive gastrointestinal involvement is increasingly being recognized, emphasizing the variable and systemic nature of SS. Copyright © 2017 Elsevier Inc. All rights reserved.

Trigeminal Nerve Root Demyelination Not Seen in Six Horses Diagnosed with Trigeminal-Mediated Headshaking

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Veronica L. Roberts

2017-05-01

Full Text Available Trigeminal-mediated headshaking is an idiopathic neuropathic facial pain syndrome in horses. There are clinical similarities to trigeminal neuralgia, a neuropathic facial pain syndrome in man, which is usually caused by demyelination of trigeminal sensory fibers within either the nerve root or, less commonly, the brainstem. Our hypothesis was that the neuropathological substrate of headshaking in horses is similar to that of trigeminal neuralgia in man. Trigeminal nerves, nerve roots, ganglia, infraorbital, and caudal nasal nerves from horse abattoir specimens and from horses euthanized due to trigeminal-mediated headshaking were removed, fixed, and processed for histological assessment by a veterinary pathologist and a neuropathologist with particular experience of trigeminal neuralgia histology. No histological differences were detected between samples from horses with headshaking and those from normal horses. These results suggest that trigeminal-mediated headshaking may have a different pathological substrate from trigeminal neuralgia in man.

Immune-mediated bone marrow failure syndromes of progenitor and stem cells: molecular analysis of cytotoxic T cell clones.

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Ramon Tiu

2007-03-01

Full Text Available The unique structure of the T cell receptor (TCR enables molecular identification of individual T cell clones and provides an unique opportunity for the design of molecular diagnostic tests based on the structure of the rearranged TCR chain e.g., using the TCR CDR3 region. Initially, clonal T cell malignancies, including T cell large granular lymphocyte leukemia (T-LGL, mucosis fungoides and peripheral T cell lymphoma were targets for the TCR-based analytic assays such as detection of clonality by T-gamma rearrangement using y-chain-specific PCR or Southern Blotting. Study of these disorders facilitated further analytic concepts and application of rational methods of TCR analysis to investigations of polyclonal T cell-mediated diseases. In hematology, such conditions include graft versus host disease (GvHD and immune-mediated bone marrow failure syndromes. In aplastic anemia (AA, myelodysplastic syndrome (MDS or paroxysmal nocturnal hemoglobinuria (PNH, cytotoxic T cell responses may be directed against certain antigens located on stem or more lineage-restricted progenitor cells in single lineage cytopenias. The nature of the antigenic targets driving polyclonal CTL responses remains unclear. Novel methods of TCR repertoire analysis, include VB flow cytometry, peptide-specific tetramer staining, in vitro stimulation assays and TCR CDR3-specific PCR. Such PCR assay can be either VB family-specific or multiplexed for all VB families. Amplified products can be characterized and quantitated to facilitate detection of the most immunodominant clonotypes. Such clonotypes may serve as markers for the global polyclonal T cell response. Identification of these clonotypes can be performed in blood and tissue biopsy material by various methods. Once immunodominant clonotypes corresponding to pathogenic CTL clones are identified they can serve as surrogate markers for the activity of the pathophysiologic process or even indicate the presence of specific

Does Autoimmunity have a Role in Myoclonic Astatic Epilepsy? A Case Report of Voltage Gated Potassium Channel Mediated Seizures.

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Sirsi, Deepa; Dolce, Alison; Greenberg, Benjamin M; Thodeson, Drew

2016-01-01

There is expanding knowledge about the phenotypic variability of patients with voltage gated potassium channel complex (VGKC) antibody mediated neurologic disorders. The phenotypes are diverse and involve disorders of the central and peripheral nervous systems. The central nervous system manifestations described in the literature include limbic encephalitis, status epilepticus, and acute encephalitis. We report a 4.5 year-old boy who presented with intractable Myoclonic Astatic Epilepsy (MAE) or Doose syndrome and positive VGKC antibodies in serum. Treatment with steroids led to resolution of seizures and electrographic normalization. This case widens the spectrum of etiologies for MAE to include autoimmunity, in particular VGKC auto-antibodies and CNS inflammation, as a primary or contributing factor. There is an evolving understanding of voltage gated potassium channel complex mediated autoimmunity in children and the role of inflammation and autoimmunity in MAE and other intractable pediatric epilepsy syndromes remains to be fully defined. A high index of suspicion is required for diagnosis and appropriate management of antibody mediated epilepsy syndromes.

NTproBNP in insulin-resistance mediated conditions: overweight/obesity, metabolic syndrome and diabetes. The population-based Casale Monferrato Study.

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Baldassarre, Stefano; Fragapani, Salvatore; Panero, Antonio; Fedele, Debora; Pinach, Silvia; Lucchiari, Manuela; Vitale, Anna Rita; Mengozzi, Giulio; Gruden, Gabriella; Bruno, Graziella

2017-09-25

NTproBNP and BNP levels are reduced in obese subjects, but population-based data comparing the pattern of this relationship in the full spectrum of insulin-resistance mediated conditions, overweight/obesity, metabolic syndrome and diabetes, are limited. The study-base were 3244 individuals aged 45-74 years, none of whom had heart failure, 1880 without diabetes and 1364 with diabetes, identified as part of two surveys of the population-based Casale Monferrato Study. All measurements were centralized. We examined with multiple linear regression and cubic regression splines the relationship between NTproBNP and BMI, independently of known risk factors and confounders. A logistic regression analysis was also performed to assess the effect of overweight/obesity (BMI ≥ 25 kg/m 2 ), diabetes and metabolic syndrome on NTproBNP values. Out of the overall cohort of 3244 people, overweight/obesity was observed in 1118 (59.4%) non-diabetic and 917 (67.2%) diabetic subjects, respectively. In logistic regression, compared to normal weight individuals, those with a BMI ≥ 25 kg/m 2 had a OR of 0.70 (95% CI 0.56-0.87) of having high NTproBNP values, independently of diabetes. As interaction between diabetes and NTproBNP was evident (p obesity or metabolic syndrome enhanced fourfold and over the OR of having high NTproBNP levels, while the presence of metabolic syndrome alone had a more modest effect (OR 1.54, 1.18-2.01) even after having excluded individuals with CVD. In the non-diabetic cohort, obesity/overweight and HOMA-IR ≥ 2.0 decreased to a similar extent the ORs of high NTproBNP [0.76 (0.60-0.95) and 0.74 (0.59-0.93)], but the association between overweight/obesity and NTproBNP was no longer significant after the inclusion into the model of HOMA-IR, whereas CRP > 3 mg/dl conferred a fully adjusted OR of 0.65 (0.49-0.86). NT-proBNP levels are lower in overweight/obesity, even in those with diabetes. Both insulin-resistance and chronic low-grade inflammation

Pre-morbid intelligence, the metabolic syndrome and mortality: the Vietnam Experience Study

DEFF Research Database (Denmark)

Batty, G D; Gale, C R; Mortensen, L H

2008-01-01

. RESULTS: In age-adjusted analyses, IQ was significantly inversely related to four of the five individual components comprising the metabolic syndrome: hypertension, high BMI, high triglycerides and high blood glucose, but not low HDL-cholesterol. After controlling for a range of covariates that included...... socioeconomic position, higher IQ scores were associated with a reduced prevalence of the metabolic syndrome itself (odds ratio(1 SD increase in IQ) 0.87, 95% CI 0.78-0.98). Structural equation modelling revealed that education was not a mediator of the relationship between IQ and the metabolic syndrome...

Pathophysiological mechanisms in antiphospholipid syndrome

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Harper, Brock E; Wills, Rohan; Pierangeli, Silvia S

2013-01-01

Antiphospholipid syndrome is a systemic autoimmune disease associated with thrombosis and recurrent fetal loss in the setting of detectable antiphospholipid (aPL) antibodies. The major antigenic target has been identifed as β2-glycoprotein I (β2GPI), which mediates binding of aPL antibodies to target cells including endothelial cells, monocytes, platelets and trophoblasts, leading to prothrombotic and proinfammatory changes that ultimately result in thrombosis and fetal loss. This article summarizes recent insights into the role of β2GPI in normal hemostasis, interactions between aPL antibodies, β2GPI and cell-surface molecules, molecular prothrombotic and proinfammatory changes induced by aPL antibodies and pathogenic changes leading to fetal loss in antiphospholipid syndrome. New directions in therapy using these insights are examined. PMID:23487578

Core self-evaluation and burnout among Nurses: the mediating role of coping styles.

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Xiaofei Li

Full Text Available OBJECTIVES: This study aimed to determine the potential association between core self-evaluation and the burnout syndrome among Chinese nurses, and the mediating role of coping styles in this relationship. METHODS: A cross-sectional survey was conducted in Shenyang, China, from May to July, 2013. A questionnaire which consisted of the Maslach Burnout Inventory-General Survey (MBI-GS, the Core Self-Evaluation Scale (CSE, and the Simplified Coping Style Questionnaire (CSQ, was completed by a total of 1,559 nurses. Hierarchical linear regression analyses and the Sobel test were performed to determine the mediating role of coping styles on the relationship between CSE and burnout. RESULTS: Nurses who had higher self-evaluation characteristics, reported less emotional exhaustion and cynicism, and higher professional efficacy. Coping style had a partial mediating effect on the relationship between CSE and the burnout syndrome among nurses. CONCLUSIONS: Core self-evaluation had effects on burnout and coping style was a mediating factor in this relationship among Chinese nurses. Therefore, the improvement of coping strategies may be helpful in the prevention of burnout among nurses, thus enhancing professional performance.

Core Self-Evaluation and Burnout among Nurses: The Mediating Role of Coping Styles

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Li, Xiaofei; Guan, Lili; Chang, Hui; Zhang, Bo

2014-01-01

Objectives This study aimed to determine the potential association between core self-evaluation and the burnout syndrome among Chinese nurses, and the mediating role of coping styles in this relationship. Methods A cross-sectional survey was conducted in Shenyang, China, from May to July, 2013. A questionnaire which consisted of the Maslach Burnout Inventory-General Survey (MBI-GS), the Core Self-Evaluation Scale (CSE), and the Simplified Coping Style Questionnaire (CSQ), was completed by a total of 1,559 nurses. Hierarchical linear regression analyses and the Sobel test were performed to determine the mediating role of coping styles on the relationship between CSE and burnout. Results Nurses who had higher self-evaluation characteristics, reported less emotional exhaustion and cynicism, and higher professional efficacy. Coping style had a partial mediating effect on the relationship between CSE and the burnout syndrome among nurses. Conclusions Core self-evaluation had effects on burnout and coping style was a mediating factor in this relationship among Chinese nurses. Therefore, the improvement of coping strategies may be helpful in the prevention of burnout among nurses, thus enhancing professional performance. PMID:25541990

THE MEDIATED DEBATE BEFORE AND AFTER THE PASSING OF THE BRAZILIAN LAW TO COMBAT DOMESTIC VIOLENCE AGAINST WOMEN – MARIA DA PENHA LAW (2001 TO 2012

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Rayza Sarmento

2014-08-01

Full Text Available In this work we propose to analyze the mediated debate on Maria da Penha Law in the newspapers Folha de São Paulo and O Globo, during the period 2001-2012. We use here the “deliberative” theoretical matrix, taking in consideration and dialoguing with the critiques of feminist theoreticians (Nancy Fraser and Iris Young, in particular who have inscribed such a conception in democratic theory. We defend that oppression which originates from gender inequalities cannot do without public debate. Thus, we seek to identify how the arguments and discursive relations on Maria da Penha Law were constructed in the two newspapers in question in two distinct periods: the phase of the construction of the law (2001-2005, and that of its sanctioning and implementation (2006-2012. Our analysis is based on a qualitative methodology focusing on the study of deliberation and media, conjugated with a qualitative analysis framework.

Enhanced Maternal Origin of the 22q11.2 Deletion in Velocardiofacial and DiGeorge Syndromes

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Delio, Maria; Guo, Tingwei; McDonald-McGinn, Donna M

2013-01-01

Velocardiofacial and DiGeorge syndromes, also known as 22q11.2 deletion syndrome (22q11DS), are congenital-anomaly disorders caused by a de novo hemizygous 22q11.2 deletion mediated by meiotic nonallelic homologous recombination events between low-copy repeats, also known as segmental duplication...

Assessing the full costs of water, liquid waste, energy and solid waste infrastructure in the Fraser Valley Regional District (FVRD)

International Nuclear Information System (INIS)

Pollard, D.

2001-01-01

This document presents a newly drafted growth strategy developed by the Fraser Valley Regional District (FVRD) in British Columbia. It guides the sustainable growth, change and development of the region for the next 25 years and deals with air pollution, water quality, traffic congestion, affordable housing, employment, energy use, parks and green space. In particular, this case study develops a method to apply full cost accounting (FCA) to a growth strategy. FCA is the most appropriate way to approach a sustainable strategy because it considers economic, social and environmental issues. The study also includes the development of a software tool consisting of an ACCESS database and an ARCVIEW GIS file for compiling and analyzing detailed infrastructure profiles which can be used to assess the full costs of different growth scenarios. The following four issue categories of environmental and economic indicators of FVRD performance were addressed: solid waste, water and wastewater, energy, and infrastructure costs. Each issue category was then used to establish a set of 5 performance indicators that can be measured and assessed over time. These included solid waste, water consumption, wastewater, energy consumption and air emissions. The database and methodology developed for this project is suitable for other regions. The software can be viewed by contacting the Sheltair Group Resource Consultants Inc. in Vancouver

Distinct gene expression profiles in ovarian cancer linked to Lynch syndrome

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Jönsson, Jenny-Maria; Bartuma, Katarina; Dominguez-Valentin, Mev

2014-01-01

Ovarian cancer linked to Lynch syndrome represents a rare subset that typically presents at young age as early-stage tumors with an overrepresentation of endometrioid and clear cell histologies. We investigated the molecular profiles of Lynch syndrome-associated and sporadic ovarian cancer...... with the aim to identify key discriminators and central tumorigenic mechanisms in hereditary ovarian cancer. Global gene expression profiling using whole-genome c-DNA-mediated Annealing, Selection, extension, and Ligation was applied to 48 histopathologically matched Lynch syndrome-associated and sporadic...... ovarian cancers. Lynch syndrome-associated and sporadic ovarian cancers differed by 349 significantly deregulated genes, including PTPRH, BIRC3, SHH and TNFRSF6B. The genes involved were predominantly linked to cell growth, proliferation, and cell-to-cell signaling and interaction. When stratified...

Inflammatory fatigue and sickness behaviour - lessons for the diagnosis and management of chronic fatigue syndrome.

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Arnett, S V; Clark, I A

2012-12-10

Persistent and severe fatigue is a common part of the presentation of a diverse range of disease processes. There is a growing body of evidence indicating a common inflammatory pathophysiology underlying many conditions where fatigue is a primary patient concern, including chronic fatigue syndrome. This review explores current models of how inflammatory mediators act on the central nervous system to produce fatigue and sickness behaviour, and the commonality of these processes in conditions as diverse as surgical trauma, infection, various cancers, inflammatory bowel disease, connective tissue diseases and autoimmune diseases. We also discuss evidence indicating chronic fatigue syndrome may have important pathophysiological similarities with cytokine mediated sickness behaviour, and what lessons can be applied from sickness behaviour to chronic fatigue syndrome with regards to the diagnosis and management. Copyright © 2012 Elsevier B.V. All rights reserved.

Epidemiological and clinical aspects of the Guillain-Barre Syndrome

NARCIS (Netherlands)

R. van Koningsveld (Rinske)

2001-01-01

textabstractThe Guillain-Barre syndrome (GBS) is an acute immune-mediated disorder of the peripheral nerves. The essential features are a rapidly progressive, more or less symmetrical weakness of the limbs and decreased or absent tendon reflexes. The weakness reaches its nadir (maximum severity) by

Behavioural mediators of genetic life-history trade-offs: a test of the pace-of-life syndrome hypothesis in field crickets.

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Santostefano, Francesca; Wilson, Alastair J; Niemelä, Petri T; Dingemanse, Niels J

2017-10-11

The pace-of-life syndrome (POLS) hypothesis predicts associations between life history and 'risky' behaviours. Individuals with 'fast' lifestyles should develop faster, reproduce earlier, exhibit more risk-prone behaviours, and die sooner than those with 'slow' lifestyles. While support for POLS has been equivocal to date, studies have relied on individual-level (phenotypic) patterns in which genetic trade-offs may be masked by environmental effects on phenotypes. We estimated genetic correlations between life history (development, lifespan, size) and risky behaviours (exploration, aggression) in a pedigreed population of Mediterranean field crickets ( Gryllus bimaculatus ). Path analyses showed that behaviours mediated some genetic relationships between life history traits, though not those involved in trade-offs. Thus, while specific predictions of POLS theory were not supported, genetic integration of behaviour and life history was present. This implies a major role for risky behaviours in life history evolution. © 2017 The Author(s).

Neurobiology of Depression and Irritable Bowel Syndrome Comorbidity

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Ozlem Donat Eker

2009-08-01

Full Text Available Irritable bowel syndrome is a disabling functional disorder with a frequent comorbidity of depression though underlying mechanisms remain yet little understood. Various signs and symptoms have been determined as diagnostic criteria in recent years and standardized as Rome-III criteria. Irritable bowel syndrome can have constipation-dominant, diarrhea-dominant or mixed clinical presentations. Main features can be summarized as continuous and recurrent abdominal pain or discomfort associated with a change of stool frequency or consistency and usually relief of symptoms with defe-cation in the absence of physical or laboratory abnormalities indicative of an organic etiology. The frequency of major depressive disorder diagnosis reaches up to two thirds of irritable bowel syndrome patients. Moreover, the comorbidity of irritable bowel syndrome among patients with major depression is highly frequent (30%. The mechanism underlying irritable bowel syndrome which have been considered as a kind of a somatization disorder for a long time and now as a functional bowel disease is in the brain-gut axis. Low grade mucosal inflammation and cytokines originating from mucosal inflammation have important functions in the pathophysiology of irritable bowel syndrome and its comorbidity with major depression. Besides the inflammatory factors lumbosacral visceral hyperexcitability which is an individual variation is proposed as the main underlying cause of irritable bowel syndrome. Visceral hyper-excitability is mediated by cytokines and neuro-mediators and stress is known to increase the effect of this mechanism. Furthermore, molecules participating in this mechanism (e.g. cytokines, corticotrophin releasing factor, neurokinins and monoamines play important roles in the pathophysiology of depression. Increased activation in the pain matrix (thalamus – insula – prefrontal cortex and insufficiency of endogenous pain inhibitory system are regarded as possible

Hepatorenal syndrome: an update

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Tércio Genzini

Full Text Available Hepatorenal syndrome (HRS is the development of renal failure in patients with chronic previous liver disease, without clinical or laboratory evidence of previous kidney disease. It affects up to 18% of cirrhotic patients with ascites during the first year of follow-up, reaching 39% in five years and presenting a survival of about two weeks after its establishment. HRS diagnosis is based on clinical and laboratory data. The occurrence of this syndrome is related to the mechanism for ascites development, involving vasoconstriction, low renal perfusion, water and sodium retention, increased plasma volume, and consequent overflow at the splanchnic level. Renal vasoactive mediators like endothelin 1, thromboxane A2, and leukotrienes are also involved in the genesis of this syndrome, which culminates in functional renal insufficiency. The treatment of choice can be pharmacological or surgical, although liver transplantation is the only permanent and effective treatment, with a four-year survival rate of up to 60%. Liver function recovery is usually followed by renal failure reversion. Early diagnosis and timely therapeutics can increase life expectancy for these patients while they are waiting for liver transplantation as a definitive treatment.

Ordovas-Oxidized LDL is associated with metabolic syndrome traits independently of central obesity and insulin resistance

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This study assesses whether oxidative stress, using oxidized LDL (ox-LDL) as a proxy, is associated with metabolic syndrome (MS), whether ox-LDL mediates the association between central obesity and MS, and whether insulin resistance mediates the association between ox-LDL and MS. We examined baselin...

Metabolic syndrome: A review of the role of vitamin D in mediating susceptibility and outcome

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Strange, Richard C; Shipman, Kate E; Ramachandran, Sudarshan

2015-01-01

Despite the well-recognised role of vitamin D in a wide range of physiological processes, hypovitaminosis is common worldwide (prevalence 30%-50%) presumably arising from inadequate exposure to ultraviolet radiation and insufficient consumption. While generally not at the very low levels associated with rickets, hypovitaminosis D has been implicated in various very different, pathophysiological processes. These include putative effects on the pathogenesis of neoplastic change, inflammatory and demyelinating conditions, cardiovascular disease (CVD) and diabetes. This review focuses on the association between hypovitaminosis D and the metabolic syndrome as well as its component characteristics which are central obesity, glucose homeostasis, insulin resistance, hypertension and atherogenic dyslipidaemia. We also consider the effects of hypovitaminosis D on outcomes associated with the metabolic syndrome such as CVD, diabetes and non-alcoholic fatty liver disease. We structure this review into 3 distinct sections; the metabolic syndrome, vitamin D biochemistry and the putative association between hypovitaminosis D, the metabolic syndrome and cardiovascular risk. PMID:26185598

Metabolic syndrome as a risk factor for neurological disorders.

Science.gov (United States)

Farooqui, Akhlaq A; Farooqui, Tahira; Panza, Francesco; Frisardi, Vincenza

2012-03-01

The metabolic syndrome is a cluster of common pathologies: abdominal obesity linked to an excess of visceral fat, insulin resistance, dyslipidemia and hypertension. At the molecular level, metabolic syndrome is accompanied not only by dysregulation in the expression of adipokines (cytokines and chemokines), but also by alterations in levels of leptin, a peptide hormone released by white adipose tissue. These changes modulate immune response and inflammation that lead to alterations in the hypothalamic 'bodyweight/appetite/satiety set point,' resulting in the initiation and development of metabolic syndrome. Metabolic syndrome is a risk factor for neurological disorders such as stroke, depression and Alzheimer's disease. The molecular mechanism underlying the mirror relationship between metabolic syndrome and neurological disorders is not fully understood. However, it is becoming increasingly evident that all cellular and biochemical alterations observed in metabolic syndrome like impairment of endothelial cell function, abnormality in essential fatty acid metabolism and alterations in lipid mediators along with abnormal insulin/leptin signaling may represent a pathological bridge between metabolic syndrome and neurological disorders such as stroke, Alzheimer's disease and depression. The purpose of this review is not only to describe the involvement of brain in the pathogenesis of metabolic syndrome, but also to link the pathogenesis of metabolic syndrome with neurochemical changes in stroke, Alzheimer's disease and depression to a wider audience of neuroscientists with the hope that this discussion will initiate more studies on the relationship between metabolic syndrome and neurological disorders. © Springer Basel AG 2011

Elevated CaMKIIα and Hyperphosphorylation of Homer Mediate Circuit Dysfunction in a Fragile X Syndrome Mouse Model

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Weirui Guo

2015-12-01

Full Text Available Abnormal metabotropic glutamate receptor 5 (mGluR5 function, as a result of disrupted scaffolding with its binding partner Homer, contributes to the pathophysiology of fragile X syndrome, a common inherited form of intellectual disability and autism caused by mutations in Fmr1. How loss of Fmr1 disrupts mGluR5-Homer scaffolds is unknown, and little is known about the dynamic regulation of mGluR5-Homer scaffolds in wild-type neurons. Here, we demonstrate that brief (minutes-long elevations in neural activity cause CaMKIIα-mediated phosphorylation of long Homer proteins and dissociation from mGluR5 at synapses. In Fmr1 knockout (KO cortex, Homers are hyperphosphorylated as a result of elevated CaMKIIα protein. Genetic or pharmacological inhibition of CaMKIIα or replacement of Homers with dephosphomimetics restores mGluR5-Homer scaffolds and multiple Fmr1 KO phenotypes, including circuit hyperexcitability and/or seizures. This work links translational control of an FMRP target mRNA, CaMKIIα, to the molecular-, cellular-, and circuit-level brain dysfunction in a complex neurodevelopmental disorder.

[Update Churg-Strauss syndrome].

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Moosig, F; Hellmich, B

2012-11-01

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

Principles and approaches to the treatment of immune-mediated movement disorders.

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Mohammad, Shekeeb S; Dale, Russell C

2018-03-01

Immune mediated movement disorders include movement disorders in the context of autoimmune encephalitis such as anti-NMDAR encephalitis, post-infectious autoimmune movement disorders such as Sydenham chorea, paraneoplastic autoimmune movement disorders such as opsoclonus myoclonus ataxia syndrome, and infection triggered conditions such as paediatric acute neuropsychiatric syndrome. This review focuses on the approach to treatment of immune mediated movement disorders, which requires an understanding of the immunopathogenesis, whether the disease is destructive or 'altering', and the natural history of disease. Factors that can influence outcome include the severity of disease, the delay before starting therapy, use of multimodal therapy and whether the course is monophasic or relapsing. Although the four main conditions listed above have different pathophysiological processes, there are general themes that broadly apply including: early diagnosis and treatment is better, minimise the severity of disease, escalate treatment if the patient is not responding to initial treatments, and minimise relapse. Copyright © 2017. Published by Elsevier Ltd.

Metabolic syndrome, activity of the hypothalamic-pituitary-adrenal axis and inflammatory mediators in depressive disorder.

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Martinac, Marko; Pehar, Davor; Karlović, Dalibor; Babić, Dragan; Marcinko, Darko; Jakovljević, Miro

2014-03-01

Depression has been associated with various cardiovascular risk factors such as hypertension, obesity, atherogenic dyslipidemia and hyperglycemia. In depressive disorder, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and changes in the immune system have been observed. On the other hand, somatic diseases such as obesity, hyperlipidemia, hypertension and diabetes mellitus type 2 are now perceived as important comorbid conditions in patients with depression. The pathogenesis of the metabolic syndrome and depression is complex and poorly researched; however, it is considered that the interaction of chronic stress, psychotrauma, hypercotisolism and disturbed immune functions contribute to the development of these disorders. The aim of the study was to investigate the relationship between depression and metabolic syndrome regarding the HPA axis dysfunction and altered inflammatory processes. Literature search in Medline and other databases included articles written in English published between 1985 and 2012. Analysis of the literature was conducted using a systematic approach with the search terms such as depression, metabolic syndrome, inflammation, cytokines, glucocorticoids, cortisol, and HPA axis. In conclusion, the relationship between depression and metabolic syndrome is still a subject of controversy. Further prospective studies are required to clarify the possible causal relationship between depression and metabolic syndrome and its components. Furthermore, it is important to explore the possibility of a common biologic mechanism in the pathogenesis of these two disorders, in which special attention should be paid to the immune system function, especially the possible specific mechanisms by which cytokines can induce and maintain depressive symptoms and metabolic disorders. The data presented here emphasize the importance of recognition and treatment of depressive disorders with consequent reduction in the incidence of metabolic syndrome, but

Stevens-Johnson syndrome associated with antimicrobial agent

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Ivo Cavalcanti Pita Neto

2008-01-01

Full Text Available Among the severe reactions to medications, immune-mediated Mucocutaneous Disorders are widely represented. Steven-Johnson’s syndrome, or great multiform erythema, appears as a systemic disturbance, involving the skin and mucous membranes, and is related to several factors, such as, viral or bacterial infections and particularly the administration of medicines, in general painkillers and antibiotics. The objective of this article is report the onset of ulcerative vesicle –blister lesions in the regions of the lips, gums, tongue and genital mucosa membrane in a 26 year-old patient, a leukoderm man, being treated with sulfamethoxazole trimethoprim for a respiratory infection, after being diagnosed as having the Steven-Johnson syndrome. SSJ1 558187121279.

Coexistence of Antiphospholipid Syndrome and Heparin-Induced Thrombocytopenia in a Patient with Recurrent Venous Thromboembolism

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Samuel Adediran

2017-01-01

Full Text Available Heparin-induced thrombocytopenia (HIT is a prothrombotic adverse drug reaction in which heparin forms complexes with platelet factor 4 forming neoantigens that are recognized by autoantibodies. Antiphospholipid syndrome (APS is similar to HIT in that it is mediated by autoantibodies that are also prothrombotic. We present a case of rare coexistence of antiphospholipid antibody syndrome and heparin-induced thrombocytopenia.

Effect of subalpine canopy removal on snowpack, soil solution, and nutrient export, Fraser Experimental Forest, CO

Science.gov (United States)

Stottlemyer, R.; Troendle, C.A.

1999-01-01

Research on the effects of vegetation manipulation on snowpack, soil water, and streamwater chemistry and flux has been underway at the Fraser Experimental Forest (FEF), CO, since 1982. Greater than 95% of FEF snowmelt passes through watersheds as subsurface flow where soil processes significantly alter meltwater chemistry. To better understand the mechanisms accounting for annual variation in watershed streamwater ion concentration and flux with snowmelt, we studied subsurface water flow, its ion concentration, and flux in conterminous forested and clear cut plots. Repetitive patterns in subsurface flow and chemistry were apparent. Control plot subsurface flow chemistry had the highest ion concentrations in late winter and fall. When shallow subsurface flow occurred, its Ca2+, SO42-, and HCO3- concentrations were lower and K+ higher than deep flow. The percentage of Ca2+, NO3-, SO42-, and HCO3- flux in shallow depths was less and K+ slightly greater than the percentage of total flow. Canopy removal increased precipitation reaching the forest floor by about 40%, increased peak snowpack water equivalent (SWE) > 35%, increased the average snowpack Ca2+, NO3-, and NH4+ content, reduced the snowpack K+ content, and increased the runoff four-fold. Clear cutting doubled the percentage of subsurface flow at shallow depths, and increased K+ concentration in shallow subsurface flow and NO3- concentrations in both shallow and deep flow. The percentage change in total Ca2+, SO42-, and HCO3- flux in shallow depths was less than the change in water flux, while that of K+ and NO3- flux was greater. Relative to the control, in the clear cut the percentage of total Ca2+ flux at shallow depths increased from 5 to 12%, SO42- 5.4 to 12%, HCO3- from 5.6 to 8.7%, K+ from 6 to 35%, and NO3- from 2.7 to 17%. The increases in Ca2+ and SO42- flux were proportional to the increase in water flux, the flux of HCO3- increased proportionally less than water flux, and NO3- and K+ were

A calcium-dependent protease as a potential therapeutic target for Wolfram syndrome.

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Lu, Simin; Kanekura, Kohsuke; Hara, Takashi; Mahadevan, Jana; Spears, Larry D; Oslowski, Christine M; Martinez, Rita; Yamazaki-Inoue, Mayu; Toyoda, Masashi; Neilson, Amber; Blanner, Patrick; Brown, Cris M; Semenkovich, Clay F; Marshall, Bess A; Hershey, Tamara; Umezawa, Akihiro; Greer, Peter A; Urano, Fumihiko

2014-12-09

Wolfram syndrome is a genetic disorder characterized by diabetes and neurodegeneration and considered as an endoplasmic reticulum (ER) disease. Despite the underlying importance of ER dysfunction in Wolfram syndrome and the identification of two causative genes, Wolfram syndrome 1 (WFS1) and Wolfram syndrome 2 (WFS2), a molecular mechanism linking the ER to death of neurons and β cells has not been elucidated. Here we implicate calpain 2 in the mechanism of cell death in Wolfram syndrome. Calpain 2 is negatively regulated by WFS2, and elevated activation of calpain 2 by WFS2-knockdown correlates with cell death. Calpain activation is also induced by high cytosolic calcium mediated by the loss of function of WFS1. Calpain hyperactivation is observed in the WFS1 knockout mouse as well as in neural progenitor cells derived from induced pluripotent stem (iPS) cells of Wolfram syndrome patients. A small-scale small-molecule screen targeting ER calcium homeostasis reveals that dantrolene can prevent cell death in neural progenitor cells derived from Wolfram syndrome iPS cells. Our results demonstrate that calpain and the pathway leading its activation provides potential therapeutic targets for Wolfram syndrome and other ER diseases.

[Syndrome X vs metabolic syndrome].

Science.gov (United States)

Morales Villegas, Enrique

2006-01-01

Himsworth in 1939 postulated that Diabetes Mellitus type 2 (DM2) was not only an insulin deficiency state but also a cellular insulin insensitivity disease. Thirty years later, DeFronzo and Reaven demonstrated that insulin resistance (IR) preceded and predisposed for DM2 and atherosclerotic-cardiovascular-disease (ACVD). Reaven was the first to point out the relationship between IR and with hyperglycemia, dyslipidosis, and hypertension as mediators for ACVD, creating the concept of Syndrome X (SX) in 1988. WHO and, thereafter, other medical societies and medical groups, mainly ATP-III, in 2002, based on the difficulty of diagnosing IR in a simple, reliable, and inexpensive way, proposed and published the Metabolic Syndrome (MS) concept, as a group of five variables, i.e., obesity, hyperglycemia, hypertriglyceridemia, low HDL, and hypertension, as an easy clinical approximation to suspect and treat an increased cardiometabolic risk. Nowadays, there are deep and extensive controversies on this issue; however, these controversies do not really exist since all discordant points of view are rather quantitative and not qualitative in nature. This article is aimed at differentiating and harmonizing the complementary concepts of SX and MS, at analyzing why MS is a good "clinical window" to look for IR and its underlying manifestations, and finally to accept that the MS concept complements, but does not substitute or antagonize, traditional scales used to asses cardiovascular risk, such as the Framingham scale.

Rethinking childhood adversity in chronic fatigue syndrome.

Science.gov (United States)

Clark, James E; Davidson, Sean L; Maclachlan, Laura; Newton, Julia L; Watson, Stuart

2018-01-01

Background: Previous studies have consistently shown increased rates of childhood adversity in chronic fatigue syndrome (CFS). However, such aetiopathogenic studies of CFS are potentially confounded by co-morbidity and misdiagnosis particularly with depression. Purpose: We examined the relationship between rates of childhood adversity using two complimentary approaches (1) a sample of CFS patients who had no lifetime history of depression and (2) a modelling approach. Methods: Childhood trauma questionnaire (CTQ) administered to a sample of 52 participants with chronic fatigue syndrome and 19 controls who did not meet criteria for a psychiatric disorder (confirmed using the Structured Clinical Interview for DSM-IV). Subsequently, Mediation Analysis (Baye's Rules) was used to establish the risk childhood adversity poses for CFS with and without depression. Results: In a cohort of CFS patients with depression comprehensively excluded, CTQ scores were markedly lower than in all previous studies and, in contrast to these previous studies, not increased compared with healthy controls. Post-hoc analysis showed that CTQ scores correlated with the number of depressive symptoms during the lifetime worst period of low mood. The probability of developing CFS given a history of childhood trauma is 4%, a two-fold increased risk compared to the general population. However, much of this risk is mediated by the concomitant development of major depression. Conclusions: The data suggests that previous studies showing a relationship between childhood adversity and CFS may be attributable to the confounding effects of co-morbid or misdiagnosed depressive disorder. Abbreviations: CFS: Chronic fatigue syndrome; CTQ: Childhood trauma questionnaire; MDD: Major depressive disorder; CA: Childhood adversity; P : Probability.

Oral allergy syndrome to chicory associated with birch pollen allergy

NARCIS (Netherlands)

Cadot, P.; Kochuyt, A.-M.; van Ree, R.; Ceuppens, J. L.

2003-01-01

BACKGROUND: A few cases of IgE-mediated chicory allergy with oral, cutaneous, and/or respiratory symptoms are reported. We present 4 patients with inhalant birch pollen allergy and oral allergy syndrome to chicory. IgE-binding proteins in chicory and cross-reactivity with birch pollen were studied.

Changes in mediators of inflammation and pro-thrombosis after 12 ...

African Journals Online (AJOL)

Changes in mediators of inflammation and pro-thrombosis after 12 months of dietary modification in adults with metabolic syndrome. S.K. Rahamon, U.A. Fabian, M.A. Charles-Davies, J.A. Olaniyi, A.A. Fasanmade, K.S. Akinlade, O.E. Oyewole, M.O. Owolabi, J.R. Adebusuyi, O.O. Hassan, B.M. Ajobo, M.O. Ebesunun, ...

Mediator subunit18 controls flowering time and floral organ identity in Arabidopsis.

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Zhengui Zheng

Full Text Available Mediator is a conserved multi-protein complex that plays an important role in regulating transcription by mediating interactions between transcriptional activator proteins and RNA polymerase II. Much evidence exists that Mediator plays a constitutive role in the transcription of all genes transcribed by RNA polymerase II. However, evidence is mounting that specific Mediator subunits may control the developmental regulation of specific subsets of RNA polymerase II-dependent genes. Although the Mediator complex has been extensively studied in yeast and mammals, only a few reports on Mediator function in flowering time control of plants, little is known about Mediator function in floral organ identity. Here we show that in Arabidopsis thaliana, MEDIATOR SUBUNIT 18 (MED18 affects flowering time and floral organ formation through FLOWERING LOCUS C (FLC and AGAMOUS (AG. A MED18 loss-of-function mutant showed a remarkable syndrome of later flowering and altered floral organ number. We show that FLC and AG mRNA levels and AG expression patterns are altered in the mutant. Our results support parallels between the regulation of FLC and AG and demonstrate a developmental role for Mediator in plants.

Pretreatment with ascorbic acid prevents lethal gastrointestinal syndrome in mice receiving a massive amount of radiation

International Nuclear Information System (INIS)

Yamamoto, Tetsuo; Kinoshita, Manabu; Shinomiya, Nariyoshi; Hiroi, Sadayuki; Sugasawa, Hidekazu; Majima, Takashi; Seki, Shuhji; Matsushita, Yoshitaro; Saitoh, Daizoh

2010-01-01

While bone marrow or stem cell transplantation can rescue bone marrow aplasia in patients accidentally exposed to a lethal radiation dose, radiation-induced irreversible gastrointestinal damage (GI syndrome) is fatal. We investigated the effects of ascorbic acid on radiation-induced GI syndrome in mice. Ascorbic acid (150 mg/kg/day) was orally administered to mice for 3 days, and then the mice underwent whole body irradiation (WBI). Bone marrow transplantation (BMT) 24 h after irradiation rescued mice receiving a WBI dose of less than 12 Gy. No mice receiving 14 Gy-WBI survived, because of radiation-induced GI syndrome, even if they received BMT. However, pretreatment with ascorbic acid significantly suppressed radiation-induced DNA damage in the crypt cells and prevented denudation of intestinal mucosa; therefore, ascorbic acid in combination with BMT rescued mice after 14 Gy-WBI. DNA microarray analysis demonstrated that irradiation up-regulated expressions of apoptosis-related genes in the small intestine, including those related to the caspase-9-mediated intrinsic pathway as well as the caspase-8-mediated extrinsic pathway, and down-regulated expressions of these genes in ascorbic acid-pretreated mice. Thus, pretreatment with ascorbic acid may effectively prevent radiation-induced GI syndrome. (author)

Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome

DEFF Research Database (Denmark)

Perry, Rachel J; Peng, Liang; Barry, Natasha A

2016-01-01

Obesity, insulin resistance and the metabolic syndrome are associated with changes to the gut microbiota; however, the mechanism by which modifications to the gut microbiota might lead to these conditions is unknown. Here we show that increased production of acetate by an altered gut microbiota i...

Interleukin-10 overexpression promotes Fas-ligand-dependent chronic macrophage-mediated demyelinating polyneuropathy.

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Dru S Dace

Full Text Available BACKGROUND: Demyelinating polyneuropathy is a debilitating, poorly understood disease that can exist in acute (Guillain-Barré syndrome or chronic forms. Interleukin-10 (IL-10, although traditionally considered an anti-inflammatory cytokine, has also been implicated in promoting abnormal angiogenesis in the eye and in the pathobiology of autoimmune diseases such as lupus and encephalomyelitis. PRINCIPAL FINDINGS: Overexpression of IL-10 in a transgenic mouse model leads to macrophage-mediated demyelinating polyneuropathy. IL-10 upregulates ICAM-1 within neural tissues, promoting massive macrophage influx, inflammation-induced demyelination, and subsequent loss of neural tissue resulting in muscle weakness and paralysis. The primary insult is to perineural myelin followed by secondary axonal loss. Infiltrating macrophages within the peripheral nerves demonstrate a highly pro-inflammatory signature. Macrophages are central players in the pathophysiology, as in vivo depletion of macrophages using clodronate liposomes reverses the phenotype, including progressive nerve loss and paralysis. Macrophage-mediate demyelination is dependent on Fas-ligand (FasL-mediated Schwann cell death. SIGNIFICANCE: These findings mimic the human disease chronic idiopathic demyelinating polyneuropathy (CIDP and may also promote further understanding of the pathobiology of related conditions such as acute idiopathic demyelinating polyneuropathy (AIDP or Guillain-Barré syndrome.

Cognitive Differences in Pictorial Reasoning between High-Functioning Autism and Asperger's Syndrome

Science.gov (United States)

Sahyoun, Cherif P.; Soulieres, Isabelle; Belliveau, John W.; Mottron, Laurent; Mody, Maria

2009-01-01

We investigated linguistic and visuospatial processing during pictorial reasoning in high-functioning autism (HFA), Asperger's syndrome (ASP), and age and IQ-matched typically developing participants (CTRL), using three conditions designed to differentially engage linguistic mediation or visuospatial processing (visuospatial, V; semantic, S;…

Diabetes and neurodegeneration in Wolfram syndrome: a multicenter study of phenotype and genotype.

Science.gov (United States)

Rohayem, Julia; Ehlers, Christian; Wiedemann, Bärbel; Holl, Reinhard; Oexle, Konrad; Kordonouri, Olga; Salzano, Giuseppina; Meissner, Thomas; Burger, Walter; Schober, Edith; Huebner, Angela; Lee-Kirsch, Min Ae

2011-07-01

To describe the diabetes phenotype in Wolfram syndrome compared with type 1 diabetes, to investigate the effect of glycemic control on the neurodegenerative process, and to assess the genotype-phenotype correlation. The clinical data of 50 patients with Wolfram syndrome-related diabetes (WSD) were reviewed and compared with the data of 24,164 patients with type 1 diabetes. Patients with a mean HbA1c during childhood and adolescence of ≤7.5 and >7.5% were compared with respect to the occurrence of additional Wolfram syndrome symptoms. The wolframin (WFS1) gene was screened for mutations in 39 patients. WFS1 genotypes were examined for correlation with age at onset of diabetes. WSD was diagnosed earlier than type 1 diabetes (5.4±3.8 vs. 7.9±4.2 years; P7.5% (P=0.031). Thirteen novel WSF1 mutations were identified. Predicted functional consequence of WFS1 mutations correlated with age at WSD onset (P=0.028). Endoplasmic reticulum stress-mediated decline of β-cells in WSD occurs earlier in life than autoimmune-mediated β-cell destruction in type 1 diabetes. This study establishes a role for WFS1 in determining the age at onset of diabetes in Wolfram syndrome and identifies glucose toxicity as an accelerating feature in the progression of disease.

What causes dryness in Sjögren's syndrome patients and how can it be targeted?

Science.gov (United States)

Pflugfelder, Stephen C

2014-04-01

Concepts regarding what causes dryness in Sjögren's syndrome have evolved over the past decade. Inflammation in the lacrimal functional unit contributes to development of dry eye by causing dysfunction and even death of tear secreting epithelium in the lacrimal gland and conjunctiva that alters tear composition and stability. Disease-relevant inflammatory mediators have been identified and therapies targeting these mediators are beginning to emerge.

TLR-mediated albuminuria needs TNFα-mediated cooperativity between TLRs present in hematopoietic tissues and CD80 present on non-hematopoietic tissues in mice

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Nidhi Jain

2016-06-01

Full Text Available Transient albuminuria induced by pathogen-associated molecular patterns (PAMPs in mice through engagement of Toll-like receptors (TLRs is widely studied as a partial model for some forms of human nephrotic syndrome (NS. In addition to TLRs, CD80 has been shown to be essential for PAMP-mediated albuminuria. However, the mechanistic relationships between TLRs, CD80 and albuminuria remain unclear. Here, we show that albuminuria and CD80-uria induced in mice by many TLR ligands are dependent on the expression of TLRs and their downstream signalling intermediate MyD88 exclusively in hematopoietic cells and, conversely, on CD80 expression exclusively in non-hematopoietic cells. TNFα is crucial for TLR-mediated albuminuria and CD80-uria, and induces CD80 expression in cultured renal podocytes. IL-10 from hematopoietic cells ameliorates TNFα production, albuminuria and CD80-uria but does not prevent TNFα-mediated induction of podocyte CD80 expression. Chitohexaose, a small molecule originally of parasite origin, mediates TLR4-dependent anti-inflammatory responses, and blocks TLR-mediated albuminuria and CD80-uria through IL-10. Thus, TNFα is a prominent mediator of renal CD80 induction and resultant albuminuria in this model, and small molecules modulating TLR-mediated inflammatory activation might have contributory or adjunct therapeutic potential in some contexts of NS development.

Potential Effects of Dams on Migratory Fish in the Mekong River: Lessons from Salmon in the Fraser and Columbia Rivers

Science.gov (United States)

Ferguson, John W.; Healey, Michael; Dugan, Patrick; Barlow, Chris

2011-01-01

We compared the effects of water resource development on migratory fish in two North American rivers using a descriptive approach based on four high-level indicators: (1) trends in abundance of Pacific salmon, (2) reliance on artificial production to maintain fisheries, (3) proportion of adult salmon that are wild- versus hatchery-origin, and (4) number of salmon populations needing federal protection to avoid extinction. The two rivers had similar biological and physical features but radically different levels of water resource development: the Fraser River has few dams and all are located in tributaries, whereas the Columbia River has more than 130 large mainstem and tributary dams. Not surprisingly, we found substantial effects of development on salmon in the Columbia River. We related the results to potential effects on migratory fish in the Mekong River where nearly 200 mainstem and tributary dams are installed, under construction, or planned and could have profound effects on its 135 migratory fish species. Impacts will vary with dam location due to differential fish production within the basin, with overall effects likely being greatest from 11 proposed mainstem dams. Minimizing impacts will require decades to design specialized fish passage facilities, dam operations, and artificial production, and is complicated by the Mekong's high diversity and productivity. Prompt action is needed by governments and fisheries managers to plan Mekong water resource development wisely to prevent impacts to the world's most productive inland fisheries, and food security and employment opportunities for millions of people in the region.

Health and air quality 2005 : phase 2 : valuation of health impacts from air quality in the Lower Fraser Valley airshed

Energy Technology Data Exchange (ETDEWEB)

Furberg, M.; Preston, K. [RWDI West Inc., Vancouver, BC (Canada); Sawyer, D. [Marbek Resource Consultants Ltd., Ottawa, ON (Canada); Brauer, M. [British Columbia Univ., Vancouver, BC (Canada). School of Occupational and Environmental Hygiene; Hanvelt, R. [British Columbia Univ., Vancouver, BC (Canada). Dept. of Health Care and Epidemiology

2005-07-15

This study provided estimates the health benefits and costs associated with specified changes in ambient air concentrations of particulate matter (PM) and ozone in the Lower Fraser Valley (LFV). Estimates were developed on a regional level. The study focused on PM and ozone, as current air quality monitoring data and scientific findings have indicated that these are the air contaminants of greatest concern in the region. Known air quality health outcome relationships were applied in a spreadsheet model to predict changes in health outcomes associated with 6 ambient air quality scenarios for 3 sub-regions within the LFV airshed. Concentration response functions based on epidemiological studies were used to estimate the number of health events associated with changes in air quality. For each scenario, the model calculated the expected number of the following health outcomes: mortality; chronic bronchitis; respiratory hospital admissions; cardiac hospital admissions; emergency room visits; child acute bronchitis; restricted activity days; asthma symptom days; minor restricted activity days and acute respiratory symptom days. The model also produced the dollar value of the health outcomes. A dollar metric was used so that the health outcomes could be aggregated and compared with other air quality management actions such the costs of improving ambient air quality. Results indicated that improving ambient air quality in the LFV will produce valued and socially desirable benefits, including reduced mortality and morbidity. The measures contemplated by decision-makers to maintain and improve air quality in the LFV will trigger benefits that are likely to be significant. 101 refs., 7 tabs., 7 figs.

Dietary phenolic acids reverse insulin resistance, hyperglycaemia, dyslipidaemia, inflammation and oxidative stress in high-fructose diet-induced metabolic syndrome rats.

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Ibitoye, Oluwayemisi B; Ajiboye, Taofeek O

2017-12-20

This study investigated the influence of caffeic, ferulic, gallic and protocatechuic acids on high-fructose diet-induced metabolic syndrome in rats. Oral administration of the phenolic acids significantly reversed high-fructose diet-mediated increase in body mass index and blood glucose. Furthermore, phenolic acids restored high-fructose diet-mediated alterations in metabolic hormones (insulin, leptin and adiponectin). Similarly, elevated tumour necrosis factor-α, interleukin-6 and -8 were significantly lowered. Administration of phenolic acids restored High-fructose diet-mediated increase in the levels of lipid parameters and indices of atherosclerosis, cardiac and cardiovascular diseases. High-fructose diet-mediated decrease in activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase) and increase in oxidative stress biomarkers (reduced glutathione, lipid peroxidation products, protein oxidation and fragmented DNA) were significantly restored by the phenolic acids. The result of this study shows protective influence of caffeic acid, ferulic acid, gallic acid and protocatechuic acid in high-fructose diet-induced metabolic syndrome.

Exercise-mediated vasodilation in human obesity and metabolic syndrome: effect of acute ascorbic acid infusion.

Science.gov (United States)

Limberg, Jacqueline K; Kellawan, J Mikhail; Harrell, John W; Johansson, Rebecca E; Eldridge, Marlowe W; Proctor, Lester T; Sebranek, Joshua J; Schrage, William G

2014-09-15

We tested the hypothesis that infusion of ascorbic acid (AA), a potent antioxidant, would alter vasodilator responses to exercise in human obesity and metabolic syndrome (MetSyn). Forearm blood flow (FBF, Doppler ultrasound) was measured in lean, obese, and MetSyn adults (n = 39, 32 ± 2 yr). A brachial artery catheter was inserted for blood pressure monitoring and local infusion of AA. FBF was measured during dynamic handgrip exercise (15% maximal effort) with and without AA infusion. To account for group differences in blood pressure and forearm size, and to assess vasodilation, forearm vascular conductance (FVC = FBF/mean arterial blood pressure/lean forearm mass) was calculated. We examined the time to achieve steady-state FVC (mean response time, MRT) and the rise in FVC from rest to steady-state exercise (Δ, exercise - rest) before and during acute AA infusion. The MRT (P = 0.26) and steady-state vasodilator responses to exercise (ΔFVC, P = 0.31) were not different between groups. Intra-arterial infusion of AA resulted in a significant increase in plasma total antioxidant capacity (174 ± 37%). AA infusion did not alter MRT or steady-state FVC in any group (P = 0.90 and P = 0.85, respectively). Interestingly, higher levels of C-reactive protein predicted longer MRT (r = 0.52, P exercise does not alter the time course or magnitude of exercise-mediated vasodilation in groups of young lean, obese, or MetSyn adults. However, systemic inflammation may limit the MRT to exercise, which can be improved with AA. Copyright © 2014 the American Physiological Society.

Determining putative vectors of the Bogia Coconut Syndrome phytoplasma using loop-mediated isothermal amplification of single-insect feeding media

Science.gov (United States)

Lu, Hengyu; Wilson, Bree A. L.; Ash, Gavin J.; Woruba, Sharon B.; Fletcher, Murray J.; You, Minsheng; Yang, Guang; Gurr, Geoff M.

2016-01-01

Phytoplasmas are insect vectored mollicutes responsible for disease in many economically important crops. Determining which insect species are vectors of a given phytoplasma is important for managing disease but is methodologically challenging because disease-free plants need to be exposed to large numbers of insects, often over many months. A relatively new method to detect likely transmission involves molecular testing for phytoplasma DNA in sucrose solution that insects have fed upon. In this study we combined this feeding medium method with a loop-mediated isothermal amplification (LAMP) assay to study 627 insect specimens of 11 Hemiptera taxa sampled from sites in Papua New Guinea affected by Bogia coconut syndrome (BCS). The LAMP assay detected phytoplasma DNA from the feeding solution and head tissue of insects from six taxa belonging to four families: Derbidae, Lophopidae, Flatidae and Ricaniidae. Two other taxa yielded positives only from the heads and the remainder tested negative. These results demonstrate the utility of combining single-insect feeding medium tests with LAMP assays to identify putative vectors that can be the subject of transmission tests and to better understand phytoplasma pathosystems. PMID:27786249

Aberrant Methylation-Mediated Suppression of APAF1 in Myelodysplastic Syndrome.

Science.gov (United States)

Zaker, Farhad; Nasiri, Nahid; Amirizadeh, Naser; Razavi, Seyed Mohsen; Yaghmaie, Marjan; Teimoori-Toolabi, Ladan; Maleki, Ali; Bakhshayesh, Masoumeh

2017-04-01

Background: Myelodysplastic syndromes (MDSs) include a diverse group of clonal bone marrow disorders characterized by ineffective hematopoiesis and pancytopenia. It was found that down regulation of APAF1, a putative tumor suppressor gene (TSG), leads to resistance to chemotherapy and disease development in some cancers. In this study, we investigated the relation of APAF1 methylation status with its expression and clinicopathological factors in myelodysplastic syndrome (MDS) patients. Materials and Methods: Methylation Sensitive-High Resolution Melting Curve Analysis (MS-HRM) was employed in studying the methylation of CpG islands in the APAF1promoter region in MDS. Gene expression was analyzed by using real time RT-PCR. Results: 42.6% of patient samples were methylated in promoter region of APAF1analyzed, while methylation of the gene was not seen in controls (P<0.05). Methylation of APAF1was significantly associated with the suppression of its mRNA expression (P=0.00). The methylation status of APAF1in advanced-stage MDS patients (80%) was significantly higher than that of the early-stage MDS patients (28.2%) (P=0.001). The difference in frequency of hypermethylatedAPAF1 gene was significant between good (37.5%) and poor (85.71%) cytogenetic risk groups (P=0.043). In addition, a higher frequency of APAF1hypermethylation was observed in higher-risk MDS group (69.2%) compared to lower-risk MDS group (34.14%) (P=0.026). Conclusion: Our study indicated that APAF1hypermethylation in MDS was associated to high-risk disease classified according to the IPSS, WHO and cytogenetic risk.

African Journal of Marine Science - Vol 30, No 2 (2008)

African Journals Online (AJOL)

Records of Fraser\\'s dolphin Lagenodelphis hosei Fraser 1956 from the Gulf of Guinea and Angola · EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. CR Weir, J Debrah, PK Ofori-Danson, C Pierpoint, K Van Waerebeek, 241-246 ...

Neuroimaging evidence of deficient axon myelination in Wolfram syndrome.

Science.gov (United States)

Lugar, Heather M; Koller, Jonathan M; Rutlin, Jerrel; Marshall, Bess A; Kanekura, Kohsuke; Urano, Fumihiko; Bischoff, Allison N; Shimony, Joshua S; Hershey, Tamara

2016-02-18

Wolfram syndrome is a rare autosomal recessive genetic disease characterized by insulin dependent diabetes and vision, hearing and brain abnormalities which generally emerge in childhood. Mutations in the WFS1 gene predispose cells to endoplasmic reticulum stress-mediated apoptosis and may induce myelin degradation in neuronal cell models. However, in vivo evidence of this phenomenon in humans is lacking. White matter microstructure and regional volumes were measured using magnetic resonance imaging in children and young adults with Wolfram syndrome (n = 21) and healthy and diabetic controls (n = 50). Wolfram patients had lower fractional anisotropy and higher radial diffusivity in major white matter tracts and lower volume in the basilar (ventral) pons, cerebellar white matter and visual cortex. Correlations were found between key brain findings and overall neurological symptoms. This pattern of findings suggests that reduction in myelin is a primary neuropathological feature of Wolfram syndrome. Endoplasmic reticulum stress-related dysfunction in Wolfram syndrome may interact with the development of myelin or promote degeneration of myelin during the progression of the disease. These measures may provide objective indices of Wolfram syndrome pathophysiology that will be useful in unraveling the underlying mechanisms and in testing the impact of treatments on the brain.

Fibroblast Growth Factor 21 Mediates Glycemic Regulation by Hepatic JNK

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Santiago Vernia

2016-03-01

Full Text Available The cJun NH2-terminal kinase (JNK-signaling pathway is implicated in metabolic syndrome, including dysregulated blood glucose concentration and insulin resistance. Fibroblast growth factor 21 (FGF21 is a target of the hepatic JNK-signaling pathway and may contribute to the regulation of glycemia. To test the role of FGF21, we established mice with selective ablation of the Fgf21 gene in hepatocytes. FGF21 deficiency in the liver caused marked loss of FGF21 protein circulating in the blood. Moreover, the protective effects of hepatic JNK deficiency to suppress metabolic syndrome in high-fat diet-fed mice were not observed in mice with hepatocyte-specific FGF21 deficiency, including reduced blood glucose concentration and reduced intolerance to glucose and insulin. Furthermore, we show that JNK contributes to the regulation of hepatic FGF21 expression during fasting/feeding cycles. These data demonstrate that the hepatokine FGF21 is a key mediator of JNK-regulated metabolic syndrome.

Graphene oxide based fluorescence resonance energy transfer and loop-mediated isothermal amplification for white spot syndrome virus detection.

Science.gov (United States)

Waiwijit, U; Phokaratkul, D; Kampeera, J; Lomas, T; Wisitsoraat, A; Kiatpathomchai, W; Tuantranont, A

2015-10-20

Graphene oxide (GO) is attractived for biological or medical applications due to its unique electrical, physical, optical and biological properties. In particular, GO can adsorb DNA via π-π stacking or non-covalent interactions, leading to fluorescence quenching phenomenon applicable for bio-molecular detection. In this work, a new method for white spot syndrome virus (WSSV)-DNA detection is developed based on loop-mediated isothermal amplification (LAMP) combined with fluorescence resonance energy transfer (FRET) between GO and fluorescein isothiocyanate-labeled probe (FITC-probe). The fluorescence quenching efficiency of FITC-probe was found to increase with increasing GO concentration and reached 98.7% at a GO concentration of 50 μg/ml. The fluorescence intensity of FITC-probe was recovered after hybridization with WSSV LAMP product with an optimal hybridization time of 10 min and increased accordingly with increasing amount of LAMP products. The detection limit was estimated to be as low as 10 copies of WSSV plasmid DNA or 0.6 fg of the total DNA extracted from shrimp infected with WSSV. In addition, no cross reaction was observed with other common shrimp viral pathogens. Therefore, the GO-FRET-LAMP technique is promising for fast, sensitive and specific detection of DNAs. Copyright © 2015 Elsevier B.V. All rights reserved.

Transcriptional changes in blood after aerobic interval training in patients with the metabolic syndrome.

Science.gov (United States)

Bye, Anja; Tjønna, Arnt E; Stølen, Tomas O; Røsbjørgen, Ragnhild E N; Wisløff, Ulrik

2009-02-01

Regular physical activity has beneficial effects on the metabolic syndrome. Eleven metabolic syndrome patients performing 16 weeks of aerobic interval training, significantly reduced their risk of cardiovascular disease, in terms of improved VO2max, endothelial function, blood pressure, insulin signaling, and plasma lipid composition. The knowledge on underlying mechanism of exercise-induced improvements is sparse, and a broad spectrum of methods is needed to gain more insight. The aim was, for the first time, to determine whether transcriptional changes occur in blood cells of metabolic syndrome patients after participating in an exercise program. Blood was collected in PAXgene and EDTA tubes before and after 16 weeks of exercise. RNA was extracted and run on microarrays. Eleven biological processes and molecular functions were upregulated after exercise, whereas seven were downregulated. Blood clotting, cell adhesion, and steroid metabolism were among the downregulated processes, whereas steroid hormone-mediated signaling was upregulated. Downregulated protein levels of arginase 1 and von Willebrand factor confirmed microarray results. Increased transcription of genes involved in steroid hormone-mediated signaling, decreased levels of arginase 1, and reduced transcription of genes involved in cell adhesion, and blood clotting are likely to be involved in exercise-induced improvements of endothelial function, and improved cardiovascular risk profile of metabolic syndrome patients. These findings have provided new insights on exercise-induced improvement of cardiovascular health.

Wolfram syndrome 1 gene negatively regulates ER stress signaling in rodent and human cells.

Science.gov (United States)

Fonseca, Sonya G; Ishigaki, Shinsuke; Oslowski, Christine M; Lu, Simin; Lipson, Kathryn L; Ghosh, Rajarshi; Hayashi, Emiko; Ishihara, Hisamitsu; Oka, Yoshitomo; Permutt, M Alan; Urano, Fumihiko

2010-03-01

Wolfram syndrome is an autosomal-recessive disorder characterized by insulin-dependent diabetes mellitus, caused by nonautoimmune loss of beta cells, and neurological dysfunctions. We have previously shown that mutations in the Wolfram syndrome 1 (WFS1) gene cause Wolfram syndrome and that WFS1 has a protective function against ER stress. However, it remained to be determined how WFS1 mitigates ER stress. Here we have shown in rodent and human cell lines that WFS1 negatively regulates a key transcription factor involved in ER stress signaling, activating transcription factor 6alpha (ATF6alpha), through the ubiquitin-proteasome pathway. WFS1 suppressed expression of ATF6alpha target genes and repressed ATF6alpha-mediated activation of the ER stress response element (ERSE) promoter. Moreover, WFS1 stabilized the E3 ubiquitin ligase HRD1, brought ATF6alpha to the proteasome, and enhanced its ubiquitination and proteasome-mediated degradation, leading to suppression of ER stress signaling. Consistent with these data, beta cells from WFS1-deficient mice and lymphocytes from patients with Wolfram syndrome exhibited dysregulated ER stress signaling through upregulation of ATF6alpha and downregulation of HRD1. These results reveal a role for WFS1 in the negative regulation of ER stress signaling and in the pathogenesis of diseases involving chronic, unresolvable ER stress, such as pancreatic beta cell death in diabetes.

Immune complex-mediated autoimmunity in a patient With Smith-Magenis syndrome (del 17p11.2).

Science.gov (United States)

Yang, Jianying; Chandrasekharappa, Settara C; Vilboux, Thierry; Smith, Ann C M; Peterson, Erik J

2014-08-01

Smith-Magenis syndrome (SMS) is a sporadic congenital disorder involving multiple organ systems caused by chromosome 17p11.2 deletions. Smith-Magenis syndrome features craniofacial and skeletal anomalies, cognitive impairment, and neurobehavioral abnormalities. In addition, some SMS patients may exhibit hypogammaglobulinemia. We report the first case of SMS-associated autoimmunity in a woman who presented with adult onset of multiple autoimmune disorders, including systemic lupus erythematosus, antiphospholipid antibody syndrome, and autoimmune hepatitis. Molecular analysis using single-nucleotide polymorphism array confirmed a de novo 3.8-Mb deletion (breakpoints, chr17: 16,660,721-20,417,975), resulting in haploinsufficiency for TACI (transmembrane activator and CAML interactor). Our data are consistent with potential loss of function for the BAFF (B cell-activating factor) receptor TACI as a contributing factor to human autoimmune phenomena.

Mediators of Inflammation in Polycystic Ovary Syndrome in Relation to Adiposity

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Thozhukat Sathyapalan

2010-01-01

Full Text Available Polycystic ovary syndrome (PCOS is a common endocrine disorder in women of reproductive age group and is associated with a higher cardiovascular risk. Obesity, mainly visceral adiposity, is prevalent in patients with PCOS. Obesity is associated with low-grade inflammation and raised inflammatory cytokines, both of which are also described in patients with PCOS. In this paper, the potential relationships between fat distribution, adipocyte dysfunction and, altered inflammatory markers in patients with PCOS have been discussed.

CXCL12/CXCR4-Axis Dysfunctions: Markers of the Rare Immunodeficiency Disorder WHIM Syndrome

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Françoise Bachelerie

2010-01-01

Full Text Available The WHIM syndrome features susceptibility to human Papillomavirus infection-induced warts and carcinomas, hypogammaglobulinemia, recurrent bacterial infections, B and T-cell lymphopenia, and neutropenia associated with retention of senescent neutrophils in the bone marrow (i.e. myelokathexis. This rare disorder is mostly linked to inherited heterozygous autosomal dominant mutations in the gene encoding CXCR4, a G protein coupled receptor with a unique ligand, the chemokine CXCL12/SDF-1. Some individuals who have full clinical forms of the syndrome carry a wild type CXCR4 gene. In spite of this genetic heterogeneity, leukocytes from WHIM patients share in common dysfunctions of the CXCR4-mediated signaling pathway upon exposure to CXCL12. Dysfunctions are characterized by impaired desensitization and receptor internalization, which are associated with enhanced responses to the chemokine. Our increasing understanding of the mechanisms that account for the aberrant CXCL12/CXCR4-mediated responses is beginning to provide insight into the pathogenesis of the disorder. As a result we can expect to identify markers of the WHIM syndrome, as well as other disorders with WHIM-like features that are associated with dysfunctions of the CXCL12/CXCR4 axis.

Chronic periaortitis and antiphospholipid syndrome: is there a link?

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Liliana Carneiro

2016-06-01

Full Text Available Chronic periaortitis (CP is a rare fibro-inflammatory disease characterized by periaortic fibrosis and/or aortic aneurysms formation, mostly localized in retroperitoneum and occasionally in the mediastinum. Recent studies have shown its common association with autoimmune diseases, therefore autoimmunity has been proposed as a contributing factor. Herein, we describe the second case in the literature of CP associated with antiphospholipid syndrome. A 64-year-old man with history of open surgery for inflammatory thoracic aneurysm and recurrent deep vein thrombosis was referred for abdominal pain and weight loss in the last 6 months. Further investigation revealed elevated acute-phase reactant levels, positive antiphospholipid autoantibodies, radiological and histological evidence of periaortic fibrosis and inflammation causing abdominal aneurysm and ureteral obstruction. Diagnosis of CP and antiphospholipid syndrome were made and steroid therapy was implemented with clinical and radiological improvement. The present report further supports the potentially immune-mediated origin of CP, highlighting its possible linkage with antiphospholipid syndrome.

Increased expression of matrix metalloproteinases in the murine zymosan-induced multiple organ dysfunction syndrome.

NARCIS (Netherlands)

Volman, T.J.H.; Goris, R.J.A.; Lomme, R.M.L.M.; Groot, J. de; Verhofstad, A.A.J.; Hendriks, T.

2004-01-01

Matrix metalloproteinases (MMPs) have been implicated as mediators of tissue damage in several inflammatory diseases. Since the multiple organ dysfunction syndrome (MODS) is thought to result from systemic inflammation, overactivation of MMPs could contribute to the organ damage observed. The

The number of hypothalamic hypocretin (orexin) neurons is not affected in Prader-Willi syndrome.

NARCIS (Netherlands)

Fronczek, R.; Lammers, G.J.; Balesar, R.; Unm, U.A.hopa; Swaab, D.F.

2005-01-01

CONTEXT: Narcoleptic patients with cataplexy have a general loss of hypocretin (orexin) in the lateral hypothalamus, possibly due to an autoimmune-mediated degeneration of the hypocretin neurons. In addition to excessive daytime sleepiness, Prader-Willi syndrome (PWS) patients may show

The number of hypothalamic hypocretin (orexin) neurons is not affected in Prader-Willi syndrome

NARCIS (Netherlands)

Fronczek, Rolf; Lammers, Gert Jan; Balesar, Rawien; Unmehopa, Unga A.; Swaab, Dick F.

2005-01-01

Narcoleptic patients with cataplexy have a general loss of hypocretin (orexin) in the lateral hypothalamus, possibly due to an autoimmune-mediated degeneration of the hypocretin neurons. In addition to excessive daytime sleepiness, Prader-Willi syndrome (PWS) patients may show narcolepsy-like

Noonan syndrome gain-of-function mutations in NRAS cause zebrafish gastrulation defects

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Vincent Runtuwene

2011-05-01

Noonan syndrome is a relatively common developmental disorder that is characterized by reduced growth, wide-set eyes and congenital heart defects. Noonan syndrome is associated with dysregulation of the Ras–mitogen-activated-protein-kinase (MAPK signaling pathway. Recently, two mutations in NRAS were reported to be associated with Noonan syndrome, T50I and G60E. Here, we report a mutation in NRAS, resulting in an I24N amino acid substitution, that we identified in an individual bearing typical Noonan syndrome features. The I24N mutation activates N-Ras, resulting in enhanced downstream signaling. Expression of N-Ras-I24N, N-Ras-G60E or the strongly activating mutant N-Ras-G12V, which we included as a positive control, results in developmental defects in zebrafish embryos, demonstrating that these activating N-Ras mutants are sufficient to induce developmental disorders. The defects in zebrafish embryos are reminiscent of symptoms in individuals with Noonan syndrome and phenocopy the defects that other Noonan-syndrome-associated genes induce in zebrafish embryos. MEK inhibition completely rescued the activated N-Ras-induced phenotypes, demonstrating that these defects are mediated exclusively by Ras-MAPK signaling. In conclusion, mutations in NRAS from individuals with Noonan syndrome activated N-Ras signaling and induced developmental defects in zebrafish embryos, indicating that activating mutations in NRAS cause Noonan syndrome.

Noonan syndrome gain-of-function mutations in NRAS cause zebrafish gastrulation defects

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Runtuwene, Vincent; van Eekelen, Mark; Overvoorde, John; Rehmann, Holger; Yntema, Helger G.; Nillesen, Willy M.; van Haeringen, Arie; van der Burgt, Ineke; Burgering, Boudewijn; den Hertog, Jeroen

2011-01-01

SUMMARY Noonan syndrome is a relatively common developmental disorder that is characterized by reduced growth, wide-set eyes and congenital heart defects. Noonan syndrome is associated with dysregulation of the Ras–mitogen-activated-protein-kinase (MAPK) signaling pathway. Recently, two mutations in NRAS were reported to be associated with Noonan syndrome, T50I and G60E. Here, we report a mutation in NRAS, resulting in an I24N amino acid substitution, that we identified in an individual bearing typical Noonan syndrome features. The I24N mutation activates N-Ras, resulting in enhanced downstream signaling. Expression of N-Ras-I24N, N-Ras-G60E or the strongly activating mutant N-Ras-G12V, which we included as a positive control, results in developmental defects in zebrafish embryos, demonstrating that these activating N-Ras mutants are sufficient to induce developmental disorders. The defects in zebrafish embryos are reminiscent of symptoms in individuals with Noonan syndrome and phenocopy the defects that other Noonan-syndrome-associated genes induce in zebrafish embryos. MEK inhibition completely rescued the activated N-Ras-induced phenotypes, demonstrating that these defects are mediated exclusively by Ras-MAPK signaling. In conclusion, mutations in NRAS from individuals with Noonan syndrome activated N-Ras signaling and induced developmental defects in zebrafish embryos, indicating that activating mutations in NRAS cause Noonan syndrome. PMID:21263000

Cardiometabolic Features of Polycystic Ovary Syndrome: Role of Androgens.

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Yanes Cardozo, Licy L; Romero, Damian G; Reckelhoff, Jane F

2017-09-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder that affects reproductive-age women. Hyperandrogenemia is present in a significant fraction (~80%) of women with PCOS. Increased prevalence of cardiometabolic risk factors is frequently observed in PCOS women. The present review aims to highlight the key role of androgens in mediating the negative cardiometabolic profile observed in PCOS women. Copyright © 2017 the American Physiological Society.

[Locus of control in girls with anorexia readiness syndrome].

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Jaros, Katarzyna; Oszwa, Urszula

2014-01-01

The aim of the research was to indicate whether there are differences between locus of control (LOC) in girls with anorexia readiness syndrome (ARS) and without this syndrome. There was also a question about the relationship between LOC and the tendency to respond in incorrect attitudes towards food, eating and their bodies under stress. The sample consisted of girls aged 13-18 years randomly selected from five public Polish middle and high schools. Tools: 1) Eating Attitudes Questionnaire (EAQ) by B. Ziółkowska; 2) Locus of Control Questionnaire (LOCQ) by G. Krasowicz, A. Kurzyp-Wojnarska, to assess LOC of the subjects. The criterion group (N=23) was formed by girls who received high score in EAQ (signs of ARS) in the first stage of research (N=189). The control group (N = 23) were girls who received a low score in EAQ (no signs of ARS). Subjects with ARS were characterized by more external LOC than girls without any signs of this syndrome (t = -2.898; p control, LOC may play a role as a mediating variable rather than a direct determinant of this syndrome.

Epigenetic priming of the metabolic syndrome.

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Bruce, Kimberley D; Cagampang, Felino R

2011-05-01

The metabolic syndrome (MetS) represents a cluster of cardiometabolic risk factors, including central obesity, insulin resistance, glucose intolerance, dyslipidemia, hypertension, hyperinsulinemia and microalbuminuria, and more recently, nonalcoholic fatty liver disease (NAFLD), polycystic ovarian syndrome (PCOS) and atherosclerosis. Although the concept of the MetS is subject to debate due to lack of a unifying underlying mechanism, the prevalence of a metabolic syndrome phenotype is rapidly increasing worldwide. Moreover, it is increasingly prevalent in children and adolescents of obese mothers. Evidence from both epidemiological and experimental animal studies now demonstrates that MetS onset is increasingly likely following exposure to suboptimal nutrition during critical periods of development, as observed in maternal obesity. Thus, the developmental priming of the MetS provides a common origin for this multifactorial disorder. Consequently, the mechanisms leading to this developmental priming have recently been the subject of intensive investigation. This review discusses recent data regarding the epigenetic modifications resulting from nutrition during early development that mediate persistent changes in the expression of key metabolic genes and contribute toward an adult metabolic syndrome phenotype. In addition, this review considers the role of the endogenous molecular circadian clock system, which has the potential to act at the interface between nutrient sensing and epigenetic processing. A continued and greater understanding of these mechanisms will eventually aid in the identification of individuals at high risk of cardiovascular disease (CVD) and type 2 diabetes, and help develop therapeutic interventions, in accordance with current global government strategy.

A Spoken-Language Intervention for School-Aged Boys with Fragile X Syndrome

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McDuffie, Andrea; Machalicek, Wendy; Bullard, Lauren; Nelson, Sarah; Mello, Melissa; Tempero-Feigles, Robyn; Castignetti, Nancy; Abbeduto, Leonard

2016-01-01

Using a single case design, a parent-mediated spoken-language intervention was delivered to three mothers and their school-aged sons with fragile X syndrome, the leading inherited cause of intellectual disability. The intervention was embedded in the context of shared storytelling using wordless picture books and targeted three empirically derived…

Action myoclonus-renal failure syndrome: diagnostic applications of activity-based probes and lipid analysis

NARCIS (Netherlands)

Gaspar, Paulo; Kallemeijn, Wouter W.; Strijland, Anneke; Scheij, Saskia; van Eijk, Marco; Aten, Jan; Overkleeft, Herman S.; Balreira, Andrea; Zunke, Friederike; Schwake, Michael; Sá Miranda, Clara; Aerts, Johannes M. F. G.

2014-01-01

Lysosomal integral membrane protein-2 (LIMP2) mediates trafficking of glucocerebrosidase (GBA) to lysosomes. Deficiency of LIMP2 causes action myoclonus-renal failure syndrome (AMRF). LIMP2-deficient fibroblasts virtually lack GBA like the cells of patients with Gaucher disease (GD), a lysosomal

The biology of myelodysplastic syndromes: unity despite heterogeneity

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Azra Raza

2010-06-01

Full Text Available Myelodysplastic syndromes (MDS traditionally have been grouped together as a disease entity based on clinical phenomena seen in association. Despite the similarities, there is great heterogeneity among the syndromes. Recent insights have shown, however, that there exists a biologically cohesive theme that unifies and thereby validates the conceptual interconnectedness. The first suggestion that such a relationship existed where biology could directly explain the observed cytopenias was the finding of excessive premature apoptosis of hematopoietic cells in MDS marrows. This apoptosis was mediated by paracrine as well as autocrine factors implicating both the seed and the soil in the pathology of the disease. Pro-inflammatory cytokines in the marrow microenvironment were mainly the paracrine mediators of apoptosis, but how the clonal cells committed suicide because of autocrine stimulation had remained a mystery for more than a decade. It has been shown now that deregulation of ribosome biogenesis can initiate a stress response in the cell through the p53 signaling pathway. Congenital anemias had been associated with mutations in ribosomal protein genes. The surprise came with the investigation of 5q- syndrome patients where haplo-insufficiency of the ribosomal protein gene RPS14 was found to be the cause of this MDS subtype. Similar ribosomal deregulation was shown to be present in all varieties of MDS patients, serving as another unifying characteristic. In addition to these findings, there are other DNA-related abnormalities such as uniparental disomy, mutations in the TET2 gene, and epigenetic phenomena that are associated with and occur across all types of MDS. This paper summarizes the themes unifying this heterogeneous group of diseases.

Real-time sequence-validated loop-mediated isothermal amplification assays for detection of Middle East respiratory syndrome coronavirus (MERS-CoV.

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Sanchita Bhadra

Full Text Available The Middle East respiratory syndrome coronavirus (MERS-CoV, an emerging human coronavirus, causes severe acute respiratory illness with a 35% mortality rate. In light of the recent surge in reported infections we have developed asymmetric five-primer reverse transcription loop-mediated isothermal amplification (RT-LAMP assays for detection of MERS-CoV. Isothermal amplification assays will facilitate the development of portable point-of-care diagnostics that are crucial for management of emerging infections. The RT-LAMP assays are designed to amplify MERS-CoV genomic loci located within the open reading frame (ORF1a and ORF1b genes and upstream of the E gene. Additionally we applied one-step strand displacement probes (OSD for real-time sequence-specific verification of LAMP amplicons. Asymmetric amplification effected by incorporating a single loop primer in each assay accelerated the time-to-result of the OSD-RT-LAMP assays. The resulting assays could detect 0.02 to 0.2 plaque forming units (PFU (5 to 50 PFU/ml of MERS-CoV in infected cell culture supernatants within 30 to 50 min and did not cross-react with common human respiratory pathogens.

Understanding Bartter syndrome and Gitelman syndrome.

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Fremont, Oliver T; Chan, James C M

2012-02-01

We aim to review the clinical features of two renal tubular disorders characterized by sodium and potassium wasting: Bartter syndrome and Gitelman syndrome. Selected key references concerning these syndromes were analyzed, together with a PubMed search of the literature from 2000 to 2011. The clinical features common to both conditions and those which are distinct to each syndrome were presented. The new findings on the genetics of the five types of Bartter syndrome and the discrete mutations in Gitelman syndrome were reviewed, together with the diagnostic workup and treatment for each condition. Patients with Bartter syndrome types 1, 2 and 4 present at a younger age than classic Bartter syndrome type 3. They present with symptoms, often quite severe in the neonatal period. Patients with classic Bartter syndrome type 3 present later in life and may be sporadically asymptomatic or mildly symptomatic. The severe, steady-state hypokalemia in Bartter syndrome and Gitelman syndrome may abruptly become life-threatening under certain aggravating conditions. Clinicians need to be cognizant of such renal tubular disorders, and promptly treat at-risk patients.

Microbe-Induced Inflammatory Signals Triggering Acquired Bone Marrow Failure Syndromes.

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Espinoza, J Luis; Kotecha, Ritesh; Nakao, Shinji

2017-01-01

Acquired bone marrow failure syndromes encompass a unique set of disorders characterized by a reduction in the effective production of mature cells by the bone marrow (BM). In the majority of cases, these syndromes are the result of the immune-mediated destruction of hematopoietic stem cells or their progenitors at various stages of differentiation. Microbial infection has also been associated with hematopoietic stem cell injury and may lead to associated transient or persistent BM failure, and recent evidence has highlighted the potential impact of commensal microbes and their metabolites on hematopoiesis. We summarize the interactions between microorganisms and the host immune system and emphasize how they may impact the development of acquired BM failure.

CXCL12 Promotes Stem Cell Recruitment and Uterine Repair after Injury in Asherman’s Syndrome

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Gulcin Sahin Ersoy

2017-03-01

Full Text Available Asherman’s syndrome is an acquired condition of uterine fibrosis and adhesions in response to injury that adversely affects fertility and pregnancy. We have previously demonstrated that bone marrow-derived mesenchymal stem cells (BMDSCs contribute to uterine repair after injury and that stem cells supplementation improves fertility. Here, we demonstrate that CXCL12 is the chemokine that mediates stem cell engraftment and functional improvement using a murine model of Asherman’s syndrome. After uterine injury, we demonstrate that CXCL12 augmentation increased BMDSC engraftment and that the CXCL12 receptor (CXCR4 antagonist, ADM3100, blocked stem cell recruitment. CXCL12 reduced, whereas ADM3100 increased fibrosis. CXCL12 treatment led to improved fertility and litter size, whereas ADM3100 treatment reduced fertility and litter size. ADM3100 prevented optimal spontaneous uterine repair mediated by endogenous CXCL12 production, reducing pregnancies after injury in the absence of supplemental CXCL12 administration; however, ADM3100 treatment could be partially rescued by CXCL12 augmentation. CXCL12 or other CXCR4 receptor agonists may be useful in the treatment of infertility or adverse pregnancy outcomes in Asherman’s syndrome and other related uterine disorders.

Phosphoproteomics-mediated identification of Fer kinase as a target of mutant Shp2 in Noonan and LEOPARD syndrome

NARCIS (Netherlands)

Paardekooper Overman, Jeroen; Preisinger, Christian; Prummel, Karin; Bonetti, Monica; Giansanti, Piero; Heck, Albert; den Hertog, Jeroen

2014-01-01

Noonan syndrome (NS) and LEOPARD syndrome (LS) cause congenital afflictions such as short stature, hypertelorism and heart defects. More than 50% of NS and almost all of LS cases are caused by activating and inactivating mutations of the phosphatase Shp2, respectively. How these biochemically

Nivolumab-associated Nephrotic Syndrome in a Patient With Renal Cell Carcinoma: A Case Report

NARCIS (Netherlands)

Daanen, R.A.; Maas, R.J.H.; Koornstra, R.H.; Steenbergen, E.J.; Herpen, C.M.L. van; Willemsen, A.E.C.A.B.

2017-01-01

INTRODUCTION: Immune checkpoint inhibitors have taken an important place in the treatment of different types of malignancies. These drugs are known to have specific immune-mediated adverse events. We describe a case of severe nephrotic syndrome secondary to treatment with nivolumab in a patient with

Virally mediated Kcnq1 gene replacement therapy in the immature scala media restores hearing in a mouse model of human Jervell and Lange-Nielsen deafness syndrome.

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Chang, Qing; Wang, Jianjun; Li, Qi; Kim, Yeunjung; Zhou, Binfei; Wang, Yunfeng; Li, Huawei; Lin, Xi

2015-08-01

Mutations in the potassium channel subunit KCNQ1 cause the human severe congenital deafness Jervell and Lange-Nielsen (JLN) syndrome. We applied a gene therapy approach in a mouse model of JLN syndrome (Kcnq1(-/-) mice) to prevent the development of deafness in the adult stage. A modified adeno-associated virus construct carrying a Kcnq1 expression cassette was injected postnatally (P0-P2) into the endolymph, which resulted in Kcnq1 expression in most cochlear marginal cells where native Kcnq1 is exclusively expressed. We also found that extensive ectopic virally mediated Kcnq1 transgene expression did not affect normal cochlear functions. Examination of cochlear morphology showed that the collapse of the Reissner's membrane and degeneration of hair cells (HCs) and cells in the spiral ganglia were corrected in Kcnq1(-/-) mice. Electrophysiological tests showed normal endocochlear potential in treated ears. In addition, auditory brainstem responses showed significant hearing preservation in the injected ears, ranging from 20 dB improvement to complete correction of the deafness phenotype. Our results demonstrate the first successful gene therapy treatment for gene defects specifically affecting the function of the stria vascularis, which is a major site affected by genetic mutations in inherited hearing loss. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

Abdominal obesity and metabolic syndrome: exercise as medicine?

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Paley, Carole A; Johnson, Mark I

2018-01-01

Metabolic syndrome is defined as a cluster of at least three out of five clinical risk factors: abdominal (visceral) obesity, hypertension, elevated serum triglycerides, low serum high-density lipoprotein (HDL) and insulin resistance. It is estimated to affect over 20% of the global adult population. Abdominal (visceral) obesity is thought to be the predominant risk factor for metabolic syndrome and as predictions estimate that 50% of adults will be classified as obese by 2030 it is likely that metabolic syndrome will be a significant problem for health services and a drain on health economies.Evidence shows that regular and consistent exercise reduces abdominal obesity and results in favourable changes in body composition. It has therefore been suggested that exercise is a medicine in its own right and should be prescribed as such. This review provides a summary of the current evidence on the pathophysiology of dysfunctional adipose tissue (adiposopathy). It describes the relationship of adiposopathy to metabolic syndrome and how exercise may mediate these processes, and evaluates current evidence on the clinical efficacy of exercise in the management of abdominal obesity. The review also discusses the type and dose of exercise needed for optimal improvements in health status in relation to the available evidence and considers the difficulty in achieving adherence to exercise programmes. There is moderate evidence supporting the use of programmes of exercise to reverse metabolic syndrome although at present the optimal dose and type of exercise is unknown. The main challenge for health care professionals is how to motivate individuals to participate and adherence to programmes of exercise used prophylactically and as a treatment for metabolic syndrome.

Coping, affect, and the metabolic syndrome in older men: how does coping get under the skin?

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Yancura, Loriena A; Aldwin, Carolyn M; Levenson, Michael R; Spiro, Avron

2006-09-01

The metabolic syndrome is a complex construct with interrelated factors of obesity, blood pressure, lipids, and glucose. It is a risk factor for a number of chronic diseases in late life. This study tested a model in which the relationship between stress and the metabolic syndrome was mediated by appraisal, coping, and affect. Data were collected from 518 male participants in the Normative Aging Study (X(age) = 68.17 years). The model was partially confirmed. Relationships among stress, appraisal, coping, and affect were valenced along positive and negative pathways. However, affect was not directly related to the metabolic syndrome. The metabolic syndrome was related to positive coping as operationalized by self-regulatory strategies. The results of this study suggest that the influence of coping on physical health may occur through emotional regulation.

Update on management of ovarian hyperstimulation syndrome

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Chin-Der Chen

2011-03-01

Full Text Available Ovarian hyperstimulation syndrome (OHSS is a relatively common complication of ovarian stimulation and can be life threatening. The pathophysiology of OHSS is characterized by increased capillary permeability, leading to leakage of fluid from the vascular compartment, with third-space fluid accumulation and intravascular dehydration. The increased intra-abdominal pressure indicated that OHSS may be considered a compartment syndrome. Vascular endothelial growth factor, also known as vascular permeability factor, has emerged as one of the mediators intrinsic to the development of OHSS. Conventional management is focused on supportive care until the spontaneous resolution of the condition. The standard of care for treatment—monitoring of appropriate clinical parameters, fluid balance management, thrombosis prophylaxis, and ascites treatment—should prevent severe morbidity in most cases. This review will cover inpatient and outpatient management. The potential therapeutic approach targeting the vascular endothelial growth factor system will be discussed.

Landscape Variation in Plant Defense Syndromes across a Tropical Rainforest

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McManus, K. M.; Asner, G. P.; Martin, R.; Field, C. B.

2014-12-01

Plant defenses against herbivores shape tropical rainforest biodiversity, yet community- and landscape-scale patterns of plant defense and the phylogenetic and environmental factors that may shape them are poorly known. We measured foliar defense, growth, and longevity traits for 345 canopy trees across 84 species in a tropical rainforest and examined whether patterns of trait co-variation indicated the existence of plant defense syndromes. Using a DNA-barcode phylogeny and remote sensing and land-use data, we investigated how phylogeny and topo-edaphic properties influenced the distribution of syndromes. We found evidence for three distinct defense syndromes, characterized by rapid growth, growth compensated by defense, or limited palatability/low nutrition. Phylogenetic signal was generally lower for defense traits than traits related to growth or longevity. Individual defense syndromes were organized at different taxonomic levels and responded to different spatial-environmental gradients. The results suggest that a diverse set of tropical canopy trees converge on a limited number of strategies to secure resources and mitigate fitness losses due to herbivory, with patterns of distribution mediated by evolutionary histories and local habitat associations. Plant defense syndromes are multidimensional plant strategies, and thus are a useful means of discerning ecologically-relevant variation in highly diverse tropical rainforest communities. Scaling this approach to the landscape level, if plant defense syndromes can be distinguished in remotely-sensed data, they may yield new insights into the role of plant defense in structuring diverse tropical rainforest communities.

[Maxillofacial and dental abnormalities in some multiple abnormality syndromes. "Cri du chat" syndrome, Wilms' tumor-aniridia syndrome; Sotos syndrome; Goldenhar syndrome].

Science.gov (United States)

Berio, A; Trucchi, R; Meliota, M

1992-05-01

The paper describes the maxillo-facial and dental anomalies observed in some chromosome and non-chromosome poly-malformative syndromes ("Cri du chat" syndrome; Wilms' tumour; Sotos' syndrome; Goldenhar's syndrome). The Authors emphasise the possibility of diagnosing these multiple deformity syndromes from maxillo-facial alterations in early infancy; anomalous tooth position and structure cal also be successfully treated immediately after the first appearance of teeth. This is a particularly promising field of pediatrics and preventive pediatric medicine.

Modelling the Future Hydroclimatology of the Lower Fraser River and its Impacts on the Spawning Migration Survival of Sockeye Salmon

Science.gov (United States)

Hague, M. J.; Ferrari, M. R.; Miller, J. R.; Patterson, D. A.; Russell, G. L.; Farrell, A.P.; Hinch, S. G.

2010-01-01

Short episodic high temperature events can be lethal for migrating adult Pacific salmon (Oncorhynchus spp.). We downscaled temperatures for the Fraser River, British Columbia to evaluate the impact of climate warming on the frequency of exceeding thermal thresholds associated with salmon migratory success. Alarmingly, a modest 1.0 C increase in average summer water temperature over 100 years (1981-2000 to 2081-2100) tripled the number of days per year exceeding critical salmonid thermal thresholds (i.e. 19.0 C). Refined thresholds for two populations (Gates Creek and Weaver Creek) of sockeye salmon (Oncorhynchus nerka) were defined using physiological constraint models based on aerobic scope. While extreme temperatures leading to complete aerobic collapse remained unlikely under our warming scenario, both populations were increasingly forced to migrate upriver at reduced levels of aerobic performance (e.g. in 80% of future simulations, => 90% of salmon encountered temperatures exceeding population specific thermal optima for maximum aerobic scope; T(sub opt)) = 16.3 C for Gates Creek and T(sub sopt)=14.5 C for Weaver Creek). Assuming recent changes to river entry timing persist, we also predicted dramatic increases in the probability of freshwater mortality for Weaver Creek salmon due to reductions in aerobic, and general physiological, performance (e.g. in 42% of future simulations =>50% of Weaver Creek fish exceeded temperature thresholds associated with 0 - 60% of maximum aerobic scope). Potential for adaptation via directional selection on run-timing was more evident for the Weaver Creek population. Early entry Weaver Creek fish experienced 25% (range: 15 - 31%) more suboptimal temperatures than late entrants, compared with an 8% difference (range: 0 - 17%) between early and late Gates Creek fish. Our results emphasize the need to consider daily temperature variability in association with population-specific differences in behaviour and physiological

Williams syndrome deletions and duplications: Genetic windows to understanding anxiety, sociality, autism, and schizophrenia.

Science.gov (United States)

Crespi, Bernard J; Procyshyn, Tanya L

2017-08-01

We describe and evaluate an integrative hypothesis for helping to explain the major neurocognitive features of individuals with Williams syndrome region deletions and duplications. First, we demonstrate how the cognitive differences between Williams syndrome individuals, individuals with duplications of this region, and healthy individuals parallel the differences between individuals subject to effects of increased or decreased oxytocin. Second, we synthesize evidence showing that variation in expression of the gene GTF2I (General Transcription Factor II-I) underlies the primary social phenotypes of Williams syndrome and that common genetic variation in GTF2I mediates oxytocin reactivity, and its correlates, in healthy populations. Third, we describe findings relevant to the hypothesis that the GTF2I gene is subject to parent of origin effects whose behavioral expression fits with predictions from the kinship theory of genomic imprinting. Fourth, we describe how Williams syndrome can be considered, in part, as an autistic syndrome of Lorna Wing's 'active-but-odd' autism subtype, in contrast to associations of duplications with both schizophrenia and autism. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mediation Analysis with Multiple Mediators.

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VanderWeele, T J; Vansteelandt, S

2014-01-01

Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects through other pathways. The approaches proposed here accommodate exposure-mediator interactions and, to a certain extent, mediator-mediator interactions as well. The methods handle binary or continuous mediators and binary, continuous or count outcomes. When the mediators affect one another, the strategy of trying to assess direct and indirect effects one mediator at a time will in general fail; the approach given in this paper can still be used. A characterization is moreover given as to when the sum of the mediated effects for multiple mediators considered separately will be equal to the mediated effect of all of the mediators considered jointly. The approach proposed in this paper is robust to unmeasured common causes of two or more mediators.

CXCL12 Mediates Aberrant Costimulation of B Lymphocytes in Warts, Hypogammaglobulinemia, Infections, Myelokathexis Immunodeficiency

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Giuliana Roselli

2017-09-01

Full Text Available The Warts, Hypogammaglobulinemia, Infections, Myelokathexis (WHIM syndrome is an immunodeficiency caused by mutations in chemokine receptor CXCR4. WHIM patient adaptive immunity defects remain largely unexplained. We have previously shown that WHIM-mutant T cells form unstable immunological synapses, affecting T cell activation. Here, we show that, in WHIM patients and WHIM CXCR4 knock-in mice, B cells are more apoptosis prone. Intriguingly, WHIM-mutant B cells were also characterized by spontaneous activation. Searching for a mechanistic explanation for these observations, we uncovered a novel costimulatory effect of CXCL12, the CXCR4 ligand, on WHIM-mutant but not wild-type B cells. The WHIM CXCR4-mediated costimulation led to increased B-cell activation, possibly involving mTOR, albeit without concurrently promoting survival. A reduction in antigenic load during immunization in the mouse was able to circumvent the adaptive immunity defects. These results suggest that WHIM-mutant CXCR4 may lead to spontaneous aberrant B-cell activation, via CXCL12-mediated costimulation, impairing B-cell survival and thus possibly contributing to the WHIM syndrome defects in adaptive immunity.

CXCL12 Mediates Aberrant Costimulation of B Lymphocytes in Warts, Hypogammaglobulinemia, Infections, Myelokathexis Immunodeficiency

Science.gov (United States)

Roselli, Giuliana; Martini, Elisa; Lougaris, Vassilios; Badolato, Raffaele; Viola, Antonella; Kallikourdis, Marinos

2017-01-01

The Warts, Hypogammaglobulinemia, Infections, Myelokathexis (WHIM) syndrome is an immunodeficiency caused by mutations in chemokine receptor CXCR4. WHIM patient adaptive immunity defects remain largely unexplained. We have previously shown that WHIM-mutant T cells form unstable immunological synapses, affecting T cell activation. Here, we show that, in WHIM patients and WHIM CXCR4 knock-in mice, B cells are more apoptosis prone. Intriguingly, WHIM-mutant B cells were also characterized by spontaneous activation. Searching for a mechanistic explanation for these observations, we uncovered a novel costimulatory effect of CXCL12, the CXCR4 ligand, on WHIM-mutant but not wild-type B cells. The WHIM CXCR4-mediated costimulation led to increased B-cell activation, possibly involving mTOR, albeit without concurrently promoting survival. A reduction in antigenic load during immunization in the mouse was able to circumvent the adaptive immunity defects. These results suggest that WHIM-mutant CXCR4 may lead to spontaneous aberrant B-cell activation, via CXCL12-mediated costimulation, impairing B-cell survival and thus possibly contributing to the WHIM syndrome defects in adaptive immunity. PMID:28928741

Guillain Barre Syndrome Following Traumatic Brain Injury: A Rare Case

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Kirac Unal

2016-06-01

Full Text Available Introduction Guillain-Barre syndrome (GBS is an immune-mediated acute inflammatory disorder of the peripheral nervous system. Infectious agents were usually accused of playing a role in the etiology of GBS. Guillain-Barre syndrome has rarely been reported following subdural and subarachnoid hemorrhage after head trauma. Case Presentation We report on a 63-year-old male patient presenting GBS following Traumatic Brain Injury (TBI. Only five other similar cases are described in the literature. Conclusions Sudden onset of GBS symptoms following trauma may erroneously be assessed as secondary complications of the TBI and can lead to unnecessary procedures such as computerized tomography (CT scan and magnetic resonance imaging (MRI for a definitive diagnosis and may be a waste of time.

Marfan syndrome masked by Down syndrome?

NARCIS (Netherlands)

Vis, J.C.; Engelen, K. van; Timmermans, J.; Hamel, B.C.J.; Mulder, B.J.

2009-01-01

Down syndrome is the most common chromosomal abnormality. A simultaneous occurrence with Marfan syndrome is extremely rare. We present a case of a 28-year-old female with Down syndrome and a mutation in the fibrillin-1 gene. The patient showed strikingly few manifestations of Marfan syndrome.

Application of the 2012 revised diagnostic definitions for paediatric multiple sclerosis and immune-mediated central nervous system demyelination disorders

NARCIS (Netherlands)

van Pelt, E. Danielle; Neuteboom, Rinze F.; Ketelslegers, Immy A.; Boon, Maartje; Catsman-Berrevoets, Coriene E.; Hintzen, Rogier Q.

Background Recently, the International Paediatric Multiple Sclerosis Study Group (IPMSSG) definitions for the diagnosis of immune-mediated acquired demyelinating syndromes (ADS) of the central nervous system, including paediatric multiple sclerosis (MS), have been revised. Objective To evaluate the

Lithium-mediated protection against ethanol neurotoxicity

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Jia Luo

2010-06-01

Full Text Available Lithium has long been used as a mood stabilizer in the treatment of manic-depressive (bipolar disorder. Recent studies suggest that lithium has neuroprotective properties and may be useful in the treatment of acute brain injuries such as ischemia and chronic neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis. One of the most important neuroprotective properties of lithium is its anti-apoptotic action. Ethanol is a neuroteratogen and fetal alcohol spectrum disorders (FASD are caused by maternal ethanol exposure during pregnancy. FASD is the leading cause of mental retardation. Ethanol exposure causes neuroapoptosis in the developing brain. Ethanol-induced loss of neurons in the central nervous system underlies many of the behavioral deficits observed in FASD. Excessive alcohol consumption is also associated with Wernicke–Korsakoff syndrome and neurodegeneration in the adult brain. Recent in vivo and in vitro studies indicate that lithium is able to ameliorate ethanol-induced neuroapoptosis. Lithium is an inhibitor of glycogen synthase kinase 3 (GSK3 which has recently been identified as a mediator of ethanol neurotoxicity. Lithium’s neuroprotection may be mediated by its inhibition of GSK3. In addition, lithium also affects many other signaling proteins and pathways that regulate neuronal survival and differentiation. This review discusses the recent evidence of lithium-mediated protection against ethanol neurotoxicity and potential underlying mechanisms.

Lentiviral-Mediated Gene Therapy in Fanconi Anemia-A Mice Reveals Long-Term Engraftment and Continuous Turnover of Corrected HSCs.

Science.gov (United States)

Molina-Estevez, F Javier; Nowrouzi, Ali; Lozano, M Luz; Galy, Anne; Charrier, Sabine; von Kalle, Christof; Guenechea, Guillermo; Bueren, Juan A; Schmidt, Manfred

2015-01-01

Fanconi anemia is a DNA repair-deficiency syndrome mainly characterized by cancer predisposition and bone marrow failure. Trying to restore the hematopoietic function in these patients, lentiviral vector-mediated gene therapy trials have recently been proposed. However, because no insertional oncogenesis studies have been conducted so far in DNA repair-deficiency syndromes such as Fanconi anemia, we have carried out a genome-wide screening of lentiviral insertion sites after the gene correction of Fanca(-/-) hematopoietic stem cells (HSCs), using LAM-PCR and 454-pyrosequencing. Our studies first demonstrated that transduction of Fanca(-/-) HSCs with a lentiviral vector designed for clinical application efficiently corrects the phenotype of Fanconi anemia repopulating cells without any sign of toxicity. The identification of more than 6,500 insertion sites in primary and secondary recipients showed a polyclonal pattern of reconstitution, as well as a continuous turnover of corrected Fanca(-/-) HSC clones, without evidences of selection towards specific common integration sites. Taken together our data show, for the first time in a DNA repair-deficiency syndrome, that lentiviral vector-mediated gene therapy efficiently corrects the phenotype of affected HSCs and promotes a healthy pattern of clonal turnover in vivo. These studies will have a particular impact in the development of new gene therapy trials in patients affected by DNA repair syndromes, particularly in Fanconi anemia.

A role for thrombospondin-1 deficits in astrocyte-mediated spine and synaptic pathology in Down's syndrome.

Directory of Open Access Journals (Sweden)

Octavio Garcia

2010-12-01

Full Text Available Down's syndrome (DS is the most common genetic cause of mental retardation. Reduced number and aberrant architecture of dendritic spines are common features of DS neuropathology. However, the mechanisms involved in DS spine alterations are not known. In addition to a relevant role in synapse formation and maintenance, astrocytes can regulate spine dynamics by releasing soluble factors or by physical contact with neurons. We have previously shown impaired mitochondrial function in DS astrocytes leading to metabolic alterations in protein processing and secretion. In this study, we investigated whether deficits in astrocyte function contribute to DS spine pathology.Using a human astrocyte/rat hippocampal neuron coculture, we found that DS astrocytes are directly involved in the development of spine malformations and reduced synaptic density. We also show that thrombospondin 1 (TSP-1, an astrocyte-secreted protein, possesses a potent modulatory effect on spine number and morphology, and that both DS brains and DS astrocytes exhibit marked deficits in TSP-1 protein expression. Depletion of TSP-1 from normal astrocytes resulted in dramatic changes in spine morphology, while restoration of TSP-1 levels prevented DS astrocyte-mediated spine and synaptic alterations. Astrocyte cultures derived from TSP-1 KO mice exhibited similar deficits to support spine formation and structure than DS astrocytes.These results indicate that human astrocytes promote spine and synapse formation, identify astrocyte dysfunction as a significant factor of spine and synaptic pathology in the DS brain, and provide a mechanistic rationale for the exploration of TSP-1-based therapies to treat spine and synaptic pathology in DS and other neurological conditions.

Effects of Hypericum perforatum extract on rat irritable bowel syndrome

OpenAIRE

Mozaffari, Shilan; Esmaily, Hadi; Rahimi, Roja; Baeeri, Maryam; Sanei, Yara; Asadi-Shahmirzadi, Azar; Salehi-Surmaghi, Mohammad-Hossein; Abdollahi, Mohammad

2011-01-01

Context: In irritable bowel syndrome (IBS), disturbance of bowel motility is associated with infiltration of inflammatory mediators and cytokines into the intestine, such as neutrophils, myeloperoxidase (MPO), tumor necrosis factor alfa (TNF-?), and lipid peroxide. Aims: Regarding promising anti-inflammatory and anti-oxidative effects of Hypericum perforatum (HP) extract, besides its anti-depressant effect, this study was designed to evaluate the effects of HP in an experimental model of IBS....

The developmental trajectory of disruptive behavior in Down syndrome, fragile X syndrome, Prader-Willi syndrome and Williams syndrome.

Science.gov (United States)

Rice, Lauren J; Gray, Kylie M; Howlin, Patricia; Taffe, John; Tonge, Bruce J; Einfeld, Stewart L

2015-06-01

The aim of this study was to investigate the developmental trajectories of verbal aggression, physical aggression, and temper tantrums in four genetic syndrome groups. Participants were part of the Australian Child to Adult Development Study (ACAD), which collected information from a cohort of individuals with an intellectual disability at five time points over 18 years. Data were examined from a total of 248 people with one of the four following syndromes: Down syndrome, Fragile X syndrome, Prader-Willi syndrome, or Williams syndrome. Changes in behaviors were measured using validated items from the Developmental Behavior Checklist (DBC). The results indicate that, while verbal aggression shows no evidence of diminishing with age, physical aggression, and temper tantrums decline with age before 19 years for people with Down syndrome, Fragile X syndrome, and William syndrome; and after 19 years for people with Prader-Willi syndrome. These findings offer a somewhat more optimistic outlook for people with an intellectual disability than has previously been suggested. Research is needed to investigate the mechanisms predisposing people with PWS to persistence of temper tantrums and physical aggression into adulthood. © 2015 Wiley Periodicals, Inc.

Bulimic symptoms and the social withdrawal syndrome.

Science.gov (United States)

Rotenberg, Ken J; Bharathi, Carla; Davies, Helen; Finch, Tom

2013-08-01

One hundred and thirty-seven undergraduates (81 females; mean age = 21 years-10 months) completed the Bulimic SEDS subscale and standardized measures of trust beliefs in close others (mother, father, and friend), disclosure to them, and loneliness. Structural Equation Modelling yielded: (1) a negative path between Bulimic Symptoms and trust beliefs, (2) a positive path between trust beliefs and disclosure, (3) a negative path between trust beliefs and loneliness, and (4) a negative path between disclosure and loneliness. As expected, trust beliefs statistically mediated the relations between Bulimic Symptoms and both disclosure and loneliness and disclosure statistically mediated the relation between trust beliefs and loneliness. The findings supported the conclusion that individuals with bulimia nervosa are prone to the social withdrawal syndrome comprising a coherent and integrated pattern of low trust beliefs in close others, low disclosure to close others, and high loneliness. Copyright © 2013 Elsevier Ltd. All rights reserved.

Hamartomatous polyposis syndromes

DEFF Research Database (Denmark)

Jelsig, Anne Marie; Qvist, Niels; Brusgaard, Klaus

2014-01-01

Hamartomatous Polyposis Syndromes (HPS) are genetic syndromes, which include Peutz-Jeghers syndrome, Juvenile polyposis syndrome, PTEN hamartoma tumour syndrome (Cowden Syndrom, Bannayan-Riley-Ruvalcaba and Proteus Syndrome) as well as hereditary mixed polyposis syndrome. Other syndromes such as ......Hamartomatous Polyposis Syndromes (HPS) are genetic syndromes, which include Peutz-Jeghers syndrome, Juvenile polyposis syndrome, PTEN hamartoma tumour syndrome (Cowden Syndrom, Bannayan-Riley-Ruvalcaba and Proteus Syndrome) as well as hereditary mixed polyposis syndrome. Other syndromes...

The relation between Bulimic symptoms and the social withdrawal syndrome during early adolescence.

Science.gov (United States)

Rotenberg, Ken J; Sangha, Rajvir

2015-12-01

The short-term longitudinal study tested the hypothesis that there was a prospective relation between the social withdrawal syndrome and Bulimic symptoms during early adolescence. Ninety-six adolescents (47 males, mean age=13 years - 10 months) completed standardized scales assessing Bulimic symptoms, trust beliefs in others and loneliness at Time 1/T1 and again 5 months later at Time 2/T2. Analyses showed that: (1) Bulimic symptoms were negatively correlated with trust beliefs, (2) Bulimic symptoms were positively correlated with loneliness, and (3) trust beliefs were negatively correlated with loneliness. The SEM and mediation analyses showed that trust beliefs at T1 were negatively and concurrently associated with Bulimic symptoms at T1 and longitudinally (and negatively) predicted changes in Bulimic symptoms. It was found that loneliness at T1 statistically mediated those concurrent and longitudinal relations. The findings yielded support for the conclusion that the social withdrawal syndrome, as assessed by low trust beliefs and resulting experiences of loneliness, contributes to Bulimia nervosa during early adolescence. Copyright © 2015 Elsevier Ltd. All rights reserved.

Violence: heightened brain attentional network response is selectively muted in Down syndrome.

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Anderson, Jeffrey S; Treiman, Scott M; Ferguson, Michael A; Nielsen, Jared A; Edgin, Jamie O; Dai, Li; Gerig, Guido; Korenberg, Julie R

2015-01-01

The ability to recognize and respond appropriately to threat is critical to survival, and the neural substrates subserving attention to threat may be probed using depictions of media violence. Whether neural responses to potential threat differ in Down syndrome is not known. We performed functional MRI scans of 15 adolescent and adult Down syndrome and 14 typically developing individuals, group matched by age and gender, during 50 min of passive cartoon viewing. Brain activation to auditory and visual features, violence, and presence of the protagonist and antagonist were compared across cartoon segments. fMRI signal from the brain's dorsal attention network was compared to thematic and violent events within the cartoons between Down syndrome and control samples. We found that in typical development, the brain's dorsal attention network was most active during violent scenes in the cartoons and that this was significantly and specifically reduced in Down syndrome. When the antagonist was on screen, there was significantly less activation in the left medial temporal lobe of individuals with Down syndrome. As scenes represented greater relative threat, the disparity between attentional brain activation in Down syndrome and control individuals increased. There was a reduction in the temporal autocorrelation of the dorsal attention network, consistent with a shortened attention span in Down syndrome. Individuals with Down syndrome exhibited significantly reduced activation in primary sensory cortices, and such perceptual impairments may constrain their ability to respond to more complex social cues such as violence. These findings may indicate a relative deficit in emotive perception of violence in Down syndrome, possibly mediated by impaired sensory perception and hypoactivation of medial temporal structures in response to threats, with relative preservation of activity in pro-social brain regions. These findings indicate that specific genetic differences associated

Anti-Yo Mediated Paraneoplastic Cerebellar Degeneration Associated with Pseudobulbar Affect in a Patient with Breast Cancer

Directory of Open Access Journals (Sweden)

Allison N. Martin

2017-01-01

Full Text Available Paraneoplastic cerebellar degeneration (PCD is a rare anti-Yo mediated paraneoplastic syndromes rarely that is infrequently associated with breast cancer. We present a case of a 52-year-old female presenting with diplopia, gait instability, dysarthria, dysphagia, nystagmus, and, most notably, new onset paroxysmal episodes of uncontrollable crying concerning for pseudobulbar affect (PBA. Serologic testing showed anti-Yo antibodies. The patient was found to have stage IIIA breast cancer as the inciting cause of the paraneoplastic syndrome. The patient was treated with neoadjuvant chemotherapy, modified radical mastectomy, adjuvant Herceptin, and pertuzumab. She was given IVIG for paraneoplastic syndrome, antidepressants, and dextromethorphan-quinidine (Nuedexta, the first FDA-approved therapy for PBA. With multimodality therapy, she demonstrated significant improvement in neurologic and mood symptoms associated with PCD and PBA.

Effects of Food Additives on Immune Cells As Contributors to Body Weight Gain and Immune-Mediated Metabolic Dysregulation.

Science.gov (United States)

Paula Neto, Heitor A; Ausina, Priscila; Gomez, Lilian S; Leandro, João G B; Zancan, Patricia; Sola-Penna, Mauro

2017-01-01

Food additives are compounds used in order to improve food palatability, texture, and shelf life. Despite a significant effort to assure safety of use, toxicological analysis of these substances, generally, rely on their direct toxicity to target organs (liver and kidney) or their genotoxic effects. Much less attention is paid to the effects of these compounds on cells of the immune system. This is of relevance given that metabolic dysregulation and obesity have a strong immune-mediated component. Obese individuals present a state of chronic low-grade inflammation that contributes to the establishment of insulin resistance and other metabolic abnormalities known as the metabolic syndrome. Obesity and metabolic syndrome are currently recognized as worldwide epidemics that pose a profound socioeconomic impact and represent a concern to public health. Cells of the immune system contribute to both the maintenance of "lean homeostasis" and the metabolic dysregulation observed in obese individuals. Although much attention has been drawn in the past decades to obesity and metabolic syndrome as a result of ingesting highly processed food containing large amounts of fat and simple sugars, mounting evidence suggest that food additives may also be important contributors to metabolic derangement. Herein, we review pieces of evidence from the literature showing that food additives have relevant effects on cells of the immune system that could contribute to immune-mediated metabolic dysregulation. Considering their potential to predispose individuals to develop obesity and metabolic syndrome, their use should be taken with caution or maybe revisited.

Cogan's syndrome: present and future directions.

LENUS (Irish Health Repository)

Murphy, Grainne

2009-08-01

Cogan\\'s syndrome, typified by the combination of interstitial keratitis and immune-mediated sensorineural hearing loss, is a rare condition, and commonly associated with a diagnostic delay. Using a standard search protocol, we review the literature to date, focusing on a number of key areas pertaining to diagnosis, presentation and treatment. Using a case illustration of atypical disease which led to fulminant aortic regurgitation, we highlight the need for continued and collaborative research in order to identify negative prognostic factors and thus tailor therapeutic regimens. Atypical Cogan\\'s syndrome is more commonly associated with systemic manifestations than typical disease, and may be refractory to immunosuppressive treatment. We discuss the application of laboratory (e.g antibodies targeting inner ear antigens) and radiological (PET-CT) aids to disease confirmation and detection of sub-clinical vascular inflammation. As illustrated by the included case description, some patients remain refractory to intense immunosuppression and delineation of adverse prognostic factors which may direct treatment, perhaps including the use of PET-CT, will contribute in the future to improving patient outcomes.

Establishment of a PRKAG2 cardiac syndrome disease model and mechanism study using human induced pluripotent stem cells.

Science.gov (United States)

Zhan, Yongkun; Sun, Xiaolei; Li, Bin; Cai, Huanhuan; Xu, Chen; Liang, Qianqian; Lu, Chao; Qian, Ruizhe; Chen, Sifeng; Yin, Lianhua; Sheng, Wei; Huang, Guoying; Sun, Aijun; Ge, Junbo; Sun, Ning

2018-04-01

PRKAG2 cardiac syndrome is a distinct form of human cardiomyopathy characterized by cardiac hypertrophy, ventricular pre-excitation and progressive cardiac conduction disorder. However, it remains unclear how mutations in the PRKAG2 gene give rise to such a complicated disease. To investigate the underlying molecular mechanisms, we generated disease-specific hiPSC-derived cardiomyocytes from two brothers both carrying a heterozygous missense mutation c.905G>A (R302Q) in the PRKAG2 gene and further corrected the R302Q mutation with CRISPR-Cas9 mediated genome editing. Disease-specific hiPSC-cardiomyocytes recapitulated many phenotypes of PRKAG2 cardiac syndrome including cellular enlargement, electrophysiological irregularities and glycogen storage. In addition, we found that the PRKAG2-R302Q mutation led to increased AMPK activities, resulting in extensive glycogen deposition and cardiomyocyte hypertrophy. Finally we confirmed that disrupted phenotypes of PRKAG2 cardiac syndrome caused by the specific PRKAG2-R302Q mutation can be alleviated by small molecules inhibiting AMPK activity and be rescued with CRISPR-Cas9 mediated genome correction. Our results showed that disease-specific hiPSC-CMs and genetically-corrected hiPSC-cardiomyocytes would be a very useful platform for understanding the pathogenesis of, and testing autologous cell-based therapies for, PRKAG2 cardiac syndrome. Copyright © 2018. Published by Elsevier Ltd.

Inflammatory cause of metabolic syndrome via brain stress and NF-κB

Science.gov (United States)

Cai, Dongsheng; Liu, Tiewen

2012-01-01

Metabolic syndrome, a network of medical disorders that greatly increase the risk for developing metabolic and cardiovascular diseases, has reached epidemic levels in many areas of today's world. Despite this alarming medicare situation, scientific understandings on the root mechanisms of metabolic syndrome are still limited, and such insufficient knowledge contributes to the relative lack of effective treatments or preventions for related diseases. Recent interdisciplinary studies from neuroendocrinology and neuroimmunology fields have revealed that overnutrition can trigger intracellular stresses to cause inflammatory changes mediated by molecules that control innate immunity. This type of nutrition-related molecular inflammation in the central nervous system, particularly in the hypothalamus, can form a common pathogenic basis for the induction of various metabolic syndrome components such as obesity, insulin resistance, and hypertension. Proinflammatory NF-κB pathway has been revealed as a key molecular system for pathologic induction of brain inflammation, which translates overnutrition and resulting intracellular stresses into central neuroendocrine and neural dysregulations of energy, glucose, and cardiovascular homeostasis, collectively leading to metabolic syndrome. This article reviews recent research advances in the neural mechanisms of metabolic syndrome and related diseases from the perspective of pathogenic induction by intracellular stresses and NF-κB pathway of the brain. PMID:22328600

Comparison of Visual-Spatial Performance Strategy Training in Children with Turner Syndrome and Learning Disabilities.

Science.gov (United States)

Williams, Janet K.; And Others

1992-01-01

Thirteen females with Turner syndrome, 13 females with nonverbal learning disabilities, and 14 males with nonverbal learning disabilities, ages 7-14, were taught via a cognitive behavioral modification approach to verbally mediate a spatial matching task. All three groups showed significant task improvement after the training, with no significant…

Low levels of nitryl chloride at ground level: nocturnal nitrogen oxides in the Lower Fraser Valley of British Columbia

Science.gov (United States)

Osthoff, Hans D.; Odame-Ankrah, Charles A.; Taha, Youssef M.; Tokarek, Travis W.; Schiller, Corinne L.; Haga, Donna; Jones, Keith; Vingarzan, Roxanne

2018-05-01

The nocturnal nitrogen oxides, which include the nitrate radical (NO3), dinitrogen pentoxide (N2O5), and its uptake product on chloride containing aerosol, nitryl chloride (ClNO2), can have profound impacts on the lifetime of NOx ( = NO + NO2), radical budgets, and next-day photochemical ozone (O3) production, yet their abundances and chemistry are only sparsely constrained by ambient air measurements. Here, we present a measurement data set collected at a routine monitoring site near the Abbotsford International Airport (YXX) located approximately 30 km from the Pacific Ocean in the Lower Fraser Valley (LFV) on the west coast of British Columbia. Measurements were made from 20 July to 4 August 2012 and included mixing ratios of ClNO2, N2O5, NO, NO2, total odd nitrogen (NOy), O3, photolysis frequencies, and size distribution and composition of non-refractory submicron aerosol (PM1). At night, O3 was rapidly and often completely removed by dry deposition and by titration with NO of anthropogenic origin and unsaturated biogenic hydrocarbons in a shallow nocturnal inversion surface layer. The low nocturnal O3 mixing ratios and presence of strong chemical sinks for NO3 limited the extent of nocturnal nitrogen oxide chemistry at ground level. Consequently, mixing ratios of N2O5 and ClNO2 were low ( formation of ClNO2 in the nocturnal residual layer aloft than at the surface and the breakup of the nocturnal boundary layer structure in the morning. When quantifiable, production of ClNO2 from N2O5 was efficient and likely occurred predominantly on unquantified supermicron-sized or refractory sea-salt-derived aerosol. After sunrise, production of Cl radicals from photolysis of ClNO2 was negligible compared to production of OH from the reaction of O(1D) + H2O except for a short period after sunrise.

Seckel syndrome: an overdiagnosed syndrome.

OpenAIRE

Thompson, E; Pembrey, M

1985-01-01

Five children in whom a diagnosis of Seckel syndrome had previously been made were re-examined in the genetic unit. One child had classical Seckel syndrome, a sib pair had the features of the syndrome with less severe short stature, and in two children the diagnosis was not confirmed. Seckel syndrome is only one of a group of low birth weight microcephalic dwarfism and careful attention should be paid to fulfillment of the major criteria defined by Seckel before the diagnosis is made. There r...

Action inhibition in Tourette syndrome.

Science.gov (United States)

Ganos, Christos; Kühn, Simone; Kahl, Ursula; Schunke, Odette; Feldheim, Jan; Gerloff, Christian; Roessner, Veit; Bäumer, Tobias; Thomalla, Götz; Haggard, Patrick; Münchau, Alexander

2014-10-01

Tourette syndrome is a neuropsychiatric disorder characterized by tics. Tic generation is often linked to dysfunction of inhibitory brain networks. Some previous behavioral studies found deficiencies in inhibitory motor control in Tourette syndrome, but others suggested normal or even better-than-normal performance. Furthermore, neural correlates of action inhibition in these patients are poorly understood. We performed event-related functional magnetic resonance imaging during a stop-signal reaction-time task in 14 uncomplicated adult Tourette patients and 15 healthy controls. In patients, we correlated activations in stop-signal reaction-time task with their individual motor tic frequency. Task performance was similar in both groups. Activation of dorsal premotor cortex was stronger in the StopSuccess than in the Go condition in healthy controls. This pattern was reversed in Tourette patients. A significant positive correlation was present between motor tic frequency and activations in the supplementary motor area during StopSuccess versus Go in patients. Inhibitory brain networks differ between healthy controls and Tourette patients. In the latter the supplementary motor area is probably a key relay of inhibitory processes mediating both suppression of tics and inhibition of voluntary action. © 2014 International Parkinson and Movement Disorder Society.

Neuroticism and maladaptive coping in patients with functional somatic syndromes

DEFF Research Database (Denmark)

Pedersen, Heidi Frølund; Frostholm, Lisbeth; Jensen, Jens Søndergaard

2016-01-01

Objectives. The cognitive-behavioural model of functional somatic syndromes (FSS) proposes a multifactorial aetiology consisting of predisposing, precipitating and perpetuating factors. In this study, we sought to investigate three questions that can be drawn from this model: (1) Do patients...... with FSS show high levels of neuroticism? (2) Does neuroticism affect physical health and social functioning, either directly or indirectly through maladaptive coping? (3) Does more adaptive coping mediate the effect of cognitive-behavioural therapy (CBT) on outcome? Design. Secondary analysis....... Reduction in symptom catastrophizing during group CBT partially mediated its long-term effect. Conclusions. The results give support to a generic cognitive-behavioural model of FSS. Targeting symptom catastrophizing may be an essential component in CBT for patients with FSS, regardless of their specific...

Frontal Encephalocele Associated With a Bilateral Tessier Number Three Cleft and Fraser Syndrome.

Science.gov (United States)

Wood, Benjamin C; Yi, Sojung; Oh, Albert K; Rogers, Gary F; Magge, Suresh N

2015-09-01

Oblique craniofacial clefts and encephaloceles are each rare conditions, and only a few instances of these findings in combination have been described. Each pathologic entity presents a unique reconstructive challenge. The authors report the case of a male infant who presented with a large right frontoencephalocele and bilateral Tessier number 3 clefts. A review of the pertinent literature, including specific considerations related to perioperative management and technical aspects of the surgical approach, is discussed.

Multiple Cranial Neuropathies Without Limb Involvements: Guillain-Barre Syndrome Variant?

OpenAIRE

Yu, Ju Young; Jung, Han Young; Kim, Chang Hwan; Kim, Hyo Sang; Kim, Myeong Ok

2013-01-01

Acute multiple cranial neuropathies are considered as variant of Guillain-Barre syndrome, which are immune-mediated diseases triggered by various cases. It is a rare disease which is related to infectious, inflammatory or systemic diseases. According to previous case reports, those affected can exhibit almost bilateral facial nerve palsy, then followed by bulbar dysfunctions (cranial nerves IX and X) accompanied by limb weakness and walking difficulties due to motor and/or sensory dysfunction...

Herança da resistência à ferrugem da folha da aveia (Puccinia coronata f. sp. avenae Fraser & Led. em genótipos brasileiros de aveia branca Inheritance of oat leaf rust (Puccinia coronata f. sp. avenae Fraser & Led. resistance in white oat brazilian genotypes

Directory of Open Access Journals (Sweden)

Eduardo Alano Vieira

2006-02-01

Full Text Available A ferrugem da folha da aveia é a moléstia mais importante que ataca a cultura da aveia, ocorrendo em praticamente todas as áreas em que a aveia é cultivada. A forma mais indicada para o seu controle é a utilização de cultivares resistentes. Contudo, para que seja alcançada a resistência durável ao patógeno, é necessário que se conheça a genética da resistência à ferrugem da folha em aveia. O objetivo foi determinar a forma de herança da resistência a três isolados de Puccinia coronata f. sp. avenae Fraser & Led., (coletados no sul do Brasil em genótipos brasileiros de aveia branca. Para a determinação da herança da resistência a cada um dos três isolados, foram utilizadas populações F2 geradas por meio de cruzamentos artificiais, entre genótipos resistentes (R e suscetíveis (S e entre genótipos resistentes (R. Desta forma, foram utilizadas populações F2 dos cruzamentos artificiais entre: i URPEL 15 (R x UFRGS 7 (S, UPF 16 (R x UFRGS 7 (S e URPEL 15 (R x UPF 16 (R, para a determinação da herança da resistência ao isolado um (1; ii URPEL 15 (R x UFRGS 7 (S, UPF 18 (R x UFRGS 7 (S e URPEL 15 (R x UPF 18 (R, para a determinação da herança da resistência ao isolado dois (2; iii URPEL 15 (R x UFRGS 7 (S e URPEL 15 (R x UPF 18 (S, para a determinação da herança da resistência ao isolado três (3. Os resultados obtidos evidenciaram que o genótipo URPEL 15 apresenta genes dominantes de resistência aos três isolados de ferrugem da folha da aveia avaliados, que o cultivar UPF 16 apresenta um gene recessivo de resistência ao isolado 1 e o cultivar UPF 18 apresenta um gene recessivo de resistência ao isolado 2. E que os genes de resistência apresentados pelos genótipos URPEL 15, UPF 16 e UPF 18, segregam de forma independente.Oat crown rust is the most important disease for the oat crop, occurring in practically all the areas where oat is cultivated. The most indicated form of control for this disease is

Epigenomics, gestational programming and risk of metabolic syndrome.

Science.gov (United States)

Desai, M; Jellyman, J K; Ross, M G

2015-04-01

Epigenetic mechanisms are emerging as mediators linking early environmental exposures during pregnancy with programmed changes in gene expression that alter offspring growth and development. There is irrefutable evidence from human and animal studies that nutrient and environmental agent exposures (for example, endocrine disruptors) during pregnancy may affect fetal/newborn development resulting in offspring obesity and obesity-associated metabolic abnormalities (metabolic syndrome). This concept of 'gestational programming' is associated with alterations to the epigenome (nongenomic) rather than changes in the DNA sequence (genomic). Epigenetic alterations induced by suboptimal maternal nutrition/endocrine factors include DNA methylation, histone modifications, chromatin remodeling and/or regulatory feedback by microRNAs, all of which have the ability to modulate gene expression and promote the metabolic syndrome phenotype. Recent studies have shown tissue-specific transcriptome patterns and phenotypes not only in the exposed individual, but also in subsequent progeny. Notably, the transmission of gestational programming effects to subsequent generations occurs in the absence of continued adverse environmental exposures, thus propagating the cycle of obesity and metabolic syndrome. This phenomenon may be attributed to an extrinsic process resulting from the maternal phenotype and the associated nutrient alterations occurring within each pregnancy. In addition, epigenetic inheritance may occur through somatic cells or through the germ line involving both maternal and paternal lineages. Since epigenetic gene modifications may be reversible, understanding how epigenetic mechanisms contribute to transgenerational transmission of obesity and metabolic dysfunction is crucial for the development of novel early detection and prevention strategies for programmed metabolic syndrome. In this review we discuss the evidence in human and animal studies for the role of

Non-IgE-mediated gastrointestinal food allergies in children.

Science.gov (United States)

Caubet, Jean-Christoph; Szajewska, Hania; Shamir, Raanan; Nowak-Węgrzyn, Anna

2017-02-01

Non-IgE-mediated gastrointestinal food allergic disorders (non-IgE-GI-FA) including food protein-induced enterocolitis syndrome (FPIES), food protein-induced enteropathy (FPE), and food protein-induced allergic proctocolitis (FPIAP) are relatively uncommon in infants and young children, but are likely under-diagnosed. Non-IgE-GI-FA have a favorable prognosis, with majority resolving by age 3-5 years. Diagnosis relies on the recognition of symptoms pattern in FPIAP and FPIES and biopsy in FPE. Further studies are needed for a better understanding of the pathomechanism, which will lead eventually to the development of diagnostic tests and treatments. Limited evidence supports the role of food allergens in subsets of constipation, gastroesophageal reflux disease, irritable bowel syndrome, and colic. The immunologic pathomechanism is not fully understood and empiric prolonged avoidance of food allergens should be limited to minimize nutrient deficiency and feeding disorders/food aversions in infants. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The pathophysiological functions mediated by D-1 dopamine receptors

International Nuclear Information System (INIS)

Goldstein, M.; Kuga, S.; Meller, E.; SHimizu, Y.

1986-01-01

This chapter describes some behavioral responses which might be mediated by D 1 and D 2 DA receptors, and the authors discuss their clinical relevance. It was of considerable interest to determine whether a selective D 1 DA antagonist, such as SCH 23390, will induce catalepsy and whether this behavior is mediated by D 1 , or by both D 1 and D 2 DA receptors. Rats were used in the experiments. The authors examined whether the addition of the S 2 antagonist ketanserin affects the displacement of 3 H-Spi by SCH 23390. Induction of self-mutilating biting (SMB) behavior in monkeys with unilateral ventromedial tegmental (VMT) lesions by DA agonists and its prevention by DA antagonists is examined. The authors also discuss the possible relationships between abnormal guanine nucleotide metabolism and dopaminergic neuronal function through the implications in LeschNyhan syndrome and in some mental disorders

Reliability and responsiveness of a graduated tuning fork in immune mediated polyneuropathies. The Inflammatory Neuropathy Cause and Treatment (INCAT) Group

NARCIS (Netherlands)

I.S.J. Merkies (Ingemar); P.I.M. Schmitz (Paul); F.G.A. van der Meché (Frans); P.A. van Doorn (Pieter)

2000-01-01

textabstractThe interobserver and intraobserver reliability of the Rydel-Seiffer (RS) graduated tuning fork was evaluated in 113 patients with a clinically stable immune mediated polyneuropathy (83 patients who had had Guillain-Barre syndrome (GBS) in the past, 22 with

A mouse model for Costello syndrome reveals an Ang II–mediated hypertensive condition

Science.gov (United States)

Schuhmacher, Alberto J.; Guerra, Carmen; Sauzeau, Vincent; Cañamero, Marta; Bustelo, Xosé R.; Barbacid, Mariano

2008-01-01

Germline activation of H-RAS oncogenes is the primary cause of Costello syndrome (CS), a neuro-cardio-facio-cutaneous developmental syndrome. Here we describe the generation of a mouse model of CS by introduction of an oncogenic Gly12Val mutation in the mouse H-Ras locus using homologous recombination in ES cells. Germline expression of the endogenous H-RasG12V oncogene, even in homozygosis, resulted in hyperplasia of the mammary gland. However, development of tumors in these mice was rare. H-RasG12V mutant mice closely phenocopied some of the abnormalities observed in patients with CS, including facial dysmorphia and cardiomyopathies. These mice also displayed alterations in the homeostasis of the cardiovascular system, including development of systemic hypertension, extensive vascular remodeling, and fibrosis in both the heart and the kidneys. This phenotype was age dependent and was a consequence of the abnormal upregulation of the renin–Ang II system. Treatment with captopril, an inhibitor of Ang II biosynthesis, prevented development of the hypertension condition, vascular remodeling, and heart and kidney fibrosis. In addition, it partially alleviated the observed cardiomyopathies. These mice should help in elucidating the etiology of CS symptoms, identifying additional defects, and evaluating potential therapeutic strategies. PMID:18483625

Superior Mesenteric Artery Syndrome or Wilkie Syndrome

International Nuclear Information System (INIS)

Castano Llano, Rodrigo; Chams Anturi, Abraham; Arango Vargas, Paula

2009-01-01

We described three cases of superior mesenteric artery (SMA) syndrome, also known as Wilkie's syndrome, chronic duodenal ileus, or cast syndrome. This syndrome occurs when the third portion of the duodenum is compressed between the SMA and the aorta. The major risk factors for development of SMA syndrome are rapid weight loss and surgical correction of spinal deformities. The clinical presentation of SMA syndrome is variable and nonspecific, including nausea, vomiting, abdominal pain, and weight loss. The diagnosis is based on endoscopic, radiographic and tomographic findings of duodenal compression by the SMA. The treatment of SMA syndrome is aimed at the precipitating factor, which usually is related to weight loss. Therefore, conservative therapy with nutritional supplementation is the initial approach, and surgery is reserved for those who do not respond to nutritional therapy.

Markers of atherosclerosis in patients with Cushing's syndrome: a meta-analysis of literature studies.

Science.gov (United States)

Lupoli, Roberta; Ambrosino, Pasquale; Tortora, Anna; Barba, Livia; Lupoli, Gelsy Arianna; Di Minno, Matteo Nicola Dario

2017-05-01

Several studies reported an increased cardiovascular (CV) risk in Cushing's syndrome (CS). We performed a meta-analysis on the impact of CS on major markers of atherosclerosis. Studies on intima-media thickness (IMT), carotid plaques prevalence, and flow-mediated dilation (FMD) in CS patients and controls were searched in the PubMed, Web of Science, Scopus, and EMBASE. Differences between cases and controls were expressed as mean difference (MD) with 95% confidence intervals (95%CI) for continuous variables, and as Odds Ratio (OR) with 95%CI for dichotomous variables. Fourteen studies (332 CS, 462 controls) were included. Compared with controls, CS patients showed higher IMT (MD: 0.20 mm; 95% CI: 0.12, 0.28; p Cushing's syndrome (CS). In the present meta-analysis we demonstrated that CS is associated with an increased intima-media thickness, higher prevalence of carotid plaques, and lower flow-mediated dilation as compared with controls. These data consistently suggest the need for a strict monitoring of early signs of subclinical atherosclerosis in CS patients.

Colorectal Cancer Risk in Patients With Lynch Syndrome and Inflammatory Bowel Disease.

Science.gov (United States)

Derikx, Lauranne A A P; Smits, Lisa J T; van Vliet, Shannon; Dekker, Evelien; Aalfs, Cora M; van Kouwen, Mariëtte C A; Nagengast, Fokko M; Nagtegaal, Iris D; Hoogerbrugge, Nicoline; Hoentjen, Frank

2017-03-01

Lynch syndrome and inflammatory bowel diseases (IBD) are associated with an increased risk of colorectal cancer (CRC). However, it is not clear whether the risk of CRC is even higher for patients with a combination of Lynch syndrome and IBD. We investigated the risk for CRC in this subgroup by establishing a Lynch syndrome cohort from the Radboud University Medical Center (Nijmegen, The Netherlands) and the Academic Medical Center (Amsterdam, The Netherlands). Patients with heterozygous germline mutations in MLH1, MSH2 (and EPCAM deletion-mediated MSH2 methylation), MSH6, or PMS2 who were tested and/or treated from 1998 through 2014 were included. Patients who developed IBD were identified by linkage of this cohort to the Dutch nationwide Pathology Registry (PALGA). Subsequently, we compared the risk of CRC between Lynch syndrome patients with IBD and without IBD. Of 1046 patients with Lynch syndrome, 15 developed IBD (1.4%). Patients with Lynch syndrome and IBD were significantly younger (median age, 38.0 y) than patients with Lynch syndrome without IBD (median age, 52.0 y; P = .001). Nevertheless, a similar proportion of patients in each group developed CRC: 4 of the 15 patients (26.7%) with Lynch syndrome and IBD compared with 311 of the 1031 patients (30.2%) with Lynch syndrome without IBD. Patients with Lynch syndrome and IBD developed CRC at a younger age (median age, 36.0 y) than patients with Lynch syndrome without IBD (median age, 46.0 y; P = .045). However, the cumulative incidence of CRC was similar between groups (P = .121). All patients with Lynch syndrome and IBD who developed CRC had ulcerative colitis, producing a higher cumulative incidence of CRC for this IBD subgroup (P Lynch syndrome and IBD develop CRC risk at a younger age than patients without IBD; patients with ulcerative colitis are at especially high risk. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Endothelial function and insulin resistance in polycystic ovary syndrome: the effects of medical therapy.

Science.gov (United States)

Teede, Helena J; Meyer, Caroline; Hutchison, Samantha K; Zoungas, Sophia; McGrath, Barry P; Moran, Lisa J

2010-01-01

To assess the interaction between insulin resistance and endothelial function and the optimal treatment strategy addressing cardiovascular risk in polycystic ovary syndrome. Randomized controlled trial. Controlled clinical study. Overweight age- and body mass index-matched women with polycystic ovary syndrome. Six months metformin (1 g two times per day, n = 36) or oral contraceptive pill (OCP) (35 microg ethinyl E(2)-2 mg cytoproterone acetate, n = 30). Fasting and oral glucose tolerance test glucose and insulin levels, endothelial function (flow-mediated dilation, asymmetric dimethylarginine, plasminogen activator inhibitor-1, von Willebrand factor), inflammatory markers (high-sensitivity C-reactive protein), lipids, and hyperandrogenism. The OCP increased levels of glucose and insulin on oral glucose tolerance test, high-sensitivity C-reactive protein, triglycerides, and sex-hormone binding globulin and decreased levels of low-density lipoprotein cholesterol and T. Metformin decreased levels of fasting insulin, oral glucose tolerance test insulin, high-density lipoprotein cholesterol, and high-sensitivity C-reactive protein. Flow-mediated dilation increased only with metformin (+2.2% +/- 4.8%), whereas asymmetric dimethylarginine decreased equivalently for OCP and metformin (-0.3 +/- 0.1 vs. -0.1 +/- 0.1 mmol/L). Greater decreases in plasminogen activator inhibitor-1 occurred for the OCP than for metformin (-1.8 +/- 1.6 vs. -0.7 +/- 1.7 U/mL). In polycystic ovary syndrome, metformin improves insulin resistance, inflammatory markers, and endothelial function. The OCP worsens insulin resistance and glucose homeostasis, inflammatory markers, and triglycerides and has neutral or positive endothelial effects. The effect of the OCP on cardiovascular risk in polycystic ovary syndrome is unclear. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Beals Syndrome

Science.gov (United States)

... the syndrome. How does Beals syndrome compare with Marfan syndrome? People with Beals syndrome have many of the ... bone) and aortic enlargement problems as people with Marfan syndrome, and treatments for these problems are the same. ...

Burnout and health among critical care professionals: The mediational role of resilience.

Science.gov (United States)

Arrogante, Oscar; Aparicio-Zaldivar, Eva

2017-10-01

To analyse the mediational role of resilience in relationships between burnout and health in critical care professionals; to determine relationships among resilience level, three burnout dimensions, and physical/mental health; and to establish demographic differences in psychological variables evaluated. Cross-sectional study. A total of 52 critical care professionals, mainly nurses, were recruited from an intensive care unit of Madrid (Spain). All participants were assessed with the questionnaires 10-item Connor-Davidson Resilience Scale, Maslach Burnout Inventory-Human Services Survey, and Short Form-12 Health Survey. No demographic differences were found. Three burnout dimensions were negatively associated with mental health and resilience. Mediational analyses revealed resilience mediated 1) the relationships between emotional exhaustion and depersonalisation with mental health (partial mediations) and 2) the relationship between personal accomplishment and mental health (total mediation). Resilience minimises and buffers the impact of negative outcomes of workplace stress on mental health of critical care professionals. As a result, resilience prevents the occurrence of burnout syndrome. Resilience improves not only their mental health, but also their ability to practice effectively. It is therefore imperative to develop resilience programs for critical care nurses in nursing schools, universities and health centres. Copyright © 2017 Elsevier Ltd. All rights reserved.

Immune mediated disorders in women with a fragile X expansion and FXTAS.

Science.gov (United States)

Jalnapurkar, Isha; Rafika, Nuva; Tassone, Flora; Hagerman, Randi

2015-01-01

Premutation alleles in fragile X mental retardation 1 (FMR1) can cause the late-onset neurodegenerative disorder, fragile X-associated tremor ataxia syndrome (FXTAS) and/or the fragile X-associated primary ovarian insufficiency in approximately 20% of heterozygotes. Heterozygotes of the FMR1 premutation have a higher incidence of immune mediated disorders such as autoimmune thyroid disorder, especially when accompanied by FXTAS motor signs. We describe the time course of symptoms of immune mediated disorders and the subsequent development of FXTAS in four women with an FMR1 CGG expansion, including three with the premutation and one with a gray zone expansion. These patients developed an immune mediated disorder followed by neurological symptoms that become consistent with FXTAS. In all patients we observed a pattern involving an initial appearance of disease symptoms-often after a period of heightened stress (depression, anxiety, divorce, general surgery) followed by the onset of tremor and/or ataxia. Immune mediated diseases are associated with the manifestations of FXTAS temporally, although further studies are needed to clarify this association. If a cause and effect relationship can be established, treatment of pre-existing immune mediated disorders may benefit patients with pathogenic FMR1 mutations. © 2014 Wiley Periodicals, Inc.

Ciliopathy proteins regulate paracrine signaling by modulating proteasomal degradation of mediators

Science.gov (United States)

Liu, Yangfan P.; Tsai, I-Chun; Morleo, Manuela; Oh, Edwin C.; Leitch, Carmen C.; Massa, Filomena; Lee, Byung-Hoon; Parker, David S.; Finley, Daniel; Zaghloul, Norann A.; Franco, Brunella; Katsanis, Nicholas

2014-01-01

Cilia are critical mediators of paracrine signaling; however, it is unknown whether proteins that contribute to ciliopathies converge on multiple paracrine pathways through a common mechanism. Here, we show that loss of cilopathy-associated proteins Bardet-Biedl syndrome 4 (BBS4) or oral-facial-digital syndrome 1 (OFD1) results in the accumulation of signaling mediators normally targeted for proteasomal degradation. In WT cells, several BBS proteins and OFD1 interacted with proteasomal subunits, and loss of either BBS4 or OFD1 led to depletion of multiple subunits from the centrosomal proteasome. Furthermore, overexpression of proteasomal regulatory components or treatment with proteasomal activators sulforaphane (SFN) and mevalonolactone (MVA) ameliorated signaling defects in cells lacking BBS1, BBS4, and OFD1, in morphant zebrafish embryos, and in induced neurons from Ofd1-deficient mice. Finally, we tested the hypothesis that other proteasome-dependent pathways not known to be associated with ciliopathies are defective in the absence of ciliopathy proteins. We found that loss of BBS1, BBS4, or OFD1 led to decreased NF-κB activity and concomitant IκBβ accumulation and that these defects were ameliorated with SFN treatment. Taken together, our data indicate that basal body proteasomal regulation governs paracrine signaling pathways and suggest that augmenting proteasomal function might benefit ciliopathy patients. PMID:24691443

Pediatric Tourette Syndrome: A Tic Disorder with a Tricky Presentation

OpenAIRE

Qurratul Warsi; Caroline Kirby; Mirza Beg

2017-01-01

Dysphagia is a condition in which disruption of the swallowing process interferes with a patient's ability to eat. This may result in coughing or choking while swallowing, food sticking in the throat, or globus sensation. Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease with a varied clinical spectrum of symptoms including dysphagia. Tourette syndrome (TS) is an inherited neurological disorder that manifests itself as a series of motor and vocal tics and may include orophar...

[A psychological content of social phobia syndrome].

Science.gov (United States)

Sagalakova, O A; Truevtsev, D V; Stoyanova, I Ya

2017-01-01

To perform a psychological analysis of social phobia syndrome. The subject area of research is the structure of mental activity and behavior in social activity. The study included 32 patients with symptoms of social phobia (ICD-10 F40.1) and 29 healthy people (controls). A complex of psychological methods (questionnaires; pathopsychological experiment) was used. Early maladaptive schemes and a tendency to mental rigidity can be a premorbid basis of the syndrome. Primary violation is in organizational target component by type of distortion of goal-setting regulation. The mechanism is a reduction in the mediation of emotions and behavior (an influence of emotions on the process of activity, excess metacognitive anxiety control leading to multi-task and exhaustion of resources of voluntary activity). Fear of negative evaluation leads to the fact that a wide class of situations is interpreted as threatening. Secondary are changes in the system of goals and motives of activity (technically performing components of social behavior act as a focus of attention, along with the target, the target replaces the suprasituational meaning). Along with a strong motivation to succeed, the motive of avoiding failure is formed, which leads to a decrease in social activity. Tertiary symptoms of syndrome dynamics (ways to cope with maladaptation) are destructive forms of decompensation (substance abuse, learned helplessness and hopelessness, suicidal behavior, etc.), repeatedly reinforcing the primary and secondary disturbances.

Supercritical fluid-mediated liposomes containing cyclosporin A for the treatment of dry eye syndrome in a rabbit model: comparative study with the conventional cyclosporin A emulsion.

Science.gov (United States)

Karn, Pankaj Ranjan; Kim, Hyun Do; Kang, Han; Sun, Bo Kyung; Jin, Su-Eon; Hwang, Sung-Joo

2014-01-01

The objective of this study was to compare the efficacy of cyclosporin (CsA)-encapsulated liposomes with the commercially available CsA emulsion (Restasis) for the treatment of dry eye syndrome in rabbits. Liposomes containing CsA were prepared by the supercritical fluid (SCF) method consisted of phosphatidylcholine from soybean (SCF-S100) and egg lecithins (SCF-EPCS). An in vitro permeation study was carried out using artificial cellulose membrane in Franz diffusion cells. Dry eye syndrome was induced in male albino rabbits and further subdivided into untreated, Restasis-treated, EPCS, and S100-treated groups. Tear formation in the dry-eye-induced rabbits was evaluated using the Schirmer tear test. All formulations were also evaluated by ocular irritation tests using the Draize eye and winking methods with the determination of CsA concentration in rabbit tears. After the treatment, the Schirmer tear test value significantly improved in EPCS-treated (P=0.005) and S100-treated (P=0.018) groups compared to the Restasis-treated group. The AUC₀₋₂₄ h for rabbit's tear film after the administration of SCF-S100 was 32.75±9.21 μg·h/mg which was significantly higher than that of 24.59±8.69 μg·h/mg reported with Restasis. Liposomal CsA formulations used in this study showed lower irritation in rabbit eyes compared with Restasis. These results demonstrate that the novel SCF-mediated liposomal CsA promises a significant improvement in overcoming the challenges associated with the treatment of dry eyes.

Breast cancer resistance protein (Bcrp1/Abcg2) is expressed in the harderian gland and mediates transport of conjugated protoporphyrin IX

NARCIS (Netherlands)

Jonker, Johan W.; Musters, Sandra; Vlaming, Maria L. H.; Plosch, Torsten; Gooijert, Karin E. R.; Hillebrand, Michel J.; Rosing, Hilde; Beijnen, Jos H.; Verkade, Henkjan J.; Schinkel, Alfred H.

Proper regulation of intracellular levels of protoporphyrin IX (PPIX), the direct precursor of heme, is important for cell survival. A deficiency in ferrochelatase, which mediates the final step in heme biosynthesis, leads to erythropoietic protoporphyria (EPP), a photosensitivity syndrome caused by

Effects of Food Additives on Immune Cells As Contributors to Body Weight Gain and Immune-Mediated Metabolic Dysregulation

Directory of Open Access Journals (Sweden)

Heitor A. Paula Neto

2017-11-01

Full Text Available Food additives are compounds used in order to improve food palatability, texture, and shelf life. Despite a significant effort to assure safety of use, toxicological analysis of these substances, generally, rely on their direct toxicity to target organs (liver and kidney or their genotoxic effects. Much less attention is paid to the effects of these compounds on cells of the immune system. This is of relevance given that metabolic dysregulation and obesity have a strong immune-mediated component. Obese individuals present a state of chronic low-grade inflammation that contributes to the establishment of insulin resistance and other metabolic abnormalities known as the metabolic syndrome. Obesity and metabolic syndrome are currently recognized as worldwide epidemics that pose a profound socioeconomic impact and represent a concern to public health. Cells of the immune system contribute to both the maintenance of “lean homeostasis” and the metabolic dysregulation observed in obese individuals. Although much attention has been drawn in the past decades to obesity and metabolic syndrome as a result of ingesting highly processed food containing large amounts of fat and simple sugars, mounting evidence suggest that food additives may also be important contributors to metabolic derangement. Herein, we review pieces of evidence from the literature showing that food additives have relevant effects on cells of the immune system that could contribute to immune-mediated metabolic dysregulation. Considering their potential to predispose individuals to develop obesity and metabolic syndrome, their use should be taken with caution or maybe revisited.

Serotonin syndrome

Science.gov (United States)

Hyperserotonemia; Serotonergic syndrome; Serotonin toxicity; SSRI - serotonin syndrome; MAO - serotonin syndrome ... brain area. For example, you can develop this syndrome if you take migraine medicines called triptans together ...

The restaurant syndromes.

Science.gov (United States)

Settipane, G A

1987-01-01

The Restaurant syndromes can be caused by five major factors: food allergens, sulfites, monosodium glutamate (MSG), tartrazine, and scombroidosis (and other seafood poisoning). A history of atopy and ingestion of known food allergens such as peanuts, egg, fish, and walnuts, together with positive results of skin tests or RAST to these foods, will favor a diagnosis of food allergy. Allergic reactions to peanuts have produced fatalities in minutes through an IgE mediated reaction. An extremely rapid onset (minutes) of symptoms consisting of flushing, bronchospasm and hypotension is consistent with a sulfite reaction. Burning, pressure, and tightness or numbness in the face, neck, and upper chest following ingestion of Chinese food favors a diagnosis of adverse reaction to MSG. Also, development of late onset bronchospasm (up to 14 hours) may be related to MSG reactions. Bronchospasm and urticaria in a patient with a history of aspirin intolerance suggests tartrazine sensitivity. If everyone ingesting a fish meal develops flushing, urticaria, pruritus, gastrointestinal complaints, or bronchospasm, this implies scombroidosis, ciguatera, or other seafood poisoning. Finally, severe headache or hypertension can result from ingestion of naturally occurring amines, such as tyramine (cheese, red wine) and phenylethylamine (chocolate). A double-blind oral challenge test may be the only way of confirming the diagnosis for most of the etiological factors of the Restaurant syndromes. The treatment of choice for acute reaction is epinephrine followed by antihistamine. Proper labeling and avoidance of these ingredients in sensitive individuals are the best preventive measures.

Dreng med diarré og svær dehydrering havde food protein-induced enterocolitis syndrome

DEFF Research Database (Denmark)

Henriksen, Pernille; Børresen, Malene Landbo; Dahl, Kathrin

2016-01-01

Food protein-induced enterocolitis syndrome (FPIES) is a rare non-IgE mediated condition. Symptoms of acute FPIES include vomiting, diarrhoea and dehydration. Symptoms are often misread as acute abdomen or sepsis. The condition can be fatal. There are no biomarkers for FPIES, and skin prick test...... confronted with the very ill, dehydrated infant....

[Association Budd Chiari syndrome, antiphospholipid syndrome and Grave's disease].

Science.gov (United States)

Mouelhi, Leila; Chaieb, Mouna; Debbeche, Radhouane; Salem, Mohamed; Sfar, Imene; Trabelsi, Sinda; Gorgi, Yosr; Najjar, Taoufik

2009-02-01

Antiphospholipid syndrome is revealed by Budd Chiari syndrome in 5% of the cases. Antiphospholipid syndrome is characterized by venous or arterial thrombosis, foetal loss and positivity of antiphospholipid antibodies, namely lupus anticoagulant, anticardiolipin antibodies and anti-beta2-glycoprotein I. Anticardiolipin antibodies was reported in auto-immune thyroid disorders, particularly in Grave's disease. Antiphospholipid syndrome associated to Grave's disease was reported in only three cases. To describe a case report of association of Grave's disease and antiphospholipid syndrome. We report the first case of Grave's disease associated with antiphospholipid syndrome, revealed by Budd Chiari syndrome. Our observation is particular by the fact that it is about a patient presenting a Grave's disease associated with antiphospholipid syndrome revealed by Budd Chiari syndrome. This triple association has never been reported in literature. Although association between antiphospholipid syndrome and Grave's disease was previously described, further studies evaluating the coexistence of these two affections in the same patient would be useful.

Duane Syndrome

Science.gov (United States)

... Frequently Asked Questions Español Condiciones Chinese Conditions Duane Syndrome En Español Read in Chinese What is Duane Syndrome? Duane syndrome, also called Duane retraction syndrome (DRS), ...

Modeling the behavior of Listeria monocytogenes during enrichment in half Fraser broth; impact of pooling and the duration of enrichment on the detection of L. monocytogenes in food.

Science.gov (United States)

Augustin, Jean-Christophe; Kalmokoff, Martin; Ells, Timothy; Favret, Sandra; Desreumaux, Jennifer; Decourseulles Brasseur, Emilie; Gnanou Besse, Nathalie

2016-12-01

A stochastic model describing the growth of Listeria monocytogenes during enrichment in half Fraser was developed for the purpose of estimating the effects of modifications to the first enrichment step of the EN ISO 11290-1 detection method. Information pertaining to the variability of growth rates, physiological state of the cell, and the behavior of individual cells contaminating the food were obtained from previously published studies. We used this model to investigate the impact of pooling enrichment broths (wet pooling) on the performance of the standard method. For validation of the model, the numbers of L. monocytogenes occurring in 88 naturally contaminated foods following pre-enrichment were compared to model-simulated microbial counts. The model was then used to perform simulations representative of the natural contamination observed for smoked salmon in the European baseline survey of 2010-2011. The model-estimated L. monocytogenes levels following individual enrichment or following the pooling of five broths where only one would be contaminated were compared. The model indicated a 10% loss of method sensitivity resulting from wet pooling. The model also predicted a 5% decrease in the sensitivity of the method when the duration of the enrichment was reduced from 24 to 22 h. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cooking birch pollen-related food: divergent consequences for IgE- and T cell-mediated reactivity in vitro and in vivo

NARCIS (Netherlands)

Bohle, Barbara; Zwölfer, Bettina; Heratizadeh, Annice; Jahn-Schmid, Beatrice; Antonia, Yuliya Dall; Alter, Mareike; Keller, Walter; Zuidmeer, Laurian; van Ree, Ronald; Werfel, Thomas; Ebner, Christof

2006-01-01

BACKGROUND: The major birch pollen allergen Bet v 1 cross-reacts with homologous food allergens, resulting in IgE-mediated oral allergy syndromes (OASs). To avoid this food, allergy allergologists and guidebooks advise patients to consume birch pollen-related foods after heating. OBJECTIVE: We

Wells syndrome and its relationship to Churg-Strauss syndrome.

Science.gov (United States)

Ratzinger, Gudrun; Zankl, Julia; Zelger, Bernhard

2013-08-01

  Wells syndrome has been described as an inflammatory disorder based on typical clinical appearance combined with the histopathological presence of eosinophilic infiltrates and flame figures in the absence of vasculitis. Churg-Strauss syndrome, on the other hand, is primarily a diffuse, necrotizing vasculitis but is also typically displaying eosinophils and flame figures. Despite several parallels, the present understanding of these two diseases excludes any pathogenetic relationship.   We describe the clinical course and histopathological appearance of three patients who had initially been diagnosed with Wells syndrome that developed into Churg-Strauss syndrome during the course of their disease.   The clinical presentation of all three patients led to the diagnosis of Wells syndrome by independent specialists. Histopathology showed an eosinophilic infiltrate and flame figures next to features of leukocytoclastic vasculitis. Detailed examination revealed asthma bronchiale and additional symptoms indicating Churg-Strauss syndrome. The initial diagnosis of Wells syndrome had to be revised to Churg-Strauss syndrome.   We conclude that Wells syndrome could be the starting point of a pathogenetic process that might reach its maximum in Churg-Strauss syndrome. As a clinical consequence, patients with Wells syndrome should be evaluated and followed for Churg-Strauss syndrome. © 2013 The International Society of Dermatology.

Goldenhar Syndrome in Association with Duane Syndrome

Directory of Open Access Journals (Sweden)

U D Shrestha

2012-03-01

Full Text Available Goldenhar syndrome (GHS is also known as Oculo-Auriculo-Vertebral (OAV syndrome or Branchial arch syndrome. Duane retraction syndrome (DRS is a congenital disorder of ocular motility characterized by limited abduction, adduction or both. It is unilateral in 80% of cases. The important and interesting part of this eight months old child is presence of GHS with DRS. She has bilateral invol-vement, which is seen in only 5-8% of GHS, as compared to high incidence of unilateral involve-ment. This child also had refractive error of + 6.00/ - 1.5 * 180. At four year of age her vision with glass was 6/9. Children with GHS and DRS should have early eye examination done to treat the problem of refractive error. Keywords: Duane retraction syndrome; goldenhar syndrome, refractive error.

Spread of white-nose syndrome on a network regulated by geography and climate.

Science.gov (United States)

Maher, Sean P; Kramer, Andrew M; Pulliam, J Tomlin; Zokan, Marcus A; Bowden, Sarah E; Barton, Heather D; Magori, Krisztian; Drake, John M

2012-01-01

Wildlife and plant diseases can reduce biodiversity, disrupt ecosystem services and threaten human health. Emerging pathogens have displayed a variety of spatial spread patterns due to differences in host ecology, including diffusive spread from an epicentre (West Nile virus), jump dispersal on a network (foot-and-mouth disease), or a combination of these (Sudden oak death). White-nose syndrome is a highly pathogenic infectious disease of bats currently spreading across North America. Understanding how bat ecology influences this spread is crucial to management of infected and vulnerable populations. Here we show that white-nose syndrome spread is not diffusive but rather mediated by patchily distributed habitat and large-scale gradients in winter climate. Simulations predict rapid expansion and infection of most counties with caves in the contiguous United States by winter 2105-2106. Our findings show the unique pattern of white-nose syndrome spread corresponds to ecological traits of the host and suggest hypotheses for transmission mechanisms acting at the local scale.

CHALLENGES IN TREATMENT OF RENAL GRAFT ACUTE ANTIBODY-MEDIATED REJECTION

Directory of Open Access Journals (Sweden)

A. I. Sushkov

2016-01-01

Full Text Available Diagnostic criteria and treatment protocols for acute antibody-mediated rejection (AMR of kidney allograft remain controversial. We report the case of early severe AMR after primary kidney transplantation. The graft removal was considered in the absence of treatment efficacy and in the presence of systemic infl ammatory response syndrome. However, at surgery the graft looked normal and it was not removed. The repeated treatment course (plasmapheresis, antithymocyte globulin, intravenous immunoglobulin and rituximab was effective. The patient has good and stable graft function in 1 year after transplantation. 

Non-IgE-mediated gastrointestinal food allergies.

Science.gov (United States)

Biermé, Priscille; Nowak-Wegrzyn, Anna; Caubet, Jean-Christoph

2017-12-01

We focus on recent advances regarding the epidemiology, physiopathology, diagnosis and managements of non-IgE-mediated gastrointestinal food allergies (non-IgE-GI-FAs), particularly food protein-induced enterocolitis syndrome (FPIES). The first international FPIES diagnostic and management guidelines have been recently published. Although FPIES largely remains a diagnosis of exclusion, it may be more prevalent than previously thought. Ondansetron has emerged as a major tool for the treatment of FPIES acute reactions. Recent data also suggest an important role for innate immune cells in FPIES pathogenesis. Despite major advances in the diagnosis and management of non-IgE-GI-FAs, particularly FPIES, the lack of specific diagnostic tests and biomarkers to guide clinical management remains challenging.

Core Self-Evaluation and Burnout among Nurses: The Mediating Role of Coping Styles

OpenAIRE

Li, Xiaofei; Guan, Lili; Chang, Hui; Zhang, Bo

2014-01-01

OBJECTIVES: This study aimed to determine the potential association between core self-evaluation and the burnout syndrome among Chinese nurses, and the mediating role of coping styles in this relationship. METHODS: A cross-sectional survey was conducted in Shenyang, China, from May to July, 2013. A questionnaire which consisted of the Maslach Burnout Inventory-General Survey (MBI-GS), the Core Self-Evaluation Scale (CSE), and the Simplified Coping Style Questionnaire (CSQ), was completed by a...

Fanconi syndrome

Science.gov (United States)

De Toni-Fanconi syndrome ... Fanconi syndrome can be caused by faulty genes, or it may result later in life due to kidney damage. Sometimes the cause of Fanconi syndrome is unknown. Common causes of Fanconi syndrome in ...

OCULO-CEREBRO-RENAL SYNDROME (LOWE'S SYNDROME)

Institute of Scientific and Technical Information of China (English)

无

1991-01-01

Oculo-cerebro-renal syndrome (Lowe's syndrome) is characterized by mental and motor retardation, cataract, glaucoma and renal abnormalities. It is an X-linked recessive metabolic disease. Two brothers suffering from Lowe's syndrome are reported. Their mother with lenticular opacities and peculiar facial appearance is in concordance with the obligate carrier. The ocular changes and heridity are discussed.

Neurofibromatosis-Noonan syndrome or LEOPARD Syndrome? A clinical dilemma.

Directory of Open Access Journals (Sweden)

Tullu M

2000-04-01

Full Text Available Neurofibromatosis (NF, Noonan syndrome (NS, and LEOPARD syndrome are all autosomal dominant conditions, each being a distinct clinical entity by itself. Rarely, one encounters cases with features of NF and NS and is termed as the ′Neurofibromatosis-Noonan syndrome′ (NF-NS. The authors report a clinical dilemma with major clinical features of the NF-NS syndrome and LEOPARD syndrome co-existing in the same patient. Also, features of Noonan syndrome and LEOPARD syndrome are compared with the case reported.

Measurement error, time lag, unmeasured confounding: Considerations for longitudinal estimation of the effect of a mediator in randomised clinical trials.

Science.gov (United States)

Goldsmith, K A; Chalder, T; White, P D; Sharpe, M; Pickles, A

2018-06-01

Clinical trials are expensive and time-consuming and so should also be used to study how treatments work, allowing for the evaluation of theoretical treatment models and refinement and improvement of treatments. These treatment processes can be studied using mediation analysis. Randomised treatment makes some of the assumptions of mediation models plausible, but the mediator-outcome relationship could remain subject to bias. In addition, mediation is assumed to be a temporally ordered longitudinal process, but estimation in most mediation studies to date has been cross-sectional and unable to explore this assumption. This study used longitudinal structural equation modelling of mediator and outcome measurements from the PACE trial of rehabilitative treatments for chronic fatigue syndrome (ISRCTN 54285094) to address these issues. In particular, autoregressive and simplex models were used to study measurement error in the mediator, different time lags in the mediator-outcome relationship, unmeasured confounding of the mediator and outcome, and the assumption of a constant mediator-outcome relationship over time. Results showed that allowing for measurement error and unmeasured confounding were important. Contemporaneous rather than lagged mediator-outcome effects were more consistent with the data, possibly due to the wide spacing of measurements. Assuming a constant mediator-outcome relationship over time increased precision.

Faulty DNA-polymerase δ/ε-mediated excision-repair in response to gamma-radiation or ultraviolet-light in P53-deficient fibroblast strains from affected members of a cancer-prone family with Li-Fraumeni syndrome

International Nuclear Information System (INIS)

Mirzayans, R.; Enns, L.; Dietrich, K.; Barley, R.D.C.; Paterson, M.C.; Alberta Univ., Edmonton, AB; Alberta Univ., Edmonton, AB

1996-01-01

Dermal fibroblast strains cultured from affected members of a cancer-prone family with Li-Fraumeni syndrome (LFS) harbor a point mutation in one allele of the p53 tumor suppressor gene, resulting in loss of normal p53-deficient strains to carry out the long-patch mode of excision repair, mediated by DNA polymerases delta and epsilon, after exposure to Co-60 gamma radiation or far ultraviolet (UV) (chiefly 254 mm) light. Repair was monitored by incubation of the irradiated cultures in the presence of aphidicolin (ape) or 1-beta-D-arabinofuranosylcytosine (araC), each a specific inhibitor of long-patch repair, followed by measurement of drug-induced DNA strand breaks (reflecting non-ligated strand incision events) by alkaline surcrose velocity sedimentation. The LFS strains displayed deficient repair capacity in response to both gamma rays and UV light. The repair anomaly in UV-irradiated LFS cultures was manifested not only in the overall genome, but also in the transcriptionally active, preferentially repaired c-myc gene. Using autoradiography we also assessed unscheduled DNA synthesis (UDS) after UV irradiation and found this conventional measure of repair replication to be deficient in LFS strains. Moreover, both ape and araC decreased the level of UV-induced UDS by similar to 75% in normal cells, but each had only a marginal effect on LFS cells. We further demonstrated that the LFS strains are impaired in the recovery of both RNA and replicative DNA syntheses after UV treatment, two molecular anomalies of the DNA repair deficiency disorders xeroderma pigmentosum and Cockayne's syndrome. Together these results imply a critical role for wild-type p53 protein in DNA polymerase delta/epsilon-mediated excision repair, both the mechanism operating on the entire genome and that acting on expressed genes. (Author)

Sweet Syndrome: A Review and Update.

Science.gov (United States)

Villarreal-Villarreal, C D; Ocampo-Candiani, J; Villarreal-Martínez, A

2016-06-01

Sweet syndrome is the most representative entity of febrile neutrophilic dermatoses. It typically presents in patients with pirexya, neutrophilia, painful tender erytomatous papules, nodules and plaques often distributed asymmetrically. Frequent sites include the face, neck and upper extremities. Affected sites show a characteristical neutrophilic infiltrate in the upper dermis. Its etiology remains elucidated, but it seems that can be mediated by a hypersensitivity reaction in which cytokines, followed by infiltration of neutrophils, may be involved. Systemic corticosteroids are the first-line of treatment in most cases. We present a concise review of the pathogenesis, classification, diagnosis and treatment update of this entity. Copyright © 2015 AEDV. Published by Elsevier España, S.L.U. All rights reserved.

Prospective investigation of FOXP1 syndrome.

Science.gov (United States)

Siper, Paige M; De Rubeis, Silvia; Trelles, Maria Del Pilar; Durkin, Allison; Di Marino, Daniele; Muratet, François; Frank, Yitzchak; Lozano, Reymundo; Eichler, Evan E; Kelly, Morgan; Beighley, Jennifer; Gerdts, Jennifer; Wallace, Arianne S; Mefford, Heather C; Bernier, Raphael A; Kolevzon, Alexander; Buxbaum, Joseph D

2017-01-01

Haploinsufficiency of the forkhead-box protein P1 ( FOXP1 ) gene leads to a neurodevelopmental disorder termed FOXP1 syndrome. Previous studies in individuals carrying FOXP1 mutations and deletions have described the presence of autism spectrum disorder (ASD) traits, intellectual disability, language impairment, and psychiatric features. The goal of the present study was to comprehensively characterize the genetic and clinical spectrum of FOXP1 syndrome. This is the first study to prospectively examine the genotype-phenotype relationship in multiple individuals with FOXP1 syndrome, using a battery of standardized clinical assessments. Genetic and clinical data was obtained and analyzed from nine children and adolescents between the ages of 5-17 with mutations in FOXP1 . Phenotypic characterization included gold standard ASD testing and norm-referenced measures of cognition, adaptive behavior, language, motor, and visual-motor integration skills. In addition, psychiatric, medical, neurological, and dysmorphology examinations were completed by a multidisciplinary team of clinicians. A comprehensive review of reported cases was also performed. All missense and in-frame mutations were mapped onto the three-dimensional structure of DNA-bound FOXP1. We have identified nine de novo mutations, including three frameshift, one nonsense, one mutation in an essential splice site resulting in frameshift and insertion of a premature stop codon, three missense, and one in-frame deletion. Reviewing prior literature, we found seven instances of recurrent mutations and another 34 private mutations. The majority of pathogenic missense and in-frame mutations, including all four missense mutations in our cohort, lie in the DNA-binding domain. Through structural analyses, we show that the mutations perturb amino acids necessary for binding to the DNA or interfere with the domain swapping that mediates FOXP1 dimerization. Individuals with FOXP1 syndrome presented with delays in early

A Case Report of Eosinophilic Esophagitis Accompanying Hypereosinophilic Syndrome

Directory of Open Access Journals (Sweden)

Mahreema Jawairia

2012-01-01

Full Text Available Hypereosinophilic syndrome is a blood disorder characterized by the overproduction of eosinophils in the bone marrow with persistent peripheral eosinophilia, associated with organ damage by the release of eosinophilic mediators. Although HES can involve multiple organ systems, GI tract involvement is very rare. Few cases of HES presenting with gastritis or enteritis have been reported worldwide. To date, HES presenting with esophagus involvement has only been reported once. Here, we present a 39-year-old Hispanic female patient with history of HES presenting with complaints of dysphagia and generalized pruritus.

LEOPARD syndrome is not linked to the Marfan syndrome and the Watson syndrome loci

Energy Technology Data Exchange (ETDEWEB)

Rass-Rothchild, A.: Abeliovitch, D.; Kornstein, A. [Tel Aviv Univ. (Israel)]|[Hebrew Univ., Jerusalem (Israel)

1994-09-01

The acronym LEOPARD stands for a syndromic association of Lentigines, Eletrocardiographic changes, Ocular hypertelorism, Pulmonic stenosis, Abnormal genitalia, Retardation of growth and sensorineural Deafness. Inheritance is autosomal dominant with high penetrance and variable expressivity. In 1990 Torok et al. reported on the association of LEOPARD and Marfan syndrome. In addition a clinical similarity (cardiac and cutaneous involvement) exists with the Watson syndrome (neurofibromatosis and pulmonic stenosis) which is linked to the marker D17S33 on chromosome 17. We studied possible linkage of LEOPARD syndrome to the Marfan syndrome locus on chromosome 15 (D15S1, MF13, and (TAAAA)n repeats) and to the NF-1 locus on chromosome 17 in a family with 9 cases of LEOPARD syndrome. Close linkage between LEOPARD syndrome and both the Marfan locus on chromosome 15 and the NF-1 locus on chromosome 17 was excluded (lod score <-2.0 through {theta} = 0.1).

A Transcriptomic Signature of the Hypothalamic Response to Fasting and BDNF Deficiency in Prader-Willi Syndrome

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Elena G. Bochukova

2018-03-01

Full Text Available Summary: Transcriptional analysis of brain tissue from people with molecularly defined causes of obesity may highlight disease mechanisms and therapeutic targets. We performed RNA sequencing of hypothalamus from individuals with Prader-Willi syndrome (PWS, a genetic obesity syndrome characterized by severe hyperphagia. We found that upregulated genes overlap with the transcriptome of mouse Agrp neurons that signal hunger, while downregulated genes overlap with the expression profile of Pomc neurons activated by feeding. Downregulated genes are expressed mainly in neuronal cells and contribute to neurogenesis, neurotransmitter release, and synaptic plasticity, while upregulated, predominantly microglial genes are involved in inflammatory responses. This transcriptional signature may be mediated by reduced brain-derived neurotrophic factor expression. Additionally, we implicate disruption of alternative splicing as a potential molecular mechanism underlying neuronal dysfunction in PWS. Transcriptomic analysis of the human hypothalamus may identify neural mechanisms involved in energy homeostasis and potential therapeutic targets for weight loss. : Prader-Willi syndrome (PWS is a genetic obesity syndrome. Bochukova et al. report gene expression changes in the hypothalamus of people with PWS that support neurodegeneration and neuroinflammation as key processes involved in this condition. Keywords: hypothalamus, Prader-Willi syndrome, BDNF, Agrp, obesity, SNORD116

Chronic graft versus host disease and nephrotic syndrome

Directory of Open Access Journals (Sweden)

Samia Barbouch

2014-01-01

Full Text Available Disturbed kidney function is a common complication after bone marrow transplantation. Recently, attention has been given to immune-mediated glomerular damage related to graft versus host disease (GVHD. We describe a 19-year-old woman who developed membranous glomerulonephritis after bone marrow transplantation (BMT. Six months later, she developed soft palate, skin and liver lesions considered to be chronic GVHD. Fifteen months after undergoing BMT, this patient presented with nephrotic syndrome. A renal biopsy showed mem-branous glomerulonephritis associated with a focal segmental glomerulosclerosis. She was started on corticosteroid treatment with good outcome.

[Mediator effect of resilience between burnout and health in nursing staff].

Science.gov (United States)

Arrogante, Óscar

2014-01-01

To determine the relationships between 3 burnout dimensions (Emotional Exhaustion, Depersonalization, and Reduced Personal Accomplishment), health (physical and mental health), and resilience, as well as to analyse the mediator role of resilience in relationships between burnout and health in a sample of Nursing staff. A correlational and cross-sectional study with probabilistic sampling was conducted on a sample of 194 Nursing staff of University Hospital of Fuenlabrada (Madrid), and composed of nurses (n=133) and nursing assistants (n=61). MBI-HSS (burnout syndrome), SF-12v1 (physical and mental components of health), 10-Item CD-RISC (resilience), and sociodemographic variables. Correlational analyses showed that mental health was negatively related with 3 burnout dimensions and positively with resilience. Furthermore, physical health was only negatively related with Emotional Exhaustion, and positively with resilience. Mediational analyses revealed that resilience mediated, on one hand, the relationship between Emotional Exhaustion and Depersonalization with mental health (partial mediation) and, on the other hand, the relationship between Reduced Personal Accomplishment and mental health (total mediation). Resilience is not only important to improve the mental health of Nursing staff, but also to buffer and minimize the negative consequences of the occupational stress to which they are at risk, with its most adverse result being signs of burnout. Therefore, resilience training should be promoted to improve nursing clinical practice. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Deep brain stimulation for Tourette’s syndrome: the case for targeting the thalamic centromedian-parafascicular complex.

Directory of Open Access Journals (Sweden)

Paola Testini

2016-11-01

Full Text Available Tourette syndrome is a neurologic condition characterized by both motor and phonic tics and is typically associated with psychiatric comorbidities, including obsessive-compulsive disorder/behavior and attention deficit hyperactivity disorder and can be psychologically and socially debilitating. It is considered a disorder of the cortico-striato-thalamo-cortical circuitry, as suggested by pathophysiology studies and therapeutic options. Among these, deep brain stimulation of the centromedian-parafascicular nuclear complex (CM-Pf of the thalamus is emerging as a valuable treatment modality for patients affected by severe, treatment resistant TS. Here we review the most recent experimental evidence for the pivotal role of CM-Pf in the pathophysiology of Tourette syndrome, discuss potential mechanisms of action that may mediate the effects of CM-Pf deep brain stimulation in Tourette syndrome, and summarize its clinical efficacy.

Low levels of nitryl chloride at ground level: nocturnal nitrogen oxides in the Lower Fraser Valley of British Columbia

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H. D. Osthoff

2018-05-01

Full Text Available The nocturnal nitrogen oxides, which include the nitrate radical (NO3, dinitrogen pentoxide (N2O5, and its uptake product on chloride containing aerosol, nitryl chloride (ClNO2, can have profound impacts on the lifetime of NOx ( =  NO + NO2, radical budgets, and next-day photochemical ozone (O3 production, yet their abundances and chemistry are only sparsely constrained by ambient air measurements.Here, we present a measurement data set collected at a routine monitoring site near the Abbotsford International Airport (YXX located approximately 30 km from the Pacific Ocean in the Lower Fraser Valley (LFV on the west coast of British Columbia. Measurements were made from 20 July to 4 August 2012 and included mixing ratios of ClNO2, N2O5, NO, NO2, total odd nitrogen (NOy, O3, photolysis frequencies, and size distribution and composition of non-refractory submicron aerosol (PM1.At night, O3 was rapidly and often completely removed by dry deposition and by titration with NO of anthropogenic origin and unsaturated biogenic hydrocarbons in a shallow nocturnal inversion surface layer. The low nocturnal O3 mixing ratios and presence of strong chemical sinks for NO3 limited the extent of nocturnal nitrogen oxide chemistry at ground level. Consequently, mixing ratios of N2O5 and ClNO2 were low ( <  30 and  <  100 parts-per-trillion by volume (pptv and median nocturnal peak values of 7.8 and 7.9 pptv, respectively. Mixing ratios of ClNO2 frequently peaked 1–2 h after sunrise rationalized by more efficient formation of ClNO2 in the nocturnal residual layer aloft than at the surface and the breakup of the nocturnal boundary layer structure in the morning. When quantifiable, production of ClNO2 from N2O5 was efficient and likely occurred predominantly on unquantified supermicron-sized or refractory sea-salt-derived aerosol. After sunrise, production of Cl radicals from photolysis of ClNO2 was negligible compared to production of OH

Metabolic syndrome and polycystic ovary syndrome: an intriguing overlapping.

Science.gov (United States)

Caserta, Donatella; Adducchio, Gloria; Picchia, Simona; Ralli, Eleonora; Matteucci, Eleonora; Moscarini, Massimo

2014-06-01

Metabolic syndrome is an increasing pathology in adults and in children, due to a parallel rise of obesity. Sedentary lifestyle, food habits, cultural influences and also a genetic predisposition can cause dyslipidemia, hypertension, abdominal obesity and insulin resistance which are the two main features of metabolic syndrome. Polycystic ovary syndrome (PCOS) is a condition directly associated with obesity, insulin resistance (HOMA index) and metabolic syndrome, and it is very interesting for its relationship and overlap with the metabolic syndrome. The relationship between the two syndromes is mutual: PCOS women have a higher prevalence of metabolic syndrome and also women with metabolic syndrome commonly present the reproductive/endocrine trait of PCOS. Prevention and treatment of metabolic syndrome and PCOS are similar for various aspects. It is necessary to treat excess adiposity and insulin resistance, with the overall goals of preventing cardiovascular disease and type 2 diabetes and improving reproductive failure in young women with PCOS. First of all, lifestyle changes, then pharmacological therapy, bariatric surgery and laparoscopic ovarian surgery represent the pillars for PCOS treatment.

Animal model of neuropathic tachycardia syndrome

Science.gov (United States)

Carson, R. P.; Appalsamy, M.; Diedrich, A.; Davis, T. L.; Robertson, D.

2001-01-01

Clinically relevant autonomic dysfunction can result from either complete or partial loss of sympathetic outflow to effector organs. Reported animal models of autonomic neuropathy have aimed to achieve complete lesions of sympathetic nerves, but incomplete lesions might be more relevant to certain clinical entities. We hypothesized that loss of sympathetic innervation would result in a predicted decrease in arterial pressure and a compensatory increase in heart rate. Increased heart rate due to loss of sympathetic innervation is seemingly paradoxical, but it provides a mechanistic explanation for clinical autonomic syndromes such as neuropathic postural tachycardia syndrome. Partially dysautonomic animals were generated by selectively lesioning postganglionic sympathetic neurons with 150 mg/kg 6-hydroxydopamine hydrobromide in male Sprague-Dawley rats. Blood pressure and heart rate were monitored using radiotelemetry. Systolic blood pressure decreased within hours postlesion (Delta>20 mm Hg). Within 4 days postlesion, heart rate rose and remained elevated above control levels. The severity of the lesion was determined functionally and pharmacologically by spectral analysis and responsiveness to tyramine. Low-frequency spectral power of systolic blood pressure was reduced postlesion and correlated with the diminished tyramine responsiveness (r=0.9572, P=0.0053). The tachycardia was abolished by treatment with the beta-antagonist propranolol, demonstrating that it was mediated by catecholamines acting on cardiac beta-receptors. Partial lesions of the autonomic nervous system have been hypothesized to underlie many disorders, including neuropathic postural tachycardia syndrome. This animal model may help us better understand the pathophysiology of autonomic dysfunction and lead to development of therapeutic interventions.

Barber-Say syndrome and Ablepharon-Macrostomia syndrome: An overview

NARCIS (Netherlands)

de Maria, Beatrice; Mazzanti, Laura; Roche, Nathalie; Hennekam, Raoul C.

2016-01-01

Barber-Say syndrome (BSS) and Ablepharon-Macrostomia syndrome (AMS) are congenital malformation syndromes caused by heterozygous mutations in TWIST2. Here we provide a critical review of all patients published with these syndromes. We excluded several earlier reports due to misdiagnosis or

Autosomal dominant syndrome resembling Coffin-Siris syndrome.

Science.gov (United States)

Flynn, Maureen A; Milunsky, Jeff M

2006-06-15

Coffin-Siris syndrome is a multiple congenital anomaly/mental retardation syndrome with phenotypic variability [OMIM 135900]. The diagnosis is based solely on clinical findings, as there is currently no molecular, biochemical, or cytogenetic analysis available to confirm a diagnosis. Although typically described as an autosomal recessive disorder, autosomal dominant inheritance has also been infrequently reported. We describe a mother and her two daughters who all have features that resemble Coffin-Siris syndrome. However, this is not a completely convincing diagnosis given that hypertelorism is not a feature of Coffin-Siris syndrome and the family is relatively mildly affected. Yet, this family provides further evidence of an autosomal dominant mode of inheritance for a likely variant of Coffin-Siris syndrome (at least in some families). In addition, Sibling 1 had premature thelarche. She is the second reported individual within the spectrum of Coffin-Siris syndrome to have premature thelarche, indicating that it may be a rare clinical feature. Copyright 2006 Wiley-Liss, Inc.

Tourette syndrome: a disorder of the social decision-making network.

Science.gov (United States)

Albin, Roger L

2018-02-01

Tourette syndrome is a common neurodevelopmental disorder defined by characteristic involuntary movements, tics, with both motor and phonic components. Tourette syndrome is usually conceptualized as a basal ganglia disorder, with an emphasis on striatal dysfunction. While considerable evidence is consistent with these concepts, imaging data suggest diffuse functional and structural abnormalities in Tourette syndrome brain. Tourette syndrome exhibits features that are difficult to explain solely based on basal ganglia circuit dysfunctions. These features include the natural history of tic expression, with typical onset of tics around ages 5 to 7 years and exacerbation during the peri-pubertal years, marked sex disparity with higher male prevalence, and the characteristic distribution of tics. The latter are usually repetitive, somewhat stereotyped involuntary eye, facial and head movements, and phonations. A major functional role of eye, face, and head movements is social signalling. Prior work in social neuroscience identified a phylogenetically conserved network of sexually dimorphic subcortical nuclei, the Social Behaviour Network, mediating many social behaviours. Social behaviour network function is modulated developmentally by gonadal steroids and social behaviour network outputs are stereotyped sex and species specific behaviours. In 2011 O'Connell and Hofmann proposed that the social behaviour network interdigitates with the basal ganglia to form a greater network, the social decision-making network. The social decision-making network may have two functionally complementary limbs: the basal ganglia component responsible for evaluation of socially relevant stimuli and actions with the social behaviour network component responsible for the performance of social acts. Social decision-making network dysfunction can explain major features of the neurobiology of Tourette syndrome. Tourette syndrome may be a disorder of social communication resulting from

West syndrome in a patient with Schinzel-Giedion syndrome.

Science.gov (United States)

Miyake, Fuyu; Kuroda, Yukiko; Naruto, Takuya; Ohashi, Ikuko; Takano, Kyoko; Kurosawa, Kenji

2015-06-01

Schinzel-Giedion syndrome is a rare recognizable malformation syndrome defined by characteristic facial features, profound developmental delay, severe growth failure, and multiple congenital anomalies. The causative gene of Schinzel-Giedion syndrome, SETBP1, has been identified, but limited cases have been confirmed by molecular analysis. We present a 9-month-old girl affected by West syndrome with Schinzel-Giedion syndrome. Congenital severe hydronephrosis, typical facial features, and multiple anomalies suggested a clinical diagnosis of Schinzel-Giedion syndrome. Hypsarrhythmia occurred at 7 months of age and was temporarily controlled by adrenocorticotropic hormone (ACTH) therapy during 5 weeks. SETBP1 mutational analysis showed the presence of a recurrent mutation, p.Ile871Thr. The implications in management of Schinzel-Giedion syndrome are discussed. © The Author(s) 2014.

Mediation Analysis with Multiple Mediators

OpenAIRE

VanderWeele, T.J.; Vansteelandt, S.

2014-01-01

Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects throu...

Cushing syndrome

Science.gov (United States)

Hypercortisolism; Cortisol excess; Glucocorticoid excess - Cushing syndrome ... The most common cause of Cushing syndrome is taking too much ... Cushing syndrome . Prednisone, dexamethasone, and prednisolone ...

Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein

Science.gov (United States)

Millet, Jean Kaoru; Whittaker, Gary R.

2014-01-01

Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly identified betacoronavirus causing high morbidity and mortality in humans. The coronavirus spike (S) protein is the main determinant of viral entry, and although it was previously shown that MERS-CoV S can be activated by various proteases, the details of the mechanisms of proteolytic activation of fusion are still incompletely characterized. Here, we have uncovered distinctive characteristics of MERS-CoV S. We identify, by bioinformatics and peptide cleavage assays, two cleavage sites for furin, a ubiquitously expressed protease, which are located at the S1/S2 interface and at the S2′ position of the S protein. We show that although the S1/S2 site is proteolytically processed by furin during protein biosynthesis, the S2′ site is cleaved upon viral entry. MERS-CoV pseudovirion infection was shown to be enhanced by elevated levels of furin expression, and entry could be decreased by furin siRNA silencing. Enhanced furin activity appeared to partially override the low pH-dependent nature of MERS-CoV entry. Inhibition of furin activity was shown to decrease MERS-CoV S-mediated entry, as well as infection by the virus. Overall, we show that MERS-CoV has evolved an unusual two-step furin activation for fusion, suggestive of a role during the process of emergence into the human population. The ability of MERS-CoV to use furin in this manner, along with other proteases, may explain the polytropic nature of the virus. PMID:25288733

Russell-Silver syndrome

Science.gov (United States)

Silver-Russell syndrome; Silver syndrome; RSS; Russell-Silver syndrome ... One in 10 children with this syndrome has a problem involving chromosome 7. In other people with the syndrome, it may affect chromosome 11. Most of the time, it ...

Psoriasis Uncovered – Comorbid Conditions with Special Reference to Metabolic Syndrome

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Belliappa Pemmanda Raju

2014-01-01

Full Text Available Introduction: Psoriasis is a chronic immune-inflammatory-mediated disease affecting approximately 1-3% of the population worldwide. All around the world, there is growing evidence of the association between psoriasis and comorbidities, especially metabolic syndrome which increases the risk of cardiovascular disease. Co-morbidities are likely linked to underlying chronic inflammatory nature of psoriasis. Aim: The objectives of our study were to determine the prevalence of diabetes, lipid abnormalities, and cardiovascular risk factors in patients with plaque psoriasis, and also to investigate metabolic syndrome associated with plaque psoriasis. Material and Methods: One hundred and twenty patients with psoriasis vulgaris diagnosed clinically and histopathologically were recruited. A detailed history and examination was recorded for all study subjects, including the age and gender of the patients, extent of psoriasis, duration, and age at onset. Metabolic syndrome was diagnosed in the presence of three or more criteria of abdominal obesity, blood pressure >130/85 mmHg, fasting blood glucose ≥100 mg/dl, hypertriglyceridemia >150 mg/dl, and low HDL cholesterol (<40 mg/dl for males, <50mg/dl for females. Results: Prevalence of various comorbidities was: central obesity (58.3%, hypertension (46.79%, dyslipidaemia (43.3%, diabetes mellitus (26.7%, metabolic syndrome (25%, ischaemic heart disease (5% and stroke (2.4%. Prevalence of metabolic syndrome was more in patients who had longer mean disease duration of psoriasis. Conclusions: The perception of psoriasis being merely ‘skin deep’ has to change among clinicians. Active screening for these cardiovascular comorbidities in all psoriasis patients is highly recommended..

Gross Motor Skills and Cardiometabolic Risk in Children: A Mediation Analysis.

Science.gov (United States)

Burns, Ryan D; Brusseau, Timothy A; Fu, You; Hannon, James C

2017-04-01

The purpose of this study was to examine the linear relationship between gross motor skills and cardiometabolic risk, with aerobic fitness as a mediator variable, in low-income children from the United States. Participants were a convenience sample of 224 children (mean ± SD age = 9.1 ± 1.1 yr; 129 girls and 95 boys) recruited from five low-income elementary schools from the Mountain West Region of the United States. Gross motor skills were assessed using the Test for Gross Motor Development, 3rd Edition. Gross motor skills were analyzed using a locomotor skill, a ball skill, and a total gross motor skill score. Aerobic fitness was assessed using the Progressive Aerobic Cardiovascular Endurance Run that was administered during physical education class. A continuous and age- and sex-adjusted metabolic syndrome score (MetS) was calculated from health and blood marker measurements collected in a fasted state before school hours. Total effects, average direct effects, and indirect effects (average causal mediation effect) were calculated using a bootstrap mediation analysis method via a linear regression algorithm. The average causal mediation effect of gross locomotor skills on MetS scores, using aerobic fitness as the mediator variable, was statistically significant (β = -0.055, 95% confidence interval = -0.097 to -0.021, P = 0.003). The model explained approximately 17.5% of the total variance in MetS with approximately 43.7% of the relationship between locomotor skills and MetS mediated through aerobic fitness. Ball skills did not significantly relate with cardiometabolic risk. There is a significant relationship between gross locomotor skills and cardiometabolic risk that is partially mediated through aerobic fitness in a sample of low-income children from the United States.

[Cockett's syndrome, May-Thurner syndrome, or iliac vein compression syndrome].

Science.gov (United States)

Gil Martín, A R; Carreras Aja, M; Arrieta Ardieta, I; Labayen Azparren, I

2014-01-01

Iliac vein compression syndrome (also known as May-Thurner syndrome or Cockett's syndrome) is a rare clinical entity in which the left common iliac vein is compressed when it passes between the right common iliac artery and the spine. The sustained compression and trauma caused by the pulsatile force of the artery on the vein damage the intima and lead to the formation of membranes or bands in the vascular lumen that hinder or obstruct the flow of blood in the vein, favoring thrombus formation. The current treatment strategy of choice is endovascular vein patch angioplasty and stenting with the aim of improving the caliber of the lumen and enabling normal venous drainage. We present two cases of May-Thurner syndrome and review the clinical and CT findings. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.

LEOPARD syndrome

Science.gov (United States)

Multiple lentigines syndrome; Noonan syndrome with multiple lentigines ... Genetics Home Reference -- ghr.nlm.nih.gov/condition/noonan-syndrome-with-multiple-lentigines National Organization for Rare Disorders -- ...

Dravets syndrom

DEFF Research Database (Denmark)

Hansen, Lars Kjaersgård; Rasmussen, Niels Henrik; Ousager, Lilian Bomme

2010-01-01

Dravet syndrome is an epileptic syndrome of infancy and early childhood. Most cases of Dravet syndrome seem to be due to a genetic defect causing the sodium channel to malfunction. We describe the main features of the syndrome. This epilepsy is medically intractable, but we call attention...... to the fact that some medications are of benefit and some could exacerbate the condition. Early recognition of the syndrome including by genetic testing could possibly improve outcome and reduce the need for other specialized investigations. Udgivelsesdato: 2010-Feb-22...

Polycystic Ovary Syndrome, Insulin Resistance, and Obesity: Navigating the Pathophysiologic Labyrinth

Science.gov (United States)

Rojas, Joselyn; Chávez, Mervin; Olivar, Luis; Rojas, Milagros; Morillo, Jessenia; Mejías, José; Calvo, María; Bermúdez, Valmore

2014-01-01

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR), and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome. PMID:25763405

Polycystic Ovary Syndrome, Insulin Resistance, and Obesity: Navigating the Pathophysiologic Labyrinth

Directory of Open Access Journals (Sweden)

Joselyn Rojas

2014-01-01

Full Text Available Polycystic ovary syndrome (PCOS is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR, and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome.

Polycystic ovary syndrome, insulin resistance, and obesity: navigating the pathophysiologic labyrinth.

Science.gov (United States)

Rojas, Joselyn; Chávez, Mervin; Olivar, Luis; Rojas, Milagros; Morillo, Jessenia; Mejías, José; Calvo, María; Bermúdez, Valmore

2014-01-01

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR), and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome.

A Chinese patient with pusher syndrome and unilateral spatial neglect syndrome.

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Chen, Xiao-Wei; Lin, Cheng-He; Zheng, Hua; Lin, Zhen-Lan

2014-07-01

To observe clinical manifestations, behavioral characteristics, and effects of rehabilitation on a patient with pusher syndrome and unilateral spatial neglect caused by right thalamic hemorrhage. Assessment of pusher syndrome was made by the Scale for Contraversive pushing (SCP), and unilateral spatial neglect syndrome was diagnosed using line cancellation, letter and star cancellation, line bisection tests and copy and continuation of graphic sequence test. Behavioral therapy, occupational therapy, reading training and traditional Chinese medicine methods were adopted for treatment of pusher syndrome and unilateral spatial neglect. The patient showed typical pusher syndrome and unilateral spatial neglect symptoms. The pusher syndrome and unilateral spatial neglect symptoms were significantly improved following rehabilitation treatments. Pusher syndrome and unilateral spatial neglect syndrome occurred simultaneously after right thalamic hemorrhage. Early rehabilitation therapy can reduce the symptoms of pusher syndrome and unilateral spatial neglect syndrome and improve motor function.

Aarskog syndrome

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Aarskog disease; Aarskog-Scott syndrome; AAS; Faciodigitogenital syndrome; Gaciogenital dysplasia ... Aarskog syndrome is a genetic disorder that is linked to the X chromosome. It affects mainly males, but females ...

Ectrodactyly-ectodermal dysplasia clefting syndrome (EEC syndrome).

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Koul, Monika; Dwivedi, Rahul; Upadhyay, Vinod

2014-01-01

Ectrodactyly-ectodermal dysplasia- clefting syndrome (also k/a. split hand- split foot malformation /split hand-split foot ectodermal dysplasia- cleft syndrome/ectodermal dysplasia cleft lip/cleft palate syndrome) a rare form of ectodermal dysplasia, is an autosomal dominant disorder inherited as a genetic trait and characterized by a triad of (i) ectrodactyly, (ii) ectodermal dysplasia and, (iii) & facial clefts.

Ectrodactyly-ectodermal dysplasia clefting syndrome (EEC syndrome)

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Koul, Monika; Dwivedi, Rahul; Upadhyay, Vinod

2014-01-01

Ectrodactyly-ectodermal dysplasia- clefting syndrome (also k/a. split hand- split foot malformation /split hand-split foot ectodermal dysplasia- cleft syndrome/ectodermal dysplasia cleft lip/cleft palate syndrome) a rare form of ectodermal dysplasia, is an autosomal dominant disorder inherited as a genetic trait and characterized by a triad of (i) ectrodactyly, (ii) ectodermal dysplasia and, (iii) & facial clefts.

Modulation of LINE-1 and Alu/SVA Retrotransposition by Aicardi-Goutières Syndrome-Related SAMHD1

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Ke Zhao

2013-09-01

Full Text Available Long interspersed elements 1 (LINE-1 occupy at least 17% of the human genome and are its only active autonomous retrotransposons. However, the host factors that regulate LINE-1 retrotransposition are not fully understood. Here, we demonstrate that the Aicardi-Goutières syndrome gene product SAMHD1, recently revealed to be an inhibitor of HIV/simian immunodeficiency virus (SIV infectivity and neutralized by the viral Vpx protein, is also a potent regulator of LINE-1 and LINE-1-mediated Alu/SVA retrotransposition. We also found that mutant SAMHD1s of Aicardi-Goutières syndrome patients are defective in LINE-1 inhibition. Several domains of SAMHD1 are critical for LINE-1 regulation. SAMHD1 inhibits LINE-1 retrotransposition in dividing cells. An enzymatic active site mutant SAMHD1 maintained substantial anti-LINE-1 activity. SAMHD1 inhibits ORF2p-mediated LINE-1 reverse transcription in isolated LINE-1 ribonucleoproteins by reducing ORF2p level. Thus, SAMHD1 may be a cellular regulator of LINE-1 activity that is conserved in mammals.

Cushing's Syndrome

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宗, 友厚; 伊藤, 勇; 諏訪, 哲也; 武田, 純; MUNE, Tomoatsu

2003-01-01

Sixteen cases of verified Cushing's syndrome, and twelve cases of probable Cushing's syndrome were reviewed and data on them were compared with various reports on Cushing's syndrome in the literature.

Can preeclampsia be considered a renal compartment syndrome? A hypothesis and analysis of the literature.

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Reuter, David G; Law, Yuk; Levy, Wayne C; Seslar, Stephen P; Zierler, R Eugene; Ferguson, Mark; Chattra, James; McQuinn, Tim; Liu, Lenna L; Terry, Mark; Coffey, Patricia S; Dimer, Jane A; Hanevold, Coral; Flynn, Joseph T; Stapleton, F Bruder

2016-11-01

The morbidity and mortality associated with preeclampsia is staggering. The physiology of the Page kidney, a condition in which increased intrarenal pressure causes hypertension, appears to provide a unifying framework to explain the complex pathophysiology. Page kidney hypertension is renin-mediated acutely and ischemia-mediated chronically. Renal venous outflow obstruction also causes a Page kidney phenomenon, providing a hypothesis for the increased vulnerability of a subset of women who have what we are hypothesizing is a "renal compartment syndrome" due to inadequate ipsilateral collateral renal venous circulation consistent with well-known variation in normal venous anatomy. Dynamic changes in renal venous anatomy and physiology in pregnancy appear to correlate with disease onset, severity, and recurrence. Since maternal recumbent position is well known to affect renal perfusion and since chronic outflow obstruction makes women vulnerable to the ischemic/inflammatory sequelae, heightened awareness of renal compartment syndrome physiology is critical. The anatomic and physiologic insights provide immediate strategies to predict and prevent preeclampsia with straightforward, low-cost interventions that make renewed global advocacy for pregnant women a realistic goal. Copyright © 2016 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Pattern Recognition of the Multiple Sclerosis Syndrome

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Stewart, Renee; Healey, Kathleen M.

2017-01-01

During recent decades, the autoimmune disease neuromyelitis optica spectrum disorder (NMOSD), once broadly classified under the umbrella of multiple sclerosis (MS), has been extended to include autoimmune inflammatory conditions of the central nervous system (CNS), which are now diagnosable with serum serological tests. These antibody-mediated inflammatory diseases of the CNS share a clinical presentation to MS. A number of practical learning points emerge in this review, which is geared toward the pattern recognition of optic neuritis, transverse myelitis, brainstem/cerebellar and hemispheric tumefactive demyelinating lesion (TDL)-associated MS, aquaporin-4-antibody and myelin oligodendrocyte glycoprotein (MOG)-antibody NMOSD, overlap syndrome, and some yet-to-be-defined/classified demyelinating disease, all unspecifically labeled under MS syndrome. The goal of this review is to increase clinicians’ awareness of the clinical nuances of the autoimmune conditions for MS and NMSOD, and to highlight highly suggestive patterns of clinical, paraclinical or imaging presentations in order to improve differentiation. With overlay in clinical manifestations between MS and NMOSD, magnetic resonance imaging (MRI) of the brain, orbits and spinal cord, serology, and most importantly, high index of suspicion based on pattern recognition, will help lead to the final diagnosis. PMID:29064441

Polycystic ovary syndrome and metabolic syndrome.

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Ali, Aus Tariq

2015-08-01

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder, where the main clinical features include menstrual irregularities, sub-fertility, hyperandrogenism, and hirsutism. The prevalence of PCOS depends on ethnicity, environmental and genetic factors, as well as the criteria used to define it. On the other hand, metabolic syndrome is a constellation of metabolic disorders which include mainly abdominal obesity, insulin resistance, impaired glucose metabolism, hypertension and dyslipidaemia. These associated disorders directly increase the risk of Type 2 diabetes mellitus (DMT2), coronary heart disease (CHD), cardiovascular diseases (CVD) and endometrial cancer. Many patients with PCOS have features of metabolic syndrome such as visceral obesity, hyperinsulinaemia and insulin resistance. These place patients with PCOS under high risk of developing cardiovascular disease (CVD), Type 2 diabetes (DMT2) and gynecological cancer, in particular, endometrial cancer. Metabolic syndrome is also increased in infertile women with PCOS. The aim of this review is to provide clear and up to date information about PCOS and its relationship with metabolic syndrome, and the possible interaction between different metabolic disorders.

Mediation analysis with time varying exposures and mediators.

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VanderWeele, Tyler J; Tchetgen Tchetgen, Eric J

2017-06-01

In this paper we consider causal mediation analysis when exposures and mediators vary over time. We give non-parametric identification results, discuss parametric implementation, and also provide a weighting approach to direct and indirect effects based on combining the results of two marginal structural models. We also discuss how our results give rise to a causal interpretation of the effect estimates produced from longitudinal structural equation models. When there are time-varying confounders affected by prior exposure and mediator, natural direct and indirect effects are not identified. However, we define a randomized interventional analogue of natural direct and indirect effects that are identified in this setting. The formula that identifies these effects we refer to as the "mediational g-formula." When there is no mediation, the mediational g-formula reduces to Robins' regular g-formula for longitudinal data. When there are no time-varying confounders affected by prior exposure and mediator values, then the mediational g-formula reduces to a longitudinal version of Pearl's mediation formula. However, the mediational g-formula itself can accommodate both mediation and time-varying confounders and constitutes a general approach to mediation analysis with time-varying exposures and mediators.

Management of a Parturient with Mast Cell Activation Syndrome: An Anesthesiologist’s Experience

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Sangeeta Kumaraswami

2018-01-01

Full Text Available Mast cell activation syndrome (MCAS is a disorder in which patients experience symptoms and signs attributable to inappropriate mast cell activation and mediator release. Multiorgan involvement in patients can result in significant morbidity and possible mortality. Limited literature exists regarding anesthetic management of patients with MCAS. We report a case of vaginal delivery with neuraxial labor analgesia in a parturient with this condition and highlight the importance of multidisciplinary planning for uneventful outcomes. Stress can trigger life-threatening symptoms, and counseling is important to allay patients’ fears. Optimum medical control, adequate premedication, avoidance of triggers, and preparedness to treat serious mediator effects are key. We review MCAS and discuss anesthetic considerations for patients with this mast cell disorder.

Atorvastatin reduces malondialdehyde concentrations in patients with polycystic ovary syndrome.

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Sathyapalan, Thozhukat; Shepherd, John; Coady, Anne-Marie; Kilpatrick, Eric S; Atkin, Stephen L

2012-11-01

It has been shown that there is an increase in oxidative stress in polycystic ovary syndrome (PCOS). Statins are considered to have a pleiotropic effect other than their lipid-lowering effect. These effects may be mediated in part by reducing oxidative stress. This randomized, double-blind, placebo-controlled study was conducted to assess the effect of atorvastatin on serum malondialdehyde (MDA) concentrations as a marker of oxidative stress in patients with PCOS. Forty medication-naïve patients with PCOS were randomized to either atorvastatin 20 mg daily or placebo for 3 months. A 3-month extension study for both groups of patients was undertaken with metformin 1500 mg daily after completing initial 3 months of atorvastatin or placebo. There was a significant decrease of MDA concentrations with atorvastatin [mean (sem)] [0.29 (0.04) vs. 0.25 (0.02) μmol/liter; P polycystic ovary syndrome that was independently predicted by changes in testosterone, 25OHD, and high-sensitivity C-reactive protein.

Insertion of an SVA element, a nonautonomous retrotransposon, in PMS2 intron 7 as a novel cause of Lynch syndrome.

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van der Klift, Heleen M; Tops, Carli M; Hes, Frederik J; Devilee, Peter; Wijnen, Juul T

2012-07-01

Heterozygous germline mutations in the mismatch repair gene PMS2 predispose carriers for Lynch syndrome, an autosomal dominant predisposition to cancer. Here, we present a LINE-1-mediated retrotranspositional insertion in PMS2 as a novel mutation type for Lynch syndrome. This insertion, detected with Southern blot analysis in the genomic DNA of the patient, is characterized as a 2.2 kb long 5' truncated SVA_F element. The insertion is not detectable by current diagnostic testing limited to MLPA and direct Sanger sequencing on genomic DNA. The molecular nature of this insertion could only be resolved in RNA from cultured lymphocytes in which nonsense-mediated RNA decay was inhibited. Our report illustrates the technical problems encountered in the detection of this mutation type. Especially large heterozygous insertions will remain unnoticed because of preferential amplification of the smaller wild-type allele in genomic DNA, and are probably underreported in the mutation spectra of autosomal dominant disorders. © 2012 Wiley Periodicals, Inc.

Tourette syndrome

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Gilles de la Tourette syndrome; Tic disorders - Tourette syndrome ... Tourette syndrome is named for Georges Gilles de la Tourette, who first described this disorder in 1885. The disorder is likely passed down through families. ...

Metabolic syndrome in acute coronary syndrome

International Nuclear Information System (INIS)

Bhalli, M.A.; Aamir, M.; Mustafa, G.

2011-01-01

Objective: To determine the frequency of metabolic syndrome in male patients presenting with acute coronary syndrome Study design: A Descriptive study Place and duration of study: Armed Forces Institute of Cardiology and National Institute of Heart Diseases, Rawalpindi, from October 2007 to September 2008 Patients and Methods: Male patients with acute coronary syndrome (ACS) were included. Patients having angioplasty (PCI), coronary artery bypass surgery in the past and other co-morbid diseases were excluded. All patients were assessed for the presence of five components of metabolic syndrome including hypertension, HDL-Cholesterol and triglycerides, glucose intolerance and abdominal obesity. Systolic, diastolic blood pressures, waist circumference (WC) and body mass index (BMI) were measured. ECG, cardiac enzymes, fasting glucose and lipid profile were also done. Results: A total of 135 male patients of ACS were studied with a mean age of 54.26 +- 11 years. Metabolic syndrome (MS) was present in 55 (40.7%) patients. MS with all five components was documented in 4 (7.27%) while MS with four and three components was seen in 23 (41.81%) and 28 (50.90%) patients respectively. Only 24 (43.63%) patients with MS had diabetes mellitus, remaining 31(56.36%) were non diabetic. Frequencies of diabetes, hypertension and family history of CAD were significantly higher (p<0.05) in patients with metabolic syndrome as compared to patients with normal metabolic status. Conclusion: Metabolic syndrome is fairly common and important risk factor in patients of IHD. Other risk factors like smoking, dyslipidemia, hypertension and diabetes were also frequently found. Public awareness to control the risk factors can reduce the prevalence of CAD in our country. (author)

Metabolic syndrome in acute coronary syndrome

Energy Technology Data Exchange (ETDEWEB)

Bhalli, M A; Aamir, M; Mustafa, G [Combined Military Hospital, Abbottabad (Pakistan)

2011-06-15

Objective: To determine the frequency of metabolic syndrome in male patients presenting with acute coronary syndrome Study design: A Descriptive study Place and duration of study: Armed Forces Institute of Cardiology and National Institute of Heart Diseases, Rawalpindi, from October 2007 to September 2008 Patients and Methods: Male patients with acute coronary syndrome (ACS) were included. Patients having angioplasty (PCI), coronary artery bypass surgery in the past and other co-morbid diseases were excluded. All patients were assessed for the presence of five components of metabolic syndrome including hypertension, HDL-Cholesterol and triglycerides, glucose intolerance and abdominal obesity. Systolic, diastolic blood pressures, waist circumference (WC) and body mass index (BMI) were measured. ECG, cardiac enzymes, fasting glucose and lipid profile were also done. Results: A total of 135 male patients of ACS were studied with a mean age of 54.26 +- 11 years. Metabolic syndrome (MS) was present in 55 (40.7%) patients. MS with all five components was documented in 4 (7.27%) while MS with four and three components was seen in 23 (41.81%) and 28 (50.90%) patients respectively. Only 24 (43.63%) patients with MS had diabetes mellitus, remaining 31(56.36%) were non diabetic. Frequencies of diabetes, hypertension and family history of CAD were significantly higher (p<0.05) in patients with metabolic syndrome as compared to patients with normal metabolic status. Conclusion: Metabolic syndrome is fairly common and important risk factor in patients of IHD. Other risk factors like smoking, dyslipidemia, hypertension and diabetes were also frequently found. Public awareness to control the risk factors can reduce the prevalence of CAD in our country. (author)

Exogenous Cushing syndrome

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Cushing syndrome - corticosteroid induced; Corticosteroid-induced Cushing syndrome; Iatrogenic Cushing syndrome ... Cushing syndrome is a disorder that occurs when your body has a higher than normal level of the hormone ...

A Rare case of Guillain-Barré syndrome in pregnancy treated with plasma exchange

Directory of Open Access Journals (Sweden)

Rahul Vasudev

2014-01-01

Full Text Available Guillain-Barre syndromé (GBS is an autoimmune disorder. It is rare in pregnancy as there is a decrease in cell-mediated immunity. A case of 28-year-old pregnant woman who presented with acute flaccid quadriplegia suffering from GBS is discussed in this study. She was treated with plasma exchange in her immediate post-partum period. The management of GBS in pregnancy has been discussed.

Targets to treat metabolic syndrome in polycystic ovary syndrome.

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Mahalingaiah, Shruthi; Diamanti-Kandarakis, Evanthia

2015-01-01

Metabolic syndrome is comprised of a combination of the following states: increased insulin resistance, dyslipidemia, cardiovascular disease, and increased abdominal obesity. Women with polycystic ovary syndrome (PCOS) have an increased risk of developing metabolic syndrome over the course of their lives. Metabolic syndrome increases risk of major cardiovascular events, morbidity, quality of life, and overall health care costs. Though metabolic syndrome in women with PCOS is an area of great concern, there is no effective individual medical therapeutic to adequately treat this issue. This article will review key aspects of metabolic syndrome in PCOS. We will discuss classic and novel therapeutics to address metabolic syndrome in women with PCOS. We will conclude with the importance of developing strategic interventions to increase the compliance to lifestyle and dietary modification, in addition to appreciation of the emerging pharmaceutical therapeutics available. Innovation in lifestyle modification, including diet, exercise, with and without dedicated stress reduction techniques is the future in treatment of metabolic syndrome in PCOS. Application of novel interventions, such as group medical care, may improve future adherence to lifestyle modification recommendations, in addition to or in combination with pharmaceutical therapeutics.

Targets to treat metabolic syndrome in polycystic ovary syndrome

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Mahalingaiah, Shruthi; Diamanti-Kandarakis, Evanthia

2016-01-01

Introduction Metabolic syndrome is comprised of a combination of the following states: increased insulin resistance, dyslipidemia, cardiovascular disease, and increased abdominal obesity. Women with polycystic ovary syndrome (PCOS) have an increased risk of developing metabolic syndrome over the course of their lives. Metabolic syndrome increases risk of major cardiovascular events, morbidity, quality of life, and overall health care costs. Though metabolic syndrome in women with PCOS is an area of great concern, there is no effective individual medical therapeutic to adequately treat this issue. Areas Covered This article will review key aspects of metabolic syndrome in PCOS. We will discuss classic and novel therapeutics to address metabolic syndrome in women with PCOS. We will conclude with the importance of developing strategic interventions to increase the compliance to lifestyle and dietary modification, in addition to appreciation of the emerging pharmaceutical therapeutics available. Expert Opinion Innovation in lifestyle modification, including diet, exercise, with and without dedicated stress reduction techniques is the future in treatment of metabolic syndrome in PCOS. Application of novel interventions, such as group medical care, may improve future adherence to lifestyle modification recommendations, in addition to or in combination with pharmaceutical therapeutics. PMID:26488852

Concurrent Van der Woude syndrome and Turner syndrome: A case report.

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Los, Evan; Baines, Hayley; Guttmann-Bauman, Ines

2017-01-01

Most cases of Van der Woude syndrome are caused by a mutation to interferon regulatory factor 6 on chromosome 1. Turner syndrome is caused by complete or partial absence of the second sex chromosome in girls. We describe a unique case of the two syndromes occurring concurrently though apparently independently in a girl with Van der Woude syndrome diagnosed at birth and Turner syndrome at 14 years 9 months. Short stature was initially misattributed to Van der Woude syndrome and pituitary insufficiency associated with clefts before correctly diagnosing Turner syndrome. We discuss the prevalence of delayed diagnosis of Turner syndrome, the rarity of reports of concurrent autosomal chromosome mutation and sex chromosome deletion, as well as the need to consider the diagnosis of Turner syndrome in all girls with short stature regardless of prior medical history.

Milk-alkali syndrome

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Calcium-alkali syndrome; Cope syndrome; Burnett syndrome; Hypercalcemia; Calcium metabolism disorder ... Milk-alkali syndrome is almost always caused by taking too many calcium supplements, usually in the form of calcium carbonate. Calcium ...

Marfan Syndrome

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Marfan syndrome is a disorder that affects connective tissue. Connective tissues are proteins that support skin, bones, blood vessels, ... A problem with the fibrillin gene causes Marfan syndrome. Marfan syndrome can be mild to severe, and ...

Genetic counseling for a three-generation Chinese family with Waardenburg syndrome type II associated with a rare SOX10 mutation.

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Chen, Kaitian; Zong, Ling; Zhan, Yuan; Wu, Xuan; Liu, Min; Jiang, Hongyan

2015-05-01

Waardenburg syndrome is clinically and genetically heterogeneous. The SOX10 mutation related with Waardenburg syndrome type II is rare in Chinese. This study aimed to uncover the genetic causes of Waardenburg syndrome type II in a three-generation family to improve genetic counseling. Complete clinical and molecular evaluations were conducted in a three-generation Han Chinese family with Waardenburg syndrome type II. Targeted genetic counseling was provided to this family. We identified a rare heterozygous dominant mutation c.621C>A (p.Y207X) in SOX10 gene in this family. The premature termination codon occurs in exon 4, 27 residues downstream of the carboxyl end of the high mobility group box. Bioinformatics prediction suggested this variant to be disease-causing, probably due to nonsense-mediated mRNA decay. Useful genetic counseling was given to the family for prenatal guidance. Identification of a rare dominant heterozygous SOX10 mutation c.621C>A in this family provided an efficient way to understand the causes of Waardenburg syndrome type II and improved genetic counseling. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Brief Report: Repetitive Behaviour Profiles in Williams Syndrome: Cross Syndrome Comparisons with Prader-Willi and Down Syndromes

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Royston, R.; Oliver, C.; Moss, J.; Adams, D.; Berg, K.; Burbidge, C.; Howlin, P.; Nelson, L.; Stinton, C.; Waite, J.

2018-01-01

This study describes the profile of repetitive behaviour in individuals with Williams syndrome, utilising cross-syndrome comparisons with people with Prader-Willi and Down syndromes. The Repetitive Behaviour Questionnaire was administered to caregivers of adults with Williams (n = 96), Prader-Willi (n = 103) and Down (n = 78) syndromes. There were…

Loeys-Dietz Syndrome

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... to the signs and symptoms of Loeys-Dietz syndrome. Marfan syndrome is different from Loeys-Dietz syndrome in that the gene mutation which causes Marfan syndrome is in fibrillin-1 (FBN-1), a protein ...

Pre-Menstrual Syndrome in Women with Down Syndrome

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Mason, Linda; Cunningham, Cliff

2009-01-01

Background: Prevalence of pre-menstrual syndrome (PMS) may be higher in women with Down syndrome due to syndrome specific characteristics in biochemistry, psychopathology and lifestyle. Recognition of PMS may be difficult for women with intellectual disabilities and their carers. Method: A daily diary, used to diagnose PMS with typical women, was…

Williams syndrome

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Williams-Beuren syndrome ... Williams syndrome is caused by not having a copy of several genes. It may be passed down in families. ... history of the condition. However, people with Williams syndrome have a 50% chance of passing the disorder ...

[Analysis and management of postoperative hemorrhage in surgery of obstructive sleep apnea hypopnea syndrome in children using plasma-mediated radio-frequency ablation at low temperature].

Science.gov (United States)

Wang, Jun; Chen, Jie; Yang, Jun

2013-09-01

To analyze retrospectively cause, prevention and management of postoperative hemorrhage in surgery of obstructive sleep apnea hypopnea syndrome (OSAHS) in children using plasma-mediated radio-frequency (pmRF) ablation at low temperature. Tonsil and adenoid ablation were carried out in 4028 cases diagnosed with OSAHS, using ENTColator lI plasma system of Arthocare company under general anesthesia. Postoperative hemorrhage occurred in 37 cases of 4028 cases, among which 1 case occurred after tonsil ablation and other 36 cases occurred after adenoid ablation. Primary hemorrhage was in 7 cases, while secondary hemorrhage in other 30 cases. Cessation of bleeding was achieved by using different methods of hemostasis in all cases. Tonsil and adenoid ablation were performed by pmRF at low temperature with advantages of less trauma, less bleeding. However, postoperative hemorrhage might occur in a few cases (accounting for 0.92%). Postoperative hemorrhage in these patients was related with preoperatively incomplete control of inflammation of tonsil or adenoid, surgeon's experience, intraoperatively incomplete hemostasis, postoperative crying and restlessness, eating improperly in two weeks after surgery, coagulation factor deficiency. In case of postoperative hemorrhage, good outcome could be achieved by management of compression, pmRF at low temperature, bipolar coagulation.

Coexistence of Reverse Capgras Syndrome, Subjective Double and Cotard Syndrome

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Azadeh Mashayekhi

2016-01-01

Full Text Available Misidentification syndrome is a condition in which the person thinks that familiar persons have been replaced with other one. Coexistence of some types of this syndrome has been reported with other psychiatric syndromes. In this report, we present a 47-year-old married man with coexistence of reverse Capgras and subjective double syndromes with Cotard syndrome. There is no previous report of coexistence of these three forms of delusions in a single case.

Adiponectin and C - reactive protein Relationship in the Polycystic Ovary Syndrome: Relation to Cardiovascular Disease

International Nuclear Information System (INIS)

Shousha, M.A.; Soliman, S.

2008-01-01

The polycystic ovary syndrome (PCOS), one of the most common reproductive abnormalities, shares some components of the metabolic cardiovascular syndrome. Therefore, PCOS patients may represent the largest group of women at high risk for the development of early-onset cardiovascular disease (CVD) and/or diabetes. The adipokine, adiponectin inhibits vascular inflammation and acts as an endogenous modulator of obesity - linked diseases. High - sensitive C-reactive protein (hs-CRP) is recently debated as a risk factor and mediator for atherosclerosis. The objective of this study was to investigate the relation between adiponectin and hs- CRP in The Polycystic Ovary Syndrome and to identify their relation to Cardiovascular Disease. Adiponectin and hs- CRP measurements were undertaken in 90 PCOS patients and 70 body mass index-matched controls with regular menstrual cycles. Whereas 36.8% of the PCOS patients had CRP levels above 5 mg/liter, only 9.6% of the controls exhibited high CRP levels (P < 0.001). The mean ± SD was 5.46 ± 7.0 in the PCOS group vs. 2.04 ± 1.9 mg/liter in the control (P < 0.001). The body mass index, white blood cell count, TSH, glucose, cholesterol, and homocysteine levels were not significantly different between the two groups. CRP levels are elevated in patients with PCOS and may be a marker of early cardiovascular risk in these patients. The plasma adiponectin levels being significantly lower in these patients. These results suggest that elevation of CRP and reduction of adiponectin could emerge as mediators of atherogenesis and insulin resistance. (author)

Evolutionary history of two endemic Appalachian conifers revealed using microsatellite markers

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Kevin M. Potter; John Frampton; Sedley A. Josserand; C. Dana Nelson

2010-01-01

Fraser fir (Abies fraseri [Pursh] Poir.) and intermediate fir (Abies balsamea [L.] Mill. var. phanerolepis Fern.) exist in small populations in the Appalachian highlands of the southeastern United States. We used ten nuclear microsatellite markers to quantify genetic variation within Fraser fir and intermediate...

Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).

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Bresler, Scott C; Padwa, Bonnie L; Granter, Scott R

2016-06-01

Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy.

Aicardi Syndrome

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... from Aicardi-Goutieres syndrome, which is an inherited encephalopathy that affects newborn infants.) × Definition Aicardi syndrome is a rare genetic ... from Aicardi-Goutieres syndrome, which is an inherited encephalopathy that affects newborn infants.) View Full Definition Treatment There is no ...

Treating metabolic syndrome's metaflammation with low level light therapy: preliminary results

Science.gov (United States)

Yoshimura, Tania M.; Kato, Ilka T.; Deana, Alessandro M.; Ribeiro, Martha S.

2014-02-01

Metabolic syndrome comprises a constellation of morbidities such as insulin resistance, hyperinsulinemia, atherogenic dyslipidemia, dysglycemia and obesity (especially abdominal). Metabolic alterations are observed in major insulin target organs, increasing the risk of cardiovascular diseases, type-2 diabetes and therefore mortality. Tissue alterations are characterized by immune cells infiltrates (especially activated macrophages). Released inflammatory mediators such as TNF-α induce chronic inflammation in subjects with metabolic syndrome, since inflammatory pathways are activated in the neighboring cells. The intra-abdominal adipose tissue appears to be of particular importance in the onset of the inflammatory state, and strategies contributing to modulate the inflammatory process within this adipose tissue can mitigate the metabolic syndrome consequences. Considering the low level light therapy (LLLT) recognized benefits in inflammatory conditions, we hypothesized this therapeutic approach could promote positive effects in modulating the inflammatory state of metabolic syndrome. That being the scope of this study, male C57BL/6 mice were submitted to a high-fat/high-fructose diet among 8 weeks to induce metabolic syndrome. Animals were then irradiated on the abdominal region during 21 days using an 850 nm LED (6 sessions, 300 seconds per session, 60 mW output power, ~6 J/cm2 fluence, ~19 mW/cm2 fluence rate). Before and during treatment, blood was sampled either from the retroorbital plexus or from tail puncture for glucose, total cholesterol and triglycerides analysis. So far our results indicate no alterations on these metabolic parameters after LLLT. For further investigations, blood was collected for plasma inflammatory cytokine quantification and fresh ex vivo samples of liver and intra-abdominal adipose tissue were harvested for immunohistochemistry purposes.

Interventional Effects for Mediation Analysis with Multiple Mediators.

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Vansteelandt, Stijn; Daniel, Rhian M

2017-03-01

The mediation formula for the identification of natural (in)direct effects has facilitated mediation analyses that better respect the nature of the data, with greater consideration of the need for confounding control. The default assumptions on which it relies are strong, however. In particular, they are known to be violated when confounders of the mediator-outcome association are affected by the exposure. This complicates extensions of counterfactual-based mediation analysis to settings that involve repeatedly measured mediators, or multiple correlated mediators. VanderWeele, Vansteelandt, and Robins introduced so-called interventional (in)direct effects. These can be identified under much weaker conditions than natural (in)direct effects, but have the drawback of not adding up to the total effect. In this article, we adapt their proposal to achieve an exact decomposition of the total effect, and extend it to the multiple mediator setting. Interestingly, the proposed effects capture the path-specific effects of an exposure on an outcome that are mediated by distinct mediators, even when-as often-the structural dependence between the multiple mediators is unknown, for instance, when the direction of the causal effects between the mediators is unknown, or there may be unmeasured common causes of the mediators.

Fournier gangrene associated with hyper IgE syndrome (Job syndrome).

Science.gov (United States)

Hori, Junichi; Yamaguchi, Satoshi; Watanabe, Masaki; Osanai, Hiroaki; Hori, Masako

2008-04-01

We report a case of a 32-year-old man with hyper IgE syndrome (Job syndrome) who developed Fournier gangrene due to infectious multiple atheromas of the scrotal skin that progressed to the right groin and thigh. The patient required surgical debridement and subsequent skin grafting. This is a rare case of Fournier gangrene associated with hyper IgE syndrome (Job syndrome). When a patient without diabetes mellitus has repeated infections and atopic-like dermatitis, Job syndrome should be considered.

Down Syndrome

Science.gov (United States)

... Down syndrome increases as a woman gets older. Down syndrome cannot be cured. Early treatment programs can help improve skills. They may include ... occupational, and/or educational therapy. With support and treatment, many ... Down syndrome live happy, productive lives. NIH: National Institute of ...

Cone responses in Usher syndrome types 1 and 2 by microvolt electroretinography.

Science.gov (United States)

Zein, Wadih M; Falsini, Benedetto; Tsilou, Ekaterina T; Turriff, Amy E; Schultz, Julie M; Friedman, Thomas B; Brewer, Carmen C; Zalewski, Christopher K; King, Kelly A; Muskett, Julie A; Rehman, Atteeq U; Morell, Robert J; Griffith, Andrew J; Sieving, Paul A

2014-11-25

Progressive decline of psychophysical cone-mediated measures has been reported in type 1 (USH1) and type 2 (USH2) Usher syndrome. Conventional cone electroretinogram (ERG) responses in USH demonstrate poor signal-to-noise ratio. We evaluated cone signals in USH1 and USH2 by recording microvolt level cycle-by-cycle (CxC) ERG. Responses of molecularly genotyped USH1 (n = 18) and USH2 (n = 24) subjects (age range, 15-69 years) were compared with those of controls (n = 12). A subset of USH1 (n = 9) and USH2 (n = 9) subjects was examined two to four times over 2 to 8 years. Photopic CxC ERG and conventional 30-Hz flicker ERG were recorded on the same visits. Usher syndrome subjects showed considerable cone flicker ERG amplitude losses and timing phase delays (P Usher subjects showed abnormal ERG response latency, but this changed less than amplitude with time. In USH syndrome, CxC ERG is more sensitive than conventional ERG and warrants consideration as an outcome measure in USH treatment trials. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Estimation of causal mediation effects for a dichotomous outcome in multiple-mediator models using the mediation formula.

Science.gov (United States)

Wang, Wei; Nelson, Suchitra; Albert, Jeffrey M

2013-10-30

Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets of mediators using the potential outcomes framework. We formulate a model of joint distribution (probit-normal) using continuous latent variables for any binary mediators to account for correlations among multiple mediators. A mediation formula approach is proposed to estimate the total mediation effect and decomposed mediation effects based on this parametric model. Estimation of mediation effects through individual or subsets of mediators requires an assumption involving the joint distribution of multiple counterfactuals. We conduct a simulation study that demonstrates low bias of mediation effect estimators for two-mediator models with various combinations of mediator types. The results also show that the power to detect a nonzero total mediation effect increases as the correlation coefficient between two mediators increases, whereas power for individual mediation effects reaches a maximum when the mediators are uncorrelated. We illustrate our approach by applying it to a retrospective cohort study of dental caries in adolescents with low and high socioeconomic status. Sensitivity analysis is performed to assess the robustness of conclusions regarding mediation effects when the assumption of no unmeasured mediator-outcome confounders is violated. Copyright © 2013 John Wiley & Sons, Ltd.

Estimation of Causal Mediation Effects for a Dichotomous Outcome in Multiple-Mediator Models using the Mediation Formula

Science.gov (United States)

Nelson, Suchitra; Albert, Jeffrey M.

2013-01-01

Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets of mediators using the potential outcomes framework. We formulate a model of joint distribution (probit-normal) using continuous latent variables for any binary mediators to account for correlations among multiple mediators. A mediation formula approach is proposed to estimate the total mediation effect and decomposed mediation effects based on this parametric model. Estimation of mediation effects through individual or subsets of mediators requires an assumption involving the joint distribution of multiple counterfactuals. We conduct a simulation study that demonstrates low bias of mediation effect estimators for two-mediator models with various combinations of mediator types. The results also show that the power to detect a non-zero total mediation effect increases as the correlation coefficient between two mediators increases, while power for individual mediation effects reaches a maximum when the mediators are uncorrelated. We illustrate our approach by applying it to a retrospective cohort study of dental caries in adolescents with low and high socioeconomic status. Sensitivity analysis is performed to assess the robustness of conclusions regarding mediation effects when the assumption of no unmeasured mediator-outcome confounders is violated. PMID:23650048

Insulin-like growth factor 1: common mediator of multiple enterotrophic hormones and growth factors.

Science.gov (United States)

Bortvedt, Sarah F; Lund, P Kay

2012-03-01

To summarize the recent evidence that insulin-like growth factor 1 (IGF1) mediates growth effects of multiple trophic factors and discuss clinical relevance. Recent reviews and original reports indicate benefits of growth hormone (GH) and long-acting glucagon-like peptide 2 (GLP2) analogs in short bowel syndrome and Crohn's disease. This review highlights the evidence that biomarkers of sustained small intestinal growth or mucosal healing and evaluation of intestinal epithelial stem cell biomarkers may improve clinical measures of intestinal growth or response to trophic hormones. Compelling evidence that IGF1 mediates growth effects of GH and GLP2 on intestine or linear growth in preclinical models of resection or Crohn's disease is presented, along with a concept that these hormones or IGF1 may enhance sustained growth if given early after bowel resection. Evidence that suppressor of cytokine signaling protein induction by GH or GLP2 in normal or inflamed intestine may limit IGF1-induced growth, but protect against risk of dysplasia or fibrosis, is reviewed. Whether IGF1 receptor mediates IGF1 action and potential roles of insulin receptors are addressed. IGF1 has a central role in mediating trophic hormone action in small intestine. Better understanding of benefits and risks of IGF1, receptors that mediate IGF1 action, and factors that limit undesirable growth are needed.

TAFRO Syndrome.

Science.gov (United States)

Igawa, Takuro; Sato, Yasuharu

2018-02-01

TAFRO syndrome is a newly recognized variant of idiopathic multicentric Castleman disease (iMCD) that involves a constellation of syndromes: thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O). Thrombocytopenia and severe anasarca accompanied by relatively low serum immunoglobulin levels are characteristic clinical findings of TAFRO syndrome that are not present in iMCD-not otherwise specified (iMCD-NOS). Lymph node biopsy is recommended to exclude other diseases and to diagnose TAFRO syndrome, which reveals characteristic histopathological findings similar to hyaline vascular-type CD. TAFRO syndrome follows a more aggressive course, compared with iMCD-NOS, and there is no standard treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Causal mediation analysis with multiple causally non-ordered mediators.

Science.gov (United States)

Taguri, Masataka; Featherstone, John; Cheng, Jing

2018-01-01

In many health studies, researchers are interested in estimating the treatment effects on the outcome around and through an intermediate variable. Such causal mediation analyses aim to understand the mechanisms that explain the treatment effect. Although multiple mediators are often involved in real studies, most of the literature considered mediation analyses with one mediator at a time. In this article, we consider mediation analyses when there are causally non-ordered multiple mediators. Even if the mediators do not affect each other, the sum of two indirect effects through the two mediators considered separately may diverge from the joint natural indirect effect when there are additive interactions between the effects of the two mediators on the outcome. Therefore, we derive an equation for the joint natural indirect effect based on the individual mediation effects and their interactive effect, which helps us understand how the mediation effect works through the two mediators and relative contributions of the mediators and their interaction. We also discuss an extension for three mediators. The proposed method is illustrated using data from a randomized trial on the prevention of dental caries.

Development and characteristics of children with Usher syndrome and CHARGE syndrome.

Science.gov (United States)

Dammeyer, Jesper

2012-09-01

Individuals with Usher syndrome or CHARGE syndrome are faced with a number of difficulties concerning hearing, vision, balance, and language development. The aim of the study is to describe the developmental characteristics of children with Usher syndrome and CHARGE syndrome, respectively. Data about the developmental characteristics of 26 children with Usher syndrome and 17 children with CHARGE syndrome was obtained. Associations between deafblindness (dual sensory loss), motor development (age of walking), language abilities, and intellectual outcome of these children were explored for each group independently. Both groups of children face a number of difficulties associated with vision, hearing, language, balance and intellectual outcome. Intellectual disability and/or language delay was found among 42% of the children with Usher syndrome and among 82% of the children with CHARGE syndrome. Intellectual disability was associated with language delay and age of walking for both groups. Even though Usher and CHARGE are two different genetic syndromes, both groups are challenged with a number of similar developmental delays. Clinicians need to be aware of several developmental issues in order to offer adequate support to children with Usher or CHARGE syndrome. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure

Directory of Open Access Journals (Sweden)

Honglei eWeng

2015-06-01

Full Text Available Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called second pathway of liver regeneration. The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell-mediated regeneration in patients with acute liver failure, the two sides of one coin.

Two sides of one coin: massive hepatic necrosis and progenitor cell-mediated regeneration in acute liver failure.

Science.gov (United States)

Weng, Hong-Lei; Cai, Xiaobo; Yuan, Xiaodong; Liebe, Roman; Dooley, Steven; Li, Hai; Wang, Tai-Ling

2015-01-01

Massive hepatic necrosis is a key event underlying acute liver failure, a serious clinical syndrome with high mortality. Massive hepatic necrosis in acute liver failure has unique pathophysiological characteristics including extremely rapid parenchymal cell death and removal. On the other hand, massive necrosis rapidly induces the activation of liver progenitor cells, the so-called "second pathway of liver regeneration." The final clinical outcome of acute liver failure depends on whether liver progenitor cell-mediated regeneration can efficiently restore parenchymal mass and function within a short time. This review summarizes the current knowledge regarding massive hepatic necrosis and liver progenitor cell-mediated regeneration in patients with acute liver failure, the two sides of one coin.

Pregnancy outcome in joint hypermobility syndrome and Ehlers-Danlos syndrome.

Science.gov (United States)

Sundelin, Heléne E K; Stephansson, Olof; Johansson, Kari; Ludvigsson, Jonas F

2017-01-01

An increased risk of preterm birth in women with joint hypermobility syndrome or Ehlers-Danlos syndrome is suspected. In this nationwide cohort study from 1997 through 2011, women with either joint hypermobility syndrome or Ehlers-Danlos syndrome or both disorders were identified through the Swedish Patient Register, and linked to the Medical Birth Register. Thereby, 314 singleton births to women with joint hypermobility syndrome/Ehlers-Danlos syndrome before delivery were identified. These births were compared with 1 247 864 singleton births to women without a diagnosis of joint hypermobility syndrome/Ehlers-Danlos syndrome. We used logistic regression, adjusted for maternal age, smoking, parity, and year of birth, to calculate adjusted odds ratios for adverse pregnancy outcomes. Maternal joint hypermobility syndrome/Ehlers-Danlos syndrome was not associated with any of our outcomes: preterm birth (adjusted odds ratio = 0.6, 95% confidence interval 0.3-1.2), preterm premature rupture of membranes (adjusted odds ratio = 0.8; 95% confidence interval 0.3-2.2), cesarean section (adjusted odds ratio = 0.9, 95% confidence interval 0.7-1.2), stillbirth (adjusted odds ratio = 1.1, 95% confidence interval 0.2-7.9), low Apgar score (adjusted odds ratio = 1.6, 95% confidence interval 0.7-3.6), small for gestational age (adjusted odds ratio = 0.9, 95% confidence interval 0.4-1.8) or large for gestational age (adjusted odds ratio = 1.2, 95% confidence interval 0.6-2.1). Examining only women with Ehlers-Danlos syndrome (n = 62), we found a higher risk of induction of labor (adjusted odds ratio = 2.6; 95% confidence interval 1.4-4.6) and amniotomy (adjusted odds ratio = 3.8; 95% confidence interval 2.0-7.1). No excess risks for adverse pregnancy outcome were seen in joint hypermobility syndrome. Women with joint hypermobility syndrome/Ehlers-Danlos syndrome do not seem to be at increased risk of adverse pregnancy outcome. © 2016 Nordic Federation of

Wasp sting induced STEMI with complete coronary artery occlusion: a case of Kounis syndrome.

Science.gov (United States)

Cross, Benjamin; Choudhury, Tawfiqur Rahman; Hindle, Mark; Galasko, Gavin

2017-09-07

A 45-year-old previously healthy man with minimal coronary artery disease on imaging presented with an acute MI after sustaining a wasp sting following previous non-eventful exposures throughout his life. This is the first case of Kounis syndrome with optical coherence tomography imaging and proven IgE wasp venom hypersensitivity. The Hymenoptera venom is composed of allergenic proteins and vasoactive amines which are responsible for venom toxicity. This patient also has a history of atopy giving a predisposition for developing IgE-mediated allergic reactions. Hymenoptera stings can be severe in atopic individuals and anaphylaxis may ensue. However, it is a rare cause of myocardial infarction (MI) (Kounis syndrome). Multiple wasp stings in the past may have contributed to sensitisation. Kounis syndrome is a rare clinical manifestation which should remain in the minds of physicians, especially with younger patients with no history of ischaemic heart disease or few risk factors. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Meditation awareness training for the treatment of fibromyalgia syndrome: A randomized controlled trial.

Science.gov (United States)

Van Gordon, William; Shonin, Edo; Dunn, Thomas J; Garcia-Campayo, Javier; Griffiths, Mark D

2017-02-01

The purpose of this study was to conduct the first randomized controlled trial (RCT) to evaluate the effectiveness of a second-generation mindfulness-based intervention (SG-MBI) for treating fibromyalgia syndrome (FMS). Compared to first-generation mindfulness-based interventions, SG-MBIs are more acknowledging of the spiritual aspect of mindfulness. A RCT employing intent-to-treat analysis. Adults with FMS received an 8-week SG-MBI known as meditation awareness training (MAT; n = 74) or an active control intervention known as cognitive behaviour theory for groups (n = 74). Assessments were performed at pre-, post-, and 6-month follow-up phases. Meditation awareness training participants demonstrated significant and sustained improvements over control group participants in FMS symptomatology, pain perception, sleep quality, psychological distress, non-attachment (to self, symptoms, and environment), and civic engagement. A mediation analysis found that (1) civic engagement partially mediated treatment effects for all outcome variables, (2) non-attachment partially mediated treatment effects for psychological distress and sleep quality, and (3) non-attachment almost fully mediated treatment effects for FMS symptomatology and pain perception. Average daily time spent in meditation was found to be a significant predictor of changes in all outcome variables. Meditation awareness training may be a suitable treatment for adults with FMS and appears to ameliorate FMS symptomatology and pain perception by reducing attachment to self. Statement of contribution What is already known on this subject? Designing interventions to treat fibromyalgia syndrome (FMS) continues to be a challenge. There is growing interest into the applications of mindfulness-based interventions for treating FMS. Second-generation mindfulness-based interventions (SG-MBIs) are a key new direction in mindfulness research. What does this study add? Meditation awareness training - an SG-MBI - resulted

Wolf-Hirschhorn (4p-) syndrome with West syndrome.

Science.gov (United States)

Motoi, Hirotaka; Okanishi, Tohru; Kanai, Sotaro; Yokota, Takuya; Yamazoe, Tomohiro; Nishimura, Mitsuyo; Fujimoto, Ayataka; Yamamoto, Takamichi; Enoki, Hideo

2016-01-01

Wolf-Hirschhorn syndrome (WHS) is a chromosome disorder (4p-syndrome) which is characterized by craniofacial features and epileptic seizures. Here, we report a case of WHS with West syndrome, in whom the seizures were refractory to several antiepileptic drugs but were responsive to the addition of lamotrigine. The patient had epileptic spasms at age seven months. The interictal electroencephalogram was hypsarrhythmic. After adding lamotrigine, seizures decreased remarkably, and spasms disappeared. We have identified and described the very rare case of a girl with WHS who also developed West syndrome. In this case, adding lamotrigine to her medications effectively treated the spasms.

Rowell syndrome

Directory of Open Access Journals (Sweden)

Ramesh Y Bhat

2014-01-01

Full Text Available Rowell syndrome is a rare disease consisting of erythema multiforme-like lesions associated with lupus erythematosus. The syndrome occurs mostly in middle-aged women. The authors describe the syndrome in a 15-year-old boy who responded well to systemic steroids and hydroxychloroquine.

Mitochondrial translocation of Nur77 induced by ROS contributed to cardiomyocyte apoptosis in metabolic syndrome

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Xu, Aibin; Liu, Jingyi [Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an (China); Institute of Cardiovascular Disease, General Hospital of Beijing Command, PLA, Beijing (China); Liu, Peilin; Jia, Min; Wang, Han [Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an (China); Tao, Ling, E-mail: lingtao2006@gmail.com [Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an (China)

2014-04-18

Highlights: • Metabolic syndrome exacerbated MI/R induced injury accompanied by decreased Nur77. • ROS led to Nur77 translocation in metabolic syndrome. • Inhibiting relocation of Nur77 to mitochondria reduced ROS-induced cardiomyocyte injury in metabolic syndrome. - Abstract: Metabolic syndrome is a major risk factor for cardiovascular diseases, and increased cardiomyocyte apoptosis which contributes to cardiac dysfunction after myocardial ischemia/reperfusion (MI/R) injury. Nur77, a nuclear orphan receptor, is involved in such various cellular events as apoptosis, proliferation, and glucose and lipid metabolism in several cell types. Apoptosis is positively correlated with mitochondrial translocation of Nur77 in the cancer cells. However, the roles of Nur77 on cardiac myocytes in patients with metabolic syndrome remain unclear. The objective of this study was to determine whether Nur77 may contribute to cardiac apoptosis in patients with metabolic syndrome after I/R injury, and, if so, to identify the underlying molecular mechanisms responsible. We used leptin-deficient (ob/ob) mice to make metabolic syndrome models. In this report, we observed that, accompanied by the substantial decline in apoptosis inducer Nur77, MI/R induced cardiac dysfunction was manifested as cardiomyopathy and increased ROS. Using the neonatal rat cardiac myocytes cultured in a high-glucose and high-fat medium, we found that excessive H{sub 2}O{sub 2} led to the significant alteration in mitochondrial membrane potential and translocation of Nur77 from the nucleus to the mitochondria. However, inhibition of the relocation of Nur77 to mitochondria via Cyclosporin A reversed the changes in membrane potential mediated by H{sub 2}O{sub 2} and reduced myocardial cell injury. Therefore, these data provide a potential underlying mechanism for cardiac dysfunction in metabolic syndrome and the suppression of Nur77 translocation may provide an effective approach to reduce cardiac injury in the

Mitochondrial translocation of Nur77 induced by ROS contributed to cardiomyocyte apoptosis in metabolic syndrome

International Nuclear Information System (INIS)

Xu, Aibin; Liu, Jingyi; Liu, Peilin; Jia, Min; Wang, Han; Tao, Ling

2014-01-01

Highlights: • Metabolic syndrome exacerbated MI/R induced injury accompanied by decreased Nur77. • ROS led to Nur77 translocation in metabolic syndrome. • Inhibiting relocation of Nur77 to mitochondria reduced ROS-induced cardiomyocyte injury in metabolic syndrome. - Abstract: Metabolic syndrome is a major risk factor for cardiovascular diseases, and increased cardiomyocyte apoptosis which contributes to cardiac dysfunction after myocardial ischemia/reperfusion (MI/R) injury. Nur77, a nuclear orphan receptor, is involved in such various cellular events as apoptosis, proliferation, and glucose and lipid metabolism in several cell types. Apoptosis is positively correlated with mitochondrial translocation of Nur77 in the cancer cells. However, the roles of Nur77 on cardiac myocytes in patients with metabolic syndrome remain unclear. The objective of this study was to determine whether Nur77 may contribute to cardiac apoptosis in patients with metabolic syndrome after I/R injury, and, if so, to identify the underlying molecular mechanisms responsible. We used leptin-deficient (ob/ob) mice to make metabolic syndrome models. In this report, we observed that, accompanied by the substantial decline in apoptosis inducer Nur77, MI/R induced cardiac dysfunction was manifested as cardiomyopathy and increased ROS. Using the neonatal rat cardiac myocytes cultured in a high-glucose and high-fat medium, we found that excessive H 2 O 2 led to the significant alteration in mitochondrial membrane potential and translocation of Nur77 from the nucleus to the mitochondria. However, inhibition of the relocation of Nur77 to mitochondria via Cyclosporin A reversed the changes in membrane potential mediated by H 2 O 2 and reduced myocardial cell injury. Therefore, these data provide a potential underlying mechanism for cardiac dysfunction in metabolic syndrome and the suppression of Nur77 translocation may provide an effective approach to reduce cardiac injury in the process

[Poland's syndrome].

Science.gov (United States)

Slezak, R; Sasiadek, M

2000-08-01

Poland's syndrome consists of the variable clinical features, but always includes unilateral aplasia of the chest wall muscles and ipsilateral anomalies of upper extremity. The incidence of Poland's syndrome, reported by different authors ranges from 1:10,000 to 1:100,000 and is observed more frequently in males than in females with the right side of the body affected more often than the left. The etiology of this syndrome is still discussed. However most of described cases were sporadic, rare familial incidence of Poland's syndrome were also presented. Therefore different etiologic factors of the Poland's syndrome are taken into account: genetic, vascular compromise during early stages of embriogenesis but also teratogenic effect of environmental xenobiotics (e.g. cigarette smoking by pregnant women). The authors present also the case of 20-years old man with inherited bilateral syndactyly with the right side aplasia of major pectoralis muscle and face asymmetry. The familial history was negative in respect to the features, associated with Poland's syndrome.

Roles of the sister chromatid cohesion apparatus in gene expression, development, and human syndromes

Science.gov (United States)

Dorsett, Dale

2006-01-01

The sister chromatid cohesion apparatus mediates physical pairing of duplicated chromosomes. This pairing is essential for appropriate distribution of chromosomes into the daughter cells upon cell division. Recent evidence shows that the cohesion apparatus, which is a significant structural component of chromosomes during interphase, also affects gene expression and development. The Cornelia de Lange (CdLS) and Roberts/SC phocomelia (RBS/SC) genetic syndromes in humans are caused by mutations affecting components of the cohesion apparatus. Studies in Drosophila suggest that effects on gene expression are most likely responsible for developmental alterations in CdLS. Effects on chromatid cohesion are apparent in RBS/SC syndrome, but data from yeast and Drosophila point to the likelihood that changes in expression of genes located in heterochromatin could contribute to the developmental deficits. PMID:16819604

Neuromyelitis optica in pregnancy complicated by posterior reversible encephalopathy syndrome, eclampsia and fetal death.

Science.gov (United States)

Igel, Catherine; Garretto, Diana; Robbins, Matthew S; Swerdlow, Michael; Judge, Nancy; Dayal, Ashlesha

2015-03-01

Neuromyelitis optica (NMO) is a demyelinating syndrome characterized by optic neuritis and acute myelitis with poor recovery and a progressive course. We report a poor outcome complicated by posterior reversible encephalopathy syndrome (PRES) and eclampsia and review available literature and current evidence for anticipation of adverse fetal and maternal effects. After a pregnancy complicated by multiple admissions for painful NMO exacerbations, a primiparous patient with seropositive NMO presented at 31 + 3/7 weeks with eclampsia, HELLP and subsequent fetal death. MRI confirmed PRES. NMO may be associated with eclampsia and leads to adverse maternal and fetal outcomes. Posited mechanisms include antibody-mediated placental damage and a heightened risk of eclampsia-associated PRES. Further characterization of the course of NMO and its relationship with pregnancy outcomes in larger series would be invaluable.

[Gardner syndrome--parent alienation syndrome (PAS). Diagnosis or family reality?].

Science.gov (United States)

Namysłowska, Irena; Heitzman, Janusz; Siewierska, Anna

2009-01-01

The authors present characteristics of Parental Alienation Syndrome (PAS) proposed by Gardner as well as data, which may help to differentiate that syndrome with real psychological, physical and sexual abuse. The consequences of Gardner Syndrome for legal decisions in the court cases of child custody and the critique of this syndrome in forensic and psychiatric literature are also discussed, and several questions posed. Authors propose to treat Gardner Syndrome not as as a child disorder but as a specific, dynamic family situation, which occurs sometimes, during divorce and fight about child custody.

Infection and immunity in Down syndrome: a trial of long-term low oral doses of zinc.

Science.gov (United States)

Lockitch, G; Puterman, M; Godolphin, W; Sheps, S; Tingle, A J; Quigley, G

1989-05-01

To determine whether orally administered zinc supplements could correct the abnormal humoral and cell-mediated immunity of Down syndrome, we randomly assigned 64 children with Down syndrome, aged 1 to 19 years and living at home, to receive either zinc gluconate or placebo daily for 6-month periods with crossover from one regimen to another. Control subjects were siblings and age-matched, unrelated children. Serum zinc, copper, and measures of immune system competence were tested at 3- or 6-month intervals. Parents kept daily logs of clinical symptoms such as cough and diarrhea and of physician visits. Mean serum zinc concentrations increased to about 150% of baseline during zinc supplementation, but we found no effect on serum levels of copper, immunoglobulins, or complement; on lymphocyte number or subset distribution; or on in vitro response to mitogens. Children with Down syndrome who were receiving zinc had a trend toward fewer days or episodes of cough and fever but no change in other clinical variables. Long-term, low-dose oral zinc supplementation to improve depressed immune response or to decrease infections in children with Down syndrome cannot be recommended.

Mediatization

DEFF Research Database (Denmark)

Hjarvard, Stig

2017-01-01

Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... to these general questions by distinguishing between two concepts: mediation and mediatization. The media effects tradition generally considers the effects of the media to be a result of individuals being exposed to media content, i.e. effects are seen as an outcome of mediated communication. Mediatization...... research is concerned with long-term structural changes involving media, culture, and society, i.e. the influences of the media are understood in relation to how media are implicated in social and cultural changes and how these processes come to create new conditions for human communication and interaction...

Burning Mouth Syndrome and "Burning Mouth Syndrome".

Science.gov (United States)

Rifkind, Jacob Bernard

2016-03-01

Burning mouth syndrome is distressing to both the patient and practitioner unable to determine the cause of the patient's symptoms. Burning mouth syndrome is a diagnosis of exclusion, which is used only after nutritional deficiencies, mucosal disease, fungal infections, hormonal disturbances and contact stomatitis have been ruled out. This article will explore the many causes and treatment of patients who present with a chief complaint of "my mouth burns," including symptomatic treatment for those with burning mouth syndrome.

Marfan Syndrome (For Teens)

Science.gov (United States)

... genetic disorder called Marfan syndrome. What Is Marfan Syndrome? Marfan syndrome is named after Antoine Marfan, the French ... immediately. What's Life Like for Teens With Marfan Syndrome? Marfan syndrome affects people differently, so life is not ...

Learning about Marfan Syndrome

Science.gov (United States)

... Additional Resources for Marfan Syndrome What is Marfan syndrome? Marfan syndrome is one of the most common inherited ... FAQ Top of page Additional Resources For Marfan Syndrome Marfan syndrome [nlm.nih.gov] From Medline Plus Marfan ...

Divorce in families of children with Down Syndrome or Rett Syndrome.

Science.gov (United States)

Lederman, Vivian Renne Gerber; Alves, Bianca dos Santos; Negrão, Juliana; Maria, Juliana Negrão; Schwartzman, José Salomão; D'Antino, Maria Eloisa Famá; Brunoni, Decio

2015-05-01

This study evaluates the impact in the stability and management of the marriage of parents of a child with Down or Rett Syndrome. Morbidity of the syndromes and the marital status of the couples before and after the birth of the affected children were considered variables. The divorce rate in families with Down syndrome was 10%, similar to the Brazilian rate population. In Rett Syndrome, the divorce rate was significantly higher, 23.5%. The higher morbidity of Rett Syndrome, and the moment of diagnosis could be relevant factors for the increased divorce rate related to this syndrome.

Post-cardiac injury syndrome: an atypical case following percutaneous coronary intervention.

Science.gov (United States)

Paiardi, Silvia; Cannata, Francesco; Ciccarelli, Michele; Voza, Antonio

2017-12-01

Post-cardiac injury syndrome (PCIS) is a syndrome characterized by pericardial and/or pleural effusion, triggered by a cardiac injury, usually a myocardial infarction or cardiac surgery, rarely a minor cardiovascular percutaneous procedure. Nowadays, the post-cardiac injury syndrome, is regaining importance and interest as an emerging cause of pericarditis, especially in developed countries, due to a great and continuous increase in the number and complexity of percutaneous cardiologic procedures. The etiopathogenesis seems mediated by the immunitary system producing immune complexes, which deposit in the pericardium and pleura and trigger an inflammatory response. We present the atypical case of a 76-year-old man presenting with a hydro-pneumothorax, low-grade fever and elevated inflammation markers, after two complex percutaneous coronary interventions, executed 30 and 75 days prior. The clinical features of our case are consistent with the diagnostic criteria of PCIS: prior injury of the pericardium and/or myocardium, fever, leucocytosis, elevated inflammatory markers, remarkable steroid responsiveness and latency period. Only one element does not fit with this diagnosis and does not find any further explanation: the air accompanying the pleural effusion, determining a hydro-pneumothorax and requiring a pleural drainage catheter positioning. Copyright © 2017 Elsevier Inc. All rights reserved.

The sick-building syndrome; Das Sick-Building-Syndrom

Energy Technology Data Exchange (ETDEWEB)

Henne, A.; Neumann, H.F.; Winneke, G.

1992-12-31

The sick-building syndrome is characterized by the presence of general, non-specific symptoms (e.g., headache, tiredness, respiratory problems, eye trouble, vertigo, nausea, unspecific hypersensitivity) in association with a particular indoor ambience. It is clearly distinguishable from `building-related illness`, referring to a well-defined clinical syndrome due to staying in a building and for which a cause can, in general, be established. Disorders in the case of the sick-building syndrome are manifold and confirmed objectifiable results are hardly available so far. Yet there are some organ-related methods for the confirmation of findings concerning, for instance, the eyes, the skin and the area of the nose. The causes of the incidence of sick-building syndrome are more or less unclear. It is a multifactorial phenomenon involving physical, biological, chemical, individual-specific and psychological factors. Buildings where sick-building syndrome occurs typically exhibit certain properties. The European Community has already made proposals for the investigation of incriminated buildings. A systematic survey by questionnaire together with individual interviews plays an import part towards clarifying the syndrome. (orig./UWA) [Deutsch] Das Sick-Building-Syndrom beschreibt das Vorhandensein von allgemeinen, nicht spezifischen Symptomen (z.B. Kopfschmerzen, Muedigkeit, Atembeschwerden, Augenreizungen, Schwindelgefuehl, Uebelkeit, unspezifische Ueberempfindlichkeit), assoziiert mit einer besonderen Innenraumumgebung. Deutlich hiervon abzugrenzen ist die ``Building related illness``, bei der ein klinisch definiertes Krankheitsbild vorliegt, das durch den Aufenthalt im Gebaeude verursacht wird und fuer das im allgemeinen eine Ursache ermittelt werden kann. Das Beschwerdebild beim Sick-Building-Syndrom ist vielfaeltig, und gesicherte, objektivierbare Befunde liegen hierzu bisher kaum vor. Dennoch gibt es einige organbezogenen Methoden zur Befundabsicherung, z.B. fuer das

Hypokalaemia: Bartter's syndrome or pseudo-Bartter's syndrome?

OpenAIRE

Robb, J D; Delargy, M A; Nolan, M; Tomkin, G H

1984-01-01

The difficulties in the diagnosis of hypokalaemia are often considerable. This paper reports three patients who presented with hypokalaemia. Investigations are described which may help to distinguish Bartter's syndrome from pseudo-Bartter's syndrome.

Considering the Future of University-Based Teacher Preparation

Science.gov (United States)

Fraser, James W.

2014-01-01

In this commentary, James W. Fraser, a noted historian of education, cites examples from several teacher education programs at more than 30 universities partnering with the Woodrow Wilson Teaching Fellowships in various ways. Additionally, Fraser reviews decades of challenges to traditional teacher preparation, looks at some current reforms, and…

Syndromes with supernumerary teeth.

Science.gov (United States)

Lubinsky, Mark; Kantaputra, Piranit Nik

2016-10-01

While most supernumerary teeth are idiopathic, they can be associated with a number of Mendelian syndromes. However, this can also be a coincidental finding, since supernumerary teeth occur in 6% or more of the normal population. To better define this relationship, we analyzed the evidence for specific associations. We excluded conditions with a single affected patient reported, supernumerary teeth adjacent to clefts or other forms of alveolar disruption (as secondary rather than primary findings), and natal teeth, which can involve premature eruption of a normal tooth. Since, the cause of supernumerary teeth shows considerable heterogeneity, certain findings are less likely to be coincidental, such as five or more supernumerary teeth in a single patient, or locations outside of the premaxilla. We found only eight genetic syndromes with strong evidence for an association: cleidocranial dysplasia; familial adenomatous polyposis; trichorhinophalangeal syndrome, type I; Rubinstein-Taybi syndrome; Nance-Horan syndrome; Opitz BBB/G syndrome; oculofaciocardiodental syndrome; and autosomal dominant Robinow syndrome. There is also suggestive evidence of an association with two uncommon disorders, Kreiborg-Pakistani syndrome (craniosynostosis and dental anomalies), and insulin-resistant diabetes mellitus with acanthosisnigricans. An association of a Mendelian disorder with a low frequency manifestation of supernumerary teeth is difficult to exclude without large numbers, but several commonly cited syndromes lacked evidence for clear association, including Hallermann-Streiff syndrome, Fabry disease, Ehlers-Danlos syndrome, Apert and Crouzon syndromes, Zimmermann-Laband syndrome, and Ellis-van Creveld syndrome. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

What Is Usher Syndrome?

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... Action You are here Home › Retinal Diseases Listen Usher Syndrome What is Usher syndrome? How is Usher syndrome ... available? Are there any related diseases? What is Usher Syndrome? Usher syndrome is an inherited condition characterized by ...

Primary Biliary Cirrhosis and Primary Sjögren's Syndrome: Insights for the Stomatologist

Directory of Open Access Journals (Sweden)

Liliane Lins

2014-08-01

Full Text Available Primary biliary cirrhosis (PBC is a chronic progressive autoimmune disease characterized by portal inflammation and immune-mediated destruction of the intrahepatic bile ducts. Primary Sjögren's syndrome is an autoimmune disease characterized by lymphocytic infiltration of exocrine glands, mainly the lachrymal and salivary glands, in the absence of other definitively diagnosed rheumatologic disease. We report a diagnosed case of primary Sjögren's syndrome associated with PBC. A 59-year-old Caucasian woman went to oral evaluation reporting dry mouth, difficulty in eating associated with burning mouth syndrome, dysgeusia and dysphagia. Intraoral examination revealed extensive cervical caries, gingivitis, gingival retraction, angular cheilitis and atrophic tongue. Hyposalivation was detected by salivary flow and Schirmer's test was positive. Antinuclear and antimitochondrial antibodies were both positive. Anti-Ro/SSA and anti-La/SSB antibodies were negative. A minor salivary gland biopsy of the lower lip was performed. Histopathologic analysis revealed lymphocytic infiltrate with destruction of salivary gland architecture in some areas and replacement of glandular tissues by mononuclear cells. Optimal management of PBC associated with Sjögren's syndrome requires a multidisciplinary approach as the key to optimal patient care. Dental practitioners should be able to recognize the clinical features of this associated condition. Appropriate dental care may prevent tooth decay, periodontal disease and oral infections as well as improve the patient's quality of life.

Mechanisms and environmental factors that underlying the intensification of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy)-induced serotonin syndrome in rats

Science.gov (United States)

Tao, Rui; Shokry, Ibrahim M.; Callanan, John J.; Adams, H. Daniel; Ma, Zhiyuan

2014-01-01

Rationale Illicit use of MDMA (3,4-methylenedioxymethamphetamine; Ecstasy) may cause a mild or severe form of the serotonin syndrome. The syndrome intensity is not just influenced by drug doses but also by environmental factors. Objectives Warm environmental temperatures and physical activity are features of raves. The purpose of this study was to assess how these two factors can potentially intensify the syndrome. Methods Rats were administered MDMA at doses of 0.3, 1 or 3 mg/kg, and examined in the absence or presence of warm temperature and physical activity. The syndrome intensity was estimated by visual scoring for behavioral syndrome and also instrumentally measuring changes in symptoms of the syndrome. Results Our results showed that MDMA at 3 mg/kg, but not 0.3 or 1 mg/kg, caused a mild serotonin syndrome in rats. Each environmental factor alone moderately intensified the syndrome. When the two factors were combined, the intensification became more severe than each factor alone highlighting a synergistic effect. This intensification was blocked by the 5-HT2A receptor antagonist M100907, competitive NMDA receptor antagonist CGS19755, autonomic ganglionic blocker hexamethonium, and the benzodiazepine-GABAA receptor agonist midazolam, but not by the 5-HT1A receptor antagonist WAY100635 or nicotinic receptor antagonist methyllycaconitine. Conclusions Our data suggest that, in the absence of environmental factors, the MDMA-induced syndrome is mainly mediated through the serotonergic transmission (5HT-dependent mechanism), and therefore, is relatively mild. Warm temperature and physical activity facilitate serotonergic and other neural systems such as glutamatergic and autonomic transmissions, resulting in intensification of the syndrome (non-5HT mechanisms). PMID:25300903

Intercultural Mediation

OpenAIRE

Dragos Marian Radulescu; Denisa Mitrut

2012-01-01

The Intercultural Mediator facilitates exchanges between people of different socio-cultural backgrounds and acts as a bridge between immigrants and national and local associations, health organizations, services and offices in order to foster integration of every single individual. As the use mediation increases, mediators are more likely to be involved in cross-cultural mediation, but only the best mediators have the opportunity to mediate cross border business disputes or international poli...

The relationship between beliefs about emotions and quality of life in irritable bowel syndrome.

Science.gov (United States)

Bowers, Hannah; Wroe, Abigail; Pincus, Tamar

2017-12-01

Suppression of undesirable emotions, as well as beliefs about the unacceptability of experiencing and expressing emotions, have both been shown to be related to poorer health-related outcomes in several clinical groups. Potential models through which these variables relate have yet to be tested in those with irritable bowel syndrome (IBS) and are therefore examined in the current article. Online questionnaires were administered to people with IBS (n = 84) to test a mediation model in which beliefs about the unacceptability of emotions are associated with greater emotional suppression, which in turn relates to increased affective distress and consequently poorer quality of life. An alternate model to test the direction of effect along with two further models using support-seeking as mediators of the same predictor and outcome were also tested. Emotional suppression and affective distress (in that particular order) mediate the relationship between beliefs about emotions and quality of life IBS. The models using support-seeking as mediators of the relationship between beliefs about emotions and the two outcomes were not supported. These findings suggest a role for emotional processing in medically unexplained symptoms and imply the need to address such beliefs about emotions in psychological therapies.

Loading of PAX3 to Mitotic Chromosomes Is Mediated by Arginine Methylation and Associated with Waardenburg Syndrome*

Science.gov (United States)

Wu, Tsu-Fang; Yao, Ya-Li; Lai, I-Lu; Lai, Chien-Chen; Lin, Pei-Lun; Yang, Wen-Ming

2015-01-01

PAX3 is a transcription factor critical to gene regulation in mammalian development. Mutations in PAX3 are associated with Waardenburg syndrome (WS), but the mechanism of how mutant PAX3 proteins cause WS remains unclear. Here, we found that PAX3 loads on mitotic chromosomes using its homeodomain. PAX3 WS mutants with mutations in homeodomain lose the ability to bind mitotic chromosomes. Moreover, loading of PAX3 on mitotic chromosomes requires arginine methylation, which is regulated by methyltransferase PRMT5 and demethylase JMJD6. Mutant PAX3 proteins that lose mitotic chromosome localization block cell proliferation and normal development of zebrafish. These results reveal the molecular mechanism of PAX3s loading on mitotic chromosomes and the importance of this localization pattern in normal development. Our findings suggest that PAX3 WS mutants interfere with the normal functions of PAX3 in a dominant negative manner, which is important to the understanding of the pathogenesis of Waardenburg syndrome. PMID:26149688

Mediation analysis with multiple versions of the mediator.

Science.gov (United States)

Vanderweele, Tyler J

2012-05-01

The causal inference literature has provided definitions of direct and indirect effects based on counterfactuals that generalize the approach found in the social science literature. However, these definitions presuppose well-defined hypothetical interventions on the mediator. In many settings, there may be multiple ways to fix the mediator to a particular value, and these various hypothetical interventions may have very different implications for the outcome of interest. In this paper, we consider mediation analysis when multiple versions of the mediator are present. Specifically, we consider the problem of attempting to decompose a total effect of an exposure on an outcome into the portion through the intermediate and the portion through other pathways. We consider the setting in which there are multiple versions of the mediator but the investigator has access only to data on the particular measurement, not information on which version of the mediator may have brought that value about. We show that the quantity that is estimated as a natural indirect effect using only the available data does indeed have an interpretation as a particular type of mediated effect; however, the quantity estimated as a natural direct effect, in fact, captures both a true direct effect and an effect of the exposure on the outcome mediated through the effect of the version of the mediator that is not captured by the mediator measurement. The results are illustrated using 2 examples from the literature, one in which the versions of the mediator are unknown and another in which the mediator itself has been dichotomized.

Fibromyalgia Syndrome in Need of Effective Treatments

Science.gov (United States)

Tsilioni, Irene; Arbetman, Lauren; Panagiotidou, Smaro; Stewart, Julia M.; Gleason, Rae M.; Russell, Irwin J.

2015-01-01

Fibromyalgia syndrome (FMS) is a chronic, idiopathic condition of widespread musculoskeletal pain, affecting primarily women. It is clinically characterized by chronic, nonarticular pain and a heightened response to pressure along with sleep disturbances, fatigue, bowel and bladder abnormalities, and cognitive dysfunction. The diagnostic criteria have changed repeatedly, and there is neither a definitive pathogenesis nor reliable diagnostic or prognostic biomarkers. Clinical and laboratory studies have provided evidence of altered central pain pathways. Recent evidence suggests the involvement of neuroinflammation with stress peptides triggering the release of neurosenzitizing mediators. The management of FMS requires a multidimensional approach including patient education, behavioral therapy, exercise, and pain management. Here we review recent data on the pathogenesis and propose new directions for research and treatment. PMID:26306765

The Biased G-Protein-Coupled Receptor Agonism Bridges the Gap between the Insulin Receptor and the Metabolic Syndrome

Science.gov (United States)

Liauchonak, Iryna; Dawoud, Fady; Riat, Yatin; Sambi, Manpreet; Jain, Justin; Kalaydina, Regina-Veronicka; Mendonza, Nicole; Bajwa, Komal

2018-01-01

Insulin signaling, as mediated through the insulin receptor (IR), plays a critical role in metabolism. Aberrations in this signaling cascade lead to several pathologies, the majority of which are classified under the umbrella term “metabolic syndrome”. Although many of these pathologies are associated with insulin resistance, the exact mechanisms are not well understood. One area of current interest is the possibility of G-protein-coupled receptors (GPCRs) influencing or regulating IR signaling. This concept is particularly significant, because GPCRs have been shown to participate in cross-talk with the IR. More importantly, GPCR signaling has also been shown to preferentially regulate specific downstream signaling targets through GPCR agonist bias. A novel study recently demonstrated that this GPCR-biased agonism influences the activity of the IR without the presence of insulin. Although GPCR-IR cross-talk has previously been established, the notion that GPCRs can regulate the activation of the IR is particularly significant in relation to metabolic syndrome and other pathologies that develop as a result of alterations in IR signaling. As such, we aim to provide an overview of the physiological and pathophysiological roles of the IR within metabolic syndrome and its related pathologies, including cardiovascular health, gut microflora composition, gastrointestinal tract functioning, polycystic ovarian syndrome, pancreatic cancer, and neurodegenerative disorders. Furthermore, we propose that the GPCR-biased agonism may perhaps mediate some of the downstream signaling effects that further exacerbate these diseases for which the mechanisms are currently not well understood. PMID:29462993

Neuroendocrine androgen action is a key extraovarian mediator in the development of polycystic ovary syndrome

OpenAIRE

Caldwell, Aimee S. L.; Edwards, Melissa C.; Desai, Reena; Jimenez, Mark; Gilchrist, Robert B.; Handelsman, David J.; Walters, Kirsty A.

2017-01-01

The cause of polycystic ovary syndrome (PCOS) is unknown, but androgen excess is a key feature. We combined a hyperandrogenized PCOS mouse model with global and tissue- and cell-specific androgen-resistant mouse lines to uncover the sites of androgen action that initiate PCOS. We demonstrate that direct androgen actions, particularly in neurons but less so in granulosa cells, are required for the development of key reproductive and metabolic PCOS features. These data highlight the previously ...

Phthalate-induced testicular dysgenesis syndrome: Leydig cell influence.

Science.gov (United States)

Hu, Guo-Xin; Lian, Qing-Quan; Ge, Ren-Shan; Hardy, Dianne O; Li, Xiao-Kun

2009-04-01

Phthalates, the most abundantly produced plasticizers, leach out from polyvinyl chloride plastics and disrupt androgen action. Male rats that are exposed to phthalates in utero develop symptoms characteristic of the human condition referred to as testicular dysgenesis syndrome (TDS). Environmental influences have been suspected to contribute to the increasing incidence of TDS in humans (i.e. cryptorchidism and hypospadias in newborn boys and testicular cancer and reduced sperm quality in adult males). In this review, we discuss the recent findings that prenatal exposure to phthalates affects Leydig cell function in the postnatal testis. This review also focuses on the recent progress in our understanding of how Leydig cell factors contribute to phthalate-mediated TDS.

A Protein Scaffold Coordinates SRC-Mediated JNK Activation in Response to Metabolic Stress.

Science.gov (United States)

Kant, Shashi; Standen, Claire L; Morel, Caroline; Jung, Dae Young; Kim, Jason K; Swat, Wojciech; Flavell, Richard A; Davis, Roger J

2017-09-19

Obesity is a major risk factor for the development of metabolic syndrome and type 2 diabetes. How obesity contributes to metabolic syndrome is unclear. Free fatty acid (FFA) activation of a non-receptor tyrosine kinase (SRC)-dependent cJun NH 2 -terminal kinase (JNK) signaling pathway is implicated in this process. However, the mechanism that mediates SRC-dependent JNK activation is unclear. Here, we identify a role for the scaffold protein JIP1 in SRC-dependent JNK activation. SRC phosphorylation of JIP1 creates phosphotyrosine interaction motifs that bind the SH2 domains of SRC and the guanine nucleotide exchange factor VAV. These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module. The JIP1 scaffold protein, therefore, plays a dual role in FFA signaling by coordinating upstream SRC functions together with downstream effector signaling by the JNK pathway. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

A Protein Scaffold Coordinates SRC-Mediated JNK Activation in Response to Metabolic Stress

Directory of Open Access Journals (Sweden)

Shashi Kant

2017-09-01

Full Text Available Obesity is a major risk factor for the development of metabolic syndrome and type 2 diabetes. How obesity contributes to metabolic syndrome is unclear. Free fatty acid (FFA activation of a non-receptor tyrosine kinase (SRC-dependent cJun NH2-terminal kinase (JNK signaling pathway is implicated in this process. However, the mechanism that mediates SRC-dependent JNK activation is unclear. Here, we identify a role for the scaffold protein JIP1 in SRC-dependent JNK activation. SRC phosphorylation of JIP1 creates phosphotyrosine interaction motifs that bind the SH2 domains of SRC and the guanine nucleotide exchange factor VAV. These interactions are required for SRC-induced activation of VAV and the subsequent engagement of a JIP1-tethered JNK signaling module. The JIP1 scaffold protein, therefore, plays a dual role in FFA signaling by coordinating upstream SRC functions together with downstream effector signaling by the JNK pathway.

mediation: R Package for Causal Mediation Analysis

Directory of Open Access Journals (Sweden)

Dustin Tingley

2014-09-01

Full Text Available In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting such an analysis. The package is organized into two distinct approaches. Using the model-based approach, researchers can estimate causal mediation effects and conduct sensitivity analysis under the standard research design. Furthermore, the design-based approach provides several analysis tools that are applicable under different experimental designs. This approach requires weaker assumptions than the model-based approach. We also implement a statistical method for dealing with multiple (causally dependent mediators, which are often encountered in practice. Finally, the package also offers a methodology for assessing causal mediation in the presence of treatment noncompliance, a common problem in randomized trials.

Li-Fraumeni-like syndrome associated with a large BRCA1 intragenic deletion

International Nuclear Information System (INIS)

Silva, Amanda Gonçalves; Achatz, Maria Isabel W; Rosenberg, Carla; Krepischi, Ana C V; Ewald, Ingrid Petroni; Sapienza, Marina; Pinheiro, Manuela; Peixoto, Ana; Nóbrega, Amanda França de; Carraro, Dirce M; Teixeira, Manuel R; Ashton-Prolla, Patricia

2012-01-01

Li-Fraumeni (LFS) and Li-Fraumeni-like (LFL) syndromes are associated to germline TP53 mutations, and are characterized by the development of central nervous system tumors, sarcomas, adrenocortical carcinomas, and other early-onset tumors. Due to the high frequency of breast cancer in LFS/LFL families, these syndromes clinically overlap with hereditary breast cancer (HBC). Germline point mutations in BRCA1, BRCA2, and TP53 genes are associated with high risk of breast cancer. Large rearrangements involving these genes are also implicated in the HBC phenotype. We have screened DNA copy number changes by MLPA on BRCA1, BRCA2, and TP53 genes in 23 breast cancer patients with a clinical diagnosis consistent with LFS/LFL; most of these families also met the clinical criteria for other HBC syndromes. We found no DNA copy number alterations in the BRCA2 and TP53 genes, but we detected in one patient a 36.4 Kb BRCA1 microdeletion, confirmed and further mapped by array-CGH, encompassing exons 9–19. Breakpoints sequencing analysis suggests that this rearrangement was mediated by flanking Alu sequences. This is the first description of a germline intragenic BRCA1 deletion in a breast cancer patient with a family history consistent with both LFL and HBC syndromes. Our results show that large rearrangements in these known cancer predisposition genes occur, but are not a frequent cause of cancer susceptibility

mediation: R package for causal mediation analysis

OpenAIRE

Tingley, Dustin; Yamamoto, Teppei; Hirose, Kentaro; Keele, Luke; Imai, Kosuke

2012-01-01

In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting su...

Craniosynostosis and Noonan syndrome with KRAS mutations: Expanding the phenotype with a case report and review of the literature.

Science.gov (United States)

Addissie, Yonit A; Kotecha, Udhaya; Hart, Rachel A; Martinez, Ariel F; Kruszka, Paul; Muenke, Maximilian

2015-11-01

Noonan syndrome (NS) is a multiple congenital anomaly syndrome caused by germline mutations in genes coding for components of the Ras-mitogen-activated protein kinase (RAS-MAPK) pathway. Features include short stature, characteristic facies, congenital heart anomalies, and developmental delay. While there is considerable clinical heterogeneity in NS, craniosynostosis is not a common feature of the condition. Here, we report on a 2 month-old girl with Noonan syndrome associated with a de novo mutation in KRAS (p.P34Q) and premature closure of the sagittal suture. We provide a review of the literature of germline KRAS mutations and find that approximately 10% of published cases have craniosynostosis. Our findings expand on the NS phenotype and suggest that germline mutations in the KRAS gene are causally involved in craniosynostosis, supporting the role of the RAS-MAPK pathway as a mediator of aberrant bone growth in cranial sutures. The inclusion of craniosynostosis as a possible phenotype in KRAS-associated Noonan Syndrome has implications in the differential diagnosis and surgical management of individuals with craniosynostosis. © 2015 Wiley Periodicals, Inc.

Toxic shock syndrome

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Staphylococcal toxic shock syndrome; Toxic shock-like syndrome; TSLS ... Toxic shock syndrome is caused by a toxin produced by some types of staphylococcus bacteria. A similar problem, called toxic shock- ...

Eosinophilic leukocytoclastic vasculitis - a spectrum ranging from Wells' syndrome to Churg-Strauss syndrome?

Science.gov (United States)

Ratzinger, Gudrun; Zankl, Julia; Eisendle, Klaus; Zelger, Bernhard

2014-01-01

Wells' syndrome is defined as an inflammatory disorder with the histopathological presence of eosinophilic infiltrates and flame figures in the absence of vasculitis. Eosinophilic leukocytoclastic vasculitis shows eosinophilic infiltrates in combination with vasculitic changes. And Churg Strauss Syndrome comprises all three characteristics - eosinophilic infiltrates, vasculitis and flame figures. To determine whether these three diseases are distinct entities or different manifestations of a similar clinicopathologic process. Histopathological samples and clinical courses of 17 patients with eosinophilic infiltrates, flame figures and clinical features of Wells' syndrome were re-evaluated. Histopathologically, we focused on the presence or absence of vasculitic features. Clinically, we included only patients who were diagnosed with Wells' syndrome at least once in the course of their disease. 4 patients were finally diagnosed with Wells' syndrome, 5 with eosinophilic leukocytoclastic vasculitis and 6 with Churg Strauss syndrome. Further, we had one case of an overlap between Wells' syndrome and eosinophilic vasculitis and one case of Wegener granulomatosis. Vasculitic features were found in the samples of all patients. Histologically, we find vasculitic features in typical presentations of Wells' syndrome. Clinically, we find typical features of Wells' syndrome in patients finally diagnosed with eosinophilic leukocytoclastic vasculitis or Churg Strauss syndrome. Furthermore, we have observed and formerly reported 3 patients with progression from Wells' syndrome to Churg Strauss syndrome. Thus, we assume that eosinophilic leukocytoclastic vasculitis might form a bridge between Wells' syndrome and Churg Strauss syndrome.

Thrombotic Management of Antiphospholipid Syndrome: Towards Novel Targeted Therapies.

Science.gov (United States)

Islam, Md Asiful; Alam, Fahmida; Wong, Kah Keng; Kamal, Mohammad Amjad; Gan, Siew Hua

2017-01-01

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombosis and/or pregnancy morbidity with persistent levels of antiphospholipid antibodies (aPLs). The development of thrombosis in APS is mediated by aPLs and contributes to the high mortality rate in APS patients. However, although APS has been reported for more than 30 years, there has been no optimal regimen for its prevention or for the management of thrombosis, mainly because the mainstay treatment strategies for managing APS are not targeted towards aPL-mediated thrombotic pathophysiology. Instead, the treatments commonly used are aimed at general thrombotic disorders. Warfarin is the most commonly used vitamin K antagonist (VKA), in addition to anti-platelet medications, such as aspirin and clopidogrel. Over the last decade, novel non-VKA oral anticoagulants, including rivaroxaban, apixaban and dabigatran, as well as immunomodulatory agents, such as rituximab, eculizumab, hydroxychloroquine, statins and sirolimus, have also been used. In this review, we discuss the current treatment strategies and future treatment outlook for thrombotic APS. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Impaired insulin activation and dephosphorylation of glycogen synthase in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment

DEFF Research Database (Denmark)

Glintborg, Dorte; Højlund, Kurt; Andersen, Nicoline Resen

2008-01-01

CONTEXT: Insulin resistance is a major risk factor for type 2 diabetes in women with polycystic ovary syndrome (PCOS). The molecular mechanisms underlying reduced insulin-mediated glycogen synthesis in skeletal muscle of patients with PCOS have not been established. SUBJECTS AND METHODS: We...... metabolically characterized by euglycemic-hyperinsulinemic clamps and indirect calorimetry. RESULTS: Reduced insulin-mediated glucose disposal (P .... No significant abnormalities in GSK-3alpha or -3beta were found in PCOS subjects. Pioglitazone treatment improved insulin-stimulated glucose metabolism and GS activity in PCOS (all P

Pathology in euthermic bats with white nose syndrome suggests a natural manifestation of immune reconstitution inflammatory syndrome.

Science.gov (United States)

Meteyer, Carol U; Barber, Daniel; Mandl, Judith N

2012-11-15

White nose syndrome, caused by Geomyces destructans, has killed more than 5 million cave hibernating bats in eastern North America. During hibernation, the lack of inflammatory cell recruitment at the site of fungal infection and erosion is consistent with a temperature-induced inhibition of immune cell trafficking. This immune suppression allows G. destructans to colonize and erode the skin of wings, ears and muzzle of bat hosts unchecked. Yet, paradoxically, within weeks of emergence from hibernation an intense neutrophilic inflammatory response to G. destructans is generated, causing severe pathology that can contribute to death. We hypothesize that the sudden reversal of immune suppression in bats upon the return to euthermia leads to a form of immune reconstitution inflammatory syndrome (IRIS). IRIS was first described in HIV-infected humans with low helper T lymphocyte counts and bacterial or fungal opportunistic infections. IRIS is a paradoxical and rapid worsening of symptoms in immune compromised humans upon restoration of immunity in the face of an ongoing infectious process. In humans with HIV, the restoration of adaptive immunity following suppression of HIV replication with anti-retroviral therapy (ART) can trigger severe immune-mediated tissue damage that can result in death. We propose that the sudden restoration of immune responses in bats infected with G. destructans results in an IRIS-like dysregulated immune response that causes the post-emergent pathology.

Pathology in euthermic bats with white nose syndrome suggests a natural manifestation of immune reconstitution inflammatory syndrome

Science.gov (United States)

Meteyer, Carol U.; Barber, Daniel; Mandl, Judith N.

2012-01-01

White nose syndrome, caused by Geomyces destructans, has killed more than 5 million cave hibernating bats in eastern North America. During hibernation, the lack of inflammatory cell recruitment at the site of fungal infection and erosion is consistent with a temperature-induced inhibition of immune cell trafficking. This immune suppression allows G. destructans to colonize and erode the skin of wings, ears and muzzle of bat hosts unchecked. Yet, paradoxically, within weeks of emergence from hibernation an intense neutrophilic inflammatory response to G. destructans is generated, causing severe pathology that can contribute to death. We hypothesize that the sudden reversal of immune suppression in bats upon the return to euthermia leads to a form of immune reconstitution inflammatory syndrome (IRIS), which was first described in HIV-infected humans with low helper T lymphocyte counts and bacterial or fungal opportunistic infections. IRIS is a paradoxical and rapid worsening of symptoms in immune compromised humans upon restoration of immunity in the face of an ongoing infectious process. In humans with HIV, the restoration of adaptive immunity following suppression of HIV replication with anti-retroviral therapy (ART) can trigger severe immune-mediated tissue damage that can result in death. We propose that the sudden restoration of immune responses in bats infected with G. destructans results in an IRIS-like dysregulated immune response that causes the post-emergent pathology.

Management of moyamoya syndrome in patients with Noonan syndrome.

Science.gov (United States)

Gupta, Mihir; Choudhri, Omar A; Feroze, Abdullah H; Do, Huy M; Grant, Gerald A; Steinberg, Gary K

2016-06-01

A few isolated reports have described an association between Noonan syndrome and cerebrovascular abnormalities, including moyamoya syndrome. These reports have been limited to pediatric patients presenting with recurrent transient ischemic attacks (TIA) or headaches. Management has primarily been pharmacologic, with only one prior report of surgical revascularization to our knowledge. We report four cases of Noonan syndrome patients presenting with headaches and/or sensorimotor strokes in childhood that caused unilateral sensorimotor impairment. Cerebral angiography and MRI revealed bilateral moyamoya syndrome. All patients underwent successful bilateral extracranial-to-intracranial revascularization. The first patient was a 10-year-old girl who presented following a hemorrhagic stroke and recovered well after indirect bypass. The second patient was an adult with a history of childhood stroke whose symptoms progressed in adulthood. She underwent a direct bypass and improved, but continued to experience TIA at her 4 year follow-up. The third patient was a 7-year-old girl with headaches and a new onset TIA who failed pharmacological therapy and subsequently underwent bilateral indirect bypass. The fourth patient was a 24-year-old woman with worsening headaches and an occluded left middle cerebral artery from unilateral moyamoya syndrome. A left sided direct bypass was completed given delayed MRI perfusion with poor augmentation. To our knowledge these are the first reported surgical cases of combined Noonan and moyamoya syndrome. These cases highlight the need to recognize moyamoya syndrome in patients with Noonan syndrome. Early surgical revascularization should be pursued in order to prevent symptom progression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multiple cranial neuropathies without limb involvements: guillain-barre syndrome variant?

Science.gov (United States)

Yu, Ju Young; Jung, Han Young; Kim, Chang Hwan; Kim, Hyo Sang; Kim, Myeong Ok

2013-10-01

Acute multiple cranial neuropathies are considered as variant of Guillain-Barre syndrome, which are immune-mediated diseases triggered by various cases. It is a rare disease which is related to infectious, inflammatory or systemic diseases. According to previous case reports, those affected can exhibit almost bilateral facial nerve palsy, then followed by bulbar dysfunctions (cranial nerves IX and X) accompanied by limb weakness and walking difficulties due to motor and/or sensory dysfunctions. Furthermore, reported cases of the acute multiple cranial neuropathies show electrophysiological abnormalities compatible with the typical Guillain-Barre syndromes (GBS). We recently experienced a patient with a benign infectious disease who subsequently developed symptoms of variant GBS. Here, we describe the case of a 48-year-old male patient who developed multiple symptoms of cranial neuropathy without limb weakness. His laboratory findings showed a positive result for anti-GQ1b IgG antibody. As compared with previously described variants of GBS, the patient exhibited widespread cranial neuropathy, which included neuropathies of cranial nerves III-XII, without limb involvement or ataxia.

What carries a mediation process? Configural analysis of mediation.

Science.gov (United States)

von Eye, Alexander; Mun, Eun Young; Mair, Patrick

2009-09-01

Mediation is a process that links a predictor and a criterion via a mediator variable. Mediation can be full or partial. This well-established definition operates at the level of variables even if they are categorical. In this article, two new approaches to the analysis of mediation are proposed. Both of these approaches focus on the analysis of categorical variables. The first involves mediation analysis at the level of configurations instead of variables. Thus, mediation can be incorporated into the arsenal of methods of analysis for person-oriented research. Second, it is proposed that Configural Frequency Analysis (CFA) can be used for both exploration and confirmation of mediation relationships among categorical variables. The implications of using CFA are first that mediation hypotheses can be tested at the level of individual configurations instead of variables. Second, this approach leaves the door open for different types of mediation processes to exist within the same set. Using a data example, it is illustrated that aggregate-level analysis can overlook mediation processes that operate at the level of individual configurations.

Obstructive sleep apnoea/hypopnoea syndrome in adults with Down syndrome

OpenAIRE

Hill, Elizabeth A.

2016-01-01

Key points Adults with Down syndrome are predisposed to obstructive sleep apnoea/hypopnoea syndrome (OSAHS) due to overlap between the Down syndrome phenotype and OSAHS risk factors. The prevalence of OSAHS in adults with Down syndrome is estimated at 35?42%. This is up to ten-times higher than in the general adult population. Symptoms of OSAHS, including behavioural and emotional disturbances as well as standard symptoms such as sleepiness, should be monitored as part of regular health surve...

Profession of mediator as the professional provider of the mediation process

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Jernej Šoštar

2017-03-01

Full Text Available The civil mediation programme, which is a court-connected programme, established as a form of alternative dispute resolution, is increasingly gaining ground as a field with its own theoretical and practical knowledge, principles and basic rules. Mediation has already set up its own body of knowledge, based on studies, classification of cases and the analyses of the results. In this article, we examine whether in the context of the development of mediation in Slovenia we might already talk about the profession of the mediator, defined as a provider of the mediation process. We examine the court-connected civil mediation and mediators who mediate at the court-connected civil mediation, and define them theoretically. By interviewing the mediation experts and mediators we examine their opinions about mediators and the court mediation. We examine the legal basis for the court-connected mediation programmes in Slovenia as well as in the European Union. Proceeding from our findings we conclude that the legal regulation of the court mediation in Slovenia is well established, and that the mediators of the court-connected civil mediation programmes can be accepted as the professional providers of the mediation process.

Evaluation of abdominal fat index by ultrasonography and its relationship with psoriasis and metabolic syndrome.

Science.gov (United States)

Gönül, Müzeyyen; Tatar, İdil; Canpolat, Filiz; Işıl Kurmus, Gökçe; Ergin, Can; Hekimoğlu, Baki

2017-10-01

Accumulating evidence indicates that psoriasis is associated with obesity and metabolic syndrome. Psoriasis and obesity share similar inflammatory mediators, and obesity may potentiate some inflammatory cytokines seen in psoriasis. Body fat distribution, particularly visceral adipose tissue (VAT), is an important factor in metabolic syndrome and atherosclerotic diseases. An association has been demonstrated between psoriasis and abdominal VAT measured by computed tomography (CT). To measure abdominal VAT noninvasively by ultrasonography (USG) in patients with psoriasis and investigated its relation to psoriasis and metabolic syndrome. The study population consisted of 41 psoriasis patients and 41 control subjects matched for age, sex, and body mass index. The maximal preperitoneal fat thickness (Pmax) at the anterior surface of the liver and the minimal subcutaneous fat thickness (Smin) of the abdomen were measured by USG. The abdominal fat index (AFI = Pmax/Smin ratio) was calculated and the results were compared between groups. The rate of metabolic syndrome was significantly higher in psoriasis patients ( p = 0.0018). The mean AFI was similar in both groups. AFI was not associated with psoriasis in subjects with metabolic syndrome ( p = 0.495) or with Psoriasis Area and Severity Index ( r = 0.123, p = 0.443). This is the first study to evaluate abdominal VAT by USG. Computed tomography may be more reliable than USG, but its high cost and radiation exposure are major disadvantages. Further studies are required to determine the relationships between psoriasis and VAT.

Vasoactive mediators and splanchnic perfusion.

Science.gov (United States)

Reilly, P M; Bulkley, G B

1993-02-01

To provide an overview of the splanchnic hemodynamic response to circulatory shock. Previous studies performed in our own laboratory, as well as a computer-assisted search of the English language literature (MEDLINE, 1966 to 1991), followed by a selective review of pertinent articles. Studies were selected that demonstrated relevance to the splanchnic hemodynamic response to circulatory shock, either by investigating the pathophysiology or documenting the sequelae. Article selection included clinical studies as well as studies in appropriate animal models. Pertinent data were abstracted from the cited articles. The splanchnic hemodynamic response to circulatory shock is characterized by a selective vasoconstriction of the mesenteric vasculature mediated largely by the renin-angiotensin axis. This vasospasm, while providing a natural selective advantage to the organism in mild-to-moderate shock (preserving relative perfusion of the heart, kidneys, and brain), may, in more severe shock, cause consequent loss of the gut epithelial barrier, or even hemorrhagic gastritis, ischemic colitis, or ischemic hepatitis. From a physiologic standpoint, nonpulsatile cardiopulmonary bypass, a controlled form of circulatory shock, has been found experimentally to significantly increase circulating levels of angiotensin II, the hormone responsible for this selective splanchnic vasoconstriction. While angiotensin II has been viewed primarily as the mediator responsible for the increased total vascular resistance seen during (and after) cardiopulmonary bypass, it may also cause the disproportionate decrease in mesenteric perfusion, as measured in human subjects by intraluminal gastric tonometry and galactose clearance by the liver, as well as the consequent development of the multiple organ failure syndrome seen in 1% to 5% of patients after cardiac surgery.

What is Metabolic Syndrome?

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... Intramural Research Home / Metabolic Syndrome Metabolic Syndrome Also known as What Is Metabolic syndrome ... metabolic risk factors to be diagnosed with metabolic syndrome. Metabolic Risk Factors A Large Waistline Having a large ...

Prune belly syndrome

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Eagle-Barrett syndrome; Triad syndrome ... The exact causes of prune belly syndrome are unknown. The condition affects mostly boys. While in the womb, the developing baby's abdomen swells with fluid. Often, the cause is ...

Gorlin-goltz syndrome

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B V Shobha

2011-01-01

Full Text Available Gorlin-Goltz syndrome also known as nevoid basal cell carcinoma syndrome (NBCCS is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by keratocystic odontogenic tumors (KCOT in the jaw, multiple basal cell carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic examination in the first decade of life, as KCOTs are usually one of the first manifestations of the NBCCS syndrome. This article reports the case of a 12-year-old girl with Gorlin-Goltz syndrome, emphasizing its clinical and radiographic manifestation. This study highlights the importance of health professionals in the early diagnosis of this syndrome and a multidisciplinary approach to provide a better diagnosis and prognosis.

Refeeding syndrome

OpenAIRE

Tripathy, Swagata; Mishra, Padmini; Dash, S. C.

2008-01-01

Refeeding syndrome is a potentially fatal medical condition that may affect malnourished patients in response to an inappropriately rapid overfeeding. This commonly occurs following the institution of nutritional support, especially parenteral or enteral nutrition. The most characteristic pathophysiology of refeeding syndrome relates to the rapid consumption of phosphate after glucose intake and subsequent hypophosphatemia. Refeeding syndrome can manifest as either metabolic changes （hypokala...

Nevoid basal cell carcinoma syndrome

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NBCC syndrome; Gorlin-Goltz syndrome; Basal cell nevus syndrome; BCNS; Basal cell cancer - nevoid basal cell carcinoma syndrome ... Nevoid basal cell carcinoma nevus syndrome is a rare genetic ... syndrome is known as PTCH ("patched"). The gene is passed down ...

The wellness syndrome

DEFF Research Database (Denmark)

Mik-Meyer, Nanna

2015-01-01

Klumme. Wellness er blevet et syndrom, og dets symptomer er angst, selvbebrejdelser og skyldfølelse. Kommentar med udgangspunkt i: Carl Cederström & Andre Spicer, "The Wellness Syndrome" (Polity Books, 2015. 200 p.).......Klumme. Wellness er blevet et syndrom, og dets symptomer er angst, selvbebrejdelser og skyldfølelse. Kommentar med udgangspunkt i: Carl Cederström & Andre Spicer, "The Wellness Syndrome" (Polity Books, 2015. 200 p.)....

Turner Syndrome: Other FAQs

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... Other FAQs Share Facebook Twitter Pinterest Email Print Turner Syndrome: Other FAQs Basic information for topics, such as " ... been diagnosed with Turner syndrome. Now what? Is Turner syndrome inherited? Turner syndrome is usually not inherited, but ...

Bardet-Biedl syndrome and Usher syndrome.

Science.gov (United States)

Koenig, Rainer

2003-01-01

Bardet-Biedl syndrome (BBS) and Usher syndrome (USH) are the most prevalent syndromic forms of retinitis pigmentosa (RP), together they make up almost a quarter of the patients with RP. BBS is defined by the association of retinopathy, obesity, hypogonadism, renal dysfunction, postaxial polydactyly and mental retardation. This clinically complex syndrome is genetically heterogeneous with linkage to more than 6 loci, and 4 genes have been cloned so far. Recent molecular data present evidence that, in some instances, the clinical manifestation of BBS requires recessive mutations in 1 of the 6 BBS loci plus one or two additional mutations in a second BBS locus (tri- or tetra-allelic inheritance). USH is characterized by the combination of congenital or early-onset sensorineural deafness, RP, and variable degrees of vestibular dysfunction. Each of the three clinical types is genetically heterogeneous: 7 loci have been mapped for type 1, three loci for type 2, and two loci for type 3. Currently, 6 USH genes (MYO7A, USH1C, CDH23, PCDH15, USH2A, USH3) have been identified. Pathogenetically, mutations of the USH1 genes seem to result in defects of auditory and retinal sensory cells, the USH 2 phenotype is caused by defects of extracellular matrix or cell surface receptor proteins, and USH3 may be due to synaptic disturbances. The considerable contribution of syndromic forms of RP requires interdisciplinary approaches to the clinical and diagnostic management of RP patients.

Abdominal compartment syndrome with acute reperfusion syndrome

International Nuclear Information System (INIS)

Maleeva, A.

2017-01-01

Abdominal compartment syndrome was recognized clinically in the 19th century when Marey and Burt observed its association with declines in respiratory function. Abdominal compartment syndrome is first used as a medical terminology from Fietsman in a case of ruptured abdominal aortic aneurysm. A condition caused by abnormally increased pressure within the abdomen. Causes of abdominal compartment syndrome include trauma, surgery, or infection. Common symptoms: abdominal distension, fast heart rate, insufficient urine production, or low blood pressure Medical procedure: nasogastric intubation Surgery: laparotomy Specialists: radiologist, primary care provider (PCP), surgeon, and emergency medicine doctor [6, 10]. Keywords: Stomach. Gastroparesis . Diabetes Mellitus [bg

Munchausen syndrome and Munchausen syndrome by proxy in dermatology.

Science.gov (United States)

Boyd, Alan S; Ritchie, Coleman; Likhari, Sunaina

2014-08-01

Patients with Munchausen syndrome purposefully injure themselves, often with the injection of foreign materials, to gain hospital admission and the attention associated with having a difficult-to-identify condition. Munchausen syndrome by proxy occurs when a child's caregiver, typically the mother, injures the child for the same reasons. Cases of Munchausen syndrome and Munchausen syndrome by proxy with primary cutaneous involvement appear to be rarely described in the literature suggesting either that diagnosis is not made readily or that it is, in fact, an uncommon disorder. At the center of both conditions is significant psychological pathology and treatment is difficult as many patients with Munchausen syndrome when confronted with these diagnostic possibilities simply leave the hospital. Little is known about the long-term outcome or prognosis of these patients. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Natural history of food protein-induced enterocolitis syndrome.

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Katz, Yitzhak; Goldberg, Michael R

2014-06-01

Because of the paucity of reports and variability in the diagnostic criteria utilized, little is known regarding the natural outcome of patients with food protein-induced enterocolitis syndrome (FPIES). Data extracted from referenced manuscripts, as well as allergists' unpublished observations from across the globe, were used to form a cohesive opinion regarding its natural outcome. All authors concur that there is a generally high rate of recovery for FPIES. The most common foods causing FPIES are milk and soy. Depending upon which study is analyzed, by the age of 3-5 years, approximately 90% of patients recover from their disease. Recovery from FPIES to solid foods, occurs at a later age, but may reflect a later stage of introduction of the food into the diet. An important clinical outcome, although not common, is a shift from FPIES food hypersensitivity to an IgE-mediated food allergy. This necessitates a change in the oral food challenge protocol, if IgE-mediated sensitization is detected. Over the past several years, there has been an increasing awareness of FPIES. This knowledge should lead to a more timely diagnosis and should reassure parents and practitioners alike regarding its favorable course.

Interferon alpha inhibits viral replication of a live-attenuated porcine reproductive and respiratory syndrome virus vaccine preventing development of an adaptive immune response in swine

Science.gov (United States)

Type I interferons, such as interferon alpha (IFNa), contribute to innate antiviral immunity by promoting production of antiviral mediators and are also involved in promoting an adaptive immune response. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most devastating and c...

Roberts-SC syndrome, a rare syndrome and cleft palate repair

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Murthy Jyotsna

2008-01-01

Full Text Available Roberts SC syndrome is a rare syndrome with only 17 previously recognized patients reported in medical literature. The syndrome is characterized by multiple malformations, particularly, symmetrical limb reduction, craniofacial anomalies such as bilateral cleft lip and palate, micrognathia, and severe growth and mental retardation. Our patient, a young child of five years having Roberts-SC, was successfully operated for cleft palate under general anesthesia. The main features of the syndrome and the technical problems of anesthesia and surgery are discussed in this report.

Loading of PAX3 to Mitotic Chromosomes Is Mediated by Arginine Methylation and Associated with Waardenburg Syndrome.

Science.gov (United States)

Wu, Tsu-Fang; Yao, Ya-Li; Lai, I-Lu; Lai, Chien-Chen; Lin, Pei-Lun; Yang, Wen-Ming

2015-08-14

PAX3 is a transcription factor critical to gene regulation in mammalian development. Mutations in PAX3 are associated with Waardenburg syndrome (WS), but the mechanism of how mutant PAX3 proteins cause WS remains unclear. Here, we found that PAX3 loads on mitotic chromosomes using its homeodomain. PAX3 WS mutants with mutations in homeodomain lose the ability to bind mitotic chromosomes. Moreover, loading of PAX3 on mitotic chromosomes requires arginine methylation, which is regulated by methyltransferase PRMT5 and demethylase JMJD6. Mutant PAX3 proteins that lose mitotic chromosome localization block cell proliferation and normal development of zebrafish. These results reveal the molecular mechanism of PAX3s loading on mitotic chromosomes and the importance of this localization pattern in normal development. Our findings suggest that PAX3 WS mutants interfere with the normal functions of PAX3 in a dominant negative manner, which is important to the understanding of the pathogenesis of Waardenburg syndrome. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Sjogren-Larsson Syndrome

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... Or In Memory Of Obituaries Contact Us Donate Sjogren-Larsson Syndrome What causes SLS? SLS is caused by mutations ... methods of diagnosing SLS. Other Clinical Names for Sjogren-Larsson Syndrome Other clinical names of Sjogren-Larsson Syndrome include: ...

Redefining syndromic surveillance

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Rebecca Katz

2011-12-01

Full Text Available With growing concerns about international spread of disease and expanding use of early disease detection surveillance methods, the field of syndromic surveillance has received increased attention over the last decade. The purpose of this article is to clarify the various meanings that have been assigned to the term syndromic surveillance and to propose a refined categorization of the characteristics of these systems. Existing literature and conference proceedings were examined on syndromic surveillance from 1998 to 2010, focusing on low- and middle-income settings. Based on the 36 unique definitions of syndromic surveillance found in the literature, five commonly accepted principles of syndromic surveillance systems were identified, as well as two fundamental categories: specific and non-specific disease detection. Ultimately, the proposed categorization of syndromic surveillance distinguishes between systems that focus on detecting defined syndromes or outcomes of interest and those that aim to uncover non-specific trends that suggest an outbreak may be occurring. By providing an accurate and comprehensive picture of this field’s capabilities, and differentiating among system types, a unified understanding of the syndromic surveillance field can be developed, encouraging the adoption, investment in, and implementation of these systems in settings that need bolstered surveillance capacity, particularly low- and middle-income countries.

Phosphoproteomics-mediated identification of Fer kinase as a target of mutant Shp2 in Noonan and LEOPARD syndrome.

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Jeroen Paardekooper Overman

Full Text Available Noonan syndrome (NS and LEOPARD syndrome (LS cause congenital afflictions such as short stature, hypertelorism and heart defects. More than 50% of NS and almost all of LS cases are caused by activating and inactivating mutations of the phosphatase Shp2, respectively. How these biochemically opposing mutations lead to similar clinical outcomes is not clear. Using zebrafish models of NS and LS and mass spectrometry-based phosphotyrosine proteomics, we identified a down-regulated peptide of Fer kinase in both NS and LS. Further investigation showed a role for Fer during development, where morpholino-based knockdown caused craniofacial defects, heart edema and short stature. During gastrulation, loss of Fer caused convergence and extension defects without affecting cell fate. Moreover, Fer knockdown cooperated with NS and LS, but not wild type Shp2 to induce developmental defects, suggesting a role for Fer in the pathogenesis of both NS and LS.

Central nervous system mechanisms contributing to the cachexia-anorexia syndrome.

Science.gov (United States)

Plata-Salamán, C R

2000-10-01

The cachexia-anorexia syndrome occurs in chronic pathophysiologic processes including cancer, infection with human immunodeficiency virus, bacterial and parasitic diseases, inflammatory bowel disease, liver disease, obstructive pulmonary disease, cardiovascular disease, and rheumatoid arthritis. Cachexia makes an organism susceptible to secondary pathologies and can result in death. Cachexia-anorexia may result from pain, depression or anxiety, hypogeusia and hyposmia, taste and food aversions, chronic nausea, vomiting, early satiety, malfunction of the gastrointestinal system (delayed digestion, malabsorption, gastric stasis and associated delayed emptying, and/or atrophic changes of the mucosa), metabolic shifts, cytokine action, production of substances by tumor cells, and/or iatrogenic causes such as chemotherapy and radiotherapy. The cachexia-anorexia syndrome also involves metabolic and immune changes (mediated by either the pathophysiologic process, i.e., tumor, or host-derived chemical factors, e.g., peptides, neurotransmitters, cytokines, and lipid-mobilizing factors) and is associated with hypertriacylglycerolemia, lipolysis, and acceleration of protein turnover. These changes result in the loss of fat mass and body protein. Increased resting energy expenditure in weight-losing cachectic patients can occur despite the reduced dietary intake, indicating a systemic dysregulation of host metabolism. During cachexia, the organism is maintained in a constant negative energy balance. This can rarely be explained by the actual energy and substrate demands by tumors in patients with cancer. Overall, the cachectic profile is significantly different than that observed during starvation. Cachexia may result not only from anorexia and a decreased caloric intake but also from malabsorption and losses from the body (ulcers, hemorrhage, effusions). In any case, the major deficit of a cachectic organism is a negative energy balance. Cytokines are proposed to participate

Gorlin-Goltz Syndrome

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Padma Pandeshwar

2012-01-01

Full Text Available The Gorlin-Goltz syndrome (GGS (the nevoid basal cell carcinoma syndrome—NBCCS is a rare autosomal dominant syndrome caused due to mutations in the PTCH (patched gene found on chromosome arm 9q. The syndrome, characterized by increased predisposition to develop basal cell carcinoma and associated multiorgan anomalies, has a high level of penetrance and variable expressiveness. GGS is a multidisciplinary problem, early diagnosis of which allows introduction of secondary prophylaxis and following an appropriate treatment to delay the progress of the syndrome. The following report emphasizes the need for awareness of the diagnostic criteria of this syndrome in cases with no typical skin lesions.

Sjögren syndrome

Science.gov (United States)

Xerostomia - Sjögren syndrome; Keratoconjunctivitis sicca - Sjögren; Sicca syndrome ... The cause of Sjögren syndrome is unknown. It is an autoimmune disorder. This means the body attacks healthy tissue by mistake. The syndrome occurs most ...

Marfan Syndrome (For Parents)

Science.gov (United States)

... en español Síndrome de Marfan What Is Marfan Syndrome? Marfan syndrome is a genetic disorder of the body's ... bones , blood vessels, and organs. What Causes Marfan Syndrome? Marfan syndrome happens because of an abnormality in one ...

Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome).

Science.gov (United States)

Kiran, N K; Tilak Raj, T N; Mukunda, K S; Rajashekar Reddy, V

2012-10-01

The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS), is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient.

Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome

Directory of Open Access Journals (Sweden)

N K Kiran

2012-01-01

Full Text Available The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS, is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient.

``Battered child`` syndrome; Das ``Battered-Child``-Syndrom

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Elsner, K.; Merk, J.; Sokiranski, R. [Ulm Univ. (Germany). Abt. Diagnostische Radiologie

1997-10-01

Synonyms for the `battered child` syndrome (BCS) are terms describing the physical and body aspects of the process, such as `child abuse`, or `non-accidental injury`. These are to be distinguished from the psychic aspects and abuse, emotional and bodily neglect, and sexual abuse. Most cases are one or another combination of these aspects. Radiology is the essential method for giving proof of such abuses, identifying the signs of maltreatment in a medical record, or for disproving suspected abuse. (orig./AJ) [Deutsch] Als Synonym fuer das `Battered-Child`-Syndrom (BCS) stehen die Begriffe der koerperlichen-/physikalischen-Kindesmisshandlung, im angelsaechsischen Sprachraum die Begriffe `Child Abuse` und `Nonaccidental Injury`. Vom Syndrom abzugrenzen sind die seelische Misshandlung, die seelische und koerperliche Vernachlaessigung, und der sexuelle Missbrauch. Kombinationsformen sind nicht selten. Bei der Diagnostik des Syndroms spielt die Radiologie eine entscheidende Rolle. So hilft der Einsatz adaequater Untersuchungsmethoden, den Tatbestand der Misshandlung zu identifizieren und zu dokumentieren, aber auch einen Verdacht zu widerlegen. (orig./AJ)

Estimation of Causal Mediation Effects for a Dichotomous Outcome in Multiple-Mediator Models using the Mediation Formula

OpenAIRE

Wang, Wei; Nelson, Suchitra; Albert, Jeffrey M.

2013-01-01

Mediators are intermediate variables in the causal pathway between an exposure and an outcome. Mediation analysis investigates the extent to which exposure effects occur through these variables, thus revealing causal mechanisms. In this paper, we consider the estimation of the mediation effect when the outcome is binary and multiple mediators of different types exist. We give a precise definition of the total mediation effect as well as decomposed mediation effects through individual or sets ...

Hepatorenal syndrome

Science.gov (United States)

... 2016:chap 153. Nevah MI, Fallon MB. Hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and other systemic complications of liver disease. In: Feldman M, Friedman LS, Brandt LJ, ...

Prevalence of metabolic syndrome in scholars from Bucaramanga, Colombia: a population-based study

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Camacho Paul A

2009-04-01

Full Text Available Abstract Background Obesity and metabolic syndrome are strongly associated with type 2 diabetes mellitus and cardiovascular diseases, thus the increasing trend in their prevalence among children and adolescents from developing countries requires a further understanding of their epidemiology and determinants. Methods and design A cross-sectional study was designed to determine the prevalence of metabolic syndrome among 6–10 year-old children from Bucaramanga, Colombia. A two-stage random-cluster (neighborhoods, houses sampling process was performed based on local city maps and local statistics. The study involves a domiciliary survey; including a comprehensive socio-demographic, nutritional and physical activity characterization of the children that participated in the study, followed by a complete clinical examination; including blood pressure, anthropometry, lipid profile determination, fasting glucose and insulin levels. The prevalence of metabolic syndrome will be determined using definitions and specific percentile cut-off points for this population. Finally, the association between components of metabolic syndrome and higher degrees of insulin resistance will be analyzed through a multivariable logistic regression model. This study protocol was designed in compliance with the Helsinki declaration and approved by the local ethics board. Consent was obtained from the children and their parents/guardians. Discussion A complete description of the environmental and non-environmental factors underlying the burden of metabolic syndrome in children from a developing country like Colombia will provide policy makers, health care providers and educators from similar settings with an opportunity to guide primary and secondary preventive initiatives at both individual and community levels. Moreover, this description may give an insight into the pathophysiological mechanisms mediating the development of cardio-metabolic diseases early in life.

Prevalence of Burnout Syndrome in patients admitted with acute coronary syndrome.

Science.gov (United States)

Prosdócimo, Ana Cláudia Giaxa; Lucina, Luciane Boreki; Marcia, Olandoski; Jobs, Priscila Megda João; Schio, Nicolle Amboni; Baldanzi, Fernanda Fachin; Costantini, Costantino Ortiz; Benevides-Pereira, Ana Maria Teresa; Guarita-Souza, Luiz Cesar; Faria-Neto, José Rocha

2015-03-01

Burnout Syndrome is the extreme emotional response to chronic occupational stress, manifesting as physical and mental exhaustion. Although associated with higher prevalence of cardiovascular risk factors, no study so far has evaluated whether the Burnout Syndrome could be a prevalent factor in non-elderly individuals active in the labor market, admitted for acute coronary syndrome (ACS). To evaluate the prevalence of the Burnout Syndrome in non-elderly, economically active patients, hospitalized with ACS. Cross-sectional study conducted in a tertiary and private cardiology center, with economically active patients aged Burnout Syndrome was evaluated with the Burnout Syndrome Inventory (BSI), which assesses workplace conditions and four dimensions that characterize the syndrome: emotional exhaustion (EE), emotional distancing (EmD), dehumanization (De) and professional fulfillment (PF). The Lipp's Stress Symptoms Inventory for Adults (LSSI) was applied to evaluate global stress. Of 830 patients evaluated with suspected ACS, 170 met the study criteria, 90% of which were men, overall average age was 52 years, and 40.5% had an average income above 11 minimum wages. The prevalence of the Burnout Syndrome was 4.1%. When we evaluated each dimension individually, we found high EE in 34.7%, high De in 52.4%, high EDi in 30.6%, and low PF in 5.9%. The overall prevalence of stress was 87.5%. We found a low prevalence of Burnout Syndrome in an economically active, non-elderly population among patients admitted for ACS in a tertiary and private hospital.

Turner Syndrome (For Teens)

Science.gov (United States)

... Staying Safe Videos for Educators Search English Español Turner Syndrome KidsHealth / For Teens / Turner Syndrome What's in this ... en español El síndrome de Turner What Is Turner Syndrome? Turner syndrome (TS) is a genetic condition found ...

Theory of Mind as a mediator variable between neurocognition and functioning in young individuals in treatment with secondary services for non-psychotic disorders.

Science.gov (United States)

Francesconi, Marta; Minichino, Amedeo; Carrión, Ricardo E; Chiaie, Roberto Delle; Bevilacqua, Arturo; Parisi, Maurizio; Rullo, Santo; Bersani, Francesco Saverio; Biondi, Massimo; Cadenhead, Kristin

2016-12-30

A large body of studies provides evidence for a link between neurocognition, theory of mind (ToM) and functioning in psychotic spectrum disorders (PSDs), with ToM mediating the effect that neurocognition has on functioning. These three constructs and the related mediation effect may characterize different psychiatric syndromes other than PSDs. Structural equation modelling (SEM) was applied to baseline data from a longitudinal study of 138 young individuals with a recent-onset psychiatric disorder. Using SEM, we tested the hypothesis that ToM mediates the effect of neurocognition on functioning independent of the level of psychosis risk and the diagnostic category. In the mediation model the bootstrapping estimate revealed a significant indirect effect that was the association of social cognition with neurocognition and with functional outcome. ToM was significantly associated with neurocognition and the path from neurocognition to functioning was no longer significant as soon as the mediator (ToM) was entered into the mediation model consistent with a complete mediation effect through ToM. This mediation was independent of the psychosis-risk status and the psychiatric diagnoses. Our results provide useful information on a young psychiatric sample, in which specific therapeutic interventions have the potential to significantly limit functional disability. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

DIDMOAD (Wolfram Syndrome

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Masoud Nashibi

2016-07-01

Full Text Available Wolfram syndrome was first described by physician D J Wolfram and Wagener in 1938. This autosomal recessive syndrome is also referred to as DIDMOAD syndrome which stands for Diabetes Insipidus, Insulin Dependent Diabetes Mellitus, Optic Atrophy and Deafness

[The Capgras syndrome].

Science.gov (United States)

Anikina, M A; Levin, O S

2013-01-01

The Capgras syndrome is one of delusional-like misidentification syndrome in which a person holds a delusion that one or several his/her friends or relatives have been replaced by an identical-looking impostor. As any other delusional disorder, the Capgras syndrome is characterized by stability despite the indisputable arguments against fault views. Initially, this syndrome was considered as a presentation of schizophrenia but later it has been described in brain organic disorders, primarily in elderly patients with dementia.

Revesz syndrome

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Dayane Cristine Issaho

2015-04-01

Full Text Available Revesz syndrome is a rare variant of dyskeratosis congenita and is characterized by bilateral exudative retinopathy, alterations in the anterior ocular segment, intrauterine growth retardation, fine sparse hair, reticulate skin pigmentation, bone marrow failure, cerebral calcification, cerebellar hypoplasia and psychomotor retardation. Few patients with this syndrome have been reported, and significant clinical variations exist among patients. This report describes the first Brazilian case of Revesz syndrome and its ocular and clinical features.

A central role of eNOS in the protective effect of wine against metabolic syndrome.

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Leighton, Federico; Miranda-Rottmann, Soledad; Urquiaga, Inés

2006-01-01

The positive health effects derived from moderate wine consumption are pleiotropic. They appear as improvements in cardiovascular risk factors such as plasma lipids, haemostatic mechanisms, endothelial function and antioxidant defences. The active principles would be ethanol and mainly polyphenols. Results from our and other laboratories support the unifying hypothesis that the improvements in risk factors after red wine consumption are mediated by endothelial nitric oxide synthase (eNOS). Many genes are involved, but the participation of eNOS would be a constant feature. The metabolic syndrome is a cluster of metabolic risk factors associated with high risk of cardiovascular disease (CVD). The National Cholesterol Education Programmmes Adult Treatment Panel III (NCEPATP III) clinical definition of the metabolic syndrome requires the presence of at least three risk factors, from among abdominal obesity, high plasma triacylglycerols, low plasma HDL, high blood pressure and high fasting plasma glucose. The molecular mechanisms responsible for the metabolic syndrome are not known. Since metabolic syndrome apparently affects 10-30% of the population in the world, research on its pathogenesis and control is needed. The recent finding that eNOS knockout mice present a cluster of cardiovascular risk factors comparable to those of the metabolic syndrome suggests that defects in eNOS function may cause human metabolic syndrome. These mice are hypertensive, insulin resistant and dyslipidemic. Further support for a pathogenic role of eNOS comes from the finding in humans that eNOS polymorphisms associate with insulin resistance and diabetes, with hypertension, with inflammatory and oxidative stress markers and with albuminuria. So, the data sustain the hypothesis that eNOS enhancement should reduce metabolic syndrome incidence and its consequences. Therefore red wine, since it enhances eNOS function, should be considered as a potential tool for the control of metabolic

Cardiorenal Syndrome in Acute Heart Failure Syndromes

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Mohammad Sarraf

2011-01-01

Full Text Available Impaired cardiac function leads to activation of the neurohumoral axis, sodium and water retention, congestion and ultimately impaired kidney function. This sequence of events has been termed the Cardiorenal Syndrome. This is different from the increase in cardiovascular complications which occur with primary kidney disease, that is, the so-called Renocardiac Syndrome. The present review discusses the pathogenesis of the Cardiorenal Syndrome followed by the benefits and potential deleterious effects of pharmacological agents that have been used in this setting. The agents discussed are diuretics, aquaretics, natriuretic peptides, vasodilators, inotropes and adenosine α1 receptor antagonists. The potential role of ultrafiltration is also briefly discussed.

Interstitial Cystitis/Painful Bladder Syndrome and Associated Medical Conditions With an Emphasis on Irritable Bowel Syndrome, Fibromyalgia and Chronic Fatigue Syndrome

DEFF Research Database (Denmark)

Nickel, J.C.; Tripp, D.A.; Pontari, M.

2010-01-01

of associated conditions increased (ie localized, regional, systemic), pain, stress, depression and sleep disturbance increased while social support, sexual functioning and quality of life deteriorated. Anxiety and catastrophizing remained increased in all groups. Symptom duration was associated......Purpose: We characterized and compared the impact of clinical phenotypic associations between interstitial cystitis/painful bladder syndrome and controls in relation to potentially related conditions, particularly irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome. Materials...... cystitis/painful bladder syndrome vs controls was irritable bowel syndrome 38.6% vs 5.2%, fibromyalgia 17.7% vs 2.6% and chronic fatigue syndrome 9.5% vs 1.7% (all p

Plummer-Vinson syndrome

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Novacek Gottfried

2006-09-01

Full Text Available Abstract Plummer-Vinson or Paterson-Kelly syndrome presents as a classical triad of dysphagia, iron-deficiency anemia and esophageal webs. Exact data about epidemiology of the syndrome are not available; the syndrome is extremely rare. Most of the patients are white middle-aged women, in the fourth to seventh decade of life but the syndrome has also been described in children and adolescents. The dysphagia is usually painless and intermittent or progressive over years, limited to solids and sometimes associated with weight loss. Symptoms resulting from anemia (weakness, pallor, fatigue, tachycardia may dominate the clinical picture. Additional features are glossitis, angular cheilitis and koilonychia. Enlargement of the spleen and thyroid may also be observed. One of the most important clinical aspects of Plummer-Vinson syndrome is the association with upper alimentary tract cancers. Etiopathogenesis of Plummer-Vinson syndrome is unknown. The most important possible etiological factor is iron deficiency. Other possible factors include malnutrition, genetic predisposition or autoimmune processes. Plummer-Vinson syndrome can be treated effectively with iron supplementation and mechanical dilation. In case of significant obstruction of the esophageal lumen by esophageal web and persistent dysphagia despite iron supplementation, rupture and dilation of the web are necessary. Since Plummer-Vinson syndrome is associated with an increased risk of squamous cell carcinoma of the pharynx and the esophagus, the patients should be followed closely.

Hypersensitivity to mosquito bite manifested as Skeeter syndrome

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Rafael Pérez-Vanzzini

2015-02-01

Full Text Available The reactions to mosquito bites are immunological reactions with involvement of IgE, IgG and T cells mediated hypersensitivity. These reactions are common and range from small local reactions, large local reactions to systemic allergic reactions. Skeeter syndrome is defined as a large local induced inflammatory reaction to mosquito bite and sometimes accompanied by systemic symptoms such as fever and vomiting. Diagnosis is based on clinical history and physical examination, supported by the identification of specific IgE by skin testing. Treatment includes prevention, antihistamines and steroids in some cases. Specific immunotherapy still requires further study. This paper reports two cases of patients with hypersensitivity reactions to mosquito bites, which were evaluated in our center presenting positive skin tests.

Causal mediation analysis with multiple mediators.

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Daniel, R M; De Stavola, B L; Cousens, S N; Vansteelandt, S

2015-03-01

In diverse fields of empirical research-including many in the biological sciences-attempts are made to decompose the effect of an exposure on an outcome into its effects via a number of different pathways. For example, we may wish to separate the effect of heavy alcohol consumption on systolic blood pressure (SBP) into effects via body mass index (BMI), via gamma-glutamyl transpeptidase (GGT), and via other pathways. Much progress has been made, mainly due to contributions from the field of causal inference, in understanding the precise nature of statistical estimands that capture such intuitive effects, the assumptions under which they can be identified, and statistical methods for doing so. These contributions have focused almost entirely on settings with a single mediator, or a set of mediators considered en bloc; in many applications, however, researchers attempt a much more ambitious decomposition into numerous path-specific effects through many mediators. In this article, we give counterfactual definitions of such path-specific estimands in settings with multiple mediators, when earlier mediators may affect later ones, showing that there are many ways in which decomposition can be done. We discuss the strong assumptions under which the effects are identified, suggesting a sensitivity analysis approach when a particular subset of the assumptions cannot be justified. These ideas are illustrated using data on alcohol consumption, SBP, BMI, and GGT from the Izhevsk Family Study. We aim to bridge the gap from "single mediator theory" to "multiple mediator practice," highlighting the ambitious nature of this endeavor and giving practical suggestions on how to proceed. © 2014 The Authors Biometrics published by Wiley Periodicals, Inc. on behalf of International Biometric Society.

mma: An R Package for Mediation Analysis with Multiple Mediators

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Qingzhao Yu

2017-04-01

Full Text Available Mediation refers to the effect transmitted by mediators that intervene in the relationship between an exposure and a response variable. Mediation analysis has been broadly studied in many fields. However, it remains a challenge for researchers to consider complicated associations among variables and to differentiate individual effects from multiple mediators. [1] proposed general definitions of mediation effects that were adaptable to all different types of response (categorical or continuous, exposure, or mediation variables. With these definitions, multiple mediators of different types can be considered simultaneously, and the indirect effects carried by individual mediators can be separated from the total effect. Moreover, the derived mediation analysis can be performed with general predictive models. That is, the relationships among variables can be modeled using not only generalized linear models but also nonparametric models such as the Multiple Additive Regression Trees. Therefore, more complicated variable transformations and interactions can be considered in analyzing the mediation effects. The proposed method is realized by the R package 'mma'. We illustrate in this paper the proposed method and how to use 'mma' to estimate mediation effects and make inferences.

Genetics Home Reference: antiphospholipid syndrome

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... Share: Email Facebook Twitter Home Health Conditions Antiphospholipid syndrome Antiphospholipid syndrome Printable PDF Open All Close All Enable ... area? Other Names for This Condition anti-phospholipid syndrome antiphospholipid antibody syndrome Hughes syndrome Related Information How are ...

Genetics Home Reference: Costello syndrome

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... other genetic conditions, cardiofaciocutaneous syndrome (CFC syndrome) and Noonan syndrome . In affected infants, it can be difficult to ... These individuals may actually have CFC syndrome or Noonan syndrome , which are caused by mutations in related genes. ...

SIRT1 and metabolic syndrome

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Katarzyna Mac-Marcjanek

2011-04-01

Full Text Available Both obesity and type 2 diabetes mellitus, two major components of metabolic syndrome, become healthepidemics in the world. Over the past decade, advances in understanding the role of some regulators participatingin lipid and carbohydrate homeostasis have been made.Of them, SIRT1, the mammalian orthologue of the yeast Sir2 protein has been identified. SIRT1 is a nuclearNAD+-dependent deacetylase that targets many transcriptional modulators, including PPAR-α and -γ (peroxisomeproliferator-activated receptors α and γ, PGC-1α (PPAR-γ coactivator-1α, FOXO (forkhead box O proteins,and nuclear factor κB (NF-κB, thereby this enzyme mediates a wide range of physiological processes like apoptosis,fat metabolism, glucose homeostasis, and neurodegeneration.In this article, we discuss how SIRT1 regulates lipid and carbohydrate metabolism, and insulin secretion indifferent metabolic organs/tissue, including liver, muscle, pancreas, and fat. Additionally, the role of this enzymein reduction of inflammatory signalling is highlighted.

Metabolic syndrome and menopause

Directory of Open Access Journals (Sweden)

Jouyandeh Zahra

2013-01-01

Full Text Available Abstract Background The metabolic syndrome is defined as an assemblage of risk factors for cardiovascular diseases, and menopause is associated with an increase in metabolic syndrome prevalence. The aim of this study was to assess the prevalence of metabolic syndrome and its components among postmenopausal women in Tehran, Iran. Methods In this cross-sectional study in menopause clinic in Tehran, 118 postmenopausal women were investigated. We used the adult treatment panel 3 (ATP3 criteria to classify subjects as having metabolic syndrome. Results Total prevalence of metabolic syndrome among our subjects was 30.1%. Waist circumference, HDL-cholesterol, fasting blood glucose, diastolic blood pressure ,Systolic blood pressure, and triglyceride were significantly higher among women with metabolic syndrome (P-value Conclusions Our study shows that postmenopausal status is associated with an increased risk of metabolic syndrome. Therefore, to prevent cardiovascular disease there is a need to evaluate metabolic syndrome and its components from the time of the menopause.

Interaction Between Syndromic and Non-Syndromic Factors Affecting Speech and Language Development in Treacher-Collins Syndrome

Directory of Open Access Journals (Sweden)

Marziyeh Poorjavad

2011-09-01

Full Text Available Background: Treacher-Collins syndrome is a congenital craniofacial disorder with multiple anomalies. This syndrome affects the maxilla, mandible, eyes, middle and outer ears, and soft palate. Conductive hearing loss due to the deformities of the middle and external ears is prevalent. The characteristics of this syndrome include multiple and serious threats to normal communication development in children. In this study, speech and language features of a Persian speaking child with this syndrome are presented.Case: The case was an 8-year old girl with Treacher-Collins syndrome and bilateral moderate conductive hearing loss due to atretic canal. In language and speech assessments, moderate hypernasality, numerous compensatory errors and morphosyntactic deficits were observed. There were 13 phonemes that were incorrectly produced at least in one position. Besides, she used 22 types of phonological processes that were abnormal and disappear before the age of three in normal Persian speaking children.Conclusion: Moderate hearing loss, velopharyngeal incompetency, malocclusion and dental anomalies, attention deficit/hyperactivity disorder (ADHD and environmental factors resulted in severe speech and language disorders in this case. These disorders affected her academic performance as well. Moderate hypernasality, numerous compensatory errors, and excessive and abnormal use of phonological processes were not presented as prevalent characteristics of Treacher-Collins syndrome in other resources.

Urofacial syndrome

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Kamal F Akl

2012-01-01

Full Text Available The urofacial syndrome is characterized by functional obstructive uropathy asso-ciated with an inverted smile. The importance of the subject is that it sheds light, not only on the muscles of facial expression, but also on the inheritance of voiding disorders and lower urinary tract malformations. We report a 10-year-old-male patient who had the urofacial syndrome. Early diagnosis of the urofacial syndrome is important to avoid upper urinary tract damage and renal failure.

Felty syndrome

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Seropositive rheumatoid arthritis (RA); Felty's syndrome ... The cause of Felty syndrome is unknown. It is more common in people who have had rheumatoid arthritis (RA) for a long time. People with ...

Pendred Syndrome

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... other possible long-term consequences of the syndrome. Children with Pendred syndrome should start early treatment to gain communication skills, such as learning sign language or cued speech or learning to ...

Unusual headache syndromes.

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Queiroz, Luiz P

2013-01-01

Some headache syndromes have few cases reported in the literature. Their clinical characteristics, pathogenesis, and treatment may have not been completely defined. They may not actually be uncommon but rather under-recognized and/or underreported. A literature review of unusual headache syndromes, searching PubMed and ISI Web of Knowledge, was performed. After deciding which disorders to study, relevant publications in scientific journals, including original articles, reviews, meeting abstracts, and letters or correspondences to the editors were searched. This paper reviewed the clinical characteristics, the pathogenesis, the diagnosis, and the treatment of five interesting and unusual headache syndromes: exploding head syndrome, red ear syndrome, neck-tongue syndrome, nummular headache, and cardiac cephalgia. Recognizing some unusual headaches, either primary or secondary, may be a challenge for many non-headache specialist physicians. It is important to study them because the correct diagnosis may result in specific treatments that may improve the quality of life of these patients, and this can even be life saving. © 2013 American Headache Society.

Burnout Syndrome of Teachers

OpenAIRE

Semrádová, Michaela

2013-01-01

The bachelor's thesis covers burnout syndrome of teachers. Defines burnout syndrome, describes its causes and symptoms. Describes teaching as helping profession and focousing on stressful situations at school. In the last chapter described different prevention strategies burnout syndrome. Key words: burnout syndrome, teaching, teacher, helping professions, beginning teacher, stress

Causal Mediation Analysis of Survival Outcome with Multiple Mediators.

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Huang, Yen-Tsung; Yang, Hwai-I

2017-05-01

Mediation analyses have been a popular approach to investigate the effect of an exposure on an outcome through a mediator. Mediation models with multiple mediators have been proposed for continuous and dichotomous outcomes. However, development of multimediator models for survival outcomes is still limited. We present methods for multimediator analyses using three survival models: Aalen additive hazard models, Cox proportional hazard models, and semiparametric probit models. Effects through mediators can be characterized by path-specific effects, for which definitions and identifiability assumptions are provided. We derive closed-form expressions for path-specific effects for the three models, which are intuitively interpreted using a causal diagram. Mediation analyses using Cox models under the rare-outcome assumption and Aalen additive hazard models consider effects on log hazard ratio and hazard difference, respectively; analyses using semiparametric probit models consider effects on difference in transformed survival time and survival probability. The three models were applied to a hepatitis study where we investigated effects of hepatitis C on liver cancer incidence mediated through baseline and/or follow-up hepatitis B viral load. The three methods show consistent results on respective effect scales, which suggest an adverse estimated effect of hepatitis C on liver cancer not mediated through hepatitis B, and a protective estimated effect mediated through the baseline (and possibly follow-up) of hepatitis B viral load. Causal mediation analyses of survival outcome with multiple mediators are developed for additive hazard and proportional hazard and probit models with utility demonstrated in a hepatitis study.

Prevalence of Burnout Syndrome in Patients Admitted with Acute Coronary Syndrome

Directory of Open Access Journals (Sweden)

Ana Cláudia Giaxa Prosdócimo

2015-03-01

Full Text Available Background: Burnout Syndrome is the extreme emotional response to chronic occupational stress, manifesting as physical and mental exhaustion. Although associated with higher prevalence of cardiovascular risk factors, no study so far has evaluated whether the Burnout Syndrome could be a prevalent factor in non-elderly individuals active in the labor market, admitted for acute coronary syndrome (ACS. Objective: To evaluate the prevalence of the Burnout Syndrome in non-elderly, economically active patients, hospitalized with ACS. Methods: Cross-sectional study conducted in a tertiary and private cardiology center, with economically active patients aged <65 years, hospitalized with diagnosis of ACS. The Burnout Syndrome was evaluated with the Burnout Syndrome Inventory (BSI, which assesses workplace conditions and four dimensions that characterize the syndrome: emotional exhaustion (EE, emotional distancing (EmD, dehumanization (De and professional fulfillment (PF. The Lipp’s Stress Symptoms Inventory for Adults (LSSI was applied to evaluate global stress. Results: Of 830 patients evaluated with suspected ACS, 170 met the study criteria, 90% of which were men, overall average age was 52 years, and 40.5% had an average income above 11 minimum wages. The prevalence of the Burnout Syndrome was 4.1%. When we evaluated each dimension individually, we found high EE in 34.7%, high De in 52.4%, high EDi in 30.6%, and low PF in 5.9%. The overall prevalence of stress was 87.5%. Conclusion: We found a low prevalence of Burnout Syndrome in an economically active, non-elderly population among patients admitted for ACS in a tertiary and private hospital.

"Nine" syndrome: A new neuro-ophthalmologic syndrome: Report of two cases

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Rohan R Mahale

2015-01-01

Full Text Available "Eight-and-a-half" syndrome is a rare condition involving the ipsilateral abducens nucleus or paramedian pontine reticular formation (PPRF, the ipsilateral medial longitudinal fasciculus (MLF, and the adjacent facial colliculus/facial nerve fascicle. The condition is often caused by a lesion (vascular or demyelinating in the dorsal tegmentum of the caudal pons. There are new variants of this syndrome caused by extension of lesion to involve new adjacent structures in pontine tegmentum. We report two patients with different etiology presenting with clinical features suggestive of eight-and-a-half syndrome associated with hemiataxia representing "nine" syndrome (8– + – = 9 adding new dimension to "eight-and-a-half" syndrome.

Mobius syndrome redefined: a syndrome of rhombencephalic maldevelopment.

NARCIS (Netherlands)

Verzijl, H.T.F.M.; Zwaag, A. van der; Cruysberg, J.R.M.; Padberg, G.W.A.M.

2003-01-01

OBJECTIVE: To investigate the variable clinical picture of Mobius syndrome (MIM no. 157900) and to further understand the pathogenesis of the disorder. METHODS: A standardized questionnaire was submitted to 37 Dutch patients with Mobius syndrome. All underwent standardized neurologic examination

Evaluation of early atherosclerotic findings in women with polycystic ovary syndrome

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Mohammadi Afshin

2011-10-01

Full Text Available Background Polycystic ovary syndrome (PCOS is the most common endocrinopathy in women of childbearing age, and it seems better to consider it as an ovarian manifestation of metabolic syndrome. The aim of the current study was to evaluate early atherosclerotic findings in patients with PCOS. Methods We enrolled 46 women with PCOS and 45 normal control subjects who were referred to our hospital's endocrinology outpatient clinic. Carotid intima media thickness (CIMT and flow-mediated dilatation (FMD were performed in both cases and matched controls. Results Patients with PCOS showed an increased mean CIMT (0.63 ± 0.16 mm when compared with the control subjects (0.33 ± 0.06 mm. This difference was statistically significant (p = 0.001. The mean FMD in young patients with PCOS was 10.07 ± 1.2%, while it was 6.5 ± 2.06% in normal subjects. This difference was also statistically significant (p = 0.001. Conclusion Our findings suggest that PCOS is related with early atherosclerotic findings.

Bartter syndrome

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... this page: //medlineplus.gov/ency/article/000308.htm Bartter syndrome To use the sharing features on this page, please enable JavaScript. Bartter syndrome is a group of rare conditions that affect ...

Dravet Syndrome

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... and supports a broad program of basic and clinical research on all types of epilepsy, including Dravet syndrome. Study of the genetic defects responsible for Dravet syndrome and related ... Publications Definition Dravet ...

Genetics Home Reference: Marfan syndrome

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