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Sample records for loss causing severe

  1. Cochlear implantation for severe sensorineural hearing loss caused by lightning.

    Science.gov (United States)

    Myung, Nam-Suk; Lee, Il-Woo; Goh, Eui-Kyung; Kong, Soo-Keun

    2012-01-01

    Lightning strike can produce an array of clinical symptoms and injuries. It may damage multiple organs and cause auditory injuries ranging from transient hearing loss and vertigo to complete disruption of the auditory system. Tympanic-membrane rupture is relatively common in patients with lightning injury. The exact pathogenetic mechanisms of auditory lesions in lightning survivors have not been fully elucidated. We report the case of a 45-year-old woman with bilateral profound sensorineural hearing loss caused by a lightning strike, who was successfully rehabilitated after a cochlear implantation. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Neospora caninum causes severe economic losses in cattle in the humid pampa region of Argentina.

    Science.gov (United States)

    Moore, Dadin; Reichel, Michael; Spath, Ernesto; Campero, Carlos

    2013-06-01

    This work estimates the economic losses due to Neospora abortions in the humid pampa region of Argentina.The total dairy and beef cattle population at risk of abortion is 1,771,326 and 9,726,684 head, respectively. In dairy cattle, there was an 8 % risk of experiencing abortion due to a variety of causes, but 16.5 % of them were due to Neospora caninum. The economic losses were estimated at US$1,415 (1,400-1,431) per abortion, which equates to a total loss of US$33,097,221 (15,622,600-119,349,693) for the dairy industry at the humid pampa region of Argentina. In beef cattle, the overall risk of abortion was estimated to be 4.5 % for all pregnancies,whereas 6.7 % are specifically due to N. caninum, with an economic loss of US$440 (range, 150-730) per abortion.This amounts to an annual loss to the beef industry of US$12,903,440 (range, 1,130,700-42,070,630) in the same area. The results of this study show that Neospora infections and thus abortions cause severe economic impacts in the dairy and beef industries in the humid pampa region of Argentina, which is one the most important areas of cattle production in the world [corrected].

  3. Severe Cenani-Lenz syndrome caused by loss of LRP4 function.

    Science.gov (United States)

    Kariminejad, Ariana; Stollfuß, Barbara; Li, Yun; Bögershausen, Nina; Boss, Karin; Hennekam, Raoul C M; Wollnik, Bernd

    2013-06-01

    Limb patterning and growth are complex embryonic processes in which the elaborately orchestrated interplay of diverse endocrine and paracrine factors is crucial to limb integrity. LRP4 is a lipoprotein receptor known for its regulatory effects on LRP5- and LRP6-mediated Wnt signaling, a pathway that plays a pivotal role in limb development. Recessive mutations in LRP4 have been shown to cause Cenani-Lenz syndrome, which is characterized by severe limb malformations, an unusual face, and renal abnormalities. We report on a child with severe Cenani-Lenz syndrome caused by a novel homozygous nonsense mutation in LRP4. The severity of the phenotype in a patient with absent residual LRP4 function may point to a genotype-phenotype correlation.

  4. Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy.

    Science.gov (United States)

    Zaharieva, Irina T; Thor, Michael G; Oates, Emily C; van Karnebeek, Clara; Hendson, Glenda; Blom, Eveline; Witting, Nanna; Rasmussen, Magnhild; Gabbett, Michael T; Ravenscroft, Gianina; Sframeli, Maria; Suetterlin, Karen; Sarkozy, Anna; D'Argenzio, Luigi; Hartley, Louise; Matthews, Emma; Pitt, Matthew; Vissing, John; Ballegaard, Martin; Krarup, Christian; Slørdahl, Andreas; Halvorsen, Hanne; Ye, Xin Cynthia; Zhang, Lin-Hua; Løkken, Nicoline; Werlauff, Ulla; Abdelsayed, Mena; Davis, Mark R; Feng, Lucy; Phadke, Rahul; Sewry, Caroline A; Morgan, Jennifer E; Laing, Nigel G; Vallance, Hilary; Ruben, Peter; Hanna, Michael G; Lewis, Suzanne; Kamsteeg, Erik-Jan; Männikkö, Roope; Muntoni, Francesco

    2016-03-01

    Congenital myopathies are a clinically and genetically heterogeneous group of muscle disorders characterized by congenital or early-onset hypotonia and muscle weakness, and specific pathological features on muscle biopsy. The phenotype ranges from foetal akinesia resulting in in utero or neonatal mortality, to milder disorders that are not life-limiting. Over the past decade, more than 20 new congenital myopathy genes have been identified. Most encode proteins involved in muscle contraction; however, mutations in ion channel-encoding genes are increasingly being recognized as a cause of this group of disorders. SCN4A encodes the α-subunit of the skeletal muscle voltage-gated sodium channel (Nav1.4). This channel is essential for the generation and propagation of the muscle action potential crucial to muscle contraction. Dominant SCN4A gain-of-function mutations are a well-established cause of myotonia and periodic paralysis. Using whole exome sequencing, we identified homozygous or compound heterozygous SCN4A mutations in a cohort of 11 individuals from six unrelated kindreds with congenital myopathy. Affected members developed in utero- or neonatal-onset muscle weakness of variable severity. In seven cases, severe muscle weakness resulted in death during the third trimester or shortly after birth. The remaining four cases had marked congenital or neonatal-onset hypotonia and weakness associated with mild-to-moderate facial and neck weakness, significant neonatal-onset respiratory and swallowing difficulties and childhood-onset spinal deformities. All four surviving cohort members experienced clinical improvement in the first decade of life. Muscle biopsies showed myopathic features including fibre size variability, presence of fibrofatty tissue of varying severity, without specific structural abnormalities. Electrophysiology suggested a myopathic process, without myotonia. In vitro functional assessment in HEK293 cells of the impact of the identified SCN4A

  5. [Severe cartilage loss caused by metallic anchors in surgical treatment of a Bankart lesion: report of three cases].

    Science.gov (United States)

    Bek, Doğan; Ege, Tolga; Erdem, Yusuf; Tunay, Servet

    2015-01-01

    Currently, arthroscopic modalities in the surgical treatment of shoulder instability using suture anchors are more popular than open surgery. However, there are some complications related to the metallic suture anchors used. One of the most common complications is cartilage loss due to shallow placement of the suture anchor. Herein, we report three cases with severe cartilage loss of the humeral head due to metallic proud anchors, including one of whom requiring total shoulder arthroplasty. In conclusion, it is essential to place the suture anchors in an appropriate position and deepness. In case of any doubt, they should be removed or in non-threaded anchors, they should be inserted fully inside the glenoid with an impactor and a hammer to avoid serious cartilage loss.

  6. Pegylated human recombinant leptin (PEG-OB) causes additional weight loss in severely energy-restricted, overweight men.

    Science.gov (United States)

    Hukshorn, Chris J; Westerterp-Plantenga, Margriet S; Saris, Wim H M

    2003-04-01

    Increasing evidence suggests that falling leptin concentrations observed during fasting act as a peripheral signal of starvation, which serves to conserve energy in the face of limited reserves. An extension of this hypothesis is that exogenous leptin should affect energy regulation during severe energy restriction. To explore this hypothesis, we assessed whether elevated leptin concentrations achieved with the use of long-acting pegylated human recombinant leptin [polyethylene glycol-OB protein (PEG-OB)] affected weight loss and changes in body composition, energy expenditure, appetite, and metabolic variables during semistarvation in healthy overweight men. A randomized, double-blind, placebo-controlled study was executed in overweight men with a mean (+/- SEM) age of 34.8 +/- 1.3 y and body mass index (in kg/m2) of 28.8 +/- 0.5. All subjects received weekly treatment with 80 mg PEG-OB (n = 12) or matching placebo (n = 10) for 46 d while their energy intake was reduced to 2.1 MJ/d by means of a very-low-energy diet. Body composition (hydrodensitometry and deuterium dilution), energy expenditure (ventilated hood), and appetite (visual analogue scales) were evaluated at the start and the end of the study. Metabolic variables were measured throughout the study period. Compared with placebo treatment, treatment with PEG-OB led to significant (P < 0.03) additional weight loss (14.6 +/- 0.8 compared with 11.8 +/- 0.9 kg) and a reduction in appetite (P < 0.05) after 46 d, but the 2 treatment groups did not differ significantly in changes in body composition, energy expenditure, and metabolic variables. Our observations support the hypothesis that the decrease in leptin concentrations during starvation increases appetite in humans.

  7. Could Anemia Cause Hearing Loss?

    Science.gov (United States)

    ... https://medlineplus.gov/news/fullstory_162793.html Could Anemia Cause Hearing Loss? Iron deficiency might keep ear ... Hearing loss may be linked to iron deficiency anemia -- a combination of low levels of iron and ...

  8. Recurrent De Novo Dominant Mutations in SLC25A4 Cause Severe Early-Onset Mitochondrial Disease and Loss of Mitochondrial DNA Copy Number.

    Science.gov (United States)

    Thompson, Kyle; Majd, Homa; Dallabona, Christina; Reinson, Karit; King, Martin S; Alston, Charlotte L; He, Langping; Lodi, Tiziana; Jones, Simon A; Fattal-Valevski, Aviva; Fraenkel, Nitay D; Saada, Ann; Haham, Alon; Isohanni, Pirjo; Vara, Roshni; Barbosa, Inês A; Simpson, Michael A; Deshpande, Charu; Puusepp, Sanna; Bonnen, Penelope E; Rodenburg, Richard J; Suomalainen, Anu; Õunap, Katrin; Elpeleg, Orly; Ferrero, Ileana; McFarland, Robert; Kunji, Edmund R S; Taylor, Robert W

    2016-10-06

    Mutations in SLC25A4 encoding the mitochondrial ADP/ATP carrier AAC1 are well-recognized causes of mitochondrial disease. Several heterozygous SLC25A4 mutations cause adult-onset autosomal-dominant progressive external ophthalmoplegia associated with multiple mitochondrial DNA deletions, whereas recessive SLC25A4 mutations cause childhood-onset mitochondrial myopathy and cardiomyopathy. Here, we describe the identification by whole-exome sequencing of seven probands harboring dominant, de novo SLC25A4 mutations. All affected individuals presented at birth, were ventilator dependent and, where tested, revealed severe combined mitochondrial respiratory chain deficiencies associated with a marked loss of mitochondrial DNA copy number in skeletal muscle. Strikingly, an identical c.239G>A (p.Arg80His) mutation was present in four of the seven subjects, and the other three case subjects harbored the same c.703C>G (p.Arg235Gly) mutation. Analysis of skeletal muscle revealed a marked decrease of AAC1 protein levels and loss of respiratory chain complexes containing mitochondrial DNA-encoded subunits. We show that both recombinant AAC1 mutant proteins are severely impaired in ADP/ATP transport, affecting most likely the substrate binding and mechanics of the carrier, respectively. This highly reduced capacity for transport probably affects mitochondrial DNA maintenance and in turn respiration, causing a severe energy crisis. The confirmation of the pathogenicity of these de novo SLC25A4 mutations highlights a third distinct clinical phenotype associated with mutation of this gene and demonstrates that early-onset mitochondrial disease can be caused by recurrent de novo mutations, which has significant implications for the application and analysis of whole-exome sequencing data in mitochondrial disease. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. Severity and pattern of bone mineral loss in endocrine causes of osteoporosis as compared to age-related bone mineral loss

    Directory of Open Access Journals (Sweden)

    D Dutta

    2016-01-01

    Full Text Available Background: Data are scant on bone health in endocrinopathies from India. This study evaluated bone mineral density (BMD loss in endocrinopathies [Graves′ disease (GD, type 1 diabetes mellitus (T1DM, hypogonadotrophic hypogonadism (HypoH, hypergonadotropic hypogonadism (HyperH, hypopituitarism, primary hyperparathyroidism (PHPT] as compared to age-related BMD loss [postmenopausal osteoporosis (PMO, andropause]. Materials and Methods: Retrospective audit of records of patients >30 years age attending a bone clinic from August 2014 to January 2016 was done. Results: Five-hundred and seven records were screened, out of which 420 (females:male = 294:126 were analyzed. A significantly higher occurrence of vitamin D deficiency and insufficiency was noted in T1DM (89.09%, HyperH (85%, and HypoH (79.59% compared to age-related BMD loss (60.02%; P < 0.001. The occurrence of osteoporosis among females and males was 55.41% and 53.97%, respectively, and of osteopenia among females and males was 28.91% and 32.54%, respectively. In females, osteoporosis was significantly higher in T1DM (92%, HyperH (85%, and HypoH (59.26% compared to PMO (49.34%; P < 0.001. Z score at LS, TF, NOF, and greater trochanter (GT was consistently lowest in T1DM women. Among men, osteoporosis was significantly higher in T1DM (76.67% and HypoH (54.55% compared to andropause (45.45%; P = 0.001. Z score at LS, TF, NOF, GT, and TR was consistently lowest in T1DM men. In GD, the burden of osteoporosis was similar to PMO and andropause. BMD difference among the study groups was not significantly different after adjusting for body mass index (BMI and vitamin D. Conclusion: Low bone mass is extremely common in endocrinopathies, warranting routine screening and intervention. Concomitant vitamin D deficiency compounds the problem. Calcium and vitamin D supplementations may improve bone health in this setting.

  10. L712V mutation in the androgen receptor gene causes complete androgen insensitivity syndrome due to severe loss of androgen function.

    Science.gov (United States)

    Rajender, Singh; Gupta, Nalini J; Chakrabarty, Baidyanath; Singh, Lalji; Thangaraj, Kumarasamy

    2013-12-11

    Inability to respond to the circulating androgens is named as androgen insensitivity syndrome (AIS). Mutations in the androgen receptor (AR) gene are the most common cause of AIS. A cause and effect relationship between some of these mutations and the AIS phenotype has been proven by in vitro studies. Several other mutations have been identified, but need to be functionally validated for pathogenicity. Screening of the AR mutations upon presumptive diagnosis of AIS is recommended. We analyzed a case of complete androgen insensitivity syndrome (CAIS) for mutations in the AR gene. Sequencing of the entire coding region revealed C>G mutation (CTT-GTT) at codon 712 (position according to the NCBI database) in exon 4 of the gene, resulting in replacement of leucine with valine in the ligand-binding domain of the AR protein. No incidence of this mutation was observed in 230 normal male individuals analyzed for comparison. In vitro androgen binding and transactivation assays using mutant clone showed approximately 71% loss of ligand binding and about 76% loss of transactivation function. We conclude that CAIS in this individual was due to L712V substitution in the androgen receptor protein.

  11. Causes of visual loss in uveitis

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    Stanković Zora

    2009-01-01

    Full Text Available Background/Aim. Epidemiological studies of blindness in a working age population require a precise definition of the true connection of uveitis and visual damage. Since most patients with more severe types of uveitis are hospitalized in tertiary referral uveitis service, our aim was to determine whether age, sex and age of onset of uveitis, as well as duration of visual loss and its causes influence the degree of visual damage in patients with different types of uveitis. Methods. The data were collected from medical records of 237 patients at the Department for Uveitis of the Institute for Eye Diseases in Belgrade over a three-year period (March 2005 to March 2008. Results. Visual acuity reduction (≤ 0.3 was found in 161/237 (67.9% patients, 85 of whom had visual acuity of ≤ 0.1 later. Working age patients (up to 60 years of age most often suffered from uveitis (173/237; 73%. The highest number of patients with visual loss was in the group suffering from panuveitis (77/94; 81.91%. The age of onset of uveitis and sex have no statistically significant influence on visual loss. The most common causes of visual loss (34/161; 21.1% were cystoid macular oedema (CMO (43/161; 26.7%, cataract (28/161; 17.39% and combination of CMO and cataract. Conclusion. The risk factors for severe visual loss (≤ 0.1 are panuveitis, bilateral inflammation, prolonged visual reduction and a significant number of relapses. The main causes of visual loss in 65.2% of our patients were CMO and cataract.

  12. Genetic background alters the severity and onset of neuromuscular disease caused by the loss of ubiquitin-specific protease 14 (usp14.

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    Andrea G Marshall

    Full Text Available In this study, we identified and characterized an N-ethyl-N-nitrosourea (ENU induced mutation in Usp14 (nmf375 that leads to adult-onset neurological disease. The nmf375 mutation causes aberrant splicing of Usp14 mRNA, resulting in a 95% reduction in USP14. We previously showed that loss of USP14 in ataxia (ax (J mice results in reduced ubiquitin levels, motor endplate disease, Purkinje cell axonal dystrophy and decreased hippocampal paired pulse facilitation (PPF during the first 4-6 weeks of life, and early postnatal lethality by two months of age. Although the loss of USP14 is comparable between the nmf375 and ax (J mice, the nmf375 mice did not exhibit these ax (J developmental abnormalities. However, by 12 weeks of age the nmf375 mutants present with ubiquitin depletion and motor endplate disease, indicating a continual role for USP14-mediated regulation of ubiquitin pools and neuromuscular junction (NMJ structure in adult mice. The observation that motor endplate disease was only seen after ubiquitin depletion suggests that the preservation of NMJ structure requires the stable maintenance of synaptic ubiquitin pools. Differences in genetic background were shown to affect ubiquitin expression and dramatically alter the phenotypes caused by USP14 deficiency.

  13. Mutation of the zebrafish glass onion locus causes early cell-nonautonomous loss of neuroepithelial integrity followed by severe neuronal patterning defects in the retina.

    Science.gov (United States)

    Pujic, Z; Malicki, J

    2001-06-15

    Mutation of the glass onion locus causes drastic neuronal patterning defects in the zebrafish retina and brain. The precise stratified appearance of the wild-type retina is absent in the mutants. The glass onion phenotype is first visible shortly after the formation of optic primordia and is characterized by the rounding of cells and disruption of the ventricular surface in the eye and brain neuroepithelia. With exception of the dorsal- and ventral-most regions of the brain, neuroepithelial cells lose their integrity and begin to distribute ectopically. At later stages, the laminar patterning of retinal neurons is severely disrupted. Despite the lack of lamination, individual retinal cell classes differentiate in the glass onion retina. Mosaic analysis reveals that the glass onion mutation acts cell nonautonomously within the retina and brain, as neuroepithelial cell morphology and polarity in these tissues are normal when mutant cells develop in wild-type hosts. We conclude that the glass onion mutation affects cell-cell signaling event(s) involved in the maintenance of the neuroepithelial cell layer shortly after its formation. The disruption of neuroepithelial integrity may be the cause of the neuronal patterning defects following neurogenesis. In addition, the expression of the glass onion phenotype in a subset of neuroepithelial cells as well as its onset following the initial formation of the neuroepithelial sheets indicate the presence of genetically distinct temporal and spatial subdivisions in the development of this histologically uniform tissue.

  14. Loss-of-function mutations in SCN4A cause severe foetal hypokinesia or 'classical' congenital myopathy

    DEFF Research Database (Denmark)

    Zaharieva, Irina T; Thor, Michael G; Oates, Emily C

    2016-01-01

    of disorders. SCN4A encodes the α-subunit of the skeletal muscle voltage-gated sodium channel (Nav1.4). This channel is essential for the generation and propagation of the muscle action potential crucial to muscle contraction. Dominant SCN4A gain-of-function mutations are a well-established cause of myotonia...

  15. Economic Loss Caused by GMOs in Denmark

    DEFF Research Database (Denmark)

    Ulfbeck, Vibe Garf

    2008-01-01

    This book presents how European jurisdictions currently respond to economic losses caused by the admixture of gentically modified crops with conventional or organic crops and what alternatives there are from a comparative perspective. Country reports from most European countries are complemented ...

  16. ESTIMATING LOSS SEVERITY DISTRIBUTION: CONVOLUTION APPROACH

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    Ro J. Pak

    2014-01-01

    Full Text Available Financial loss can be classified into two types such as expected loss and unexpected loss. A current definition seeks to separate two losses from a total loss. In this article, however, we redefine a total loss as the sum of expected and unexpended losses; then the distribution of loss can be considered as the convolution of the distributions of both expected and unexpended losses. We propose to use a convolution of normal and exponential distribution for modelling a loss distribution. Subsequently, we compare its performance with other commonly used loss distributions. The examples of property insurance claim data are analyzed to show the applicability of this normal-exponential convolution model. Overall, we claim that the proposed model provides further useful information with regard to losses compared to existing models. We are able to provide new statistical quantities which are very critical and useful.

  17. Pediatric hearing loss: common causes, diagnosis and therapeutic approach.

    Science.gov (United States)

    Alzahrani, M; Tabet, P; Saliba, I

    2015-02-01

    Pediatric hearing loss limits the child ability to develop effective auditory and speech capabilities. Early rehabilitation of hearing loss results in higher levels of linguistic, academic and social skills. To achieve the best outcomes, proper and timely diagnosis is essential. The etiology of hearing loss can be classified according to its nature as sensorineural hearing loss (SNHL), conductive hearing loss (CHL) or mixed hearing loss (MHL). Congenital hearing loss could be genetic or non genetic (acquired), syndromic or non-syndromic. Hearing loss can be classified according to the severity into mild (26-40 dB HL), moderate (41-70 dB HL), severe (71-90 dB HL) and profound (more than 90 dB HL). Management of hearing loss is mainly influenced by the nature, the bilaterality, the severity and the age at diagnosis. Severe to profound bilateral SNHL can be managed by cochlear implantation (unilateral or bilateral), if picked up at early age while mild to moderate bilateral SNHL are easier to manage with conventional hearing aids. CHL has less impact on the speech development of the child. It is usually managed by correcting the underlying etiology such as otitis media with effusion or even surgically in cases of external ear atresia or ossicular malformations. Unilateral SNHL have fortunately no impact on the language development of the child and can be passed undiagnosed until preschool-aged children. The implementation of national newborn hearing screening programs has improved the management of affected children by rehabilitating them at early stages to allow for normal speech development. In this review article, we aim to highlight the most common causes of pediatric hearing loss, their character and presentation and to review the diagnostic and therapeutic approaches of a deaf child.

  18. Outcomes of Severe to Profound Idiopathic Sudden Sensorineural Hearing Loss

    OpenAIRE

    Jo, Si-Young; Lee, Sungsu; Eom, Tae-Ho; Jeun, Eun-Sun; Cho, Hyong-Ho; Cho, Yong-Beom

    2015-01-01

    Objectives While a severe to profound sudden sensorineural hearing loss (SSNHL) may cause serious disability in verbal communication, there have been little studies focusing on this high degree SSNHL. The present study was aimed to investigate the characteristics of hearing recovery in a high degree SSNHL (>70 dB). Methods Three hundred and two SSNHL patients were enrolled. For a long-term follow-up, 46 patients were evaluated. Hearing level was examined by pure tone audiometry on day 1, week...

  19. An Unexpected Cause of Severe Hypokalemia

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    Fernando Caravaca-Fontan

    2015-01-01

    Full Text Available We describe an unusual case of severe hypokalemia with electrocardiographic changes, due to licorice consumption, in a 15-year-old female student with no previous medical history. Prompt replacement of potassium and cessation of licorice ingestion resulted in a favourable outcome. We also discuss the pathophysiology and diagnosis, emphasizing the importance of a detailed anamnesis to rule out an often forgotten cause of hypokalemia as the licorice poisoning.

  20. 7 CFR 1437.9 - Causes of loss.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Causes of loss. 1437.9 Section 1437.9 Agriculture... Provisions § 1437.9 Causes of loss. (a) To be eligible for benefits under this part, an eligible cause of... causes of loss include: (1) Damaging weather occurring before or during harvest, including but...

  1. Major depression and severe weight loss

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    Ntrogkounta Α.

    2015-10-01

    Full Text Available Α 25-year old patient was referred to the casualty department of the Community Mental Health Center of Central Sector of Thessaloniki from the emergency department of the Psychiatric Hospital of Thessaloniki, in order to manage symptoms of depression as long as her life- threating loss of weight. A. appeared to have depressive feelings, lack of appetite, lack of interest, withdrawal, sleep disorders, sexual disorders, low self-esteem and ideas of guilt. There were held 27 conferences. In the beginning there were supportive intervations in order to improve the depressive symptoms and to gain weight. Moreover we applied medication (SSRI's that after 6 months was stopped gradually, without any setback. There was an increase of weight, about 10 kg, which remained until the follow up one year later.

  2. FEMA Hazard Mitigation Assistance Severe Repetitive Loss (SRL) Data

    Data.gov (United States)

    Department of Homeland Security — This dataset contains closed and obligated projects funded under the following Hazard Mitigation Assistance (HMA) grant programs: Severe Repetitive Loss (SRL). The...

  3. Hormonal causes of recurrent pregnancy loss (RPL).

    Science.gov (United States)

    Pluchino, Nicola; Drakopoulos, Panagiotis; Wenger, Jean Marie; Petignat, Patrick; Streuli, Isabelle; Genazzani, Andrea Riccardo

    2014-01-01

    Endocrine disorders play a major role in approximately 8% to 12% of recurrent pregnancy loss (RPL). Indeed, the local hormonal milieu is crucial in both embryo attachment and early pregnancy. Endocrine abnormalities, including thyroid disorders, luteal phase defects, polycystic ovary syndrome, hyperprolactinaemia and diabetes have to be evaluated in any case of RPL. Moreover, elevated androgen levels and some endocrinological aspects of endometriosis are also factors contributing to RPL. In the present article, we review the significance of endocrine disease on RPL.

  4. Weight-Loss Surgery Pays Off for Severely Obese Teens

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_161700.html Weight-Loss Surgery Pays Off for Severely Obese Teens Boosts ... 26, 2016 WEDNESDAY, Oct. 26, 2016 (HealthDay News) -- Weight-loss surgeries can help severely obese teens shed pounds. ...

  5. Severe Vitamin D Deficiency Causing Kyphoscoliosis.

    Science.gov (United States)

    Singhai, Abhishek; Banzal, Subodh

    2013-01-01

    Vitamin D deficiency is common among Indian population. Women are especially at risk for severe vitamin D deficiency. The risk is higher for those who are multiparous and postmenopausal. Poor exposure to sunlight, higher latitude, winter season, inadequate diet, older age, obesity and malabsorption are also important risk factors. Symptoms of hypovitaminosis D, including diffuse or migratory pain affecting several sites (especially the shoulder, pelvis, ribcage and lower back) have also been misdiagnosed as musculoskeletal disorders, including fibromyalgia, polymyalgia rheumatica and ankylosing spondylitis. Here, we report two cases presented with kyphoscoliosis, diagnosed to have severe vitamin D deficiency.

  6. Severe Vitamin D Deficiency Causing Kyphoscoliosis

    OpenAIRE

    Singhai, Abhishek; Banzal, Subodh

    2013-01-01

    Vitamin D deficiency is common among Indian population. Women are especially at risk for severe vitamin D deficiency. The risk is higher for those who are multiparous and postmenopausal. Poor exposure to sunlight, higher latitude, winter season, inadequate diet, older age, obesity and malabsorption are also important risk factors. Symptoms of hypovitaminosis D, including diffuse or migratory pain affecting several sites (especially the shoulder, pelvis, ribcage and lower back) have also been ...

  7. Urinothorax: an unexpected cause of severe dyspnea.

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    Tortora, Alessandra; Casciani, Emanuele; Kharrub, Zaher; Gualdi, Gianfranco

    2006-05-01

    We report an unusual cause of the pleural effusion due to extravasation of urine from the retroperitoneal space into the thoracic cavity. In our case, the urinoma occurred owing to obstructing urinary tract lesion due to opaque stone. Although rare, urinothorax should be considered when pleural effusion occurs in patients with urinary tract obstruction accompanied by retroperitoneal urinoma.

  8. Recent Advances in Understanding Audiovestibular Loss of a Vascular Cause

    Science.gov (United States)

    Kim, Hyun-Ah; Lee, Hyung

    2017-01-01

    Acute audiovestibular loss is characterized by abrupt onset of prolonged (lasting days) vertigo and hearing loss. Acute ischemic stroke in the distribution of the anterior inferior cerebellar artery (AICA) is known to be the leading cause of acute audiovestibular loss. So far, eight subgroups of AICA territory infarction have been identified according to the patterns of audiovestibular dysfunctions, among which the most common pattern is the combined loss of auditory and vestibular functions. Unlike inner ear dysfunction of a viral cause, which can commonly present as an isolated vestibular (i.e., vestibular neuritis) or cochlear loss (i.e., sudden deafness), labyrinthine dysfunction of a vascular cause rarely results in isolated loss of vestibular or auditory function. As audiovestibular loss may precede the central symptoms or signs of an ischemic stroke in the posterior circulation, early diagnosis and proper management of audiovestiubular loss may provide a window to prevent the progression of infarction to larger areas of the posterior circulation. A clinician should consider the possibility that acute audiovestibular loss may herald impending AICA territory infarction, especially when patients have basilar artery occlusive disease close to the origin of the AICA on brain MRA. This review aims to highlight the recent advances in understanding audiovestibular loss of a vascular cause and to address its clinical significance. PMID:28030893

  9. Forgotten Kirschner Wire Causing Severe Hematuria

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    Santosh Kumar

    2014-01-01

    Full Text Available Kirschner wire (K-wire is commonly used in the treatment of hip fracture and its migration into pelvis leading to bladder injury is a very rare complication. Nonremoval of these devices either because of lack of followup or because of prolonged requirement due to disease process is associated with this complication. We report a case of a patient who presented with acute onset severe hematuria with clot retention secondary to perforation of bladder by a migrated K-wire placed earlier, for the treatment of hip fracture. Initial imaging showed its presence in the soft tissues of the pelvis away from the major vascular structures. Patient was taken for emergency laparotomy and wire was removed after cystotomy. Postoperative period was uneventful and patient was discharged in satisfactory condition. K-wires are commonly used in the management of fracture bones and their migration has been reported in the literature although such migration in the intrapelvic region involving bladder is very rare. Early diagnosis and prompt removal of such foreign bodies are required to avert potentially fatal involvement of major structures.

  10. Heat losses in power boilers caused by thermal bridges

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    Kocot Monika

    2017-01-01

    Full Text Available In this article the analysis of heat losses caused by thermal bridges that occur in the steam boiler OP-140 is presented. Identification of these bridges were conducted with use of thermographic camera. Heat losses were evaluated based on methodology of VDI 4610 standard, but instead of its simplified equations, criterial equations based on Nusselt number were used. Obtained values of annual heat losses and heat flux density corresponding to the fully insulated boiler surfaces were compared to heat losses generated by thermal bridges located in the same areas. The emphasis is put on the role of industrial insulation in heat losses reduction.

  11. ECONOMIC LOSSES CAUSED BY TRAUMATIC BRAIN INJURY IN CHILDREN

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    S. A. Valiulina

    2015-01-01

    Full Text Available Background: Currently, analyzing the economic losses caused by health problems in population is of particular importance since it stipulates calculations of the volumes invested in healthcare systems in order to improve population’s health. Objective: The aim of our study was to find out economic losses caused by traumatic brain injury (TBI in children. Methods: The given work has utilized governmental statistical reports for Russia, for federal regions as well as for individual subjects. Direct medical expenses (medical services and indirect expenses (losses due to a temporary disability of parents having a sick child were calculated both in general and per patient. Results: Among all the direct medical costs of treatment of children with TBI inpatient care costs account for 85%. In the Central and Volga Federal District accounted for half of nationwide spending in general, brain injury and to provide certain kinds of healthcare. The structure of Russian costs as a result of the incidence of TBI children Moscow accounts for 20%. In Moscow, the cost of treating cases of traumatic brain injury in children is 3.2 times higher than the average for Russia. The resulting calculations of the value of health care costs attributable to a case of child head injury, behind the cost of treatment of the case of a child with head trauma, calculated according to the standards of Russia and the territories. This difference in the whole RF is 23%. Conclusion: The obtained findings have shown that in 2010 in Russia the magnitude of losses caused by TBI incidence in children amounted to 3 billion roubles or 0.008% of the gross product 1.2 billion roubles of which were direct expenses. However, this figure is considerably lower of the real amount; it becomes evident after the analysis of direct medical expenses per one case of pediatric TBI. Our calculations have shown that in Russia and in its regions the amount of expenses per one TBI patient is a quarter less

  12. Heat stress causes substantial labour productivity loss in Australia

    Science.gov (United States)

    Zander, Kerstin K.; Botzen, Wouter J. W.; Oppermann, Elspeth; Kjellstrom, Tord; Garnett, Stephen T.

    2015-07-01

    Heat stress at the workplace is an occupational health hazard that reduces labour productivity. Assessment of productivity loss resulting from climate change has so far been based on physiological models of heat exposure. These models suggest productivity may decrease by 11-27% by 2080 in hot regions such as Asia and the Caribbean, and globally by up to 20% in hot months by 2050. Using an approach derived from health economics, we describe self-reported estimates of work absenteeism and reductions in work performance caused by heat in Australia during 2013/2014. We found that the annual costs were US$655 per person across a representative sample of 1,726 employed Australians. This represents an annual economic burden of around US$6.2 billion (95% CI: 5.2-7.3 billion) for the Australian workforce. This amounts to 0.33 to 0.47% of Australia’s GDP. Although this was a period when many Australians experienced what is at present considered exceptional heat, our results suggest that adaptation measures to reduce heat effects should be adopted widely if severe economic impacts from labour productivity loss are to be avoided if heat waves become as frequent as predicted.

  13. Does a loss of TDP-43 function cause neurodegeneration?

    Directory of Open Access Journals (Sweden)

    Xu Zuo-Shang

    2012-06-01

    Full Text Available Abstract In 2006, TAR-DNA binding protein 43 kDa (TDP-43 was discovered to be in the intracellular aggregates in the degenerating cells in amyotrophic lateral sclerosis (ALS and frontotemporal lobar degeneration (FTLD, two fatal neurodegenerative diseases [1,2]. ALS causes motor neuron degeneration leading to paralysis [3,4]. FTLD causes neuronal degeneration in the frontal and temporal cortices leading to personality changes and a loss of executive function [5]. The discovery triggered a flurry of research activity that led to the discovery of TDP-43 mutations in ALS patients and the widespread presence of TDP-43 aggregates in numerous neurodegenerative diseases. A key question regarding the role of TDP-43 is whether it causes neurotoxicity by a gain of function or a loss of function. The gain-of-function hypothesis has received much attention primarily based on the striking neurodegenerative phenotypes in numerous TDP-43-overexpression models. In this review, I will draw attention to the loss-of-function hypothesis, which postulates that mutant TDP-43 causes neurodegeneration by a loss of function, and in addition, by exerting a dominant-negative effect on the wild-type TDP-43 allele. Furthermore, I will discuss how a loss of function can cause neurodegeneration in patients where TDP-43 is not mutated, review the literature in model systems to discuss how the current data support the loss-of-function mechanism and highlight some key questions for testing this hypothesis in the future.

  14. Anterior cruciate ligament remnants nodule: potential factor causing extension loss

    Institute of Scientific and Technical Information of China (English)

    WANG Jian; AO Ying-fang

    2013-01-01

    Background Extension loss caused by anterior cruciate ligament (ACL) remnants nodule was usually reported by case reports.There is no systematic report analyzing ACL remnants nodule.The purpose of this study was to investigate the characteristics of extension loss caused by remnants of ACL after injury.Methods From June 2008 to December 2011,ACL remnants were observed by atthroscopy in 1012 cases with ACL injuries at the time of primary reconstruction.ACL remnants nodules were recorded.The time of extension loss occurrence caused by ACL remnants nodule,associated symptom and sign,magnetic resonance imaging (MRI),and arthroscopic findings were observed.Histological examination was performed on the lesion resected.Results Twenty-four cases with ACL remnants nodules were found by arthroscopy.Among them extension loss caused by remnants of ACL happened in 19 cases (male 13; female 6).The average extension loss were 9.1° (range,5°-20°).The average time from injury to operation was 8.9 weeks (range,3-26 weeks).The remnants of ACL depressed in the inter-condylar notch were found on MRI in 15 cases with extension loss.The rupture locations of ACL were all close to the upper insertion of ACL.The microscopic examination of the resected remnants of ACL revealed disorganized fibrous connective tissue and tissue of ACL ligament.Conclusions Among 1012 ACL injury cases,24 ACL remnants nodules were found with arthroscopy and 19 nodules could cause knee extension loss.ACL remnants nodule should be paid attention to as a potential cause of extension loss.

  15. Sensorineural hearing loss caused by MYH14 gene mutation. A case report

    Directory of Open Access Journals (Sweden)

    Pedro CARNEIRO-SOUSA

    2016-11-01

    Full Text Available Introduction and objective: Hereditary causes are responsible for half of cases of sensorineural hearing loss in young people. MYH14 mutation is autosomal dominant. Description: A 33 years-old patient with moderate-to-severe sensorineural hearing loss. Genetic study revealed MYH14 mutation. Discussion: This is a case of post-lingual sensorineural deafness, compatible with autosomal dominant inheritance. MYH14 mutation seems to increase susceptibility to acoustic trauma, which may justify the late onset of hearing loss. Conclusions: MYH14 mutation is, probably, a cause for hearing loss. Genetic study has, therefore, a growing importance.

  16. Homozygous SLC2A9 mutations cause severe renal hypouricemia.

    Science.gov (United States)

    Dinour, Dganit; Gray, Nicola K; Campbell, Susan; Shu, Xinhua; Sawyer, Lindsay; Richardson, William; Rechavi, Gideon; Amariglio, Ninette; Ganon, Liat; Sela, Ben-Ami; Bahat, Hilla; Goldman, Michael; Weissgarten, Joshua; Millar, Michael R; Wright, Alan F; Holtzman, Eliezer J

    2010-01-01

    Hereditary hypouricemia may result from mutations in the renal tubular uric acid transporter URAT1. Whether mutation of other uric acid transporters produces a similar phenotype is unknown. We studied two families who had severe hereditary hypouricemia and did not have a URAT1 defect. We performed a genome-wide homozygosity screen and linkage analysis and identified the candidate gene SLC2A9, which encodes the glucose transporter 9 (GLUT9). Both families had homozygous SLC2A9 mutations: A missense mutation (L75R) in six affected members of one family and a 36-kb deletion, resulting in a truncated protein, in the other. In vitro, the L75R mutation dramatically impaired transport of uric acid. The mean concentration of serum uric acid of seven homozygous individuals was 0.17 +/- 0.2 mg/dl, and all had a fractional excretion of uric acid >150%. Three individuals had nephrolithiasis, and three had a history of exercise-induced acute renal failure. In conclusion, homozygous loss-of-function mutations of GLUT9 cause a total defect of uric acid absorption, leading to severe renal hypouricemia complicated by nephrolithiasis and exercise-induced acute renal failure. In addition to clarifying renal handling of uric acid, our findings may provide a better understanding of the pathophysiology of acute renal failure, nephrolithiasis, hyperuricemia, and gout.

  17. Acute sensorineural hearing loss and severe otalgia due to scrub typhus

    Directory of Open Access Journals (Sweden)

    Kim Dong-Min

    2009-10-01

    Full Text Available Abstract Background Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi. Case presentations We encountered a patient with sensorineural hearing loss complicating scrub typhus, and three patients with scrub typhus who complained of otalgia, which was sudden onset, severe, paroxysmal, intermittent yet persistent pain lasting for several seconds, appeared within 1 week after the onset of fever and rash. The acute sensorineural hearing loss and otalgia were resolved after antibiotic administration. Conclusion When patients in endemic areas present with fever and rash and have sensorineural hearing loss or otalgia without otoscopic abnormalities, clinicians should suspect scrub typhus and consider empirical antibiotic therapy.

  18. Loss of Dignity in Severe Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Solomon, Brahm K; Wilson, Keith G; Henderson, Peter R; Poulin, Patricia A; Kowal, John; McKim, Douglas A

    2016-03-01

    The maintenance of dignity is an important concept in palliative care, and the loss of dignity is a significant concern among patients with advanced cancer. The goals of this study were to examine whether loss of dignity is also a concern for patients receiving interdisciplinary rehabilitation for Stage III or IV chronic obstructive pulmonary disease. We examined the prevalence and correlates of loss of dignity and determined whether it improves with treatment. Inpatients underwent a structured interview inquiry around their sense of dignity and completed measures of pulmonary, physical, and psychological function at admission (n = 195) and discharge (n = 162). Loss of dignity was identified as a prominent ongoing concern for 13% of patients. It was correlated with measures of depression and anxiety sensitivity, but not with pulmonary capacity or functional performance. A robust improvement in loss of dignity was demonstrated, with 88% of those who reported a significant problem at admission no longer reporting one at discharge. The prevalence of a problematic loss of dignity among patients with severe chronic obstructive pulmonary disease is at least as high as among those receiving palliative cancer care. Loss of dignity may represent a concern among people with medical illnesses more broadly, and not just in the context of "death with dignity" at the end of life. Furthermore, interdisciplinary care may help to restore a sense of dignity to those individuals who are able to participate in rehabilitation. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  19. Severe hearing loss in Pallister-Killian syndrome.

    Science.gov (United States)

    Schuster, Maria; Hoppe, U; Eysholdt, U; Rosanowski, F

    2002-01-01

    Pallister-Killian syndrome is a rare disorder characterised by a specific combination of anatomic anomalies, mental retardation and lack of speech acquisition due to tetrasomy 12p. Hearing loss does not seem to be characteristic for this syndrome, although it was reported in several cases. We present the case of a girl first seen in our department at the age of 6 months. A severe sensory hearing loss was confirmed by subjective and objective audiometry. The child was successfully equipped with hearing aids. In the literature almost all children with Pallister-Killian syndrome are described as not developing verbal speech. Surprisingly their hearing abilities were not examined systematically. We advise audiological testing of children with Pallister-Killian syndrome.

  20. Assessment of Economic Loss Caused by Agricultural Non-point Source Nutrient Loss

    Institute of Scientific and Technical Information of China (English)

    FAN Liang-qian; CHEN Feng-hui

    2012-01-01

    Taking Zhejiang Province as an example, we use the JOHNES export coefficient model to estimate the total nitrogen (TN) and total phosphorus (TP) load of agricultural planting, livestock and poultry breeding and rural living non-point source in 2009. Based on the protection cost method in environmental economics, we quantitatively assess the economic loss caused by these three types of non-point source nutrient loss. The results show that in TN non-point source load, the load of land for planting accounts for 57.48%, the load of rural living accounts for 30.22%, and the load of livestock and poultry breeding accounts for 12.30%; in TP non-point source load, the load of rural living accounts for 46.18%, the load of livestock and poultry breeding accounts for 29.00%, and the load of land for planting accounts for 24.82%. The economic loss arising from the agricultural non-point source nutrient loss is equivalent to 2.329 424 7 billion yuan per year (the loss from land for planting accounts for 55.46%; the loss from rural living accounts for 31.21%; the loss from livestock and poultry breeding accounts for 13.33%). It indicates that in order to reduce the loss arising from agricultural non-point source nutrient loss, we should pay attention to controlling the land for planting and rural living source.

  1. A rare cause of severe hepatomegaly with an improving outcome

    DEFF Research Database (Denmark)

    Godskesen, Line Elberg; Abildgaard, Niels; Kjeldsen, Jens;

    2014-01-01

    A previously healthy 43-year-old man presented with dyspnoea, 15 kg weight loss, severe hepatomegaly and alkaline phosphatase at 5400 U/L. Examinations seemed to suggest cirrhosis, but blood samples did not show any signs of underlying liver disease. Liver biopsy revealed amyloid light chain (AL...

  2. Plasma cell gingivitis with severe alveolar bone loss.

    Science.gov (United States)

    Kumar, Vivek; Tripathi, Amitandra Kumar; Saimbi, Charanjit Singh; Sinha, Jolly

    2015-01-16

    Plasma cell gingivitis is a rare benign condition of the gingiva characterised by sharply demarcated erythaematous and oedematous gingiva often extending up to the muco gingival junction. It is considered a hypersensitive reaction. It presents clinically as a diffuse, erythaematous and papillary lesion of the gingiva, which frequently bleeds, with minimal trauma. This paper presents a case of a 42-year-old man who was diagnosed with plasma cell gingivitis, based on the presence of plasma cells in histological sections, and severe alveolar bone loss at the affected site, which was managed by surgical intervention.

  3. Fungal ball within Onodi cell mucocele causing visual loss.

    Science.gov (United States)

    Cheon, Yong-Il; Hong, Sung-Lyong; Roh, Hwan-Jung; Cho, Kyu-Sup

    2014-03-01

    The Onodi cell is a pneumatized posterior ethmoid cell located laterally and superiorly to the sphenoid sinus and closely related to the optic nerve. A mucocele is a benign, expansile, cystlike lesion of the paranasal sinuses that is filled with mucoid secretion. Therefore, optic neuropathy caused by an infected mucocele in an Onodi cell is uncommon. Furthermore, fungal infection superimposed on an Onodi cell mucocele is extremely rare and has not been reported previously. Here, we describe the first case of fungal ball within Onodi cell mucocele causing visual loss, which was completely removed via transnasal endoscopic approach.

  4. Coupling model for calculating prestress loss caused by relaxation loss, shrinkage, and creep of concrete

    Institute of Scientific and Technical Information of China (English)

    曹国辉; 胡佳星; 张锴

    2016-01-01

    The calculation model for the relaxation loss of concrete mentioned in the Code for Design of Highway Reinforced Concrete and Prestressed Concrete Bridges and Culverts(JTG D62—2004) wasmodified according to experimental data. Time-varying relaxation loss was considered in the new model. Moreover, prestressed reinforcement with varying lengths (caused by the shrinkage and creep of concrete) might influence the final values and the time-varying function of the forecast relaxation loss. Hence, the effects of concrete shrinkage and creep were considered when calculating prestress loss, which reflected the coupling relation between these effects and relaxation loss in concrete. Hence, the forecast relaxation loss of prestressed reinforcement under the effects of different initial stress levels at any time point can be calculated using the modified model. To simplify the calculation, the integral expression of the model can be changed into an algebraic equation. The accuracy of the result is related to the division of the periods within the ending time of deriving the final value of the relaxation loss of prestressed reinforcement. When the time division is reasonable, result accuracy is high. The modified model works excellently according to the comparison of the test results. The calculation result of the modified model mainly reflects the prestress loss values of prestressed reinforcement at each time point, which confirms that adopting the finding in practical applications is reasonable.

  5. Does post-infectious olfactory loss affect mood more severely than chronic sinusitis with olfactory loss?

    Science.gov (United States)

    Jung, Yong G; Lee, Jun-Seok; Park, Gi C

    2014-11-01

    Olfactory deficits that develop after viral upper respiratory infection (URI) may have different effects on patient depression index compared to chronic sinusitis with olfactory loss. However, there have been no controlled trials to evaluate the different effects of chronic sinusitis and URI on depression index. Prospective study of 25 subjects in two groups. This study enrolled 25 participants who were diagnosed with post-URI olfactory loss as the study group and 25 patients with chronic sinusitis and olfactory loss as a control group. Control group participants were matched for age, sex, and degree of olfactory loss (threshold, discrimination, and identification [TDI]). We compared the Beck Depression Inventory (BDI) scores of each group and analyzed the correlation between TDI and BDI. The mean BDI score of the post-URI group was significantly higher than that of the control group (14.52 ± 6.59 vs. 9.32 ± 5.23; P=.002). Age, sex, and TDI score did not affect BDI score in the post-URI olfactory loss group. However, BDI score in the sinusitis group was inversely correlated with TDI score (R=-0.423; P=.035), and the BDI score of female subjects (11.00 ± 5.13) was significantly higher than that of male subjects (5.00 ± 2.16; P = .047). Post-URI olfactory loss affected patient mood more severely than chronic sinusitis with a similar degree of olfactory loss. This influence was not affected by sex, age, or TDI score in the post-URI olfactory loss group. 3b. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  6. Blackleg (Leptosphaeria maculans) Severity and Yield Loss in Canola in Alberta, Canada

    OpenAIRE

    Sheau-Fang Hwang; Strelkov, Stephen E.; Gary Peng; Hafiz Ahmed; Qixing Zhou; George Turnbull

    2016-01-01

    Blackleg, caused by Leptosphaeria maculans, is an important disease of oilseed rape (Brassica napus L.) in Canada and throughout the world. Severe epidemics of blackleg can result in significant yield losses. Understanding disease-yield relationships is a prerequisite for measuring the agronomic efficacy and economic benefits of control methods. Field experiments were conducted in 2013, 2014, and 2015 to determine the relationship between blackleg disease severity and yield in a susceptible c...

  7. Weeds Cause Losses in Field Crops through Allelopathy

    Directory of Open Access Journals (Sweden)

    Tasawer ABBAS

    2016-03-01

    Full Text Available A large number of weeds are known to be associated with crops and causing economic losses. Weeds interfere with crops through competition and allelopathy. They produce secondary metabolites known as allelochemicals, which belong to numerous chemical classes such as phenolics, alkaloids, fatty acids, indoles, terpens etc. However, phenolics are the predominant class of allelochemicals. The allelochemicals release from weed plants takes place through leaf leachates, decomposition of plant residues, volatilization and root exudates. Weeds leave huge quantities of their residues in field and affect the associated, as well as succeeding crops, in various cropping systems. Liberation of allelochemicals from weeds affects the germination, stand establishment, growth, yield and physiology of crop plants. They cause substantial reduction in germination and growth of the crop plants by altering various physiological processes such as enzyme activity, protein synthesis, photosynthesis, respiration, cell division and enlargement, which ultimately leads to a significant reduction in crop yield. In crux, allelopathic weeds represent a potential threat for crop plants and cause economic losses.

  8. Rhabdomyolysis following severe hypokalemia caused by familial hypokalemic periodic paralysis

    Science.gov (United States)

    Jung, Young-Lee; Kang, Jae-Young

    2017-01-01

    Rhabdomyolysis continues to appear with increasing frequency and represents a medical emergency requiring rapid appropriate treatment. One of the unusual causes of nontraumatic rhabdomyolysis is hypokalemic periodic paralysis without secondary causes. Primary hypokalemic periodic paralysis is a rare genetic disease characterized by episodic attacks of muscle weakness due to decreases in serum potassium. A 30-year-old woman who had 3 episodic attacks of hypokalemic periodic paralysis was admitted in emergency room with sudden onset symmetrical muscle weakness. After several hours, she started to complain myalgia and severe ache in both calves without any changes. Laboratory test showed markedly elevated creatine phosphokinase, lactic dehydrogenase levels with hypokalemia, rhabdomyolysis resulting from hypokalemia was diagnosed. Here, we report an unusual case of rhabdomyolysis caused by severe hypokalemia, which was suggested a result of familial hypokalemic periodic paralysis. PMID:28255549

  9. Rhabdomyolysis following severe hypokalemia caused by familial hypokalemic periodic paralysis.

    Science.gov (United States)

    Jung, Young-Lee; Kang, Jae-Young

    2017-02-16

    Rhabdomyolysis continues to appear with increasing frequency and represents a medical emergency requiring rapid appropriate treatment. One of the unusual causes of nontraumatic rhabdomyolysis is hypokalemic periodic paralysis without secondary causes. Primary hypokalemic periodic paralysis is a rare genetic disease characterized by episodic attacks of muscle weakness due to decreases in serum potassium. A 30-year-old woman who had 3 episodic attacks of hypokalemic periodic paralysis was admitted in emergency room with sudden onset symmetrical muscle weakness. After several hours, she started to complain myalgia and severe ache in both calves without any changes. Laboratory test showed markedly elevated creatine phosphokinase, lactic dehydrogenase levels with hypokalemia, rhabdomyolysis resulting from hypokalemia was diagnosed. Here, we report an unusual case of rhabdomyolysis caused by severe hypokalemia, which was suggested a result of familial hypokalemic periodic paralysis.

  10. AIDS in an infant causing severe failure to thrive.

    Science.gov (United States)

    Elias-Jones, A C; Larcher, V F; Price, E H

    1987-07-01

    A nine-month-old female Jamaican infant presented with a history of severe failure to thrive, recurrent pneumonia and developmental delay. She was found to have hepatosplenomegaly, generalised lymphadenopathy and hypotonia. Investigations revealed polyclonal hypergammaglobulinaemia, cytomegalovirus in her urine, and patchy lung infiltrates on her chest radiographs. Three separate tests were positive for human immunodeficiency virus in both the infant and her mother, suggesting vertical transmission, and confirming AIDS as the cause of the severe failure to thrive.

  11. Congenital cytomegalovirus infection - a common cause of hearing loss of unknown aetiology.

    Science.gov (United States)

    Karltorp, Eva; Hellström, Sten; Lewensohn-Fuchs, Ilona; Carlsson-Hansén, Eva; Carlsson, Per-Inge; Engman, Mona-Lisa

    2012-08-01

    The aim of this study was to investigate the role of congenital cytomegalovirus (CMV) infection as a cause of various types of sensorineural hearing loss (SNHL) in a group of nonsyndromic children with otherwise unknown aetiology of hearing loss. Furthermore, the occurrence of combined congenital CMV infection and connexin 26 (Cx26) mutations was investigated. The dried blood spot (DBS) cards of 45 children with various degrees of hearing deficits and 46 children with severe/profound hearing loss were tested for CMV DNA with polymerase chain reaction (PCR) technique. The DBS cards of the 46 children with severe/profound hearing loss were also analysed for Cx26 mutations. Of the 45 children with various degrees of hearing loss, nine were positive for CMV DNA (20%). The nine children represented severe/profound, mild and unilateral hearing loss. From the 46 children with severe/profound hearing loss, nine of 46 (20%) were positive for CMV DNA. In addition, three of the CMV DNA-positive children were carriers of mutations of Cx26. Congenital CMV infection is a high risk factor in hearing impairment among children. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.

  12. PERIPHERAL HEARING LOSS CAUSES HYPEREXCITABILITY OF THE INFERIOR COLLICULUS

    Institute of Scientific and Technical Information of China (English)

    Sun Wei

    2013-01-01

    Growing evidence has been found to suggest that early development of the central auditory system is dependent on acoustic stimuli. Peripheral damage caused by noise exposure and ototoxic drugs can induce functional and anatomical changes along the auditory pathways. The inferior colliculus (IC) is a unique structure in the auditory system located between the primary auditory nuclei of the brainstem and the thala-mus. Damage to the IC inhibitory circuitry may affect central auditory processing and sound perception. Here, we review some of the striking electrophysiological changes in the IC that occur after noise exposure and ototoxic drug treatment. A common occurrence that emerges in the IC after peripheral damage is hyper-excitability of sound-evoked response. The hyperexcitability of the IC is likely related with reduced inhibi-tory response that requires normal peripheral inputs. Early age hearing loss can result in a long lasting in-creased susceptibility to audiogenic seizure which is related to hyperactivity in the IC evoked by loud sounds. Our studies suggest that hearing loss can cause increased IC neuron responsiveness which may be related to tinnitus, hyperacusis, and audiogenic seizure.

  13. A frameshift mutation in GRXCR2 causes recessively inherited hearing loss.

    Science.gov (United States)

    Imtiaz, Ayesha; Kohrman, David C; Naz, Sadaf

    2014-05-01

    More than 360 million humans are affected with some degree of hearing loss, either early or later in life. A genetic cause for the disorder is present in a majority of the cases. We mapped a locus (DFNB101) for hearing loss in humans to chromosome 5q in a consanguineous Pakistani family. Exome sequencing revealed an insertion mutation in GRXCR2 as the cause of moderate-to-severe and likely progressive hearing loss in the affected individuals of the family. The frameshift mutation is predicted to affect a conserved, cysteine-rich region of GRXCR2, and to result in an abnormal extension of the C-terminus. Functional studies by cell transfections demonstrated that the mutant protein is unstable and mislocalized relative to wild-type GRXCR2, consistent with a loss-of-function mutation. Targeted disruption of Grxcr2 is concurrently reported to cause hearing loss in mice. The structural abnormalities in this animal model suggest a role for GRXCR2 in the development of stereocilia bundles, specialized structures on the apical surface of sensory cells in the cochlea that are critical for sound detection. Our results indicate that GRXCR2 should be considered in differential genetic diagnosis for individuals with early onset, moderate-to-severe and progressive hearing loss.

  14. [Severe phimosis as cause of urosepsis with Actinobaculum schaalii].

    Science.gov (United States)

    Jöhnk, Maria Louise; Olsen, Anne Buchhave; Prag, Jørgen Brorson; Søby, Karen Marie

    2012-05-28

    Actinobaculum schaalii is a small, Gram-positive, facultative anaerobic, CO2-requiring rod. It is now an acknowledged uropathogen, but often overlooked because of its slow growth. It is part of the normal bacterial flora in the urogenital area, but can be the cause of both local and invasive infections. We present a case of A. schaalii urosepsis in a 68-year-old male with phimosis caused by a severe lichen sclerosus et atrophicus. The only bacteria found in blood and urine was A. schaalii.

  15. Hormonal Treatment for Severe Hydronephrosis Caused by Bladder Endometriosis

    Directory of Open Access Journals (Sweden)

    Erkan Efe

    2014-01-01

    Full Text Available The incidence of endometriosis cases involving the urinary system has recently increased, and the bladder is a specific zone where endometriosis is most commonly seen in the urinary system. In the case presented here, a patient presented to the emergency department with the complaint of side pain and was examined and diagnosed with severe hydronephrosis and bladder endometriosis was determined in the etiology. After the patient was pathologically diagnosed, Levonorgestrel-Releasing Intrauterine System (LNG-IUS was administered to the uterine cavity. At the 12-month follow-up, endometriosis was not observed in the cystoscopy and symptoms had completely regressed. Hydronephrosis may be observed after exposure of the ureter, and silent renal function loss may develop in patients suffering from endometriosis with bladder involvement. For patients with moderate or severe hydronephrosis associated with bladder endometriosis, LNG-IUS application may be separately and successfully used after conservative surgery.

  16. Group points to underlying causes of ecosystem, blodiversity loss

    Science.gov (United States)

    Showstack, Randy

    Freshwater diversion, urban water pollution,and overfishing are leading to the decline of some of Pakistan's coastal mangrove ecosystems. In Mexico's Calakmul Biosphere Reserve, near the border of Guatemala, population growth and poverty are pushing forest clearing. Meanwhile, in Chilika Lake in southeast India, changes in economic policies and global markets have led to changes in commercial aquaculture that is partly responsible for the decline of local fisheries and the bird population.These are the conclusions of some of the 10 case studies contained in a World Wildlife Fund (WWF) report, issued on July 6, that examines forests, wetlands, steppes, mangroves, and other habitats to determine the underlying causes for biodiversity loss.

  17. Technetium-99m DMSA preparation: Trivial issues causing severe problems

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, V. [Westmead and The Children`s Hospital, Westmead, NSW (Australia)

    1997-12-01

    Urinary tract infection (UTI) in children involving renal parenchyma, upper collecting system or bladder is one of the major causes for consideration in the diagnosis and management of paediatric nuclear medicine. Acute pyelonephritis is one of the prime causes of morbidity associated with urinary tract infection in children which can lead to progressive renal damage. Technetium-99m dimercaptosuccinic acid (DMSA) is used extensively for the assessment of UTI in paediatrics. The radiopharmaceutical preparation could be influenced by several factors, most of them are trivial, but invariably have severe impact on the quality of the scintiphotographs. This communication is mainly to highlight some of the issues related to {sup 99}mTc-DMSA preparation and the possible precautionary measures that need to be taken to obviate unwarranted problems. (author) 2 refs., 4 figs.

  18. Cystathionine beta-synthase deficiency causes fat loss in mice.

    Directory of Open Access Journals (Sweden)

    Sapna Gupta

    Full Text Available Cystathionine beta synthase (CBS is the rate-limiting enzyme responsible for the de novo synthesis of cysteine. Patients with CBS deficiency have greatly elevated plasma total homocysteine (tHcy, decreased levels of plasma total cysteine (tCys, and often a marfanoid appearance characterized by thinness and low body-mass index (BMI. Here, we characterize the growth and body mass characteristics of CBS deficient TgI278T Cbs(-/- mice and show that these animals have significantly decreased fat mass and tCys compared to heterozygous sibling mice. The decrease in fat mass is accompanied by a 34% decrease in liver glutathione (GSH along with a significant decrease in liver mRNA and protein for the critical fat biosynthesizing enzyme Stearoyl CoA desaturase-1 (Scd-1. Because plasma tCys has been positively associated with fat mass in humans, we tested the hypothesis that decreased tCys in TgI278T Cbs(-/- mice was the cause of the lean phenotype by placing the animals on water supplemented with N-acetyl cysteine (NAC from birth to 240 days of age. Although NAC treatment in TgI278T Cbs(-/- mice caused significant increase in serum tCys and liver GSH, there was no increase in body fat content or in liver Scd-1 levels. Our results show that lack of CBS activity causes loss of fat mass, and that this effect appears to be independent of low serum tCys.

  19. Severe cranial neuropathies caused by falls from heights in children.

    Science.gov (United States)

    Zahavi, A; Luckman, J; Yassur, I; Michowiz, S; Goldenberg-Cohen, N

    2016-04-01

    Falls from heights are the most common traumatic event associated with emergency department visits in children. This study investigated the incidence and clinical course of cranial neuropathies caused by falls from heights in children. The computerized records of a tertiary pediatric medical center were searched for all patients admitted to the emergency department in 2004-2014 with a head injury caused by falling from a height. Those with cranial neuropathies involving optic and eye-motility disturbances were identified, and their clinical, imaging, and outcome data were evaluated. Of the estimated 61,968 patients who presented to the emergency department during the study period because of a fall, 18,758 (30.3 %) had head trauma. Only 12 (seven boys, five girls, average age 6.7 years) had a visual disturbance. Eight were diagnosed with traumatic optic neuropathy, one after a 6-month delay, including two with accompanying cranial nerve (CN) III injuries. Five patients had anisocoria or an abnormal pupillary response to light at presentation, one patient had CN VI paralysis and temporary vision loss, and one patient had an isolated CN III injury diagnosed on follow-up. Visual improvement varied among the patients. Cranial neuropathies due to falls from heights are rare in children and are associated with high visual morbidity. Vision or ocular motility impairment, especially monocular vision loss, may be missed during acute intake to the emergency department, and a high index of suspicion is needed. Assessment of the pupillary response to light is essential.

  20. Loss of binocular vision as direct cause for misrouting of temporal retinal fibers in albinism.

    Science.gov (United States)

    Banihani, Saleh M

    2015-10-01

    In humans, the nasal retina projects to the contralateral hemisphere, whereas the temporal retina projects ipsilaterally. The nasotemporal line that divides the retina into crossed and uncrossed parts coincides with the vertical meridian through the fovea. This normal projection of the retina is severely altered in albinism, in which the nasotemporal line shifted into the temporal retina with temporal retinal fibers cross the midline at the optic chiasm. This study proposes the loss of binocular vision as direct cause for misrouting of temporal retinal fibers and shifting of the nasotemporal line temporally in albinism. It is supported by many observations that clearly indicate that loss of binocular vision causes uncrossed retinal fibers to cross the midline. This hypothesis may alert scientists and clinicians to find ways to prevent or minimize the loss of binocular vision that may occur in some diseases such as albinism and early squint. Hopefully, this will minimize the misrouting of temporal fibers and improve vision in such diseases.

  1. A Large Deletion Affecting TPM3, Causing Severe Nemaline Myopathy.

    Science.gov (United States)

    Kiiski, K; Lehtokari, V-L; Manzur, A Y; Sewry, C; Zaharieva, I; Muntoni, F; Pelin, K; Wallgren-Pettersson, C

    2015-09-21

    Nemaline myopathy may be caused by pathogenic variants in the TPM3 gene and is then called NEM1. All previously identified disease-causing variants are point mutations including missense, nonsense and splice-site variants. The aim of the study was to identify the disease-causing gene in this patient and verify the NM diagnosis. Mutation analysis methods include our self-designed nemaline myopathy array, The Nemaline Myopathy Comparative Genomic Hybridisation Array (NM-CGH array), whole-genome array-CGH, dHPLC, Sanger sequencing and whole-exome sequencing. The diagnostic muscle biopsy was investigated further by routine histopathological methods. We present here the first large (17-21 kb) aberration in the α-tropomyosinslow gene (TPM3), identified using the NM-CGH array. This homozygous deletion removes the exons 1a and 2b as well as the promoter of the TPM3 isoform encoding Tpm3.12st. The severe phenotype included paucity of movement, proximal and axial weakness and feeding difficulties requiring nasogastric tube feeding. The infant died at the age of 17.5 months. Muscle biopsy showed variation in fibre size and rods in a population of hypotrophic muscle fibres expressing slow myosin, often with internal nuclei, and abnormal immunolabelling revealing many hybrid fibres. This is the only copy number variation we have identified in any NM gene other than nebulin (NEB), suggesting that large deletions or duplications in these genes are very rare, yet possible, causes of NM.

  2. Dose L1 Retrotransposition Cause Neuronal Loss in Neurodegenerative Disorders?

    Directory of Open Access Journals (Sweden)

    Laleh Habibi

    2010-10-01

    Full Text Available "nNeurodegenerative disorders are among debilitating diseases that could affect many aspects of patient's life. Several mechanisms were shown to be involved in neuronal degeneration. However, the direct role of genomic instability is little considered in such disorders. L1 retrotransposons could cause genomic instability in different ways. Studies have shown increasing in L1 retrotransposition due to some reagents like heavy metals, stressors and the ones that may cause neuronal degeneration; Therefore cause cell to die. On the other hand, L1s retrotransposition was shown in neuronal precursor cells (NPCs providing the first evidence for movement of theses elements in nervous system."nHere, we propose that stimulation of L1 retrotransposition by environmental and genetic factors in neurons of central nervous system may lead them to apoptosis and result in neurodegenerative disorders. This hypothesis will be verified using L1-RP vector transfecting to definite neuronal cell line. By adding toxic agents including oxidative stress reagents and heavy metals to cell culture, we may track L1 retrotransposition and effects of this movement on cell physiology. Finding the involvement of mechanism in neurodegeneration may result in inventing new drugs for these disorders.

  3. Recessive mutations of TMC1 associated with moderate to severe hearing loss.

    Science.gov (United States)

    Imtiaz, Ayesha; Maqsood, Azra; Rehman, Atteeq U; Morell, Robert J; Holt, Jeffrey R; Friedman, Thomas B; Naz, Sadaf

    2016-04-01

    TMC1 encodes a protein required for the normal function of mechanically activated channels that enable sensory transduction in auditory and vestibular hair cells. TMC1 protein is localized at the tips of the hair cell stereocilia, the site of conventional mechanotransduction. In many populations, loss-of-function recessive mutations of TMC1 are associated with profound deafness across all frequencies tested. In six families reported here, variable moderate-to-severe or moderate-to-profound hearing loss co-segregated with STR (short tandem repeats) markers at the TMC1 locus DFNB7/11. Massively parallel and Sanger sequencing of genomic DNA revealed each family co-segregating hearing loss with a homozygous TMC1 mutation: two reported mutations (p.R34X and p.R389Q) and three novel mutations (p.S596R, p.N199I, and c.1404 + 1G > T). TMC1 cDNA sequence from affected subjects homozygous for the donor splice site transversion c.1404 + 1G > T revealed skipping of exon 16, deleting 60 amino acids from the TMC1 protein. Since the mutations in our study cause less than profound hearing loss, we speculate that there is hypo-functional TMC1 mechanotransduction channel activity and that other even less damaging variants of TMC1 may be associated with more common mild-to-severe sensorineural hearing loss.

  4. CD45-deficient severe combined immunodeficiency caused by uniparental disomy

    Science.gov (United States)

    Roberts, Joseph L.; Buckley, Rebecca H.; Luo, Biao; Pei, Jianming; Lapidus, Alla; Peri, Suraj; Wei, Qiong; Shin, Jinwook; Parrott, Roberta E.; Dunbrack, Roland L.; Testa, Joseph R.; Zhong, Xiao-Ping; Wiest, David L.

    2012-01-01

    Analysis of the molecular etiologies of SCID has led to important insights into the control of immune cell development. Most cases of SCID result from either X-linked or autosomal recessive inheritance of mutations in a known causative gene. However, in some cases, the molecular etiology remains unclear. To identify the cause of SCID in a patient known to lack the protein-tyrosine phosphatase CD45, we used SNP arrays and whole-exome sequencing. The patient’s mother was heterozygous for an inactivating mutation in CD45 but the paternal alleles exhibited no detectable mutations. The patient exhibited a single CD45 mutation identical to the maternal allele. Patient SNP array analysis revealed no change in copy number but loss of heterozygosity for the entire length of chromosome 1 (Chr1), indicating that disease was caused by uniparental disomy (UPD) with isodisomy of the entire maternal Chr1 bearing the mutant CD45 allele. Nonlymphoid blood cells and other mesoderm- and ectoderm-derived tissues retained UPD of the entire maternal Chr1 in this patient, who had undergone successful bone marrow transplantation. Exome sequencing revealed mutations in seven additional genes bearing nonsynonymous SNPs predicted to have deleterious effects. These findings are unique in representing a reported case of SCID caused by UPD and suggest UPD should be considered in SCID and other recessive disorders, especially when the patient appears homozygous for an abnormal gene found in only one parent. Evaluation for alterations in other genes affected by UPD should also be considered in such cases. PMID:22689986

  5. Posterior mediastinal melanoma causing severe dysphagia: A case report

    Directory of Open Access Journals (Sweden)

    Meacci Elisa

    2008-09-01

    Full Text Available Abstract Introduction We describe an original case of progressive severe dysphagia caused by a posterior mediastinal metastatic melanoma of unknown origin. To the best of our knowledge, such an event has never been described before in the literature. Case presentation A progressive severe dysphagia case is reported induced by a melanoma of unknown origin (metastatic to a posterior mediastinal lymph node. At the time of diagnosis, the lesion appeared as a large posterior mediastinal mass mimicking a neurogenic tumour with oesophageal involvement. After complete resection, pathological assessment of the tumour by immunohistochemistry was consistent with nodal metastatic melanoma. Conclusion This report of a posterior mediastinal lymph node melanoma is unique. The nodal origin is definitely unusual: a primary melanoma should always be carefully ruled out. In fact no other evidence, a part from the absence of the tumour elsewhere, can support the diagnosis of a primary nodal melanoma.

  6. Severe atrophic vaginitis causing vaginal synechiae and hematocolpos at menopause.

    Science.gov (United States)

    Segal, Saya; Harvie, Heidi S; Siegelman, Evan; Arya, Lily A

    2011-03-01

    Vaginal atrophy caused by decreased levels of ovarian estrogen production is common at menopause. Atrophic vaginitis severe enough to result in vaginal stricture of the upper two thirds of the vagina and subsequent hematocolpos is unusual. A 53-year-old woman presented with nonvisualization of the cervix at the time of her annual examination. Pelvic ultrasound reported a "vaginal cyst," and the final diagnosis of hematocolpos was made by magnetic resonance imaging. The woman was managed with surgical excision of vaginal synechiae followed by local vaginal estrogen therapy and dilators, with satisfactory results. Untreated severe atrophic vaginitis at menopause can result in a shortened vagina and hematocolpos. Magnetic resonance imaging is useful to characterize vaginal pathology in postmenopausal women.

  7. Loss of lung WWOX expression causes neutrophilic inflammation.

    Science.gov (United States)

    Singla, Sunit; Chen, Jiwang; Sethuraman, Shruthi; Sysol, Justin R; Gampa, Amulya; Zhao, Shuangping; Machado, Roberto F

    2017-06-01

    The tumor suppressor WW domain-containing oxidoreductase (WWOX) exhibits regulatory interactions with an array of transcription factors and signaling molecules that are positioned at the well-known crossroads between inflammation and cancer. WWOX is also subject to downregulation by genotoxic environmental exposures, making it of potential interest to the study of lung pathobiology. Knockdown of lung WWOX expression in mice was observed to cause neutrophil influx and was accompanied by a corresponding vascular leak and inflammatory cytokine production. In cultured human alveolar epithelial cells, loss of WWOX expression resulted in increased c-Jun- and IL-8-dependent neutrophil chemotaxis toward cell monolayers. WWOX was observed to directly interact with c-Jun in these cells, and its absence resulted in increased nuclear translocation of c-Jun. Finally, inhibition of the c-Jun-activating kinase JNK abrogated the lung neutrophil influx observed during WWOX knockdown in mice. Altogether, these observations represent a novel mechanism of pulmonary neutrophil influx that is highly relevant to the pathobiology and potential treatment of a number of different lung inflammatory conditions. Copyright © 2017 the American Physiological Society.

  8. Effect of weight loss on the severity of psoriasis

    DEFF Research Database (Denmark)

    Jensen, P; Zachariae, Claus; Christensen, R

    2013-01-01

    Psoriasis is associated with adiposity and weight gain increases the severity of psoriasis and the risk of incident psoriasis. Therefore, we aimed to measure the effect of weight reduction on the severity of psoriasis in obese patients with psoriasis.......Psoriasis is associated with adiposity and weight gain increases the severity of psoriasis and the risk of incident psoriasis. Therefore, we aimed to measure the effect of weight reduction on the severity of psoriasis in obese patients with psoriasis....

  9. Severe Sensorineural Hearing Loss in Children with Cochlear Implants Causes of the Failure before the ECG and Nursing%重度感音聋患儿人工耳蜗植入术前心电图检查失败原因分析及护理对策

    Institute of Scientific and Technical Information of China (English)

    于莉; 刘伟萍; 李爱军

    2013-01-01

    Objective:To investigate severe sensorineural hearing loss in children with cochlear implants before ECG failure and develop appropriate nursing measures. Methods:A retrospective analysis of our hospital in February 2011~February 2012 period 428 cases (236males, 192females) with severe sensorineural hearing loss in children with cochlear implants preoperative clinical and ECG data, statistics, analysis and classification severe sensorineural hearing loss in children with preoperative ECG failure cases causes of the failure to develop nursing measures. Results:Preoperative ECG successful children with 188 cases, accounting for 44%;quadratic successful children with 232 cases, accounting for 54.2%;three successful children with eight cases, accounting for 1.87%;6 cases in 428 cases diagnosed with long QT syndrome, inoperable. Failure:(1) children with parents and children on a larger preoperative ECG lack of understanding of the necessity and importance. (2) ECG before taking on the role of drugs and side effects do not. (3) environmental factors and children with their own factors.Conclusion:Compliance behavior of parents of children with poor children is not fully implemented by your doctor right preoperative ECG preparation before;severe sensorineural hearing loss in children with cochlear implants before ECG targeted for parents of children and children with nursing intervention is necessary.%目的:探讨重度感音聋患儿人工耳蜗植入术前心电图检查失败的原因和制定相应的护理对策的措施。方法:回顾性分析我院2011年2月~2012年2月期间收治行人工耳蜗植入术重度感音聋患儿428例(男236例,女192例)术前的临床资料和心电图,统计、分类及分析重度感音聋患儿术前心电图检查失败病例的失败原因,制定相应的护理对策。结果:术前心电图检查一次成功的患儿有188例,占44%;二次成功的患儿有232例,占54.2%;三次成功的患儿有8

  10. MECP2 duplication: possible cause of severe phenotype in females.

    Science.gov (United States)

    Scott Schwoerer, Jessica; Laffin, Jennifer; Haun, Joanne; Raca, Gordana; Friez, Michael J; Giampietro, Philip F

    2014-04-01

    MECP2 duplication syndrome, originally described in 2005, is an X-linked neurodevelopmental disorder comprising infantile hypotonia, severe to profound intellectual disability, autism or autistic-like features, spasticity, along with a variety of additional features that are not always clinically apparent. The syndrome is due to a duplication (or triplication) of the gene methyl CpG binding protein 2 (MECP2). To date, the disorder has been described almost exclusively in males. Female carriers of the duplication are thought to have no or mild phenotypic features. Recently, a phenotype for females began emerging. We describe a family with ∼290 kb duplication of Xq28 region that includes the MECP2 gene where the proposita and affected family members are female. Twin sisters, presumed identical, presented early with developmental delay, and seizures. Evaluation of the proposita at 25 years of age included microarray comparative genomic hybridization (aCGH) which revealed the MECP2 gene duplication. The same duplication was found in the proposita's sister, who is more severely affected, and the proband's mother who has mild intellectual disability and depression. X-chromosome inactivation studies showed significant skewing in the mother, but was uninformative in the twin sisters. We propose that the MECP2 duplication caused for the phenotype of the proband and her sister. These findings support evidence for varied severity in some females with MECP2 duplications.

  11. Lingual tonsil hypertrophy causing severe dysphagia: treatment with plasma-mediated radiofrequency-based ablation (Coblation).

    Science.gov (United States)

    Mowry, Sarah E; Ament, Marvin; Shapiro, Nina L

    2010-03-01

    Lingual tonsil hypertrophy is an uncommon cause of upper aerodigestive tract pathology. We present the case of a 17-year-old boy who developed severe dysphagia and subsequent weight loss as a result of lingual tonsil hypertrophy. He was successfully treated with plasma-mediated radiofrequency-based ablation (Coblation). In the past, traditional surgical procedures for lingual tonsil hypertrophy were difficult to perform and recovery was difficult, but the introduction of Coblation has made lingual tonsillectomy much easier.

  12. Losses in superconducting Niobium Films caused by Interface Tunnel Exchange

    CERN Document Server

    Junginger, Tobias; Welsch, Carsten

    2012-01-01

    Identifying the loss mechanisms of niobium film cavities enables an accurate determination of applications for future accelerator projects and points to research topics required to mitigate their limitations. Measurements on samples show that the electric field is a dominant loss mechanism for niobium films, acting through interface tunneling between localized states in surface oxides and delocalized states in the superconducting niobium.

  13. Acute Liver Injury with Severe Coagulopathy in Marasmus Caused by a Somatic Delusional Disorder

    Directory of Open Access Journals (Sweden)

    Lance L. Stein

    2011-01-01

    Full Text Available Marasmus is a severe form of protein-calorie malnutrition characterized by the depletion of fat stores, muscle wasting, and the lack of edema. In developed countries, marasmus is often the result of anorexia nervosa. Abnormal transaminases with liver synthetic dysfunction have rarely been reported with anorexia nervosa. To our knowledge, we report the first detailed case of acute liver injury with severe coagulopathy (INR>1.5 in a patient with marasmus due to self-induced calorie restriction caused by a somatic delusional disorder. This case highlights the severity of liver injury that may occur with significant weight loss from self-induced calorie restriction and the rapid normalization of this injury with treatment. It is important for clinicians to be aware of patterns of acute liver injury in patients with severe protein-calorie malnutrition, regardless of the underlying cause.

  14. The Influence of Weight-Loss Expectations on Weight Loss and of Weight-Loss Satisfaction on Weight Maintenance in Severe Obesity.

    Science.gov (United States)

    Calugi, Simona; Marchesini, Giulio; El Ghoch, Marwan; Gavasso, Ilaria; Dalle Grave, Riccardo

    2017-01-01

    Conflicting evidence exists as to whether cognitive mechanisms contribute to weight loss and maintenance. To assess the influence of weight-loss expectations on weight loss, and of weight-loss satisfaction on weight maintenance, in individuals with severe obesity. A randomized controlled trial comparing two types of energy-restricted diets (high protein vs high carbohydrate) combined with weight-loss cognitive behavioral therapy, conducted over 51 weeks and divided into two phases: weight-loss phase (3 weeks of inpatient treatment and 24 weeks of outpatient treatment) and weight maintenance phase (24 weeks of outpatient treatment). Eighty-eight participants with severe obesity (mean age=46.7 years and mean body mass index=45.6), referred to an eating and weight disorders clinical service, were studied. Body weight was assessed at baseline, and after 3, 27 (end of weight-loss phase), and 51 weeks (end of weight maintenance phase). Weight loss expectations were assessed at the time of enrollment, and weight-loss satisfaction was assessed after 27 weeks. The relationship between weight-loss expectations and weight loss was assessed using a linear mixed model. The association between weight-loss satisfaction and final outcomes was tested by linear regression. The two groups had similar weight-loss expectations and satisfaction, and their results were therefore pooled. In general, the total amount of expected weight loss (in kilograms), but not the percentage of expected weight loss, predicted weight loss, and both satisfaction with weight loss and the amount of weight lost (in kilograms) were independent predictors of weight maintenance. Higher expected weight loss improves weight loss, and both the total amount of weight lost and satisfaction with weight loss are associated with weight-loss maintenance at 1-year follow-up. Copyright © 2017 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  15. Trends and causes of historical wetland loss in coastal Louisiana

    Science.gov (United States)

    Bernier, Julie

    2013-01-01

    Wetland losses in the northern Gulf Coast region of the United States are so extensive that they represent critical concerns to government environmental agencies and natural resource managers. In Louisiana, almost 3,000 square kilometers (km2) of low-lying wetlands converted to open water between 1956 and 2004, and billions of dollars in State and Federal funding have been allocated for coastal restoration projects intended to compensate for some of those wetland losses. Recent research at the St. Petersburg Coastal and Marine Science Center (SPCMSC) focused on understanding the physical processes and human activities that contributed to historical wetland loss in coastal Louisiana and the spatial and temporal trends of that loss. The physical processes (land-surface subsidence and sediment erosion) responsible for historical wetland loss were quantified by comparing marsh-surface elevations, water depths, and vertical displacements of stratigraphic contacts at 10 study areas in the Mississippi River delta plain and 6 sites at Sabine National Wildlife Refuge (SNWR) in the western chenier plain. The timing and extent of land loss at the study areas was determined by comparing historical maps, aerial photographs, and satellite imagery; the temporal and spatial trends of those losses were compared with historical subsidence rates and hydrocarbon production trends.

  16. Hibernation Based Therapy to Improve Survival of Severe Blood Loss

    Science.gov (United States)

    2016-06-01

    hydroxybutyrate, melatonin, shock, poly- trauma 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON...for injured casualties suffering from polytrauma and blast injuries. 2 Key Words: Beta-hydroxybutyrate Melatonin Poly- trauma Resuscitation...perivascular hemorrhage • DMSO may cause more significant lesions ( vascular damage and thrombosis, dermal leukocyte infiltrates etc.), presumably if it

  17. Edge-related loss of tree phylogenetic diversity in the severely fragmented Brazilian Atlantic forest.

    Science.gov (United States)

    Santos, Bráulio A; Arroyo-Rodríguez, Víctor; Moreno, Claudia E; Tabarelli, Marcelo

    2010-09-08

    Deforestation and forest fragmentation are known major causes of nonrandom extinction, but there is no information about their impact on the phylogenetic diversity of the remaining species assemblages. Using a large vegetation dataset from an old hyper-fragmented landscape in the Brazilian Atlantic rainforest we assess whether the local extirpation of tree species and functional impoverishment of tree assemblages reduce the phylogenetic diversity of the remaining tree assemblages. We detected a significant loss of tree phylogenetic diversity in forest edges, but not in core areas of small (tree phylogenetic diversity in the severely fragmented Brazilian Atlantic forest.

  18. Sleep Loss in Resident Physicians: The Cause of Medical Errors?

    Directory of Open Access Journals (Sweden)

    Milton eKramer

    2010-10-01

    Full Text Available This review begins with the history of the events starting with the death of Libby Zion that lead to the Bell Commission, that the studied her death and made recommendations for improvement that were codified into law in New York state as the 405 law that the ACGME essentially adopted in putting a cap on work hours and establishing the level of staff supervision that must be available to residents in clinical situations particularly the emergency room and acute care units. A summary is then provided of the findings of the laboratory effects of total sleep deprivation including acute total sleep loss and the consequent widespread physiologic alterations, and of the effects of selective and chronic sleep loss. Generally the sequence of responses to increasing sleep loss goes from mood changes to cognitive effects to performance deficits. In the laboratory situation, deficits resulting from sleep deprivation are clearly and definitively demonstrable. Sleep loss in the clinical situation is usually sleep deprivation superimposed on chronic sleep loss. An examination of questionnaire studies, the literature on reports of sleep loss, studies of the reduction of work hours on performance as well as observational and a few interventional studies have yielded contradictory and often equivocal results. The residents generally find they feel better working fewer hours but improvements in patient care are often not reported or do not occur. A change in the attitude of the resident toward his role and his patient has not been salutary. Decreasing sleep loss should have had a positive effect on patient care in reducing medical error, but this remains to be unequivocally demonstrated.

  19. Portable Low-Volume Therapy for Severe Blood Loss

    Science.gov (United States)

    2014-06-01

    Mel=melatonin. 23 Tables Table 1. Histopathological scoring system. Lung Intestine Brain 0 No Evidence 1 Mild Alveolitis (2-3X...Perivascular edema Development of subepithelial Gruenhagen’s space, vacuolization at the villus tip Focal pyknosis 2 Moderate Alveolitis (3-4X...3 Severe Alveolitis (>5X), Alveolar edema, Inflammatory infiltrate, Hemorrhage Epithelial lifting and vacuolization from the tip to lower portion

  20. Fire-derived charcoal causes loss of forest humus.

    Science.gov (United States)

    Wardle, David A; Nilsson, Marie-Charlotte; Zackrisson, Olle

    2008-05-01

    Fire is a global driver of carbon storage and converts a substantial proportion of plant biomass to black carbon (for example, charcoal), which remains in the soil for thousands of years. Black carbon is therefore often proposed as an important long-term sink of soil carbon. We ran a 10-year experiment in each of three boreal forest stands to show that fire-derived charcoal promotes loss of forest humus and that this is associated with enhancement of microbial activity by charcoal. This result shows that charcoal-induced losses of belowground carbon in forests can partially offset the benefits of charcoal as a long-term carbon sink.

  1. sesame harvest loss caused by sesame seed bug, elasmolomus ...

    African Journals Online (AJOL)

    ADMIN

    is one of the reasons. In this study, sesame seed weight loss due to sesame seed bug was determined at ..... are woven polypropylene bags made to store and transport grain products. ... taking away the whole seed to their resting or sheltering ...

  2. Blackleg (Leptosphaeria maculans Severity and Yield Loss in Canola in Alberta, Canada

    Directory of Open Access Journals (Sweden)

    Sheau-Fang Hwang

    2016-07-01

    Full Text Available Blackleg, caused by Leptosphaeria maculans, is an important disease of oilseed rape (Brassica napus L. in Canada and throughout the world. Severe epidemics of blackleg can result in significant yield losses. Understanding disease-yield relationships is a prerequisite for measuring the agronomic efficacy and economic benefits of control methods. Field experiments were conducted in 2013, 2014, and 2015 to determine the relationship between blackleg disease severity and yield in a susceptible cultivar and in moderately resistant to resistant canola hybrids. Disease severity was lower, and seed yield was 120%–128% greater, in the moderately resistant to resistant hybrids compared with the susceptible cultivar. Regression analysis showed that pod number and seed yield declined linearly as blackleg severity increased. Seed yield per plant decreased by 1.8 g for each unit increase in disease severity, corresponding to a decline in yield of 17.2% for each unit increase in disease severity. Pyraclostrobin fungicide reduced disease severity in all site-years and increased yield. These results show that the reduction of blackleg in canola crops substantially improves yields.

  3. Blackleg (Leptosphaeria maculans) Severity and Yield Loss in Canola in Alberta, Canada

    Science.gov (United States)

    Hwang, Sheau-Fang; Strelkov, Stephen E.; Peng, Gary; Ahmed, Hafiz; Zhou, Qixing; Turnbull, George

    2016-01-01

    Blackleg, caused by Leptosphaeria maculans, is an important disease of oilseed rape (Brassica napus L.) in Canada and throughout the world. Severe epidemics of blackleg can result in significant yield losses. Understanding disease-yield relationships is a prerequisite for measuring the agronomic efficacy and economic benefits of control methods. Field experiments were conducted in 2013, 2014, and 2015 to determine the relationship between blackleg disease severity and yield in a susceptible cultivar and in moderately resistant to resistant canola hybrids. Disease severity was lower, and seed yield was 120%–128% greater, in the moderately resistant to resistant hybrids compared with the susceptible cultivar. Regression analysis showed that pod number and seed yield declined linearly as blackleg severity increased. Seed yield per plant decreased by 1.8 g for each unit increase in disease severity, corresponding to a decline in yield of 17.2% for each unit increase in disease severity. Pyraclostrobin fungicide reduced disease severity in all site-years and increased yield. These results show that the reduction of blackleg in canola crops substantially improves yields. PMID:27447676

  4. Causes and Consequences of Exceptional North Atlantic Heat Loss in Recent Winters

    Science.gov (United States)

    Josey, Simon; Grist, Jeremy; Duchez, Aurelie; Frajka-Williams, Eleanor; Hirschi, Joel; Marsh, Robert; Sinha, Bablu

    2016-04-01

    The mid-high latitude North Atlantic loses large amounts of heat to the atmosphere in winter leading to dense water formation. An examination of reanalysis datasets (ERA-Interim, NCEP/NCAR) reveals that heat loss in the recent winters 2013-14 and 2014-15 was exceptionally strong. The causes and consequences of this extraordinary ocean heat loss will be discussed. In 2013-2014, the net air-sea heat flux anomaly averaged over the whole winter exceeded 100 Wm-2 in the eastern subpolar gyre (the most extreme in the period since 1979 spanned by ERA-Interim). The causes of this extreme heat loss will be shown to be severe latent and sensible heat fluxes driven primarily by anomalously strong westerly airflows from North America and northerly airflows originating in the Nordic Seas. The associated sea level pressure anomaly field reflects the dominance of the second mode of atmospheric variability, the East Atlantic Pattern (EAP) over the North Atlantic Oscillation (NAO) in this winter. The extreme winter heat loss had a significant impact on the ocean extending from the sea surface into the deeper layers and a re-emergent cold Sea Surface Temperature (SST) anomaly is evident in November 2014. The following winter 2014-15 experienced further extreme heat loss that served to amplify the strength of the re-emergent SST anomaly. By summer 2015, an unprecedented cold mid-latitude North Atlantic Ocean surface temperature anomaly is evident in observations and has been widely referred to as the 'big blue blob'. The role played by the extreme surface heat loss in the preceding winters in generating this feature and it subsequent evolution through winter 2015-16 will be explored.

  5. Loss of Ikbkap Causes Slow, Progressive Retinal Degeneration in a Mouse Model of Familial Dysautonomia

    Science.gov (United States)

    Ramirez, Grisela

    2016-01-01

    Abstract Familial dysautonomia (FD) is an autosomal recessive congenital neuropathy that is caused by a mutation in the gene for inhibitor of kappa B kinase complex-associated protein (IKBKAP). Although FD patients suffer from multiple neuropathies, a major debilitation that affects their quality of life is progressive blindness. To determine the requirement for Ikbkap in the developing and adult retina, we generated Ikbkap conditional knockout (CKO) mice using a TUBA1a promoter-Cre (Tα1-Cre). In the retina, Tα1-Cre expression is detected predominantly in retinal ganglion cells (RGCs). At 6 months, significant loss of RGCs had occurred in the CKO retinas, with the greatest loss in the temporal retina, which is the same spatial phenotype observed in FD, Leber hereditary optic neuropathy, and dominant optic atrophy. Interestingly, the melanopsin-positive RGCs were resistant to degeneration. By 9 months, signs of photoreceptor degeneration were observed, which later progressed to panretinal degeneration, including RGC and photoreceptor loss, optic nerve thinning, Müller glial activation, and disruption of layers. Taking these results together, we conclude that although Ikbkap is not required for normal development of RGCs, its loss causes a slow, progressive RGC degeneration most severely in the temporal retina, which is later followed by indirect photoreceptor loss and complete retinal disorganization. This mouse model of FD is not only useful for identifying the mechanisms mediating retinal degeneration, but also provides a model system in which to attempt to test therapeutics that may mitigate the loss of vision in FD patients. PMID:27699209

  6. Loss of ceramide synthase 3 causes lethal skin barrier disruption.

    Science.gov (United States)

    Jennemann, Richard; Rabionet, Mariona; Gorgas, Karin; Epstein, Sharon; Dalpke, Alexander; Rothermel, Ulrike; Bayerle, Aline; van der Hoeven, Franciscus; Imgrund, Silke; Kirsch, Joachim; Nickel, Walter; Willecke, Klaus; Riezman, Howard; Gröne, Hermann-Josef; Sandhoff, Roger

    2012-02-01

    The stratum corneum as the outermost epidermal layer protects against exsiccation and infection. Both the underlying cornified envelope (CE) and the intercellular lipid matrix contribute essentially to these two main protective barriers. Epidermis-unique ceramides with ultra-long-chain acyl moities (ULC-Cers) are key components of extracellular lipid lamellae (ELL) and are bound to CE proteins, thereby contributing to the cornified lipid envelope (CLE). Here, we identified human and mouse ceramide synthase 3 (CerS3), among CerS1-6, to be exclusively required for the ULC-Cer synthesis in vitro and of mouse CerS3 in vivo. Deficiency of CerS3 in mice results in complete loss of ULC-Cers (≥C26), lack of continuous ELL and a non-functional CLE. Consequently, newborn mutant mice die shortly after birth from transepidermal water loss. Mutant skin is prone to Candida albicans infection highlighting ULC-Cers to be pivotal for both barrier functions. Persistent periderm, hyperkeratosis and deficient cornification are hallmarks of mutant skin demonstrating loss of Cers to trigger a keratinocyte maturation arrest at an embryonic pre-barrier stage.

  7. case report successful treatment of bilateral visual loss caused by ...

    African Journals Online (AJOL)

    2011-12-02

    Dec 2, 2011 ... opportunistic infections, neoplasms and inflammatory causes.1 HIV infection ... brain illustrated enhancement of the optic nerves post-. CASE REPORT .... to activated microglia and macrophages releasing neurotoxic agents.1.

  8. Tricuspid regurgitation: noninvasive techniques for determining causes and severity.

    Science.gov (United States)

    DePace, N L; Ross, J; Iskandrian, A S; Nestico, P F; Kotler, M N; Mintz, G S; Segal, B L; Hakki, A H; Morganroth, J

    1984-06-01

    Tricuspid regurgitation is often not apparent on physical examination and several methods are now available to aid in this difficult assessment. Cardiac catheterization using right ventriculography, previously considered the diagnostic standard, has several limitations. Currently available noninvasive tools such as M-mode and two-dimensional echocardiography (with or without contrast), Doppler techniques and even radionuclide cardiologic imaging have added significantly to the precise assessment of the presence and severity of tricuspid regurgitation. This review examines the comparative use and limitations of these various techniques.

  9. Megadolicho basilar artery as a cause of asymmetrical sensorineural hearing loss - case report

    Directory of Open Access Journals (Sweden)

    Melo, Antonio Antunes

    2011-07-01

    Full Text Available Introduction: At the differentiated diagnosis of asymmetrical sensorineural hearing losses, vascular disorders are present, one of which is megadolicho basilar artery. This disease is generally asymptomatic, and when symptoms are found, they can be caused by a compression or ischemia. Clinically, sensorineural hearing loss, tinnitus, headache, facial hypoesthesia, trigeminal neuralgia, vertigo, diplopia and facial palsy, among others, are likely to occur. The image examination of choice for its diagnosis is nuclear magnetic resonance. The megadolicho basilar artery therapy can be surgical or conservative, according to the associated findings. A multidisciplinary approach, including a neurologist, neurosurgeon and an otorhinolaryngologist is recommended for a proper administration of the case. Objective: Report the case of a patient with asymmetrical sensorineural hearing loss, diagnosed of megadolicho basilar artery. Case report: JBS, 57-year-old white male with a history of asymmetrical sensorineural hearing loss and bilateral whistle-like tinnitus for several years. The otorhinolaryngologic evaluation, including otoscopy, anterior rhinoscopy and oral pharynx, was normal. Final Comments: The treatment consisted in following up with the patient, controlling the tinnitus by drugs and using an individual sound amplification apparatus on the left ear.

  10. A cause of severe thigh injury: Battery explosion

    Directory of Open Access Journals (Sweden)

    Tahsin Görgülü

    2016-02-01

    Discussion: Battery explosion causing lower extremity tissue defect is a type of injury that is rarely seen in the literature. Regardless of battery size and energy level, they should be considered as potential explosive material and protector masks, clothing should be worn during contact with this type of material.

  11. Cause of Death and the Quest for Meaning after the Loss of a Child

    Science.gov (United States)

    Lichtenthal, Wendy G.; Neimeyer, Robert A.; Currier, Joseph M.; Roberts, Kailey; Jordan, Nancy

    2013-01-01

    This study examined patterns of making meaning among 155 parents whose children died from a variety of violent and non-violent causes. Findings indicated 53% of violent loss survivors could not make sense of their loss, as compared to 32% of non-violent loss survivors. Overall, there was overlap in sense-making strategies across different causes…

  12. The More the Worse: the Grade of Noise-Induced Hearing Loss Associates with the Severity of Tinnitus

    Directory of Open Access Journals (Sweden)

    Agnieszka J. Szczepek

    2010-08-01

    Full Text Available Tinnitus disturbs lives and negatively affects the quality of life of about 2% of the adult world population. Research has shown that the main cause of tinnitus is hearing loss. To analyze a possible association of the degree of hearing loss with the severity of tinnitus, we have performed a retrospective study using admission data on 531 patients suffering from chronic tinnitus. We have found that 83% of our tinnitus patients had a high frequency hearing loss corresponding to a noise-induced hearing loss (NIHL. There was a significant correlation between the mean hearing loss and the tinnitus loudness (p < 0.0001. Interestingly, patients suffering from decompensated chronic tinnitus had a greater degree of hearing loss than the patients with compensated form of tinnitus. In addition, we demonstrate that the degree of hearing loss positively correlates with the two subscales (“intrusiveness” and “auditory perceptional difficulties” of the Tinnitus Questionnaire. Our retrospective study provides indirect evidence supporting the hypothesis that the degree of noise-induced hearing loss influences the severity of tinnitus.

  13. Severe early onset osteopenia and osteoporosis caused by antiepileptic drugs.

    NARCIS (Netherlands)

    Beerhorst, K.; Huvers, F.C.; Renier, W.O.

    2005-01-01

    We describe two adult patients with epilepsy who received long-term antiepileptic drug therapy, a woman aged 39 years and a man aged 38 years, in whom severe osteopenia and osteoporosis, respectively, were diagnosed. Both had had epilepsy since childhood, both were seizure free and off medication

  14. Bed bugs can cause severe anaemia in adults.

    Science.gov (United States)

    Paulke-Korinek, Maria; Széll, Marton; Laferl, Hermann; Auer, Herbert; Wenisch, Christoph

    2012-06-01

    A 60-year-old woman and her 67-year-old male partner, admitted for pneumonia and non-ST elevation myocardial infarction, respectively, had severe anaemia (Hb 5.3 and 5.2 g/dL, respectively), as a result from massive infestation with Cimex lectularius. After two erythrocyte transfusions and thorough decontamination, their clinical course was unremarkable.

  15. HUMAN RHINOVIRUS CAUSES SEVERE INFECTION IN PRETERM INFANTS

    NARCIS (Netherlands)

    van Piggelen, Renee O.; van Loon, Anton M.; Krediet, Tanette G.; Verboon-Maciolek, Malgorzata A.

    2010-01-01

    Data of 11 infants (median gestational age and birth weight 30 weeks and 1520 g, respectively) with severe human rhinovirus infection (HRV) are described. Nine of 11 (82%) were preterm infants and 7 of these 9 (78%) became infected during their stay in the neonatal intensive care unit. All infants p

  16. Acute starvation in pregnancy: a cause of severe metabolic acidosis.

    Science.gov (United States)

    Patel, A; Felstead, D; Doraiswami, M; Stocks, G M; Waheed, U

    2011-07-01

    We report a case of starvation-induced metabolic ketoacidosis in a previously healthy 29-year-old, nulliparous woman at 32 weeks of gestation. She was admitted to hospital with mild preeclampsia associated with persistent nausea and vomiting that progressed to severe preeclampsia requiring urgent control of hypertension before caesarean delivery. Prolonged and severe vomiting limited oral caloric intake and led to starvation ketoacidosis, characterised by ketonuria and a raised anion gap metabolic acidosis that required intensive care support. Despite significant metabolic derangement the patient appeared clinically well. Intravascular volume was replenished. Fluid restriction used as part of our preeclampsia treatment regimen delayed the therapeutic administration of sufficient dextrose, which rapidly corrected her metabolic derangement when commenced after delivery. Electrolyte supplementation was given to prevent re-feeding syndrome. Both mother and baby were discharged without sequelae.

  17. Piriformis syndrome surgery causing severe sciatic nerve injury.

    Science.gov (United States)

    Justice, Phillip E; Katirji, Bashar; Preston, David C; Grossman, Gerald E

    2012-09-01

    Piriformis syndrome is a controversial entrapment neuropathy in which the sciatic nerve is thought to be compressed by the piriformis muscle. Two patients developed severe left sciatic neuropathy after piriformis muscle release. One had a total sciatic nerve lesion, whereas the second had a predominantly high common peroneal nerve lesion. Follow-up studies showed reinnervation of the hamstrings only. We conclude that piriformis muscle surgery may be hazardous and result in devastating sciatic nerve injury.

  18. Severe Hemorrhage from the Umbilical Cord at Birth: A Preventable Cause of Neonatal Shock

    Directory of Open Access Journals (Sweden)

    Neetu Singh

    2013-01-01

    Full Text Available Posthemorrhagic anemia is a rare but important cause of anemia in neonates, second only to hemolytic anemia of newborn. Most cases of posthemorrhagic anemia are reported from fetomaternal hemorrhage or umbilical cord accidents in utero. This case report describes a preterm infant who developed severe anemia and shock immediately after delivery related to an acute hemorrhage through patent umbilical cord vessels secondary to a tear in the umbilical cord at the site of cord clamping. We believe that umbilical cord bleeding from errors in cord clamping could be an important cause of acute blood loss in the delivery room and that it may result in significant clinical morbidity, especially in extremely premature infants.

  19. Neurogenic vision loss: Causes and outcome. An experience from a tertiary center in Northern India

    Directory of Open Access Journals (Sweden)

    Rajesh Verma

    2014-01-01

    Full Text Available Introduction: Vision loss can be a consequence of numerous disorders of eye and neural pathway conveying visual input to brain. A variety of conditions can affect visual pathway producing neurogenic vision loss. The presentation and course of vision loss depends on the site of involvement and underlying etiology. We conducted this unprecedented study to evaluate the characteristics and outcome of various diseases of the visual pathway. Materials and Methods: In this prospective cohort study, we evaluated 64 patients with neurogenic visual impairment. Ophthalmological causes were excluded in all of them. Their presentation, ophthalmological characteristics and investigation findings were recorded. These patients were followed up till 6 months. Results: Out of 69 patients evaluated, 5 were excluded as they had ophthalmological abnormalities. The remaining 64 cases (113 eyes were enrolled. 54 cases were due to diseases of anterior visual pathway and rest 10 had cortical vision loss. The etiologic distribution is as follows: Isolated optic neuritis- 12 (19%, multiple sclerosis- 4 (6.3%, neuromyelitis optica- 5 (7.9%, tubercular meningitis- 15 (23.8%, non-arteritic ischemic optic neuropathy, ischemic optic neuropathy complicating cavernous sinus thrombosis, cryptococcal meningitis, malignant infiltration of optic nerve, Crouzon′s syndrome, calvarial thickening and traumatic occipital gliosis- 1 (1.6% case each, idiopathic intracranial hypertension, pituitary adenoma, acute disseminated encephalomyelitis, posterior reversible leukoencephalopathy- 3 (4.8% cases each, cortical venous thrombosis 5 (7.9%, subacute scleroing panencephalitis- 4 (6.3% cases. Conclusions: The diseases of anterior visual pathway were much more common than cortical vision loss. A majority of our patients had severe impairment of vision at presentation.

  20. A Novel Mutation in the EDAR Gene Causes Severe Autosomal Recessive Hypohidrotic Ectodermal Dysplasia

    DEFF Research Database (Denmark)

    Henningsen, Emil; Svendsen, Mathias Tiedemann; Lildballe, D. L.

    2014-01-01

    We report on a 2-year-old girl presenting with a severe form of hypohidrotic ectodermal dysplasia (HED). The patient presented with hypotrichosis, anodontia, hypohidrosis, frontal bossing, prominent lips and ears, dry, pale skin, and dermatitis. The patient had chronic rhinitis with malodorous na......-mediated NF-kB signalling. This complete loss-of-function mutation likely accounts for the severe clinical abnormalities in ectodermal structures in the described patient. (C) 2014 Wiley Periodicals, Inc....... nasal discharge. The girl was the second born child of first-cousin immigrants from Northern Iraq. A novel homozygous mutation (c.84delC) in the EDAR gene was identified. This mutation most likely causes a frameshift in the protein product (p.S29fs*74). This results in abolition of all ectodysplasin...

  1. Viral Causes of Hearing Loss: A Review for Hearing Health Professionals

    Science.gov (United States)

    Cohen, Brandon E.; Durstenfeld, Anne

    2014-01-01

    A number of viral infections can cause hearing loss. Hearing loss induced by these viruses can be congenital or acquired, unilateral or bilateral. Certain viral infections can directly damage inner ear structures, others can induce inflammatory responses which then cause this damage, and still others can increase susceptibility or bacterial or fungal infection, leading to hearing loss. Typically, virus-induced hearing loss is sensorineural, although conductive and mixed hearing losses can be seen following infection with certain viruses. Occasionally, recovery of hearing after these infections can occur spontaneously. Most importantly, some of these viral infections can be prevented or treated. For many of these viruses, guidelines for their treatment or prevention have recently been revised. In this review, we outline many of the viruses that cause hearing loss, their epidemiology, course, prevention, and treatment. PMID:25080364

  2. Viral causes of hearing loss: a review for hearing health professionals.

    Science.gov (United States)

    Cohen, Brandon E; Durstenfeld, Anne; Roehm, Pamela C

    2014-07-29

    A number of viral infections can cause hearing loss. Hearing loss induced by these viruses can be congenital or acquired, unilateral or bilateral. Certain viral infections can directly damage inner ear structures, others can induce inflammatory responses which then cause this damage, and still others can increase susceptibility or bacterial or fungal infection, leading to hearing loss. Typically, virus-induced hearing loss is sensorineural, although conductive and mixed hearing losses can be seen following infection with certain viruses. Occasionally, recovery of hearing after these infections can occur spontaneously. Most importantly, some of these viral infections can be prevented or treated. For many of these viruses, guidelines for their treatment or prevention have recently been revised. In this review, we outline many of the viruses that cause hearing loss, their epidemiology, course, prevention, and treatment.

  3. Severe head injury caused by motorcycle traffic accident

    Institute of Scientific and Technical Information of China (English)

    李钢

    1999-01-01

    Objective To explore the characteristic and treatment of the severe head injury due to motorcycle accident.Methods Review and analysis of 27 motorcycle traffic trauma cases who were admitted to our hospital from Oct.1995 to Sep.1997.Results Young men were the main composition of these patients.Multiple injuries associated with brain ste or diffuse axonal injury were common,which were the main factors influencing the consciousness and prognosis of the patients.The wound was usually severely contaminated.Evacuation of hematomas,decompression by depleting skull flap,hypotheymia and artificial hibernation were conducted in this series.Among them,14 cases were cured ,3 cases were seriously disabled,10 cases died.Conclusions Motorcycle's weight is light so it easily loses its balance.The riders and the passengers are exposed and lack protection.Driving against traffic regulations is frquently seen.All these are the reasons why the motorcycle traffic accidents often take place. When the traffic accident happens,the patients' head generally is thrown a long distance and dashed against the barrier or the ground.The psture nd mechanism of injury were complicated and varied.The decelerated injury and rolling injury occurred frequently and they were the main reasons for brain stem or diffuse axonal injury.The patients who have surgical indication should be operated upon as soon as possible.Hibernation and low temoerature therapy are conducive to the protection of the brain function at the early stage of postinjury or postoperation.A careful epluchage is essential to reduce infection of the open injury.

  4. Seawater Immersion Aggravates Burn Injury Causing Severe Blood Coagulation Dysfunction

    Directory of Open Access Journals (Sweden)

    Hong Yan

    2016-01-01

    Full Text Available This study aimed to investigate the endothelial function in a canine model of burn injury combined with seawater immersion. The model of burn injury was established. The dogs were randomly divided into four groups including dogs with burn injury (B group, or burn injury combined with seawater immersion (BI group, or only immersion in seawater (I group, or control animals with no injury or immersion (C group. The circulating endothelial cell (CEC count and coagulation-fibrinolysis parameters were measured. The CEC count in B group increased at 4 h, 7 h, and 10 h after injury and then reduced, whereas it continuously increased to a greater extent in BI group (P<0.05. The von Willebrand factor (vWF activity, plasminogen activator inhibitor (PAI-1, and the ratio of thromboxane B2 (TXB2 to 6-keto-prostaglandin F1α (6-K-PGF1α in BI group had a marked increase after injury, and the tissue-type plasminogen activator (tPA in the BI group decreased. Microscope observations revealed thrombus formation in lungs of the animals in BI group, but not in C, I, or B groups. Burn injury causes endothelial dysfunction, and seawater immersion lastingly aggravates this injury, leading to a higher risk of developing thrombosis.

  5. Radiotherapy on the neck nodes predicts severe weight loss in patients with early stage laryngeal cancer

    NARCIS (Netherlands)

    Langius, Jacqueline A. E.; Doornaert, Patricia; Spreeuwenberg, Marieke D.; Langendijk, Johannes A.; Leemans, C. Rene; van Bokhorst-de van der Schueren, Marian A. E.

    2010-01-01

    Background and purpose: Although patients with early stage (T1/T2) laryngeal cancer (LC) are thought to have a low incidence of malnutrition, severe weight loss is observed in a subgroup of these patients during radiotherapy (RI). The objective of this study was to evaluate weight loss and nutrition

  6. [Scorpionism causing severe acute flaccid paralysis. Case report].

    Science.gov (United States)

    Villa-Manzano, Alberto I; Vázquez-Solís, Ma Guadalupe; Zamora-López, Xochitl Xitlalli; Arias-Corona, Fernando; Palomera-Ávila, Francisco Miguel; Pulido-Galaviz, Carlos; Pacifuentes-Orozco, Adán

    2016-01-01

    Introducción: el alacranismo es un problema de salud pública en diversas regiones del mundo, siendo México el país que tiene mayor número de casos. Las manifestaciones clínicas oscilan desde sintomatología local hasta cuadros graves con repercusiones a nivel cardiovascular, respiratorio y neurológico, e incluso la muerte. No existen reportes de parálisis flácida como una manifestación del cuadro clínico por picadura del alacrán del género Centruroides, familia Buthidae, especie altamente tóxica, endémica y causante de altos índices de morbimortalidad en nuestra región. Caso clínico: documentamos un caso de alacranismo grave, provocado por escorpión de la familia Buthidae del género Centruroides, que causó parálisis flácida aguda, posterior a resolución de otras manifestaciones severas. Solo existe un reporte de caso de alacranismo que produce parálisis flácida aguda en la literatura médica, pero relacionado con el escorpión de la familia Parabuthus, endémico de Sudáfrica, el cual no es endémico en México. Conclusiones: conocer esta complicación, nueva para nuestra región, permitirá maximizar esfuerzos para diagnosticar y manejar oportunamente esta entidad con la aplicación temprana de faboterápico específico y soporte vital avanzado.

  7. Canine and feline pregnancy loss due to viral and non-infectious causes: a review.

    Science.gov (United States)

    Verstegen, J; Dhaliwal, G; Verstegen-Onclin, K

    2008-08-01

    Among the causes for pregnancy loss, viruses and non-infectious factors are among the most important. In both dogs and cats, research and clinical evidence provide proof that there is an increasing incidence of pregnancy loss associated with infectious diseases like herpesvirus, as well as the presence of toxicants or chemicals in the animal's diet and environment. Endocrine causes must be taken into consideration when dealing with pregnancy loss. This review will cover the most recent knowledge regarding viral and non-infectious of pregnancy losses in the dog and cat.

  8. Loss of presenilin function causes Alzheimer's disease-like neurodegeneration in the mouse.

    Science.gov (United States)

    Chen, Qian; Nakajima, Akira; Choi, Se Hoon; Xiong, Xiaoli; Tang, Ya-Ping

    2008-05-15

    Accumulating evidence has indicated that gain-of-function in beta-amyloid production may be not the necessary mechanism for mutant presenilin-1 (PS1) or PS2 to cause familial Alzheimer's disease (AD). In the present article, we show that conditional knockout of PS1 from the adult stage in the forebrain of mice with the PS2 null mutation triggers robust AD-like neurodegeneration including brain shrinkage, cortical and hippocampal atrophy,ventricular enlargement, severe neuronal loss, gliosis, tau hyperphosphorylation, neurofillament tangle-like structures, and intracellular filaments. Learning and memory functions in these mice are almost completely lost. Notably, there is no beta-amyloid deposition, indicating that presenilin dysfunction can directly cause neurodegeneration without the involvement of beta-amyloid. Furthermore, neurodegeneration occurs in a progressive manner following aging, suggesting that an accumulating effect of presenilin dysfunction over time might be a pathogenic mechanism for the involvement of mutant PS1/PS2 in causing AD. These results validate a mouse model characterized by the presence of many features of AD pathology. Furthermore, the demonstration of AD-like neurodegeneration in the absence of beta-amyloid deposition challenges the long-standing beta-amyloid cascade hypothesis and encourages an open debate on the role of beta-amyloid in causing AD. Most important, our results strongly suggest that to develop gamma-secretase inhibitors for the pharmacological treatment of AD may be not a reasonable strategy because antagonism of presenilin function may worsen neurodegeneration.

  9. Perception of Discomfort Caused by a Unilateral Hearing Loss in People Suffering from a Total Bilateral Vestibular Loss.

    Science.gov (United States)

    Gay, Annietta; Guinand, Nils; Miffon, Maëva; Guyot, Jean-Philippe

    2015-09-15

    The quality of life of patients suffering from a bilateral vestibular loss is severely altered. Patients mainly complain of oscillopsia, imbalance, and spatial disorientation. Up to now, there is no efficient treatment. Some teams around the world are working on the development of a vestibular implant for the restoration of the vestibular function based on the concept similar to that of a cochlear implant, stimulating the neural vestibular pathways through electrical pulses. There are different potential stimulation sites of the vestibular system, all raising the major concern about a potential hearing loss in the implanted ear. As this implant does not exist yet, patients cannot be informed of the risk of hearing loss due to the surgical intervention versus the benefits brought by the vestibular prosthesis. In order to better inform future vestibular implant candidates, we need to evaluate the handicap of patients with an actual unilateral hearing loss, and to compare it to the way that patients suffering from a bilateral vestibular loss perceive a potential unilateral hearing loss. For this, we used the HHIA questionnaire (Hearing Handicap Inventory for Adults) on 3 groups of participants, i.e. patients with a unilateral hearing loss, patients suffering from a bilateral vestibular loss but having normal hearing, and healthy subjects. The scores reported by patients with a unilateral hearing loss were much lower than those of the other 2 groups, indicating that people whose hearing is normal overstate the disability related to a unilateral hearing loss. Patients to whom a vestibular implant is proposed in order to correct their balance disorders may use this information to decide whether or not to choose an operation. © 2015 S. Karger AG, Basel.

  10. Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy.

    Science.gov (United States)

    Ravenscroft, Gianina; Miyatake, Satoko; Lehtokari, Vilma-Lotta; Todd, Emily J; Vornanen, Pauliina; Yau, Kyle S; Hayashi, Yukiko K; Miyake, Noriko; Tsurusaki, Yoshinori; Doi, Hiroshi; Saitsu, Hirotomo; Osaka, Hitoshi; Yamashita, Sumimasa; Ohya, Takashi; Sakamoto, Yuko; Koshimizu, Eriko; Imamura, Shintaro; Yamashita, Michiaki; Ogata, Kazuhiro; Shiina, Masaaki; Bryson-Richardson, Robert J; Vaz, Raquel; Ceyhan, Ozge; Brownstein, Catherine A; Swanson, Lindsay C; Monnot, Sophie; Romero, Norma B; Amthor, Helge; Kresoje, Nina; Sivadorai, Padma; Kiraly-Borri, Cathy; Haliloglu, Goknur; Talim, Beril; Orhan, Diclehan; Kale, Gulsev; Charles, Adrian K; Fabian, Victoria A; Davis, Mark R; Lammens, Martin; Sewry, Caroline A; Manzur, Adnan; Muntoni, Francesco; Clarke, Nigel F; North, Kathryn N; Bertini, Enrico; Nevo, Yoram; Willichowski, Ekkhard; Silberg, Inger E; Topaloglu, Haluk; Beggs, Alan H; Allcock, Richard J N; Nishino, Ichizo; Wallgren-Pettersson, Carina; Matsumoto, Naomichi; Laing, Nigel G

    2013-07-11

    Nemaline myopathy (NEM) is a common congenital myopathy. At the very severe end of the NEM clinical spectrum are genetically unresolved cases of autosomal-recessive fetal akinesia sequence. We studied a multinational cohort of 143 severe-NEM-affected families lacking genetic diagnosis. We performed whole-exome sequencing of six families and targeted gene sequencing of additional families. We identified 19 mutations in KLHL40 (kelch-like family member 40) in 28 apparently unrelated NEM kindreds of various ethnicities. Accounting for up to 28% of the tested individuals in the Japanese cohort, KLHL40 mutations were found to be the most common cause of this severe form of NEM. Clinical features of affected individuals were severe and distinctive and included fetal akinesia or hypokinesia and contractures, fractures, respiratory failure, and swallowing difficulties at birth. Molecular modeling suggested that the missense substitutions would destabilize the protein. Protein studies showed that KLHL40 is a striated-muscle-specific protein that is absent in KLHL40-associated NEM skeletal muscle. In zebrafish, klhl40a and klhl40b expression is largely confined to the myotome and skeletal muscle, and knockdown of these isoforms results in disruption of muscle structure and loss of movement. We identified KLHL40 mutations as a frequent cause of severe autosomal-recessive NEM and showed that it plays a key role in muscle development and function. Screening of KLHL40 should be a priority in individuals who are affected by autosomal-recessive NEM and who present with prenatal symptoms and/or contractures and in all Japanese individuals with severe NEM. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  11. Models for predicting potential yield loss of wheat caused by stripe rust in the U.S. Pacific Northwest.

    Science.gov (United States)

    Sharma-Poudyal, D; Chen, X M

    2011-05-01

    Climatic variation in the U.S. Pacific Northwest (PNW) affects epidemics of wheat stripe rust caused by Puccinia striiformis f. sp. tritici. Previous models only estimated disease severity at the flowering stage, which may not predict the actual yield loss. To identify weather factors correlated to stripe rust epidemics and develop models for predicting potential yield loss, correlation and regression analyses were conducted using weather parameters and historical yield loss data from 1993 to 2007 for winter wheat and 1995 to 2007 for spring wheat. Among 1,376 weather variables, 54 were correlated to yield loss of winter wheat and 18 to yield loss of spring wheat. Among the seasons, winter temperature variables were more highly correlated to wheat yield loss than the other seasons. The sum of daily temperatures and accumulated negative degree days of February were more highly correlated to winter wheat yield loss than the other monthly winter variables. In addition, the number of winter rainfall days was found correlated with yield loss. Six yield loss models were selected for each of winter and spring wheats based on their better correlation coefficients, time of weather data availability during the crop season, and better performance in validation tests. Compared with previous models, the new system of using a series of the selected models has advantages that should make it more suitable for forecasting and managing stripe rust in the major wheat growing areas in the U.S. PNW, where the weather conditions have become more favorable to stripe rust.

  12. Loss of Tgif function causes holoprosencephaly by disrupting the SHH signaling pathway.

    Science.gov (United States)

    Taniguchi, Kenichiro; Anderson, Anoush E; Sutherland, Ann E; Wotton, David

    2012-01-01

    Holoprosencephaly (HPE) is a severe human genetic disease affecting craniofacial development, with an incidence of up to 1/250 human conceptions and 1.3 per 10,000 live births. Mutations in the Sonic Hedgehog (SHH) gene result in HPE in humans and mice, and the Shh pathway is targeted by other mutations that cause HPE. However, at least 12 loci are associated with HPE in humans, suggesting that defects in other pathways contribute to this disease. Although the TGIF1 (TG-interacting factor) gene maps to the HPE4 locus, and heterozygous loss of function TGIF1 mutations are associated with HPE, mouse models have not yet explained how loss of Tgif1 causes HPE. Using a conditional Tgif1 allele, we show that mouse embryos lacking both Tgif1 and the related Tgif2 have HPE-like phenotypes reminiscent of Shh null embryos. Eye and nasal field separation is defective, and forebrain patterning is disrupted in embryos lacking both Tgifs. Early anterior patterning is relatively normal, but expression of Shh is reduced in the forebrain, and Gli3 expression is up-regulated throughout the neural tube. Gli3 acts primarily as an antagonist of Shh function, and the introduction of a heterozygous Gli3 mutation into embryos lacking both Tgif genes partially rescues Shh signaling, nasal field separation, and HPE. Tgif1 and Tgif2 are transcriptional repressors that limit Transforming Growth Factor β/Nodal signaling, and we show that reducing Nodal signaling in embryos lacking both Tgifs reduces the severity of HPE and partially restores the output of Shh signaling. Together, these results support a model in which Tgif function limits Nodal signaling to maintain the appropriate output of the Shh pathway in the forebrain. These data show for the first time that Tgif1 mutation in mouse contributes to HPE pathogenesis and provide evidence that this is due to disruption of the Shh pathway.

  13. Loss of Tgif function causes holoprosencephaly by disrupting the SHH signaling pathway.

    Directory of Open Access Journals (Sweden)

    Kenichiro Taniguchi

    Full Text Available Holoprosencephaly (HPE is a severe human genetic disease affecting craniofacial development, with an incidence of up to 1/250 human conceptions and 1.3 per 10,000 live births. Mutations in the Sonic Hedgehog (SHH gene result in HPE in humans and mice, and the Shh pathway is targeted by other mutations that cause HPE. However, at least 12 loci are associated with HPE in humans, suggesting that defects in other pathways contribute to this disease. Although the TGIF1 (TG-interacting factor gene maps to the HPE4 locus, and heterozygous loss of function TGIF1 mutations are associated with HPE, mouse models have not yet explained how loss of Tgif1 causes HPE. Using a conditional Tgif1 allele, we show that mouse embryos lacking both Tgif1 and the related Tgif2 have HPE-like phenotypes reminiscent of Shh null embryos. Eye and nasal field separation is defective, and forebrain patterning is disrupted in embryos lacking both Tgifs. Early anterior patterning is relatively normal, but expression of Shh is reduced in the forebrain, and Gli3 expression is up-regulated throughout the neural tube. Gli3 acts primarily as an antagonist of Shh function, and the introduction of a heterozygous Gli3 mutation into embryos lacking both Tgif genes partially rescues Shh signaling, nasal field separation, and HPE. Tgif1 and Tgif2 are transcriptional repressors that limit Transforming Growth Factor β/Nodal signaling, and we show that reducing Nodal signaling in embryos lacking both Tgifs reduces the severity of HPE and partially restores the output of Shh signaling. Together, these results support a model in which Tgif function limits Nodal signaling to maintain the appropriate output of the Shh pathway in the forebrain. These data show for the first time that Tgif1 mutation in mouse contributes to HPE pathogenesis and provide evidence that this is due to disruption of the Shh pathway.

  14. Estimating grain yield losses caused by septoria leaf blotch on durum wheat in Tunisia

    Directory of Open Access Journals (Sweden)

    Samia Berraies

    2014-12-01

    Full Text Available Septoria leaf blotch (SLB, caused by Zymoseptoria tritici (Desm. Quaedvlieg & Crous, 2011 (teleomorph: Mycosphaerella graminicola (Fuckel J. Schrot., is an important wheat disease in the Mediterranean region. In Tunisia, SLB has become a major disease of durum wheat (Triticum turgidum L. subsp. durum [Desf.] Husn. particularly during favorable growing seasons where significant yield losses and increase of fungicides use were recorded over the last three decades. The objectives of this study were to evaluate the effect of SLB severity on grain yield of new elite durum wheat breeding lines and to measure the relative effect of fungicide control on grain yield. Experiments were conducted during 2007-2008 and 2008-2009 cropping seasons. A set of 800 breeding lines were screened for reaction to SLB under natural infection at Beja research station. To estimate the disease effect, correlation between disease severity at early grain filling stage and grain yield was performed. Results showed that susceptible varieties yield was significantly reduced by SLB. Average yield reduction was as high as 384 and 325 kg ha-1 for every increment in disease severity on a 0-9 scale in both seasons, respectively. A negative correlation coefficient varied between -0.61 and -0.66 in both seasons. Treated and untreated trials conducted during 2008-2009 and 2009-2010 showed that yield of treated plots increased by 50% on the commonly cultivated susceptible varieties. The results of this investigation suggested that septoria incidence is related to large grain yield losses particularly on susceptible high yielding cultivars. However, appropriate fungicide application at booting growth stage could be beneficial for farmers. The development and use of more effective fungicide could be sought to alleviate the disease effects and therefore could be considered as a part of the integrated pest management and responsible use strategy on septoria leaf blotch in Tunisia.

  15. Trends in the incidence and causes of severe visual impairment and blindness in children from Israel.

    Science.gov (United States)

    Mezer, Eedy; Chetrit, Angela; Kalter-Leibovici, Ofra; Kinori, Michael; Ben-Zion, Itay; Wygnanski-Jaffe, Tamara

    2015-06-01

    To describe trends in the incidence and causes of legal childhood blindness in Israel, one of the few countries worldwide that maintain a national registry of the blind. We performed a historical cohort study of annual reports of the National Registry of the Blind (NRB) between 1999 and 2013. All data regarding demographic information, year of registration and cause of blindness of children 0-18 years of age registered for blind certification were obtained from the annual reports of the NRB. Causes of legal blindness analyzed were optic atrophy, retinitis pigmentosa, retinopathy of prematurity (ROP), albinism, other retinal disorders, cataract, and glaucoma. The main outcome measure was the incidence of new cases of certified legal blindness. The incidence of newly registered legally blind children in Israel almost halved from 7.7 per 100,000 in 1999 to 3.1 per 100,000 in 2013. The decline was mainly attributable to a decreased incidence of blindness resulting from retinitis pigmentosa and ROP. The incidence of registered cases due to cerebral visual impairment increased. During the past decade the incidence of severe childhood visual impairment and blindness declined in Israel. A continuous decline in consanguineous marriages among the Jewish and Arab populations in Israel may have contributed to the decrease in the rate of vision loss due to retinitis pigmentosa in children. Copyright © 2015 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.

  16. Oral Health Problems And Causes Of Tooth Loss At The University ...

    African Journals Online (AJOL)

    Context Several oral diseases and conditions are associated with tooth loss. Objective: The aim of this study was to determine the prevalence of oral health ... The data were computer- analysed; Chi square statistics was used to test for ...

  17. Norepinephrine-induced nerve growth factor depletion causes cardiac sympathetic denervation in severe heart failure.

    Science.gov (United States)

    Kimura, Kensuke; Kanazawa, Hideaki; Ieda, Masaki; Kawaguchi-Manabe, Haruko; Miyake, Yoshiko; Yagi, Takashi; Arai, Takahide; Sano, Motoaki; Fukuda, Keiichi

    2010-08-25

    In severe congestive heart failure (CHF), sympathetic overactivity correlates with the exacerbation of cardiac performance. To test the hypothesis that the cardiac sympathetic nerve density dramatically changes with the acceleration of circulating norepinephrine (NE) concentration, we investigated the temporal association of nerve growth factor (NGF) expression in the heart and cardiac sympathetic nerve density during the development of CHF in the continuous NE-infused rats. The animals were analyzed at 0-, 1-, 3-, 7-, 14-, and 28-day after implantation of osmotic pump at a rate of 0.05 mg/kg/hr. The cardiac performance was temporally facilitated in NE-exposed rats at 3-day in accordance with the sympathetic hyper-innervation induced by the augmentation of NGF mRNA expression in the heart. In NE-treated rats, left ventricular end-diastolic pressure was significantly increased after 7-day and marked left ventricular hypertrophy and systemic fluid retention were observed at 28-day. CHF-induced sympathetic overactivity further increased plasma NE concentration in NE-treated rats and finally reached to 16.1+/-5.6 ng/ml at 28-day (control level was 0.39+/-0.1 ng/ml, pcardiac performance. The cardiac sympathetic fiber loss was also confirmed in NE-exposed DBH (dopamine beta-hydroxylase)-Cre/Floxed-EGFP (enhanced green fluorescent protein) mice with severe CHF, in which sympathetic nerve could be traced by EGFP. Our results suggest that the cardiac sympathetic nerve density is strictly regulated by the NGF expression in the heart and long-exposure of high plasma NE concentration caused myocardial NGF reduction, following sympathetic fiber loss in severe CHF animals.

  18. Staged Custom, Intramedullary Antibiotic Spacers for Severe Segmental Bone Loss in Infected Total Hip Arthroplasty

    Directory of Open Access Journals (Sweden)

    Atul F. Kamath

    2011-01-01

    Full Text Available Introduction. Total hip arthroplasty (THA infections with severe bone loss pose significant reconstructive challenges. We present our experience with two-stage hip reimplantation using an intramedullary, antibiotic-impregnated nail. Methods. Three patients with infected THA with severe proximal femoral bone loss (Mallory type IIIB or greater were treated using a custom antibiotic spacer. Clinical outcomes and any complications were recorded. Average followup was 49 months from final reimplantation. Results. Mean age at spacer placement (stage 1 was 53 years. The mean Harris Hip Score at final followup was 80. Two patients had asymptomatic heterotopic ossification, and one patient had a 2 cm leg-length discrepancy. Conclusions. A custom intramedullary nail antibiotic spacer is a reliable option in the staged management of the infected THA with severe proximal femoral bone loss. Benefits of this technique include limb salvage with maintenance of leg length, soft tissue tension, and functional status.

  19. Risk finance for catastrophe losses with Pareto-calibrated Lévy-stable severities.

    Science.gov (United States)

    Powers, Michael R; Powers, Thomas Y; Gao, Siwei

    2012-11-01

    For catastrophe losses, the conventional risk finance paradigm of enterprise risk management identifies transfer, as opposed to pooling or avoidance, as the preferred solution. However, this analysis does not necessarily account for differences between light- and heavy-tailed characteristics of loss portfolios. Of particular concern are the decreasing benefits of diversification (through pooling) as the tails of severity distributions become heavier. In the present article, we study a loss portfolio characterized by nonstochastic frequency and a class of Lévy-stable severity distributions calibrated to match the parameters of the Pareto II distribution. We then propose a conservative risk finance paradigm that can be used to prepare the firm for worst-case scenarios with regard to both (1) the firm's intrinsic sensitivity to risk and (2) the heaviness of the severity's tail.

  20. Prevalence of Auditory Neuropathy in a Population of Children with Severe to Profound Hearing Loss

    Directory of Open Access Journals (Sweden)

    Nader Saki

    2013-04-01

    Full Text Available Background: The purpose of this investigation is to determine auditory neuropathy in the students with severe to profound hearing losses in Ahwaz.Materials and Methods: In this cross-sectional study, 212 children of 7-11 year old with severe to profound hearing loss performed ordinary audiometric evaluations as well as ABR and OAE. The patients with normal DPOAE who had no record of acoustic reflex having normal ABR, were considered as the patients with auditory neuropathy. Results: The neuropathic complication found in 14 children was appeared in 8 ones as one-sided (57.14% and in 6 ones (42.86% as two-sided. 68% of the patients as diagnosed had a very low Speech Discrimination Score (SDS.Conclusion: we must be very vigilant in auditory neuropathy diagnosis for the purpose to be successful in appropriate treatment of severe to profound hearing losses.

  1. Minimally invasive intervention in a case of a noncarious lesion and severe loss of tooth structure.

    Science.gov (United States)

    Reston, Eduardo G; Corba, Vanessa D; Broliato, Gustavo; Saldini, Bruno P; Stefanello Busato, Adair L

    2012-01-01

    The present article describes a minimally invasive technique used for the restoration of loss of tooth structure caused by erosion of intrinsic etiology. First, the cause of erosion was treated and controlled. Subsequently, taking into consideration patient characteristics, especially a young age, a more conservative technique was chosen for dental rehabilitation with the use of composite resin. The advantages and disadvantages of the technique employed are discussed.

  2. Spontaneous recovery of cochlear fibrocytes after severe degeneration caused by acute energy failure

    Directory of Open Access Journals (Sweden)

    Kunio eMizutari

    2014-08-01

    Full Text Available Cochlear fibrocytes in the lateral wall region play a critical role in the regulation of inner ear ion and fluid homeostasis, although these are nonsensory cells. Along with other nonsensory cells, fibrocytes in the spiral ligament have been reported to repopulate themselves after damage. However, the studies of regeneration of cochlear fibrocytes have been difficult because a suitable fibrocyte-specific degeneration model did not exist. Therefore, we analyzed cochlear fibrocytes using a rat model of acute cochlear energy failure induced by a mitochondrial toxin. This model is unique because hearing loss is caused by apoptosis of fibrocytes in the cochlear lateral wall not by damage to sensory cells. Although this model involves severe damage to the cochlear lateral wall, delayed spontaneous regeneration occurs without any treatment. Moreover, partial hearing recovery is accompanied by morphological remodeling of the cochlear lateral wall. Two hypotheses are conceivable regarding this spontaneous recovery of cochlear fibrocytes. One is that residual cochlear fibrocytes proliferate spontaneously, followed by remodeling of the functional region of the lateral wall. Another is that some foreign cells such as bone marrow-derived cells promote morphological and functional recovery of the lateral wall. Acceleration of the lateral wall recovery promoted by these mechanisms may be a new therapeutic strategy against hearing loss.

  3. Edge-related loss of tree phylogenetic diversity in the severely fragmented Brazilian Atlantic forest.

    Directory of Open Access Journals (Sweden)

    Bráulio A Santos

    Full Text Available Deforestation and forest fragmentation are known major causes of nonrandom extinction, but there is no information about their impact on the phylogenetic diversity of the remaining species assemblages. Using a large vegetation dataset from an old hyper-fragmented landscape in the Brazilian Atlantic rainforest we assess whether the local extirpation of tree species and functional impoverishment of tree assemblages reduce the phylogenetic diversity of the remaining tree assemblages. We detected a significant loss of tree phylogenetic diversity in forest edges, but not in core areas of small (<80 ha forest fragments. This was attributed to a reduction of 11% in the average phylogenetic distance between any two randomly chosen individuals from forest edges; an increase of 17% in the average phylogenetic distance to closest non-conspecific relative for each individual in forest edges; and to the potential manifestation of late edge effects in the core areas of small forest remnants. We found no evidence supporting fragmentation-induced phylogenetic clustering or evenness. This could be explained by the low phylogenetic conservatism of key life-history traits corresponding to vulnerable species. Edge effects must be reduced to effectively protect tree phylogenetic diversity in the severely fragmented Brazilian Atlantic forest.

  4. GABAergic neuron-specific loss of Ube3a causes Angelman syndrome-like EEG abnormalities and enhances seizure susceptibility

    Science.gov (United States)

    Judson, Matthew C.; Wallace, Michael L.; Sidorov, Michael S.; Burette, Alain C.; Gu, Bin; van Woerden, Geeske M.; King, Ian F.; Han, Ji Eun; Zylka, Mark J.; Elgersma, Ype; Weinberg, Richard J.; Philpot, Benjamin D.

    2016-01-01

    SUMMARY Loss of maternal UBE3A causes Angelman syndrome (AS), a neurodevelopmental disorder associated with severe epilepsy. We previously implicated GABAergic deficits onto layer (L) 2/3 pyramidal neurons in the pathogenesis of neocortical hyperexcitability, and perhaps epilepsy, in AS model mice. Here we investigate consequences of selective Ube3a loss from either GABAergic or glutamatergic neurons, focusing on the development of hyperexcitability within L2/3 neocortex and in broader circuit and behavioral contexts. We find that GABAergic Ube3a loss causes AS-like increases in neocortical EEG delta power, enhances seizure susceptibility, and leads to presynaptic accumulation of clathrin-coated vesicles (CCVs) – all without decreasing GABAergic inhibition onto L2/3 pyramidal neurons. Conversely, glutamatergic Ube3a loss fails to yield EEG abnormalities, seizures, or associated CCV phenotypes, despite impairing tonic inhibition onto L2/3 pyramidal neurons. These results substantiate GABAergic Ube3a loss as the principal cause of circuit hyperexcitability in AS mice, lending insight into ictogenic mechanisms in AS. PMID:27021170

  5. GABAergic Neuron-Specific Loss of Ube3a Causes Angelman Syndrome-Like EEG Abnormalities and Enhances Seizure Susceptibility.

    Science.gov (United States)

    Judson, Matthew C; Wallace, Michael L; Sidorov, Michael S; Burette, Alain C; Gu, Bin; van Woerden, Geeske M; King, Ian F; Han, Ji Eun; Zylka, Mark J; Elgersma, Ype; Weinberg, Richard J; Philpot, Benjamin D

    2016-04-01

    Loss of maternal UBE3A causes Angelman syndrome (AS), a neurodevelopmental disorder associated with severe epilepsy. We previously implicated GABAergic deficits onto layer (L) 2/3 pyramidal neurons in the pathogenesis of neocortical hyperexcitability, and perhaps epilepsy, in AS model mice. Here we investigate consequences of selective Ube3a loss from either GABAergic or glutamatergic neurons, focusing on the development of hyperexcitability within L2/3 neocortex and in broader circuit and behavioral contexts. We find that GABAergic Ube3a loss causes AS-like increases in neocortical EEG delta power, enhances seizure susceptibility, and leads to presynaptic accumulation of clathrin-coated vesicles (CCVs)-all without decreasing GABAergic inhibition onto L2/3 pyramidal neurons. Conversely, glutamatergic Ube3a loss fails to yield EEG abnormalities, seizures, or associated CCV phenotypes, despite impairing tonic inhibition onto L2/3 pyramidal neurons. These results substantiate GABAergic Ube3a loss as the principal cause of circuit hyperexcitability in AS mice, lending insight into ictogenic mechanisms in AS.

  6. Body Mass Index, Weight Loss, and Cause-Specific Mortality in Rheumatoid Arthritis.

    Science.gov (United States)

    England, Bryant R; Baker, Joshua F; Sayles, Harlan; Michaud, Kaleb; Caplan, Liron; Davis, Lisa A; Cannon, Grant W; Sauer, Brian C; Solow, E Blair; Reimold, Andreas M; Kerr, Gail S; Mikuls, Ted R

    2017-04-20

    To examine associations of body mass index (BMI) and weight loss with cause-specific mortality in rheumatoid arthritis (RA). A cohort of U.S. Veterans with RA were followed until death or through 2013. BMI was categorized as underweight, normal, overweight, and obese. Weight loss was calculated as the: 1) annualized rate of change over the preceding 13 months and 2) cumulative percent. Vital status and cause of death were obtained from the National Death Index. Multivariable competing-risks regression models were utilized to assess the time-varying associations of BMI and weight loss with cause-specific mortality. Among 1,600 participants and 5,789 patient-years of follow-up, 303 deaths occurred (95 cardiovascular, 74 cancer, 46 respiratory). The highest weight loss rate and weight loss percentage were associated with a higher risk of cardiovascular (rate: sHR 2.27 [95% CI 1.61-3.19]; percent: sHR 2.31[1.06-5.01]) and cancer mortality (rate: sHR 2.36 [1.11-5.01]; percent: sHR 1.90 [1.00-3.62]). Overweight BMI was protective of cardiovascular mortality (sHR 0.59 [0.38-0.91]), while underweight BMI was associated with a near 3-fold increased risk of respiratory mortality (sHR 2.93 [1.28-6.67]). Incorporation of time-varying BMI and weight loss in the same models did not substantially alter individual associations for cardiovascular and cancer mortality, but an association between weight loss percent and respiratory mortality was attenuated after BMI adjustment. Both BMI and weight loss are predictors of cause-specific mortality in RA. Weight loss is a strong predictor of cardiovascular and cancer mortality, while underweight BMI is a stronger predictor of respiratory mortality. This article is protected by copyright. All rights reserved. © 2017, American College of Rheumatology.

  7. Family factors that characterize adolescents with severe obesity and their role in weight loss surgery outcomes.

    Science.gov (United States)

    Zeller, Meg H; Hunsaker, Sanita; Mikhail, Carmen; Reiter-Purtill, Jennifer; McCullough, Mary Beth; Garland, Beth; Austin, Heather; Washington, Gia; Baughcum, Amy; Rofey, Dana; Smith, Kevin

    2016-12-01

    To comprehensively assess family characteristics of adolescents with severe obesity and whether family factors impact weight loss outcomes following weight loss surgery (WLS). Multisite prospective data from 138 adolescents undergoing WLS and primary caregivers (adolescent: Mage  = 16.9; MBMI = 51.5 kg/m(2) ; caregiver: Mage  = 44.5; 93% female) and 83 nonsurgical comparators (NSComp: adolescent: Mage  = 16.1; MBMI = 46.9 kg/m(2) ; caregiver: Mage  = 43.9; 94% female) were collected using standardized measures at presurgery/baseline and at 1 and 2 years. The majority (77.3%) of caregivers had obesity, with rates of caregiver WLS significantly higher in the WLS (23.8%) versus NSComp group (3.7%, P Family dysfunction was prevalent (≈1 in every two to three families), with rates higher for NSComp than the WLS group. For the WLS group, preoperative family factors (i.e., caregiver BMI or WLS history, dysfunction, social support) were not significant predictors of adolescent weight loss at 1 and 2 years postoperatively, although change in family functioning over time emerged as a significant correlate of percent weight loss. Rates of severe obesity in caregivers as well as family dysfunction were clinically noteworthy, although not related to adolescent weight loss success following WLS. However, change in family communication and emotional climate over time emerged as potential targets to optimize weight loss outcomes. © 2016 The Obesity Society.

  8. Investigations of the factors causing performance losses of lead/acid traction batteries

    Science.gov (United States)

    Kronberger, H.; Fabjan, Ch.; Gofas, N.

    A failure analysis is carried out with a lead/acid traction battery after a two-years' test run in an electric passenger car. A survey of the operational data, in combination with laboratory tests and chemical and physical analyses, reveals the main causes of battery damage and performance loss: insufficiencies of the charging procedure, inadequate maintainance (water-refilling system), antimony-contamination and loss of the active material due to grid corrosion and shedding of PbO 2.

  9. Application of active middle ear implants in patients with severe mixed hearing loss.

    NARCIS (Netherlands)

    Verhaegen, V.J.O.; Mulder, J.J.S.; Cremers, C.W.R.J.; Snik, A.F.M.

    2012-01-01

    OBJECTIVE: To determine the long-term benefit of the Vibrant Soundbridge (VSB) middle ear implant in patients with severe mixed hearing loss and to compare it with other hearing devices. DESIGN: A retrospective analysis. SETTING: University-affiliated medical center. PATIENTS: Six patients with seve

  10. Predictors of Hearing Aid Use Time in Children with Mild-to-Severe Hearing Loss

    Science.gov (United States)

    Walker, Elizabeth A.; Spratford, Meredith; Moeller, Mary Pat; Oleson, Jacob; Ou, Hua; Roush, Patricia; Jacobs, Shana

    2013-01-01

    Purpose: This study investigated predictors of hearing aid (HA) use time for children with mild-to-severe hearing loss (HL). Barriers to consistent HA use and reliability of parent report measures were also examined. Method: Participants included parents of 272 children with HL. Parents estimated the amount of time the child used HAs daily.…

  11. Unilateral posterior vertebral column resection for severe thoracolumbar kyphotic deformity caused by old compressive vertebrae fracture: a technical improvement.

    Science.gov (United States)

    Wang, Hui; Zhang, Di; Sun, Ya-Peng; Ma, Lei; Ding, Wen-Yuan; Shen, Yong; Zhang, Ying-Ze

    2015-01-01

    Severe thoracolumbar kyphotic deformity caused by old compressive vertebrae fracture remains a big challenge for spine surgeons. When symptoms related to significant deformities cannot be adequately managed conservatively, posterior vertebral column resection (PVCR) is required, but with long operating time and severe blood loss. We develop a UPVCR technique, which is done through a unilateral approach instead of a bilateral approach, vertebral body resection advancing to cross the midline in an abrasive way from an extreme oblique orientation enable the resection of most contralateral vertebral body. In the present study, the effects of UPVCR for severe thoracolumbar kyphotic deformity were investigated. We did find that satisfactory correction of sagittal deformity, functional improvement and pain relief can be achieved by UPVCR, and it has the advantage of shortening surgery time, reducing blood loss and incidence of nerve root impingement over PVCR.

  12. Sex differences in severity of inflammation-induced anorexia and weight loss.

    Science.gov (United States)

    Lennie, Terry A

    2004-04-01

    Food intake and body weight changes in response to induction of acute inflammation were examined in intact cycling females, ovariectomized females, and sham-operated male rats. In intact females, body weight and feeding responses were compared between rats in which inflammation was induced on day of estrus with rats in which inflammation was induced on day of diestrus. Anorexia and weight loss were more severe in the female rats with inflammation induced on estrus day, which coincides with peak serum estrogen levels. In ovariectomized females, inflammation was induced the day after rats received injections of estrogen, progesterone, or sesame oil (vehicle). Males received vehicle injections. Among female rats, the group that received estradiol injections the previous day displayed the most severe anorexia. The least severe anorexia was observed in female rats that received progesterone the previous day. Food intake of female rats that received vehicle injections prior to induction of inflammation was greater than the rats receiving estrogen but less than the rats receiving progesterone. Male rats displayed the most severe anorexia and greatest weight loss. These data suggest that, although females exposed to estradiol prior to induction of acute inflammation display more severe anorexia than those exposed to progesterone, it may be that progesterone attenuates severity of anorexia rather than estrogen solely potentiating severity. Male rats, however, appear to experience the most severe anorexia in response to this form of inflammation.

  13. Loss-of-function variants in HIVEP2 are a cause of intellectual disability.

    Science.gov (United States)

    Srivastava, Siddharth; Engels, Hartmut; Schanze, Ina; Cremer, Kirsten; Wieland, Thomas; Menzel, Moritz; Schubach, Max; Biskup, Saskia; Kreiß, Martina; Endele, Sabine; Strom, Tim M; Wieczorek, Dagmar; Zenker, Martin; Gupta, Siddharth; Cohen, Julie; Zink, Alexander M; Naidu, SakkuBai

    2016-04-01

    Intellectual disability (ID) affects 2-3% of the population. In the past, many genetic causes of ID remained unidentified due to its vast heterogeneity. Recently, whole exome sequencing (WES) studies have shown that de novo variants underlie a significant portion of sporadic cases of ID. Applying WES to patients with ID or global developmental delay at different centers, we identified three individuals with distinct de novo variants in HIVEP2 (human immunodeficiency virus type I enhancer binding protein), which belongs to a family of zinc-finger-containing transcriptional proteins involved in growth and development. Two of the variants were nonsense changes, and one was a 1 bp deletion resulting in a premature stop codon that was reported previously without clinical detail. In silico prediction programs suggest loss-of-function in the mutated allele leading to haploinsufficiency as a putative mechanism in all three individuals. All three patients presented with moderate-to-severe ID, minimal structural brain anomalies, hypotonia, and mild dysmorphic features. Growth parameters were in the normal range except for borderline microcephaly at birth in one patient. Two of the patients exhibited behavioral anomalies including hyperactivity and aggression. Published functional data suggest a neurodevelopmental role for HIVEP2, and several of the genes regulated by HIVEP2 are implicated in brain development, for example, SSTR-2, c-Myc, and genes of the NF-κB pathway. In addition, HIVEP2-knockout mice exhibit several working memory deficits, increased anxiety, and hyperactivity. On the basis of the genotype-phenotype correlation and existing functional data, we propose HIVEP2 as a causative ID gene.

  14. Diabetic macular oedema and visual loss: relationship to location, severity and duration

    DEFF Research Database (Denmark)

    Gardner, Thomas W; Larsen, Michael; Girach, Aniz;

    2009-01-01

    Abstract. Purpose: To assess the relationship between visual acuity (VA) and diabetic macular oedema (DMO) in relation to the location of retinal thickening and the severity and duration of central macular thickening. Methods: Data from 584 eyes in 340 placebo-treated patients in the 3-years...... the relationship between duration of DMO and progressive vision loss, and the key role of central foveal involvement in patients with diabetic retinopathy. These data will help to develop future strategies to prevent vision loss.......-long Protein Kinase C Diabetic Retinopathy Study (PKC-DRS2) trial were used to investigate the relationship between VA and DMO. Eligible eyes had moderately severe to very severe non-proliferative diabetic retinopathy and VA of at least 45 letters on Early Treatment Diabetic Retinopathy Study (ETDRS) charts...

  15. Lagged association between powdery mildew leaf severity, airborne inoculum, weather, and crop losses in strawberry.

    Science.gov (United States)

    Carisse, O; Morissette-Thomas, V; Van der Heyden, H

    2013-08-01

    Knowledge about epidemiology and the impact of disease on yield is fundamental for establishing effective management strategies. The purpose of this study was to investigate the relationship between foliar strawberry mildew severity, Podosphaera aphanis airborne inoculum concentration, weather, and subsequent crop losses for day-neutral strawberry. The experiment was conducted at three, five, and four sites in 2006, 2007, and 2008, respectively, for a total of 12 epidemics. At each site, data were collected on 25 plants at 2-day intervals from the end of May to early October for a total of 60 to 62 samplings annually. First, seasonal crop losses were statistically described; then, a lagged regression model was developed to describe crop losses from the parameters that were significantly associated with losses. There was a strong positive linear relationship between seasonal crop losses and the area under the leaf disease progress curve (R(2) = 0.90) and daily mean airborne conidia concentration (R(2) = 0.86), and a negative linear relationship between crop losses and time to 5% loss (R(2) = 0.76) and time to 5% leaf area diseased (R(2) = 0.61). Among the 53 monitoring- and weather-based variables analyzed, percent leaf area diseased, log10-transformed airborne inoculum concentration, and weather variables related to temperature were significantly associated with crop losses. However, polynomial distributed lag regression models built with weather variables were not accurate in predicting losses, with the exception of a model based on a combined temperature and humidity variable, which provided accurate prediction of the data used to construct the model but not of independent data. Overall, the model based on log10-transformed airborne inoculum concentration did not provide accurate crop loss predictions. The model built using percent leaf area diseased with a time lag of 8 days (n = 4) and a polynomial degree of 2 provided a good description of the crop-loss data

  16. Effectiveness of a Low-Calorie Weight Loss Program in Moderately and Severely Obese Patients

    Directory of Open Access Journals (Sweden)

    Julia K. Winkler

    2013-10-01

    Full Text Available Aims: To compare effectiveness of a 1-year weight loss program in moderately and severely obese patients. Methods: The study sample included 311 obese patients participating in a weight loss program, which comprised a 12-week weight reduction phase (low-calorie formula diet and a 40-week weight maintenance phase. Body weight and glucose and lipid values were determined at the beginning of the program as well as after the weight reduction and the weight maintenance phase. Participants were analyzed according to their BMI class at baseline (30-34.9 kg/m2; 35-39.9 kg/m2; 40-44.9 kg/m2; 45-49.9 kg/m2; ≥50 kg/m2. Furthermore, moderately obese patients (BMI 2 were compared to severely obese participants (BMI ≥ 40 kg/m2. Results: Out of 311 participants, 217 individuals completed the program. Their mean baseline BMI was 41.8 ± 0.5 kg/m2. Average weight loss was 17.9 ± 0.6%, resulting in a BMI of 34.3 ± 0.4 kg/m2 after 1 year (p Conclusion: 1-year weight loss intervention improves body weight as well as lipid and glucose metabolism not only in moderately, but also in severely obese individuals.

  17. Localization training results in individuals with unilateral severe to profound hearing loss.

    Science.gov (United States)

    Firszt, Jill B; Reeder, Ruth M; Dwyer, Noël Y; Burton, Harold; Holden, Laura K

    2015-01-01

    Adults with unilateral hearing loss often demonstrate decreased sound localization ability and report that situations requiring spatial hearing are especially challenging. Few studies have evaluated localization abilities combined with training in this population. The present pilot study examined whether localization of two sound types would improve after training, and explored the relation between localization ability or training benefit and demographic factors. Eleven participants with unilateral severe to profound hearing loss attended five training sessions; localization cues gradually decreased across sessions. Localization ability was assessed pre- and post-training. Assessment stimuli were monosyllabic words and spectral and temporal random spectrogram sounds. Root mean square errors for each participant and stimulus type were used in group and correlation analyses; individual data were examined with ordinary least squares regression. Mean pre-to post-training test results were significantly different for all stimulus types. Among the participants, eight significantly improved following training on at least one localization measure, whereas three did not. Participants with the poorest localization ability improved the most and likewise, those with the best pre-training ability showed the least training benefit. Correlation results suggested that test age, age at onset of severe to profound hearing loss and better ear high frequency audibility may contribute to localization ability. Results support the need for continued investigation of localization training efficacy and consideration of localization training within rehabilitation protocols for individuals with unilateral severe to profound hearing loss.

  18. Severe renal bleeding caused by a ruptured renal sheath: case report of a rare complication of percutaneous nephrolithotomy

    Directory of Open Access Journals (Sweden)

    Gunes Ali

    2002-09-01

    Full Text Available Abstract Background Percutaneous nephrolithotomy is a minimally invasive intervention for renal stone disease. Complications, which are rare and usually presented as case reports, are diversified as the utilization of the procedure is expanded. The procedure causes less blood loss and less morbidity when compared to open surgical procedures. Yet, there are some reports involving severe bleeding and relevant morbidity during surgery. These are usually related with the surgical technique or experience of the surgeon. Renal sheaths are designed to cause minimal trauma inside the kidney and, to our knowledge, there are no reports presenting the rupture of a sheath causing severe bleeding during the procedure. Case report We present an adult patient who had severe bleeding during percutaneous nephrolithotomy due to parenchymal injury caused by a ruptured renal sheath. During retrieval, due probably to rough handling of the equipment, a piece of stone with serrated edges ruptured the tip of the sheath, and this tip caused damage inside the kidney. The operation was terminated and measures were taken to control bleeding. The patient was transfused with a total of 1600 ml of blood, and the stones were cleared in a second look operation. Conclusion Although considered to be a minimally invasive procedure, some unexpected complications may arise during percutaneous nephrolithotomy. After being fragmanted, stone pieces may damage surgical equipment, causing acute and severe harm to the kidney. Surgeons must manipulate the equipment with fine and careful movements in order to prevent this situation.

  19. Recent Advances in Cerebellar Ischemic Stroke Syndromes Causing Vertigo and Hearing Loss.

    Science.gov (United States)

    Kim, Hyun-Ah; Yi, Hyon-Ah; Lee, Hyung

    2016-12-01

    Cerebellar ischemic stroke is one of the common causes of vascular vertigo. It usually accompanies other neurological symptoms or signs, but a small infarct in the cerebellum can present with vertigo without other localizing symptoms. Approximately 11 % of the patients with isolated cerebellar infarction simulated acute peripheral vestibulopathy, and most patients had an infarct in the territory of the medial branch of the posterior inferior cerebellar artery (PICA). A head impulse test can differentiate acute isolated vertigo associated with PICA territory cerebellar infarction from more benign disorders involving the inner ear. Acute hearing loss (AHL) of a vascular cause is mostly associated with cerebellar infarction in the territory of the anterior inferior cerebellar artery (AICA), but PICA territory cerebellar infarction rarely causes AHL. To date, at least eight subgroups of AICA territory infarction have been identified according to the pattern of neurotological presentations, among which the most common pattern of audiovestibular dysfunction is the combined loss of auditory and vestibular functions. Sometimes acute isolated audiovestibular loss can be the initial symptom of impending posterior circulation ischemic stroke (particularly within the territory of the AICA). Audiovestibular loss from cerebellar infarction has a good long-term outcome than previously thought. Approximately half of patients with superior cerebellar artery territory (SCA) cerebellar infarction experienced true vertigo, suggesting that the vertigo and nystagmus in the SCA territory cerebellar infarctions are more common than previously thought. In this article, recent findings on clinical features of vertigo and hearing loss from cerebellar ischemic stroke syndrome are summarized.

  20. Profound bilateral visual loss after hysterectomy indicated for severe postpartum haemorrhage

    DEFF Research Database (Denmark)

    Ostri, Christoffer; Zibrandtsen, Nathalie; Larsen, Michael;

    2014-01-01

    ) and visual evoked potentials (VEP) testing. During 1 year of follow-up, repeated optical coherence tomography (OCT) scans demonstrated optic disc atrophy, which was interpreted as a sign of direct retrograde ganglion cell degeneration after ischaemic damage to the retrolaminar part of the optic nerves....... The diagnosis of perioperative posterior ischaemic optic neuropathy is mostly a clinical diagnosis. However, MRI plays a major role in excluding other causes of visual loss, and VEP, ERG and OCT are valuable supplemental diagnostic tools....

  1. Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris.

    Science.gov (United States)

    Smith, Frances J D; Irvine, Alan D; Terron-Kwiatkowski, Ana; Sandilands, Aileen; Campbell, Linda E; Zhao, Yiwei; Liao, Haihui; Evans, Alan T; Goudie, David R; Lewis-Jones, Sue; Arseculeratne, Gehan; Munro, Colin S; Sergeant, Ann; O'Regan, Gráinne; Bale, Sherri J; Compton, John G; DiGiovanna, John J; Presland, Richard B; Fleckman, Philip; McLean, W H Irwin

    2006-03-01

    Ichthyosis vulgaris (OMIM 146700) is the most common inherited disorder of keratinization and one of the most frequent single-gene disorders in humans. The most widely cited incidence figure is 1 in 250 based on a survey of 6,051 healthy English schoolchildren. We have identified homozygous or compound heterozygous mutations R501X and 2282del4 in the gene encoding filaggrin (FLG) as the cause of moderate or severe ichthyosis vulgaris in 15 kindreds. In addition, these mutations are semidominant; heterozygotes show a very mild phenotype with incomplete penetrance. The mutations show a combined allele frequency of approximately 4% in populations of European ancestry, explaining the high incidence of ichthyosis vulgaris. Profilaggrin is the major protein of keratohyalin granules in the epidermis. During terminal differentiation, it is cleaved into multiple filaggrin peptides that aggregate keratin filaments. The resultant matrix is cross-linked to form a major component of the cornified cell envelope. We find that loss or reduction of this major structural protein leads to varying degrees of impaired keratinization.

  2. Loss of Rb proteins causes genomic instability in the absence of mitogenic signaling

    NARCIS (Netherlands)

    van Harn, Tanja; Foijer, Floris; van Vugt, Marcel; Banerjee, Ruby; Yang, Fentang; Oostra, Anneke; Joenje, Hans; te Riele, Hein

    2010-01-01

    Loss of G1/S control is a hallmark of cancer, and is often caused by inactivation of the retinoblastoma pathway. However, mouse embryonic fibroblasts lacking the retinoblastoma genes RB1, p107, and p130 (TKO MEFs) are still subject to cell cycle control: Upon mitogen deprivation, they enter and

  3. Does amikacin treatment cause subclinical hearing loss in patients with cystic fibrosis?

    Directory of Open Access Journals (Sweden)

    Fevzi Solmaz

    2016-01-01

    Conclusion: Repetitive exposure to AGs can cause permanent, although mild, sensorineural hearing loss. For prevention, hearing status of the patient should be closely monitored and treatment of choice should be precisely tailored according to the audiological evaluation. This is especially important in patients with CF who frequently experience medical conditions necessitating AGs use.

  4. Methodology used in Cuba for estimating economic losses caused by forest fires

    Science.gov (United States)

    Marcos Pedro Ramos Rodríguez; Raúl González Rodríguez

    2013-01-01

    Assessment of economic losses caused by forest fires is a highly complex but important activity. It is complicated first by the large number of effects, in different periods, brought about in the social, economic and environmental fields. Secondly, the difficulty of assigning a market value to resources such as biodiversity or endangered species should be mentioned. It...

  5. Reducing power losses caused by ionic shortcut currents in reverse electrodialysis stacks by a validated model

    NARCIS (Netherlands)

    Veerman, J.; Post, J. W.; Saakes, M.; Metz, S. J.; Harmsen, G. J.

    2008-01-01

    Both in electrodialysis and in reverse electrodialysis ionic shortcut currents through feed and drain channels cause a considerable loss in efficiency. Model calculations based on an equivalent electric system of a reverse electrodialysis stack reveal that the effect of these salt bridges could be r

  6. [Analysis of the causes of loss of tolerance to standard G-loads by fighter pilots].

    Science.gov (United States)

    Sinopal'nikov, V I; Donin, K M; Boltikov, A N; Pugachev, I V; Migachev, S D

    2003-01-01

    Analytical treatment has been given to causes for the loss of tolerance to radial accelerations by fighter pilots subjected to clinical tests during flight medical certification in recent years. The diagnostic necessity of implementation of additional tests by this cohort of pilots has been demonstrated and methods to improve pilots' cardiovascular adaptability to g-loads during the inpatient medical examination have been proposed.

  7. Mutations in OTOGL, encoding the inner ear protein otogelin-like, cause moderate sensorineural hearing loss

    NARCIS (Netherlands)

    Yariz, K.O.; Duman, D.; Seco, C.Z.; Dallman, J.; Huang, M.; Peters, T.A.; Sirmaci, A.; Lu, N.; Schraders, M.; Skromne, I.; Oostrik, J.; Diaz-Horta, O.; Young, J.I.; Tokgoz-Yilmaz, S.; Konukseven, O.; Shahin, H.; Hetterschijt, L.; Kanaan, M.; Oonk, A.M.M.; Edwards, Y.J.; Li, H.; Atalay, S.; Blanton, S.; Desmidt, A.A.; Liu, X.Z.; Pennings, R.J.E.; Lu, Z.; Chen, Z.Y.; Kremer, J.M.J.; Tekin, M.

    2012-01-01

    Hereditary hearing loss is characterized by a high degree of genetic heterogeneity. Here we present OTOGL mutations, a homozygous one base pair deletion (c.1430 delT) causing a frameshift (p.Val477Glufs( *)25) in a large consanguineous family and two compound heterozygous mutations, c.547C>T (p.Arg1

  8. Radiation-induced magnetization reversal causing a large flux loss in undulator permanent magnets.

    Science.gov (United States)

    Bizen, Teruhiko; Kinjo, Ryota; Hasegawa, Teruaki; Kagamihata, Akihiro; Kida, Yuichiro; Seike, Takamitsu; Watanabe, Takahiro; Hara, Toru; Itoga, Toshiro; Asano, Yoshihiro; Tanaka, Takashi

    2016-11-29

    We report an unexpectedly large flux loss observed in permanent magnets in one of the undulators operated in SACLA, the x-ray free electron laser facility in Japan. Characterizations of individual magnets extracted from the relevant undulator have revealed that the flux loss was caused by a homogeneous magnetization reversal extending over a wide area, but not by demagnetization of individual magnets damaged by radiation. We show that the estimated flux-loss rate is much higher than what is reported in previous papers, and its distribution is much more localized to the upstream side. Results of numerical and experimental studies carried out to validate the magnetization reversal and quantify the flux loss are presented, together with possible countermeasures against rapid degradation of the undulator performance.

  9. Radiation-induced magnetization reversal causing a large flux loss in undulator permanent magnets

    Science.gov (United States)

    Bizen, Teruhiko; Kinjo, Ryota; Hasegawa, Teruaki; Kagamihata, Akihiro; Kida, Yuichiro; Seike, Takamitsu; Watanabe, Takahiro; Hara, Toru; Itoga, Toshiro; Asano, Yoshihiro; Tanaka, Takashi

    2016-11-01

    We report an unexpectedly large flux loss observed in permanent magnets in one of the undulators operated in SACLA, the x-ray free electron laser facility in Japan. Characterizations of individual magnets extracted from the relevant undulator have revealed that the flux loss was caused by a homogeneous magnetization reversal extending over a wide area, but not by demagnetization of individual magnets damaged by radiation. We show that the estimated flux-loss rate is much higher than what is reported in previous papers, and its distribution is much more localized to the upstream side. Results of numerical and experimental studies carried out to validate the magnetization reversal and quantify the flux loss are presented, together with possible countermeasures against rapid degradation of the undulator performance.

  10. Major losses of nutrients following a severe drought in a boreal forest.

    Science.gov (United States)

    Houle, Daniel; Lajoie, Geneviève; Duchesne, Louis

    2016-11-28

    Because of global warming, the frequency and severity of droughts are expected to increase, which will have an impact on forest ecosystem health worldwide(1). Although the impact of drought on tree growth and mortality is being increasingly documented(2-4), very little is known about the impact on nutrient cycling in forest ecosystems. Here, based on long-term monitoring data, we report nutrient fluxes in a boreal forest before, during and following a severe drought in July 2012. During and shortly after the drought, we observed high throughfall (rain collected below the canopy) concentrations of nutrient base cations (potassium, calcium and magnesium), chlorine, phosphorus and dissolved organic carbon (DOC), differing by one to two orders of magnitude relative to the long-term normal, and resulting in important canopy losses. The high throughfall fluxes had repercussions in the soil solution at a depth of 30 cm, leading to high DOC, chlorine and potassium concentrations. The net potassium losses (atmospheric deposition minus leaching losses) following the drought were especially important, being the equivalent of nearly 20 years of net losses under 'normal' conditions. Our data show that droughts have unexpected impacts on nutrient cycling through impacts on tree canopy and soils and may lead to important episodes of potassium losses from boreal forest ecosystems. The potassium losses associated with drought will add to those originating from tree harvesting and from forest fires and insect outbreaks(5-7) (with the last two being expected to increase in the future as a result of climate change), and may contribute to reduced potassium availability in boreal forests in a warming world.

  11. Output Loss Severity across EU Countries. Evidence for the 2008 Financial Crisis

    Directory of Open Access Journals (Sweden)

    Iustina Alina Boitan

    2015-08-01

    Full Text Available Financial crises are complex phenomena, in terms of the triggering factors, duration and severity, impact on both financial system and macroeconomic fundamentals and the full range of costs arising from its occurrence. The paper aims at providing an updated picture on the magnitude the 2008 financial crisis had, in terms of economic costs incurred by EU member states. It has been briefly reviewed crises’ main monetary and economic effects and costs. Then it has been employed International Monetary Fund’s approach for measuring crisis severity, expressed as an output loss indicator. To check the stability of the results, the basic methodology relying on a 3-year GDP trend has been complemented with a 7-year GDP trend. The output losses recorded by each EU country, under both trend assumptions, showed that Baltic states and Greece had been the most affected as they cumulated the highest losses. The lowest output losses have been registered in Western Europe countries (Austria, Belgium, France, Germany and Poland. Most EU economies’ growth still hasn’t entered on a robust ascending path, as they haven’t reached the level of GDP trend computed for the period preceding the onset of the financial crisis.

  12. Lifestyle interventions for weight loss in adults with severe obesity: a systematic review.

    Science.gov (United States)

    Hassan, Y; Head, V; Jacob, D; Bachmann, M O; Diu, S; Ford, J

    2016-12-01

    Severe obesity is an increasingly prevalent condition and is often associated with long-term comorbidities, reduced survival and higher healthcare costs. Non-surgical methods avoid the side effects, complications and costs of surgery, but it is unclear which non-surgical method is most effective. The objective of this article was to systematically review the effectiveness of lifestyle interventions compared to standard or minimal care for weight loss in adults with severe obesity. MEDLINE, EMBASE, CENTRAL, databases of on-going studies, reference lists of any relevant systematic reviews and the Cochrane Library database were searched from inception to February 2016 for relevant randomized controlled trials (RCTs). Inclusion criteria were participants with severe obesity (body mass index [BMI] > 40 kg/m(2) or BMI > 35 kg/m(2) with comorbidity) and interventions with a minimal duration of 12 weeks that were multi-component combinations of diet, exercise and behavioural therapy. Risk of bias was evaluated using the Cochrane risk of bias criteria. Meta-analysis was not possible because of methodological heterogeneity. Seventeen RCTs met the inclusion criteria. Weight change in kilograms of participants from baseline to follow-up was reported for 14 studies. Participants receiving the lifestyle intervention had a greater decrease in weight than participants in the control group for all studies (1.0-11.5 kg). Lifestyle interventions varied greatly between the studies. Overall lifestyle interventions with combined diet and exercise components achieved the greatest weight loss. Lifestyle interventions for weight loss in adults with severe obesity were found to result in increased weight loss when compared to minimal or standard care, especially those with combined diet and exercise components. © 2016 World Obesity Federation.

  13. Irrigation affects severity of root rot caused by Phythophthora plurivora and P. cinnamomi on rhododendron

    Science.gov (United States)

    Plant pathogens in the genus Phytophthora cause root rot that decrease product quality and result in plant death and economic losses to the nursery industry. Recently, we found Phytophthora plurivora prevalent on rhododendron in nurseries in the Pacific Northwest, USA, but there is little informatio...

  14. Cochlear implants as a treatment option for unilateral hearing loss, severe tinnitus and hyperacusis.

    Science.gov (United States)

    Ramos Macías, Angel; Falcón González, Juan Carlos; Manrique, Manuel; Morera, Constantino; García-Ibáñez, Luis; Cenjor, Carlos; Coudert-Koall, Chrystellel; Killian, Matthijs

    2015-01-01

    Tinnitus is an incapacitating condition commonly affecting cochlear implant (CI) candidates. The aim of this clinical study is to assess the long-term effects of CI treatment in patients with severe-to-profound, sensorineural, unilateral hearing loss (UHL) and incapacitating tinnitus. We performed a prospective Cochlear™ company-sponsored multicentre study in five Spanish centres. Sixteen patients with UHL and incapacitating tinnitus, which was indicated by a Tinnitus Handicap Inventory (THI) score >58%, received a Nucleus® CI in their deaf ear. The study design includes repeated within-subject measures on hearing, tinnitus, hyperacusis and quality of life up to 12 months after initial CI fitting. In addition to hearing loss and tinnitus, all patients suffered from hyperacusis. Most patients had a sudden hearing loss and received a CI within 2 years after their hearing loss. Preliminary 6-month, post-CI activation data of 13 subjects showed that the majority of patients perceived a subjective benefit from CI treatment, which was assessed using the THI, a Visual Analogue Scale of tinnitus loudness/annoyance and the Speech, Spatial and Qualities of Hearing Scale. Preliminary 12-month data of 7 subjects showed that most patients also perceived a degree of relief from their hyperacusis. One patient showed no improvements in any of the applied scales, which could be explained by partial insertion of the electrode due to obstruction of the cochlea by otosclerosis. In conclusion, CI can successfully be used in the treatment of UHL patients with accompanying severe tinnitus and hyperacusis. Implantation resulted in hearing benefits and a durable relief from tinnitus and hyperacusis in the majority of patients. These findings support the hypothesis that pathophysiological mechanisms after peripheral sensorineural hearing loss are at least partly reversible when hearing is restored with a CI.

  15. Middle ear osteoma: a rare cause of conductive hearing loss with normal tympanic membrane.

    Science.gov (United States)

    Vérillaud, B; Guilleré, L; Williams, M T; El Bakkouri, W; Ayache, D

    2011-01-01

    Osteomas of the temporal bone are benign osseous tumors usually located to the external auditory canal. Osteomas involving the middle ear are very rare. We report the case of a patient presenting with a progressive hearing loss caused by a middle ear osteoma involving the incus and contiguous to the tympanic segment of the facial nerve. This report highlights the value of CT scan in the work-up of conductive or mixed hearing loss with normal tympanic membrane. The management of middle ear osteoma is discussed.

  16. Tibiocalcaneal Fusion for Charcot Ankle With Severe Talar Body Loss: Case Report and a Review of the Surgical Literature.

    Science.gov (United States)

    Aikawa, Takao; Watanabe, Koji; Matsubara, Hidenori; Nomura, Issei; Tsuchiya, Hiroyuki

    2016-01-01

    Severe bone loss resulting from talar body necrosis in the Charcot ankle can be challenging to treat. In particular, the Charcot ankle will demonstrate progressive instability and deformity, causing protrusion of the medial or lateral malleolus, which will mostly lead to skin ulcers or osteomyelitis and, in some cases, will ultimately require transtibial amputation. Problems such as bone fragility, poor compliance with load-bearing restrictions, susceptibility to infection, and circulatory disorders cause difficulties in the surgical treatment of the Charcot ankle. We believe that tibiocalcaneal fusion is a reliable method to obtain satisfactory outcomes in these difficult cases. However, no study has reported on the use of a locking plate for tibiocalcaneal fusion. Therefore, we report on tibiocalcaneal fusion using a locking plate in 3 patients with Charcot ankle and severe talar body loss. All patients achieved bony union with a plantigrade foot and without any skin complications. We have concluded that a locking plate provides rigid fixation and easier insertion of additional screws, when necessary.

  17. The magnetisation profiles and ac magnetisation losses in a single layer YBCO thin film caused by travelling magnetic field waves

    Science.gov (United States)

    Wang, Wei; Coombs, Timothy

    2015-05-01

    This paper studies the magnetisation and ac magnetisation losses caused by a travelling magnetic wave on a single-layer YBCO thin film. This work provides thorough investigations on how the critical magnetic field gradient has been changed by the application of a travelling wave. Several conditions were studied such as zero-field cooling (ZFC), field cooling (FC) and a delta-shaped trapped field. It was found that the travelling wave tends to attenuate the existing critical magnetic field gradients in all these conditions. This interesting magnetic behaviour can be well predicted by the finite element (FEM) software with the E-J power law and Maxwell’s equations. The numerical simulations show that the existing critical current density has been compromised after applying the travelling wave. The magnetisation profile caused by the travelling wave is very different from the standing wave, while the magnetisation based on the standing wave can be interpreted by the Bean model and constant current density assumption. Based on the numerical method, which has reliability that has been solidly proven in the study, we have extended the study to the ac magnetisation losses. Comparisons were made between the travelling wave and the standing wave for this specific YBCO sample. It was found that by applying the magnetic wave of the same amplitude, the ac magnetisation loss caused by the travelling wave is about 1/3 of that caused by the standing wave. These results are helpful in understanding the general magnetism problems and ac magnetisation loss in the travelling magnetic wave conditions such as inside a high temperature superconducting (HTS) rotating machine, etc.

  18. Functional photoreceptor loss revealed with adaptive optics: an alternate cause of color blindness.

    Science.gov (United States)

    Carroll, Joseph; Neitz, Maureen; Hofer, Heidi; Neitz, Jay; Williams, David R

    2004-06-01

    There is enormous variation in the X-linked L/M (long/middle wavelength sensitive) gene array underlying "normal" color vision in humans. This variability has been shown to underlie individual variation in color matching behavior. Recently, red-green color blindness has also been shown to be associated with distinctly different genotypes. This has opened the possibility that there may be important phenotypic differences within classically defined groups of color blind individuals. Here, adaptive optics retinal imaging has revealed a mechanism for producing dichromatic color vision in which the expression of a mutant cone photopigment gene leads to the loss of the entire corresponding class of cone photoreceptor cells. Previously, the theory that common forms of inherited color blindness could be caused by the loss of photoreceptor cells had been discounted. We confirm that remarkably, this loss of one-third of the cones does not impair any aspect of vision other than color.

  19. Prandial subcutaneous injections of glucagon-like peptide-1 cause weight loss in obese human subjects

    DEFF Research Database (Denmark)

    Näslund, Erik; King, N; Mansten, S

    2004-01-01

    Recombinant glucagon-like peptide-1 (7-36)amide (rGLP-1) was recently shown to cause significant weight loss in type 2 diabetics when administered for 6 weeks as a continuous subcutaneous infusion. The mechanisms responsible for the weight loss are not clarified. In the present study, rGLP-1.......05) was registered after 5 d with PSI of rGLP-1. Gastric emptying rate was reduced during both PSI (Pmore rapidly and to a greater extent with PSI of rGLP-1. To conclude, a 5 d treatment of rGLP-1 at high doses by PSI, but not CSI, promptly slowed gastric emptying...... as a probable mechanism of action of increased satiety, decreased hunger and, hence, reduced food intake with an ensuing weight loss....

  20. Tooth loss caused by displaced elastic during simple preprosthetic orthodontic treatment

    Science.gov (United States)

    Dianiskova, Simona; Calzolari, Chiara; Migliorati, Marco; Silvestrini-Biavati, Armando; Isola, Gaetano; Savoldi, Fabio; Dalessandri, Domenico; Paganelli, Corrado

    2016-01-01

    The use of elastics to close a diastema or correct tooth malpositions can create unintended consequences if not properly controlled. The American Association of Orthodontists recently issued a consumer alert, warning of “a substantial risk for irreparable damage” from a new trend called “do-it-yourself” orthodontics, consisting of patients autonomously using elastics to correct tooth position. The elastics can work their way below the gums and around the roots of the teeth, causing damage to the periodontium and even resulting in tooth loss. The cost of implants to replace these teeth would well exceed the cost of proper orthodontic care. This damage could also occur in a dental office, when a general dentist tries to perform a simplified orthodontic correction of a minor tooth malposition. The present case report describes a case of tooth loss caused by a displaced intraoral elastic, which occurred during a simple preprosthetic orthodontic treatment. PMID:27672645

  1. The housing loss assessment of rural villages caused by earthquake disaster in Yunnan Province

    Institute of Scientific and Technical Information of China (English)

    WANG Ying; SHI Pei-jun; WANG Jing-ai

    2005-01-01

    Based on the assessment report of destructive housings caused by more than 20 earthquakes occurred in Yunnan Province in 1990~2004, the vulnerability models of 4 types housings of rural residents in Yunnan Province are setup. The scenario earthquake disaster loss model is used to simulate the housing loss if the historical earthquakes that occurred since A.D. 886 in Yunnan Province reoccur in 2002. The analyses show the simulation deviation of the usual earthquakes is less than 30% and the method is of high practicality. Meanwhile, the simulation result of 398 historical earthquakes in Yunnan Province shows that the annual economic loss caused by the earthquakes is about RMB 410 million Yuan that accounts for 0.18% of GDP of Yunnan Province for the year. Because the per capita living area and the price of the housing increases year by year, if the historical destructive earthquake reoccurs today, the loss of Yunnan Province will be greater than in those years.

  2. A guinea pig model of selective severe high-frequency hearing loss.

    Science.gov (United States)

    Havenith, Sarah; Klis, Sjaak F L; Versnel, Huib; Grolman, Wilko

    2013-10-01

    Using an appropriate dose of an aminoglycoside antibiotic cotreated with a loop diuretic a guinea pig model of high-frequency loss can be obtained mimicking cochlear implant candidates with low-frequency residual hearing. We examined the stability of this model over time. A well-established method to create an animal model for profound deafness is cotreatment with an aminoglycoside antibiotic and a loop diuretic. Recent data indicated that reduction of the aminoglycoside dose might yield selective high-frequency hearing loss. Such a model is relevant for studies related to hybrid cochlear implant devices, for example, with respect to preservation of residual hearing. Guinea pigs received an electrode for chronic recording of compound action potentials to tones to assess thresholds. They were treated with a coadministration of kanamycin (200 mg/kg) and furosemide (100 mg/kg), after which, the animals were sacrificed for histologic analysis at 2, 4, or 7 weeks. After 2 to 7 weeks threshold shifts were greater than 50 dB for 8 to 16 kHz in 15 of 17 animals, whereas threshold shifts at 2 kHz or lower were less than 50 dB in 13 animals. Major threshold shifts occurred the first 2 to 4 days; subsequently, some spontaneous recovery occurred and, after 2-3 weeks thresholds, remained stable. Inner hair cell loss still progressed between 2 and 4 weeks in the most basal cochlear region; thereafter, hair cell loss was stable. An appropriate animal model for selective severe high-frequency hearing loss was obtained, which is stable at 4 weeks after ototoxic treatment.

  3. A missense mutation P136L in the arylsulfatase A gene causes instability and loss of activity of the mutant enzyme.

    Science.gov (United States)

    Kafert, S; Heinisch, U; Zlotogora, J; Gieselmann, V

    1995-02-01

    Metachromatic leukodystrophy is a lysosomal storage disease caused by deficiency of arylsulfatase A. Sequencing of the arylsulfatase A genes of an Ashkenazi Jewish patient suffering from the severe late infantile form of the disease revealed a point mutation in exon 2 causing proline 136 to be substituted by leucine. The patient was homozygous for this mutation. Studies on Ltk- cells stably expressing the mutant enzyme show that the mutation causes complete loss of enzyme activity and rapid degradation in an early biosynthetic compartment.

  4. Causes of Land Loss in Tuvalu, a Small Island Nation in the Pacific

    Institute of Scientific and Technical Information of China (English)

    XUE Chunting

    2005-01-01

    Studies on land loss in Tuvalu reveal the following findings. Although both sea level rise and coastal erosion can cause land loss in the tropic Pacific oceanic islands, their mechanisms are different. When sea level rises, the low elevation coastal zone submerges and the erosion datum plane rises, the beach process progresses normally as always, resulting in no beach sediment coarsening. When the sea level is stable, coastal erosion removes finer sediment from reef flat, beach and land, resulting in beach sediment coarsening. The human-induced coastal erosion in the tropic Pacific oceanic islands has the following features. 1) Erosion occurs or intensifies immediately after inappropriate human activities. 2) It occurs near the places having human activities and places related to the above places in sediment supply. 3) It often occurs on original prograding or stable coasts (on lagoon coasts for atolls) because there are more coastal engineering projects and other human activities on such coasts. 4) It is chronic, covering a long period of time. The coastal geological events in Tuvalu islands do not accord with the features resulted from sea level rise but do accord with the features resulted from coastal erosion, particularly from human-induced erosion. The land loss in Tuvalu is mainly caused by inappropriate human activities including coastal engineering and aggregate mining, and partly caused by cyclones. Moreover, all recent measurements (satellite altimetry,thermosteric sea level data and tide observations) so far have not been able to verify any sea level rise around Tuvalu islands.

  5. Incidence, Risk Factors and Causes of Severe Neonatal Hyperbilirubinemia in the South of Iran (Fars Province)

    Science.gov (United States)

    Najib, Khadije Sadat; Saki, Forough; Hemmati, Fariba; Inaloo, Soroor

    2013-01-01

    Background Today, Severe hyperbilirubinemia is the most common cause of neonatal readmissions. Identification of the cause of neonatal hyperbilirubinemia is useful in determining whether therapeutic interventions can prevent severe hyperbilirubinemia. Objectives We conducted this study to estimate the incidence of severe hyperbilirubinemia in Fars province and to determine the underlying causes and risk factors, which would be of value in identifying and implementing strategies to prevent morbidity from this condition. Patients and Methods All infants less than 28 days referred due to severe indirect hyperbilirubinemia were included. Complete history, physical examination and lab work up were performed. This is a longitudinal prospective study in 2009-2010. Results More common causes of severe indirect hyperbilirubinemia were blood group incompatibility, G6PD deficiency, sepsis and unknown. Risk factors of severe hyperbilirubinemia were Male sex, previous siblings with severe hyperbilirubinemia, early discharge, NVD, Breast feeding and cultural background of mothers. Conclusions Our study showed severe neonate indirect hyperbilirubinemia is still prevalence in Fars province and ethnic and cultural background of the mothers was more effective than school education in preventing hyperbilirubinemia complication. PMID:23984010

  6. Severe Gastroenteritis and Hypovolemic Shock Caused by Grimontia (Vibrio) hollisae Infection▿

    OpenAIRE

    2007-01-01

    Vibrio hollisae is a halophilic species that was recently reclassified as Grimontia hollisae. This organism is known to cause moderate to severe cases of gastroenteritis. We report a case of an individual who suffered a more severe form of this disease, presenting with profound hypotension and acute renal failure, secondary to hypovolemic shock.

  7. Prelinguistic Vocal Development in Infants with Typical Hearing and Infants with Severe-to-Profound Hearing Loss

    Science.gov (United States)

    Iyer, Suneeti Nathani; Oller, D. Kimbrough

    2008-01-01

    Delays in the onset of canonical babbling with hearing loss are extensively documented. Relatively little is known about other aspects of prelinguistic vocal development and hearing loss. Eight infants with typical hearing and eight with severe-to-profound hearing loss were matched with regard to a significant vocal development milestone, the…

  8. Prelinguistic Vocal Development in Infants with Typical Hearing and Infants with Severe-to-Profound Hearing Loss

    Science.gov (United States)

    Iyer, Suneeti Nathani; Oller, D. Kimbrough

    2008-01-01

    Delays in the onset of canonical babbling with hearing loss are extensively documented. Relatively little is known about other aspects of prelinguistic vocal development and hearing loss. Eight infants with typical hearing and eight with severe-to-profound hearing loss were matched with regard to a significant vocal development milestone, the…

  9. Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss.

    Science.gov (United States)

    Bonafede, Lucas; Ficicioglu, Can H; Serrano, Leona; Han, Grace; Morgan, Jessica I W; Mills, Monte D; Forbes, Brian J; Davidson, Stefanie L; Binenbaum, Gil; Kaplan, Paige B; Nichols, Charles W; Verloo, Patrick; Leroy, Bart P; Maguire, Albert M; Aleman, Tomas S

    2015-12-01

    To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC.

  10. A rare cause for severe recurrent lower gastrointestinal bleeding in a 12 year old patient

    Directory of Open Access Journals (Sweden)

    D. Belsha

    2015-09-01

    Full Text Available The cause for severe, recurrent lower gastrointestinal (LGI bleeding in children can usually be diagnosed readily by means of the commonly used investigative/diagnostic techniques such as colonoscopy, laparoscopy ± laparotomy. Occasionally less commonly used investigations may be necessary to look for more elusive causes of LGI bleeding such as capsule endoscopy, angiography, technetium-99m (99m Tc-labeled red blood cell (RBC scintigraphy, cross-sectional imaging such as CT/MRI (including angiography and laparotomy combined with on-table small bowel enteroscopy. We report a case of severe, recurrent LGI bleeding that had occurred over several years, where the cause remained elusive despite numerous investigations and interventions. The etiology of this was eventually found to be a gastric duplication cyst infiltrating into adjacent transverse colon and causing bleeding from peptic ulceration in the colon. The process by which this diagnosis was made and the lessons learned are discussed.

  11. Bariatric surgery-induced weight loss causes remission of food addiction in extreme obesity.

    Science.gov (United States)

    Pepino, Marta Yanina; Stein, Richard I; Eagon, J Christopher; Klein, Samuel

    2014-08-01

    To test the hypotheses that bariatric surgery-induced weight loss: induces remission of food addiction (FA), and normalizes other eating behaviors associated with FA. Forty-four obese subjects (BMI= 48 ± 8 kg/m(2) ) were studied before and after ∼20% weight loss induced by bariatric surgery (25 Roux-en-Y gastric bypass, 11 laparoscopic adjustable gastric banding, and eight sleeve gastrectomy). We assessed: FA (Yale Food Addiction Scale), food cravings (Food Craving Inventory), and restrictive, emotional and external eating behaviors (Dutch Eating Behavior Questionnaire). FA was identified in 32% of subjects before surgery. Compared with non-FA subjects, those with FA craved foods more frequently, and had higher scores for emotional and external eating behaviors (all P-values 0.8). Surgery-induced weight loss resulted in remission of FA in 93% of FA subjects; no new cases of FA developed after surgery. Surgery-induced weight loss decreased food cravings, and emotional and external eating behaviors in both groups (all P-values 1.1). Bariatric surgery-induced weight loss induces remission of FA and improves several eating behaviors that are associated with FA. Copyright © 2014 The Obesity Society.

  12. High dietary sodium chloride causes further protein loss during head-down tilt bed rest (HDBR)

    Science.gov (United States)

    Buehlmeier, Judith; Frings-Meuthen, Petra; Baecker, Natalie; Stehle, Peter; Heer, Martina

    Human spaceflight is associated with a loss of body protein most likely caused by muscle degradation. Additionally astronauts tend towards a high dietary intake of sodium chloride (NaCl), which has recently been shown to induce low grade metabolic acidosis (Frings-Meuthen et al. JBMR, Epub 2007). In several patterns, e.g. chronical renal failure, metabolic acidosis is associated with protein catabolism. We therefore hypothesized that high dietary intake of NaCl enforces protein losses in HDBR, a model for physiological changes in microgravity (µG). Eight healthy male subjects (mean age 26.25 ± 3.5; mean body weight: 78.5 ± 4.1 kg) participated in a 14-day bed rest study in the metabolic ward of the DLR - Institute of Aerospace Medicine, Cologne, Germany. The study was carried out in a cross over design, consisting of two phases, each lasting 22 days (5 days adaptation, 14 days 6° HDBR and 3 days recovery). Both study phases were identical with respect to environmental conditions and study protocol. Subjects received an individually tailored, weight-maintaining diet containing 1.3 g protein/kg/day. The diet was identical in both study phases with the exception of NaClintake: Every subject received a low NaCl diet (0.7 mmol/kg/day) in one phase and a high NaCl diet (7.7 mmol/kg/day) in another one. Blood gas for analysis of acid-base balance was implemented at days 4 and 5 of adaptation, days 2, 5, 7, 10, 12, 14 of HDBR and days 2, 3 of recovery. Continuous urine collection started on the first day in the metabolic ward to analyze nitrogen excretion. Nitrogen balance was calculated from the difference between protein intake and urinary nitrogen excretion, determined by use of chemiluminescence (Grimble et al. JPEN, 1988). Plasma pH did not change significantly (p=0.285), but plasma bicarbonate and base excess decreased (p=0.0175; p=0.0093) with high NaCl intake in HDBR compared to the low NaCl diet. Nitrogen balance in HDBR was negative, as expected in

  13. An economic assessment of the health effects and crop yield losses caused by air pollution in mainland China.

    Science.gov (United States)

    Miao, Weijie; Huang, Xin; Song, Yu

    2017-06-01

    Air pollution is severe in China, and pollutants such as PM2.5 and surface O3 may cause major damage to human health and crops, respectively. Few studies have considered the health effects of PM2.5 or the loss of crop yields due to surface O3 using model-simulated air pollution data in China. We used gridded outputs from the WRF-Chem model, high resolution population data, and crop yield data to evaluate the effects on human health and crop yield in mainland China. Our results showed that outdoor PM2.5 pollution was responsible for 1.70-1.99 million cases of all-cause mortality in 2006. The economic costs of these health effects were estimated to be 151.1-176.9 billion USD, of which 90% were attributed to mortality. The estimated crop yield losses for wheat, rice, maize, and soybean were approximately 9, 4.6, 0.44, and 0.34 million tons, respectively, resulting in economic losses of 3.4 billion USD. The total economic losses due to ambient air pollution were estimated to be 154.5-180.3 billion USD, accounting for approximately 5.7%-6.6% of the total GDP of China in 2006. Our results show that both population health and staple crop yields in China have been significantly affected by exposure to air pollution. Measures should be taken to reduce emissions, improve air quality, and mitigate the economic loss. Copyright © 2016. Published by Elsevier B.V.

  14. Loss of Control as a Discriminating Factor Between Different Latent Classes of Disordered Gambling Severity.

    Science.gov (United States)

    James, Richard J E; O'Malley, Claire; Tunney, Richard J

    2016-12-01

    Analyses of disordered gambling assessment data have indicated that commonly used screens appear to measure latent categories. This stands in contrast to the oft-held assumption that problem gambling is at the extreme of a continuum. To explore this further, we report a series of latent class analyses of a number of prevalent problem gambling assessments (PGSI, SOGS, DSM-IV Pathological Gambling based assessments) in nationally representative British surveys between 1999 and 2012, analysing data from nearly fifty thousand individuals. The analyses converged on a three class model in which the classes differed by problem gambling severity. This identified an initial class of gamblers showing minimal problems, a additional class predominantly endorsing indicators of preoccupation and loss chasing, and a third endorsing a range of disordered gambling criteria. However, there was considerable evidence to suggest that classes of intermediate and high severity disordered gamblers differed systematically in their responses to items related to loss of control, and not simply on the most 'difficult' items. It appeared that these differences were similar between assessments. An important exception to this was one set of DSM-IV criteria based analyses using a specific cutoff, which was also used in an analysis that identified an increase in UK problem gambling prevalence between 2007 and 2010. The results suggest that disordered gambling has a mixed latent structure, and that present assessments of problem gambling appear to converge on a broadly similar construct.

  15. Losses in electric motors caused by harmonics; Harmoniske overtoners betydning for tabene i elmotorer

    Energy Technology Data Exchange (ETDEWEB)

    Johansson, M. [Dansk Energi Analyse A/S, Glostrup (Denmark); Kehr, J.M. [ABB A/S, Skovlunde (Denmark); Hoejte Hansen, H. [Balslev A/S, Glostrup (Denmark)

    2012-03-15

    the motor. The results of the lab measurements correspond very well to the losses calculated. On this basis it is concluded that harmonic currents and voltages cause energy losses in induction motors directly supplied, but that the energy losses are fairly low at the levels of distortion, a THDU of up to 6 to 8 %, which occur in Danish industry. Motors, which are supplied through a frequency converter, are not influenced by the harmonics in the supply mains. The analysis of the motor losses shows that the losses from the load torque, caused by the 5., 11., 17. etc harmonics, are considerably lower than the (very small) current heat losses in the motor, which have been caused by the same harmonics. The analysis also shows that the current displacement in the motors reduces the currents and the losses from the higher harmonics. Considering losses consequently the lower harmonics and especially 5. and 7. harmonics are most important. (LN)

  16. Guanylate cyclase C deficiency causes severe inflammation in a murine model of spontaneous colitis.

    Directory of Open Access Journals (Sweden)

    Eleana Harmel-Laws

    Full Text Available BACKGROUND: Guanylate Cyclase C (GC-C; Gucy2c is a transmembrane receptor expressed in intestinal epithelial cells. Activation of GC-C by its secreted ligand guanylin stimulates intestinal fluid secretion. Familial mutations in GC-C cause chronic diarrheal disease or constipation and are associated with intestinal inflammation and infection. Here, we investigated the impact of GC-C activity on mucosal immune responses. METHODS: We utilized intraperitoneal injection of lipopolysaccharide to elicit a systemic cytokine challenge and then measured pro-inflammatory gene expression in colonic mucosa. GC-C(+/+ and GC-C(-/- mice were bred with interleukin (IL-10 deficient animals and colonic inflammation were assessed. Immune cell influx and cytokine/chemokine expression was measured in the colon of wildtype, IL-10(-/-, GC-C(+/+IL-10(-/- and GC-C(-/-IL-10(-/- mice. GC-C and guanylin production were examined in the colon of these animals and in a cytokine-treated colon epithelial cell line. RESULTS: Relative to GC-C(+/+ animals, intraperitoneal lipopolysaccharide injection into GC-C(-/- mice increased proinflammatory gene expression in both whole colon tissue and in partially purified colonocyte isolations. Spontaneous colitis in GC-C(-/-IL-10(-/- animals was significantly more severe relative to GC-C(+/+IL-10(-/- mice. Unlike GC-C(+/+IL-10(-/- controls, colon pathology in GC-C(-/-IL-10(-/- animals was apparent at an early age and was characterized by severely altered mucosal architecture, crypt abscesses, and hyperplastic subepithelial lesions. F4/80 and myeloperoxidase positive cells as well as proinflammatory gene expression were elevated in GC-C(-/-IL-10(-/- mucosa relative to control animals. Guanylin was diminished early in colitis in vivo and tumor necrosis factor α suppressed guanylin mRNA and protein in intestinal goblet cell-like HT29-18-N2 cells. CONCLUSIONS: The GC-C signaling pathway blunts colonic mucosal inflammation that is initiated by

  17. Comparison of echocardiography and angiography in determining the cause of severe aortic regurgitation.

    Science.gov (United States)

    DePace, N L; Nestico, P F; Kotler, M N; Mintz, G S; Kimbiris, D; Goel, I P; Glazier-Laskey, E E; Ross, J

    1984-01-01

    To assess the accuracy of echocardiography in determining the cause of aortic regurgitation M mode and cross sectional echocardiography were compared with angiography in 43 patients with predominant aortic regurgitation. Each patient had all three investigations performed during the same admission to hospital. In each instance, the cause of aortic regurgitation was confirmed at surgery or necropsy. Seventeen patients had rheumatic aortic valve disease, 13 bacterial endocarditis with a perforated or partially destroyed cusp, five a bicuspid aortic valve (four with a history of endocarditis), and eight aortic regurgitation secondary to aortic root dilatation or aneurysm. Overall sensitivity of echocardiography and aortography was 84% in determining the cause of aortic regurgitation. Thus, rheumatic valve disease and endocarditis appear to be the most common causes of severe aortic regurgitation in this hospital based population. Furthermore, echocardiography is a sensitive non-invasive technique for determining the cause of aortic regurgitation and allows differentiation of valvular from root causes of aortic regurgitation.

  18. Severe progressive sensorineural hearing loss improved after removal of large jugular foramen schwannoma.

    Science.gov (United States)

    Oishi, Naoki; Kohno, Naoyuki; Shiokawa, Yoshiaki

    2011-06-01

    We report a very rare case of hearing improvement after removal of the intracranial part of a jugular foramen schwannoma (JFS) presenting with chronic and severe progressive sensorineural hearing loss (SNHL). The patient presented with progressive hearing impairment in his right ear, lasting 2 years. The patient's pure tone audiogram revealed severe SNHL. His speech discrimination score (SDS) was 0%. Auditory-evoked brain responses (ABRs) comprised only I waves following 30-100dB stimulation, although distortion-product otoacoustic emissions (DPOAEs) had good responses. These test results indicated that his hearing impairment was retrocochlear SNHL. Magnetic resonance imaging revealed within the right jugular foramen a large intracranial-extracranial tumor that compressed the brainstem. The intracranial part of the tumor was resected through retrosigmoidal craniotomy, and the tumor was pathologically diagnosed as a schwannoma. Several months after the operation, the patient's auditory thresholds improved to a level consistent with mild SNHL, ABR V waves emerged following 60-90dB stimulation, and SDS improved significantly to 95%. This case demonstrates that hearing improvement can be achieved after surgery for JFS presenting with severe and chronic progressive SNHL, and that good DPOAE responses and the presence of ABR I waves may be predictors of postoperative hearing recovery in JFS.

  19. The Econometric Assessment of Losses Caused by Water Pollution in Chongqing, Southwest China

    Institute of Scientific and Technical Information of China (English)

    杨钢; 陈刚才; 常永官

    2004-01-01

    As an important industrial city, Chongqing has experienced rapid economic growth in recent years, but at the same time the growth has been accompanied by serious pollution problems. Water quality monitoring shows that the waters of Chongqing are widely polluted. In this paper, the human capital approach is applied to assessing the economic losses and damages caused by water pollution in Chongqing. Based on previous studies and empirical investigations,water pollution-induced damage can be categorized into two general types: damage to ecosystems, including agriculture; and damage to non-ecosystems, including industry. The economic loss estimation of each type of the damage is conducted by taking into account a group of relevant parameters and methods.

  20. Craniopharyngioma causing bilateral vision loss 4 months after unremarkable magnetic resonance imaging of the brain

    Directory of Open Access Journals (Sweden)

    Rainy Betts

    2015-01-01

    Full Text Available A 65-year-old man developed bilateral vision loss 4 months after magnetic resonance imaging demonstrated no lesion in the vicinity of the optic chiasm, hypothalamus, and suprasellar tissues. Repeat computed tomography 3 months later showed a predominantly cystic mass of the suprasellar cistern with extension into the anterior third ventricle, which histologically was a craniopharyngioma. The clinical course of this case fuels the controversy whether craniopharyngiomas arise from embryonic rests or can be acquired. From a clinical perspective, it raises questions about when to obtain imaging studies dedicated to the chiasm and the appropriate interval in which a scan should be repeated to exclude structural causes of bilateral vision loss.

  1. Causes of non-adherence to therapeutic guidelines in severe community-acquired pneumonia

    OpenAIRE

    Gattarello,Simone; Ramírez, Sergio; Almarales,José Rafael; Borgatta, Bárbara; Lagunes, Leonel; Encina, Belén; Rello, Jordi; ,

    2015-01-01

    Objective To assess the adherence to Infectious Disease Society of America/American Thoracic Society guidelines and the causes of lack of adherence during empirical antibiotic prescription in severe pneumonia in Latin America. Methods A clinical questionnaire was submitted to 36 physicians from Latin America; they were asked to indicate the empirical treatment in two fictitious cases of severe respiratory infection: community-acquired pneumonia and nosocomial pneumonia. Results In the case of...

  2. Severe chronic diarrhea and weight loss in cholesteryl ester storage disease: A case report

    Institute of Scientific and Technical Information of China (English)

    Uta Drebber; Matthias Andersen; Hans U Kasper; Peter Lohse; Manfred Stolte; Hans P Dienes

    2005-01-01

    AIM: An inherited deficiency of human lysosomal acid lipase (LAL)results in the rare conditions of Wolman disease and cholesteryl ester storage disease (CESD). We want to present the rare case of CESD in an adult.METHODS: We report about an adult female patient with severe chronic diarrhea and weight loss as a consequence of CESD. Clinical examination revealed signs of malabsorption and slightly elevated liver enzymes.RESULTS: Histopathologic changes in the liver tissue and DNA sequence analysis confirmed the diagnosis of CESD due to homozygosity for the most common CESD mutation,a G934A splice site defect encoded by exon 8 of the lysosomal acid lipase (LIPA) gene.CONCLUSION: It is the first case in the literature with diarrhea as a putative symptom of CESD in adult patients.

  3. Compound Heterozygosity for Y Box Proteins Causes Sterility Due to Loss of Translational Repression.

    Directory of Open Access Journals (Sweden)

    Elizabeth Snyder

    2015-12-01

    Full Text Available The Y-box proteins YBX2 and YBX3 bind RNA and DNA and are required for metazoan development and fertility. However, possible functional redundancy between YBX2 and YBX3 has prevented elucidation of their molecular function as RNA masking proteins and identification of their target RNAs. To investigate possible functional redundancy between YBX2 and YBX3, we attempted to construct Ybx2-/-;Ybx3-/- double mutants using a previously reported Ybx2-/- model and a newly generated global Ybx3-/- model. Loss of YBX3 resulted in reduced male fertility and defects in spermatid differentiation. However, homozygous double mutants could not be generated as haploinsufficiency of both Ybx2 and Ybx3 caused sterility characterized by extensive defects in spermatid differentiation. RNA sequence analysis of mRNP and polysome occupancy in single and compound Ybx2/3 heterozygotes revealed loss of translational repression almost exclusively in the compound Ybx2/3 heterozygotes. RNAseq analysis also demonstrated that Y-box protein dose-dependent loss of translational regulation was inversely correlated with the presence of a Y box recognition target sequence, suggesting that Y box proteins bind RNA hierarchically to modulate translation in a range of targets.

  4. Partial least squares regression for predicting economic loss of vegetables caused by acid rain

    Institute of Scientific and Technical Information of China (English)

    WANG Ju; MENG He; DONG De-ming; LI Wei; FANG Chun-sheng

    2009-01-01

    To predict the economic loss of crops caused by acid rain, we used partial least squares (PLS) regression to build a model of single dependent variable-the economic loss calculated with the decrease in yield related to the pH value and levels of Ca2+, NH4+, Na+, K+, Mg2+, SO42-, NO3-, and Cl- in acid rain. We selected vegetables which were sensitive to acid rain as the sample crops, and collected 12 groups of data, of which 8 groups were used for modeling and 4 groups for testing. Using the cross validation method to evaluate the performace of this prediction model indicates that the optimum number of principal components was 3, determined by the minimum of prediction residual error sum of squares, and the prediction error of the regression equation ranges from-2.25% to 4.32%. The model predicted that the economic loss of vegetables from acid rain is negatively corrrelated to pH and the concentrations of NH4+, SO42-, NO3-, and Cl- in the rain, and positively correlated to the concentrations of Ca2+, Na+, K+ and Mg2+. The precision of the model may be improved if the non-linearity of original data is addressed.

  5. Severe hemolysis caused by graft-derived anti-B production after lung transplantation

    DEFF Research Database (Denmark)

    Taaning, E; Morling, N; Mortensen, S A

    1996-01-01

    Anti-B antibody causing sever hemolytic anemia and renal failure was found in the serum of a blood group B patient who had received a bilateral lung transplant from a blood group O donor. Although the donor origin of the antibody was not confirmed, it is likely that the anti-B antibody was produced...

  6. Risk assessment on severe hazards to China caused by West Nile virus

    Institute of Scientific and Technical Information of China (English)

    CHEN Jiming; SUN Yingxue; WANG Zhiliang; SHEN Chaojian; XIE Zhonglun; WANG Ximing

    2004-01-01

    Recent West Nile virus epidemics in USA draw worldwide concerns. Here the basic biological and epidemiologicai features of the virus are analyzed along with the special immunity of humans and animals, the immigration of birds and the natural environments in China. The risk of severe hazards to China caused by West Nile virus is assessed not high thereafter.

  7. Two cases of severe sepsis caused by Bacillus pumilus in neonatal infants

    NARCIS (Netherlands)

    Kimouli, Maria; Vrioni, Georgia; Papadopoulou, Magdalini; Koumaki, Vasiliki; Petropoulou, Dimitra; Gounaris, Antonios; Friedrich, Alexander W.; Tsakris, Athanassios

    Bacillus pumilus is an environmental contaminant that has been rarely associated with clinical infections. Here, two cases of severe sepsis caused by B. pumilus are described in two full-term neonates; one in a female infant with no factors predisposing her to infection and the other in a male

  8. Unique clone of Coxiella burnetii causing severe Q fever, French Guiana.

    Science.gov (United States)

    Mahamat, Aba; Edouard, Sophie; Demar, Magalie; Abboud, Philippe; Patrice, Jean-Yves; La Scola, Bernard; Okandze, Antoine; Djossou, Félix; Raoult, Didier

    2013-07-01

    Acute Q fever is an emergent and severe disease in French Guiana. We obtained 5 Coxiella burnetii isolates from samples of patients from Cayenne and found an epidemic clone circulating in Cayenne. This clone has caused pneumonia and endocarditis and seems to be more virulent than previously described strains.

  9. Two cases of severe sepsis caused by Bacillus pumilus in neonatal infants

    NARCIS (Netherlands)

    Kimouli, Maria; Vrioni, Georgia; Papadopoulou, Magdalini; Koumaki, Vasiliki; Petropoulou, Dimitra; Gounaris, Antonios; Friedrich, Alexander W.; Tsakris, Athanassios

    2012-01-01

    Bacillus pumilus is an environmental contaminant that has been rarely associated with clinical infections. Here, two cases of severe sepsis caused by B. pumilus are described in two full-term neonates; one in a female infant with no factors predisposing her to infection and the other in a male infan

  10. Tatumella ptyseos causing severe human infection: report of the first two Brazilian cases

    Directory of Open Access Journals (Sweden)

    Paulo Sérgio Gonçalves da Costa

    2008-10-01

    Full Text Available Tatumella ptyseos is the type species of the Tatumella genus (Enterobacteriaceae. This fermentative Gram-negative rod has only rarely been reported as a cause of human infections; there is very little information about it in the medical literature. We report here the first two Brazilian cases of T. ptyseos infections, both evolving to severe sepsis.

  11. Mutations in the nebulin gene can cause severe congenital nemaline myopathy

    NARCIS (Netherlands)

    Wallgren-Pettersson, C; Donner, K; Sewry, C; Lammens, M; Bushby, K; Uzielli, MLG; Lapi, E; Odent, S; Akcoren, Z; Topaloglu, H; Pelin, K; Bijlsma, E.

    2002-01-01

    Previously, we reported results indicating that nebulin was the gene causing the typical form of autosomal recessive nemaline (rod) myopathy. Here we describe the identification of mutations in the nebulin gene in seven offspring of five families affected by the severe congenital form of nemaline

  12. Mutations in the nebulin gene can cause severe congenital nemaline myopathy.

    NARCIS (Netherlands)

    Wallgren-Pettersson, C.; Donner, K.; Sewry, C.A.; Bijlsma, E.; Lammens, M.M.Y.; Bushby, K.; Giovannucci Uzielli, M.L.; Lapi, E.; Odent, S.; Akcoren, Z.; Topaloglu, H.; Pelin, K.

    2002-01-01

    Previously, we reported results indicating that nebulin was the gene causing the typical form of autosomal recessive nemaline (rod) myopathy. Here we describe the identification of mutations in the nebulin gene in seven offspring of five families affected by the severe congenital form of nemaline

  13. Loss of pRB causes centromere dysfunction and chromosomal instability.

    Science.gov (United States)

    Manning, Amity L; Longworth, Michelle S; Dyson, Nicholas J

    2010-07-01

    Chromosome instability (CIN) is a common feature of tumor cells. By monitoring chromosome segregation, we show that depletion of the retinoblastoma protein (pRB) causes rates of missegregation comparable with those seen in CIN tumor cells. The retinoblastoma tumor suppressor is frequently inactivated in human cancers and is best known for its regulation of the G1/S-phase transition. Recent studies have shown that pRB inactivation also slows mitotic progression and promotes aneuploidy, but reasons for these phenotypes are not well understood. Here we describe the underlying mitotic defects of pRB-deficient cells that cause chromosome missegregation. Analysis of mitotic cells reveals that pRB depletion compromises centromeric localization of CAP-D3/condensin II and chromosome cohesion, leading to an increase in intercentromeric distance and deformation of centromeric structure. These defects promote merotelic attachment, resulting in failure of chromosome congression and an increased propensity for lagging chromosomes following mitotic delay. While complete loss of centromere function or chromosome cohesion would have catastrophic consequences, these more moderate defects allow pRB-deficient cells to proliferate but undermine the fidelity of mitosis, leading to whole-chromosome gains and losses. These observations explain an important consequence of RB1 inactivation, and suggest that subtle defects in centromere function are a frequent source of merotely and CIN in cancer.

  14. Four-Rod Stabilization of Severely Destabilized Lumbar Spine Caused by Metastatic Tumor

    Directory of Open Access Journals (Sweden)

    Isao Shibuya

    2013-01-01

    Full Text Available We report a case of a 67-year-old female with severely destabilized lumbar spine caused by metastatic malignant tumor. The primary lesion was a thyroid follicular adenocarcinoma. Complete destruction of the L3, L4, and L5 vertebrae had resulted in severe instability, which left the patient with severe back pain and bed-ridden. Since the vertebrae were so severely damaged at 3 levels, 4 rods were used to stabilize the spine. Following stabilization, the pain was alleviated and the patient’s quality of life improved. We introduce here the 4-rod technique to stabilize the spine over 3 vertebral levels following severe destruction by metastatic tumor.

  15. Fast detection of manufacturing systematic design pattern failures causing device yield loss

    Science.gov (United States)

    Le Denmat, Jean-Christophe; Feldman, Nelly; Riewer, Olivia; Yesilada, Emek; Vallet, Michel; Suzor, Christophe; Talluto, Salvatore

    2015-03-01

    Starting from the 45nm technology node, systematic defectivity has a significant impact on device yield loss with each new technology node. The effort required to achieve patterning maturity with zero yield detractor is also significantly increasing with technology nodes. Within the manufacturing environment, new in-line wafer inspection methods have been developed to identify device systematic defects, including the process window qualification (PWQ) methodology used to characterize process robustness. Although patterning is characterized with PWQ methodology, some questions remain: How can we demonstrate that the measured process window is large enough to avoid design-based defects which will impact the device yield? Can we monitor the systematic yield loss on nominal wafers? From device test engineering point of view, systematic yield detractors are expected to be identified by Automated Test Pattern Generator (ATPG) test results diagnostics performed after electrical wafer sort (EWS). Test diagnostics can identify failed nets or cells causing systematic yield loss [1],[2]. Convergence from device failed nets and cells to failed manufacturing design pattern are usually based on assumptions that should be confirmed by an electrical failure analysis (EFA). However, many EFA investigations are required before the design pattern failures are found, and thus design pattern failure identification was costly in time and resources. With this situation, an opportunity to share knowledge exists between device test engineering and manufacturing environments to help with device yield improvement. This paper presents a new yield diagnostics flow dedicated to correlation of critical design patterns detected within manufacturing environment, with the observed device yield loss. The results obtained with this new flow on a 28nm technology device are described, with the defects of interest and the device yield impact for each design pattern. The EFA done to validate the design

  16. Loss of CARD9-mediated innate activation attenuates severe influenza pneumonia without compromising host viral immunity.

    Science.gov (United States)

    Uematsu, Takayuki; Iizasa, Ei'ichi; Kobayashi, Noritada; Yoshida, Hiroki; Hara, Hiromitsu

    2015-12-02

    Influenza virus (IFV) infection is a common cause of severe viral pneumonia associated with acute respiratory distress syndrome (ARDS), which is difficult to control with general immunosuppressive therapy including corticosteroids due to the unfavorable effect on viral replication. Studies have suggested that the excessive activation of the innate immunity by IFV is responsible for severe pathologies. In this study, we focused on CARD9, a signaling adaptor known to regulate innate immune activation through multiple innate sensor proteins, and investigated its role in anti-IFV defense and lung pathogenesis in a mouse model recapitulating severe influenza pneumonia with ARDS. We found that influenza pneumonia was dramatically attenuated in Card9-deficient mice, which showed improved mortality with reduced inflammatory cytokines and chemokines in the infected lungs. However, viral clearance, type-I interferon production, and the development of anti-viral B and T cell immunity were not compromised by CARD9 deficiency. Syk or CARD9-deficient DCs but not macrophages showed impaired cytokine but not type-I interferon production in response to IFV in vitro, indicating a possible role for the Syk-CARD9 pathway in DCs in excessive inflammation of IFV-infected lungs. Therefore, inhibition of this pathway is an ideal therapeutic target for severe influenza pneumonia without affecting viral clearance.

  17. Ciliopathy-associated protein CEP290 modifies the severity of retinal degeneration due to loss of RPGR.

    Science.gov (United States)

    Rao, Kollu N; Zhang, Wei; Li, Linjing; Ronquillo, Cecinio; Baehr, Wolfgang; Khanna, Hemant

    2016-05-15

    Mutations in RPGR (retinitis pigmentosa GTPase regulator) are the most common cause of X-linked RP, a severe blindness disorder. RPGR mutations result in clinically variable disease with early- to late-onset phenotypic presentation. Molecular mechanisms underlying such heterogeneity are unclear. Here we show that phenotypic expression of Rpgr-loss in mice is influenced genetically by the loss of Cep290, a human ciliopathy gene. We found that Rpgr(ko/Y) mice with a heterozygous hypomorphic allele of Cep290 (Cep290(rd16/+)) but not of a heterozygous null allele of Cep290 (Cep290(null/+)) or of other ciliopathy genes, Rpgrip1, Nphp1, Nphp4 and Nphp5, exhibit relatively early onset (by 3 months of age) retinal degeneration and dysfunction when compared with the onset at ∼7 months of age in the Rpgr(ko/Y) mice. We also observed disorganized photoreceptor outer-segment morphology and defective trafficking of opsins in the Rpgr(ko/Y)::Cep290(rd16/+) mice. Together with a physical interaction between RPGR and the C-terminal domain of CEP290, our data suggest that RPGR and CEP290 genetically interact and highlight the involvement of hypomorphic alleles of genes as potential modifiers of heterogeneous retinal ciliopathies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Root-cause failure analysis of photocurrent loss in polythiophene:fullerene-based inverted solar cells.

    Science.gov (United States)

    Voroshazi, Eszter; Uytterhoeven, Griet; Cnops, Kjell; Conard, Thierry; Favia, Paola; Bender, Hugo; Muller, Robert; Cheyns, David

    2015-01-14

    Metal oxide transport layers have played a crucial role in recent progress in organic photovoltaic (OPV) device stability. Here, we measure the stability of inverted and encapsulated polythiophene:fullerene cells with MoO3/Ag/Al composite anode in operational conditions combining solar radiation and 65 °C. Performance loss of over 50% in the first 100 h of the aging is dominated by a drop in the short-circuit current (Jsc). We reveal a concurrent loss in reflectance from 85% to 50% above 650 nm, which is below the optical gap of the used photoactive materials, hence, excluding any major degradation in the bulk of this layer. Correlating the responses of aged devices to a series of test structures comprised of ITO/ZnO cathode, MoO3/Ag, and MoO3/Ag/Al anodes and their combinations with the active layer allowed us to identify that the presence of Al causes the reduced reflectance in these devices, independent of the presence of the active layer. Systematic single-stress aging on the test structures further indicates that elevated heat is the cause of the reflectance loss. Cross-section transmission electron microscopy coupled with elemental analysis revealed the unsuspected role of Al; notably, it diffuses through the entire 150 nm thick Ag layer and accumulates at the MoO3/Ag interface. Moreover, XRD analysis of the aged MoO3/Ag/Al anode indicates the formation of Ag2Al alloy. Depth profiling with X-ray photoelectron spectroscopy advanced our understanding by confirming the formation of Ag-Al intermetallic alloy and the presence of oxidized Al only at the MoO3/Ag interface suggesting a concomitant reduction of MoO3 to most probably MoO2. This latter compound is less reflective than MoO3, which can explain the reduced reflectance in aged devices as proven by optical simulations. On the basis of these results, we could estimate that 20% of the loss in Jsc is ascribed to reduction of MoO3 triggered by its direct contact with Al.

  19. Severe signal loss in diamond beam loss monitors in high particle rate environments by charge trapping in radiation-induced defects

    CERN Document Server

    Kassel, Florian; Dabrowski, Anne; de Boer, Wim

    2016-01-01

    The beam condition monitoring leakage (BCML) system is a beam monitoring device in the compact muon solenoid (CMS) experiment at the large hadron collider (LHC). As detectors 32 poly-crystalline (pCVD) diamond sensors are positioned in rings around the beam pipe. Here, high particle rates occur from the colliding beams scattering particles outside the beam pipe. These particles cause defects, which act as traps for the ionization, thus reducing the charge collection efficiency (CCE). However, the loss in CCE was much more severe than expected from low rate laboratory measurements and simulations, especially in single-crystalline (sCVD) diamonds, which have a low initial concentration of defects. The reason why in real experiments the CCE is much worse than in laboratory experiments is related to the ionization rate. At high particle rates the trapping rate of the ionization is so high compared with the detrapping rate, that space charge builds up. This space charge reduces locally the internal electric field,...

  20. A case of odontogenic orbital cellulitis causing blindness by severe tension orbit.

    Science.gov (United States)

    Park, Chang Hyun; Jee, Dong Hyun; La, Tae Yoon

    2013-02-01

    We report a very rare case of odontogenic orbital cellulitis causing blindness by severe tension orbit. A 41-yr old male patient had visited the hospital due to severe periorbital swelling and nasal stuffiness while he was treated for a periodontal abscess. He was diagnosed with odontogenic sinusitis and orbital cellulitis, and treated with antibiotics. The symptoms were aggravated and emergency sinus drainage was performed. On the next day, a sudden decrease in vision occurred with findings of ischemic optic neuropathy and central retinal artery occlusion. Deformation of the eyeball posterior pole into a cone shape was found from the orbital CT. A high-dose steroid was administered immediately resulting in improvements of periorbital swelling, but the patient's vision had not recovered. Odontogenic orbital cellulitis is relatively rare, but can cause blindness via rapidly progressing tension orbit. Therefore even the simplest of dental problems requires careful attention.

  1. Drug Use Severity, Mortality, and Cause of Death in Primary Care Patients With Substance Use Disorders

    Directory of Open Access Journals (Sweden)

    Charles Maynard

    2016-01-01

    Full Text Available This article examines the association between drug use severity and mortality in primary care patients with substance use disorders. In 848 individuals with known vital status, severity was low in 32%, intermediate in 38%, or substantial/severe in 30%. Two-year survival was 93% in the low group, 96% in the medium group, and 92% in the high group (p = .19. The age-adjusted risk of death for the high-severity group was twice that of the medium-risk group (hazard ratio = 2.00, 95% confidence interval = [1.02, 3.93]. Individuals in the high group were more likely to die from accidents than those in the low- or medium-severity groups (50% vs. 20%, p = .021. Compared with low- and medium-severity groups, age at death was 5 years younger in the high-severity group (52 ± 9 vs. 57 ± 6, p = .017. Premature death due to accidental causes in persons with substance use disorders is a persistent yet complex problem.

  2. Is recent Eurasian winter cooling caused by Arctic sea ice loss?

    Science.gov (United States)

    Kim, Hye-Jin; Son, Seok-Woo; Kim, Kwang-Yul; Kug, Jong-Seong; Kim, Baek-Min; Jeong, Jee-Hoon

    2016-04-01

    The observed surface air temperature in the northern mid-latitudes shows a significant cooling trend in recent winters despite greenhouse gas concentrations continuing to rise. Such an unexpected cooling trend since late 1990's is especially strong over the Eurasia. Here, by performing statistical analyses and climate model experiment, we show that the recent Eurasian cooling trend is at least in part caused by Arctic sea ice loss over the Barents and Kara (BK) seas. A significant time-lagged co-variability is observed between autumn sea ice concentrations over BK seas and winter surface air temperature over the Eurasia. More importantly, the timing of a rapid sea ice loss is consistent with the timing of Eurasian cooling. These results indicate that both interannual variability and long-term trend of Eurasian winter surface air temperature are likely influenced by regional sea ice changes over BK seas. This conjecture is confirmed by climate model experiment. A coupled model, GFDL CM2.1, is integrated with a pre-industrial condition except for the Arctic regions where observed sea surface temperature is relaxed. Ensemble simulations successfully reproduce the recent cooling trend over the Eurasia although the timing is bit delayed (i.e., early 2000's instead of late 1990's). However, it is found that this cooling trend is unlikely explained by linear dynamics, and is not associated with changes in atmospheric blocks.

  3. Agricultural land-use history causes persistent loss of plant phylogenetic diversity.

    Science.gov (United States)

    Turley, Nash E; Brudvig, Lars A

    2016-09-01

    Intensive land use activities, such as agriculture, are a leading cause of biodiversity loss and can have lasting impacts on ecological systems. Yet, few studies have investigated how land-use legacies impact phylogenetic diversity (the total amount of evolutionary history in a community) or how restoration activities might mitigate legacy effects on biodiversity. We studied ground-layer plant communities in 27 pairs of Remnant (no agricultural history) and Post-agricultural (agriculture abandoned >60 yr ago) longleaf pine savannas, half of which we restored by thinning trees to reinstate open savanna conditions. We found that agricultural history had no impact on species richness, but did alter community composition and reduce phylogenetic diversity by 566 million years/1,000 m(2) . This loss of phylogenetic diversity in post-agricultural savannas was due to, in part, a reduction in the average evolutionary distance between pairs of closely related species, that is, increased phylogenetic clustering. Habitat restoration increased species richness by 27% and phylogenetic diversity by 914 million years but did not eliminate the effects of agricultural land use on community composition and phylogenetic structure. These results demonstrate the persistence of agricultural legacies, even in the face of intensive restoration efforts, and the importance of considering biodiversity broadly when evaluating human impacts on ecosystems.

  4. Can use of a cold light source in endoscopic middle ear surgery cause sensorineural hearing loss?

    Directory of Open Access Journals (Sweden)

    Suat Terzi

    2016-01-01

    Full Text Available Objectives: To investigate possible sensorineural hearing loss created by the use of a cold light source in patients undergoing endoscopic tympanoplasty surgery. Materials and Methods: The medical records of 203 patients, who underwent endoscopic Type 1 tympanoplasty surgery in our ear, nose, and throat clinic between 2012 and 2015, were checked retrospectively. Ninety-one patients were male and 112 were female, and their mean age was 34.4 ± 11.2 years. Results of audiometric measurements performed during the preoperative period and repeated 1 and 3 months postsurgery were compared to each other. Results: The mean duration of the operations was determined to be 52.4 ± 9.1 min. In addition, average preoperative bone-conduction was 11.4 ± 7.4 dB nHL. However, it was 9.57 ± 7.1 dB nHL and 9.51 ± 7.4 dB nHL, respectively, in the 1st and 3rd postoperative months. Levels of postoperative average bone-conduction at the 1st and 3rd month, as well as the thresholds of bone-conduction at 500, 1000, and 2000 Hz, were significantly lower than the preoperative results (P 0.05. Conclusion: Based on our findings, the increased heat generated by the use of a cold light source during an endoscopic tympanoplasty surgery is unlikely to cause the development of sensorineural hearing loss.

  5. Loss-of-function mutations in sodium channel Nav1.7 cause anosmia.

    Science.gov (United States)

    Weiss, Jan; Pyrski, Martina; Jacobi, Eric; Bufe, Bernd; Willnecker, Vivienne; Schick, Bernhard; Zizzari, Philippe; Gossage, Samuel J; Greer, Charles A; Leinders-Zufall, Trese; Woods, C Geoffrey; Wood, John N; Zufall, Frank

    2011-04-14

    Loss of function of the gene SCN9A, encoding the voltage-gated sodium channel Na(v)1.7, causes a congenital inability to experience pain in humans. Here we show that Na(v)1.7 is not only necessary for pain sensation but is also an essential requirement for odour perception in both mice and humans. We examined human patients with loss-of-function mutations in SCN9A and show that they are unable to sense odours. To establish the essential role of Na(v)1.7 in odour perception, we generated conditional null mice in which Na(v)1.7 was removed from all olfactory sensory neurons. In the absence of Na(v)1.7, these neurons still produce odour-evoked action potentials but fail to initiate synaptic signalling from their axon terminals at the first synapse in the olfactory system. The mutant mice no longer display vital, odour-guided behaviours such as innate odour recognition and avoidance, short-term odour learning, and maternal pup retrieval. Our study creates a mouse model of congenital general anosmia and provides new strategies to explore the genetic basis of the human sense of smell.

  6. Recurrent Acute Decompensated Heart Failure Owing to Severe Iron Deficiency Anemia Caused by Inappropriate Habitual Bloodletting

    Science.gov (United States)

    Lim, Woo-Hyun; Kim, Hack-Lyoung; Kim, Ki-Hwan; Na, Sang Hoon; Lee, Hyun-Jung; Kang, Eun Gyu; Seo, Jae-Bin; Chung, Woo-Young; Zo, Joo-Hee; Hong, Jung Ae; Kim, Kwangyoun; Kim, Myung-A

    2015-01-01

    A 68-year-old woman visited the emergency department twice with symptoms of acute heart failure including shortness of breath, general weakness, and abdominal distension. Laboratory findings showed extremely low level of serum hemoglobin at 1.4 g/dL. Echocardiographic examination demonstrated dilated left ventricular cavity with systolic dysfunction and moderate amount of pericardial effusion. In this patient, acute heart failure due to severe iron deficiency anemia was caused by inappropriate habitual bloodletting. PMID:26755934

  7. Loss of TBK1 is a frequent cause of frontotemporal dementia in a Belgian cohort

    Science.gov (United States)

    Gijselinck, Ilse; Van Mossevelde, Sara; van der Zee, Julie; Sieben, Anne; Philtjens, Stéphanie; Heeman, Bavo; Engelborghs, Sebastiaan; Vandenbulcke, Mathieu; De Baets, Greet; Bäumer, Veerle; Cuijt, Ivy; Van den Broeck, Marleen; Peeters, Karin; Mattheijssens, Maria; Rousseau, Frederic; Vandenberghe, Rik; De Jonghe, Peter; Cras, Patrick; De Deyn, Peter P.; Martin, Jean-Jacques

    2015-01-01

    Objective: To assess the genetic contribution of TBK1, a gene implicated in amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and FTD-ALS, in Belgian FTD and ALS patient cohorts containing a significant part of genetically unresolved patients. Methods: We sequenced TBK1 in a hospital-based cohort of 482 unrelated patients with FTD and FTD-ALS and 147 patients with ALS and an extended Belgian FTD-ALS family DR158. We followed up mutation carriers by segregation studies, transcript and protein expression analysis, and immunohistochemistry. Results: We identified 11 patients carrying a loss-of-function (LOF) mutation resulting in an overall mutation frequency of 1.7% (11/629), 1.1% in patients with FTD (5/460), 3.4% in patients with ALS (5/147), and 4.5% in patients with FTD-ALS (1/22). We found 1 LOF mutation, p.Glu643del, in 6 unrelated patients segregating with disease in family DR158. Of 2 mutation carriers, brain and spinal cord was characterized by TDP-43-positive pathology. The LOF mutations including the p.Glu643del mutation led to loss of transcript or protein in blood and brain. Conclusions: TBK1 LOF mutations are the third most frequent cause of clinical FTD in the Belgian clinically based patient cohort, after C9orf72 and GRN, and the second most common cause of clinical ALS after C9orf72. These findings reinforce that FTD and ALS belong to the same disease continuum. PMID:26581300

  8. Loss of Melanopsin-Expressing Retinal Ganglion Cells in Severely Staged Glaucoma Patients

    DEFF Research Database (Denmark)

    Obara, Elisabeth Anne; Hannibal, Jens; Heegaard, Steffen;

    2016-01-01

    Purpose: Multiple studies have shown overwhelming evidence supporting the impairment of melanopsin function due to glaucoma. However, few studies have been carried out in humans analyzing the histology of melanopsin-expressing retinal ganglion cells (mRGCs) in retinas with glaucoma. The aim...... of this study was to analyze the pattern of expression of mRGCs relative to RGCs in the normal retina and retinas harboring varying stages of glaucoma. Methods: Paraffin-embedded human donor eyes with glaucoma (n = 11) and age-matched controls (n = 10) were obtained from Department of Pathology at Rigshospital...... difference was observed in mRGC expression in the normal retinas and mild-staged retinas with glaucoma; the densities of mRGCs were 3.08 ± 0.47 and 3.00 ± 0.13 cell counts/mm2, respectively. However, the severely staged retinas with glaucoma showed a significant loss in mRGCs density, 1.09 ± 0.35 cell counts...

  9. Acoustic analysis of monophthong and diphthong production in acquired severe to profound hearing loss

    Science.gov (United States)

    Palethorpe, Sallyanne; Watson, Catherine I.; Barker, Rosalind

    2003-08-01

    The effect of diminished auditory feedback on monophthong and diphthong production was examined in postlingually deafened Australian-English speaking adults. The participants were 4 female and 3 male speakers with severe to profound hearing loss, who were compared to 11 age- and accent-matched normally hearing speakers. The test materials were 5 repetitions of hVd words containing 18 vowels. Acoustic measures that were studied included F1, F2, discrete cosine transform coefficients (DCTs), and vowel duration information. The durational analyses revealed increased total vowel durations with a maintenance of the tense/lax vowel distinctions in the deafened speakers. The deafened speakers preserved a differentiated vowel space, although there were some gender-specific differences seen. For example, there was a retraction of F2 in the front vowels for the female speakers that did not occur in the males. However, all deafened speakers showed a close correspondence between the monophthong and diphthong formant movements that did occur. Gaussian classification highlighted vowel confusions resulting from changes in the deafened vowel space. The results support the view that postlingually deafened speakers maintain reasonably good speech intelligibility, in part by employing production strategies designed to bolster auditory feedback.

  10. Loss of the smallest subunit of cytochrome c oxidase, COX8A, causes Leigh-like syndrome and epilepsy.

    Science.gov (United States)

    Hallmann, Kerstin; Kudin, Alexei P; Zsurka, Gábor; Kornblum, Cornelia; Reimann, Jens; Stüve, Burkhard; Waltz, Stephan; Hattingen, Elke; Thiele, Holger; Nürnberg, Peter; Rüb, Cornelia; Voos, Wolfgang; Kopatz, Jens; Neumann, Harald; Kunz, Wolfram S

    2016-02-01

    Isolated cytochrome c oxidase (complex IV) deficiency is one of the most frequent respiratory chain defects in humans and is usually caused by mutations in proteins required for assembly of the complex. Mutations in nuclear-encoded structural subunits are very rare. In a patient with Leigh-like syndrome presenting with leukodystrophy and severe epilepsy, we identified a homozygous splice site mutation in COX8A, which codes for the ubiquitously expressed isoform of subunit VIII, the smallest nuclear-encoded subunit of complex IV. The mutation, affecting the last nucleotide of intron 1, leads to aberrant splicing, a frame-shift in the highly conserved exon 2, and decreased amount of the COX8A transcript. The loss of the wild-type COX8A protein severely impairs the stability of the entire cytochrome c oxidase enzyme complex and manifests in isolated complex IV deficiency in skeletal muscle and fibroblasts, similar to the frequent c.845_846delCT mutation in the assembly factor SURF1 gene. Stability and activity of complex IV could be rescued in the patient's fibroblasts by lentiviral expression of wild-type COX8A. Our findings demonstrate that COX8A is indispensable for function of human complex IV and its mutation causes human disease.

  11. Yield loss in apple caused by Monilinia fructigena (Aderh. & Rhul.) Honey, and spatio-temporal dynamics of disease development

    NARCIS (Netherlands)

    Leeuwen, van G.C.M.; Stein, A.; Holb, I.; Jeger, M.J.

    2000-01-01

    Monilinia fructigena (Aderh. & Ruhl.) Honey causes considerable yield losses in pome fruit culture. During a field study in the Netherlands in 1997 and 1998, the increase in disease incidence in time was assessed and final pre- and post-harvest losses were recorded in the susceptible apple culti

  12. Early microgliosis precedes neuronal loss and behavioural impairment in mice with a frontotemporal dementia-causing CHMP2B mutation

    DEFF Research Database (Denmark)

    Clayton, Emma L; Mancuso, Renzo; Nielsen, Troels Tolstrup

    2017-01-01

    Frontotemporal dementia (FTD)-causing mutations in the CHMP2B gene lead to the generation of mutant C-terminally truncated CHMP2B. We report that transgenic mice expressing endogenous levels of mutant CHMP2B developed late-onset brain volume loss associated with frank neuronal loss and FTD...

  13. Recessive Inactivating Mutations in TBCK, Encoding a Rab GTPase-Activating Protein, Cause Severe Infantile Syndromic Encephalopathy

    Science.gov (United States)

    Chong, Jessica X.; Caputo, Viviana; Phelps, Ian G.; Stella, Lorenzo; Worgan, Lisa; Dempsey, Jennifer C.; Nguyen, Alina; Leuzzi, Vincenzo; Webster, Richard; Pizzuti, Antonio; Marvin, Colby T.; Ishak, Gisele E.; Ardern-Holmes, Simone; Richmond, Zara; Bamshad, Michael J.; Ortiz-Gonzalez, Xilma R.; Tartaglia, Marco; Chopra, Maya; Doherty, Dan

    2016-01-01

    Infantile encephalopathies are a group of clinically and biologically heterogeneous disorders for which the genetic basis remains largely unknown. Here, we report a syndromic neonatal encephalopathy characterized by profound developmental disability, severe hypotonia, seizures, diminished respiratory drive requiring mechanical ventilation, brain atrophy, dysgenesis of the corpus callosum, cerebellar vermis hypoplasia, and facial dysmorphism. Biallelic inactivating mutations in TBCK (TBC1-domain-containing kinase) were independently identified by whole-exome sequencing as the cause of this condition in four unrelated families. Matching these families was facilitated by the sharing of phenotypic profiles and WES data in a recently released web-based tool (Geno2MP) that links phenotypic information to rare variants in families with Mendelian traits. TBCK is a putative GTPase-activating protein (GAP) for small GTPases of the Rab family and has been shown to control cell growth and proliferation, actin-cytoskeleton dynamics, and mTOR signaling. Two of the three mutations (c.376C>T [p.Arg126∗] and c.1363A>T [p.Lys455∗]) are predicted to truncate the protein, and loss of the major TBCK isoform was confirmed in primary fibroblasts from one affected individual. The third mutation, c.1532G>A (p.Arg511His), alters a conserved residue within the TBC1 domain. Structural analysis implicated Arg511 as a required residue for Rab-GAP function, and in silico homology modeling predicted impaired GAP function in the corresponding mutant. These results suggest that loss of Rab-GAP activity is the underlying mechanism of disease. In contrast to other disorders caused by dysregulated mTOR signaling associated with focal or global brain overgrowth, impaired TBCK function results in progressive loss of brain volume. PMID:27040692

  14. Severe Hemolytic Anemia Associated with Mild Pneumonia Caused by Mycoplasma pneumonia

    Directory of Open Access Journals (Sweden)

    Zafer Kurugol

    2012-01-01

    Full Text Available We report a case of M. pneumoniae infection presenting with severe hemolytic anemia in a 4-year-old girl, with a ten-day history of paleness, weakness, and nonproductive cough. She was very pale and tachycardic. However, she was not tachypneic. Chest examination showed normal breath sounds. No rhoncus or whistling was heard. As the erythrocyte sedimentation rate was excessively elevated, the differential diagnosis primarily comprised hematological malignancies. Direct Coombs' test was positive. Diagnosis of M. pneumoniae infection was confirmed by elevated levels of M. pneumoniae IgG and IgM antibodies and a chest X-ray suggestive of atypical pneumonia. The patient was treated with clarithromycin and packed red cell transfusion and showed a favorable recovery within ten days after admission. In conclusion, this case demonstrates that severe hemolytic anemia caused by M. pneumoniae is not always associated with severe pulmonary involvement, even when the respiratory infection is very mild, M. pneumoniae may be the cause of severe anemia.

  15. Root causes and impacts of severe accidents at large nuclear power plants.

    Science.gov (United States)

    Högberg, Lars

    2013-04-01

    The root causes and impacts of three severe accidents at large civilian nuclear power plants are reviewed: the Three Mile Island accident in 1979, the Chernobyl accident in 1986, and the Fukushima Daiichi accident in 2011. Impacts include health effects, evacuation of contaminated areas as well as cost estimates and impacts on energy policies and nuclear safety work in various countries. It is concluded that essential objectives for reactor safety work must be: (1) to prevent accidents from developing into severe core damage, even if they are initiated by very unlikely natural or man-made events, and, recognizing that accidents with severe core damage may nevertheless occur; (2) to prevent large-scale and long-lived ground contamination by limiting releases of radioactive nuclides such as cesium to less than about 100 TBq. To achieve these objectives the importance of maintaining high global standards of safety management and safety culture cannot be emphasized enough. All three severe accidents discussed in this paper had their root causes in system deficiencies indicative of poor safety management and poor safety culture in both the nuclear industry and government authorities.

  16. Abrupt fire regime change may cause landscape-wide loss of mature obligate seeder forests.

    Science.gov (United States)

    Bowman, David M J S; Murphy, Brett P; Neyland, Dominic L J; Williamson, Grant J; Prior, Lynda D

    2014-03-01

    Obligate seeder trees requiring high-severity fires to regenerate may be vulnerable to population collapse if fire frequency increases abruptly. We tested this proposition using a long-lived obligate seeding forest tree, alpine ash (Eucalyptus delegatensis), in the Australian Alps. Since 2002, 85% of the Alps bioregion has been burnt by several very large fires, tracking the regional trend of more frequent extreme fire weather. High-severity fires removed 25% of aboveground tree biomass, and switched fuel arrays from low loads of herbaceous and litter fuels to high loads of flammable shrubs and juvenile trees, priming regenerating stands for subsequent fires. Single high-severity fires caused adult mortality and triggered mass regeneration, but a second fire in quick succession killed 97% of the regenerating alpine ash. Our results indicate that without interventions to reduce fire severity, interactions between flammability of regenerating stands and increased extreme fire weather will eliminate much of the remaining mature alpine ash forest. © 2013 John Wiley & Sons Ltd.

  17. Sepsis Caused by Achromobacter Xylosoxidans in a Child with Cystic Fibrosis and Severe Lung Disease.

    Science.gov (United States)

    Stobbelaar, Kim; Van Hoorenbeeck, Kim; Lequesne, Monique; De Dooy, Jozef; Ho, Erwin; Vlieghe, Erika; Ieven, Margaretha; Verhulst, Stijn

    2016-08-08

    BACKGROUND Achromobacter xylosoxidans is an aerobic, motile, Gram-negative, opportunistic pathogen that can be responsible for various severe nosocomial and community-acquired infections. It has been found in immunocompromised patients and patients with several other underlying conditions, but the clinical role of this microorganism in cystic fibrosis is unclear. CASE REPORT We describe a case of septic shock caused by A. xylosoxidans in a 10-year-old child with cystic fibrosis and severe lung disease. CONCLUSIONS As the prevalence of A. xylosoxidans in cystic fibrosis patients is rising and patient-to-patient transmission is highly probable, further studies are warranted to determine its role and to document the appropriate treatment strategy for eradication and long-term treatment of this organism.

  18. HYPERTENSIVE CHOROIDOPATHY AS AN UNCOMMON CAUSE S OF VISUAL LOSS IN PREGNANCY

    Directory of Open Access Journals (Sweden)

    Bijnya Birajita

    2015-08-01

    Full Text Available INTRODUCTION: HISTORY: A 30 year old lady in her 32 weeks gestation period was referred to our ophthalmology clinic with chief complaints of diminution of vision in both eyes for 4 months duration. Her medical history was suggestive of uncontrolled hypertension. On Ophthalmic evaluation she had best corrected visual acuity of 20/200 in both eyes with normal color vision. Her pupils were bilaterally equal in size and normally reacting to light. The intraocular pressure was within normal range and anterior segment evaluation was within normal limits. Dilated fundus evaluation revealed only arterio - venous crossing changes, mottled retina and resolving hard exudates in both eyes [Fig 1a, & 1 b]. The fundus picture could not explain the severity of vision loss in the patient which prompted us for further workup.

  19. A retrspective study of rescuing severe open craniocerebral injuries caused by traffic accidents

    Institute of Scientific and Technical Information of China (English)

    陈长才; 宁可; 等

    1999-01-01

    Objective:To investigate the rescuing principles of severe open craniocerebral injuries caused by traffic accidents.Methods:A retrospective study was performed for 36 patients admitted to our hospital from January 1986 to December 1995,who suffered from severe open craniocerebral injuries in traffic accidents.Results:These 36 cases occupied 52.10% of all the severe open craniocerebral injuries during the same period.The clinical features included confusion of consciousness, extensive cerebral contusion and laceration,severe contamination of the wound,high incidence of intracranial hematoma and multiple system injuries.Nineteen patients.(63.34%)ecovered normal neurological function,7 were (23.33%)mild disabled,4(13.33%)severe disabled,2(5.56%) vegetative survival,and 4(11.11%)dead.Conclusions:The main principles of salvage should emphasize the importance of emergent prehospital rescue,and be transfered to a specialized hospital as soon as possible.Postoperative complications included severe brain edema,intracerebral infection,and pneumonia,Debriding thoroughly at early stage and treating complications effectively would lower the rate of mortality and disability.

  20. Loss of phosphodiesterase 10A expression is associated with progression and severity in Parkinson's disease.

    Science.gov (United States)

    Niccolini, Flavia; Foltynie, Thomas; Reis Marques, Tiago; Muhlert, Nils; Tziortzi, Andri C; Searle, Graham E; Natesan, Sridhar; Kapur, Shitij; Rabiner, Eugenii A; Gunn, Roger N; Piccini, Paola; Politis, Marios

    2015-10-01

    The mechanisms underlying neurodegeneration and loss of dopaminergic signalling in Parkinson's disease are still only partially understood. Phosphodiesterase 10A (PDE10A) is a basal ganglia expressed dual substrate enzyme, which regulates cAMP and cGMP signalling cascades, thus having a key role in the regulation of dopaminergic signalling in striatal pathways, and in promoting neuronal survival. This study aimed to assess in vivo the availability of PDE10A in patients with Parkinson's disease using positron emission tomography molecular imaging with (11)C-IMA107, a highly selective PDE10A radioligand. We studied 24 patients with levodopa-treated, moderate to advanced Parkinson's disease. Their positron emission tomography imaging data were compared to those from a group of 12 healthy controls. Parametric images of (11)C-IMA107 binding potential relative to non-displaceable binding (BPND) were generated from the dynamic (11)C-IMA107 scans using the simplified reference tissue model with the cerebellum as the reference tissue. Corresponding region of interest analysis showed lower mean (11)C-IMA107 BPND in the caudate (P Parkinson's disease compared to healthy controls, which was confirmed with voxel-based analysis. Longer Parkinson's duration correlated with lower (11)C-IMA107 BPND in the caudate (r = -0.65; P = 0.005), putamen (r = -0.51; P = 0.025), and globus pallidus (r = -0.47; P = 0.030). Higher Unified Parkinson's Disease Rating Scale part-III motor scores correlated with lower (11)C-IMA107 BPND in the caudate (r = -0.54; P = 0.011), putamen (r = -0.48; P = 0.022), and globus pallidus (r = -0.70; P Parkinson's disease with levodopa-induced dyskinesias (n = 12), correlated with lower (11)C-IMA107 BPND in the caudate (r = -0.73; P = 0.031) and putamen (r = -0.74; P = 0.031). Our findings demonstrate striatal and pallidal loss of PDE10A expression, which is associated with Parkinson's duration and severity of motor symptoms and complications. PDE10A is an

  1. The molecular basis of variable phenotypic severity among common missense mutations causing Rett syndrome.

    Science.gov (United States)

    Brown, Kyla; Selfridge, Jim; Lagger, Sabine; Connelly, John; De Sousa, Dina; Kerr, Alastair; Webb, Shaun; Guy, Jacky; Merusi, Cara; Koerner, Martha V; Bird, Adrian

    2016-02-01

    Rett syndrome is caused by mutations in the X-linked MECP2 gene, which encodes a chromosomal protein that binds to methylated DNA. Mouse models mirror the human disorder and therefore allow investigation of phenotypes at a molecular level. We describe an Mecp2 allelic series representing the three most common missense Rett syndrome (RTT) mutations, including first reports of Mecp2[R133C] and Mecp2[T158M] knock-in mice, in addition to Mecp2[R306C] mutant mice. Together these three alleles comprise ∼25% of all RTT mutations in humans, but they vary significantly in average severity. This spectrum is mimicked in the mouse models; R133C being least severe, T158M most severe and R306C of intermediate severity. Both R133C and T158M mutations cause compound phenotypes at the molecular level, combining compromised DNA binding with reduced stability, the destabilizing effect of T158M being more severe. Our findings contradict the hypothesis that the R133C mutation exclusively abolishes binding to hydroxymethylated DNA, as interactions with DNA containing methyl-CG, methyl-CA and hydroxymethyl-CA are all reduced in vivo. We find that MeCP2[T158M] is significantly less stable than MeCP2[R133C], which may account for the divergent clinical impact of the mutations. Overall, this allelic series recapitulates human RTT severity, reveals compound molecular aetiologies and provides a valuable resource in the search for personalized therapeutic interventions.

  2. Comment on "Fire-derived charcoal causes loss of forest humus".

    Science.gov (United States)

    Lehmann, Johannes; Sohi, Saran

    2008-09-01

    Wardle et al. (Brevia, 2 May 2008, p. 629) reported that fire-derived charcoal can promote loss of forest humus and belowground carbon (C). However, C loss from charcoal-humus mixtures can be explained not only by accelerated loss of humus but also by loss of charcoal. It is also unclear whether such loss is related to mineralization to carbon dioxide or to physical export.

  3. Transgenerational effects alleviate severe fecundity loss during ocean acidification in a ubiquitous planktonic copepod.

    Science.gov (United States)

    Thor, Peter; Dupont, Sam

    2015-06-01

    Ocean acidification (OA) caused by anthropogenic CO2 emission is projected for thousands of years to come, and significant effects are predicted for many marine organisms. While significant evolutionary responses are expected during such persistent environmental change, most studies consider only short-term effects. Little is known about the transgenerational effects of parental environments or natural selection on the capacity of populations to counter detrimental OA effects. In this study, six laboratory populations of the calanoid copepod Pseudocalanus acuspes were established at three different CO2 partial pressures (pCO2 of 400, 900 and 1550 μatm) and grown for two generations at these conditions. Our results show evidence of alleviation of OA effects as a result of transgenerational effects in P. acuspes. Second generation adults showed a 29% decrease in fecundity at 900 μatm CO2 compared to 400 μatm CO2 . This was accompanied by a 10% increase in metabolic rate indicative of metabolic stress. Reciprocal transplant tests demonstrated that this effect was reversible and the expression of phenotypic plasticity. Furthermore, these tests showed that at a pCO2 exceeding the natural range experienced by P. acuspes (1550 μatm), fecundity would have decreased by as much as 67% compared to at 400 μatm CO2 as a result of this plasticity. However, transgenerational effects partly reduced OA effects so that the loss of fecundity remained at a level comparable to that at 900 μatm CO2 . This also relieved the copepods from metabolic stress, and respiration rates were lower than at 900 μatm CO2 . These results highlight the importance of tests for transgenerational effects to avoid overestimation of the effects of OA.

  4. Comparison of severe pneumonia caused by Human metapneumovirus and respiratory syncytial virus in hospitalized children

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    Yuqing Wang

    2014-01-01

    Full Text Available Objectives: The objective of this study is to compare the incidence and clinical characteristics of severe pneumonia caused by Human metapneumovirus (hMPV to respiratory syncytial virus (RSV infection in children. Patients and Methods: A total of 151 children hospitalized with severe pneumonia, were tested for hMPV using reverse-transcription polymerase chain reaction. At the same time, samples were tested for RSV and other common respiratory viruses. Medical records, including clinical, laboratory data, and chest radiography findings, were reviewed for all children. Results: Of the 151 samples, 88 (58.3% were positive for respiratory viruses. Of the 88 positive, there were 6 (4.0% with hMPV, 66 (43.7% with RSV, 13 (8.6% with influenza A, 2 (1.3% with parainfluenza virus III, 1 (0.7% with parainfluenza virus I, 1 (0.7% with adenovirus and 1 (0.7% with influenza B. hMPV-infected patients were significantly older than RSV-infected patients (P < 0.001. Children with hMPV pneumonia had fever more frequently (P = 0.03. Two hMPV-positive patients (33.3% required admission to an intensive care unit, and two patients (33.3% required mechanical ventilation. The duration of illness was 18.33 ± 7.09 days. These characteristics of hMPV infections were similar to patients with RSV infections. Conclusion: Human metapneumovirus is an infrequent viral pathogen causing severe pneumonia in children. Children with hMPV were older than those with RSV. The disease caused by hMPV was similar in presentation and severity to RSV, with a minority of children requiring additional respiratory support.

  5. Loss of PTEN causes SHP2 activation, making lung cancer cells unresponsive to IFN-γ

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Chia-Ling [Translational Research Center, Taipei Medical University, Taipei 110, Taiwan (China); Chiang, Tzu-Hui; Tseng, Po-Chun [Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China); Wang, Yu-Chih [Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan (China); Lin, Chiou-Feng, E-mail: cflin2014@tmu.edu.tw [Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan (China); Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan (China)

    2015-10-23

    Src homology-2 domain-containing phosphatase (SHP) 2, an oncogenic phosphatase, inhibits type II immune interferon (IFN)-γ signaling by subverting signal transducers and activators of transcription 1 tyrosine phosphorylation and activation. For cancer immunoediting, this study aimed to investigate the decrease of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumor suppressor protein, leading to cellular impairment of IFN-γ signaling. In comparison with human lung adenocarcinoma A549 cells, the natural PTEN loss in another human lung adenocarcinoma line, PC14PE6/AS2 cells, presents reduced responsiveness in IFN-γ-induced IFN regulatory factor 1 activation and CD54 expression. Artificially silencing PTEN expression in A549 cells also caused cells to be unresponsive to IFN-γ without affecting IFN-γ receptor expression. IFN-γ-induced inhibition of cell proliferation and cytotoxicity were demonstrated in A549 cells but were defective in PC14PE6/AS2 cells and in PTEN-deficient A549 cells. Aberrant activation of SHP2 by ROS was specifically shown in PC14PE6/AS2 cells and PTEN-deficient A549 cells. Inhibiting ROS and SHP2 rescued cellular responses to IFN-γ-induced cytotoxicity and inhibition of cell proliferation in PC14PE6/AS2 cells. These results demonstrate that a decrease in PTEN facilitates ROS/SHP2 signaling, causing lung cancer cells to become unresponsive to IFN-γ. - Highlights: • This study demonstrates that PTEN decrease causes cellular unresponsive to IFN-γ. • Lung cancer cells with PTEN deficiency show unresponsive to IFN-γ signaling. • PTEN decrease inhibits IFN-γ-induced CD54, cell proliferation inhibition, and cytotoxicity. • ROS-mediated SHP2 activation makes PTEN-deficient cells unresponsive to IFN-γ.

  6. B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C δ.

    Science.gov (United States)

    Salzer, Elisabeth; Santos-Valente, Elisangela; Klaver, Stefanie; Ban, Sol A; Emminger, Wolfgang; Prengemann, Nina Kathrin; Garncarz, Wojciech; Müllauer, Leonhard; Kain, Renate; Boztug, Heidrun; Heitger, Andreas; Arbeiter, Klaus; Eitelberger, Franz; Seidel, Markus G; Holter, Wolfgang; Pollak, Arnold; Pickl, Winfried F; Förster-Waldl, Elisabeth; Boztug, Kaan

    2013-04-18

    Primary B-cell disorders comprise a heterogeneous group of inherited immunodeficiencies, often associated with autoimmunity causing significant morbidity. The underlying genetic etiology remains elusive in the majority of patients. In this study, we investigated a patient from a consanguineous family suffering from recurrent infections and severe lupuslike autoimmunity. Immunophenotyping revealed progressive decrease of CD19(+) B cells, a defective class switch indicated by low numbers of IgM- and IgG-memory B cells, as well as increased numbers of CD21(low) B cells. Combined homozygosity mapping and exome sequencing identified a biallelic splice-site mutation in protein C kinase δ (PRKCD), causing the absence of the corresponding protein product. Consequently, phosphorylation of myristoylated alanine-rich C kinase substrate was decreased, and mRNA levels of nuclear factor interleukin (IL)-6 and IL-6 were increased. Our study uncovers human PRKCD deficiency as a novel cause of common variable immunodeficiency-like B-cell deficiency with severe autoimmunity.

  7. Severe Facet Joint Arthrosis Caused C7/T1 Myelopathy: A Case Report

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    Toshimi Aizawa

    2009-01-01

    Full Text Available Cervical myelopathy is caused by degenerative processes of the spine including intervertebral disc herniation and posterior spur usually developing at C3/4 to C5/6. C7/T1 single level myelopathy is very rare because of the anatomical characteristics. Facet joint arthrosis can be a cause of cervical myelopathy but only a few cases have been reported. The authors report an extremely rare case of C7/T1 myelopathy caused by facet joint arthrosis. A 58-year-old male presented with hand and gait clumsiness. The radiological examinations revealed severe C7/T1 facet joint arthrosis with bony spur extending into the spinal canal, which compressed the spinal cord laterally. The T1 spinous process indicated nonunion of a “clay-shoveler's” fracture, which suggested that his cervico-thoracic spine had been frequently moved, and thus severe arthrosis had occurred in the facet joints. A right hemilaminectomy of C7 and C7/T1 facetectomy with single level spinal fusion led to complete neurological improvement.

  8. Mutations in MDH2, Encoding a Krebs Cycle Enzyme, Cause Early-Onset Severe Encephalopathy.

    Science.gov (United States)

    Ait-El-Mkadem, Samira; Dayem-Quere, Manal; Gusic, Mirjana; Chaussenot, Annabelle; Bannwarth, Sylvie; François, Bérengère; Genin, Emmanuelle C; Fragaki, Konstantina; Volker-Touw, Catharina L M; Vasnier, Christelle; Serre, Valérie; van Gassen, Koen L I; Lespinasse, Françoise; Richter, Susan; Eisenhofer, Graeme; Rouzier, Cécile; Mochel, Fanny; De Saint-Martin, Anne; Abi Warde, Marie-Thérèse; de Sain-van der Velde, Monique G M; Jans, Judith J M; Amiel, Jeanne; Avsec, Ziga; Mertes, Christian; Haack, Tobias B; Strom, Tim; Meitinger, Thomas; Bonnen, Penelope E; Taylor, Robert W; Gagneur, Julien; van Hasselt, Peter M; Rötig, Agnès; Delahodde, Agnès; Prokisch, Holger; Fuchs, Sabine A; Paquis-Flucklinger, Véronique

    2017-01-05

    MDH2 encodes mitochondrial malate dehydrogenase (MDH), which is essential for the conversion of malate to oxaloacetate as part of the proper functioning of the Krebs cycle. We report bi-allelic pathogenic mutations in MDH2 in three unrelated subjects presenting with early-onset generalized hypotonia, psychomotor delay, refractory epilepsy, and elevated lactate in the blood and cerebrospinal fluid. Functional studies in fibroblasts from affected subjects showed both an apparently complete loss of MDH2 levels and MDH2 enzymatic activity close to null. Metabolomics analyses demonstrated a significant concomitant accumulation of the MDH substrate, malate, and fumarate, its immediate precursor in the Krebs cycle, in affected subjects' fibroblasts. Lentiviral complementation with wild-type MDH2 cDNA restored MDH2 levels and mitochondrial MDH activity. Additionally, introduction of the three missense mutations from the affected subjects into Saccharomyces cerevisiae provided functional evidence to support their pathogenicity. Disruption of the Krebs cycle is a hallmark of cancer, and MDH2 has been recently identified as a novel pheochromocytoma and paraganglioma susceptibility gene. We show that loss-of-function mutations in MDH2 are also associated with severe neurological clinical presentations in children.

  9. Loss of Bace1 in mice does not alter the severity of caerulein induced pancreatitis.

    Directory of Open Access Journals (Sweden)

    Mario Heindl

    Full Text Available Beta-site alpha-amyloid protein cleaving enzyme1 (BACE1 plays a key role in the pathogenesis of Alzheimer's disease. Additional to its moderate expression in the brain, high levels of BACE1 mRNA were found in the pancreas. Murine Bace1 has been immunohistochemicaly detected at the apical pole of acinar cells within the exocrine pancreas of mice and Bace1 activity was observed in pancreatic juice. In vitro experiments revealed enteropeptidase as a putative substrate for Bace1 suggesting a role in acute pancreatitis.The aim of this study was to address a protective mechanism of Bace1 in acute experimental pancreatitis in mice.Acute experimental pancreatitis was induced by intraperitoneal injection of caerulein in homozygote Bace1-/- mice and wild type mice. Serum and tissue analyses were carried out after 4 h, 8 h and 24 h. Measurement of plasma amylase and lipase was performed to confirm pancreatitis induction. In order to assess the severity of pancreatitis H&E stained pancreatic sections were examined regarding edema, inflammation and apoptosis. Immunohistochemical detection of myeloperoxidase (MPO positive cells was carried out to further quantify the extent of inflammation. Expression of Bace2 within the pancreas was analyzed by immunohistochemistry and RT-qPCR.We demonstrate that total loss of Bace1 in mice leads to no alterations in the course of acute experimental caerulein-pancreatitis. Bace1-/- mice develop a moderate pancreatitis that is comparable in histomorphological and serological features with those seen in wild type mice.We discuss the results in the context of the applied caerulein induced edematous pancreatitis model and possible compensatory mechanisms via Bace2 that might be responsible for the observed results.

  10. Two Cases of Severe Combined Immunodeficiency Caused By Adenosine Deaminase Deficiency

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    Turkan Patiroglu

    2014-08-01

    Full Text Available Severe Combined Immune Deficiency (SCID is a primary immune deficiency disorder manifested with severe infections upon first months of life, which is characterized by diverse genetic defects in T and B lymphocyte functions and occasionally in NK cells. ADA deficiency is a form of SCID progressing with severe lymphopenia and immune deficiency caused by toxic metabolites of ADA. Bone marrow transplantation (BMT is the only curative treatment although prophylactic anti-microbial therapy, intravenous immunoglobulin (IVIG and enzyme replacement can achieve transient improvements. Early diagnosis before development of severe infections and organ injury and referral to pediatric immunology clinics will make considerable contributions to prognosis. Here, we presented 2 cousins with SCID who had positive family history with deceased sibling; presented with tanning at skin, severe neonatal infections and Q246X (c736C>T non-sense mutation in exon 8 in ADA gene  in order to emphasize this rare mutation and pediatric emergencies associated with this disorder.

  11. Upper gastrointestinal bleeding caused by severe esophagitis: a unique clinical syndrome.

    Science.gov (United States)

    Guntipalli, Prathima; Chason, Rebecca; Elliott, Alan; Rockey, Don C

    2014-12-01

    We have recognized a unique clinical syndrome in patients with upper gastrointestinal bleeding who are found to have severe esophagitis. We aimed to more clearly describe the clinical entity of upper gastrointestinal bleeding in patients with severe esophagitis. We conducted a retrospective matched case-control study designed to investigate clinical features in patients with carefully defined upper gastrointestinal bleeding and severe esophagitis. Patient data were captured prospectively via a Gastrointestinal Bleeding Healthcare Registry, which collects data on all patients admitted with gastrointestinal bleeding. Patients with endoscopically documented esophagitis (cases) were matched with randomly selected controls that had upper gastrointestinal bleeding caused by other lesions. Epidemiologic features in patients with esophagitis were similar to those with other causes of upper gastrointestinal bleeding. However, hematemesis was more common in patients with esophagitis 86% (102/119) than in controls 55% (196/357) (p bleeding than those without cirrhosis. We have described a unique clinical syndrome in patients with upper gastrointestinal bleeding who have erosive esophagitis. This syndrome is manifest by typical clinical features and is associated with favorable outcomes.

  12. Biological and Molecular Characterization of Cucumber mosaic virus Subgroup II Isolate Causing Severe Mosaic in Cucumber.

    Science.gov (United States)

    Kumari, Reenu; Bhardwaj, Pooja; Singh, Lakhmir; Zaidi, Aijaz A; Hallan, Vipin

    2013-06-01

    Cucumber mosaic virus (CMV) has a wide host range causing severe damage in many important agricultural and ornamental crops. Earlier reports showed the prevalence of CMV subgroup I isolates in India. However, some recent reports point towards increasing incidence of subgroup II isolates in the country. The complete genome of a CMV isolate causing severe mosaic in cucumber was characterized and its phylogenetic analysis with other 21 CMV isolates reported worldwide clustered it with subgroup II strains. The genome comprised of RNA 1 (3,379 nucleotides), RNA 2 (3,038 nucleotides) and RNA 3 (2,206 nucleotides). The isolate showed highest homology with subgroup II isolates: 95.1-98.7, 87.7-98.0, and 85.4-97.1 % within RNA1, RNA2, and RNA3, respectively. RNA1 and RNA2 were closely related to the Japanese isolate while RNA3 clustered with an American isolate. Host range studies revealed that isolate showed severe mosaic symptoms on Nicotiana spp. and Cucumis spp. The isolate induced leaf deformation and mild filiform type symptoms in tomato. To best of our knowledge this is the first report of complete genome of CMV subgroup II isolate from India.

  13. Causes and Severity of Fatal Injuries in Autopsies of Victims of Fatal Traffic Accidents

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    F Panahi

    2010-03-01

    Full Text Available Introduction: In this retrospective study, we decided to determine the death causes and severity of injuries in traffic accidents according to reports of the forensic medical center of Yazd. Methods: A total of 251 fatalities due to traffic accidents that had undergone autopsy examinations at the Yazd forensic medicine center from2006 till 2008 were included in the study by census method. Data regarding gender, road user type, type of vehicle (car, motorcycle, autobus or minibus, consciousness level, and intensive care unit (ICU admission was gathered. For evaluation of injury severity, we used Injury Severity Score (ISS. Results: The population under study consisted of 202 men (80.5% and 49 women (19.5% with an average age of 34.1 years (range: 1-89 years. Motorcycle-pedestrian accidents were the most common type of injury (100, 39.8%. Head (220, 87.6% and face (169, 67.3% were the two most common sites of injuries. Mean (±SD of ISS was 23.2 (±10.4. According to autopsy records, the main cause of death was head trauma (146, 58.1%. Conclusion: Public awareness in terms of primary prevention of road accidents should be considered important. Also, regarding the high prevalence of brain injuries and complications associated with skull fractures, accessibility to neurosurgeons and availability of imaging devices have an important role in decreasing the mortality rate of traffic accidents.

  14. A founder TMIE mutation is a frequent cause of hearing loss in southeastern Anatolia.

    Science.gov (United States)

    Sirmaci, A; Oztürkmen-Akay, H; Erbek, S; Incesulu, A; Duman, D; Taşir-Yilmaz, S; Ozdağ, H; Tekin, M

    2009-06-01

    Using Affymetrix 10K arrays, we searched for regions of homozygosity in 51 Turkish families including at least three members with either congenital or prelingual autosomal recessive non-syndromic sensorineural hearing loss (ARNSSNHL), and identified four families whose deafness mapped to the DFNB6 locus on 3p21 containing the TMIE gene. Mutation analysis revealed the p.R84W mutation in all four families. Screening of this mutation in 254 families with ARNSSNHL, without GJB2 mutations, revealed four additional affected families. A novel mutation was found in a non-complementary marriage between a deaf couple who were homozygous for p.R84W and p.W57X, respectively with two affected children who were compound heterozygotes. Six of the TMIE families originated from southeastern Anatolia, making p.R84W a common cause of hearing loss in that region with a relative frequency of 10.3% (95% CI is 2.5-18.1%). The overall prevalence of the p.R84W mutation in ARNSSNHL in Turkey is 2.4% (95% CI is 0.7-4.0%). Genotyping of single-nucleotide polymorphisms flanking the TMIE gene revealed a conserved haplotype, suggesting a single origin for p.R84W from a common ancestor 1250 years ago (95% CI is 650-2500 years). We conclude that p.R84W could be a common mutation in other Middle Eastern populations and should be included in mutation screening offered to individuals with ARNSSNHL.

  15. Loss of function mutations in HARS cause a spectrum of inherited peripheral neuropathies.

    Science.gov (United States)

    Safka Brozkova, Dana; Deconinck, Tine; Griffin, Laurie Beth; Ferbert, Andreas; Haberlova, Jana; Mazanec, Radim; Lassuthova, Petra; Roth, Christian; Pilunthanakul, Thanita; Rautenstrauss, Bernd; Janecke, Andreas R; Zavadakova, Petra; Chrast, Roman; Rivolta, Carlo; Zuchner, Stephan; Antonellis, Anthony; Beg, Asim A; De Jonghe, Peter; Senderek, Jan; Seeman, Pavel; Baets, Jonathan

    2015-08-01

    Inherited peripheral neuropathies are a genetically heterogeneous group of disorders characterized by distal muscle weakness and sensory loss. Mutations in genes encoding aminoacyl-tRNA synthetases have been implicated in peripheral neuropathies, suggesting that these tRNA charging enzymes are uniquely important for the peripheral nerve. Recently, a mutation in histidyl-tRNA synthetase (HARS) was identified in a single patient with a late-onset, sensory-predominant peripheral neuropathy; however, the genetic evidence was lacking, making the significance of the finding unclear. Here, we present clinical, genetic, and functional data that implicate HARS mutations in inherited peripheral neuropathies. The associated phenotypic spectrum is broad and encompasses axonal and demyelinating motor and sensory neuropathies, including four young patients presenting with pure motor axonal neuropathy. Genome-wide linkage studies in combination with whole-exome and conventional sequencing revealed four distinct and previously unreported heterozygous HARS mutations segregating with autosomal dominant peripheral neuropathy in four unrelated families (p.Thr132Ile, p.Pro134His, p.Asp175Glu and p.Asp364Tyr). All mutations cause a loss of function in yeast complementation assays, and p.Asp364Tyr is dominantly neurotoxic in a Caenorhabditis elegans model. This study demonstrates the role of HARS mutations in peripheral neuropathy and expands the genetic and clinical spectrum of aminoacyl-tRNA synthetase-related human disease. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy.

    Science.gov (United States)

    Syrbe, Steffen; Hedrich, Ulrike B S; Riesch, Erik; Djémié, Tania; Müller, Stephan; Møller, Rikke S; Maher, Bridget; Hernandez-Hernandez, Laura; Synofzik, Matthis; Caglayan, Hande S; Arslan, Mutluay; Serratosa, José M; Nothnagel, Michael; May, Patrick; Krause, Roland; Löffler, Heidrun; Detert, Katja; Dorn, Thomas; Vogt, Heinrich; Krämer, Günter; Schöls, Ludger; Mullis, Primus E; Linnankivi, Tarja; Lehesjoki, Anna-Elina; Sterbova, Katalin; Craiu, Dana C; Hoffman-Zacharska, Dorota; Korff, Christian M; Weber, Yvonne G; Steinlin, Maja; Gallati, Sabina; Bertsche, Astrid; Bernhard, Matthias K; Merkenschlager, Andreas; Kiess, Wieland; Gonzalez, Michael; Züchner, Stephan; Palotie, Aarno; Suls, Arvid; De Jonghe, Peter; Helbig, Ingo; Biskup, Saskia; Wolff, Markus; Maljevic, Snezana; Schüle, Rebecca; Sisodiya, Sanjay M; Weckhuysen, Sarah; Lerche, Holger; Lemke, Johannes R

    2015-04-01

    Epileptic encephalopathies are a phenotypically and genetically heterogeneous group of severe epilepsies accompanied by intellectual disability and other neurodevelopmental features. Using next-generation sequencing, we identified four different de novo mutations in KCNA2, encoding the potassium channel KV1.2, in six isolated patients with epileptic encephalopathy (one mutation recurred three times independently). Four individuals presented with febrile and multiple afebrile, often focal seizure types, multifocal epileptiform discharges strongly activated by sleep, mild to moderate intellectual disability, delayed speech development and sometimes ataxia. Functional studies of the two mutations associated with this phenotype showed almost complete loss of function with a dominant-negative effect. Two further individuals presented with a different and more severe epileptic encephalopathy phenotype. They carried mutations inducing a drastic gain-of-function effect leading to permanently open channels. These results establish KCNA2 as a new gene involved in human neurodevelopmental disorders through two different mechanisms, predicting either hyperexcitability or electrical silencing of KV1.2-expressing neurons.

  17. Cameron Ulcer Causing Severe Anemia in a Patient with Diaphragmatic Hernia

    Science.gov (United States)

    Gupta, Prashant; Suryadevara, Madhu; Das, Avash; Falterman, James

    2015-01-01

    Patient: Female, 51 Final Diagnosis: Cameron’s ulcer Symptoms: — Medication: — Clinical Procedure: Endoscopy Specialty: Gastroenterology and Hepatology Objective: Rare co-existance of disease or pathology Background: Cameron lesions are linear gastric erosions on the mucosal folds at the diaphragmatic impressions found in patients with large hiatal hernias. While usually asymptomatic, hiatal hernias can result in serious sequelae, as this case report will clearly illustrate. Cameron lesions are clinically significant because of their ability to cause significant acute, chronic, or obscure gastrointestinal bleeding, often requiring blood transfusions. Case Report: In this report, we present the case of a 51-year-old white woman who originally presented to the Emergency Department with complaints of a runny nose, dry cough, generalized weakness, and muscle cramping ascribed to a viral infection. However, closer examination revealed substantial pallor with pale conjunctiva prompting further workup that revealed substantial anaemia. Upon further inquiry of her past medical history, she revealed the need for previous blood transfusions, and meticulous review of her medical record indicated a previous diagnosis of hiatal hernia with the presence of Cameron lesions based on esophagogastroduodenoscopy 2 years prior. Conclusions: This case emphasizes the need for a high index of suspicion for Cameron lesions as a causative agent of substantial blood loss in patients with hiatal hernias after other common causes of gastrointestinal bleeding have been ruled out. PMID:26467083

  18. Successful Immunoglobulin Treatment in Severe Cryptogenic Organizing Pneumonia Caused by Dermatomyositis

    Directory of Open Access Journals (Sweden)

    Dong Hoon Lee

    2015-08-01

    Full Text Available In connective tissue diseases, autoantibodies cause pulmonary interstitial inflammation and fibrosis, and patients require treatment with an immunosuppressive agent such as a steroid. Dermatomyositis is an incurable, uncommon form of connective tissue disease that occasionally causes diffuse pulmonary inflammation leading to acute severe respiratory failure. In such cases, the prognosis is very poor despite treatment with high-dose steroid. In the present case, a 46-year-old man was admitted to our hospital with dyspnea. He was diagnosed with dermatomyositis combined with cryptogenic organizing pneumonia (COP with respiratory failure and underwent treatment with steroid and an immunosuppressive agent, but the COP was not improved. However, the respiratory failure did improve after treatment with intravenous immunoglobulin, which therefore can be considered a treatment option in cases where steroids and immunosuppressive agents are ineffective.

  19. Causes of non-adherence to therapeutic guidelines in severe community-acquired pneumonia.

    Science.gov (United States)

    Gattarello, Simone; Ramírez, Sergio; Almarales, José Rafael; Borgatta, Bárbara; Lagunes, Leonel; Encina, Belén; Rello, Jordi

    2015-01-01

    To assess the adherence to Infectious Disease Society of America/American Thoracic Society guidelines and the causes of lack of adherence during empirical antibiotic prescription in severe pneumonia in Latin America. A clinical questionnaire was submitted to 36 physicians from Latin America; they were asked to indicate the empirical treatment in two fictitious cases of severe respiratory infection: community-acquired pneumonia and nosocomial pneumonia. In the case of community acquired pneumonia, 11 prescriptions of 36 (30.6%) were compliant with international guidelines. The causes for non-compliant treatment were monotherapy (16.0%), the unnecessary prescription of broad-spectrum antibiotics (40.0%) and the use of non-recommended antibiotics (44.0%). In the case of nosocomial pneumonia, the rate of adherence to the Infectious Disease Society of America/American Thoracic Society guidelines was 2.8% (1 patient of 36). The reasons for lack of compliance were monotherapy (14.3%) and a lack of dual antibiotic coverage against Pseudomonas aeruginosa (85.7%). If monotherapy with an antipseudomonal antibiotic was considered adequate, the antibiotic treatment would be adequate in 100% of the total prescriptions. The compliance rate with the Infectious Disease Society of America/American Thoracic Society guidelines in the community-acquired pneumonia scenario was 30.6%; the most frequent cause of lack of compliance was the indication of monotherapy. In the case of nosocomial pneumonia, the compliance rate with the guidelines was 2.8%, and the most important cause of non-adherence was lack of combined antipseudomonal therapy. If the use of monotherapy with an antipseudomonal antibiotic was considered the correct option, the treatment would be adequate in 100% of the prescriptions.

  20. Increased progerin expression associated with unusual LMNA mutations causes severe progeroid syndromes.

    Science.gov (United States)

    Moulson, Casey L; Fong, Loren G; Gardner, Jennifer M; Farber, Emily A; Go, Gloriosa; Passariello, Annalisa; Grange, Dorothy K; Young, Stephen G; Miner, Jeffrey H

    2007-09-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare precocious aging syndrome caused by mutations in LMNA that lead to synthesis of a mutant form of prelamin A, generally called progerin, that cannot be processed to mature lamin A. Most HGPS patients have a recurrent heterozygous de novo mutation in exon 11 of LMNA, c.1824C>T/p.G608G; this synonymous mutation activates a nearby cryptic splice donor site, resulting in synthesis of the mutant prelamin A, progerin, which lacks 50 amino acids within the carboxyl-terminal domain. Abnormal splicing is incomplete, so the mutant allele produces some normally-spliced transcripts. Nevertheless, the synthesis of progerin is sufficient to cause misshapen nuclei in cultured cells and severe disease phenotypes in affected patients. Here we present two patients with extraordinarily severe forms of progeria caused by unusual mutations in LMNA. One had a splice site mutation (c.1968+1G>A; or IVS11+1G>A), and the other had a novel synonymous coding region mutation (c.1821G>A/p.V607V). Both mutations caused very frequent use of the same exon 11 splice donor site that is activated in typical HGPS patients. As a consequence, the ratios of progerin mRNA and protein to wild-type were higher than in typical HGPS patients. Fibroblasts from both patients exhibited nuclear shape abnormalities typical of HGPS, and cells treated with a protein farnesyltransferase inhibitor exhibited fewer misshapen nuclei. Thus, farnesyltransferase inhibitors may prove to be useful even when progerin expression levels are higher than those in typical HGPS patients.

  1. A pilot study examining garment severance damage caused by a trained sharp-weapon user

    OpenAIRE

    Cowper, E J; Mahoney, P F; Godhania, K; Carr, D. J.; Harrison, K.

    2016-01-01

    The pilot study summarized in this paper aimed to raise awareness of a gap that exists in the forensic textile science literature about damage caused to clothing by trained sharp-weapon users. A male trained in the Filipino martial arts discipline of Eskrima performed attack techniques on a physical model of a male torso covered with a 97% cotton/3% elastane knitted T-shirt, that is, a garment commonly worn by males. Fabric severance appearance created by three different, but commonly availab...

  2. Incidence, causes, severity and treatment of throat discomfort: a four-region online questionnaire survey

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    Addey Dilys

    2012-08-01

    Full Text Available Abstract Background Acute sore throat is commonly associated with viral infections. Consumers typically rely on over-the-counter treatments and other remedies to treat symptoms; however, limited information is available regarding consumer perceptions of sore throat or treatment needs. The aim of this study was to investigate perceptions of throat discomfort and how these influence attitudes and consumer behaviour with regard to treatment. Methods Online consumer surveys were completed by participants invited by email between 2003 and 2004 in four markets: the UK, France, Poland, and Malaysia. The questionnaire consisted of 24 questions that covered key issues surrounding throat discomfort including incidence in the past 12 months, causes, severity, effects on functionality and quality of life, actions taken to relieve throat discomfort, the efficacy of these approaches and the reasons behind using specific products. Results In total, 6465 men and women aged ≥18 years were surveyed, identifying 3514 participants who had suffered throat discomfort/irritation in the past 12 months (response rate of 54%. These participants completed the full survey. The breakdown of throat discomfort sufferers was: UK, 912; France, 899; Poland, 871; Malaysia, 832. A high proportion of respondents experienced one or more instances of throat discomfort in the previous 12 months, with an overall incidence of 54%. Infections including the common cold/influenza and other bacteria/viruses were commonly perceived causes of throat discomfort (72% and 46%, respectively. Physical and environmental factors were also perceived to be causative, including airborne pollution (28%, smoking (23%, and air conditioning (31%. Symptoms perceived to be caused by an infection were associated with a higher degree of suffering (mean degree of suffering for bacteria/virus and common cold/influenza; 3.4 and 3.0, respectively. Medicinal products were used for all perceived causes, but more

  3. Incidence, causes, severity and treatment of throat discomfort: a four-region online questionnaire survey.

    Science.gov (United States)

    Addey, Dilys; Shephard, Adrian

    2012-08-10

    Acute sore throat is commonly associated with viral infections. Consumers typically rely on over-the-counter treatments and other remedies to treat symptoms; however, limited information is available regarding consumer perceptions of sore throat or treatment needs. The aim of this study was to investigate perceptions of throat discomfort and how these influence attitudes and consumer behaviour with regard to treatment. Online consumer surveys were completed by participants invited by email between 2003 and 2004 in four markets: the UK, France, Poland, and Malaysia. The questionnaire consisted of 24 questions that covered key issues surrounding throat discomfort including incidence in the past 12 months, causes, severity, effects on functionality and quality of life, actions taken to relieve throat discomfort, the efficacy of these approaches and the reasons behind using specific products. In total, 6465 men and women aged ≥18 years were surveyed, identifying 3514 participants who had suffered throat discomfort/irritation in the past 12 months (response rate of 54%). These participants completed the full survey. The breakdown of throat discomfort sufferers was: UK, 912; France, 899; Poland, 871; Malaysia, 832. A high proportion of respondents experienced one or more instances of throat discomfort in the previous 12 months, with an overall incidence of 54%. Infections including the common cold/influenza and other bacteria/viruses were commonly perceived causes of throat discomfort (72% and 46%, respectively). Physical and environmental factors were also perceived to be causative, including airborne pollution (28%), smoking (23%), and air conditioning (31%). Symptoms perceived to be caused by an infection were associated with a higher degree of suffering (mean degree of suffering for bacteria/virus and common cold/influenza; 3.4 and 3.0, respectively). Medicinal products were used for all perceived causes, but more commonly for sore throats thought to be caused by

  4. Loss of Polycomb Group Protein Pcgf1 Severely Compromises Proper Differentiation of Embryonic Stem Cells

    Science.gov (United States)

    Yan, Yun; Zhao, Wukui; Huang, Yikai; Tong, Huan; Xia, Yin; Jiang, Qing; Qin, Jinzhong

    2017-01-01

    The Polycomb repressive complex 1 (PRC1) is essential for fate decisions of embryonic stem (ES) cells. Emerging evidence suggests that six major variants of PRC1 complex, defined by the mutually exclusive presence of Pcgf subunit, regulate distinct biological processes, yet very little is known about the mechanism by which each version of PRC1 instructs and maintains cell fate. Here, we disrupted the Pcgf1, also known as Nspc1 and one of six Pcgf paralogs, in mouse ES cells by the CRISPR/Cas9 technology. We showed that although these mutant cells were viable and retained normal self-renewal, they displayed severe defects in differentiation in vitro. To gain a better understanding of the role of Pcgf1 in transcriptional control of differentiation, we analysed mRNA profiles from Pcgf1 deficient cells using RNA-seq. Interestingly, we found that Pcgf1 positively regulated expression of essential transcription factors involved in ectoderm and mesoderm differentiation, revealing an unexpected function of Pcgf1 in gene activation during ES cell lineage specification. Chromatin immunoprecipitation experiments demonstrated that Pcgf1 deletion caused a decrease in Ring1B and its associated H2AK119ub1 mark binding to target genes. Altogether, our results suggested an unexpected function of Pcgf1 in gene activation during ES cell maintenance. PMID:28393894

  5. Progressive troponin I loss impairs cardiac relaxation and causes heart failure in mice.

    Science.gov (United States)

    Liu, Jing; Du, Jianfeng; Zhang, Chi; Walker, Jeffery W; Huang, Xupei

    2007-08-01

    Cardiac troponin I (TnI) knockout mice exhibit a phenotype of sudden death at 17-18 days after birth due to a progressive loss of TnI. The objective of this study was to gain insight into the physiological consequences of TnI depletion and the cause of death in these mice. Cardiac function was monitored serially between 12 and 17 days of age by using high-resolution ultrasonic imaging and Doppler echocardiography. Two-dimensional B-mode and anatomical M-mode imaging and Doppler echocardiography were performed using a high-frequency ( approximately 20-45 MHz) ultrasound imaging system on homozygous cardiac TnI mutant mice (cTnI(-/-)) and wild-type littermates. On day 12, cTnI(-/-) mice were indistinguishable from wild-type mice in terms of heart rate, atrial and LV (LV) chamber dimensions, LV posterior wall thickness, and body weight. By days 16 through 17, wild-type mice showed up to a 40% increase in chamber dimensions due to normal growth, whereas cTnI(-/-) mice showed increases in atrial dimensions of up to 97% but decreases in ventricular dimensions of up to 70%. Mitral Doppler analysis revealed prolonged isovolumic relaxation time and pronounced inversion of the mitral E/A ratio (early ventricular filling wave-to-late atrial contraction filling wave) only in cTnI(-/-) mice indicative of impaired LV relaxation. cTnI(-/-) mouse hearts showed clear signs of failure on day 17, characterized by >50% declines in cardiac output, ejection fraction, and fractional shortening. B-mode echocardiography showed a profoundly narrowed tube-like LV and enlarged atria at this time. Our data are consistent with TnI deficiency causing impaired LV relaxation, which leads to diastolic heart failure in this model.

  6. Lymphatic Endothelial Cells Produce M-CSF, Causing Massive Bone Loss in Mice.

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    Wang, Wensheng; Wang, Hua; Zhou, Xichao; Li, Xing; Sun, Wen; Dellinger, Michael; Boyce, Brendan F; Xing, Lianping

    2017-01-04

    Gorham-Stout disease (GSD) is a rare bone disorder characterized by aggressive osteolysis associated with lymphatic vessel invasion within bone marrow cavities. The etiology of GSD is not known, and there is no effective therapy or animal model for the disease. Here, we investigated if lymphatic endothelial cells (LECs) affect osteoclasts (OCs) to cause a GSD osteolytic phenotype in mice. We examined the effect of a mouse LEC line on osteoclastogenesis in co-cultures. LECs significantly increased receptor activator of NF-κB ligand (RANKL)-mediated OC formation and bone resorption. LECs expressed high levels of macrophage colony-stimulating factor (M-CSF), but not RANKL, interleukin-6 (IL-6), and tumor necrosis factor (TNF). LEC-mediated OC formation and bone resorption were blocked by an M-CSF neutralizing antibody or Ki20227, an inhibitor of the M-CSF receptor, c-Fms. We injected LECs into the tibias of wild-type (WT) mice and observed massive osteolysis on X-ray and micro-CT scans. Histology showed that LEC-injected tibias had significant trabecular and cortical bone loss and increased OC numbers. M-CSF protein levels were significantly higher in serum and bone marrow plasma of mice given intra-tibial LEC injections. Immunofluorescence staining showed extensive replacement of bone and marrow by podoplanin+ LECs. Treatment of LEC-injected mice with Ki20227 significantly decreased tibial bone destruction. In addition, lymphatic vessels in a GSD bone sample were stained positively for M-CSF. Thus, LECs cause bone destruction in vivo in mice by secreting M-CSF, which promotes OC formation and activation. Blocking M-CSF signaling may represent a new therapeutic approach for treatment of patients with GSD. Furthermore, tibial injection of LECs is a useful mouse model to study GSD. © 2017 American Society for Bone and Mineral Research.

  7. TUBA1A mutation can cause a hydranencephaly-like severe form of cortical dysgenesis.

    Science.gov (United States)

    Yokoi, Setsuri; Ishihara, Naoko; Miya, Fuyuki; Tsutsumi, Makiko; Yanagihara, Itaru; Fujita, Naoko; Yamamoto, Hiroyuki; Kato, Mitsuhiro; Okamoto, Nobuhiko; Tsunoda, Tatsuhiko; Yamasaki, Mami; Kanemura, Yonehiro; Kosaki, Kenjiro; Kojima, Seiji; Saitoh, Shinji; Kurahashi, Hiroki; Natsume, Jun

    2015-10-23

    TUBA1A mutations cause a wide spectrum of lissencephaly and brain malformations. Here, we report two patients with severe cortical dysgeneses, one with an extremely thin cerebral parenchyma apparently looking like hydranencephaly and the other with lissencephaly accompanied by marked hydrocephalus, both harbouring novel de novo missense mutations of TUBA1A. To elucidate how the various TUBA1A mutations affect the severity of the phenotype, we examined the capacity of the mutant protein to incorporate into the endogenous microtubule network in transfected COS7 cells by measuring line density using line extraction in an immunofluorescence study. The mutants responsible for severe phenotypes were found to incorporate extensively into the network. To determine how each mutant alters the microtubule stability, we examined cold-induced microtubule depolymerisation in fibroblasts. The depolymerisation of patients' fibroblasts occurred earlier than that of control fibroblasts, suggesting that microtubules bearing mutated tubulins are unstable. Both mutations are predicted to participate in lateral interactions of microtubules. Our data suggest that the TUBA1A mutations disrupting lateral interactions have pronounced dominant-negative effects on microtubule dynamics that are associated with the severe end of the lissencephaly spectrum.

  8. Comparing the Pain Severity Caused by Muscular Injection of Tramadole in Z and Bulb Methods

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    SH Najafi Doulatabad

    2008-01-01

    Full Text Available ABSTRACT: Introduction & Objective: Pain, rather than any other problems, would persuade people to pursue remedy and treatment. Muscular injections are among pain producing factors. This technique of prescription can be followed by some complications from which pain is the most prevalent one. This study was performed to compare the pain severity caused by muscular injection of Tramadole in Z and Bulb methods. Materials & Methods: This is a clinical trial study in which 90 women who referred to the emergency ward of Shahid Beheshti hospital in Yasooj in 2006 were randomly selected. Data collection instrument was questionnaire. The pain severity was evaluated by visual scale. Data were analyzed by descriptive statistical method, independent T and chi square test using SPSS software. Results: Mean of pain severity in bulb method was 2.84±1.242 and in Z method was 4.56±1.659. The independent T test indicated that the differences in pain severity in two injection methods were statistically significant (p=0.036. No significant differences were found between age, educational level, job, marriatal status, number of previous injections and BMI of samples between two groups. Conclusion: Bulb method injection induces less pain in comparison with Z method therefore it is an ideal method for muscular injections. As such, health care workers, especially nurses, can, through this method, minimize the patients’ pain, which is one of the most important injection complaints.

  9. Severe hyponatremia caused by nab-paclitaxel-induced syndrome of inappropriate antidiuretic hormone secretion

    Science.gov (United States)

    Neuzillet, Cindy; Babai, Samy; Kempf, Emmanuelle; Pujol, Géraldine; Rousseau, Benoît; Le-Louët, Hervé; Christophe Tournigand

    2016-01-01

    Abstract Incidence of pancreatic ductal adenocarcinoma (PDAC) is increasing. Most patients have advanced disease at diagnosis and therapeutic options in this setting are limited. Gemcitabine plus nab-paclitaxel regimen was demonstrated to increase survival compared with gemcitabine monotherapy and is therefore indicated as first-line therapy in patients with metastatic PDAC and performance status Eastern Cooperative Oncology Group (ECOG) 0-2. The safety profile of gemcitabine and nab-paclitaxel combination includes neutropenia, fatigue, and neuropathy as most common adverse events of grade 3 or higher. No case of severe hyponatremia associated with the use of nab-paclitaxel for the treatment of PDAC has been reported to date. We report the case of a 72-year-old Caucasian man with a metastatic PDAC treated with gemcitabine and nab-paclitaxel regimen, who presented with a severe hyponatremia (grade 4) caused by a documented syndrome of inappropriate antidiuretic hormone secretion (SIADH). This SIADH was attributed to nab-paclitaxel after a rigorous imputability analysis, including a rechallenge procedure with dose reduction. After dose and schedule adjustment, nab-paclitaxel was pursued without recurrence of severe hyponatremia and with maintained efficacy. Hyponatremia is a rare but potentially severe complication of nab-paclitaxel therapy that medical oncologists and gastroenterologists should be aware of. Nab-paclitaxel-induced hyponatremia is manageable upon dose and schedule adaptation, and should not contraindicate careful nab-paclitaxel reintroduction. This is of particular interest for a disease in which the therapeutic options are limited. PMID:27368013

  10. Superior Mesenteric Vein Occlusion Causing Severe Gastrointestinal Haemorrhage in Two Paediatric Cases

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    Anna L. Fox

    2012-01-01

    Full Text Available Reports about superior mesenteric vein thrombosis in childhood are very rare and have not been associated with gastrointestinal bleeding. We describe two cases of severe bleeding from the upper and lower gastrointestinal tract in children who had undergone complex abdominal surgery at considerable time before. The first child had a tracheoesophageal fistula, corrected by division, gastrostomy insertion, and repair of duodenal rupture. The child presented with severe bleeding from the gastrostomy site and was diagnosed with a thrombosis of the proximal superior mesenteric vein. The second child had a gastroschisis and duodenal atresia, and required duodenoplasty, gastrostomy insertion, hemicolectomy, and adhesiolysis. The child presented with intermittent severe lower gastrointestinal bleeding, resulting from collateral vessels at location of the surgical connections. He was diagnosed with a thrombosis of the superior mesenteric vein. In both children, the extensive previous surgery and anastomosis were considered the cause of the mesenteric thrombosis. CT angiography confirmed the diagnosis in both cases, in addition to characteristic findings on endoscopy. Paediatricians should suspect this condition in children with severe gastrointestinal bleeding, particularly in children with previous, complex abdominal surgery.

  11. Comparative genomics of Tunisian Leishmania major isolates causing human cutaneous leishmaniasis with contrasting clinical severity.

    Science.gov (United States)

    Ghouila, Amel; Guerfali, Fatma Z; Atri, Chiraz; Bali, Aymen; Attia, Hanene; Sghaier, Rabiaa M; Mkannez, Ghada; Dickens, Nicholas J; Laouini, Dhafer

    2017-06-01

    Zoonotic cutaneous leishmaniasis caused by Leishmania (L.) major parasites affects urban and suburban areas in the center and south of Tunisia where the disease is endemo-epidemic. Several cases were reported in human patients for which infection due to L. major induced lesions with a broad range of severity. However, very little is known about the mechanisms underlying this diversity. Our hypothesis is that parasite genomic variability could, in addition to the host immunological background, contribute to the intra-species clinical variability observed in patients and explain the lesion size differences observed in the experimental model. Based on several epidemiological, in vivo and in vitro experiments, we focused on two clinical isolates showing contrasted severity in patients and BALB/c experimental mice model. We used DNA-seq as a high-throughput technology to facilitate the identification of genetic variants with discriminating potential between both isolates. Our results demonstrate that various levels of heterogeneity could be found between both L. major isolates in terms of chromosome or gene copy number variation (CNV), and that the intra-species divergence could surprisingly be related to single nucleotide polymorphisms (SNPs) and Insertion/Deletion (InDels) events. Interestingly, we particularly focused here on genes affected by both types of variants and correlated them with the observed gene CNV. Whether these differences are sufficient to explain the severity in patients is obviously still open to debate, but we do believe that additional layers of -omic information is needed to complement the genomic screen in order to draw a more complete map of severity determinants.

  12. The Influence of the Weight Loss upon Natural Frequency Changes in Case of Severe Defects

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    Petru Florin Minda

    2012-01-01

    Full Text Available The paper presents a research regarding the use of a "virtual" material in order to compensate the loss of mass in the case of the damaged beam. Because of the loss of mass, the frequency of the beam suffer an increase over the natural frequency of the undamaged beam and so we have proposed the use of this material, having the same density with the density of the beam, in the gap left by damage.

  13. Diaphragmatic Hernias: A Cause of Unilateral Loss of The Cardiophrenic Sinus Angle

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    Elcin Zan

    2014-12-01

    Full Text Available Aim: Cardiophrenic space is the most basal portion of the mediastinum and surrounded by heart, diaphragm and chest wall. Cardiophrenic space full with fatty tissue shows a sharp angles. However, some space-occupying lesions, infections, inflammations and diaphragmatic herniation can be the cause of the blunt cardiophrenic sinus angle. The aim of this study is to determine the incidence of loss of the cardiophrenic sinus angle due to diaphragmatic hernias. Material and Method: Nine hundred eighty three consecutive chest MDCTs performed at our department were evaluated for the presence of one-sided increased cardiophrenic fat tissue. Two hundred patients who had blunting in the cardiophrenic (right or left sinus were included in the study. Density measurements proved the presence of adipose tissue in the cardiophrenic sinus in all patients. The relationship between age, gender and right or left sided atelectasis and associated diaphragmatic hernias were statistically analyzed. Results: One hundred and seven patients were female (53.5% and ninety three (46.5% were male. 28% of patients had diaphragmatic hernia. 31% of females and 24% of males had diaphragmatic hernia. Incidence of the Morgagni hernia was 14.5% and it was significantly higher in females than in males (p

  14. Oil sands mining and reclamation cause massive loss of peatland and stored carbon

    Science.gov (United States)

    Rooney, Rebecca C.; Bayley, Suzanne E.; Schindler, David W.

    2012-01-01

    We quantified the wholesale transformation of the boreal landscape by open-pit oil sands mining in Alberta, Canada to evaluate its effect on carbon storage and sequestration. Contrary to claims made in the media, peatland destroyed by open-pit mining will not be restored. Current plans dictate its replacement with upland forest and tailings storage lakes, amounting to the destruction of over 29,500 ha of peatland habitat. Landscape changes caused by currently approved mines will release between 11.4 and 47.3 million metric tons of stored carbon and will reduce carbon sequestration potential by 5,734–7,241 metric tons C/y. These losses have not previously been quantified, and should be included with the already high estimates of carbon emissions from oil sands mining and bitumen upgrading. A fair evaluation of the costs and benefits of oil sands mining requires a rigorous assessment of impacts on natural capital and ecosystem services. PMID:22411786

  15. Loss of the anaphase-promoting complex in quiescent cells causes unscheduled hepatocyte proliferation

    Science.gov (United States)

    Wirth, Karin G.; Ricci, Romeo; Giménez-Abián, Juan F.; Taghybeeglu, Shahryar; Kudo, Nobuaki R.; Jochum, Wolfram; Vasseur-Cognet, Mireille; Nasmyth, Kim

    2004-01-01

    The anaphase-promoting complex or cyclosome (APC/C) is an ubiquitin protein ligase that together with Cdc20 and Cdh1 targets mitotic proteins for degradation by the proteosome. APC–Cdc20 activity during mitosis triggers anaphase by destroying securin and cyclins. APC–Cdh1 promotes degradation of cyclins and other proteins during G1. We show that loss of APC/C during embryogenesis is early lethal before embryonic day E6.5 (E6.5). To investigate the role of APC/C in quiescent cells, we conditionally inactivated the subunit Apc2 in mice. Deletion of Apc2 in quiescent hepatocytes caused re-entry into the cell cycle and arrest in metaphase, resulting in liver failure. Re-entry into the cell cycle either occurred without any proliferative stimulus or could be easily induced. We demonstrate that the APC has an additional function to prevent hepatocytes from unscheduled re-entry into the cell cycle. PMID:14724179

  16. Severe Community-Acquired Pneumonia Caused by Human Adenovirus in Immunocompetent Adults: A Multicenter Case Series.

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    Dingyu Tan

    Full Text Available Severe community-acquired pneumonia (CAP caused by human adenovirus (HAdV, especially HAdV type 55 (HAdV-55 in immunocompetent adults has raised increasing concerns. Clinical knowledge of severe CAP and acute respiratory distress syndrome induced by HAdV-55 is still limited, though the pathogen has been fully characterized by whole-genome sequencing.We conducted a multicentre retrospective review of all consecutive patients with severe CAP caused by HAdV in immunocompetent adults admitted to the Emergency Department Intensive Care Unit of two hospitals in Northern China between February 2012 and April 2014. Clinical, laboratory, radiological characteristics, treatments and outcomes of these patients were collected and analyzed.A total of 15 consecutive severe CAP patients with laboratory-confirmed adenovirus infections were included. The median age was 30 years and all cases were identified during the winter and spring seasons. HAdV-55 was the most frequently (11/15 detected HAdV type. Persistent high fever, cough and rapid progression of dyspnea were typically reported in these patients. Significantly increased pneumonia severity index (PSI, respiratory rate, and lower PaO2/FiO2, hypersensitive CRP were reported in non-survivors compared to survivors (P = 0.013, 0.022, 0.019 and 0.026, respectively. The rapid development of bilateral consolidations within 10 days after illness onset were the most common radiographic finding, usually accompanied by adjacent ground glass opacities and pleural effusions. Total mortality was 26.7% in this study. Corticosteroids were prescribed to 14 patients in this report, but the utilization rate between survivors and non-survivors was not significant.HAdV and the HAdV-55 sub-type play an important role among viral pneumonia pathogens in hospitalized immunocompetent adults in Northern China. HAdV should be tested in severe CAP patients with negative bacterial cultures and a lack of response to antibiotic

  17. Mutations in FKBP10 can cause a severe form of isolated Osteogenesis imperfecta

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    Steinlein Ortrud K

    2011-11-01

    Full Text Available Abstract Background Mutations in the FKBP10 gene were first described in patients with Osteogenesis imperfecta type III. Two follow up reports found FKBP10 mutations to be associated with Bruck syndrome type 1, a rare disorder characterized by congenital contractures and bone fragility. This raised the question if the patients in the first report indeed had isolated Osteogenesis imperfecta or if Bruck syndrome would have been the better diagnosis. Methods The patients described here are affected by severe autosomal recessive Osteogenesis imperfecta without contractures. Results Homozygosity mapping identified FKBP10 as a candidate gene, and sequencing revealed a base pair exchange that causes a C-terminal premature stop codon in this gene. Conclusions Our study demonstrates that FKBP10 mutations not only cause Bruck syndrome or Osteogenesis imperfecta type III but can result in a severe type of isolated Osteogenesis imperfecta type IV with prenatal onset. Furthermore, it adds dentinogenesis imperfecta to the spectrum of clinical symptoms associated with FKBP10 mutations.

  18. Starvation Ketoacidosis: A Cause of Severe Anion Gap Metabolic Acidosis in Pregnancy

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    Nupur Sinha

    2014-01-01

    Full Text Available Pregnancy is a diabetogenic state characterized by relative insulin resistance, enhanced lipolysis, elevated free fatty acids and increased ketogenesis. In this setting, short period of starvation can precipitate ketoacidosis. This sequence of events is recognized as “accelerated starvation.” Metabolic acidosis during pregnancy may have adverse impact on fetal neural development including impaired intelligence and fetal demise. Short periods of starvation during pregnancy may present as severe anion gap metabolic acidosis (AGMA. We present a 41-year-old female in her 32nd week of pregnancy, admitted with severe AGMA with pH 7.16, anion gap 31, and bicarbonate of 5 mg/dL with normal lactate levels. She was intubated and accepted to medical intensive care unit. Urine and serum acetone were positive. Evaluation for all causes of AGMA was negative. The diagnosis of starvation ketoacidosis was established in absence of other causes of AGMA. Intravenous fluids, dextrose, thiamine, and folic acid were administered with resolution of acidosis, early extubation, and subsequent normal delivery of a healthy baby at full term. Rapid reversal of acidosis and favorable outcome are achieved with early administration of dextrose containing fluids.

  19. Severe cervical kyphotic deformity caused by postural disorders in a child with schizophrenia.

    Science.gov (United States)

    Saito, Wataru; Imura, Takayuki; Ueno, Masaki; Nakazawa, Toshiyuki; Takahira, Naonobu; Takaso, Masashi

    2013-08-01

    Although severe cervical kyphotic deformity results from a number of causes, the psychiatric disease itself did not play a metabolic role in the development of the deformity. However, we diagnosed a case of cervical deformity caused by postural disorders associated with schizophrenia. The purpose of this case report is to describe a rare episode in a schizophrenic patient with a fixed cervical flexion deformity caused by postural disorders. A case report. An 18-year-old woman with a history of schizophrenia and a persistent behavioral cervical flexion posture presented for evaluation. At the initial examination, a significant fixed cervical flexion measuring 100° was noted. Her chin was in contact with her manubrium, and left scars developed on both her chin and manubrium. She had hyperreflexia in all extremities but no further neurologic deficits, although her initial magnetic resonance imaging (MRI) indicated multilevel cervical cord compression. She was initially treated conservatively but had a progression in fixed cervical flexion positioning. She complained of a persistent inability to ambulate within the community, as she was unable to bring her head into a neutral position to be able to see objects in her path. She also complained of inability to drink from a water bottle as she had difficulty depressing her mandible. The patient and her family requested a surgical correction. Although she had no significant clinical neurologic deficit, she did have significant MRI findings and limitation of functional activities. We felt her limitations were significant enough to warrant surgical correction. A combined anterior and posterior procedure was performed resulting in an improved cervical head posture. She was able to return to community activities and resume drinking from a water bottle. Although this technique has been well described previously, this is the first report of a rare episode in a schizophrenic patient with severe cervical kyphosis deformity

  20. Loss of caveolin-1 causes blood-retinal barrier breakdown, venous enlargement, and mural cell alteration.

    Science.gov (United States)

    Gu, Xiaowu; Fliesler, Steven J; Zhao, You-Yang; Stallcup, William B; Cohen, Alex W; Elliott, Michael H

    2014-02-01

    Blood-retinal barrier (BRB) breakdown and related vascular changes are implicated in several ocular diseases. The molecules and mechanisms regulating BRB integrity and pathophysiology are not fully elucidated. Caveolin-1 (Cav-1) ablation results in loss of caveolae and microvascular pathologies, but the role of Cav-1 in the retina is largely unknown. We examined BRB integrity and vasculature in Cav-1 knockout mice and found a significant increase in BRB permeability, compared with wild-type controls, with branch veins being frequent sites of breakdown. Vascular hyperpermeability occurred without apparent alteration in junctional proteins. Such hyperpermeability was not rescued by inhibiting eNOS activity. Veins of Cav-1 knockout retinas exhibited additional pathological features, including i) eNOS-independent enlargement, ii) altered expression of mural cell markers (eg, down-regulation of NG2 and up-regulation of αSMA), and iii) dramatic alterations in mural cell phenotype near the optic nerve head. We observed a significant NO-dependent increase in retinal artery diameter in Cav-1 knockout mice, suggesting that Cav-1 plays a role in autoregulation of resistance vessels in the retina. These findings implicate Cav-1 in maintaining BRB integrity in retinal vasculature and suggest a previously undefined role in the retinal venous system and associated mural cells. Our results are relevant to clinically significant retinal disorders with vascular pathologies, including diabetic retinopathy, uveoretinitis, and primary open-angle glaucoma.

  1. Vestibular loss and balance training cause similar changes in human cerebral white matter fractional anisotropy.

    Science.gov (United States)

    Hummel, Nadine; Hüfner, Katharina; Stephan, Thomas; Linn, Jennifer; Kremmyda, Olympia; Brandt, Thomas; Flanagin, Virginia L

    2014-01-01

    Patients with bilateral vestibular loss suffer from severe balance deficits during normal everyday movements. Ballet dancers, figure skaters, or slackliners, in contrast, are extraordinarily well trained in maintaining balance for the extreme balance situations that they are exposed to. Both training and disease can lead to changes in the diffusion properties of white matter that are related to skill level or disease progression respectively. In this study, we used diffusion tensor imaging (DTI) to compare white matter diffusivity between these two study groups and their age- and sex-matched controls. We found that vestibular patients and balance-trained subjects show a reduction of fractional anisotropy in similar white matter tracts, due to a relative increase in radial diffusivity (perpendicular to the main diffusion direction). Reduced fractional anisotropy was not only found in sensory and motor areas, but in a widespread network including long-range connections, limbic and association pathways. The reduced fractional anisotropy did not correlate with any cognitive, disease-related or skill-related factors. The similarity in FA between the two study groups, together with the absence of a relationship between skill or disease factors and white matter changes, suggests a common mechanism for these white matter differences. We propose that both study groups must exert increased effort to meet their respective usual balance requirements. Since balance training has been shown to effectively reduce the symptoms of vestibular failure, the changes in white matter shown here may represent a neuronal mechanism for rehabilitation.

  2. Massive hard coral loss after a severe bleaching event in 2010 at Los Roques, Venezuela

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    Carolina Bastidas

    2012-03-01

    Full Text Available Thermal anomalies have become more severe, frequent and well-documented across the Caribbean for the past 30 years. This increase in temperature has caused coral bleaching resulting in reef decline. At Los Roques National Park, Venezuela, temperature has been monitored at four reef sites. In mid-September 2010, seawater temperature reached 30.85°C at 5 m depth in Los Roques, an archipelago only slightly affected by previous bleaching events. For example, bleaching in Los Roques in 2005 was mild compared to the rest of the Caribbean and to the results in this study. In 2010, seawater temperatures remained above 29.0°C from mid-August until the first week of November, resulting in +16 Degree Heating Weeks by that time. Our annual survey of four reef sites indicated that 72% of 563 scleractinian colonies were partial or totally bleached (white or pale (discolored in October 2010. In February 2011, there were still 46% of coral colonies affected; but most of them were pale and only 2% were bleached. By February, coral cover had declined 4 to 30% per transect, with a mean of 14.3%. Thus, mean coral cover dropped significantly from 45 to 31% cover (a 34% reduction. In addition to bleaching, corals showed a high prevalence (up to 16% of black band disease in October 2010 and of white plague (11% in February 2011. As a consequence, coral mortality is expected to be larger than reported here. Reef surveys since 2002 and personal observations for more than 20 years indicated that this bleaching event and its consequences in Los Roques have no precedent. Our results suggest that reef sites with no previous record of significant deterioration are more likely to become affected by thermal anomalies. However, this archipelago is relatively unaffected by local anthropogenic disturbance and has a high coral recruitment, which may contribute to its recovery

  3. Severe visual Impairment and blindness in infants: Causes and opportunities for control

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    Parikshit Gogate

    2011-01-01

    Full Text Available Childhood blindness has an adverse effect on growth, development, social, and economic opportunities. Severe visual impairment (SVI and blindness in infants must be detected as early as possible to initiate immediate treatment to prevent deep amblyopia. Although difficult, measurement of visual acuity of an infant is possible. The causes of SVI and blindness may be prenatal, perinatal, and postnatal. Congenital anomalies such as anophthalmos, microphthalmos, coloboma, congenital cataract, infantile glaucoma, and neuro-ophthalmic lesions are causes of impairment present at birth. Ophthalmia neonatorum, retinopathy of prematurity, and cortical visual impairment are acquired during the perinatal period. Leukocoria or white pupillary reflex can be cause by congenital cataract, persistent hyperplastic primary vitreous, or retinoblastoma. While few medical or surgical options are available for congenital anomalies or neuro-ophthalmic disorders, many affected infants can still benefit from low vision aids and rehabilitation. Ideally, surgery for congenital cataracts should occur within the first 4 months of life. Anterior vitrectomy and primary posterior capsulotomy are required, followed by aphakic glasses with secondary intraocular lens implantation at a later date. The treatment of infantile glaucoma is surgery followed by anti-glaucoma medication. Retinopathy of prematurity is a proliferation of the retinal vasculature in response to relative hypoxia in a premature infant. Screening in the first few weeks of life can prevent blindness. Retinoblastoma can be debulked with chemotherapy; however, enucleation may still be required. Neonatologists, pediatricians, traditional birth attendants, nurses, and ophthalmologists should be sensitive to a parent′s complaints of poor vision in an infant and ensure adequate follow-up to determine the cause. If required, evaluation under anesthesia should be performed, which includes funduscopy, refraction

  4. A nairovirus isolated from African bats causes haemorrhagic gastroenteritis and severe hepatic disease in mice.

    Science.gov (United States)

    Ishii, Akihiro; Ueno, Keisuke; Orba, Yasuko; Sasaki, Michihito; Moonga, Ladslav; Hang'ombe, Bernard M; Mweene, Aaron S; Umemura, Takashi; Ito, Kimihito; Hall, William W; Sawa, Hirofumi

    2014-12-02

    Bats can carry important zoonotic pathogens. Here we use a combination of next-generation sequencing and classical virus isolation methods to identify novel nairoviruses from bats captured from a cave in Zambia. This nairovirus infection is highly prevalent among giant leaf-nosed bats, Hipposideros gigas (detected in samples from 16 individuals out of 38). Whole-genome analysis of three viral isolates (11SB17, 11SB19 and 11SB23) reveals a typical bunyavirus tri-segmented genome. The strains form a single phylogenetic clade that is divergent from other known nairoviruses, and are hereafter designated as Leopards Hill virus (LPHV). When i.p. injected into mice, the 11SB17 strain causes only slight body weight loss, whereas 11SB23 produces acute and lethal disease closely resembling that observed with Crimean-Congo Haemorrhagic Fever virus in humans. We believe that our LPHV mouse model will be useful for research on the pathogenesis of nairoviral haemorrhagic disease.

  5. Airbag-Associated Severe Blunt Eye Injury Causes Choroidal Rupture and Retinal Hemorrhage: A Case Report

    Directory of Open Access Journals (Sweden)

    Shih Hao Wang

    2017-01-01

    Full Text Available A case of choroidal rupture caused by airbag-associated blunt eye trauma and complicated with massive subretinal hemorrhage and vitreous hemorrhage that was successfully treated with intravitreal injection of expansile gas and bevacizumab is presented. A 53-year-old man suffered from loss of vision in his right eye due to blunt eye trauma by a safety airbag after a traffic accident. On initial examination, the patient had no light perception in his right eye. Dilated ophthalmoscopy revealed massive subretinal hemorrhage with macular invasion and faint vitreous hemorrhage. We performed intravitreal injection of pure sulfur hexafluoride twice for displacement, after which visual acuity improved to 0.03. For persistent subretinal hemorrhage and suspicion of choroidal neovascularization (CNV, intravitreal bevacizumab (1.25 mg/0.05 mL injection was administered. After 3 weeks, the visual acuity of his right eye recovered to 0.4. For early-stage choroidal rupture-induced subretinal hemorrhage and complications of suspected CNV, intravitreal injection of expandable gas and intraocular injection of antiangiogenesis drugs seem to be an effective treatment.

  6. Double knockout of pendrin and Na-Cl cotransporter (NCC) causes severe salt wasting, volume depletion, and renal failure.

    Science.gov (United States)

    Soleimani, Manoocher; Barone, Sharon; Xu, Jie; Shull, Gary E; Siddiqui, Faraz; Zahedi, Kamyar; Amlal, Hassane

    2012-08-14

    The Na-Cl cotransporter (NCC), which is the target of inhibition by thiazides, is located in close proximity to the chloride-absorbing transporter pendrin in the kidney distal nephron. Single deletion of pendrin or NCC does not cause salt wasting or excessive diuresis under basal conditions, raising the possibility that these transporters are predominantly active during salt depletion or in response to excess aldosterone. We hypothesized that pendrin and NCC compensate for loss of function of the other under basal conditions, thereby masking the role that each plays in salt absorption. To test our hypothesis, we generated pendrin/NCC double knockout (KO) mice by crossing pendrin KO mice with NCC KO mice. Pendrin/NCC double KO mice displayed severe salt wasting and sharp increase in urine output under basal conditions. As a result, animals developed profound volume depletion, renal failure, and metabolic alkalosis without hypokalemia, which were all corrected with salt replacement. We propose that the combined inhibition of pendrin and NCC can provide a strong diuretic regimen without causing hypokalemia for patients with fluid overload, including patients with congestive heart failure, nephrotic syndrome, diuretic resistance, or generalized edema.

  7. Natural Disasters under the Form of Severe Storms in Europe: the Cause-Effect Analysis

    Directory of Open Access Journals (Sweden)

    Virginia Câmpeanu

    2009-07-01

    Full Text Available For more than 100 years, from 1900 to 2008, there were almost 400 storms natural disasters in Europe, 40% of which occurred in the 1990s. The international prognoses for the world weather suggest a tendency toward increasing in frequency and intensity of the severe storms as the climate warms. In these circumstances, for a researcher in the field of Environmental Economics, a natural question occurs, on whether people can contribute to reducing the frequency and the magnitude of severe storms that produce disastreous social and economic effects, by acting on their causes. In researching an answer to support the public policies in the field, a cause-effect analysis applied to Europe might make a contribution to the literature in the field. This especially considering the fact that international literature regarding the factors influencing global warming contains certainties in regard to the natural factors of influence, but declared incertitudes or skepticism in regard to anthropogenic ones. Skepticism, and even tension arised during the international negotiations in Copenhagen (December 2009 in regard to the agreement for limiting global warming, with doubts being raised about the methods used by experts of the International Climate Experts Group (GIEC, and thus the results obtained, which served as a basis for the negotiations. The object of critics was in regard to the form, and at times in regard to the content. It was not about contesting the phenomenon of Global warming during the negotiations, but the methods of calculation. The methodology relies on qualitative (type top down and quantitative (type correlations bottom up cause-effect analysis of the storm disasters in Europe. Based on the instruments used, we proposed a dynamic model of association of the evolution of storm disasters in Europe with anthropogenic factors, with 3 variants. Results: The diagram cause-effect (Ishikawa or fishbone diagram and quantitative correlation of sub

  8. Economic valuation of environmental costs of soil erosion and the loss of biodiversity and ecosystem services caused by food wastage

    OpenAIRE

    Patrizia Schwegler

    2015-01-01

    Food wastage costs society far more than the direct economic loss of US$ 750 billion per year. When food is discarded, all embodied natural resources are wasted, too. The aim of this study is to estimate global environmental costs of soil erosion and the loss of biodiversity and ecosystem services caused by food wastage. Firstly, environmental indicators and their quantities such as soil erosion rates, N, P and pesticide inputs and land use changes to agricultural production were assessed thr...

  9. Staphylococcus aureus seroproteomes discriminate ruminant isolates causing mild or severe mastitis

    Science.gov (United States)

    2011-01-01

    Staphylococcus aureus is a major cause of mastitis in ruminants. In ewe mastitis, symptoms range from subclinical to gangrenous mastitis. S. aureus factors or host-factors contributing to the different outcomes are not completely elucidated. In this study, experimental mastitis was induced on primiparous ewes using two S. aureus strains, isolated from gangrenous (strain O11) or subclinical (strain O46) mastitis. Strains induced drastically distinct clinical symptoms when tested in ewe and mice experimental mastitis. Notably, they reproduced mild (O46) or severe (O11) mastitis in ewes. Ewe sera were used to identify staphylococcal immunoreactive proteins commonly or differentially produced during infections of variable severity and to define core and accessory seroproteomes. Such SERological Proteome Analysis (SERPA) allowed the identification of 89 immunoreactive proteins, of which only 52 (58.4%) were previously identified as immunogenic proteins in other staphylococcal infections. Among the 89 proteins identified, 74 appear to constitute the core seroproteome. Among the 15 remaining proteins defining the accessory seroproteome, 12 were specific for strain O11, 3 were specific for O46. Distribution of one protein specific for each mastitis severity was investigated in ten other strains isolated from subclinical or clinical mastitis. We report here for the first time the identification of staphylococcal immunogenic proteins common or specific to S. aureus strains responsible for mild or severe mastitis. These findings open avenues in S. aureus mastitis studies as some of these proteins, expressed in vivo, are likely to account for the success of S. aureus as a pathogen of the ruminant mammary gland. PMID:21324116

  10. Staphylococcus aureus seroproteomes discriminate ruminant isolates causing mild or severe mastitis

    Directory of Open Access Journals (Sweden)

    Le Maréchal Caroline

    2011-02-01

    Full Text Available Abstract Staphylococcus aureus is a major cause of mastitis in ruminants. In ewe mastitis, symptoms range from subclinical to gangrenous mastitis. S. aureus factors or host-factors contributing to the different outcomes are not completely elucidated. In this study, experimental mastitis was induced on primiparous ewes using two S. aureus strains, isolated from gangrenous (strain O11 or subclinical (strain O46 mastitis. Strains induced drastically distinct clinical symptoms when tested in ewe and mice experimental mastitis. Notably, they reproduced mild (O46 or severe (O11 mastitis in ewes. Ewe sera were used to identify staphylococcal immunoreactive proteins commonly or differentially produced during infections of variable severity and to define core and accessory seroproteomes. Such SERological Proteome Analysis (SERPA allowed the identification of 89 immunoreactive proteins, of which only 52 (58.4% were previously identified as immunogenic proteins in other staphylococcal infections. Among the 89 proteins identified, 74 appear to constitute the core seroproteome. Among the 15 remaining proteins defining the accessory seroproteome, 12 were specific for strain O11, 3 were specific for O46. Distribution of one protein specific for each mastitis severity was investigated in ten other strains isolated from subclinical or clinical mastitis. We report here for the first time the identification of staphylococcal immunogenic proteins common or specific to S. aureus strains responsible for mild or severe mastitis. These findings open avenues in S. aureus mastitis studies as some of these proteins, expressed in vivo, are likely to account for the success of S. aureus as a pathogen of the ruminant mammary gland.

  11. Neurodevelopmental Disorders in Children with Severe to Profound Sensorineural Hearing Loss: A Clinical Study

    Science.gov (United States)

    Chilosi, Anna M.; Comparini, Alessandro; Scusa, Maria F.; Berrettini, Stefano; Forli, Francesca; Battini, Roberta; Cipriani, Paola; Cioni, Giovanni

    2010-01-01

    Aim: The effects of sensorineural hearing loss (SNHL) are often complicated by additional disabilities, but the epidemiology of associated disorders is not clearly defined. The aim of this study was to evaluate the frequency and type of additional neurodevelopmental disabilities in a sample of children with SNHL and to investigate the relation…

  12. Recovery of Populus tremuloides seedlings following severe drought causing total leaf mortality and extreme stem embolism.

    Science.gov (United States)

    Lu, Yanyuan; Equiza, Maria Alejandra; Deng, Xiping; Tyree, Melvin T

    2010-11-01

    In contrast with other native Populus species in North America, Populus tremuloides (aspen) can successfully establish itself in drought-prone areas, yet no comprehensive analysis has been performed on the ability of seedlings to withstand and recover from a severe drought resulting in complete leaf mortality. Here, we subjected 4-month-old aspen seedlings grown in two contrasting soil media to a progressive drought until total leaf mortality, followed by a rewatering cycle. Stomatal conductance (g(s) ), photosynthesis and transpiration followed a sigmoid decline with declining fraction of extractable soil water values. Cessation of leaf expansion occurred close to the end of the linear-decrease phase, when g(s) was reduced by 95%. Leaf mortality started after g(s) reached the lowest values, which corresponded to a stem-xylem pressure potential (Ψ(xp)) of -2.0 MPa and a percent loss of stem hydraulic conductivity (PLC) of 50%. In plants with 50% leaf mortality, PLC values remained around 50%. Complete leaf mortality occurred at an average stem PLC of 90%, but all seedlings were able to resprout after 6-10 days of being rewatered. Plants decapitated at soil level before rewatering developed root suckers, while those left with a 4-cm stump or with their stems intact resprouted exclusively from axillary buds. Resprouting was accompanied by recovery of stem hydraulic conductivity, with PLC values around 30%. The percentage of resprouted buds was negatively correlated with the stem %PLC. Thus, the recovery of stem hydraulic conductivity appears as an important factor in the resprouting capacity of aspen seedlings following a severe drought. Copyright © Physiologia Plantarum 2010.

  13. Temporary management of permanent central incisors loss caused by trauma in primary dentition with natural crowns: a case report.

    Science.gov (United States)

    Tüzüner, Tamer; Kuşgöz, Adem; Nur, Bilge Gülsüm

    2009-10-01

    Primary teeth injuries may cause developmental disturbances in the permanent dentition and loss of permanent incisors could be treated with different options. In this case report, an 11-year-old boy, with a history of trauma at the age of 4 years, is presented. Premature loss of permanent upper right central and upper left central teeth because of the mobility and arrest in root development were treated using patient's own natural crowns on a removable appliance. This treatment option could be considered as an esthetic and functional temporary management of permanent central incisors loss until the definitive treatment will be completed in the future.

  14. Macrophage-restricted interleukin-10 receptor deficiency, but not IL-10 deficiency, causes severe spontaneous colitis.

    Science.gov (United States)

    Zigmond, Ehud; Bernshtein, Biana; Friedlander, Gilgi; Walker, Catherine R; Yona, Simon; Kim, Ki-Wook; Brenner, Ori; Krauthgamer, Rita; Varol, Chen; Müller, Werner; Jung, Steffen

    2014-05-15

    Interleukin-10 (IL-10) is a pleiotropic anti-inflammatory cytokine produced and sensed by most hematopoietic cells. Genome-wide association studies and experimental animal models point at a central role of the IL-10 axis in inflammatory bowel diseases. Here we investigated the importance of intestinal macrophage production of IL-10 and their IL-10 exposure, as well as the existence of an IL-10-based autocrine regulatory loop in the gut. Specifically, we generated mice harboring IL-10 or IL-10 receptor (IL-10Rα) mutations in intestinal lamina propria-resident chemokine receptor CX3CR1-expressing macrophages. We found macrophage-derived IL-10 dispensable for gut homeostasis and maintenance of colonic T regulatory cells. In contrast, loss of IL-10 receptor expression impaired the critical conditioning of these monocyte-derived macrophages and resulted in spontaneous development of severe colitis. Collectively, our results highlight IL-10 as a critical homeostatic macrophage-conditioning agent in the colon and define intestinal CX3CR1(hi) macrophages as a decisive factor that determines gut health or inflammation.

  15. Types and severity of operated supraclavicular brachial plexus injuries caused by traffic accidents.

    Science.gov (United States)

    Kaiser, Radek; Waldauf, Petr; Haninec, Pavel

    2012-07-01

    Brachial plexus injuries occur in up to 5% of polytrauma cases involving motorcycle accidents and in approximately 4% of severe winter sports injuries. One of the criteria for a successful operative therapy is the type of lesion. Upper plexus palsy has the best prognosis, whereas lower plexus palsy is surgically untreatable. The aim of this study was to evaluate a group of patients with brachial plexus injury caused by traffic accidents, categorize the injuries according to type of accident, and look for correlations between type of palsy (injury) and specific accidents. A total of 441 brachial plexus reconstruction patients from our department were evaluated retrospectively(1993 to 2011). Sex, age, neurological status, and the type and cause of injury were recorded for each case. Patients with BPI caused by a traffic accident were assessed in detail. Traffic accidents were the cause of brachial plexus injury in most cases (80.7%). The most common type of injury was avulsion of upper root(s) (45.7%) followed by rupture (28.2%), complete avulsion (16.9%) and avulsion of lower root(s) (9.2%). Of the patients, 73.9% had an upper,22.7% had a complete and only 3.4% had a lower brachial plexus palsy. The main cause was motorcycle accidents(63.2%) followed by car accidents (23.5%), bicycle accidents(10.7%) and pedestrian collisions (3.1%) (paccidents had a higher percentage of lower avulsion (22.7%) and a lower percentage of upper avulsion (29.3%), whereas cyclists had a higher percentage of upper avulsion (68.6%) based on the data from the entire group of patients (paccidents (9.3%,paccidents),significantly more upper and fewer lower palsies were present. In the bicycle accident group, upper palsy was the most common (89%). Study results indicate that the most common injury was an upper plexus palsy. It was characteristic of bicycle accidents, and significantly more common in car and motorcycle accidents. The results also indicate that it is important to consider the

  16. Severe scalp hair loss in a female patient with acromegaly treated with lanreotide autogel after unsuccessful surgery.

    Science.gov (United States)

    Alvarez-Escola, Cristina; Cárdenas-Salas, Jersy J; Pelegrina, Beatriz; Sanz-Valtierra, Angel; Lecumberri, Beatriz

    2015-11-01

    Scalp hair loss is an underreported adverse event of somatostatin analogs therapy that in severe cases may require treatment withdrawal. It can be related to an acute decrease in GH/IGF-1 levels, but a direct effect cannot be ruled out.

  17. Cytolethal distending toxin-producing Escherichia coli strains causing severe diarrhoea in young Mexican children

    Science.gov (United States)

    Maldonado-Puga, Samantha; Huerta-Cantillo, Jazmin; Chavez-Dueñas, Lucia; Navarro-Garcia, Fernando

    2017-01-01

    Introduction. Cytolethal distending toxins (CDTs), encoded by cdt genes, have DNase activity leading to cellular and nuclear distension, resulting in irreversible cell cycle arrest and apoptosis of target cells. cdt-positive Escherichia coli strains have been isolated from children with diarrhoea. There is, however, scant information on the prevalence and clinical presentation of diarrhoeal disease caused by these strains. Furthermore, toxin production of cdt-positive strains is rarely confirmed. We report five young children with diarrhoea caused by CDT-producing E. coli in whom stools were negative for other bacterial or enteric pathogens. Case presentation. On admission to hospital, all children presented watery diarrhoea with high stool output (range 7–20 stools/24 h); five had fever of 38 °C or more and four presented vomiting. Dehydration was present in four patients, one of whom had hypovolaemic shock; one child also presented hyponatraemia and hypokalaemia. In two children, cdt-positive strains were classified as typical and atypical enteropathogenic E. coli, and the remaining three harboured cdt-positive strains that did not belong to any diarrhoeagenic pathogroup. One cdt-positive strain from each case was characterized by a CDT cytotoxic assay and a cdt type-specific PCR. All strains produced the characteristic cellular intoxication due to CDT. Two strains carried the cdt-I, one cdt-III, one cdt-IV, and one concurrently had cdt-I, cdt-II and cdt-III genes. Conclusion. Our results suggest that CDT-producing E. coli strains are an infrequent, albeit significant, cause of severe diarrhoeal illness in children. Future research should measure the true burden of cdt-positive E. coli diarrhoea among children.

  18. "I am nothing": experiences of loss among women suffering from severe birth injuries in Tanzania

    Directory of Open Access Journals (Sweden)

    Mselle Lilian T

    2011-11-01

    Full Text Available Abstract Background Despite the increased attention on maternal mortality during recent decades, which has resulted in maternal health being defined as a Millennium Development Goal (MDG, the disability and suffering from obstetric fistula remains a neglected issue in global health. Continuous leaking of urine and the physical, emotional and social suffering associated with it, has a profound impact on women's quality of life. This study seeks to explore the physical, cultural and psychological dimensions of living with obstetric fistula, and demonstrate how these experiences shape the identities of women affected by the condition. Methods A cross-sectional study with qualitative and quantitative components was used to explore the experiences of Tanzanian women living with obstetric fistula and those of their husbands. The study was conducted at the Comprehensive Community Based Rehabilitation Tanzania hospital in Dar es Salaam, Bugando Medical Centre in Mwanza, and Mpwapwa district, in Dodoma region. Conveniently selected samples of 16 women were interviewed, and 151 additional women responded to a questionnaire. In addition, 12 women affected by obstetric fistula and six husbands of these affected women participated in a focus group discussions. Data were analysed using content data analysis framework and statistical package for the social sciences (SPSS version 15 for Microsoft windows. Results The study revealed a deep sense of loss. Loss of body control, loss of the social roles as women and wives, loss of integration in social life, and loss of dignity and self-worth were located at the core of these experiences. Conclusion The women living with obstetric fistula experience a deep sense of loss that had negative impact on their identity and quality of life. Acknowledging affected women's real-life experiences is important in order to understand the occurrence and management of obstetric fistula, as well as prospects after treatment. This

  19. Why do lesions in the rodent anterior thalamic nuclei cause such severe spatial deficits?

    Science.gov (United States)

    Aggleton, John P.; Nelson, Andrew J.D.

    2015-01-01

    Lesions of the rodent anterior thalamic nuclei cause severe deficits to multiple spatial learning tasks. Possible explanations for these effects are examined, with particular reference to T-maze alternation. Anterior thalamic lesions not only impair allocentric place learning but also disrupt other spatial processes, including direction learning, path integration, and relative length discriminations, as well as aspects of nonspatial learning, e.g., temporal discriminations. Working memory tasks, such as T-maze alternation, appear particularly sensitive as they combine an array of these spatial and nonspatial demands. This sensitivity partly reflects the different functions supported by individual anterior thalamic nuclei, though it is argued that anterior thalamic lesion effects also arise from covert pathology in sites distal to the thalamus, most critically in the retrosplenial cortex and hippocampus. This two-level account, involving both local and distal lesion effects, explains the range and severity of the spatial deficits following anterior thalamic lesions. These findings highlight how the anterior thalamic nuclei form a key component in a series of interdependent systems that support multiple spatial functions. PMID:25195980

  20. Diagnosing the Causes and Severity of One-sided Message Contention

    Energy Technology Data Exchange (ETDEWEB)

    Tallent, Nathan R.; Vishnu, Abhinav; van Dam, Hubertus; Daily, Jeffrey A.; Kerbyson, Darren J.; Hoisie, Adolfy

    2015-02-11

    Two trends suggest network contention for one-sided messages is poised to become a performance problem that concerns application developers: an increased interest in one-sided programming models and a rising ratio of hardware threads to network injection bandwidth. Unfortunately, it is difficult to reason about network contention and one-sided messages because one-sided tasks can either decrease or increase contention. We present effective and portable techniques for diagnosing the causes and severity of one-sided message contention. To detect that a message is affected by contention, we maintain statistics representing instantaneous (non-local) network resource demand. Using lightweight measurement and modeling, we identify the portion of a message's latency that is due to contention and whether contention occurs at the initiator or target. We attribute these metrics to program statements in their full static and dynamic context. We characterize contention for an important computational chemistry benchmark on InfiniBand, Cray Aries, and IBM Blue Gene/Q interconnects. We pinpoint the sources of contention, estimate their severity, and show that when message delivery time deviates from an ideal model, there are other messages contending for the same network links. With a small change to the benchmark, we reduce contention up to 50% and improve total runtime as much as 20%.

  1. Obstructive sleep apnoea in Treacher Collins syndrome: prevalence, severity and cause.

    Science.gov (United States)

    Plomp, R G; Bredero-Boelhouwer, H H; Joosten, K F M; Wolvius, E B; Hoeve, H L J; Poublon, R M L; Mathijssen, I M J

    2012-06-01

    This cohort study in 35 patients (13 children) evaluates the prevalence, severity and anatomical cause of obstructive sleep apnoea syndrome (OSAS) in patients with Treacher Collins syndrome. Ambulatory polysomnography was performed cross-sectionally to determine OSAS prevalence and severity. All upper airway related surgical interventions were evaluated retrospectively. In 11 patients, sleep endoscopy, and flexible and rigid endoscopy were applied to determine the level of anatomical obstruction of the upper airway. The overall prevalence of OSAS in Treacher Collins patients was 46% (54% in children; 41% in adults). Thirty-eight upper airway related surgical interventions were performed in 17 patients. Examination of the upper airway revealed various anatomical levels of obstruction, from the nasal septum to the trachea. Most significant obstruction was found at the level of the oro/hypopharynx. OSAS in Treacher Collins patients is an important problem so all patients should be screened for OSAS by polysomnography. Endoscopy of the upper airways was helpful in determining the level of obstruction. Surgical treatment at one level will not resolve OSAS in most patients because OSAS in Treacher Collins has a multilevel origin. Non-invasive ventilation (continuous positive airway pressure or bilevel positive airway pressure) or tracheotomy should be considered as a treatment modality.

  2. Severe signal loss in diamond beam loss monitors in high particle rate environments by charge trapping in radiation-induced defects

    Energy Technology Data Exchange (ETDEWEB)

    Kassel, Florian; Boer, Wim de [Institute for Experimental Nuclear Physics (IEKP), KIT, Karlsruhe (Germany); Guthoff, Moritz; Dabrowski, Anne [CERN, Meyrin (Switzerland)

    2016-10-15

    The beam condition monitoring leakage (BCML) system is a beam monitoring device in the compact muon solenoid (CMS) experiment at the large hadron collider (LHC). As detectors 32 poly-crystalline (pCVD) diamond sensors are positioned in rings around the beam pipe. Here, high particle rates occur from the colliding beams scattering particles outside the beam pipe. These particles cause defects, which act as traps for the ionization, thus reducing the charge collection efficiency (CCE). However, the loss in CCE was much more severe than expected from low rate laboratory measurements and simulations, especially in single-crystalline (sCVD) diamonds, which have a low initial concentration of defects. After an integrated luminosity of a few fb{sup -1} corresponding to a few weeks of LHC operation, the CCE of the sCVD diamonds dropped by a factor of five or more and quickly approached the poor CCE of pCVD diamonds. The reason why in real experiments the CCE is much worse than in laboratory experiments is related to the ionization rate. At high particle rates the trapping rate of the ionization is so high compared with the detrapping rate, that space charge builds up. This space charge reduces locally the internal electric field, which in turn increases the trapping rate and recombination and hence reduces the CCE in a strongly non-linear way. A diamond irradiation campaign was started to investigate the rate-dependent electrical field deformation with respect to the radiation damage. Besides the electrical field measurements via the transient current technique (TCT), the CCE was measured. The experimental results were used to create an effective deep trap model that takes the radiation damage into account. Using this trap model, the rate-dependent electrical field deformation and the CCE were simulated with the software SILVACO TCAD. The simulation, tuned to rate-dependent measurements from a strong radioactive source, was able to predict the non-linear decrease of the

  3. Loss of desmoplakin isoform I causes early onset cardiomyopathy and heart failure in a Naxos‐like syndrome

    Science.gov (United States)

    Uzumcu, A; Norgett, E E; Dindar, A; Uyguner, O; Nisli, K; Kayserili, H; Sahin, S E; Dupont, E; Severs, N J; Leigh, I M; Yuksel‐Apak, M; Kelsell, D P; Wollnik, B

    2006-01-01

    Background Desmosomes are cellular junctions important for intercellular adhesion and anchoring the intermediate filament (IF) cytoskeleton to the cell membrane. Desmoplakin (DSP) is the most abundant desmosomal protein with 2 isoforms produced by alternative splicing. Methods We describe a patient with a recessively inherited arrhythmogenic dilated cardiomyopathy with left and right ventricular involvement, epidermolytic palmoplantar keratoderma, and woolly hair. The patient showed a severe heart phenotype with an early onset and rapid progression to heart failure at 4 years of age. Results A homozygous nonsense mutation, R1267X, was found in exon 23 of the desmoplakin gene, which results in an isoform specific truncation of the larger DSPI isoform. The loss of most of the DSPI specific rod domain and C‐terminal area was confirmed by Western blotting and immunofluorescence. We further showed that the truncated DSPI transcript is unstable, leading to a loss of DSPI. DSPI is reported to be an obligate constituent of desmosomes and the only isoform present in cardiac tissue. To address this, we reviewed the expression of DSP isoforms in the heart. Our data suggest that DSPI is the major cardiac isoform but we also show that specific compartments of the heart have detectable DSPII expression. Conclusions This is the first description of a phenotype caused by a mutation affecting only one DSP isoform. Our findings emphasise the importance of desmoplakin and desmosomes in epidermal and cardiac function and additionally highlight the possibility that the different isoforms of desmoplakin may have distinct functional properties within the desmosome. PMID:16467215

  4. The effects of weight loss surgery on blood rheology in severely obese patients.

    Science.gov (United States)

    Wiewiora, Maciej; Piecuch, Jerzy; Glűck, Marek; Slowinska-Lozynska, Ludmila; Sosada, Krystyn

    2015-01-01

    The effects of dieting on blood rheology in obese individuals suggest that improving the rheologic profiles depends on the amount of weight lost and its long-term maintenance. The aim of this study was to evaluate the effects of weight loss after surgery on blood rheology at 12-month follow-up. We studied 38 obese patients who underwent laparoscopic weight loss surgery, 22 of whom had sleeve gastrectomy (SG) and 16 of whom had gastric banding (LAGB). We evaluated rheologic parameters such as blood viscosity, plasma viscosity, and erythrocyte deformability (as measured by elongation index [EI]) preoperatively and 12 months after surgery. Whole blood viscosity at 150 s(-1) shear rate (Prheology in obese patients at 12 months after surgery. The increased red blood cell rigidity after surgery requires further study because the physiologic importance of this change has not yet been established. Copyright © 2015 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  5. Bilateral idiopathic optic perineuritis with severe vision loss: A case report

    Directory of Open Access Journals (Sweden)

    Wee-Min Teh

    2015-07-01

    Full Text Available Optic perineuritis is an orbital inflammatory disorder that is either idiopathic or secondary to other conditions such as infection or systemic inflammatory disorders. This condition is very similar to demyelinating optic neuritis, but certain features of the history and magnetic resonance imaging findings are characteristic for and aid in the diagnosis of optic perineuritis. Vision loss varies greatly, from minimal clouding of vision up to only light perception. We report a case of a 44-year-old female with idiopathic bilateral optic perineuritis with vision loss of up to no light perception in both eyes. Radio imaging studies were typical of optic perineuritis and she was started on systemic corticosteroids. She responded very well to steroid therapy and achieved nearly complete visual recovery. There had been no relapse despite cessation of therapy.

  6. Pulmonary Veno-Occlusive Disease: A Newly Recognized Cause of Severe Pulmonary Hypertension in Dogs.

    Science.gov (United States)

    Williams, K; Andrie, K; Cartoceti, A; French, S; Goldsmith, D; Jennings, S; Priestnall, S L; Wilson, D; Jutkowitz, A

    2016-07-01

    Pulmonary hypertension is a well-known though poorly characterized disease in veterinary medicine. In humans, pulmonary veno-occlusive disease (PVOD) is a rare cause of severe pulmonary hypertension with a mean survival time of 2 years without lung transplantation. Eleven adult dogs (5 males, 6 females; median age 10.5 years, representing various breeds) were examined following the development of severe respiratory signs. Lungs of affected animals were evaluated morphologically and with immunohistochemistry for alpha smooth muscle actin, desmin, CD31, CD3, CD20, and CD204. All dogs had pulmonary lesions consistent with PVOD, consisting of occlusive remodeling of small- to medium-sized pulmonary veins, foci of pulmonary capillary hemangiomatosis (PCH), and accumulation of hemosiderophages; 6 of 11 dogs had substantial pulmonary arterial medial and intimal thickening. Ultrastructural examination and immunohistochemistry showed that smooth muscle cells contributed to the venous occlusion. Increased expression of CD31 was evident in regions of PCH indicating increased numbers of endothelial cells in these foci. Spindle cells strongly expressing alpha smooth muscle actin and desmin co-localized with foci of PCH; similar cells were present but less intensely labeled elsewhere in non-PCH alveoli. B cells and macrophages, detected by immunohistochemistry, were not co-localized with the venous lesions of canine PVOD; small numbers of CD3-positive T cells were occasionally in and around the wall of remodeled veins. These findings indicate a condition in dogs with clinically severe respiratory disease and pathologic features resembling human PVOD, including foci of pulmonary venous remodeling and PCH.

  7. Status of several Stirling loss characterization efforts and their significance for Stirling space power development

    Science.gov (United States)

    Tew, Roy C., Jr.

    1988-01-01

    NASA-Lewis and other U.S. Government agencies have supported experimental and analytical programs for the characterization of Stirling cycle engines' thermodynamic losses, with a view to the improvement of Stirling engine design capabilities. The Space Power Demonstrator Engine is noted to have benefited from these efforts; test data and model predictions suggest that even greater performance improvements would be obtainable through additional modifications of engine regenerator and heater hardware.

  8. Bilateral sudden sensorineural hearing loss caused by leptomeningeal carcinomatosis: case report and review.

    Science.gov (United States)

    Öztürk, Murat; Ila, Kadri; Düzgöl, Cihan; Akansel, Gür; Almaç, Ahmet

    2014-01-01

    Leptomeningeal carcinomatosis is a rare condition characterized by diffuse infiltration of the meninges after the metastasis of the solid tumors. Bilateral sudden hearing loss is a rare initial symptom. In this article, we report a 44-year-old male patient with bilateral sudden hearing loss and dizziness. Magnetic resonance imaging showed involvement of the bilateral vestibulocochlear nerves. Malignant cells were detected in cerebrospinal fluid cytology. To the best of our knowledge, leptomeningeal carcinomatosis due to duodenum adenocarcinoma has not been reported before in the English literature. Leptomeningeal carcinomatosis should be kept in mind in patients who have bilateral sudden sensorineural hearing loss.

  9. Massive hard coral loss after a severe bleaching event in 2010 at Los Roques, Venezuela

    Directory of Open Access Journals (Sweden)

    Carolina Bastidas

    2012-03-01

    Full Text Available Thermal anomalies have become more severe, frequent and well-documented across the Caribbean for the past 30 years. This increase in temperature has caused coral bleaching resulting in reef decline. At Los Roques National Park, Venezuela, temperature has been monitored at four reef sites. In mid-September 2010, seawater temperature reached 30.85°C at 5 m depth in Los Roques, an archipelago only slightly affected by previous bleaching events. For example, bleaching in Los Roques in 2005 was mild compared to the rest of the Caribbean and to the results in this study. In 2010, seawater temperatures remained above 29.0°C from mid-August until the first week of November, resulting in +16 Degree Heating Weeks by that time. Our annual survey of four reef sites indicated that 72% of 563 scleractinian colonies were partial or totally bleached (white or pale (discolored in October 2010. In February 2011, there were still 46% of coral colonies affected; but most of them were pale and only 2% were bleached. By February, coral cover had declined 4 to 30% per transect, with a mean of 14.3%. Thus, mean coral cover dropped significantly from 45 to 31% cover (a 34% reduction. In addition to bleaching, corals showed a high prevalence (up to 16% of black band disease in October 2010 and of white plague (11% in February 2011. As a consequence, coral mortality is expected to be larger than reported here. Reef surveys since 2002 and personal observations for more than 20 years indicated that this bleaching event and its consequences in Los Roques have no precedent. Our results suggest that reef sites with no previous record of significant deterioration are more likely to become affected by thermal anomalies. However, this archipelago is relatively unaffected by local anthropogenic disturbance and has a high coral recruitment, which may contribute to its recoveryDurante las últimas décadas las anomalías térmicas han sido más frecuentes y severas en el Caribe

  10. Duplication of the MECP2 region is a frequent cause of severe mental retardation and progressive neurological symptoms in males.

    Science.gov (United States)

    Van Esch, Hilde; Bauters, Marijke; Ignatius, Jaakko; Jansen, Mieke; Raynaud, Martine; Hollanders, Karen; Lugtenberg, Dorien; Bienvenu, Thierry; Jensen, Lars Riff; Gecz, Jozef; Moraine, Claude; Marynen, Peter; Fryns, Jean-Pierre; Froyen, Guy

    2005-09-01

    Loss-of-function mutations of the MECP2 gene at Xq28 are associated with Rett syndrome in females and with syndromic and nonsyndromic forms of mental retardation (MR) in males. By array comparative genomic hybridization (array-CGH), we identified a small duplication at Xq28 in a large family with a severe form of MR associated with progressive spasticity. Screening by real-time quantitation of 17 additional patients with MR who have similar phenotypes revealed three more duplications. The duplications in the four patients vary in size from 0.4 to 0.8 Mb and harbor several genes, which, for each duplication, include the MR-related L1CAM and MECP2 genes. The proximal breakpoints are located within a 250-kb region centromeric of L1CAM, whereas the distal breakpoints are located in a 300-kb interval telomeric of MECP2. The precise size and location of each duplication is different in the four patients. The duplications segregate with the disease in the families, and asymptomatic carrier females show complete skewing of X inactivation. Comparison of the clinical features in these patients and in a previously reported patient enables refinement of the genotype-phenotype correlation and strongly suggests that increased dosage of MECP2 results in the MR phenotype. Our findings demonstrate that, in humans, not only impaired or abolished gene function but also increased MeCP2 dosage causes a distinct phenotype. Moreover, duplication of the MECP2 region occurs frequently in male patients with a severe form of MR, which justifies quantitative screening of MECP2 in this group of patients.

  11. Severe phenotype in an apparent homozygosity caused by a large deletion in the CFTR gene: a case report.

    Science.gov (United States)

    Martins, Raisa da Silva; Fonseca, Ana Carolina Proença; Acosta, Franklyn Enrique Samudio; Folescu, Tania Wrobel; Higa, Laurinda Yoko Shinzato; Sad, Izabela Rocha; Chaves, Célia Regina Moutinho de Miranda; Cabello, Pedro Hernan; Cabello, Giselda Maria Kalil

    2014-08-30

    Over 1900 mutations have been identified in the cystic fibrosis conductance transmembrane regulator gene, including single nucleotide substitutions, insertions, and deletions. Unidentified mutations may still lie in introns or in regulatory regions, which are not routinely investigated, or in large genomic deletions, which are not revealed by conventional molecular analysis. The apparent homozygosity for a rare, cystic fibrosis conductance transmembrane regulator mutation screened by standard molecular analysis should be further investigated to confirm if the mutation is in fact homozygous. We describe a patient presenting with an apparent homozygous S4X mutation. A 13-year-old female patient of African descent with clinical symptoms of classic cystic fibrosis and a positive sweat test (97 mEq/L, diagnosed at age 3 years) presented with pancreatic insufficiency and severe pulmonary symptoms (initial lung colonization with Pseudomonas aeruginosa at age 4 years; forced vital capacity: 69%; forced expiratory volume: 51%; 2011). Furthermore, she developed severe acute lung disease and recurrent episodes of dehydration requiring hospitalization. The girl carried the CFTR mutation S4X in apparent homozygosity. However, further analysis revealed a large deletion in the second allele that included the region of the mutation. The deletion that we describe includes nucleotides 120-142, which correspond to a loss of 23 nucleotides that abolishes the normal translation initiation codon. This study reiterates the view that large, cystic fibrosis conductance transmembrane regulator deletions are an important cause of severe cystic fibrosis and emphasizes the importance of including large deletions/duplications in cystic fibrosis conductance transmembrane regulator diagnostic tests.

  12. A mutation in synaptojanin 2 causes progressive hearing loss in the ENU-mutagenised mouse strain Mozart.

    Science.gov (United States)

    Manji, Shehnaaz S M; Williams, Louise H; Miller, Kerry A; Ooms, Lisa M; Bahlo, Melanie; Mitchell, Christina A; Dahl, Hans-Henrik M

    2011-03-15

    Hearing impairment is the most common sensory impairment in humans, affecting 1:1,000 births. We have identified an ENU generated mouse mutant, Mozart, with recessively inherited, non-syndromic progressive hearing loss caused by a mutation in the synaptojanin 2 (Synj2), a central regulatory enzyme in the phosphoinositide-signaling cascade. The hearing loss in Mozart is caused by a p.Asn538Lys mutation in the catalytic domain of the inositol polyphosphate 5-phosphatase synaptojanin 2. Within the cochlea, Synj2 mRNA expression was detected in the inner and outer hair cells but not in the spiral ganglion. Synj2(N538K) mutant protein showed loss of lipid phosphatase activity, and was unable to degrade phosphoinositide signaling molecules. Mutant Mozart mice (Synj2(N538K/N538K)) exhibited progressive hearing loss and showed signs of hair cell degeneration as early as two weeks of age, with fusion of stereocilia followed by complete loss of hair bundles and ultimately loss of hair cells. No changes in vestibular or neurological function, or other clinical or behavioral manifestations were apparent. Phosphoinositides are membrane associated signaling molecules that regulate many cellular processes including cell death, proliferation, actin polymerization and ion channel activity. These results reveal Synj2 as a critical regulator of hair cell survival that is essential for hair cell maintenance and hearing function.

  13. Chronic plus binge ethanol exposure causes more severe pancreatic injury and inflammation.

    Science.gov (United States)

    Ren, Zhenhua; Yang, Fanmuyi; Wang, Xin; Wang, Yongchao; Xu, Mei; Frank, Jacqueline A; Ke, Zun-Ji; Zhang, Zhuo; Shi, Xianglin; Luo, Jia

    2016-10-01

    Alcohol abuse increases the risk for pancreatitis. The pattern of alcohol drinking may impact its effect. We tested a hypothesis that chronic ethanol consumption in combination with binge exposure imposes more severe damage to the pancreas. C57BL/6 mice were divided into four groups: control, chronic ethanol exposure, binge ethanol exposure and chronic plus binge ethanol exposure. For the control group, mice were fed with a liquid diet for two weeks. For the chronic ethanol exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks. In the binge ethanol exposure group, mice were treated with ethanol by gavage (5g/kg, 25% ethanol w/v) daily for 3days. For the chronic plus binge exposure group, mice were fed with a liquid diet containing 5% ethanol for two weeks and exposed to ethanol by gavage during the last 3days. Chronic and binge exposure alone caused minimal pancreatic injury. However, chronic plus binge ethanol exposure induced significant apoptotic cell death. Chronic plus binge ethanol exposure altered the levels of alpha-amylase, glucose and insulin. Chronic plus binge ethanol exposure caused pancreatic inflammation which was shown by the macrophages infiltration and the increase of cytokines and chemokines. Chronic plus binge ethanol exposure increased the expression of ADH1 and CYP2E1. It also induced endoplasmic reticulum stress which was demonstrated by the unfolded protein response. In addition, chronic plus binge ethanol exposure increased protein oxidation and lipid peroxidation, indicating oxidative stress. Therefore, chronic plus binge ethanol exposure is more detrimental to the pancreas.

  14. Brachial plexus palsy caused by halo traction before posterior correction in patients with severe scoliosis

    Institute of Scientific and Technical Information of China (English)

    QIAN Bang-ping; QIU Yong; WANG Bin; YU Yang; ZHU Ze-zhang

    2007-01-01

    Objective: To explore the clinical features and treatment results of brachial plexus palsy caused by halo traction before posterior correction in patients with severe scoliosis.Methods: A total of 300 cases of severe scoliosis received halo traction before posterior correction in our department from July 1997 to November 2004. Among them, 7 cases were complicated with brachial plexus palsy.The average Cobb angle was 110° (range, 90°-135°).Diagnoses were made as idiopathic scoliosis in 1 case,congenital scoliosis in 3 cases, and neuromuscular scoliosis in 3 cases. Additionally, diastematomyelia and tethered cord syndrome were found in 3 cases and thoracolumbar kyphosis in 2 cases. Weight of traction was immediately reduced when the patient developed any abnormal neurological symptoms in the upper extremity, and rehabilitation training was undertaken. Simultaneously,neurotrophic pharmacotherapy was applied, and the neurological function restoration of the upper limbs and the recovery time were documented.Results: Traction was used for an average of 3.5 weeks (range, 2-6 weeks) before spinal fusion for these 7 patients. The average traction weight was 8 kg, which was 19% on average (range, 13%-26%) of the average body weight (40.2 kg). These 7 patients had long and thin body configuration with a mean height of 175 cm. The duration between symptoms of brachial plexus paralysis and the diagnosis was 1-3 hours. All of these 7 patients presented various degrees of numbness in the ulnar side of the hand and forearm. Median nerve paresis was found in 3 cases and ulnar nerve paresis in 4 cases. Complete recovery of the neurological function had been achieved by the end of three months.Conclusions: The clinical features of brachial plexus palsy caused by halo traction include median nerve paresis,ulnar nerve paralysis, and numbness in the ulnar side of the hand and forearm, which may be due to the injury of the inferior part of the brachial plexus, i.e. , damage of Cs and

  15. Economic Estimation of the Losses Caused by Surface Water Pollution Accidents in China From the Perspective of Water Bodies' Functions.

    Science.gov (United States)

    Yao, Hong; You, Zhen; Liu, Bo

    2016-01-22

    The number of surface water pollution accidents (abbreviated as SWPAs) has increased substantially in China in recent years. Estimation of economic losses due to SWPAs has been one of the focuses in China and is mentioned many times in the Environmental Protection Law of China promulgated in 2014. From the perspective of water bodies' functions, pollution accident damages can be divided into eight types: damage to human health, water supply suspension, fishery, recreational functions, biological diversity, environmental property loss, the accident's origin and other indirect losses. In the valuation of damage to people's life, the procedure for compensation of traffic accidents in China was used. The functional replacement cost method was used in economic estimation of the losses due to water supply suspension and loss of water's recreational functions. Damage to biological diversity was estimated by recovery cost analysis and damage to environmental property losses were calculated using pollutant removal costs. As a case study, using the proposed calculation procedure the economic losses caused by the major Songhuajiang River pollution accident that happened in China in 2005 have been estimated at 2263 billion CNY. The estimated economic losses for real accidents can sometimes be influenced by social and political factors, such as data authenticity and accuracy. Besides, one or more aspects in the method might be overestimated, underrated or even ignored. The proposed procedure may be used by decision makers for the economic estimation of losses in SWPAs. Estimates of the economic losses of pollution accidents could help quantify potential costs associated with increased risk sources along lakes/rivers but more importantly, highlight the value of clean water to society as a whole.

  16. Economic Estimation of the Losses Caused by Surface Water Pollution Accidents in China From the Perspective of Water Bodies’ Functions

    Science.gov (United States)

    Yao, Hong; You, Zhen; Liu, Bo

    2016-01-01

    The number of surface water pollution accidents (abbreviated as SWPAs) has increased substantially in China in recent years. Estimation of economic losses due to SWPAs has been one of the focuses in China and is mentioned many times in the Environmental Protection Law of China promulgated in 2014. From the perspective of water bodies’ functions, pollution accident damages can be divided into eight types: damage to human health, water supply suspension, fishery, recreational functions, biological diversity, environmental property loss, the accident’s origin and other indirect losses. In the valuation of damage to people’s life, the procedure for compensation of traffic accidents in China was used. The functional replacement cost method was used in economic estimation of the losses due to water supply suspension and loss of water’s recreational functions. Damage to biological diversity was estimated by recovery cost analysis and damage to environmental property losses were calculated using pollutant removal costs. As a case study, using the proposed calculation procedure the economic losses caused by the major Songhuajiang River pollution accident that happened in China in 2005 have been estimated at 2263 billion CNY. The estimated economic losses for real accidents can sometimes be influenced by social and political factors, such as data authenticity and accuracy. Besides, one or more aspects in the method might be overestimated, underrated or even ignored. The proposed procedure may be used by decision makers for the economic estimation of losses in SWPAs. Estimates of the economic losses of pollution accidents could help quantify potential costs associated with increased risk sources along lakes/rivers but more importantly, highlight the value of clean water to society as a whole. PMID:26805869

  17. Economic Estimation of the Losses Caused by Surface Water Pollution Accidents in China From the Perspective of Water Bodies’ Functions

    Directory of Open Access Journals (Sweden)

    Hong Yao

    2016-01-01

    Full Text Available The number of surface water pollution accidents (abbreviated as SWPAs has increased substantially in China in recent years. Estimation of economic losses due to SWPAs has been one of the focuses in China and is mentioned many times in the Environmental Protection Law of China promulgated in 2014. From the perspective of water bodies’ functions, pollution accident damages can be divided into eight types: damage to human health, water supply suspension, fishery, recreational functions, biological diversity, environmental property loss, the accident’s origin and other indirect losses. In the valuation of damage to people’s life, the procedure for compensation of traffic accidents in China was used. The functional replacement cost method was used in economic estimation of the losses due to water supply suspension and loss of water’s recreational functions. Damage to biological diversity was estimated by recovery cost analysis and damage to environmental property losses were calculated using pollutant removal costs. As a case study, using the proposed calculation procedure the economic losses caused by the major Songhuajiang River pollution accident that happened in China in 2005 have been estimated at 2263 billion CNY. The estimated economic losses for real accidents can sometimes be influenced by social and political factors, such as data authenticity and accuracy. Besides, one or more aspects in the method might be overestimated, underrated or even ignored. The proposed procedure may be used by decision makers for the economic estimation of losses in SWPAs. Estimates of the economic losses of pollution accidents could help quantify potential costs associated with increased risk sources along lakes/rivers but more importantly, highlight the value of clean water to society as a whole.

  18. Etiology of hypercoagulable state in women with recurrent fetal loss without other causes of miscarriage from Southern Italy: new clinical target for antithrombotic therapy

    Directory of Open Access Journals (Sweden)

    Maristella D’Uva

    2008-10-01

    Full Text Available Maristella D’Uva1, Pierpaolo Di Micco2, Ida Strina1, Antonio Ranieri1, Carlo Alviggi1, Antonio Mollo1, Francesca Fabozzi1, Lucia Cacciapuoti1, Maria Teresa Scotto di Frega1, Mariateresa Iannuzzo2, Giuseppe De Placido11Dipartimento Universitario di Scienze Ostetriche Ginecologiche e Medicina della Riproduzione, Area Funzionale di Medicina della Riproduzione ed Endoscopia Ginecologica, Università degli Studi di Napoli Federico II, via Pansini 5 Building 9, 80131, Naples, Italy; 2Internal Medicine Division, Fatebenefratelli Hospital of Naples, Naples, ItalyBackground: Recurrent fetal loss (RPL is one of the most common cause of sterility. Several studies identified thrombophilia as the principal cause of recurrent pregnancy loss. However, reported studies often do not evaluate other causes of miscarriages in their inclusion and exclusion criteria. So the aim of our study was to investigate the role of inherited thrombophilia in patients with RPL and without other causes of RPL.Patients and methods: Patients with 2 or more first trimester abortion or with 1 or more late pregnancy loss were considered for this study. In order to evaluate the causes of RPL we looked for chromosomal, endocrine, chronic inflammatory, and infectious alterations. 90 patients affected by unexplained RPL were enrolled and tested for hemostatic alterations. These women were tested for inherited and/or acquired thrombophilia by MTHFR C677T gene polymorphism, factor V Leiden gene polymorphism, PTHRA20210G gene polymorphism, protein S deficiency, protein C deficiency, antithrombin III deficiency, lupus anticoagulant, and anticardiolipin antibodies Ig G and Ig M.Results: Acquired and/or inherited thrombophilia are strongly associated with RPL when other common causes of miscarriage were excluded. 78% of tested women showed hemostatic abnormalities. Several women with combined thrombophilic defects were also identified by our data.Conclusion: After a thorough evaluation of

  19. External validity of a randomised controlled trial on the treatment of severe infections caused by MRSA

    Science.gov (United States)

    Paul, Mical; Bronstein, Ella; Yahav, Dafna; Goldberg, Elad; Bishara, Jihad; Leibovici, Leonard

    2015-01-01

    Objectives To assess the external validity of a pragmatic, investigator-initiated RCT on treatment of severe infections caused by methicillin-resistant Staphylococcus aureus (MRSA), we compared patient characteristics and treatment effect estimates for patients included in the RCT versus those excluded. Participants and outcomes The RCT included hospitalised patients with documented or highly-probable invasive MRSA infections who were randomised to vancomycin versus trimethoprim-sulfamethoxazole (TMP-SMX) treatment, between 2007 and 2014. A concomitant observational study prospectively included all consecutive patients, between 2008 and 2011, who were excluded from the RCT due to no consent, meningitis, left-sided endocarditis, severe neutropaenia, chronic renal dialysis or treatment with study medications for longer than 48 h. The primary outcomes were clinical failure at day 7 and 30-day mortality for both studies. We compared baseline and infection characteristics, outcome rates and treatment effect estimates for included versus excluded patients. Results The RCT included 252 patients who were compared with 220 excluded patients who were observed. Inability to provide informed consent was the main reason for patient exclusion. Excluded patients’ functional and cognitive performance was significantly poorer than that of included patients. Sepsis was more severe among excluded patients (higher rates of mechanical ventilation, indwelling catheters, septic shock and organ failure). Clinical failure occurred in 83/252 (32.9%) versus 175/220 (79.5%) and deaths in 32 (12.7%) versus 64 (29.1%) for included versus excluded patients, p<0.001 for both comparisons. Comparing vancomycin to TMP-SMX, in the RCT mortality, was non-significantly lower with vancomycin (OR 0.76, 95% CIs 0.36 to 1.62), while in the observational analysis of excluded patients, mortality was significantly higher with vancomycin (OR 2.63, 1.04 to 6.65), p=0.04 for the difference. Conclusions

  20. Dumping syndrome: an unusual cause of severe hyperinsulinemic hypoglycemia in neurologically impaired children with gastrostomy.

    Science.gov (United States)

    Bizzarri, C; Cervoni, M; Crea, F; Cutrera, R; Schiavino, A; Schiaffini, R; Cappa, M

    2011-02-01

    This paper describes severe hyperinsulinemic hypoglycemia during bolus enteral feeding in two neurologically impaired children. Both children were affected by dysphagia with swallowing difficulties; caloric intake was inadequate. For these reasons, percutaneous endoscopic gastrostomy had been positioned during the first months of life. In one patient due to persisting vomiting, after a few months, a gastrojejunal tube (PEG-J) was inserted. Hypoglycemia was revealed by routine blood tests, without evidence of specific symptoms. Continuous subcutaneous glucose monitoring showed wide glucose excursions, ranging from hypoglycemia to hyperglycemia. Extremely high levels of insulin were detected at the time of hypoglycemia. A diagnosis of dumping syndrome (DS) was suspected in both children. In the child with PEG, the tip of the gastrostomy catheter was found to be lying in the bulbus duodeni. Once this had been pulled back, hypoglycemic episodes disappeared. The child with PEG-J needed continuous enteral feeding to reach a normal glucose balance. DS is a relatively common complication in children with gastrostomy, but extremely irregular glucose levels, ranging from hypoglycemia to hyperglycemia, and increased insulin secretion had not been previously demonstrated. The incidence of DS is probably underestimated in children receiving enteral feeding for neurological impairment. In these patients intensive monitoring of blood glucose levels should be performed to calibrate meals. Repeated underestimated hypoglycemic episodes could worsen neurological damage and cause a deterioration in clinical conditions.

  1. Severe stress following bereavement during pregnancy and risk of pregnancy loss: results from a population-based cohort study.

    Science.gov (United States)

    Plana-Ripoll, Oleguer; Parner, Erik; Olsen, Jørn; Li, Jiong

    2016-05-01

    Previous findings on the association between stress during pregnancy and pregnancy loss are inconsistent. We aimed to estimate this association using a large prospective cohort. This population-based study included all 1 303 660 clinically recognised pregnancies in Denmark between 1995 and 2008. We categorised women as exposed to severe stress if they lost a child, sibling or parent during pregnancy. Cox Proportional Hazards models were used to study the association between exposure and rate of fetal death, starting with the follow-up on the day of completion of week 4 of pregnancy. In an attempt to control for unknown potential confounders, we also designed a pregnancy-matched analysis in which each woman had her own baseline risk of pregnancy loss and controls therefore for genetic and time-stable environmental factors. A total of 146 031 pregnancies ended in clinically recognised fetal loss (11.2%) and a total of 10 808 (0.8%) women were categorised as exposed. The overall risk of pregnancy loss was similar in the exposed and unexposed (aHR=1.05, 95% CI 0.95 to 1.15). Results from the pregnancy-matched analysis (performed in 423 women) showed stronger and significant associations (aHR=1.83, 95% CI 1.49 to 2.25). All the analyses indicated a stronger effect of bereavement when the mother lost a child or when the death was unexpected. Our main results suggested no strong association between severe stress during pregnancy and risk of pregnancy loss. Results from the pregnancy-matched analyses considered information from a selected and small group of women for whom there may exist a stronger association between stress during pregnancy and pregnancy loss. The fact that an unexpected death or the loss of a child had a stronger effect in both analyses may indicate that severe stressful situations increase the risk of pregnancy loss. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  2. Two mutational hotspots in the interleukin-2 receptor {gamma} chain gene causing human X-linked severe combined immunodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Pepper, A.E.; Puck, J.M. [National Institutes of Health, Bethesda, MD (United States); Buckley, R.H. [and others

    1995-09-01

    Human severe combined immunodeficiency (SCID), a syndrome of profoundly impaired cellular and humoral immunity, is most commonly caused by mutations in the X-linked gene for interleukin-2 (IL-2) receptor {gamma} chain (IL2RG). For mutational analysis of IL2RG in males with SCID, SSCP screening was followed by DNA sequencing. Of 40 IL2RG mutations found in unrelated SCID patients, 6 were point mutations at the CpG dinucleotide at cDNA 690-691, encoding amino acid R226. This residue lies in the extracellular domain of the protein in a region not previously recognized to be significantly conserved in the cytokine receptor gene family, 11 amino acids upstream from the highly conserved WSXWS motif. Three additional instances of mutation at another CpG dinucleotide at cDNA 879 produced a premature termination signal in the intracellular domain of IL2RG, resulting in loss of the SH2-homologous intracellular domain known to be essential for signaling from the IL-2 receptor complex. Mutations at these two hotspots constitute >20% of the X-linked SCID mutations found by our group and a similar proportion of all reported IL2RG mutations. 41 refs., 5 figs., 1 tab.

  3. Drought, epidemic disease, and the fall of classic period cultures in Mesoamerica (AD 750-950). Hemorrhagic fevers as a cause of massive population loss.

    Science.gov (United States)

    Acuna-Soto, Rodolfo; Stahle, David W; Therrell, Matthew D; Gomez Chavez, Sergio; Cleaveland, Malcolm K

    2005-01-01

    The classical period in Mexico (AD 250-750) was an era of splendor. The city of Teotihuacan was one of the largest and most sophisticated human conglomerates of the pre-industrial world. The Mayan civilization in southeastern Mexico and the Yucatan peninsula reached an impressive degree of development at the same time. This time of prosperity came to an end during the Terminal Classic Period (AD 750-950) a time of massive population loss throughout Mesoamerica. A second episode of massive depopulation in the same area was experienced during the sixteenth century when, in less than one century, between 80% and 90% of the entire indigenous population was lost. The 16th century depopulation of Mexico constitutes one of the worst demographic catastrophes in human history. Although newly imported European and African diseases caused high mortality among the native population, the major 16th century population losses were caused by a series of epidemics of a hemorrhagic fever called Cocoliztli, a highly lethal disease unknown to both Aztec and European physicians during the colonial era. The cocoliztli epidemics occurred during the 16th century megadrought, when severe drought extended at times from central Mexico to the boreal forest of Canada, and from the Pacific to the Atlantic coast. The collapse of the cultures of the Classic Period seems also to have occurred during a time of severe drought. Tree ring and lake sediment records indicate that some of the most severe and prolonged droughts to impact North America-Mesoamerica in the past 1000-4000 years occurred between AD 650 and 1000, particularly during the 8th and 9th centuries, a period of time that coincides with the Terminal Classic Period. Based on the similarities of the climatic (severe drought) and demographic (massive population loss) events in Mesoamerica during the sixteenth century, we propose that drought-associated epidemics of hemorrhagic fever may have contributed to the massive population loss

  4. Severe Bone Loss as Part of the Life History Strategy of Bowhead Whales.

    Directory of Open Access Journals (Sweden)

    John C George

    Full Text Available The evolution of baleen constituted a major evolutionary change that made it possible for baleen whales to reach enormous body sizes while filter feeding on tiny organisms and migrating over tremendous distances. Bowhead whales (Balaena mysticetus live in the Arctic where the annual cycle of increasing and decreasing ice cover affects their habitat, prey, and migration. During the nursing period, bowheads grow rapidly; but between weaning and approximately year 5, bowhead whales display sustained baleen and head growth while limiting growth in the rest of their bodies. During this period, they withdraw resources from the skeleton, in particular the ribs, which may lose 40% of bone mass. Such dramatic changes in bones of immature mammals are rare, although fossil cetaceans between 40 and 50 million years ago show an array of rib specializations that include bone loss and are usually interpreted as related to buoyancy control.

  5. Trends and causes of historical wetland loss, Sabine National Wildlife Refuge, southwest Louisiana

    Science.gov (United States)

    Bernier, Julie C.; Morton, Robert A.; Kelso, Kyle W.

    2011-01-01

    Prior U.S. Geological Survey studies (Open-File Reports 2005-1216 and 2009-1158) examined historical land- and water-area changes and estimated magnitudes of land subsidence and erosion at 10 wetland sites in the Mississippi River delta plain. The present study extends that work by analyzing interior wetland loss and relative magnitudes of subsidence and erosion at five additional wetland sites in Sabine National Wildlife Refuge (SNWR) in the western chenier plain. The study sites were selected because their geologic setting differed from that of the delta plain; also, although the refuge marshes had been managed partly to minimize wetland loss, interior wetland losses there were extensive. Historical aerial photography, datum-corrected marsh elevations and water depths, and sediment cores were integrated to evaluate historical land- and water-area changes at SNWR.

  6. A model for the estimation of storm losses and the identification of severe winter storms in Germany

    Directory of Open Access Journals (Sweden)

    M. Klawa

    2003-01-01

    Full Text Available A storm loss model for Germany is presented. Input data to the model are the daily maximum gust wind speeds measured at stations distributed over the country. The individual daily peak gust values are scaled with the local climatological upper 2% quantile at each station. This scaling serves to take local conditions at the stations into account, and thus permits a simple spatial interpolation of the storm field. The next step is the computation of a loss index for each storm. It is based on the excess of (scaled wind speed over the upper 2% quantile, and on population numbers in the individual districts within Germany, with the latter serving as a proxy for the spatial distribution of values that could be affected by a storm. Using wind speeds in excess of the percentile value also serves to take spatial heterogeneity of vulnerability against storms into account. The aggregated storm index gives an estimate of the severity of an individual storm. Finally, the relation between actual loss produced by a storm and the index is estimated using published annual insurance loss due to windstorm in Germany. Index values are accumulated for each year, and the relation to actual loss is computed. The average ratio for the whole reference period is eventually used. It is shown that the interannual variability of storm-related losses can be reproduced with a correlation coefficient of r = 0.96, and even individual storm damages can be estimated. Based on these evaluations we found that only 50 storms account for about 80% of insured storm losses between 1970 and 1997.

  7. Dengue hemorrhagic fever: A rare cause of pituitary tumor hemorrhage and reversible vision loss

    Directory of Open Access Journals (Sweden)

    Vimal Kumar

    2011-01-01

    Full Text Available Dengue hemorrhagic fever leading to hemorrhage in pituitary adenoma is not reported till date: We herein report the first case of bilateral visual loss secondary to pituitary adenoma hemorrhage associated with dengue hemorrhagic fever. Urgent transnasal trans sphenoidal decompression of the macroadenoma prevented permanent visual loss in this patient. Pituitary apoplexy should be considered as differential diagnosis of visual deterioration apart from retinal hemorrhage, maculopathy, and optic neuropathy in cases of dengue hemorrhagic fever. Early decompression of optic nerves helped in the restoration of vision.

  8. A Case Report of Unilateral Severe Visual Loss Along with Bilateral Optic Disc Cupping Secondary to Metastatic Brain Tumor

    Directory of Open Access Journals (Sweden)

    M Mahdavi

    2006-07-01

    Full Text Available Purpose: To report a case of unilateral severe visual loss and bilateral optic disc cupping secondary to brain metastasis of bronchogenic carcinoma Patient and findings: A 48 year-old woman presented with severe visual loss of left eye without redness or pain or any systemic findings .Clinical findings included decreased visual acuity of left eye to 4 m CF and (+3 positive Marcus-Gunn reflex .There was asymmetric optic disc cupping associated with visual field defect in left eye The neurologic investigations showed a secondary metastatic tumor in the brain from bronchogenic carcinoma. Conclusion: Before making a diagnosis of normal -tension glaucoma in asymmetric optic disc cupping and normal intraocular pressure, ophthalmologists should rule out neurologic defects and brain tumors.

  9. Anaphylaxis and severe systemic reactions caused by skin contact with persulfates in hair-bleaching products

    NARCIS (Netherlands)

    Hoekstra, Margriet; van der Heide, Sicco; Coenraads, Pieter Jan; Schuttelaar, Marielouise

    2012-01-01

    BACKGROUND: Persulfates have been reported to cause both delayed-type and immediate skin reactions. They may also cause immediate reactions of the mucous membranes of the bronchial system through inhalation, leading to asthma and rhinitis. Anaphylactic reactions caused by contact with persulfates ar

  10. Anaphylaxis and severe systemic reactions caused by skin contact with persulfates in hair-bleaching products

    NARCIS (Netherlands)

    Hoekstra, Margriet; van der Heide, Sicco; Coenraads, Pieter Jan; Schuttelaar, Marielouise

    BACKGROUND: Persulfates have been reported to cause both delayed-type and immediate skin reactions. They may also cause immediate reactions of the mucous membranes of the bronchial system through inhalation, leading to asthma and rhinitis. Anaphylactic reactions caused by contact with persulfates

  11. Weight Loss After Laparoscopic Adjustable Gastric Banding is not Caused by Altered Gastric Emptying

    NARCIS (Netherlands)

    de Jong, J. R.; van Ramshorst, B.; Gooszen, H. G.; Smout, A. J. P. M.; Buul, M. M. C. Tiel-Van

    2009-01-01

    In order to know the role of gastric emptying in the mechanism of weight loss and early satiety after a restrictive surgical procedure for treatment of morbid obesity, a consecutive series of patients were scintigraphically investigated before and after laparoscopic adjustable gastric banding. Sixte

  12. Raptor/mTORC1 loss in adipocytes causes progressive lipodystrophy and fatty liver disease

    Directory of Open Access Journals (Sweden)

    Peter L. Lee

    2016-06-01

    Conclusions: mTORC1 activity in mature adipocytes is essential for maintaining normal adipose tissue growth and its selective loss in mature adipocytes leads to a progressive lipodystrophy disorder and systemic metabolic disease that shares many of the hallmarks of human congenital generalized lipodystrophy.

  13. Java project on periodontal diseases: causes of tooth loss in a cohort of untreated individuals

    NARCIS (Netherlands)

    U. van der Velden; A. Amaliya; B.G. Loos; M.F. Timmerman; F.A. van der Weijden; E.G. Winkel; F. Abbas

    2015-01-01

    Objective To assess the relative contribution of caries and periodontal disease to tooth loss over 24 years in a cohort deprived of regular dental care. Material & Methods The study population consisted of 98 subjects from a tea estate on West Java, Indonesia, that had been part of a prospective lon

  14. Java project on periodontal diseases : causes of tooth loss in a cohort of untreated individuals

    NARCIS (Netherlands)

    van der Velden, Ubele; Amaliya, Amaliya; Loos, Bruno G.; Timmerman, Mark F.; van der Weijden, Fridus A.; Winkel, Edwin G.; Abbas, Frank

    2015-01-01

    ObjectiveTo assess the relative contribution of caries and periodontal disease to tooth loss over 24years in a cohort deprived of regular dental care. Material & MethodsThe study population consisted of 98 subjects from a tea estate on West Java, Indonesia, that had been part of a prospective longit

  15. Prevalence of Various Reproductive Disorders and Economic Losses Caused by Genital Prolapse in Buffaloes

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    Rasheed A. Rabbani, I. Ahmad*, L. A. Lodhi, N. Ahmad and G. Muhammad1

    2010-01-01

    Full Text Available The present study was conducted to investigate the prevalence of various reproductive disorders and to estimate the economic losses due to genital prolapse in buffaloes in Sir Shamir area of District Faisalabad, Pakistan. The survey was conducted in 8 villages during the 12 months period from June 2005 to May 2006 and the data from 400 farmers (50 farmers from each village were collected. The total buffalo population of this area was 7,785, out of which 2,135 (27.42% animals were included in the study. The overall prevalence of reproductive disorders in buffaloes was recorded as 46.18%. Among all the reproductive disorders, repeat breeding showed the highest prevalence (15.69%, followed by anestrous (9.74%, genital prolapse (7.73%, abortion (5.99%, retained placenta (2.58%, uterine torsion (2.39% and dystocia (2.06%. The total economic losses due to genital prolapse in buffaloes in eight villages during the period of study were estimated to be Rs. 4,59,500/- Among these, the highest losses were due to mortality of dam (39.17%, followed by milk losses (25.14%, service charges (21.33% and medicine cost (14.36%. Thus, repeat breeding, anoestrus and genital prolapse seem to be the major reproductive problems in buffaloes in the study area.

  16. Energy loss caused by shielding effect of steel cage outside source tube

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The energy loss, produced by shielding effect of steel cage outside the source tube, is quite considerable.With PENELOPE software package, MC results have been obtained based on the simulation of different source conformations. The result illustrates that the naked source tubes can improve the utilization ratio of the cobalt facilities. It demonstrates the applied value of the naked source tube in engineering.

  17. Effect of reinforced flowable resin restoration on periodontal tissue in patients with severe periodontitis and anterior tooth loss

    Institute of Scientific and Technical Information of China (English)

    Zhao-Ran Fu

    2016-01-01

    Objective:To study the effect of traditional flowable resin and reinforced flowable resin restoration on periodontal tissue in patients with severe periodontitis and anterior tooth loss. Methods: A total of 76 patients with severe periodontitis and anterior tooth loss who received treatment in our hospital from May 2012 to October 2015 were selected and randomly divided into reinforced group and traditional group who received reinforced flowable resin restoration and traditional flowable resin restoration respectively. Inflammation indexes, oxidative stress indexes, bone metabolism indexes and apoptotic indexes in gingival crevicular fluid were compared between two groups.Results:2 weeks after treatment, NLRP3, IL-1β, IL-18, RANKL, MDA, O2-, H2O2, Fas, FasL, Bax, Smac, Apaf-1 and Caspase-3 levels as well as caspase-1 vitality in gingival crevicular fluid of reinforced group were significantly lower than those of traditional group while SOD, GSH-Px, OPG, ALP, Runx2, OCN and Col-1 levels were significantly higher than those of traditional group.Conclusion: Reinforced flowable resin restoration can alleviate inflammation and oxidative stress in periodontal tissue, and inhibit alveolar bone resorption and cell apoptosis in patients with severe periodontitis and anterior tooth loss.

  18. Loss of interstitial cells of Cajal network in severe idiopathic gastroparesis

    Institute of Scientific and Technical Information of China (English)

    Edda Battaglia; Gabrio Bassotti; Graziella Bellone; Luca Dughera; Anna Maria Serra; Luigi Chiusa; Alessandro Repici; Pierroberto Mioli; Giorgio Emanuelli

    2006-01-01

    AIM: To report a case of severe idiopathic gastroparesis in complete absence of Kit-positive gastric interstitial cells of Cajal (ICC).METHODS: Gastric tissue from a patient with severe idiopathic gastroparesis unresponsive to medical treatment and requiring surgery was analyzed by conventional histology and immunohistochemistry.RESULTS: Gastric pacemaker cells expressing Kit receptor had completely disappeared while the local level of stem cell factor, the essential ligand for its development and maintenance, was increased. No signs of cell death were observed in the pacemaker region.CONCLUSION: These results are consistent with the hypothesis that a lack of Kit expression may lead to impaired functioning of ICC. Total gastrectomy proves to be curative.

  19. No Association between Loss-of-Function Mutations in filaggrin and Diabetes, Cardiovascular Disease, and All-Cause Mortality

    Science.gov (United States)

    Husemoen, Lise Lotte N.; Skaaby, Tea; Jørgensen, Torben; Thyssen, Jacob P.; Meldgaard, Michael; Szecsi, Pal B.; Stender, Steen; Johansen, Jeanne Duus; Linneberg, Allan

    2013-01-01

    Background Common loss-of-function mutations in the filaggrin gene (FLG) are a major predisposing risk factor for atopic disease due to reduced epidermal filaggrin protein levels. We previously observed an association between these mutations and type 2 diabetes and hypothesized that an inherited impairment of skin barrier functions could facilitate low-grade inflammation and hence increase the risk of diabetes and cardiovascular disease. We examined the association between loss-of-function mutations in FLG and diabetes, stroke, ischemic heart disease (IHD), and all-cause mortality in the general population. Methods The R501X and 2282del4 loss-of function mutations in FLG were genotyped in four Danish study populations including a total of 13373 adults aged 15-77 years. Two of the studies also genotyped the R2447X mutation. By linkage to Danish national central registers we obtained information for all participants on dates of diagnoses of diabetes, stroke, and IHD, as well as all-cause mortality. Data were analyzed by Cox proportional hazard models and combined by fixed effect meta-analyses. Results In meta-analyses combining the results from the four individual studies, carriage of loss-of-function mutations in FLG was not associated with incident diabetes (hazard ratio (HR) (95% confidence intervals (CI)) = 0.95 (0.73, 1.23), stroke (HR (95% CI) = 1.27 (0.97, 1.65), ischemic heart disease (HR (95%CI) = 0.92 (0.71, 1.19), and all-cause mortality (HR (95%CI) = 1.02 (0.83, 1.25)). Similar results were obtained when including prevalent cases in logistic regression models. Conclusion Our results suggest that loss-of-function mutations in FLG are not associated with type 2 diabetes, cardiovascular disease, and all-cause mortality. However, larger studies with longer follow-up are needed to exclude any associations. PMID:24367652

  20. No association between loss-of-function mutations in filaggrin and diabetes, cardiovascular disease, and all-cause mortality.

    Directory of Open Access Journals (Sweden)

    Lise Lotte N Husemoen

    Full Text Available BACKGROUND: Common loss-of-function mutations in the filaggrin gene (FLG are a major predisposing risk factor for atopic disease due to reduced epidermal filaggrin protein levels. We previously observed an association between these mutations and type 2 diabetes and hypothesized that an inherited impairment of skin barrier functions could facilitate low-grade inflammation and hence increase the risk of diabetes and cardiovascular disease. We examined the association between loss-of-function mutations in FLG and diabetes, stroke, ischemic heart disease (IHD, and all-cause mortality in the general population. METHODS: The R501X and 2282del4 loss-of function mutations in FLG were genotyped in four Danish study populations including a total of 13373 adults aged 15-77 years. Two of the studies also genotyped the R2447X mutation. By linkage to Danish national central registers we obtained information for all participants on dates of diagnoses of diabetes, stroke, and IHD, as well as all-cause mortality. Data were analyzed by Cox proportional hazard models and combined by fixed effect meta-analyses. RESULTS: In meta-analyses combining the results from the four individual studies, carriage of loss-of-function mutations in FLG was not associated with incident diabetes (hazard ratio (HR (95% confidence intervals (CI = 0.95 (0.73, 1.23, stroke (HR (95% CI = 1.27 (0.97, 1.65, ischemic heart disease (HR (95%CI = 0.92 (0.71, 1.19, and all-cause mortality (HR (95%CI = 1.02 (0.83, 1.25. Similar results were obtained when including prevalent cases in logistic regression models. CONCLUSION: Our results suggest that loss-of-function mutations in FLG are not associated with type 2 diabetes, cardiovascular disease, and all-cause mortality. However, larger studies with longer follow-up are needed to exclude any associations.

  1. The emotional impact of loss narratives: event severity and narrative perspectives.

    Science.gov (United States)

    Habermas, Tilmann; Diel, Verena

    2010-06-01

    Out of the complex influences of event, narrative and listener characteristics on narrative emotions, this paper focuses on event severity, narrative perspectives, mood, and dispositions for emotion regulation and empathy. Event severity and perspective representation were systematically varied in sad autobiographical narratives to study their influence on quantity and quality of readers' emotional response. Each of three stories were manipulated to contain elaborated perspectives, only the past protagonists' perspective (dramatic narration), and very little perspectives at all (impersonal narration). We predicted that event severity influences the quantity of emotional response, while degree of perspective representation influences plausibility and whether emotional responses are sympathetic or interactional, that is, directed against the narrator. Hypotheses were confirmed except for plausibility, and perspective representation had an effect only on anger against and dislike of the narrator. In a second study, impersonal narration evoked anger at and negative evaluations of the narrator which were related to blaming the narrator for showing too little emotional involvement. The generalizability of findings across emotions and implications for sharing of emotions in everyday and clinical settings are discussed.

  2. Progressive loss of vision caused by asymptomatic pituitary macroadenoma: role of OCT

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    Asensio-Sánchez VM

    2016-09-01

    Full Text Available Víctor Manuel Asensio-Sánchez, Javier Foncubierta Ophthalmology Department, Clinical University Hospital of Valladolid, Valladolid, Spain Introduction: Most pituitary adenomas are clinically inactive. In patients with long-standing compression of the optic chiasm, ganglion cells may undergo axonal degeneration. Spectral domain optical coherence tomography (SD-OCT is able to identify retinal nerve fiber layer (RNFL and ganglion cell loss in the retina. We present a case in which SD-OCT was used to diagnose an asymptomatic pituitary macroadenoma.Clinical case: A 48-year-old female presented with progressive vision loss in both eyes. SD-OCT identified atrophy of the ganglion cell and nerve layers, with preservation of outer layers bilaterally. Magnetic resonance imaging of the brain showed a pituitary macroadenoma. The pathological diagnosis was nonfunctioning adenoma.Discussion: As macroadenomas enlarge, they can induce uncrossed axon loss, resulting in nasal field defects and reduced visual acuity. In these cases, there is atrophy of the nasal and temporal portions of the optic disc, thus occupying a horizontal band across the disc. SD-OCT is able to identify RNFL loss in eyes with band atrophy of the optic nerve, which correlates with visual field defects found in perimetry. SD-OCT is a useful tool to assess the structural and functional damage of ganglion cells. In our case the SD-OCT demonstrated a symmetrical loss of the RNFL and the ganglion cell layer in both eyes, indicating important optic nerve damage. Keywords: OCT, pituitary, adenoma, RNFL, ganglion cell layer

  3. Biallelic Mutations in TMEM126B Cause Severe Complex I Deficiency with a Variable Clinical Phenotype.

    Science.gov (United States)

    Alston, Charlotte L; Compton, Alison G; Formosa, Luke E; Strecker, Valentina; Oláhová, Monika; Haack, Tobias B; Smet, Joél; Stouffs, Katrien; Diakumis, Peter; Ciara, Elżbieta; Cassiman, David; Romain, Nadine; Yarham, John W; He, Langping; De Paepe, Boel; Vanlander, Arnaud V; Seneca, Sara; Feichtinger, René G; Płoski, Rafal; Rokicki, Dariusz; Pronicka, Ewa; Haller, Ronald G; Van Hove, Johan L K; Bahlo, Melanie; Mayr, Johannes A; Van Coster, Rudy; Prokisch, Holger; Wittig, Ilka; Ryan, Michael T; Thorburn, David R; Taylor, Robert W

    2016-07-01

    Complex I deficiency is the most common biochemical phenotype observed in individuals with mitochondrial disease. With 44 structural subunits and over 10 assembly factors, it is unsurprising that complex I deficiency is associated with clinical and genetic heterogeneity. Massively parallel sequencing (MPS) technologies including custom, targeted gene panels or unbiased whole-exome sequencing (WES) are hugely powerful in identifying the underlying genetic defect in a clinical diagnostic setting, yet many individuals remain without a genetic diagnosis. These individuals might harbor mutations in poorly understood or uncharacterized genes, and their diagnosis relies upon characterization of these orphan genes. Complexome profiling recently identified TMEM126B as a component of the mitochondrial complex I assembly complex alongside proteins ACAD9, ECSIT, NDUFAF1, and TIMMDC1. Here, we describe the clinical, biochemical, and molecular findings in six cases of mitochondrial disease from four unrelated families affected by biallelic (c.635G>T [p.Gly212Val] and/or c.401delA [p.Asn134Ilefs(∗)2]) TMEM126B variants. We provide functional evidence to support the pathogenicity of these TMEM126B variants, including evidence of founder effects for both variants, and establish defects within this gene as a cause of complex I deficiency in association with either pure myopathy in adulthood or, in one individual, a severe multisystem presentation (chronic renal failure and cardiomyopathy) in infancy. Functional experimentation including viral rescue and complexome profiling of subject cell lines has confirmed TMEM126B as the tenth complex I assembly factor associated with human disease and validates the importance of both genome-wide sequencing and proteomic approaches in characterizing disease-associated genes whose physiological roles have been previously undetermined.

  4. Severe sepsis caused by Aeromonas hydrophila in a patient using tocilizumab: a case report

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    Makino Ichiro

    2011-10-01

    Full Text Available Abstract Introduction Aeromonas species do not commonly cause disease in humans. However, when disease is seen, it often occurs in patients with underlying immunosuppression or malignancy and has a high fatality rate. Case presentation A 72-year-old Japanese woman with rheumatoid arthritis treated with tocilizumab (which has an immunosuppressive effect presented with severe epigastric pain. She had a fever with chills, hypotension and jaundice. She was diagnosed with acute suppurative cholangitis and treated with cefoperazone-sulbactam and an endoscopic drainage was performed. Jaundice was slightly improved, but the shock state and inflammatory reactions were prolonged as typical of septic shock. On the second day after admission, an electrocardiogram showed ST segment elevation and echocardiography showed ventricular wall dysfunction. Coronary arteries were patent in coronary angiography and she was diagnosed with stress-induced cardiomyopathy. Blood cultures showed Aeromonas hydrophila. A stool culture was negative for A. hydrophila. On day six, her white blood cell count and neutrophils were normalized and cefoperazone-sulbactam treatment was halted. Left ventricular function normalized on day twelve and a laparoscopic cholecystectomy for cholelithiasis was performed on the 16th day of hospitalization. A culture from the bile showed A. hydrophila. Eighteen days after surgery, tocilizumab treatment was restarted and there were no complications. Two months after restarting tocilizumab, our patient is stable without any serious events. Conclusion We present a rare case of A. hydrophila sepsis and acute suppurative cholangitis in an elderly patient with gallstones and rheumatoid arthritis using tocilizumab. This clinical course may suggest that preemptive treatment for cholelithiasis prior to using molecular-targeting agents might be feasible in elderly patients.

  5. Divergent Simian Arteriviruses Cause Simian Hemorrhagic Fever of Differing Severities in Macaques

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    Victoria Wahl-Jensen

    2016-02-01

    Full Text Available Simian hemorrhagic fever (SHF is a highly lethal disease in captive macaques. Three distinct arteriviruses are known etiological agents of past SHF epizootics, but only one, simian hemorrhagic fever virus (SHFV, has been isolated in cell culture. The natural reservoir(s of the three viruses have yet to be identified, but African nonhuman primates are suspected. Eleven additional divergent simian arteriviruses have been detected recently in diverse and apparently healthy African cercopithecid monkeys. Here, we report the successful isolation in MARC-145 cell culture of one of these viruses, Kibale red colobus virus 1 (KRCV-1, from serum of a naturally infected red colobus (Procolobus [Piliocolobus] rufomitratus tephrosceles sampled in Kibale National Park, Uganda. Intramuscular (i.m. injection of KRCV-1 into four cynomolgus macaques (Macaca fascicularis resulted in a self-limiting nonlethal disease characterized by depressive behavioral changes, disturbance in coagulation parameters, and liver enzyme elevations. In contrast, i.m. injection of SHFV resulted in typical lethal SHF characterized by mild fever, lethargy, lymphoid depletion, lymphoid and hepatocellular necrosis, low platelet counts, increased liver enzyme concentrations, coagulation abnormalities, and increasing viral loads. As hypothesized based on the genetic and presumed antigenic distance between KRCV-1 and SHFV, all four macaques that had survived KRCV-1 injection died of SHF after subsequent SHFV injection, indicating a lack of protective heterotypic immunity. Our data indicate that SHF is a disease of macaques that in all likelihood can be caused by a number of distinct simian arteriviruses, although with different severity depending on the specific arterivirus involved. Consequently, we recommend that current screening procedures for SHFV in primate-holding facilities be modified to detect all known simian arteriviruses.

  6. Perceived causes of severe mental disturbance and preferred interventions by the Borana semi-nomadic population in southern Ethiopia: a qualitative study

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    Teferra Solomon

    2012-07-01

    Full Text Available Abstract Background Culture affects the way people conceptualize causes of severe mental disturbance which may lead to a variation in the preferred intervention methods. There is a seemingly dichotomous belief regarding what causes severe mental disturbance: people living in western countries tend to focus mainly on biological and psychosocial risk factors; whereas, in non-western countries the focus is mainly on supernatural and religious factors. These belief systems about causation potentially dictate the type of intervention preferred. Studying such belief systems in any society is expected to help in planning and implementation of appropriate mental health services. Methods A qualitative study was conducted among the Borana semi-nomadic population in southern Ethiopia to explore perceived causes of severe mental disturbance and preferred interventions. We selected, using purposive sampling, key informants from three villages and conducted a total of six focus group discussions: three for males and three for females. Results The views expressed regarding the causes of mental disturbance were heterogeneous encompassing supernatural causes such as possession by evil spirits, curse, bewitchment, ‘exposure to wind’ and subsequent attack by evil spirit in postnatal women and biopsychosocial causes such as infections (malaria, loss, ‘thinking too much’, and alcohol and khat abuse. The preferred interventions for severe mental disturbance included mainly indigenous approaches, such as consulting Borana wise men or indigenous healers, prayer, holy water treatment and seeking modern mental health care as a last resort. Conclusions These findings will be of value for health care planners who wish to expand modern mental health care to this population, indicating the need to increase awareness about the causes of severe mental disturbance and their interventions and collaborate with influential people and indigenous healers to increase

  7. Hibernation-Based Therapy to Improve Survival of Severe Blood Loss

    Science.gov (United States)

    2014-10-01

    had more severe outcomes and measures . Therefore, improved outcomes are not associated with a higher dose of BHB/M and in fact would appear...animals survived until end of experiment (Figure 1).   4   Figure 1. Kaplan Meier Curve for observation of Maximum Tolerated Dose (MTD...2X or 4X BHB/M 0 10 20 30 40 50 Ba se lin e Sh oc k 35 LR 1 FR 2 FR 1 90 FR 7 FR 2 0 BHB-2X (n=6) BHB-4X (n=5) BH B co nc en tr at io n

  8. Genetic frequencies related to severe or profound sensorineural hearing loss in Inner Mongolia Autonomous Region

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    Yongzhi Liu

    Full Text Available Abstract The aim was to study the frequencies of common deafness-related mutations and their contribution to hearing loss in different regions of Inner Mongolia. A total of 738 deaf children were recruited from five different ethnic groups of Inner Mongolia, including Han Chinese (n=486, Mongolian (n=216, Manchurian (n=24, Hui (n=6 and Daur (n=6. Nine common mutations in four genes (GJB2, SLC26A4, GJB3 and mitochondrial MT-RNR1 gene were detected by allele-specific PCR and universal array. At least one mutated allele was detected in 282 patients. Pathogenic mutations were detected in 168 patients: 114 were homozygotes and 54 were compound heterozygotes. The 114 patients were carriers of only one mutated allele. The frequency of GJB2 variants in Han Chinese (21.0% was higher than that in Mongolians (16.7%, but not significantly different. On the other hand, the frequency of SLC26A4 variants in Han Chinese (14.8% was lower than that in Mongolians (19.4%, but also not significantly different. The frequency of patients with pathogenic mutations was different in Ulanqab (21.4%, Xilingol (40.0%, Chifeng (40.0%, Hulunbeier (30.0%, Hohhot (26.3%, and in Baotou (0%. In conclusion, the frequency of mutated alleles in deafness-related genes did not differ between Han Chinese and Mongolians. However, differences in the distribution of common deafness-related mutations were found among the investigated areas of Inner Mongolia.

  9. Granulomatosis with Polyangiitis with Bilateral Facial Palsy and Severe Mixed Hearing Loss

    Directory of Open Access Journals (Sweden)

    Agnieszka Wawrzecka

    2016-01-01

    Full Text Available Granulomatosis with polyangiitis is autoimmune and rare disease. It affects many organs, but the most often affected organs are the nose, lungs, and kidneys. It is part of vasculitis and causes an autoimmune attack by an abnormal type of circulating antibody termed ANCAs against small blood vessels. Disease concerns both men and women with a peak age of presentation in the sixth and seven decades. Typically upper and lower respiratory tract and kidneys are involved. Otitis externa, otitis media, or mastoiditis rarely occurs in granulomatosis with polyangiitis. Deafness is the most dangerous aural complication. Histological examination of biopsy is often not specific. A case of GPA with bilateral otitis media, bilateral deafness, and bilateral facial palsy with fatal course is presented.

  10. [Ocular myositis as a rare cause of vision loss].

    Science.gov (United States)

    Rollnik, J D; Requadt, H

    2016-12-22

    Ocular myositis is a rare disease characterized by painful diplopia but loss of vision rarely occurs. The article reviews the literature focusing on the differential diagnostics. We report the case of an 80-year-old women suffering from slowly progressive loss of vision in the left eye. Diplopia was only present at the beginning and there was only moderate pain. Computed tomography and magnetic resonance imaging revealed a swelling of the left medial, lateral and inferior rectus muscles of the orbit leading to compression of the optic nerve in the orbital cone. An intravenous prednisolone stoss therapy (1000 mg per day for 3 consecutive days) was initiated, followed by oral medication of 100 mg per day then tapering over 10 weeks. Vision improved and no relapses were observed. Physicians should be aware of this rare disease to ensure quick diagnosis and treatment of ocular myositis.

  11. A rare cause of conductive hearing loss: High lateralized jugular bulb with bony dehiscence.

    Science.gov (United States)

    Barr, James G; Singh, Pranay K

    2016-06-01

    We present a rare case of pediatric conductive hearing loss due to a high lateralized jugular bulb. An 8-year-old boy with a right-sided conductive hearing loss of 40 dB was found to have a pink bulge toward the inferior part of the right eardrum. Computed tomography showed a high, lateralized right jugular bulb that had a superolaterally pointing diverticulum that bulged into the lower mesotympanum and posterior external auditory meatus. It was explained to the child's parents that it is important never to put any sharp objects into the ears because of the risk of injury to the jugular vein. A high, lateralized jugular bulb with a diverticulum is a rare anatomic abnormality. Correct diagnosis of this abnormality is important so that inappropriate intervention does not occur.

  12. The occurrence of, and economic losses caused by Armillaria in the Western Carpathian Mts

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    Adam Kaliszewski

    2013-12-01

    Full Text Available An investigation carried out in the Western Carpathian Mountains (Ujsoły, Węgierska Górka, Ustroń and Wisła Forest Districts demonstrated a strong relationship between dieback in Norway spruce stands and the intensity of occurrence of Armillaria ostoyae. For the most endangered site types – mountain deciduous forest (LG and mountain mixed forest (LMG, analyses of losses of annual volume increment and of stand productivity were performed, and their financial dimensions determined. The greatest losses – of about 8 m3/ha/year for tree stands of the age of 100 years, and 400 m3/ha for the rotation period – were found for LG (Mountain broadleaved forest site type.

  13. The Causes for the loss of Inflection and Its Impact upon the English Language

    Institute of Scientific and Technical Information of China (English)

    余佳

    2015-01-01

    As one of the linguistic phenomena,inflection has embodied strong brands of times,experiencing enormous change of which the trend is the loss of inflection.This thesis analyzed the reasons of the development trend of inflection from the internal and external factors,explaining the profound influences of the reduction of inflection on the English language which are both on the micro level and on the macro level.

  14. International trade causes large net economic losses in tropical countries via the destruction of ecosystem services.

    Science.gov (United States)

    Chang, Junning; Symes, William S; Lim, Felix; Carrasco, L Roman

    2016-05-01

    Despite the large implications of the use of tropical land for exports ("land absorption") on ecosystem services (ES) and global biodiversity conservation, the magnitude of these externalities is not known. We quantify the net value of ES lost in tropical countries as a result of cropland, forestland and pastureland absorption for exports after deducting ES gains through imports ("land displacement"). We find that net ES gains occur only in 7 out of the 41 countries and regions considered. We estimate global annual net losses of over 1.7 x 10(12) international dollars (I$) (I$1.1 x 10(12) if carbon-related services are not considered). After deducting the benefits from agricultural, forest and livestock rents in land replacing tropical forests, the net annual losses are I$1.3 and I$0.7 x 10(12), respectively. The results highlight the large magnitude of tropical ES losses through international trade that are not compensated by the rents of land uses in absorbed land.

  15. Species-area relationships and extinctions caused by habitat loss and fragmentation.

    Science.gov (United States)

    Rybicki, Joel; Hanski, Ilkka

    2013-05-01

    The species-area relationship (SAR) has been used to predict the numbers of species going extinct due to habitat loss, but other researchers have maintained that SARs overestimate extinctions and instead one should use the endemics-area relationship (EAR) to predict extinctions. Here, we employ spatially explicit simulations of large numbers of species in spatially heterogeneous landscapes to investigate SARs and extinctions in a dynamic context. The EAR gives the number of species going extinct immediately after habitat loss, but typically many other species have unviable populations in the remaining habitat and go extinct soon afterwards. We conclude that the EAR underestimates extinctions due to habitat loss, the continental SAR (with slope ~0.1 or somewhat less) gives a good approximation of short-term extinctions, while the island SAR calculated for discrete fragments of habitat (with slope ~0.25) predicts the long-term extinctions. However, when the remaining area of land-covering habitat such as forest is roughly less than 20% of the total landscape and the habitat is highly fragmented, all current SARs underestimate extinction rate. We show how the 'fragmentation effect' can be incorporated into a predictive SAR model. When the remaining habitat is highly fragmented, an effective way to combat the fragmentation effect is to aggregate habitat fragments into clusters rather than to place them randomly across the landscape. © 2013 John Wiley & Sons Ltd/CNRS.

  16. Salivary Melatonin and the Severity of Attachment Loss: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Leila Golpasand-Hagh

    2014-01-01

    Full Text Available Background. Melatonin (MT: N-acetyl-5-methoxytryptamine is a neuroendocrine hormone secreted mainly by the pineal gland in the brain. MT is produced with a circadian rhythm characterized by elevated blood levels during the night. In healthy individuals, maximal secretion of MT occurs between midnight and 2:00 am, whereas the minimal production occurs during the day. MT can be determined by repeated measurement of plasma or salivary MT or urine sulfatoxy-melatonin. Melatonin has powerful antioxidant effects, has an immunomodulatory role, stimulates the synthesis of type I collagen fibers, and promotes bone formation. Melatonin is also secreted in the saliva, although its role in the mouth is not known well. The purpose of this study was to examine the correlation between salivary melatonin level and periodontal diseases. Methods. Fifty subjects by mean age of 40.44±6.38 years were equally divided into 5 groups: 10 healthy subjects, 10 subjects with gingivitis, 10 subjects with localized moderate chronic periodontitis, 10 subjects with generalized moderate chronic periodontitis, and 10 subjects with generalized severe chronic periodontitis. Saliva samples were collected from all the subjects and melatonin levels were determined using an enzyme-linked immunosorbent assay. Two-way and one-way ANOVA and Tukey test were used to analyze relationships among variables. Results. Healthy subjects had significantly higher salivary melatonin level (5.29±0.50 pg/mL compared to patients with gingivitis (4.35±0.30 pg/mL (P<0.001. The difference between salivary melatonin level in patients with gingivitis and periodontitis was significant (P<0.001. Level of melatonin in patients with generalized severe chronic periodontitis (3.39±0.10 pg/mL was significantly lower than that in other groups (P<0.01. Conclusions. This study determined that salivary melatonin level in patients with periodontal diseases is lower than that in healthy subjects. Consequently

  17. Localization of the large-angle foil-scattering beam loss caused by the multiturn charge-exchange injection

    Science.gov (United States)

    Kato, Shinichi; Yamamoto, Kazami; Yoshimoto, Masahiro; Harada, Hiroyuki; Kinsho, Michikazu

    2013-07-01

    In the 3 GeV rapid cycling synchrotron of the Japan Proton Accelerator Research Complex, significant losses were observed at the branching of the H0 dump line and the beam position monitor that was inserted downstream of the H0 dump branch duct. These losses were caused by the large-angle scattering of the injection and circulating beams at the charge-exchange foil. To realize high-power operation, these losses must be mitigated. Therefore, a new collimation system was developed and installed in October 2011. To efficiently optimize this system, the behavior of particles scattered by the foil and produced by the absorber were simulated, and the optimal position and angle of the absorber were investigated. During this process, an angle regulation method for the absorber was devised. An outline of this system, the angle regulation method for the absorber, and the performance of this new collimation system are described.

  18. Arthroscopic Remplissage and Open Latarjet Procedure for the Treatment of Anterior Glenohumeral Instability With Severe Bipolar Bone Loss.

    Science.gov (United States)

    Katthagen, J Christoph; Anavian, Jack; Tahal, Dimitri S; Millett, Peter J

    2016-10-01

    Bipolar bone loss in patients with anterior glenohumeral instability is challenging to treat. The goal of the treatment is to restore stability by ensuring that the humeral head remains within the glenoid vault. This can be achieved either with the combination of an arthroscopic Bankart procedure and remplissage (glenoid bone loss Latarjet procedure (glenoid bone loss >25%). In cases with more severe bipolar bone loss of both the glenoid and the humeral head, the conventional approach has been to lengthen the articular arc of the glenoid and to ignore the Hill-Sachs lesion. However, it has recently been shown that this can still lead to an "off-track" situation with persistent shoulder instability from engagement of the Hill-Sachs on the anterior glenoid. In these cases, the combination of a Hill-Sachs remplissage and the Latarjet procedure can be effective in preventing persistent instability. In this technical note, the surgical technique of an arthroscopic Hill-Sachs remplissage in combination with an open Latarjet procedure is presented.

  19. TDP-43 Loss-of-Function Causes Neuronal Loss Due to Defective Steroid Receptor-Mediated Gene Program Switching in Drosophila

    Directory of Open Access Journals (Sweden)

    Lies Vanden Broeck

    2013-01-01

    Full Text Available TDP-43 proteinopathy is strongly implicated in the pathogenesis of amyotrophic lateral sclerosis and related neurodegenerative disorders. Whether TDP-43 neurotoxicity is caused by a novel toxic gain-of-function mechanism of the aggregates or by a loss of its normal function is unknown. We increased and decreased expression of TDP-43 (dTDP-43 in Drosophila. Although upregulation of dTDP-43 induced neuronal ubiquitin and dTDP-43-positive inclusions, both up- and downregulated dTDP-43 resulted in selective apoptosis of bursicon neurons and highly similar transcriptome alterations at the pupal-adult transition. Gene network analysis and genetic validation showed that both up- and downregulated dTDP-43 directly and dramatically increased the expression of the neuronal microtubule-associated protein Map205, resulting in cytoplasmic accumulations of the ecdysteroid receptor (EcR and a failure to switch EcR-dependent gene programs from a pupal to adult pattern. We propose that dTDP-43 neurotoxicity is caused by a loss of its normal function.

  20. Premature closure of the upper esophageal sphincter as a cause of severe deglutition disorder in infancy

    DEFF Research Database (Denmark)

    Nielsen, Rasmus; Husby, Steffen; Kruse-Andersen, Søren

    2005-01-01

    of these causes. An 8-week-old infant was referred because of suspicion of cricopharyngeal achalasia causing persistent swallowing problems and failure to thrive. Manometry results showed normal resting tone and relaxation but premature closure of the upper esophageal sphincter. The infant was treated...

  1. Disruption of germination and seedling development in Brassica napus by mutations causing severe seed hormonal imbalance

    Directory of Open Access Journals (Sweden)

    Tung eNguyen

    2016-03-01

    Full Text Available The Brassica napus (oilseed rape accession 1012-98 shows a disturbed germination phenotype that was thought to be associated with its lack of testa pigmentation and thin seed coat. Here we demonstrate that the disturbed germination and seedling development are actually due to independent mutations that disrupt the balance of hormone metabolites and their regulators in the seeds. High-throughput UPLC-MS/MS hormone profiling of seeds and seedlings before and after germination revealed that 1012-98 has a severely disturbed hormone balance with extremely atypical, excessive quantities of auxin and ABA metabolites. The resulting hypersensitivity to abscisic acid (ABA and a corresponding increase in dormancy often results in death of the embryo after imbibition or high frequencies of disturbed, often lethal developmental phenotypes, resembling Arabidopsis mutants for the auxin regulatory factor gene ARF10 or the auxin-overproducing transgenic line iaaM-OX. Molecular cloning of Brassica ARF10 orthologues revealed four loci in normal B. napus, two derived from the Brassica A genome and two from the C genome. On the other hand, the phenotypic mutant 1012-98 exhibited amplification of C-genome BnaC.ARF10 copy number along with a chimeric allele originating from recombination between homoeologous A and C genome loci which lead to minor increase of Bna.ARF10 transcription on the critical timepoint for seed germination, the indirect regulator of ABI3, the germinative inhibitor. Bna.GH3.5 expression was upregulated to conjugate free auxin to IAA-asp between 2-6 DAS. Functional amino acid changes were also found in important DNA binding domains of one BnaC.ARF10 locus, suggesting that regulatory changes in Bna.ARF10 are collectively responsible for the observed phenotpyes in 1012-98. To our knowledge, this study is the first to report disruption of germination and seedling development in Brassica napus caused by the crosstalk of auxin-ABA and the

  2. Impact of Orlistat-Induced Weight Loss on Diastolic Function and Heart Rate Variability in Severely Obese Subjects with Diabetes

    Directory of Open Access Journals (Sweden)

    Julie Martin

    2011-01-01

    Full Text Available Objective. Determine the impact of Orlistat-induced weight loss on metabolic profile and cardiovascular function in severely obese patients with type 2 diabetes. Methods. Twenty-nine patients were randomized either to a nonplacebo control group or to a treatment group with Orlistat thrice a day. Metabolic profile, anthropometric parameters, heart rate variability indices, and echocardiographic variables were measured before and after a 12-week treatment period. Results. Treatment with Orlistat induced a modest but significant weight loss compared to controls (3.7 ± 3.0 versus 0.5 ± 2.2 kg, resp.; P=.003. There was significant decrease in fasting glycemia (7.9 ± 3.0 versus 6.7 ± 2.2 mmol/L; P=.03 and significant improvements in left ventricular diastolic function (P=.03 and in the sympathovagal balance (LF/HF ratio (P=.04 in the Orlistat group. Conclusion. These results suggest that a modest weight loss improves fasting glycemia, left ventricular diastolic function, and sympathovagal balance in severely obese patients with type 2 diabetes.

  3. A theoretical approach to thermal noise caused by an inhomogeneously distributed loss -- Physical insight by the advanced modal expansion

    OpenAIRE

    Yamamoto, Kazuhiro; Ando, Masaki; Kawabe, Keita; Tsubono, Kimio

    2006-01-01

    We modified the modal expansion, which is the traditional method used to calculate thermal noise. This advanced modal expansion provides physical insight about the discrepancy between the actual thermal noise caused by inhomogeneously distributed loss and the traditional modal expansion. This discrepancy comes from correlations between the thermal fluctuations of the resonant modes. The thermal noise spectra estimated by the advanced modal expansion are consistent with the results of measurem...

  4. Pathogenic Variant in ACTB, p.Arg183Trp, Causes Juvenile-Onset Dystonia, Hearing Loss, and Developmental Delay without Midline Malformation

    Directory of Open Access Journals (Sweden)

    Erin Conboy

    2017-01-01

    Full Text Available ACTB encodes the β-actin, and pathogenic variations in this gene have typically been associated with Baraitser-Winter cerebrofrontofacial syndrome, a congenital malformation syndrome characterized by short stature, craniofacial anomalies, and cerebral anomalies. Here, we describe the third case with the p.Arg183Trp variant in ACTB causing juvenile-onset dystonia. Our patient has severe, intractable dystonia, developmental delay, and sensorineural hearing loss, besides hyperintensities in the caudate nuclei and putamen on the brain MRI, which is a distinct but overlapping phenotype with the previously reported case of identical twins with the same alteration in ACTB.

  5. Severe loss of suitable climatic conditions for marsupial species in Brazil: challenges and opportunities for conservation.

    Directory of Open Access Journals (Sweden)

    Rafael D Loyola

    Full Text Available A wide range of evidences indicate climate change as one the greatest threats to biodiversity in the 21st century. The impacts of these changes, which may have already resulted in several recent species extinction, are species-specific and produce shifts in species phenology, ecological interactions, and geographical distributions. Here we used cutting-edge methods of species distribution models combining thousands of model projections to generate a complete and comprehensive ensemble of forecasts that shows the likely impacts of climate change in the distribution of all 55 marsupial species that occur in Brazil. Consensus projections forecasted range shifts that culminate with high species richness in the southeast of Brazil, both for the current time and for 2050. Most species had a significant range contraction and lost climate space. Turnover rates were relatively high, but vary across the country. We also mapped sites retaining climatic suitability. They can be found in all Brazilian biomes, especially in the pampas region, in the southern part of the Brazilian Atlantic Forest, in the north of the Cerrado and Caatinga, and in the northwest of the Amazon. Our results provide a general overview on the likely effects of global climate change on the distribution of marsupials in the country as well as in the patterns of species richness and turnover found in regional marsupial assemblages.

  6. Cortical blindness following spinal surgery: very rare cause of perioperative vision loss.

    Science.gov (United States)

    Goni, Vijay; Tripathy, Sujit Kumar; Goyal, Tarun; Tamuk, Tajir; Panda, Bijnya Birajita; Bk, Shashidhar

    2012-12-01

    A 38-year-old man was operated with posterior spinal decompression and pedicle screw instrumentation for his L2 fracture with incomplete neurological deficit. In the recovery, he complained of blindness in both eyes after twelve hours. Computed tomographic scan and magnetic resonance angiography revealed bilateral occipital lobe infarcts. He remained permanently blind even after three years follow-up. Though rare, perioperative vision loss is a potential complication following spine surgery in prone position. We report a rare occurrence of cortical blindness following lumbar spine surgery.

  7. Solid cystic trigeminal schwannoma with intraorbital extension causing proptosis and vision loss

    Science.gov (United States)

    Gupta, Pankaj; Sharma, Arvind; Singh, Jitendra

    2016-01-01

    Schwannomas are slowly growing, well capsulated, benign tumors. Involvement of vestibular nerve is most commonly followed by trigeminal nerve. Trigeminal schwannoma is rare entity, and cystic degeneration with intraorbital extension of trigeminal schwannoma is even rarer. These tumors occur in fourth and fifth decades of life and patients have variable presentation depending on which cranial compartment is involved. Orbital schwannoma usually presents with proptosis with or without vision loss. We are reporting such a rare case of solid cystic trigeminal schwannoma with intraorbital extension through superior orbital fissure that was removed surgically. PMID:27695572

  8. Incidence and main causes of severe maternal morbidity in São Luís, Maranhão, Brazil: a longitudinal study

    Directory of Open Access Journals (Sweden)

    Ana Paula Pierre Moraes

    Full Text Available CONTEXT AND OBJECTIVE: Evaluation of severe maternal morbidity has been used in monitoring of maternal health. The objective of this study was to estimate its incidence and main causes in São Luís, Maranhão, Brazil. DESIGN AND SETTING: Prospective longitudinal study, carried out in two public high-risk maternity hospitals and two public intensive care units (ICUs for referral of obstetric cases from the municipality. METHODS: Between March 1, 2009, and February 28, 2010, all cases of severe maternal morbidity according to the Mantel and Waterstone criteria were identified. The sociodemographic and healthcare characteristics of the extremely severe cases were compared with the less severe cases, using the Fisher, Χ2, Student t and Mann-Whitney tests, with a significance level of < 0.05. RESULTS: 127 cases of severe maternal morbidity were identified among 8,493 deliveries, i.e. an incidence of 15.0/1000 deliveries. Out of 122 cases interviewed, 121 cases were within the Waterstone criteria and 29 were within the Mantel criteria, corresponding to incidences of 14.1/1000 and 3.4/1000 deliveries, respectively. These rates were lower than those described in the literature, possibly due to case loss. The main causes were hypertension during pregnancy, which was more frequent in less severe cases (P = 0.001 and obstetric hemorrhage, which was more common among extremely severe cases (P = 0.01. CONCLUSIONS: Direct obstetric disorders were the main causes of severe maternal morbidity in São Luís, Maranhão. Investigation and monitoring of severe morbidity may contribute towards improving obstetric care in the municipality.

  9. Lacrimal punctum occlusion in the treatment of severe keratoconjunctivitis sicca caused by Sjogren syndrome - A uniocular evaluation

    NARCIS (Netherlands)

    Mansour, Khaled; Leonhardt, Carolien J.; Kalk, Wouter W.; Bootsma, Hendrika; Bruin, Klaas J.; Blanksma, Lieuwe J.

    Purpose: A controlled uniocular study to evaluate the short-term efficacy of lacrimal punctum occlusion in the treatment of severe dry eye caused by Sjogren syndrome. Methods: Uniocular punctum occlusion by punctum plug in the upper and lower puncta in 1 eye was performed in 20 patients with severe

  10. Tau causes synapse loss without disrupting calcium homeostasis in the rTg4510 model of tauopathy.

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    Katherine J Kopeikina

    Full Text Available Neurofibrillary tangles (NFTs of tau are one of the defining hallmarks of Alzheimer's disease (AD, and are closely associated with neuronal degeneration. Although it has been suggested that calcium dysregulation is important to AD pathogenesis, few studies have probed the link between calcium homeostasis, synapse loss and pathological changes in tau. Here we test the hypothesis that pathological changes in tau are associated with changes in calcium by utilizing in vivo calcium imaging in adult rTg4510 mice that exhibit severe tau pathology due to over-expression of human mutant P301L tau. We observe prominent dendritic spine loss without disruptions in calcium homeostasis, indicating that tangles do not disrupt this fundamental feature of neuronal health, and that tau likely induces spine loss in a calcium-independent manner.

  11. Inner ear anomalies causing congenital sensorineural hearing loss: CT and MR imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Hyun Sook; Paik, Sang Hyun; Cha, Jang Gyu; Park, Seong Jin; Joh, Joon Hee; Park, Jai Soung; Kim, Dae Ho; Lee, Hae Kyung; Kim, Shi Chan [Soonchunhyang University Bucheon Hospital, Buchon(Korea, Republic of)

    2005-07-15

    Many congenital dysplasias of the osseous labyrinth have been identified, and the differential diagnosis of these dysplasias is essential for delivering proper patient management. We retrospectively reviewed the computed tomography (CT) and magnetic resonance (MR) imaging findings of 20 children who had congenital sensorineural hearing loss. The children included cases of enlarged vestibular aqueduct and endolymphatic sac (n=8), aplasia of the semicircular canal (n=4), lateral semicircular canal-vestibule dysplasia (n=3), common cavity malformations with a large vestibule (n=1), cochlear hypoplasia (n=1), Mondini's dysplasia with large vestibular aqueduct (n=1), Mondini's dysplasia with a large vestibule (n=1), and small internal auditory canal (n=1). Six cases were unilateral. Nine cases had combined deformities, and nine cased had cochlear implants. CT was performed with a 1.0-mm thickness in the direct coronal and axial sections with using bone algorithms. MR was performed with a temporal 3D T2 FSE 10-mm scan and with routine brain images. We describe here the imaging features for the anomalies of the inner ear in patients suffering from congenital sensorineural hearing loss.

  12. Study On Budget Revenue Collection, Shadow Economy and Tax Losses Caused By It

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    Radu Claudia Florina

    2017-06-01

    Full Text Available Tax avoidance is a phenomenon faced by all countries, to a lesser or greater extent, and we can say that it has begun to manifest itself since the introduction of taxes. It is known that generally taxes are not pleasing to taxpayers, especially when their level is high. However, it is important for individuals, as a whole, not to evade from their tax obligations. In this context taxes can be regarded as a necessary evil to ensure the resources needed for state functioning. But often some taxpayers are looking for ways to avoid taxes, engaging either in tax evasion to the shelter of the law or in fraudulent evasion. In this paper we present some of the aspects that motivate individuals to pay taxes. Also we analyze the situation of budgetary revenues in Alba County and also the evolution of the main income of consolidated general budget in Romania. In the end of the paper we intend to draw a parallel between shadow economy, tax burden and tax losses due to shadow economy for a sample of 32 countries. In this way we can see where underground economy and tax losses have the highest values and where are required measures to mitigate them.

  13. Anthropogenic causes of wetland loss and degradation in the lower Kłodnica valley (southern Poland

    Directory of Open Access Journals (Sweden)

    Wójcicki Krzysztof J.

    2015-12-01

    Full Text Available Loss and degradation of wetlands is now one of the most important environmental issues on a global scale. Previous research based on analyses of cartographic materials allow for quantification of changes in wetland area in recent centuries. The results of lithological research of peat cores, reported in this publication, have established that the processes of anthropogenic loss of wetlands can be much older and in the Kłodnica valley were initiated in the first millennium BC. As a result of increased mineral sedimentation accompanying soil erosion some peatlands have been fossilized whilst the area of others has been reduced. In total, the surface area of peat-forming wetlands in the bottom of the Kłodnica valley decreased by over 60% between the time of the Lusatian Culture settlement and the Middle Ages. Post-peatland habitats are recently used for agricultural or colonized by non-peat forming vegetation. These processes have played a more important role in the degradation of peatland ecosystems than the direct human impact in historic times. Changes in hydrographic networks, land drainage and regulation of water levels in rivers and canals in the last century have contributed to further reducing the wetland areas by almost 50% compared to the 1880s. These processes, however, have mainly affected ephemeral non-peat forming wetlands.

  14. Mutations in CHD7 in patients with CHARGE syndrome cause T-B + natural killer cell + severe combined immune deficiency and may cause Omenn-like syndrome.

    NARCIS (Netherlands)

    Gennery, A.R.; Slatter, M.A.; Rice, J.; Hoefsloot, L.H.; Barge, D.; McLean-Tooke, A.; Montgomery, T.; Goodship, J.A.; Burt, A.D.; Flood, T.J.; Abinun, M.; Cant, A.J.; Johnson, D.

    2008-01-01

    More than 11 genetic causes of severe combined immunodeficiency (SCID) have been identified, affecting development and/or function of T lymphocytes, and sometimes B lymphocytes and natural killer (NK) cells. Deletion of 22q11.2 is associated with immunodeficiency, although less than 1% of cases are

  15. Anaphylaxis and severe systemic reactions caused by skin contact with persulfates in hair-bleaching products.

    Science.gov (United States)

    Hoekstra, Margriet; van der Heide, Sicco; Coenraads, Pieter Jan; Schuttelaar, Marie Louise Anna

    2012-06-01

    Persulfates have been reported to cause both delayed-type and immediate skin reactions. They may also cause immediate reactions of the mucous membranes of the bronchial system through inhalation, leading to asthma and rhinitis. Anaphylactic reactions caused by contact with persulfates are rare. The mechanism of immediate reactions caused by persulfates is unclear. To report 2 cases with systemic reactions after skin contact with persulfates, and to propose a test protocol for diagnosing immediate reactions caused by persulfates. Prick tests with serial dilutions of ammonium and potassium persulfate were performed. Patch tests were also performed with the two agents. Persulfate-specific IgE was detected with two different IgE immunoblotting techniques. Prick tests were positive with ammonium and potassium persufate, but no specific IgE was detected in the serum. Patch tests showed early positive reactions to both persulfates in 1 patient. Prick tests and patch tests can be valuable in the testing of patients with a suspicion of an immediate-type reaction caused by persulfates. The mechanism of these reactions remains unclear. © 2012 John Wiley & Sons A/S.

  16. Rapid onset of severe twin-twin transfusion syndrome caused by placental venous thrombosis

    NARCIS (Netherlands)

    Nikkels, PGJ; van Gemert, MJC; Sollie-Szarynska, KM; Molendijk, H; Timmer, B; Machin, GA

    2002-01-01

    We report a case of rapid onset of severe twin-twin transfusion syndrome (TTTS) at 25 weeks gestation in a monochorionic twin pregnancy that was uneventful before that time. Thrombosis of a main venous branch draining several arteriovenous (AV) anastomoses to the donor changed the previous hemodynam

  17. Renal allograft loss in the first post-operative month: causes and consequences.

    LENUS (Irish Health Repository)

    Phelan, Paul J

    2013-01-15

    Early transplant failure is a devastating outcome after kidney transplantation. We report the causes and consequences of deceased donor renal transplant failure in the first 30 d at our center between January 1990 and December 2009. Controls were adult deceased donor transplant patients in the same period with an allograft that functioned >30 d. The incidence of early graft failure in our series of 2381 consecutive deceased donor transplants was 4.6% (n = 109). The causes of failure were allograft thrombosis (n = 48; 44%), acute rejection (n = 19; 17.4%), death with a functioning allograft (n = 17; 15.6%), primary non-function (n = 14;12.8%), and other causes (n = 11; 10.1%). Mean time to allograft failure was 7.3 d. There has been a decreased incidence of all-cause early failure from 7% in 1990 to <1% in 2009. Patients who developed early failure had longer cold ischemia times when compared with patients with allografts lasting >30 d (p < 0.001). Early allograft failure was strongly associated with reduced patient survival (p < 0.001). In conclusion, early renal allograft failure is associated with a survival disadvantage, but has thankfully become less common in recent years.

  18. Loss of stability and hydrophobicity of presenilin 1 mutations causing Alzheimer's Disease

    DEFF Research Database (Denmark)

    Somavarapu, Arun Kumar; Kepp, Kasper Planeta

    2016-01-01

    Nearly 200 mutations in the gene coding for presenilin 1 (PSEN1) cause early-onset Alzheimer's Disease, yet the molecular mechanism remains obscure. As a meta-analysis, we compiled available clinical and biochemical data for PSEN1 variants and correlated these to chemical properties of the mutants...

  19. Elevated mutant dynorphin A causes Purkinje cell loss and motor dysfunction in spinocerebellar ataxia type 23

    NARCIS (Netherlands)

    Smeets, Cleo J. L. M.; Jezierska, Justyna; Watanabe, Hiroyuki; Duarri Pique, Anna; Fokkens, Michiel R.; Meijer, Michel; Zhou, Qin; Yakovleva, Tania; Boddeke, Erik; den Dunnen, Wilfred; van Deursen, Jan; Bakalkin, Georgy; Kampinga, Harm H.; van de Sluis, Bart; Verbeek, Dineke S.

    2015-01-01

    Spinocerebellar ataxia type 23 is caused by mutations in PDYN, which encodes the opioid neuropeptide precursor protein, prodynorphin. Prodynorphin is processed into the opioid peptides, a-neoendorphin, and dynorphins A and B, that normally exhibit opioid-receptor mediated actions in pain signalling

  20. A case report of primary orbital non-Hodgkin’s lymphoma causing complete vision loss

    Directory of Open Access Journals (Sweden)

    Lamba, Neerav

    2016-04-01

    Full Text Available A 29-year-old male with acquired immunodeficiency syndrome presented with a week of left eye blurriness, which then progressed to complete vision loss. On exam, the left pupil was nonreactive to light, and fundoscopy showed significant optic nerve edema. CT and MRI of the left orbit showed a mass lesion compressing the posterior aspect of the sclera with diffuse thickening and contrast enhancement of the retrobulbar portion of the left optic nerve. The lesion demonstrated low T1 and intermediate T2 intensities and heterogeneous contrast enhancement and measured 17.4 mm x 15 mm x 10.6 mm. Anterior orbitotomy with exploration and biopsy were performed. Immunohistochemical studies confirmed diffuse large B-cell lymphoma and a workup showed no systemic involvement. Plans for treatment with chemotherapy and radiation were initiated. Even though rare, primary orbital NHL should be in the differential for relatively acute blindness without other symptoms, especially in patients with AIDS.

  1. Loss of RMI2 Increases Genome Instability and Causes a Bloom-Like Syndrome.

    Science.gov (United States)

    Hudson, Damien F; Amor, David J; Boys, Amber; Butler, Kathy; Williams, Lorna; Zhang, Tao; Kalitsis, Paul

    2016-12-01

    Bloom syndrome is a recessive human genetic disorder with features of genome instability, growth deficiency and predisposition to cancer. The only known causative gene is the BLM helicase that is a member of a protein complex along with topoisomerase III alpha, RMI1 and 2, which maintains replication fork stability and dissolves double Holliday junctions to prevent genome instability. Here we report the identification of a second gene, RMI2, that is deleted in affected siblings with Bloom-like features. Cells from homozygous individuals exhibit elevated rates of sister chromatid exchange, anaphase DNA bridges and micronuclei. Similar genome and chromosome instability phenotypes are observed in independently derived RMI2 knockout cells. In both patient and knockout cell lines reduced localisation of BLM to ultra fine DNA bridges and FANCD2 at foci linking bridges are observed. Overall, loss of RMI2 produces a partially active BLM complex with mild features of Bloom syndrome.

  2. Unusual cause of weight loss in a patient with HIV-hepatitis C virus coinfection

    Directory of Open Access Journals (Sweden)

    Gogia A

    2010-01-01

    Full Text Available Recombinant interferon α (IFN α, alone or in combination, is used extensively in the treatment of hepatitis C infection. IFN therapy is not free of side-effects and autoimmune thyroiditis is one of its rare side-effects. We present here a case of a patient with hepatitis C virus-human immunodeficiency virus coinfection on interferon therapy who presented with significant weight loss. He was found to have IFN-related autoimmune thyrotoxicosis and responded to antithyroid drugs and propanolol. Therefore, this case highlights that IFN-induced thyroiditis is an unusual side-effect and that during treatment, a thyroid-stimulating hormone assay should be performed at regular intervals (every 8-12 weeks.

  3. Air bubble contact with endothelial cells causes a calcium-independent loss in mitochondrial membrane potential.

    Directory of Open Access Journals (Sweden)

    Peter Sobolewski

    Full Text Available OBJECTIVE: Gas microembolism remains a serious risk associated with surgical procedures and decompression. Despite this, the signaling consequences of air bubbles in the vasculature are poorly understood and there is a lack of pharmacological therapies available. Here, we investigate the mitochondrial consequences of air bubble contact with endothelial cells. METHODS AND RESULTS: Human umbilical vein endothelial cells were loaded with an intracellular calcium indicator (Fluo-4 and either a mitochondrial calcium indicator (X-Rhod-1 or mitochondrial membrane potential indicator (TMRM. Contact with 50-150 µm air bubbles induced concurrent rises in intracellular and mitochondrial calcium, followed by a loss of mitochondrial membrane potential. Pre-treating cells with 1 µmol/L ruthenium red, a TRPV family calcium channel blocker, did not protect cells from the mitochondrial depolarization, despite blocking the intracellular calcium response. Mitigating the interactions between the air-liquid interface and the endothelial surface layer with 5% BSA or 0.1% Pluronic F-127 prevented the loss of mitochondrial membrane potential. Finally, inhibiting protein kinase C-α (PKCα, with 5 µmol/L Gö6976, protected cells from mitochondrial depolarization, but did not affect the intracellular calcium response. CONCLUSIONS: Our results indicate that air bubble contact with endothelial cells activates a novel, calcium-independent, PKCα-dependent signaling pathway, which results in mitochondrial depolarization. As a result, mitochondrial dysfunction is likely to be a key contributor to the pathophysiology of gas embolism injury. Further, this connection between the endothelial surface layer and endothelial mitochondria may also play an important role in vascular homeostasis and disease.

  4. Connexin43 mutation causes heterogeneous gap junction loss and sudden infant death.

    Science.gov (United States)

    Van Norstrand, David W; Asimaki, Angeliki; Rubinos, Clio; Dolmatova, Elena; Srinivas, Miduturu; Tester, David J; Saffitz, Jeffrey E; Duffy, Heather S; Ackerman, Michael J

    2012-01-24

    An estimated 10% to 15% of sudden infant death syndrome (SIDS) cases may stem from channelopathy-mediated lethal arrhythmias. Loss of the GJA1-encoded gap junction channel protein connexin43 is known to underlie formation of lethal arrhythmias. GJA1 mutations have been associated with cardiac diseases, including atrial fibrillation. Therefore, GJA1 is a plausible candidate gene for premature sudden death. GJA1 open reading frame mutational analysis was performed with polymerase chain reaction, denaturing high-performance liquid chromatography, and direct DNA sequencing on DNA from 292 SIDS cases. Immunofluorescence and dual whole-cell patch-clamp studies were performed to determine the functionality of mutant gap junctions. Immunostaining for gap junction proteins was performed on SIDS-associated paraffin-embedded cardiac tissue. Two rare, novel missense mutations, E42K and S272P, were detected in 2 of 292 SIDS cases, a 2-month-old white boy and a 3-month-old white girl, respectively. Analysis of the E42K victim's parental DNA demonstrated a de novo mutation. Both mutations involved highly conserved residues and were absent in >1000 ethnically matched reference alleles. Immunofluorescence demonstrated no trafficking abnormalities for either mutation, and S272P demonstrated wild-type junctional conductance. However, junctional conductance measurements for the E42K mutation demonstrated a loss of function not rescued by wild type. Moreover, the E42K victim's cardiac tissue demonstrated a mosaic immunostaining pattern for connexin43 protein. This study provides the first molecular and functional evidence implicating a GJA1 mutation as a novel pathogenic substrate for SIDS. E42K-connexin43 demonstrated a trafficking-independent reduction in junctional coupling in vitro and a mosaic pattern of mutational DNA distribution in deceased cardiac tissue, suggesting a novel mechanism of connexin43-associated sudden death.

  5. Konjac Glucomannan Dietary Supplementation Causes Significant Fat Loss in Compliant Overweight Adults.

    Science.gov (United States)

    Kaats, Gilbert R; Bagchi, Debasis; Preuss, Harry G

    2015-10-22

    Changes in body composition and blood chemistries between overweight adult subjects receiving a supplement containing either 3 g of konjac glucomannan/300 mg calcium carbonate or a placebo containing only 300 mg of calcium carbonate were compared as the primary objective. A secondary objective was to compare outcome differences between compliant and partially compliant subjects. A total of 83 overweight adults (66 women and 17 men) completed a randomized, double-blind, placebo-controlled protocol in which they received either a glucomannan or placebo supplement for 60 days. Dual-energy x-ray absorptiometry (DEXA) total body scans and a 42-measurement blood test were completed at baseline and 60 days later. Compliance was assessed by rating self-reports of (1) how many tablets were taken, (2) adherence to taking the tablets 30 minutes before eating, and (3) a sum of the ratings for (1) and (2). An anonymous poststudy questionnaire and telephone calls were also completed by 80 (96%) of the participants who were used as the study cohort. No statistically significant differences were found between the groups on changes from baseline on the DEXA and blood tests. However, when subjects were classified as either compliant or partially compliant using the compliance measures, statistically significant reductions in scale weight, percentage body fat, fat mass, total cholesterol, and low-density lipoprotein (LDL) cholesterol were found in the glucomannan group compared to the placebo group. This study supports the efficacy glucomannan supplementation to reduce body weight, body fat, and circulating cholesterol levels without the concomitant loss of lean mass and bone density often associated with weight loss. However, these positive outcomes were not observable until corrections for compliance were applied.

  6. Loss-of-function HDAC8 mutations cause a phenotypic spectrum of Cornelia de Lange syndrome-like features, ocular hypertelorism, large fontanelle and X-linked inheritance

    Science.gov (United States)

    Kaiser, Frank J.; Ansari, Morad; Braunholz, Diana; Concepción Gil-Rodríguez, María; Decroos, Christophe; Wilde, Jonathan J.; Fincher, Christopher T.; Kaur, Maninder; Bando, Masashige; Amor, David J.; Atwal, Paldeep S.; Bahlo, Melanie; Bowman, Christine M.; Bradley, Jacquelyn J.; Brunner, Han G.; Clark, Dinah; Del Campo, Miguel; Di Donato, Nataliya; Diakumis, Peter; Dubbs, Holly; Dyment, David A.; Eckhold, Juliane; Ernst, Sarah; Ferreira, Jose C.; Francey, Lauren J.; Gehlken, Ulrike; Guillén-Navarro, Encarna; Gyftodimou, Yolanda; Hall, Bryan D.; Hennekam, Raoul; Hudgins, Louanne; Hullings, Melanie; Hunter, Jennifer M.; Yntema, Helger; Innes, A. Micheil; Kline, Antonie D.; Krumina, Zita; Lee, Hane; Leppig, Kathleen; Lynch, Sally Ann; Mallozzi, Mark B.; Mannini, Linda; Mckee, Shane; Mehta, Sarju G.; Micule, Ieva; Mohammed, Shehla; Moran, Ellen; Mortier, Geert R.; Moser, Joe-Ann S.; Noon, Sarah E.; Nozaki, Naohito; Nunes, Luis; Pappas, John G.; Penney, Lynette S.; Pérez-Aytés, Antonio; Petersen, Michael B.; Puisac, Beatriz; Revencu, Nicole; Roeder, Elizabeth; Saitta, Sulagna; Scheuerle, Angela E.; Schindeler, Karen L.; Siu, Victoria M.; Stark, Zornitza; Strom, Samuel P.; Thiese, Heidi; Vater, Inga; Willems, Patrick; Williamson, Kathleen; Wilson, Louise C.; Hakonarson, Hakon; Quintero-Rivera, Fabiola; Wierzba, Jolanta; Musio, Antonio; Gillessen-Kaesbach, Gabriele; Ramos, Feliciano J.; Jackson, Laird G.; Shirahige, Katsuhiko; Pié, Juan; Christianson, David W.; Krantz, Ian D.; Fitzpatrick, David R.; Deardorff, Matthew A.

    2014-01-01

    Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder with distinct facies, growth failure, intellectual disability, distal limb anomalies, gastrointestinal and neurological disease. Mutations in NIPBL, encoding a cohesin regulatory protein, account for >80% of cases with typical facies. Mutations in the core cohesin complex proteins, encoded by the SMC1A, SMC3 and RAD21 genes, together account for ∼5% of subjects, often with atypical CdLS features. Recently, we identified mutations in the X-linked gene HDAC8 as the cause of a small number of CdLS cases. Here, we report a cohort of 38 individuals with an emerging spectrum of features caused by HDAC8 mutations. For several individuals, the diagnosis of CdLS was not considered prior to genomic testing. Most mutations identified are missense and de novo. Many cases are heterozygous females, each with marked skewing of X-inactivation in peripheral blood DNA. We also identified eight hemizygous males who are more severely affected. The craniofacial appearance caused by HDAC8 mutations overlaps that of typical CdLS but often displays delayed anterior fontanelle closure, ocular hypertelorism, hooding of the eyelids, a broader nose and dental anomalies, which may be useful discriminating features. HDAC8 encodes the lysine deacetylase for the cohesin subunit SMC3 and analysis of the functional consequences of the missense mutations indicates that all cause a loss of enzymatic function. These data demonstrate that loss-of-function mutations in HDAC8 cause a range of overlapping human developmental phenotypes, including a phenotypically distinct subgroup of CdLS. PMID:24403048

  7. Loss of MAFB Function in Humans and Mice Causes Duane Syndrome, Aberrant Extraocular Muscle Innervation, and Inner-Ear Defects.

    Science.gov (United States)

    Park, Jong G; Tischfield, Max A; Nugent, Alicia A; Cheng, Long; Di Gioia, Silvio Alessandro; Chan, Wai-Man; Maconachie, Gail; Bosley, Thomas M; Summers, C Gail; Hunter, David G; Robson, Caroline D; Gottlob, Irene; Engle, Elizabeth C

    2016-06-02

    Duane retraction syndrome (DRS) is a congenital eye-movement disorder defined by limited outward gaze and retraction of the eye on attempted inward gaze. Here, we report on three heterozygous loss-of-function MAFB mutations causing DRS and a dominant-negative MAFB mutation causing DRS and deafness. Using genotype-phenotype correlations in humans and Mafb-knockout mice, we propose a threshold model for variable loss of MAFB function. Postmortem studies of DRS have reported abducens nerve hypoplasia and aberrant innervation of the lateral rectus muscle by the oculomotor nerve. Our studies in mice now confirm this human DRS pathology. Moreover, we demonstrate that selectively disrupting abducens nerve development is sufficient to cause secondary innervation of the lateral rectus muscle by aberrant oculomotor nerve branches, which form at developmental decision regions close to target extraocular muscles. Thus, we present evidence that the primary cause of DRS is failure of the abducens nerve to fully innervate the lateral rectus muscle in early development.

  8. Increasing losses caused by natural disasters: what are the drivers, how is the insurance industry affected, what has to be done?

    Science.gov (United States)

    Hoppe, P.

    2016-12-01

    Losses caused by natural disasters are a major factor influencing the balance sheet of insurers, especially reinsurers. Such events have a high potential of creating extreme accumulation losses by affecting different business lines at the same time. The basis for long term profitable business in the insurance industry is to be able to calculate and also get risk adequate premiums for the covers of natural perils. Risk adequate means that on average over several years the losses occurring can be paid by the premium income. Losses caused by natural disasters have increased tremendously worldwide in the last decades. The main drivers have been changes in the exposed values, i.e. growth of population and wealth in affected regions. For the insurance industry this loss increasing process in general is not a problem as the premiums normally are proportional to the sum insured, i.e. the exposed value. These factors can be quantified and the loss trends can be adjusted for these changes. Munich Re just recently has developed a very sophisticated method for such a normalisation of losses. After this normalization in respect to exposed values a still residual loss trend can be either driven by changes in the vulnerability of assets or on the hazard side. Trends in both factors are not automatically considered in the premiums, they have to be detected, quantified and then built into the risk models of the insurers. Many studies as well as data from the Munich Re NatCatSERVICE suggest that weather related hazards already have changed for some perils and in some regions. Climate research implies that due to global warming such trends will increase in the coming decades. Very little quantitative data, however, on such changes still is available to allow the adjustment of the risk models of insurers. In order to do this, data with high regional resolution and also probabilities of certain scenarios would be necessary. The other gap of information is quantitative data on changes

  9. A shutoff and exonuclease mutant of murine gammaherpesvirus-68 yields infectious virus and causes RNA loss in type I interferon receptor knockout cells.

    Science.gov (United States)

    Sheridan, Victoria; Polychronopoulos, Louise; Dutia, Bernadette M; Ebrahimi, Bahram

    2014-05-01

    Significant loss of RNA followed by severely reduced cellular protein pool, a phenomenon termed host shutoff, is associated with a number of lytic virus infections and is a critical player in viral pathogenesis. Until recently, viral DNA exonucleases were associated only with processing of viral genomic DNA and its encapsidation. However, recent observations have identified host shutoff and exonuclease function for the highly conserved viral exonucleases in γ-herpesviruses, which include Kaposi's sarcoma-associated herpesvirus, Epstein-Barr virus and the mouse model murine gammaherpesvirus-68, also referred to as MHV-68. In this study, we show that although ablation of the MHV-68 exonuclease ORF37 caused a restrictive phenotype in WT IFN-α/β receptor-positive cells such as NIH 3T3, lack of ORF37 was tolerated in cells lacking the IFN-α/β receptor: the ORF37Stop virus was capable of forming infectious particles and caused loss of mRNA in IFN-α/β receptor knockout cells. Moreover, ORF37Stop virus was able to establish lytic infection in the lungs of mice lacking the IFN-α/β receptor. These observations provide evidence that lytic MHV-68 infection and subsequent loss of mRNA can take place independently of ORF37. Moreover, efficient growth of ORF37Stop virus also identifies a role for this family of viral nucleases in providing a window of opportunity for virus growth by overcoming type I IFN-dependent responses.

  10. Sexual conflict over breeding substrate causes female expulsion and offspring loss in a cichlid fish

    NARCIS (Netherlands)

    Maan, Martine E.; Taborsky, Michael

    2008-01-01

    Females of the Lake Tanganyika cichlid Lamprologus callipterus exclusively breed in empty snail shells that males collect in their territories. Male-male competition for shells is severe, leading to frequent shell stealing and territory takeover. As a consequence, males have breeding females in thei

  11. Diarrhea and loss of production on Dutch dairy farms caused by the Schmallenberg virus

    NARCIS (Netherlands)

    Muskens, J.; Smolenaars, A.J.; Poel, van der W.H.M.; Mars, M.H.; Wuijckhuise, van L.; Holzhauer, M.; Weering, van H.; Kock, P.

    2012-01-01

    At the end of August and the first two weeks of September 2011 dozens of veterinary practitioners reported to GD Veekijker (Animal Health Service) several dairy herds with cows with sudden decreased milk production, watery diarrhea and sometimes fever. In the beginning these reports came from the Ea

  12. Electric shock ear torture: a rare cause of tympanic membrane perforation and mixed hearing loss.

    Science.gov (United States)

    Barber, Brittany; Côté, David W J; Liu, Richard

    2011-06-01

    Summary of case report findings: Picana (electric shock torture) is a globally used form of torture. This is the first documented case of picana applied to the tympanic membrane. Two other types of ear torture have been documented, including picana of the helix and telefono. Several types of head and neck torture are applied globally.

  13. [A severe anaphylactic shock caused by spraying the oak processionary caterpillar (Thaumetopoea processionea) in North Brabant].

    Science.gov (United States)

    Bosma, A H; Jans, H W

    1998-07-04

    The processionary caterpillar, Thaumetopoea processionea, caused much inconvenience in the Netherlands in 1996-1997; from the medical point of view, mostly itching and skin rash. After contact with stinging bristles of the caterpillar and with the pesticide Dimilin SC-48, of which diflubenzurone is the active agent, a 72-year-old man had to be resuscitated because of ventricular fibrillation caused by hypotension related to relative underfilling and low systemic vascular resistance. He made a good recovery. Such life-threatening situations can be prevented by publicly announcing plague control measures and closing of the affected areas to the population, with ample margins.

  14. Severe chronic osteomyelitis caused by Morganella morganii with high population diversity

    Directory of Open Access Journals (Sweden)

    Jialiang Zhu

    2016-09-01

    Full Text Available A case of chronic osteomyelitis probably caused by Morganella morganii, occurring over a period of 30 years, is reported. The organism was identified through a combination of sample culture, direct sequencing, and 16S RNA gene amplicon sequencing. Further whole-genome sequencing and population structure analysis of the isolates from the patient showed the bacterial population to be highly diverse. This case provides a valuable example of a long-term infection caused by an opportunistic pathogen, M. morganii, with high diversity, which might evolve during replication within the host.

  15. Severe chronic osteomyelitis caused by Morganella morganii with high population diversity.

    Science.gov (United States)

    Zhu, Jialiang; Li, Haifeng; Feng, Li; Yang, Min; Yang, Ronggong; Yang, Lin; Li, Li; Li, Ruoyan; Liu, Minshan; Hou, Shuxun; Ke, Yuehua; Li, Wenfeng; Bai, Fan

    2016-09-01

    A case of chronic osteomyelitis probably caused by Morganella morganii, occurring over a period of 30 years, is reported. The organism was identified through a combination of sample culture, direct sequencing, and 16S RNA gene amplicon sequencing. Further whole-genome sequencing and population structure analysis of the isolates from the patient showed the bacterial population to be highly diverse. This case provides a valuable example of a long-term infection caused by an opportunistic pathogen, M. morganii, with high diversity, which might evolve during replication within the host.

  16. Chromosome loss caused by DNA fragmentation induced in main nuclei and micronuclei of human lymphoblastoid cells treated with colcemid.

    Science.gov (United States)

    Yamamoto, Mika; Wakata, Akihiro; Aoki, Yoshinobu; Miyamae, Yoichi; Kodama, Seiji

    2014-04-01

    Aneuploidy, a change in the number of chromosomes, plays an essential role in tumorigenesis. Our previous study demonstrated that a loss of a whole chromosome is induced in human lymphocytes by colcemid, a well-known aneugen. Here, to clarify the mechanism for colcemid-induced chromosome loss, we investigated the relationship between chromosome loss and DNA fragmentation in human lymphoblastoid cells treated with colcemid (an aneugen) compared with methyl methanesulfonate (MMS; a clastogen). We analyzed the number of fluorescence in situ hybridization (FISH) signals targeted for a whole chromosome 2 in cytokinesis-blocked binucleated TK6 cells and WTK-1 cells treated with colcemid and MMS, and concurrently detected DNA fragmentation by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Results revealed that DNA fragmentation occurred in 60% of all binucleated TK6 cells harboring colcemid-induced chromosome loss (30% of micronuclei and 30% of main nuclei). DNA fragmentation was observed in colcemid-induced micronuclei containing a whole chromosome but not in MMS-induced micronuclei containing chromosome fragments. In contrast, colcemid-induced nondisjunction had no effect on induction of DNA fragmentation, suggesting that DNA fragmentation was triggered by micronuclei containing a whole chromosome but not by micronuclei containing chromosome fragments or nondisjunction. In addition, the frequency of binucleated cells harboring chromosome loss with DNA fragmentation in micronuclei or main nuclei was higher in wild-type p53 TK6 cells than in mutated-p53 WTK-1 cells treated with colcemid. Taken together, these present and previous results suggest that colcemid-induced chromosome loss is caused by DNA fragmentation, which is triggered by a micronucleus with a whole chromosome and controlled by the p53-dependent pathway. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Retinopathy of prematurity as a major cause of severe visual impairment and blindness in children in schools for the blind in Guadalajara city, Mexico.

    Science.gov (United States)

    Zepeda-Romero, L C; Barrera-de-Leon, J C; Camacho-Choza, C; Gonzalez Bernal, C; Camarena-Garcia, E; Diaz-Alatorre, C; Gutierrez-Padilla, J A; Gilbert, C

    2011-11-01

    To determine the causes of blindness in students attending schools for the blind in Guadalajara city, Mexico and to assess the availability of screening for retinopathy of prematurity (ROP) in local neonatal intensive care units. Information on causes of blindness was obtained by interview with parents and teachers, review of records and examination. Causes of visual loss in children with a distance visual acuity of <6/60 (ie, severely visually impaired or blind) were determined and classified according to the WHO's classification system for children. Of 153 children in the two participating schools, 144 were severely visual impaired or blind. Their ages ranged from 4 months to 15 years and 58% were female. ROP was the most common cause of visual loss (34.7%), followed by optic nerve lesions (17.4%) and glaucoma (14.6%). 25/59 (42.3%) children aged 0-4 years were blind from ROP compared with 6/32 (18.8%) children aged 10-15 years. 78% of children blind from ROP had psychomotor delay and less than half (46%) had not received treatment for ROP. All five privately funded neonatal intensive care units in the city regularly screen for ROP compared with only four of the 12 units in the public sector. ROP is the leading cause of blindness in children in Mexico despite national guidelines being in place. Health policies promoting primary prevention through improved neonatal care need to be implemented. Advocacy is required so that the time ophthalmologists spend screening and treating ROP is included in their job description and hence salaried.

  18. LOWER DOSE OF AMINOGLYCOSIDE OTOTOXIC EXPOSURE CAUSES PRESYNAPTIC ALTERATIONS ASSOICATED WITH HEARING LOSS

    Institute of Scientific and Technical Information of China (English)

    LIU Ke; WANG Xiaoyu; LI Sijun; TANG Siquan; XU Yice; WANG Xuefeng; SUN Jianhe; YANG Weiyan; YANG Shiming

    2014-01-01

    Objective To study presynaptic alternations of cochlear ribbons arising from aminoglycoside ototoxic stimuli in C57BL/6J mice. Methods Animals were injected with low dose gentamicin (100 mg/kg/day) for 14 days, From the 14th to 28th days, the mice were maintained free of gentamicin treatment. Immunohisto-chemistry labeling was employed to trace RIBEYE, a major presynaptic componment of ribbon synapses. RIBEYE/CtBP2 expression levels were assessed and compared with hearing threshold shifts. Auditory func-tion was assessed by auditory brainstem responses. The stereocilia of outer hair cells (OHCs) and IHCs was examined by scanning electron microscopy (SEM). Results Hearing thresholds were elevated with peak hearing loss observed on the 7th day after gentamicin exposure, followed by improvement after the 7th day. RIBEYE/CtBP2 expression directly correlated with observed hearing threshold shifts. Strikingly, we did not see any obvious changes in stereocilia in both OHCs and IHCs until the 28th day. Mild changes in stereocil-ia were only observed in OHCs on the 28th day. Conclusions These findings indicate that presynapse co-chlear ribbons, rather than stereocilia, may be sensitive to aminoglycoside ototoxic exposure in mice cochle-ae. A pattern of RIBEYE/CtBP2 expression changes seems to parallel hearing threshold shifts and suggests presynaptic response properties to lower dosage of aminoglycoside ototoxic stimuli.

  19. Study on the radiation problem caused by electron beam loss in accelerator tubes

    Institute of Scientific and Technical Information of China (English)

    LI Quan-Feng; GUO Bing-Qi; ZHANG Jie-Xi; CHEN Huai-Bi

    2008-01-01

    The beam dynamic code PARMELA was used to simulate the transportation process of accelerating electrons in S-band SW linacs with different energies of 2.5, 6 and 20 MeV. The results indicated that in the ideal condition, the percentage of electron beam loss was 50% in accelerator tubes. Also we calculated the spectrum, the location and angular distribution of the lost electrons. Calculation performed by Monte Carlo code MCNP demonstrated that the radiation distribution of lost electrons was nearly uniform along the tube axis, the angular distributions of the radiation dose rates of the three tubes were similar, and the highest leaking dose was at the angle of 160° with respect to the axis. The lower the energy of the accelerator, the higher the radiation relative leakage. For the 2.5 MeV accelerator, the maximum dose rate reached 5% of the main dose and the one on the head of the electron gun was 1%, both of which did not meet the eligible protection requirement for accelerators. We adopted different shielding designs for different accelerators. The simulated result showed that the shielded radiation leaking dose rates fulfilled the requirement.

  20. Hedgehog inhibition causes complete loss of limb outgrowth and transformation of digit identity in Xenopus tropicalis.

    Science.gov (United States)

    Stopper, Geffrey F; Richards-Hrdlicka, Kathryn L; Wagner, Günter P

    2016-03-01

    The study of the tetrapod limb has contributed greatly to our understanding of developmental pathways and how changes to these pathways affect the evolution of morphology. Most of our understanding of tetrapod limb development comes from research on amniotes, with far less known about mechanisms of limb development in amphibians. To better understand the mechanisms of limb development in anuran amphibians, we used cyclopamine to inhibit Hedgehog signaling at various stages of development in the western clawed frog, Xenopus tropicalis, and observed resulting morphologies. We also analyzed gene expression changes resulting from similar experiments in Xenopus laevis. Inhibition of Hedgehog signaling in X. tropicalis results in limb abnormalities including reduced digit number, missing skeletal elements, and complete absence of limbs. In addition, posterior digits assume an anterior identity by developing claws that are usually only found on anterior digits, confirming Sonic hedgehog's role in digit identity determination. Thus, Sonic hedgehog appears to play mechanistically separable roles in digit number specification and digit identity specification as in other studied tetrapods. The complete limb loss observed in response to reduced Hedgehog signaling in X. tropicalis, however, is striking, as this functional role for Hedgehog signaling has not been found in any other tetrapod. This changed mechanism may represent a substantial developmental constraint to digit number evolution in frogs. J. Exp. Zool. (Mol. Dev. Evol.) 9999B:XX-XX, 2016. © 2016 Wiley Periodicals, Inc.

  1. Successful treatment of bilateral visual loss caused by HIV-associated optic neuritis

    Directory of Open Access Journals (Sweden)

    Claire Cullen

    2011-12-01

    Full Text Available Optic neuritis is not an uncommon diagnosis in HIV-infected patients, but it is rarely idiopathic. We report a case of a young HIV-infected woman who developed optic neuritis as her presenting manifestation of HIV infection. She had initially experienced sudden-onset right-sided painful visual loss; the left eye had become involved within days. Bilateral swollen discs were apparent on fundoscopy. Investigations were performed for meningitis (including bacterial, cryptococcal, tuberculous and syphilitic types, auto-immune diseases, toxoplasma, rubella, cytomegalovirus, viral hepatitis, HTLV-1/2, HIV-1/2 and syphilis. The only positive result was a reactive HIV enzyme-linked immunosorbent assay. The CD4 count was 85 cells/µl. A post-contrast magnetic resonance imaging scan of the brain illustrated enhancement of the optic nerves. Treatment was 3 days of intravenous methylprednisolone 1 g daily, followed by 11 days of oral prednisone 60 mg daily. Highly active antiretroviral therapy was initiated after 2 weeks. Vision improved from day 6 after commencement of steroid therapy, with ongoing recovery at 5 months.

  2. Severe structural and functional visual system damage leads to profound loss of vision-related quality of life in patients with neuromyelitis optica spectrum disorders.

    Science.gov (United States)

    Schmidt, Felix; Zimmermann, Hanna; Mikolajczak, Janine; Oertel, Frederike C; Pache, Florence; Weinhold, Maria; Schinzel, Johann; Bellmann-Strobl, Judith; Ruprecht, Klemens; Paul, Friedemann; Brandt, Alexander U

    2017-01-01

    Neuromyelitis optica spectrum disorders (NMOSD) are characterized by devastating optic neuritis attacks causing more structural damage and visual impairment than in multiple sclerosis (MS). The objective of this study was to compare vision-related quality of life in NMOSD and MS patients and correlate it to structural retinal damage and visual function. Thirty-one NMOSD and 31 matched MS patients were included. Vision-related quality of life was assessed with the 39-item National Eye Institute Visual Function Questionnaire (NEI-VFQ). All patients underwent retinal optical coherence tomography and visual acuity and contrast sensitivity measurements. Vision-related quality of life was reduced in NMOSD compared to MS patients. This difference was driven by a higher incidence of bilateral and more severe optic neuritis in the NMOSD group. Retinal thinning and visual impairment were significantly greater in the NMOSD cohort. Lower vision-related quality of life was associated with more retinal damage and reduced visual function as assessed by visual acuity and contrast sensitivity. NMOSD-related bilateral ON-attacks cause severe structural damage and visual impairment that lead to severe loss of vision-related quality of life. The NEI-VFQ is a helpful tool to monitor vision-related quality of life in NMOSD patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Loss of function mutation in LOX causes thoracic aortic aneurysm and dissection in humans.

    Science.gov (United States)

    Lee, Vivian S; Halabi, Carmen M; Hoffman, Erin P; Carmichael, Nikkola; Leshchiner, Ignaty; Lian, Christine G; Bierhals, Andrew J; Vuzman, Dana; Mecham, Robert P; Frank, Natasha Y; Stitziel, Nathan O

    2016-08-01

    Thoracic aortic aneurysms and dissections (TAAD) represent a substantial cause of morbidity and mortality worldwide. Many individuals presenting with an inherited form of TAAD do not have causal mutations in the set of genes known to underlie disease. Using whole-genome sequencing in two first cousins with TAAD, we identified a missense mutation in the lysyl oxidase (LOX) gene (c.893T > G encoding p.Met298Arg) that cosegregated with disease in the family. Using clustered regularly interspaced short palindromic repeats (CRISPR)/clustered regularly interspaced short palindromic repeats-associated protein-9 nuclease (Cas9) genome engineering tools, we introduced the human mutation into the homologous position in the mouse genome, creating mice that were heterozygous and homozygous for the human allele. Mutant mice that were heterozygous for the human allele displayed disorganized ultrastructural properties of the aortic wall characterized by fragmented elastic lamellae, whereas mice homozygous for the human allele died shortly after parturition from ascending aortic aneurysm and spontaneous hemorrhage. These data suggest that a missense mutation in LOX is associated with aortic disease in humans, likely through insufficient cross-linking of elastin and collagen in the aortic wall. Mutation carriers may be predisposed to vascular diseases because of weakened vessel walls under stress conditions. LOX sequencing for clinical TAAD may identify additional mutation carriers in the future. Additional studies using our mouse model of LOX-associated TAAD have the potential to clarify the mechanism of disease and identify novel therapeutics specific to this genetic cause.

  4. Deletion of the WD40 domain of LRRK2 in Zebrafish causes Parkinsonism-like loss of neurons and locomotive defect.

    Directory of Open Access Journals (Sweden)

    Donglai Sheng

    2010-04-01

    Full Text Available LRRK2 plays an important role in Parkinson's disease (PD, but its biological functions are largely unknown. Here, we cloned the homolog of human LRRK2, characterized its expression, and investigated its biological functions in zebrafish. The blockage of zebrafish LRRK2 (zLRRK2 protein by morpholinos caused embryonic lethality and severe developmental defects such as growth retardation and loss of neurons. In contrast, the deletion of the WD40 domain of zLRRK2 by morpholinos targeting splicing did not induce severe embryonic developmental defects; rather it caused Parkinsonism-like phenotypes, including loss of dopaminergic neurons in diencephalon and locomotion defects. These neurodegenerative and locomotion defects could be rescued by over-expressing zLRRK2 or hLRRK2 mRNA. The administration of L-dopa could also rescue the locomotion defects, but not the neurodegeneration. Taken together, our results demonstrate that zLRRK2 is an ortholog of hLRRK2 and that the deletion of WD40 domain of zLRRK2 provides a disease model for PD.

  5. A ghost covered in lice: a case of severe blood loss with long-standing heavy pediculosis capitis infestation.

    Science.gov (United States)

    Hau, Veronica; Muhi-Iddin, Nadia

    2014-12-19

    An 11-year-old child presented with poor school attendance, and signs and symptoms of severe anaemia. He was heavily covered in lice. He was investigated for other causes of anaemia. Following treatment for head lice and also iron supplementation, he was back in full-time education. This case highlights the link between head lice (pediculosis capitis) infestation and iron-deficiency anaemia. 2014 BMJ Publishing Group Ltd.

  6. cAMP and cGMP in nasal mucus related to severity of smell loss in patients with smell dysfunction.

    Science.gov (United States)

    Henkin, R I; Velicu, I

    2008-01-01

    To evaluate nasal mucus levels of cAMP and cGMP in patients with taste and smell dysfunction with respect to severity of their smell loss. cAMP and cGMP were measured in nasal mucus using a sensitive spectrophotometric 96 plate ELISA technique. Smell loss was measured in patients with taste and smell dysfunction by standardized psychophysical measurements of olfactory function and classified by severity of loss into four types from most severe to least severe such that anosmia > Type I hyposmia > Type II hyposmia > Type III hyposmia. Measurements of nasal mucus cyclic nucleotides and smell loss were made independently. As smell loss severity increased stepwise cAMP and cGMP levels decreased stepwise [cAMP, cGMP (in pmol/ml); anosmia - 0.004, 0.008: Type I hyposmia - 0.12+/-0.03, 0.10+/-0.03: Type II hyposmia - 0.15+/-0.02, 0.16+/-0.01: Type III hyposmia - 0.23+/-0.05, 0.20+/-0.15]. These results confirm the association of biochemical changes in cyclic nucleotides with systematic losses of smell acuity. These results confirm the usefulness of the psychophysical methods we defined to determine the systematic classification of smell loss severity. These changes can form the basis for the biochemical definition of smell loss among some patients with smell loss as well as for their therapy.

  7. Severe community-acquired pneumonia caused by Mycoplasma pneumoniae in young female patient

    Directory of Open Access Journals (Sweden)

    Milačić Nena

    2015-07-01

    Full Text Available Mycoplasma pneumonia is common agent causing community acquired pneumonia in younger population. However, the course of illness is usually benign and is rarely associated with pulmonary complications. We report a 27 years old female patient with unilateral pneumonia followed by pleural effusion and adhesions on the same side. This potential source of infection should be considered in young patients where resolution of symptoms from pneumonia is delayed.

  8. Severe disseminated phaeohyphomycosis in an immunocompetent patient caused by Veronaea botryosa

    NARCIS (Netherlands)

    Bonifaz, A.; Davoudi, M.M.; de Hoog, G.S.; Padilla-Desgarennes, C.; Vazquez-Gonzalez, D.; Navarrete, G.; Meis, J.F.G.M.; Badali, H.

    2013-01-01

    We present a severe case of disseminated phaeohyphomycosis due to Veronaea botryosa. A 32-year-old female, native from Cuautla, Morelos, Mexico, presented a chronic dermatosis which started 10 years earlier with multiple exophytic, multilobulated, soft, and pedunculated or sessile neoformations of d

  9. Severe disseminated phaeohyphomycosis in an immunocompetent patient caused by Veronaea botryosa

    NARCIS (Netherlands)

    Bonifaz, A.; Davoudi, M.M.; de Hoog, G.S.; Padilla-Desgarennes, C.; Vázquez-González, D.; Navarrete, G.; Meis, J.F.; Badali, H.

    2013-01-01

    We present a severe case of disseminated phaeohyphomycosis due to Veronaea botryosa. A 32-year-old female, native from Cuautla, Morelos, Mexico, presented a chronic dermatosis which started 10 years earlier with multiple exophytic, multilobulated, soft, and pedunculated or sessile neoformations of d

  10. Frequency, severity and causes of unexpected allergic reactions to food: A systematic literature review

    NARCIS (Netherlands)

    Versluis, A.; Knulst, A.C.; Kruizinga, A.G.; Michelsen, A.; Houben, G.F.; Baumert, J.L.; Os-Medendorp, H. van

    2015-01-01

    Summary: Food allergic patients have to deal with an avoidance diet. Confusing labelling terms or precautionary labels can result in misinterpretation and risk-taking behaviour. Even those patients that strictly adhere to their diet experience (sometimes severe) unexpected allergic reactions to

  11. SEVERE BLEEDING CAUSED BY AN INHIBITOR TO COAGULATION-FACTOR-V - A CASE-REPORT

    NARCIS (Netherlands)

    SMID, WM; DEWOLF, JTM; NIJLAND, JH; BOM, VJJ; VANDERMEER, J

    1994-01-01

    A 67-year-old man with a severe bleeding due to a high level of factor V inhibitor (maximum level of 350 Bethesda units) is described. Coagulation abnormalities improved initially during treatment with prednisolone in combination with cyclophosphamide. Subsequent treatment with either cyclophosphami

  12. HMGB1 in severe soft tissue infections caused by Streptococcus pyogenes

    Directory of Open Access Journals (Sweden)

    Linda eJohansson

    2014-01-01

    Full Text Available Extracellular High Mobility Group Box 1 (HMGB1 has been associated with acute and chronic inflammatory conditions. However, little is known about HMGB1 in necrotizing bacterial infections. We hypothesized that the local HMGB1 response is excessive in severe soft tissue infections, which are characterized by necrosis and hyperinflammation. To explore this, tissue biopsies were collected from patients with varying severity of Streptococcus pyogenes skin and soft tissue infections, including erysipelas, cellulitis, and necrotizing fasciitis. Tissue sections were immunostained for HMGB1, S. pyogenes, and inflammatory cell infiltrates and results quantified by acquired computerized image analysis. HMGB1 expression increased in parallel to disease severity and was significantly higher in necrotizing fasciitis than in erysipelas (p=0.0023. Confocal microscopy of sections co-stained for HMGB1 and cell markers revealed both extracellular and cytoplasmic HMGB1, the latter of which was found predominantly in macrophages. To further verify macrophages as main source of activation triggered HMGB1 release, human macrophages were infected with clinical S. pyogenes isolates. The results demonstrated infection triggered release of HMGB1. Dual staining’s visualized HMGB1 in areas close to, but not overlapping, with neutrophils, indicating a potential chemotactic role. In vitro transmigration experiments showed a chemotactic effect of HMGB1 on neutrophils. The data furthermore provided in vivo support that HGMB1 may form immunostimulatory complexes with IL-1β. Taken together, the findings provide the first in vivo evidence that HMGB1 is abundant at the local site of severe bacterial soft tissue infections and its levels correlated to severity of infections; hence, indicating its potential value as a biomarker for tissue pathology.

  13. HMGB1 in severe soft tissue infections caused by Streptococcus pyogenes.

    Science.gov (United States)

    Johansson, Linda; Snäll, Johanna; Sendi, Parham; Linnér, Anna; Thulin, Pontus; Linder, Adam; Treutiger, Carl-Johan; Norrby-Teglund, Anna

    2014-01-01

    Extracellular High Mobility Group Box 1 (HMGB1) has been associated with acute and chronic inflammatory conditions. However, little is known about HMGB1 in necrotizing bacterial infections. We hypothesized that the local HMGB1 response is excessive in severe soft tissue infections (STIs), which are characterized by necrosis and hyperinflammation. To explore this, tissue biopsies were collected from patients with varying severity of Streptococcus pyogenes skin and STIs, including erysipelas, cellulitis, and necrotizing fasciitis. Tissue sections were immunostained for HMGB1, S. pyogenes, and inflammatory cell infiltrates and results quantified by acquired computerized image analysis (ACIA). HMGB1 expression increased in parallel to disease severity and was significantly higher in necrotizing fasciitis than in erysipelas (p = 0.0023). Confocal microscopy of sections co-stained for HMGB1 and cell markers revealed both extracellular and cytoplasmic HMGB1, the latter of which was found predominantly in macrophages. To further verify macrophages as main source of activation triggered HMGB1 release, human macrophages were infected with clinical S. pyogenes isolates. The results demonstrated infection triggered release of HMGB1. Dual staining's visualized HMGB1 in areas close to, but not overlapping, with neutrophils, indicating a potential chemotactic role. In vitro transmigration experiments showed a chemotactic effect of HMGB1 on neutrophils. The data furthermore provided in vivo support that HGMB1 may form immunostimulatory complexes with IL-1β. Taken together, the findings provide the first in vivo evidence that HMGB1 is abundant at the local site of severe bacterial STIs and its levels correlated to severity of infections; hence, indicating its potential value as a biomarker for tissue pathology.

  14. Hippocampal damage causes retrograde but not anterograde memory loss for context fear discrimination in rats.

    Science.gov (United States)

    Lee, Justin Q; Sutherland, Robert J; McDonald, Robert J

    2017-09-01

    There is a substantial body of evidence that the hippocampus (HPC) plays and essential role in context discrimination in rodents. Studies reporting anterograde amnesia (AA) used repeated, alternating, distributed conditioning and extinction sessions to measure context fear discrimination. In addition, there is uncertainty about the extent of damage to the HPC. Here, we induced conditioned fear prior to discrimination tests and rats sustained extensive, quantified pre- or post-training HPC damage. Unlike previous work, we found that extensive HPC damage spares context discrimination, we observed no AA. There must be a non-HPC system that can acquire long-term memories that support context fear discrimination. Post-training HPC damage caused retrograde amnesia (RA) for context discrimination, even when rats are fear conditioned for multiple sessions. We discuss the implications of these findings for understanding the role of HPC in long-term memory. © 2017 Wiley Periodicals, Inc.

  15. Changes in selection regime cause loss of phenotypic plasticity in planktonic freshwater copepods.

    Science.gov (United States)

    Sereda, Sergej Vital'evič; Wilke, Thomas; Schultheiß, Roland

    2014-01-01

    Rapid phenotypic adaptation is critical for populations facing environmental changes and can be facilitated by phenotypic plasticity in the selected traits. Whereas recurrent environmental fluctuations can favour the maintenance or de novo evolution of plasticity, strong selection is hypothesized to decrease plasticity or even fix the trait (genetic assimilation). Despite advances in the theoretical understanding of the impact of plasticity on diversification processes, comparatively little empirical data of populations undergoing diversification mediated by plasticity are available. Here we use the planktonic freshwater copepod Acanthodiaptomus denticornis from two lakes as model system to study UV stress responses of two phenotypically different populations under laboratory conditions. Our study reveals heritable lake- and sex-specific differences of behaviour, physiological plasticity, and mortality. We discuss specific selective scenarios causing these differences and argue that phenotypic plasticity will be higher when selection pressure is moderate, but will decrease or even be lost under stronger pressure.

  16. Attribution of Causes of Weight Loss and Weight Gain to 3-Year Mortality in Older Adults : Results From the Longitudinal Aging Study Amsterdam

    NARCIS (Netherlands)

    Wijnhoven, Hanneke A. H.; van Zon, Sander K. R.; Twisk, Jos; Visser, Marjolein

    2014-01-01

    Background. Weight loss is associated with a higher mortality risk in old age, but the underlying cause may impact this association. We examined associations between causes of intentional and unintentional weight loss and weight gain and mortality. Methods. We used data of five triannual examination

  17. Attribution of Causes of Weight Loss and Weight Gain to 3-Year Mortality in Older Adults : Results From the Longitudinal Aging Study Amsterdam

    NARCIS (Netherlands)

    Wijnhoven, Hanneke A. H.; van Zon, Sander K. R.; Twisk, Jos; Visser, Marjolein

    2014-01-01

    Background. Weight loss is associated with a higher mortality risk in old age, but the underlying cause may impact this association. We examined associations between causes of intentional and unintentional weight loss and weight gain and mortality. Methods. We used data of five triannual examination

  18. Apparent effect of chronic Plasmodium infections on disease severity caused by experimental infections with Mycoplasma gallisepticum in house finches

    Directory of Open Access Journals (Sweden)

    André A. Dhondt

    2017-08-01

    Full Text Available An epidemic caused by a successful host jump of the bacterial pathogen Mycoplasma gallisepticum from poultry to house finches in the 1990s has by now spread across most of North America. M. gallisepticum causes severe conjunctivitis in house finches. We experimentally show that M. gallisepticum transmission to birds with or without chronic Plasmodium infection does not differ. However, once infected with M. gallisepticum house finches chronically infected with Plasmodium develop more severe clinical disease than birds without such infection. We speculate as to possible effects of coinfection.

  19. Impact of the combined loss of BOK, BAX and BAK on the hematopoietic system is slightly more severe than compound loss of BAX and BAK.

    Science.gov (United States)

    Ke, F; Grabow, S; Kelly, G L; Lin, A; O'Reilly, L A; Strasser, A

    2015-10-22

    It is well established that BAX and BAK play crucial, overlapping roles in the intrinsic pathway of apoptosis. Gene targeted mice lacking both BAX and BAK have previously been generated, but the majority of these animals died perinatally. BOK is a poorly studied relative of BAX and BAK that shares extensive amino acid sequence homology to both proteins, but its function remains largely unclear to date. To determine whether BOK plays an overlapping role with BAX and BAK, we utilized a hematopoietic reconstitution model where lethally irradiated wild type mice were transplanted with Bok(-/-)Bax(-/-)Bak(-/-) triple knockout (TKO) fetal liver cells, and compared alongside mice reconstituted with a Bax(-/-)Bak(-/-) double knockout (DKO) hematopoietic compartment. We report here that mice with a TKO and DKO hematopoietic system died at a similar rate and much earlier than control animals, mostly due to severe autoimmune pathology. Both TKO and DKO reconstituted mice also had altered frequencies of various leukocyte subsets in the thymus, bone marrow and spleen, displayed leukocyte infiltrates and autoimmune pathology in multiple tissues, as well as elevated levels of anti-nuclear autoantibodies. Interestingly, the additional deletion of BOK (on top of BAX and BAK loss) led to a further increase in peripheral blood lymphocytes, as well as enhanced lymphoid infiltration in some organs. These findings suggest that BOK may have some functions that are redundant with BAX and BAK in the hematopoietic system.

  20. Loss-of-function mutations in PTPN11 cause metachondromatosis, but not Ollier disease or Maffucci syndrome.

    Science.gov (United States)

    Bowen, Margot E; Boyden, Eric D; Holm, Ingrid A; Campos-Xavier, Belinda; Bonafé, Luisa; Superti-Furga, Andrea; Ikegawa, Shiro; Cormier-Daire, Valerie; Bovée, Judith V; Pansuriya, Twinkal C; de Sousa, Sérgio B; Savarirayan, Ravi; Andreucci, Elena; Vikkula, Miikka; Garavelli, Livia; Pottinger, Caroline; Ogino, Toshihiko; Sakai, Akinori; Regazzoni, Bianca M; Wuyts, Wim; Sangiorgi, Luca; Pedrini, Elena; Zhu, Mei; Kozakewich, Harry P; Kasser, James R; Seidman, Jon G; Kurek, Kyle C; Warman, Matthew L

    2011-04-01

    Metachondromatosis (MC) is a rare, autosomal dominant, incompletely penetrant combined exostosis and enchondromatosis tumor syndrome. MC is clinically distinct from other multiple exostosis or multiple enchondromatosis syndromes and is unlinked to EXT1 and EXT2, the genes responsible for autosomal dominant multiple osteochondromas (MO). To identify a gene for MC, we performed linkage analysis with high-density SNP arrays in a single family, used a targeted array to capture exons and promoter sequences from the linked interval in 16 participants from 11 MC families, and sequenced the captured DNA using high-throughput parallel sequencing technologies. DNA capture and parallel sequencing identified heterozygous putative loss-of-function mutations in PTPN11 in 4 of the 11 families. Sanger sequence analysis of PTPN11 coding regions in a total of 17 MC families identified mutations in 10 of them (5 frameshift, 2 nonsense, and 3 splice-site mutations). Copy number analysis of sequencing reads from a second targeted capture that included the entire PTPN11 gene identified an additional family with a 15 kb deletion spanning exon 7 of PTPN11. Microdissected MC lesions from two patients with PTPN11 mutations demonstrated loss-of-heterozygosity for the wild-type allele. We next sequenced PTPN11 in DNA samples from 54 patients with the multiple enchondromatosis disorders Ollier disease or Maffucci syndrome, but found no coding sequence PTPN11 mutations. We conclude that heterozygous loss-of-function mutations in PTPN11 are a frequent cause of MC, that lesions in patients with MC appear to arise following a "second hit," that MC may be locus heterogeneous since 1 familial and 5 sporadically occurring cases lacked obvious disease-causing PTPN11 mutations, and that PTPN11 mutations are not a common cause of Ollier disease or Maffucci syndrome.

  1. Loss-of-function mutations in PTPN11 cause metachondromatosis, but not Ollier disease or Maffucci syndrome.

    Directory of Open Access Journals (Sweden)

    Margot E Bowen

    2011-04-01

    Full Text Available Metachondromatosis (MC is a rare, autosomal dominant, incompletely penetrant combined exostosis and enchondromatosis tumor syndrome. MC is clinically distinct from other multiple exostosis or multiple enchondromatosis syndromes and is unlinked to EXT1 and EXT2, the genes responsible for autosomal dominant multiple osteochondromas (MO. To identify a gene for MC, we performed linkage analysis with high-density SNP arrays in a single family, used a targeted array to capture exons and promoter sequences from the linked interval in 16 participants from 11 MC families, and sequenced the captured DNA using high-throughput parallel sequencing technologies. DNA capture and parallel sequencing identified heterozygous putative loss-of-function mutations in PTPN11 in 4 of the 11 families. Sanger sequence analysis of PTPN11 coding regions in a total of 17 MC families identified mutations in 10 of them (5 frameshift, 2 nonsense, and 3 splice-site mutations. Copy number analysis of sequencing reads from a second targeted capture that included the entire PTPN11 gene identified an additional family with a 15 kb deletion spanning exon 7 of PTPN11. Microdissected MC lesions from two patients with PTPN11 mutations demonstrated loss-of-heterozygosity for the wild-type allele. We next sequenced PTPN11 in DNA samples from 54 patients with the multiple enchondromatosis disorders Ollier disease or Maffucci syndrome, but found no coding sequence PTPN11 mutations. We conclude that heterozygous loss-of-function mutations in PTPN11 are a frequent cause of MC, that lesions in patients with MC appear to arise following a "second hit," that MC may be locus heterogeneous since 1 familial and 5 sporadically occurring cases lacked obvious disease-causing PTPN11 mutations, and that PTPN11 mutations are not a common cause of Ollier disease or Maffucci syndrome.

  2. X-ray analysis of 80 patients with severe endemic fluorosis caused by coal burning

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Z.P.; Yuan, M.B.; Liu, G.F. [Luzhou Medical College, Luzhou (China)

    1996-05-01

    Radiographs of 80 patients with severe endemic fluorosis of coalburning type (CBFF) - 49 males and 31 females aged 30 to 70 years - were analysed to examine the changes to the bone substance, peripheral structure of bone, and joints. The changes to bone substance were: (1) osteosclerosis type, 62 cases (77.5%); (2) mixed type, 16 cases (21.25%); (3) osteoporosis type, one case (1.25%); (4) osteomalacia type, one case (1.25%). The changes to the joints were found in the hips and elbows in 79 cases (98.75%), and in the knees in 75 cases (93.75%). When combinations of the above three changes occur, the classification of the disease is according to the most severe one of the three. Our findings can increase the accuracy of X-ray diagnosis, making it more consistent with clinical diagnosis, thus improving prevention and treatment of CBEF.

  3. Novel mutations in DNAJB6 gene cause a very severe early-onset limb-girdle muscular dystrophy 1D disease.

    Science.gov (United States)

    Palmio, Johanna; Jonson, Per Harald; Evilä, Anni; Auranen, Mari; Straub, Volker; Bushby, Kate; Sarkozy, Anna; Kiuru-Enari, Sari; Sandell, Satu; Pihko, Helena; Hackman, Peter; Udd, Bjarne

    2015-11-01

    DNAJB6 is the causative gene for limb-girdle muscular dystrophy 1D (LGMD1D). Four different coding missense mutations, p.F89I, p.F93I, p.F93L, and p.P96R, have been reported in families from Europe, North America and Asia. The previously known mutations cause mainly adult-onset proximal muscle weakness with moderate progression and without respiratory involvement. A Finnish family and a British patient have been studied extensively due to a severe muscular dystrophy. The patients had childhood-onset LGMD, loss of ambulation in early adulthood and respiratory involvement; one patient died of respiratory failure aged 32. Two novel mutations, c.271T > A (p.F91I) and c.271T > C (p.F91L), in DNAJB6 were identified by whole exome sequencing as a cause of this severe form of LGMD1D. The results were confirmed by Sanger sequencing. The anti-aggregation effect of the mutant DNAJB6 was investigated in a filter-trap based system using transient transfection of mammalian cell lines and polyQ-huntingtin as a model for an aggregation-prone protein. Both novel mutant proteins show a significant loss of ability to prevent aggregation.

  4. Severe Acute Infection Due to Serratia marcescens Causing Respiratory Distress in An Immunocompetent Adult.

    Science.gov (United States)

    Ruiz-Sada, Pablo; Escalante, Mikel; Lizarralde, Eva

    2016-01-01

    The role of Serratia marcescens changed from a harmless saprophytic microorganism to an important opportunistic human pathogen. It often causes nosocomial device-associated outbreaks and rarely serious invasive community acquired infections. We present a case of a community-acquired Serratia marcescens bacteremia leading to Respiratory Distress Syndrome in a previously healthy 51-year-old man without identifiable risk factors. Full recovery was achieved with solely medical treatment and observation in ICU during three days. To our knowledge it is an extremely uncommon presentation and just few cases have been previously reported in the literature.

  5. Adult Javanese migrants to Indonesian Papua at high risk of severe disease caused by malaria.

    Science.gov (United States)

    Baird, J K; Basri, H; Weina, P; MaGuire, J D; Barcus, M J; Picarema, H; Elyazar, I R F; Ayomi, E; Sekartuti

    2003-08-01

    Migrants from Java arrive in hyperendemic Papua, Indonesia lacking exposure to endemic malaria. We evaluated records of evacuation to hospital with a diagnosis of severe malaria from a transmigration village in northeastern Papua. During the first 30 months, 198 residents with severe disease were evacuated (7.5 evacuations/100 person-years). During this period the risk of evacuation for adults (> 15 years of age) was 2.8. (95% CI = 2.1-3.8; P 16; 95% CI > or = 2.0-129; P = 0.0009), and diminished during the second 6 months (RR = 9.4; 95% CI = 2.7-32.8; P < 0.0001) and the third 6 months (RR = 3.7; 95% CI = 1.7-7.9; P = 0.0004). During the next two 6-month intervals, the RR for adults was 1.6 and 1.5 (95 % CI range 0.8-2.6; P < 0.18). Adults lacking chronic exposure were far more likely to progress to severe disease compared to children during initial exposure, but not after chronic exposure to infection.

  6. Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study

    OpenAIRE

    Sun, Bing; He, Hangyong; Wang, Zheng; Qu, Jiuxin; Li, Xuyan; Chengjun BAN; Wan, Jun; Cao, Bin; Tong, Zhaohui; Wang, Chen

    2014-01-01

    Introduction Since 2008, severe cases of emerging human adenovirus type 55 (HAdV-55) in immunocompetent adults have been reported sporadically in China. The clinical features and outcomes of the most critically ill patients with severe acute respiratory distress syndrome (ARDS) caused by HAdV-55 requiring invasive mechanical ventilation (IMV) and/or extracorporeal membrane oxygenation (ECMO) are lacking. Methods We conducted a prospective, single-center observational study of pneumonia with A...

  7. Monoallelic and biallelic CREB3L1 variant causes mild and severe osteogenesis imperfecta, respectively.

    Science.gov (United States)

    Keller, Rachel B; Tran, Thao T; Pyott, Shawna M; Pepin, Melanie G; Savarirayan, Ravi; McGillivray, George; Nickerson, Deborah A; Bamshad, Michael J; Byers, Peter H

    2017-08-17

    PurposeOsteogenesis imperfecta (OI) is a heritable skeletal dysplasia. Dominant pathogenic variants in COL1A1 and COL1A2 explain the majority of OI cases. At least 15 additional genes have been identified, but those still do not account for all OI phenotypes that present. We sought the genetic cause of mild and lethal OI phenotypes in an unsolved family.MethodsWe performed exome sequencing on seven members of the family, both affected and unaffected.ResultsWe identified a variant in cyclic AMP responsive element binding protein 3-like 1 (CREB3L1) in a consanguineous family. The variant caused a prenatal/perinatal lethal OI in homozygotes, similar to that seen in OI type II as a result of mutations in type I collagen genes, and a mild phenotype (fractures, blue sclerae) in multiple heterozygous family members. CREB3L1 encodes old astrocyte specifically induced substance (OASIS), an endoplasmic reticulum stress transducer. The variant disrupts a DNA-binding site and prevents OASIS from acting on its transcriptional targets including SEC24D, which encodes a component of the coat protein II complex.ConclusionThis report confirms that CREB3L1 is an OI-related gene and suggests the pathogenic mechanism of CREB3L1-associated OI involves the altered regulation of proteins involved in cellular secretion.GENETICS in MEDICINE advance online publication, 17 August 2017; doi:10.1038/gim.2017.115.

  8. Severe aromatic hydrocarbon pollution in the Arctic town of Longyearbyen (Svalbard) caused by snowmobile emissions.

    Science.gov (United States)

    Reimann, Stefan; Kallenborn, Roland; Schmidbauer, Norbert

    2009-07-01

    The aromatic hydrocarbons benzene, toluene and C2-benzenes (ethyl benzene and m,p,o-xylene) (BTEX) were measured during a 2-month monitoring campaign in 2007 in the Arctic town of Longyearbyen (Spitsbergen, Svalbard). Reflecting the remoteness of the location, very low mixing ratios were observed during night and in windy conditions. In late spring (April-May), however, the high frequency of guided snowmobile tours resulted in "rush-hour" maximum values of more than 10 ppb of BTEX. These concentration levels are comparable to those in European towns and are caused predominately by the outdated 2-stroke engines, which are still used by approximately 30% of the snowmobiles in Longyearbyen. During summer, peak events were about a factor of 100 lower compared to those during the snowmobile season. Emissions in summer were mainly caused by diesel-fueled heavy duty vehicles (HDVs), permanently used for coal transport from the adjacent coal mines. The documented high BTEX mixing ratios from snowmobiles in the Arctic provide an obvious incentive to change the regulation practice to a cleaner engine technology.

  9. Myofibroblastic tumor causing severe neonatal distress. Successful surgical resection after embolization.

    Science.gov (United States)

    Castañón, Montserrat; Saura, Laura; Weller, Santiago; Prat, Jordi; Thio, Marta; Sorolla, Juan P; Albert, Asteria; Morales, Lluís

    2005-06-01

    This report describes a case of a term male 3.1 kg, normal delivery, 38 weeks of gestation with a record of hydramnios by prenatal sonography. He had fetal acute suffering and respiratory distress. The first radiographic study showed a mass filling the whole left thorax cage causing erosion of the inferior edge of the third rib. The mediastinum was displaced to the right. Computed tomography scan confirmed a homogeneous tumor that filled the left thorax and displaced the mediastinum to the right without invasion. Surgical biopsy informed of a highly vascularized mesenchymal tumor. The tumor was embolized with Ivalon microparticles obtaining a nearly avascular mass. Complete surgical excision was made, including the whole mass and costal segments. Microscopically, it was an inflammatory myofibroblastic tumor. It was composed mainly of spindle-shaped cells without malignant features. On immunohistochemistry, the tumor showed positive staining for vimentin, whereas antidesmin antibodies and S-100 protein were negative. The aim of this article is to present an extremely uncommon case of neonatal distress caused by an intrathoracic, extrapulmonary myofibroblastic tumor. Complete surgical resection was possible after embolization.

  10. Strong ELA increase causes fast mass loss of glaciers in central Spitsbergen

    Science.gov (United States)

    Małecki, J.

    2015-11-01

    Svalbard is a heavily glacier covered archipelago in the Arctic. Its central regions, including Dickson Land (DL), are occupied by small alpine glaciers, which post-Little Ice Age (LIA) changes remain only sporadically investigated. This study presents a comprehensive analysis of glacier changes in DL based on inventories compiled from topographic maps and digital elevation models (DEMs) for LIA, 1960's, 1990 and 2009/11. The 37.9 ± 12.1 % glacier area decrease in DL (i.e. from 334.1 ± 38.4 km2 during LIA to 207.4 ± 4.6 km2 in 2009/11) has been primarily caused by accelerating termini retreat. The mean 1990-2009/11 geodetic mass balance of glaciers was -0.70 ± 0.06 m a-1 (-0.63 ± 0.05 m w.e. a-1), being one of the most negative from Svalbard regional means known from the literature. If the same figure was to be applied for other similar regions of central Spitsbergen, that would result in a considerable contribution to total Svalbard mass balance despite negligible proportion to total glacier area. Glacier changes in Dickson Land were linked to dramatic equilibrium line altitude (ELA) shift, which in the period 1990-2009/11 has been located ca. 500 m higher than required for steady-state. The mass balance of central Spitsbergen glaciers seems to be therefore more sensitive to climate change than previously thought.

  11. Loss of Ahi1 impairs neurotransmitter release and causes depressive behaviors in mice.

    Directory of Open Access Journals (Sweden)

    Liyan Ren

    Full Text Available Major depression is becoming one of the most prevalent forms of psychiatric disorders. However, the mechanisms of major depression are still not well-understood. Most antidepressants are only effective in some patients and produce some serious side effects. Animal models of depression are therefore essential to unravel the mechanisms of depression and to develop novel therapeutic strategies. Our previous studies showed that Abelson helper integration site-1 (Ahi1 deficiency causes depression-like behaviors in mice. In this study, we characterized the biochemical and behavioral changes in Ahi1 knockout (KO mice. In Ahi1 KO mice, neurotransmitters including serotonin and dopamine were significantly decreased in different brain regions. However, glutamate and GABA levels were not affected by Ahi1 deficiency. The antidepressant imipramine attenuated depressive behaviors and partially restored brain serotonin level in Ahi1 KO mice. Our findings suggest that Ahi1 KO mice can be used for studying the mechanisms of depression and screening therapeutic targets.

  12. Loss of the actin remodeler Eps8 causes intestinal defects and improved metabolic status in mice.

    Directory of Open Access Journals (Sweden)

    Arianna Tocchetti

    Full Text Available BACKGROUND: In a variety of organisms, including mammals, caloric restriction improves metabolic status and lowers the incidence of chronic-degenerative diseases, ultimately leading to increased lifespan. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that knockout mice for Eps8, a regulator of actin dynamics, display reduced body weight, partial resistance to age- or diet-induced obesity, and overall improved metabolic status. Alteration in the liver gene expression profile, in behavior and metabolism point to a calorie restriction-like phenotype in Eps8 knockout mice. Additionally, and consistent with a calorie restricted metabolism, Eps8 knockout mice show increased lifespan. The metabolic alterations in Eps8 knockout mice correlated with a significant reduction in intestinal fat absorption presumably caused by a 25% reduction in intestinal microvilli length. CONCLUSIONS/SIGNIFICANCE: Our findings implicate actin dynamics as a novel variable in the determination of longevity. Additionally, our observations suggest that subtle differences in energy balance can, over time, significantly affect bodyweight and metabolic status in mice.

  13. Deoxyribonuclease IIalpha is required during the phagocytic phase of apoptosis and its loss causes perinatal lethality.

    Science.gov (United States)

    Krieser, R J; MacLea, K S; Longnecker, D S; Fields, J L; Fiering, S; Eastman, A

    2002-09-01

    Deoxyribonuclease IIalpha (DNase IIalpha) is one of many endonucleases implicated in DNA digestion during apoptosis. We produced mice with targeted disruption of DNase IIalpha and defined its role in apoptosis. Mice deleted for DNase IIalpha die at birth with many tissues exhibiting large DNA-containing bodies that result from engulfed but undigested cell corpses. These DNA-containing bodies are pronounced in the liver where fetal definitive erythropoiesis occurs and extruded nuclei are degraded. They are found between the digits, where apoptosis occurs, and in many other regions of the embryo. Defects in the diaphragm appear to cause death of the mice due to asphyxiation. The DNA in these bodies contains 3'-hydroxyl ends and therefore stain positive in the TUNEL assay. In addition, numerous unengulfed TUNEL-positive cells are observed throughout the embryo. Apoptotic cells are normally cleared rapidly from a tissue; hence the persistence of the DNA-containing bodies and TUNEL-positive cells identifies sites where apoptosis occurs during development. These results demonstrate that DNase IIalpha is not required for the generation of the characteristic DNA fragmentation that occurs during apoptosis but is required for degrading DNA of dying cells and this function is necessary for proper fetal development.

  14. [Successful treatment of people with severe body injuries caused rabid animal bites].

    Science.gov (United States)

    Golubović, S

    1998-01-01

    Seven patients were presented with severe injuries seeking medical help 3-10 days after being bitten by rabid animals. Just one of those subjects underwent timely and correct surgical management. Three patients were with complete, and four with incomplete antirabic prophylaxis. Two patients did not receive human rabies immunoglobulin, and another two did not receive HDC-RV vaccine. At least 3 patients were expected to develop rabies, but it did not happen. The course of these cases could be explained by the existence of less pathogenic strains of virus in Banja Luka region.

  15. ITGB6 loss-of-function mutations cause autosomal recessive amelogenesis imperfecta.

    Science.gov (United States)

    Wang, Shih-Kai; Choi, Murim; Richardson, Amelia S; Reid, Bryan M; Lin, Brent P; Wang, Susan J; Kim, Jung-Wook; Simmer, James P; Hu, Jan C-C

    2014-04-15

    Integrins are cell-surface adhesion receptors that bind to extracellular matrices (ECM) and mediate cell-ECM interactions. Some integrins are known to play critical roles in dental enamel formation. We recruited two Hispanic families with generalized hypoplastic amelogenesis imperfecta (AI). Analysis of whole-exome sequences identified three integrin beta 6 (ITGB6) mutations responsible for their enamel malformations. The female proband of Family 1 was a compound heterozygote with an ITGB6 transition mutation in Exon 4 (g.4545G > A c.427G > A p.Ala143Thr) and an ITGB6 transversion mutation in Exon 6 (g.27415T > A c.825T > A p.His275Gln). The male proband of Family 2 was homozygous for an ITGB6 transition mutation in Exon 11 (g.73664C > T c.1846C > T p.Arg616*) and hemizygous for a transition mutation in Exon 6 of Nance-Horan Syndrome (NHS Xp22.13; g.355444T > C c.1697T > C p.Met566Thr). These are the first disease-causing ITGB6 mutations to be reported. Immunohistochemistry of mouse mandibular incisors localized ITGB6 to the distal membrane of differentiating ameloblasts and pre-ameloblasts, and then ITGB6 appeared to be internalized by secretory stage ameloblasts. ITGB6 expression was strongest in the maturation stage and its localization was associated with ameloblast modulation. Our findings demonstrate that early and late amelogenesis depend upon cell-matrix interactions. Our approach (from knockout mouse phenotype to human disease) demonstrates the power of mouse reverse genetics in mutational analysis of human genetic disorders and attests to the need for a careful dental phenotyping in large-scale knockout mouse projects.

  16. Homozygous loss of DIAPH1 is a novel cause of microcephaly in humans.

    Science.gov (United States)

    Ercan-Sencicek, A Gulhan; Jambi, Samira; Franjic, Daniel; Nishimura, Sayoko; Li, Mingfeng; El-Fishawy, Paul; Morgan, Thomas M; Sanders, Stephan J; Bilguvar, Kaya; Suri, Mohnish; Johnson, Michele H; Gupta, Abha R; Yuksel, Zafer; Mane, Shrikant; Grigorenko, Elena; Picciotto, Marina; Alberts, Arthur S; Gunel, Murat; Šestan, Nenad; State, Matthew W

    2015-02-01

    The combination of family-based linkage analysis with high-throughput sequencing is a powerful approach to identifying rare genetic variants that contribute to genetically heterogeneous syndromes. Using parametric multipoint linkage analysis and whole exome sequencing, we have identified a gene responsible for microcephaly (MCP), severe visual impairment, intellectual disability, and short stature through the mapping of a homozygous nonsense alteration in a multiply-affected consanguineous family. This gene, DIAPH1, encodes the mammalian Diaphanous-related formin (mDia1), a member of the diaphanous-related formin family of Rho effector proteins. Upon the activation of GTP-bound Rho, mDia1 generates linear actin filaments in the maintenance of polarity during adhesion, migration, and division in immune cells and neuroepithelial cells, and in driving tangential migration of cortical interneurons in the rodent. Here, we show that patients with a homozygous nonsense DIAPH1 alteration (p.Gln778*) have MCP as well as reduced height and weight. diap1 (mDia1 knockout (KO))-deficient mice have grossly normal body and brain size. However, our histological analysis of diap1 KO mouse coronal brain sections at early and postnatal stages shows unilateral ventricular enlargement, indicating that this mutant mouse shows both important similarities as well as differences with human pathology. We also found that mDia1 protein is expressed in human neuronal precursor cells during mitotic cell division and has a major impact in the regulation of spindle formation and cell division.

  17. orco Mutagenesis Causes Loss of Antennal Lobe Glomeruli and Impaired Social Behavior in Ants.

    Science.gov (United States)

    Trible, Waring; Olivos-Cisneros, Leonora; McKenzie, Sean K; Saragosti, Jonathan; Chang, Ni-Chen; Matthews, Benjamin J; Oxley, Peter R; Kronauer, Daniel J C

    2017-08-10

    Life inside ant colonies is orchestrated with diverse pheromones, but it is not clear how ants perceive these social signals. It has been proposed that pheromone perception in ants evolved via expansions in the numbers of odorant receptors (ORs) and antennal lobe glomeruli. Here, we generate the first mutant lines in the clonal raider ant, Ooceraea biroi, by disrupting orco, a gene required for the function of all ORs. We find that orco mutants exhibit severe deficiencies in social behavior and fitness, suggesting they are unable to perceive pheromones. Surprisingly, unlike in Drosophila melanogaster, orco mutant ants also lack most of the ∼500 antennal lobe glomeruli found in wild-type ants. These results illustrate that ORs are essential for ant social organization and raise the possibility that, similar to mammals, receptor function is required for the development and/or maintenance of the highly complex olfactory processing areas in the ant brain. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Loss of Axin2 Causes Ocular Defects During Mouse Eye Development

    Science.gov (United States)

    Alldredge, Ashley; Fuhrmann, Sabine

    2016-01-01

    Purpose The scaffold protein Axin2 is an antagonist and universal target of the Wnt/β-catenin pathway. Disruption of Axin2 may lead to developmental eye defects; however, this has not been examined. The purpose of this study was to investigate the role of Axin2 during ocular and extraocular development in mouse. Methods Animals heterozygous and homozygous for a Axin2lacZ knock-in allele were analyzed at different developmental stages for reporter expression, morphology as well as for the presence of ocular and extraocular markers using histologic and immunohistochemical techniques. Results During early eye development, the Axin2lacZ reporter was expressed in the periocular mesenchyme, RPE, and optic stalk. In the developing retina, Axin2lacZ reporter expression was initiated in ganglion cells at late embryonic stages and robustly expressed in subpopulations of amacrine and horizontal cells postnatally. Activation of the Axin2lacZ reporter overlapped with labeling of POU4F1, PAX6, and Calbindin. Germline deletion of Axin2 led to variable ocular phenotypes ranging from normal to severely defective eyes exhibiting microphthalmia, coloboma, lens defects, and expanded ciliary margin. These defects were correlated with abnormal tissue patterning in individual affected tissues, such as the optic fissure margins in the ventral optic cup and in the expanded ciliary margin. Conclusions Our results reveal a critical role for Axin2 during ocular development, likely by restricting the activity of the Wnt/β-catenin pathway. PMID:27701636

  19. Secondary oxalosis due to excess vitamin C intake: A cause of graft loss in a renal transplant recipient

    Directory of Open Access Journals (Sweden)

    S Yaich

    2014-01-01

    Full Text Available Renal oxalate deposition can be seen with primary hyperoxaluria, malabsorptive states, ethylene glycol toxicity and, rarely, with excessive vitamin C ingestion. We report a case of secondary hyperoxaluria in which the diagnosis was not considered initially because there was no past history of urinary calculi and no evidence of nephrocalcinosis on plain X-ray of the abdomen and ultrasonography. The disease was detected and diagnosed only after kidney transplantation. Secondary oxalosis can cause graft loss or delayed graft function. Biopsy of the allograft should be carefully examined for oxalate deposits even in the absence of a family history. When oxalosis is diagnosed, intensifying hemodialysis (HD to eliminate calcium oxalate can help in the recovery of renal function in some cases. Systematic vitamin C supplementation in HD patients should be avoided as it can be a cause of secondary oxalosis.

  20. Severe fungal sclerokeratitis caused by Metarhizium anisopliae: a case report and literature review.

    Science.gov (United States)

    Eguchi, Hiroshi; Toibana, Toshi; Hotta, Fumika; Miyamoto, Tatsuro; Mitamura, Yoshinori; Yaguchi, Takashi

    2015-02-01

    To date, there has been only one published report on the infectious sclerokeratitis caused by Metarhizium anisopliae, which is an entomopathogenic fungus. Regarding corneal infection, three reports have been published to date. Although the prognoses of the corneal infections are favourable, prognosis when scleral infection is involved is very poor. A 76-year-old patient presented with foreign body sensation in the left eye. Microscopic examination with Fungi Flora Y staining of the corneal scraping revealed fungal infection. The conjunctiva was melted by the infection over a wide area. Although intensive medications were administered, an emergency surgery was necessary because scleral thinning, corneal perforation and lens prolapse occurred. The fungal isolate was identified as M. anisopliae by sequencing the internal transcribed spacer region. Herein, we report the second known case worldwide of M. anisopliae sclerokeratitis, and we review the literature related to the ocular infections.

  1. Maternal perception of cause, signs and severity of diarrhoea in a suburban west African community

    DEFF Research Database (Denmark)

    Sodemann, Morten; Jakobsen, M S; Mølbak, Kare

    1996-01-01

    With the aim of investigating perceived morbidity and care seeking behaviour, a household survey was conducted, where 319 episodes of diarrhoea were followed by interviews every second day. The chance of consultation increased with the number of symptoms reported by the mother. The appearance...... of the eyes and how the child breastfed were early warnings that mothers recognized best. By contrast, there was an 80% reduction in the likelihood of seeking consultation when the mother perceived the diarrhoea as caused by teeth eruption (n = 96). Children with "teething diarrhoea" were, however, just...... as likely to develop signs of dehydration as children with non-teething diarrhoea. We conclude that health education concerning diarrhoea should emphasize early signs of dehydration and the discouragement of "teething" as an explanation of natural diarrhoea....

  2. Compound heterozygous mutations in TTC7A cause familial multiple intestinal atresias and severe combined immunodeficiency.

    Science.gov (United States)

    Yang, W; Lee, P P W; Thong, M-K; Ramanujam, T M; Shanmugam, A; Koh, M-T; Chan, K-W; Ying, D; Wang, Y; Shen, J J; Yang, J; Lau, Y L

    2015-12-01

    Familial multiple intestinal atresias is an autosomal recessive disease with or without combined immunodeficiency. In the last year, several reports have described mutations in the gene TTC7A as causal to the disease in different populations. However, exact correlation between different genotypes and various phenotypes are not clear. In this study, we report identification of novel compound heterozygous mutations in TTC7A gene in a Malay girl with familial multiple intestinal atresias and severe combined immunodeficiency (MIA-SCID) by whole exome sequencing. We found two mutations in TTC7A: one that destroyed a putative splicing acceptor at the junction of intron 17/exon 18 and one that introduced a stop codon that would truncate the last two amino acids of the encoded protein. Reviewing the recent reports on TTC7A mutations reveals correlation between the position and nature of the mutations with patient survival and clinical manifestations. Examination of public databases also suggests carrier status for healthy individuals, making a case for population screening on this gene, especially in populations with suspected frequent founder mutations.

  3. Spinster homolog 2 (spns2 deficiency causes early onset progressive hearing loss.

    Directory of Open Access Journals (Sweden)

    Jing Chen

    2014-10-01

    Full Text Available Spinster homolog 2 (Spns2 acts as a Sphingosine-1-phosphate (S1P transporter in zebrafish and mice, regulating heart development and lymphocyte trafficking respectively. S1P is a biologically active lysophospholipid with multiple roles in signalling. The mechanism of action of Spns2 is still elusive in mammals. Here, we report that Spns2-deficient mice rapidly lost auditory sensitivity and endocochlear potential (EP from 2 to 3 weeks old. We found progressive degeneration of sensory hair cells in the organ of Corti, but the earliest defect was a decline in the EP, suggesting that dysfunction of the lateral wall was the primary lesion. In the lateral wall of adult mutants, we observed structural changes of marginal cell boundaries and of strial capillaries, and reduced expression of several key proteins involved in the generation of the EP (Kcnj10, Kcnq1, Gjb2 and Gjb6, but these changes were likely to be secondary. Permeability of the boundaries of the stria vascularis and of the strial capillaries appeared normal. We also found focal retinal degeneration and anomalies of retinal capillaries together with anterior eye defects in Spns2 mutant mice. Targeted inactivation of Spns2 in red blood cells, platelets, or lymphatic or vascular endothelial cells did not affect hearing, but targeted ablation of Spns2 in the cochlea using a Sox10-Cre allele produced a similar auditory phenotype to the original mutation, suggesting that local Spns2 expression is critical for hearing in mammals. These findings indicate that Spns2 is required for normal maintenance of the EP and hence for normal auditory function, and support a role for S1P signalling in hearing.

  4. Geminin loss causes neural tube defects through disrupted progenitor specification and neuronal differentiation.

    Science.gov (United States)

    Patterson, Ethan S; Waller, Laura E; Kroll, Kristen L

    2014-09-01

    Geminin is a nucleoprotein that can directly bind chromatin regulatory complexes to modulate gene expression during development. Geminin knockout mouse embryos are preimplantation lethal by the 32-cell stage, precluding in vivo study of Geminin's role in neural development. Therefore, here we used a conditional Geminin allele in combination with several Cre-driver lines to define an essential role for Geminin during mammalian neural tube (NT) formation and patterning. Geminin was required in the NT within a critical developmental time window (embryonic day 8.5-10.5), when NT patterning and closure occurs. Geminin excision at these stages resulted in strongly diminished expression of genes that mark and promote dorsal NT identities and decreased differentiation of ventral motor neurons, resulting in completely penetrant NT defects, while excision after embryonic day 10.5 did not result in NT defects. When Geminin was deleted specifically in the spinal NT, both NT defects and axial skeleton defects were observed, but neither defect occurred when Geminin was excised in paraxial mesenchyme, indicating a tissue autonomous requirement for Geminin in developing neuroectoderm. Despite a potential role for Geminin in cell cycle control, we found no evidence of proliferation defects or altered apoptosis. Comparisons of gene expression in the NT of Geminin mutant versus wild-type siblings at embryonic day 10.5 revealed decreased expression of key regulators of neurogenesis, including neurogenic bHLH transcription factors and dorsal interneuron progenitor markers. Together, these data demonstrate a requirement for Geminin for NT patterning and neuronal differentiation during mammalian neurulation in vivo.

  5. Irreversible loss of ice nucleation active sites in mineral dust particles caused by sulphuric acid condensation

    Directory of Open Access Journals (Sweden)

    R. C. Sullivan

    2010-07-01

    sulphuric acid. This implies that the sulphuric acid coating caused permanent chemical and/or physical modification of the ice active surface sites; the possible dissolution of the coating during droplet activation did not restore all immersion/condensation-freezing ability.

  6. NK cells are intrinsically functional in pigs with Severe Combined Immunodeficiency (SCID) caused by spontaneous mutations in the Artemis gene

    Science.gov (United States)

    We have identified Severe Combined Immunodeficiency (SCID) in a line of Yorkshire pigs at Iowa State University. These SCID pigs lack B-cells and T-cells, but possess Natural Killer (NK) cells. This SCID phenotype is caused by recessive mutations in the Artemis gene. Interestingly, two human tumor c...

  7. Duplication Cyst in the Third Part of the Duodenum Presenting with Gastric Outlet Obstruction and Severe Weight Loss

    Science.gov (United States)

    Shaheen, Osama; Sara, Samer; Safadi, Mhd Firas; Alsaid, Bayan

    2015-01-01

    Duodenal duplication is a rare developmental abnormality which is usually diagnosed in infancy and childhood, but less frequently in adulthood. We report a case of a 16-year-old female with a duplication cyst in the third part of the duodenum. The patient presented with symptoms of gastric outlet obstruction, including severe anorexia and weight loss. The diagnosis was made preoperatively by CT scan and upper endoscopy. The cyst was successfully treated by marsupialization on the duodenum using a GIA stapler. Duodenal duplication presents with a wide variety of symptoms. Although illusive, many cases can be properly diagnosed preoperatively by using the appropriate imaging modalities. Treatment choices are tailored according to the size and location of the cyst, in addition to its relation to adjacent structures. The outcomes are favorable in the majority of patients. PMID:26649220

  8. [TNF blockade in rheumatoid arthritis can cause severe fibrosing alveolitis. Six case reports].

    Science.gov (United States)

    Tengstrand, Birgitta; Ernestam, Sofia; Engvall, Inga-Lill; Rydvald, Ylva; Hafström, Ingiäld

    TNF-blockade has been increasingly used in the treatment of rheumatoid arthritis (RA). However, the safety is unclear and an increased risk of both tuberculosis and other infections has been identified. Recently severe fibrosing alveolitis has also been reported in RA-patients treated with TNF-blockade. We report a further six RA patients, who during treatment with infliximab or etanercept developed fulminant lung fibrosis with alveolitis. For four of the patients, the fibrosing alveolitis was fatal. All patients were RF positive and above 60 years and five had mild fibrosis associated with RA before TNF-blockade treatment. Duration of TNF-blockade treatment was for three patients only two months and for the other three, 20-51 months. Age above 60 years and previous lung fibrosis appear to be risk factors for developing fibrosing alveolitis in RA patients treated with TNF-blockade.

  9. Paternal Somatic Mosaicism of a Novel Frameshift Mutation in ELANE Causing Severe Congenital Neutropenia.

    Science.gov (United States)

    Kim, Hee-Jung; Song, Min-Jung; Lee, Ki-O; Kim, Sun-Hee; Kim, Hee-Jin

    2015-12-01

    Severe congenital neutropenia (SCN) is a bone marrow failure disease with an autosomal dominant inheritance from mutations in ELANE. Here, we report a 7-week-old Korean male with SCN. His elder sister died from pneumonia at 2 years. Direct sequencing of ELANE in the proband identified a heterozygous novel frameshift mutation: c.658delC (p.Arg220Glyfs20*). Family study involving his asymptomatic parents with normal cell counts revealed that his father had the same mutation, but at a lower burden than expected in a typical heterozygous state. Further molecular investigation demonstrated somatic mosaicism with ~18% mutant alleles. We concluded the proband inherited the mutation from his somatic mosaic father.

  10. Severe necrotizing myocarditis caused by serratia marcescens infection in an axolotl (Ambystoma mexicanum).

    Science.gov (United States)

    Del-Pozo, J; Girling, S; Pizzi, R; Mancinelli, E; Else, R W

    2011-05-01

    This report provides the first account of the pathological changes associated with infection by Serratia marcescens in an adult male axolotl. The infection resulted in septicaemia with severe multifocal necrotizing myocarditis. The latter lesion evolved to cardiac rupture, haemopericardium and death resulting from cardiac tamponade. This animal was exposed to higher than usual temperatures (24-25 °C) 2 weeks before the onset of disease and this may have resulted in immunocompromise and opportunistic bacterial infection. S. marcescens was isolated from the coelomic and pericardial cavity. Both isolates were identical and were resistant to β-lactam antibiotics, but not to aminoglycosides or fluoroquinolones. The production of red prodigiosin pigment by the bacterium suggested an environmental origin. Overall, the clinical and histopathological presentation suggests that S. marcescens should be included in the list of aetiological agents of the 'red-leg'/bacterial dermatosepticaemia syndrome of amphibians.

  11. Severe acute respiratory distress syndrome caused by unintentional sewing machine lubricant ingestion: A case report.

    Science.gov (United States)

    Kishore, Sunil; Chandelia, Sudha; Patharia, Neha; Swarnim

    2016-11-01

    Sewing machine oil ingestion is rare but is possible due to its availability at home. Chemically, it belongs to hydrocarbon family which is toxic if aspirated, owing to their physical properties such as high volatility and low viscosity. On the contrary, sewing machine lubricant has high viscosity and low volatility which makes it aspiration less likely. The main danger of hydrocarbon ingestion is chemical pneumonitis which may be as severe as acute respiratory distress syndrome (ARDS). We report a case of a 5-year-old girl with accidental ingestion of sewing machine lubricant oil, who subsequently developed ARDS refractory to mechanical ventilation. There was much improvement with airway pressure release ventilation mode of ventilation, but the child succumbed to death due to pulmonary hemorrhage.

  12. Multi-drug-resistant hypertension caused by severe aortic coarctation presenting in late adulthood.

    Science.gov (United States)

    Meller, Stephanie M; Fahey, John T; Setaro, John F; Forrest, John K

    2015-04-01

    Aortic coarctation, a congenital narrowing in the region of the ligamentum arteriosium, is a rare etiology for multi-drug-resistant hypertension in adulthood; however, advances in stenting modalities may offer long-term improvements in morbidity and possibly even cure. We report on a female patient in her late 50s presenting with refractory hypertension and severely elevated renin levels, ultimately diagnosed with aortic coarctation and treated with percutaneous stent implantation, which resulted in successful blood pressure control with verapamil monotherapy. This case highlights the efficacy of endovascular stent implantation for the treatment of coarctation and the need for clinicians to consider this disease entity in the differential diagnosis of refractory hypertension even in late adulthood.

  13. Severe acute respiratory distress syndrome caused by unintentional sewing machine lubricant ingestion: A case report

    Directory of Open Access Journals (Sweden)

    Sunil Kishore

    2016-01-01

    Full Text Available Sewing machine oil ingestion is rare but is possible due to its availability at home. Chemically, it belongs to hydrocarbon family which is toxic if aspirated, owing to their physical properties such as high volatility and low viscosity. On the contrary, sewing machine lubricant has high viscosity and low volatility which makes it aspiration less likely. The main danger of hydrocarbon ingestion is chemical pneumonitis which may be as severe as acute respiratory distress syndrome (ARDS. We report a case of a 5-year-old girl with accidental ingestion of sewing machine lubricant oil, who subsequently developed ARDS refractory to mechanical ventilation. There was much improvement with airway pressure release ventilation mode of ventilation, but the child succumbed to death due to pulmonary hemorrhage.

  14. Severe esophageal injuries caused by accidental button battery ingestion in children.

    Science.gov (United States)

    Fuentes, Sara; Cano, Indalecio; Benavent, María Isabel; Gómez, Andrés

    2014-10-01

    Button batteries represent a low percentage of all foreign bodies swallowed by children and esophageal location is even less frequent. However, these cases are more likely to develop severe injuries. The aim of this essay is to report three cases treated in our institution and review previous reports. Chart review and literature search. We treated three children between 2-7- years old with button batteries lodged at esophagus. They all presented esophageal burns (EB), which evolved in esophageal stenosis in two out of the three cases. We found 29 more cases in literature and the injuries included EB, esophageal perforation (EP) and tracheoesophageal fistula (TEF). Swallowed button batteries rarely remain in esophagus, but these cases present a higher risk of tisular damage. Injuries can take place even after few hours; and therefore, endoscopy must be performed as soon as possible. Further study on button batteries' safety and the establishment of a maximum size for them would be good preventive measures.

  15. Levamisole tainted cocaine causing severe neutropenia in Alberta and British Columbia

    Science.gov (United States)

    2009-01-01

    Background Five cases of severe neutropenia (neutrophil counts < 0.5 per 109 cells/L) associated with exposure to cocaine and levamisole, an antihelimithic agent no longer available in Canada, were identified in Alberta in 2008. Alberta and British Columbia (BC) public health officials issued an advisory and urged health care professionals to report cases to public health. This paper presents the findings of the public health investigations. Methods Cases were identified prospectively through reporting by clinicians and a retrospective review of laboratory and medical examiners data from January 1, 2006 to March 31, 2009. Cases were categorized as confirmed, probable or suspect. Only the confirmed and probable cases are included in this paper. Results We compare cases of severe neutropenia associated with tainted cocaine (NATC) identified in Alberta and BC between January 1, 2008 to March 31, 2009. Of the 42 NATC cases: 23(55%) were from Alberta; 19(45%) were from British Columbia; 57% of these cases reported crack cocaine use (93% of those who identified type of cocaine used); 7% reported using cocaine powder; and the main route of cocaine administration was from smoking (72%). Fifty percent of the NATC cases had multiple episodes of neutropenia associated with cocaine use. Cases typically presented with bacterial/fungal infections and fever. One Alberta NATC case produced anti-neutrophil antibodies, and four were positive for anti-neutrophil cytoplasmic antibody (ANCA). Analysis of two crack pipes and one drug sample obtained from NATC cases confirmed the presence of both cocaine and levamisole. A further 18 cases were identified through the retrospective review of laboratory and medical examiner data in Alberta Interpretation Our findings support a link between neutropenia and levamisole tainted cocaine; particularly from smoking the crack form of cocaine. Some patients may be genetically predisposed to develop levamisole-related neutropenia. Awareness of the

  16. Levamisole tainted cocaine causing severe neutropenia in Alberta and British Columbia

    Directory of Open Access Journals (Sweden)

    Fan Shihe

    2009-11-01

    Full Text Available Abstract Background Five cases of severe neutropenia (neutrophil counts 9 cells/L associated with exposure to cocaine and levamisole, an antihelimithic agent no longer available in Canada, were identified in Alberta in 2008. Alberta and British Columbia (BC public health officials issued an advisory and urged health care professionals to report cases to public health. This paper presents the findings of the public health investigations. Methods Cases were identified prospectively through reporting by clinicians and a retrospective review of laboratory and medical examiners data from January 1, 2006 to March 31, 2009. Cases were categorized as confirmed, probable or suspect. Only the confirmed and probable cases are included in this paper. Results We compare cases of severe neutropenia associated with tainted cocaine (NATC identified in Alberta and BC between January 1, 2008 to March 31, 2009. Of the 42 NATC cases: 23(55% were from Alberta; 19(45% were from British Columbia; 57% of these cases reported crack cocaine use (93% of those who identified type of cocaine used; 7% reported using cocaine powder; and the main route of cocaine administration was from smoking (72%. Fifty percent of the NATC cases had multiple episodes of neutropenia associated with cocaine use. Cases typically presented with bacterial/fungal infections and fever. One Alberta NATC case produced anti-neutrophil antibodies, and four were positive for anti-neutrophil cytoplasmic antibody (ANCA. Analysis of two crack pipes and one drug sample obtained from NATC cases confirmed the presence of both cocaine and levamisole. A further 18 cases were identified through the retrospective review of laboratory and medical examiner data in Alberta Interpretation Our findings support a link between neutropenia and levamisole tainted cocaine; particularly from smoking the crack form of cocaine. Some patients may be genetically predisposed to develop levamisole-related neutropenia. Awareness

  17. Blue rubber bleb naevus syndrome: a rare cause of chronic occult blood loss and iron deficiency anaemia.

    Science.gov (United States)

    Lybecker, Martin Bell; Stawowy, Marek; Clausen, Niels

    2016-12-20

    Blue rubber bleb naevus syndrome (BRBNS) is a rare vascular disorder with malformed veins, or blebs, appearing in the skin or internal organs. Gastrointestinal tract involvement is the most common feature and often subject to bleeding, potentially resulting in chronic occult blood loss and iron deficiency anaemia. We present the case of a 10-year-old boy with venous malformations on the feet and severe anaemia. Although massive sudden haemorrhage rarely occurs, awareness of the illness is necessary to prevent complications. 2016 BMJ Publishing Group Ltd.

  18. Duplication and Loss of Function of Genes Encoding RNA Polymerase III Subunit C4 Causes Hybrid Incompatibility in Rice

    Directory of Open Access Journals (Sweden)

    Giao Ngoc Nguyen

    2017-08-01

    Full Text Available Reproductive barriers are commonly observed in both animals and plants, in which they maintain species integrity and contribute to speciation. This report shows that a combination of loss-of-function alleles at two duplicated loci, DUPLICATED GAMETOPHYTIC STERILITY 1 (DGS1 on chromosome 4 and DGS2 on chromosome 7, causes pollen sterility in hybrid progeny derived from an interspecific cross between cultivated rice, Oryza sativa, and an Asian annual wild rice, O. nivara. Male gametes carrying the DGS1 allele from O. nivara (DGS1-nivaras and the DGS2 allele from O. sativa (DGS2-T65s were sterile, but female gametes carrying the same genotype were fertile. We isolated the causal gene, which encodes a protein homologous to DNA-dependent RNA polymerase (RNAP III subunit C4 (RPC4. RPC4 facilitates the transcription of 5S rRNAs and tRNAs. The loss-of-function alleles at DGS1-nivaras and DGS2-T65s were caused by weak or nonexpression of RPC4 and an absence of RPC4, respectively. Phylogenetic analysis demonstrated that gene duplication of RPC4 at DGS1 and DGS2 was a recent event that occurred after divergence of the ancestral population of Oryza from other Poaceae or during diversification of AA-genome species.

  19. Surdez súbita causada por hemorragia intralabiríntica Sudden hearing loss caused by labyrinthine hemorrhage

    Directory of Open Access Journals (Sweden)

    Raquel Salomone

    2008-10-01

    Full Text Available A surdez súbita sensorioneural é uma perda auditiva súbita ou rapidamente progressiva. Na maioria dos casos a etiologia não é descoberta. Uma das causas possíveis de surdez súbita é a hemorragia intralabiríntica que, antes do surgimento da ressonância magnética, não era corretamente diagnosticada. O objetivo deste trabalho é relatar um caso de surdez súbita causada por hemorragia intralabiríntica e realizar uma revisão da literatura sobre este assunto.Sudden sensorineural hearing loss is relatively frequent. In most cases, the etiology is not discovered. One of the possible causes for sudden deafness is inner labyrinth bleeding, which was difficult to diagnose before the advent of magnetic resonance imaging. The purpose of this paper is to report a case of sudden hearing loss caused by a labyrinthine hemorrhage, and to present a review of the literature on this topic.

  20. Loss-of-function mutations in CAST cause peeling skin, leukonychia, acral punctate keratoses, cheilitis, and knuckle pads.

    Science.gov (United States)

    Lin, Zhimiao; Zhao, Jiahui; Nitoiu, Daniela; Scott, Claire A; Plagnol, Vincent; Smith, Frances J D; Wilson, Neil J; Cole, Christian; Schwartz, Mary E; McLean, W H Irwin; Wang, Huijun; Feng, Cheng; Duo, Lina; Zhou, Eray Yihui; Ren, Yali; Dai, Lanlan; Chen, Yulan; Zhang, Jianguo; Xu, Xun; O'Toole, Edel A; Kelsell, David P; Yang, Yong

    2015-03-05

    Calpastatin is an endogenous specific inhibitor of calpain, a calcium-dependent cysteine protease. Here we show that loss-of-function mutations in calpastatin (CAST) are the genetic causes of an autosomal-recessive condition characterized by generalized peeling skin, leukonychia, acral punctate keratoses, cheilitis, and knuckle pads, which we propose to be given the acronym PLACK syndrome. In affected individuals with PLACK syndrome from three families of different ethnicities, we identified homozygous mutations (c.607dup, c.424A>T, and c.1750delG) in CAST, all of which were predicted to encode truncated proteins (p.Ile203Asnfs∗8, p.Lys142∗, and p.Val584Trpfs∗37). Immunohistochemistry shows that staining of calpastatin is reduced in skin from affected individuals. Transmission electron microscopy revealed widening of intercellular spaces with chromatin condensation and margination in the upper stratum spinosum in lesional skin, suggesting impaired intercellular adhesion as well as keratinocyte apoptosis. A significant increase of apoptotic keratinocytes was also observed in TUNEL assays. In vitro studies utilizing siRNA-mediated CAST knockdown revealed a role for calpastatin in keratinocyte adhesion. In summary, we describe PLACK syndrome, as a clinical entity of defective epidermal adhesion, caused by loss-of-function mutations in CAST.

  1. Loss of Acid sensing ion channel-1a and bicarbonate administration attenuate the severity of traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Terry Yin

    Full Text Available Traumatic brain injury (TBI is a common cause of morbidity and mortality in people of all ages. Following the acute mechanical insult, TBI evolves over the ensuing minutes and days. Understanding the secondary factors that contribute to TBI might suggest therapeutic strategies to reduce the long-term consequences of brain trauma. To assess secondary factors that contribute to TBI, we studied a lateral fluid percussion injury (FPI model in mice. Following FPI, the brain cortex became acidic, consistent with data from humans following brain trauma. Administering HCO3 (- after FPI prevented the acidosis and reduced the extent of neurodegeneration. Because acidosis can activate acid sensing ion channels (ASICs, we also studied ASIC1a(-/- mice and found reduced neurodegeneration after FPI. Both HCO3 (- administration and loss of ASIC1a also reduced functional deficits caused by FPI. These results suggest that FPI induces cerebral acidosis that activates ASIC channels and contributes to secondary injury in TBI. They also suggest a therapeutic strategy to attenuate the adverse consequences of TBI.

  2. A novel mutation in the ADA gene causing severe combined immunodeficiency in an Arab patient: a case report

    Directory of Open Access Journals (Sweden)

    Hellani Ali

    2009-04-01

    Full Text Available Abstract Introduction About 20% of the cases of human severe combined immunodeficiency are the result of the child being homozygous for defective genes encoding the enzyme adenosine deaminase. To our knowledge, the mutation pattern in Arab patients with severe combined immunodeficiency has never been reported previously. Case presentation A 14-month-old Arab boy had clinical features typical of severe combined immunodeficiency. His clinical picture and flow cytometric analysis raised the diagnosis of adenosine deaminase deficiency and prompted us to screen the adenosine deaminase gene for mutation(s. We detected a novel mutation in exon 9 of the adenosine deaminase gene (p.Arg282>Gln, which we believe is the cause of the severe combined immunodeficiency phenotype observed in our patient. Conclusion This is the first report of adenosine deaminase mutation in an Arab patient with severe combined immunodeficiency due to a novel pathogenic mutation in the adenosine deaminase gene.

  3. Outbreak of severe Pseudomonas aeruginosa infections caused by a contaminated drain in a whirlpool bathtub.

    Science.gov (United States)

    Berrouane, Y F; McNutt, L A; Buschelman, B J; Rhomberg, P R; Sanford, M D; Hollis, R J; Pfaller, M A; Herwaldt, L A

    2000-12-01

    During a 14-month period, 7 patients with hematological malignancies acquired serious infections caused by a single strain of multiply resistant Pseudomonas aeruginosa. A case-control study, culture surveys, and pulsed-field gel electrophoresis implicated a whirlpool bathtub on the unit as the reservoir. All case patients and 32% of control patients used this bathtub (P=.003). The epidemic strain was found only in cultures of samples taken from the bathtub. The drain of the whirlpool bathtub, which was contaminated with the epidemic strain, closed approximately 2.54 cm below the drain's strainer. Water from the faucet, which was not contaminated, became contaminated with P. aeruginosa from the drain when the tub was filled. The design of the drain allowed the epidemic strain to be transmitted to immunocompromised patients who used the whirlpool bathtub. Such tubs are used in many hospitals, and they may be an unrecognized source of nosocomial infections. This potential source of infection could be eliminated by using whirlpool bathtubs with drains that seal at the top.

  4. An oblique muscle hematoma as a rare cause of severe abdominal pain: a case report

    Directory of Open Access Journals (Sweden)

    Shimodaira Masanori

    2013-01-01

    Full Text Available Abstract Background Abdominal wall hematomas are an uncommon cause of acute abdominal pain and are often misdiagnosed. They are more common in elderly individuals, particularly in those under anticoagulant therapy. Most abdominal wall hematomas occur in the rectus sheath, and hematomas within the oblique muscle are very rare and are poorly described in the literature. Here we report the case of an oblique muscle hematoma in a middle-aged patient who was not under anticoagulant therapy. Case presentation A 42-year-old Japanese man presented with a painful, enlarging, lateral abdominal wall mass, which appeared after playing baseball. Abdominal computed tomography and ultrasonography showed a large soft tissue mass located in the patient’s left internal oblique muscle. A diagnosis of a lateral oblique muscle hematoma was made and the patient was treated conservatively. Conclusion Physicians should consider an oblique muscle hematoma during the initial differential diagnosis of pain in the lateral abdominal wall even in the absence of anticoagulant therapy or trauma.

  5. [Life threatening salicylate poisoning caused by percutaneous absorption in severe ichthyosis vulgaris].

    Science.gov (United States)

    Germann, R; Schindera, I; Kuch, M; Seitz, U; Altmeyer, S; Schindera, F

    1996-08-01

    In a 7-year-old boy, ichthyosis vulgaris was treated with a 10% ointment for application over a large area of the body surface. In this way, the child received 400 g salicylic acid (0.6 g/kg body weight per day) percutaneously over a period of 4 weeks. The patient was referred to hospital by the family doctor: he was in a deep somnolent state, apparently caused by hyperventilation following wheezing, vomiting, tinnitus and vertigo. Salicylate intoxication was suspected because of metabolic acidosis, an anion gap and respiratory overcompensation. The diagnosis was confirmed by a serum salicylate level of 985 micrograms/ml (therapeutic level 150-300 micrograms/ml). Following forced diuresis and alkalization with sodium bicarbonate, haemodialysis was unnecessary. As the salicylate level declined to values within the therapeutic range, the patient started to recover consciousness, waking on the 4th day. By day 6 there were still obvious neurological deficiencies. Fecal incontinence, bilateral ptosis and intermittent diverging strabismus on the right persisted for some weeks. It was 6 months before complete neurological resolution was achieved. The pathogenesis of salicylate toxicity and the need for safer therapies for ichthyosis vulgaris are discussed.

  6. Mucormycosis as a rare cause of severe gastrointestinal bleeding after multivisceral transplantation.

    Science.gov (United States)

    Irtan, S; Lamerain, M; Lesage, F; Verkarre, V; Bougnoux, M-E; Lanternier, F; Zahar, J R; Salvi, N; Talbotec, C; Lortholary, O; Lacaille, F; Chardot, C

    2013-12-01

    Mucormycosis, an emerging fungal infection in solid organ transplant patients, is mostly located in rhino-orbito-cerebral, pulmonary, and cutaneous areas, or disseminated with poor prognosis. A 4-year-old girl with chronic intestinal pseudo-obstruction syndrome underwent a modified multivisceral transplantation, including half of the stomach, the duodeno-pancreas, the small bowel, and the right colon. On postoperative day 5, a digestive perforation was suspected. Surgical exploration found a small necrotic area on the native stomach, which was externally drained. The next day, massive gastric bleeding occurred. During the emergency laparotomy, 2 hemorrhagic ulcers were found and resected from the transplanted stomach. Pathology and fungal culture showed mucormycosis caused by Lichtheimia (formerly Absidia) ramosa in both the transplanted and native stomach. High-dose intravenous liposomal amphotericin B was immediately started. No other site of fungal infection was found. The child recovered, and 3 years after transplantation, is alive and well, off parenteral nutrition. The originality of this case is the very early presentation after transplantation, the unusual site, and the complete recovery after rapid medico-surgical management. The origin of the fungus and treatment are discussed.

  7. Impact of severe disease caused by respiratory syncytial virus in children living in developed countries.

    Science.gov (United States)

    Simoes, Eric A; Carbonell-Estrany, Xavier

    2003-02-01

    Among industrialized nations, the rate of rehospitalization in the United States for respiratory syncytial virus (RSV) is approximately 30 per 1000, exceptions being noted for American Indians and Alaskan natives, two ethnic groups who tend toward higher rates of RSV hospitalization. In distinction Japan reports an admission rate of 60 per 1000 for RSV disease. Yet Japan ranks considerably lower than many of its western counterparts in premature births. Whether an RSV subtype, a new viral genotype or some other unifying characteristic exists that might explain the severity of adenovirus, parainfluenza and RSV infections in this region of Asia remains to be determined. Outcomes trials in the United States, Canada, United Kingdom, Denmark and Japan all identified crowding and exposure to tobacco smoke as significant and independent risk factors for disease severity of RSV. The epidemiology of RSV is largely consistent throughout Europe, with peak outbreaks occurring in December and January. In Europe RSV accounts for 42 to 45% of hospital admissions for lower respiratory tract infections in children younger than 2 years of age, and inpatient populations tend to be younger and to experience greater disease severity. For RSV bronchiolitis lengths of stay in European hospitals range from a low of 4 days to a high of 10 days. The Infección Respiratoria Infantil por Virus Respiratorio Sincitial Study Group in Spain conducted 2 prospective observational studies in 14 and 26 neonatal units, respectively, on nonprophylaxed neonates to determine hospitalization rates for respiratory syncytial viral illness during 2 consecutive RSV seasons. Throughout each respiratory season the study group followed premature infants of < or =32 weeks gestational age at birth, representing an annual birth cohort of approximately 100 000 infants. A total of 584 infants who were < or =32 weeks gestational age in the first season and 999 in the second season were followed at monthly intervals

  8. No-Reference Video Quality Assessment Model for Distortion Caused by Packet Loss in the Real-Time Mobile Video Services

    Directory of Open Access Journals (Sweden)

    Jiarun Song

    2014-01-01

    Full Text Available Packet loss will make severe errors due to the corruption of related video data. For most video streams, because the predictive coding structures are employed, the transmission errors in one frame will not only cause decoding failure of itself at the receiver side, but also propagate to its subsequent frames along the motion prediction path, which will bring a significant degradation of end-to-end video quality. To quantify the effects of packet loss on video quality, a no-reference objective quality assessment model is presented in this paper. Considering the fact that the degradation of video quality significantly relies on the video content, the temporal complexity is estimated to reflect the varying characteristic of video content, using the macroblocks with different motion activities in each frame. Then, the quality of the frame affected by the reference frame loss, by error propagation, or by both of them is evaluated, respectively. Utilizing a two-level temporal pooling scheme, the video quality is finally obtained. Extensive experimental results show that the video quality estimated by the proposed method matches well with the subjective quality.

  9. ALDH1A3 loss of function causes bilateral anophthalmia/microphthalmia and hypoplasia of the optic nerve and optic chiasm.

    Science.gov (United States)

    Yahyavi, Mani; Abouzeid, Hana; Gawdat, Ghada; de Preux, Anne-Sophie; Xiao, Tong; Bardakjian, Tanya; Schneider, Adele; Choi, Alex; Jorgenson, Eric; Baier, Herwig; El Sada, Mohamad; Schorderet, Daniel F; Slavotinek, Anne M

    2013-08-15

    The major active retinoid, all-trans retinoic acid, has long been recognized as critical for the development of several organs, including the eye. Mutations in STRA6, the gene encoding the cellular receptor for vitamin A, in patients with Matthew-Wood syndrome and anophthalmia/microphthalmia (A/M), have previously demonstrated the importance of retinol metabolism in human eye disease. We used homozygosity mapping combined with next-generation sequencing to interrogate patients with anophthalmia and microphthalmia for new causative genes. We used whole-exome and whole-genome sequencing to study a family with two affected brothers with bilateral A/M and a simplex case with bilateral anophthalmia and hypoplasia of the optic nerve and optic chiasm. Analysis of novel sequence variants revealed homozygosity for two nonsense mutations in ALDH1A3, c.568A>G, predicting p.Lys190*, in the familial cases, and c.1165A>T, predicting p.Lys389*, in the simplex case. Both mutations predict nonsense-mediated decay and complete loss of function. We performed antisense morpholino (MO) studies in Danio rerio to characterize the developmental effects of loss of Aldh1a3 function. MO-injected larvae showed a significant reduction in eye size, and aberrant axonal projections to the tectum were noted. We conclude that ALDH1A3 loss of function causes anophthalmia and aberrant eye development in humans and in animal model systems.

  10. Protective effects of penehyclidine hydrochloride on acute lung injury caused by severe dichlorvos poisoning in swine

    Institute of Scientific and Technical Information of China (English)

    CUI Juan; LI Chun-sheng; HE Xin-hua; SONG Yu-guo

    2013-01-01

    Background Organophosphate poisoning is an important health problem in developing countries which causes death mainly by inducing acute lung injury.In this study,we examined the effects of penehyclidine hydrochloride (PHC),a selective M-receptor inhibitor,on dichlorvos-induced acute lung injury in swine.Methods Twenty-two female swines were randomly divided into control (n=5),dichlorvos (n=6),atropine (n=6),and PHC (n=5) groups.Hemodynamic data,extravascular lung water index (EVLWI),and pulmonary vascular permeability index (PVPI) were monitored; blood gas analysis and acetylcholinesterase (AchE) levels were measured.PaO2/FiO2,cardiac index (Cl),and pulmonary vascular resistance indices (PVRI) were calculated.At termination of the study,pulmonary tissue was collected for ATPase activity determination and wet to dry weight ratio (W/D) testing 6 hours post-poisoning.TUNEL assay,and Bax,Bcl-2,and caspase-3 expression were applied to pulmonary tissue,and histopathology was observed.Results After poisoning,PHC markedly decreased PVRI,increased CI more effectively than atropine.Anticholinergic treatment reduced W/D,apoptosis index (AI),and mitigated injury to the structure of lung; however,PHC reduced AI and caspase-3 expression and improved Bcl-2/Bax more effectively than atropine.Atropine and PHC improved ATPase activities; a significant difference between groups was observed in Ca2+-ATPase activity,but not Na+-K+-ATPase activity.Conclusions The PHC group showed mild impairment in pathology,less apoptotic cells,and little impact on cardiac function compared with the atropine group in dichlorvos-induced acute lung injury.

  11. Morphological adjustments in a meandering reach of the middle Yangtze River caused by severe human activities

    Science.gov (United States)

    Zhou, Meirong; Xia, Junqiang; Lu, Jinyou; Deng, Shanshan; Lin, Fenfen

    2017-05-01

    In the past 50 years, the Shishou reach in the middle Yangtze River underwent significant channel evolution owing to the implementation of an artificial cutoff, the construction of bank revetment works and the operation of the Three Gorges Project (TGP). Based on the measured hydrological data and topographic data, the processes of channel evolution in this reach were investigated mainly from the adjustments in planform and cross-sectional geometries. The variation in planform geometry obtained in this study indicates that (i) the artificial cutoff at Zhongzhouzi caused the river regime to adjust drastically, with the mean rate of thalweg migration at reach scale of 42.0 m/a over the period 1966-1975; (ii) then the effect of this artificial cutoff reduced gradually, with the mean migration rate decreasing to 40 m/a owing to the occurrence of high water levels in 1993-1998; and (iii) the average annual rate of thalweg migration decreased to 29.3 m/a because of the impacts of various bank protection engineering and the TGP operation during the period 2002-2015. However, remarkable thalweg migration processes still occurred in local regions after the TGP operation, which resulted in significant bankline migration in local reaches of Beimenkou, Shijiatai, and Tiaoxiankou. In addition, the adjustments of bankfull channel geometry were investigated at section and reach scales after the TGP operation. Calculated results show that lateral channel migration in this reach was restricted by various river regulation works and that channel evolution was mainly characterized by an increase in bankfull depth and cross-sectional area. Empirical relationships were developed between the reach-scale bankfull dimensions (depth and area), the bankfull widths at specified sections, and the previous 5-year average fluvial erosion intensity during flood seasons, with high correlation degrees between them being obtained.

  12. Severe disseminated phaeohyphomycosis in an immunocompetent patient caused by Veronaea botryosa.

    Science.gov (United States)

    Bonifaz, Alexandro; Davoudi, Mehrnaz Mohammad; de Hoog, G S; Padilla-Desgarennes, Carmen; Vázquez-González, Denisse; Navarrete, Gisela; Meis, Jacques F; Badali, Hamid

    2013-06-01

    We present a severe case of disseminated phaeohyphomycosis due to Veronaea botryosa. A 32-year-old female, native from Cuautla, Morelos, Mexico, presented a chronic dermatosis which started 10 years earlier with multiple exophytic, multilobulated, soft, and pedunculated or sessile neoformations of diverse sizes from 2 to 10 cm in diameter, which became verrucose and increased in size. The patient was immunocompetent, and no hereditary or familiar precedents of importance were known. No treatment was given, and the dermatosis remained relatively stable until the patient became pregnant in 2001 and 2003. The infection then exacerbated and worsened, leading to dissemination to the extremities, trunk, and face. The initial diagnosis was chromoblastomycosis which was treated with terbinafine and itraconazole but without visible improvement. Histopathology revealed pigmented, irregular, unbranched, and septate hyphae. Veronaea botryosa was isolated (CBS 127264 = JX566723), and its identity was confirmed by sequencing the internal transcribed spacer (ITS) rDNA. Therapy with posaconazole (800 mg/day) was started showing a gradual improvement of lesions with a reduction in size and flattening of the eruptions.

  13. Lighter Ingestion as an Uncommon Cause of Severe Vomiting in a Schizophrenia Patient

    Directory of Open Access Journals (Sweden)

    Yahya Atayan

    2016-01-01

    Full Text Available Background. Foreign bodies in the gastrointestinal tract are important morbid and mortal clinical conditions. Particularly, emergency treatment is required for cutting and drilling bodies. The majority of ingested foreign bodies (80–90% leave gastrointestinal tract without creating problems. In 10–20% of cases, intervention is absolutely required. Less than 1% of cases need surgery. In this paper, we present a schizophrenia patient who swallowed multiple lighters. Case. A 21-year-old male schizophrenic patient who uses psychotic drugs presented to the emergency department with the complaints of abdominal pain, severe vomiting, and inability to swallow for a week. His physical examination revealed epigastric tenderness. A plain radiograph of the abdomen revealed multiple tiny metallic densities. Gastroscopy was performed. The lighters were not allowing the passage, and some of them had penetrated the gastric mucosa, and bezoars were observed. One lighter was extracted with the help of the polypectomy snare. Other lighters as a bezoar were removed by surgery. Conclusion. Excessive vomiting of swallowed foreign bodies in the etiology of psychotic patients should be kept in mind. Endoscopic therapy can be performed in the early stages in these patients, but in the late stage surgery is inevitable.

  14. TFIIH subunit alterations causing xeroderma pigmentosum and trichothiodystrophy specifically disturb several steps during transcription.

    Science.gov (United States)

    Singh, Amita; Compe, Emanuel; Le May, Nicolas; Egly, Jean-Marc

    2015-02-01

    Mutations in genes encoding the ERCC3 (XPB), ERCC2 (XPD), and GTF2H5 (p8 or TTD-A) subunits of the transcription and DNA-repair factor TFIIH lead to three autosomal-recessive disorders: xeroderma pigmentosum (XP), XP associated with Cockayne syndrome (XP/CS), and trichothiodystrophy (TTD). Although these diseases were originally associated with defects in DNA repair, transcription deficiencies might be also implicated. By using retinoic acid receptor beta isoform 2 (RARB2) as a model in several cells bearing mutations in genes encoding TFIIH subunits, we observed that (1) the recruitment of the TFIIH complex was altered at the activated RARB2 promoter, (2) TFIIH participated in the recruitment of nucleotide excision repair (NER) factors during transcription in a manner different from that observed during NER, and (3) the different TFIIH variants disturbed transcription by having distinct consequences on post-translational modifications of histones, DNA-break induction, DNA demethylation, and gene-loop formation. The transition from heterochromatin to euchromatin was disrupted depending on the variant, illustrating the fact that TFIIH, by contributing to NER factor recruitment, orchestrates chromatin remodeling. The subtle transcriptional differences found between various TFIIH variants thus participate in the phenotypic variability observed among XP, XP/CS, and TTD individuals.

  15. Pulmonary sequestration causing severe cardiac failure requiring lobectomy in an extreme preterm infant

    Directory of Open Access Journals (Sweden)

    Rohit Nagar

    2015-10-01

    Full Text Available We report a case of a large, extralobar pulmonary sequestration in a preterm infant born at 25 weeks gestational age. A computed tomography (CT angiogram demonstrated that the arterial supply arose from the celiac trunk while an abnormally large, single left pulmonary vein drained the sequestration. This, along with the large patent ductus arteriosus (PDA, created a double left to right shunt, which resulted in severe, high output cardiac failure. Despite aggressive medical management for 3 weeks, he remained critically ill and developed renal failure. Therefore, after multiple, extensive multi-disciplinary discussions with the family, resection was offered as the only possibility for survival. He underwent a left thoracotomy and resection of the extra-lobar sequestration, which was occupying the lower two-thirds of his left hemithorax. To our knowledge, this is the youngest patient in the literature to undergo resection of an extra-lobar sequestration. Management challenges in terms of balancing the cardiac failure against the timing, approach and success of surgical intervention are also discussed along with a review of the literature.

  16. Premature myogenic differentiation and depletion of progenitor cells cause severe muscle hypotrophy in Delta1 mutants.

    Science.gov (United States)

    Schuster-Gossler, Karin; Cordes, Ralf; Gossler, Achim

    2007-01-09

    In vertebrates, skeletal myogenesis is initiated by the generation of myoblasts followed by their differentiation to myocytes and the formation of myofibers. The determination of myoblasts and their differentiation are controlled by muscle regulatory factors that are activated at specific stages during myogenesis. During late embryonic and fetal stages a distinct population of resident proliferating progenitor cells is the major source of myogenic cells. How the differentiation of myoblasts and progenitor cells is regulated is not clear. We show that in mouse embryos the Notch ligand Delta1 (Dll1) controls both differentiation of early myoblasts and maintenance of myogenic progenitor cells. Early dermomyotome-derived myoblasts are determined normally in Dll1 mutant embryos, but their differentiation is accelerated, leading to a transient excess of myotomal muscle fibers. Similarly, migratory hypaxial myogenic cells colonize the limb buds and activate muscle regulatory factor expression normally, but muscle differentiation progresses more rapidly. Resident progenitor cells defined by Pax3/Pax7 expression are formed initially, but they are progressively lost and virtually absent at embryonic day 14.5. Muscle growth declines beginning around embryonic day 12, leading to subsequent severe muscle hypotrophy in hypomorphic Dll1 fetuses. We suggest that premature and excessive differentiation leads to depletion of progenitor cells and cessation of muscle growth, and we conclude that Dll1 provides essential signals that are required to prevent uncontrolled differentiation early and ensure sustained muscle differentiation during development.

  17. Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy.

    Science.gov (United States)

    Habarou, Florence; Hamel, Yamina; Haack, Tobias B; Feichtinger, René G; Lebigot, Elise; Marquardt, Iris; Busiah, Kanetee; Laroche, Cécile; Madrange, Marine; Grisel, Coraline; Pontoizeau, Clément; Eisermann, Monika; Boutron, Audrey; Chrétien, Dominique; Chadefaux-Vekemans, Bernadette; Barouki, Robert; Bole-Feysot, Christine; Nitschke, Patrick; Goudin, Nicolas; Boddaert, Nathalie; Nemazanyy, Ivan; Delahodde, Agnès; Kölker, Stefan; Rodenburg, Richard J; Korenke, G Christoph; Meitinger, Thomas; Strom, Tim M; Prokisch, Holger; Rotig, Agnes; Ottolenghi, Chris; Mayr, Johannes A; de Lonlay, Pascale

    2017-08-03

    Lipoate serves as a cofactor for the glycine cleavage system (GCS) and four 2-oxoacid dehydrogenases functioning in energy metabolism (α-oxoglutarate dehydrogenase [α-KGDHc] and pyruvate dehydrogenase [PDHc]), or amino acid metabolism (branched-chain oxoacid dehydrogenase, 2-oxoadipate dehydrogenase). Mitochondrial lipoate synthesis involves three enzymatic steps catalyzed sequentially by lipoyl(octanoyl) transferase 2 (LIPT2), lipoic acid synthetase (LIAS), and lipoyltransferase 1 (LIPT1). Mutations in LIAS have been associated with nonketotic hyperglycinemia-like early-onset convulsions and encephalopathy combined with a defect in mitochondrial energy metabolism. LIPT1 deficiency spares GCS deficiency and has been associated with a biochemical signature of combined 2-oxoacid dehydrogenase deficiency leading to early death or Leigh-like encephalopathy. We report on the identification of biallelic LIPT2 mutations in three affected individuals from two families with severe neonatal encephalopathy. Brain MRI showed major cortical atrophy with white matter abnormalities and cysts. Plasma glycine was mildly increased. Affected individuals' fibroblasts showed reduced oxygen consumption rates, PDHc, α-KGDHc activities, leucine catabolic flux, and decreased protein lipoylation. A normalization of lipoylation was observed after expression of wild-type LIPT2, arguing for LIPT2 requirement in intramitochondrial lipoate synthesis. Lipoic acid supplementation did not improve clinical condition nor activities of PDHc, α-KGDHc, or leucine metabolism in fibroblasts and was ineffective in yeast deleted for the orthologous LIP2. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  18. Severe combined immunodeficiency caused by a new homozygous RAG1 mutation with progressive encephalopathy.

    Science.gov (United States)

    Dhingra, Nivedita; Yadav, Satya Prakash; de Villartay, Jean-Pierre; Picard, Capucine; Sabharwal, R K; Dinand, Veronique; Ghuman, Samarjit Singh; Sachdeva, Anupam

    2014-03-01

    We describe an unusual case of severe combined immunodeficiency (SCID) with neutropenia and central nervous system (CNS) manifestations in which a novel RAG1 mutation was identified. A 15-month-old boy presented with failure to thrive, neutropenia and recurrent infections. He was diagnosed with T-B-NK+ SCID. He subsequently developed right partial seizures with ipsilateral hemiparesis and became comatose. Magnetic resonance imaging (MRI) of the brain revealed an inflammatory lesion in the left thalamus which later progressed to diffuse meningo-encephalitis on serial imaging. No CNS infection was documented. Genetic work-up in the child revealed a novel homozygous deleterious mutation in the RAG1 gene (c:2881T>C; p:I794T), for which both parents were heterozygous. He underwent a haploidentical bone marrow transplant without conditioning and died on day +35 with no improvement in his neurological status. The features of neutropenia and progressive encephalopathy could be linked to the novel genetic defect but more data is required to establish this conclusively.

  19. Auditory agnosia due to long-term severe hydrocephalus caused by spina bifida - specific auditory pathway versus nonspecific auditory pathway.

    Science.gov (United States)

    Zhang, Qing; Kaga, Kimitaka; Hayashi, Akimasa

    2011-07-01

    A 27-year-old female showed auditory agnosia after long-term severe hydrocephalus due to congenital spina bifida. After years of hydrocephalus, she gradually suffered from hearing loss in her right ear at 19 years of age, followed by her left ear. During the time when she retained some ability to hear, she experienced severe difficulty in distinguishing verbal, environmental, and musical instrumental sounds. However, her auditory brainstem response and distortion product otoacoustic emissions were largely intact in the left ear. Her bilateral auditory cortices were preserved, as shown by neuroimaging, whereas her auditory radiations were severely damaged owing to progressive hydrocephalus. Although she had a complete bilateral hearing loss, she felt great pleasure when exposed to music. After years of self-training to read lips, she regained fluent ability to communicate. Clinical manifestations of this patient indicate that auditory agnosia can occur after long-term hydrocephalus due to spina bifida; the secondary auditory pathway may play a role in both auditory perception and hearing rehabilitation.

  20. Severe Human Illness Caused by Rift Valley Fever Virus in Mauritania, 2015.

    Science.gov (United States)

    Boushab, Boushab Mohamed; Fall-Malick, Fatima Zahra; Ould Baba, Sidi El Wafi; Ould Salem, Mohamed Lemine; Belizaire, Marie Roseline Darnycka; Ledib, Hamade; Ould Baba Ahmed, Mohamed Mahmoud; Basco, Leonardo Kishi; Ba, Hampaté

    2016-10-01

    Rift Valley Fever epizootics are characterized by numerous abortions and mortality among young animals. In humans, the illness is usually characterized by a mild self-limited febrile illness, which could progress to more serious complications.Objectives. The aim of the present prospective study was to describe severe clinical signs and symptoms of Rift Valley Fever in southern Mauritania. Suspected cases were enrolled in Kiffa (Assaba) and Aleg (Brakna) Hospital Centers from September 1 to November 7, 2015, based on the presence of fever, hemorrhagic or meningoencephalitic syndromes, and probable contact with sick animals. Suspected cases were confirmed by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR). There were thirty-one confirmed cases. The sex ratio M/F and the average age were 2.9 and 25 years old [range, 4-70 years old], respectively. Mosquito bites, direct contact with aborted or dead animals, and frequent ingestion of milk from these animals were risk factors observed in all patients. Hemorrhagic and neurological manifestations were observed in 81% and 13% of cases, respectively. The results of laboratory analysis showed high levels of transaminases, creatinine, and urea associated with thrombocytopenia, anemia, and leukopenia. All patients who died (42%) had a hemorrhagic syndrome and 3 of them had a neurological complication. Among the cured patients, none had neurologic sequelae. The hemorrhagic form was the most common clinical manifestation of RVF found in southern Mauritania and was responsible for a high mortality rate. Our results justify the implementation of a continuous epidemiological surveillance.

  1. Identification of Mutations in TMEM5 and ISPD as a Cause of Severe Cobblestone Lissencephaly

    Science.gov (United States)

    Vuillaumier-Barrot, Sandrine; Bouchet-Séraphin, Céline; Chelbi, Malika; Devisme, Louise; Quentin, Samuel; Gazal, Steven; Laquerrière, Annie; Fallet-Bianco, Catherine; Loget, Philippe; Odent, Sylvie; Carles, Dominique; Bazin, Anne; Aziza, Jacqueline; Clemenson, Alix; Guimiot, Fabien; Bonnière, Maryse; Monnot, Sophie; Bole-Feysot, Christine; Bernard, Jean-Pierre; Loeuillet, Laurence; Gonzales, Marie; Socha, Koryna; Grandchamp, Bernard; Attié-Bitach, Tania; Encha-Razavi, Férechté; Seta, Nathalie

    2012-01-01

    Cobblestone lissencephaly is a peculiar brain malformation with characteristic radiological anomalies. It is defined as cortical dysplasia that results when neuroglial overmigration into the arachnoid space forms an extracortical layer that produces agyria and/or a “cobblestone” brain surface and ventricular enlargement. Cobblestone lissencephaly is pathognomonic of a continuum of autosomal-recessive diseases characterized by cerebral, ocular, and muscular deficits. These include Walker-Warburg syndrome, muscle-eye-brain disease, and Fukuyama muscular dystrophy. Mutations in POMT1, POMT2, POMGNT1, LARGE, FKTN, and FKRP identified these diseases as alpha-dystroglycanopathies. Our exhaustive screening of these six genes, in a cohort of 90 fetal cases, led to the identification of a mutation in only 53% of the families, suggesting that other genes might also be involved. We therefore decided to perform a genome-wide study in two multiplex families. This allowed us to identify two additional genes: TMEM5 and ISPD. Because TMEM has a glycosyltransferase domain and ISPD has an isoprenoid synthase domain characteristic of nucleotide diP-sugar transferases, these two proteins are thought to be involved in the glycosylation of dystroglycan. Further screening of 40 families with cobblestone lissencephaly identified nonsense and frameshift mutations in another four unrelated cases for each gene, increasing the mutational rate to 64% in our cohort. All these cases displayed a severe phenotype of cobblestone lissencephaly A. TMEM5 mutations were frequently associated with gonadal dysgenesis and neural tube defects, and ISPD mutations were frequently associated with brain vascular anomalies. PMID:23217329

  2. Copper Oxide Nanoparticles Impact Several Toxicological Endpoints and Cause Neurodegeneration in Caenorhabditis elegans.

    Science.gov (United States)

    Mashock, Michael J; Zanon, Tyler; Kappell, Anthony D; Petrella, Lisa N; Andersen, Erik C; Hristova, Krassimira R

    2016-01-01

    Engineered nanoparticles are becoming increasingly incorporated into technology and consumer products. In 2014, over 300 tons of copper oxide nanoparticles were manufactured in the United States. The increased production of nanoparticles raises concerns regarding the potential introduction into the environment or human exposure. Copper oxide nanoparticles commonly release copper ions into solutions, which contribute to their toxicity. We quantified the inhibitory effects of both copper oxide nanoparticles and copper sulfate on C. elegans toxicological endpoints to elucidate their biological effects. Several toxicological endpoints were analyzed in C. elegans, including nematode reproduction, feeding behavior, and average body length. We examined three wild C. elegans isolates together with the Bristol N2 laboratory strain to explore the influence of different genotypic backgrounds on the physiological response to copper challenge. All strains exhibited greater sensitivity to copper oxide nanoparticles compared to copper sulfate, as indicated by reduction of average body length and feeding behavior. Reproduction was significantly reduced only at the highest copper dose, though still more pronounced with copper oxide nanoparticles compared to copper sulfate treatment. Furthermore, we investigated the effects of copper oxide nanoparticles and copper sulfate on neurons, cells with known vulnerability to heavy metal toxicity. Degeneration of dopaminergic neurons was observed in up to 10% of the population after copper oxide nanoparticle exposure. Additionally, mutants in the divalent-metal transporters, smf-1 or smf-2, showed increased tolerance to copper exposure, implicating both transporters in copper-induced neurodegeneration. These results highlight the complex nature of CuO nanoparticle toxicity, in which a nanoparticle-specific effect was observed in some traits (average body length, feeding behavior) and a copper ion specific effect was observed for other traits

  3. Mycoplasma ovipneumoniae - A Primary Cause of Severe Pneumonia Epizootics in the Norwegian Muskox (Ovibos moschatus) Population

    Science.gov (United States)

    Handeland, Kjell; Tengs, Torstein; Kokotovic, Branko; Vikøren, Turid; Ayling, Roger D.; Bergsjø, Bjarne; Sigurðardóttir, Ólöf G.; Bretten, Tord

    2014-01-01

    The Norwegian muskox (Ovibos moschatus) population lives on the high mountain plateau of Dovre and originates from animals introduced from Greenland. In the late summers of 2006 and 2012, severe outbreaks of pneumonia with mortality rates of 25-30% occurred. During the 2012 epidemic high quality samples from culled sick animals were obtained for microbiological and pathological examinations. High throughput sequencing (pyrosequencing) of pneumonic lung tissue revealed high concentrations of Mycoplasma ovipneumoniae in all six animals examined by this method and Pasteurella multocida subsp. multocida in four animals, whereas no virus sequences could be identified. Mycoplasma ovipneumoniae and P. multocida multocida were also isolated by culture. Using real time PCR on lung swabs, M. ovipneumoniae was detected in all of the 19 pneumonic lungs examined. Gross pathological examination revealed heavy consolidations primarily in the cranial parts of the lungs and it also identified one case of otitis media. Histologically, lung lesions were characterized as acute to subacute mixed exudative and moderately proliferative bronchoalveolar pneumonia. Immunohistochemical (IHC) examination revealed high load of M. ovipneumoniae antigens within lung lesions, with particularly intensive staining in the neutrophils. Similar IHC finding were observed in archived lung tissue blocks from animals examined during the 2006 epidemic. An M. ovipneumoniae specific ELISA was applied on bio-banked muskox sera from stray muskoxen killed in the period 2004–2013 and sick muskoxen culled, as well as sera from wild reindeer (Rangifer tarandus tarandus) on Dovre and muskoxen from Greenland. Serology and mycoplasma culturing was also carried out on sheep that had been on pasture in the muskox area during the outbreak in 2012. Our findings indicated separate introductions of M. ovipneumoniae infection in 2006 and 2012 from infected co-grazing sheep. Salt licks shared by the two species were a

  4. Apoptosis of Corneal Epithelial Cells Caused by Ultraviolet B-induced Loss of K(+) is Inhibited by Ba(2.).

    Science.gov (United States)

    Glupker, Courtney D; Boersma, Peter M; Schotanus, Mark P; Haarsma, Loren D; Ubels, John L

    2016-07-01

    UVB exposure at ambient outdoor levels triggers rapid K(+) loss and apoptosis in human corneal limbal epithelial (HCLE) cells cultured in medium containing 5.5 mM K(+), but considerably less apoptosis occurs when the medium contains the high K(+) concentration that is present in tears (25 mM). Since Ba(2+) blocks several K(+) channels, we tested whether Ba(2+)-sensitive K(+) channels are responsible for some or all of the UVB-activated K(+) loss and subsequent activation of the caspase cascade and apoptosis. Corneal epithelial cells in culture were exposed to UVB at 80 or 150 mJ/cm(2). Patch-clamp recording was used to measure UVB-induced K(+) currents. Caspase-activity and TUNEL assays were performed on HCLE cells exposed to UVB followed by incubation in the presence or absence of Ba(2+). K(+) currents were activated in HCLE cells following UVB-exposure. These currents were reversibly blocked by 5 mM Ba(2+). When HCLE cells were incubated with 5 mM Ba(2+) after exposure to UVB, activation of caspases-9, -8, and -3 and DNA fragmentation were significantly decreased. The data confirm that UVB-induced K(+) current activation and loss of intracellular K(+) leads to activation of the caspase cascade and apoptosis. Extracellular Ba(2+) inhibits UVB-induced apoptosis by preventing loss of intracellular K(+) when K(+) channels are activated. Ba(2+) therefore has effects similar to elevated extracellular K(+) in protecting HCLE cells from UVB-induced apoptosis. This supports our overall hypothesis that elevated K(+) in tears contributes to protection of the corneal epithelium from adverse effects of ambient outdoor UVB.

  5. A combined deficiency of vitamins E and C causes severe central nervous system damage in guinea pigs.

    Science.gov (United States)

    Burk, Raymond F; Christensen, Joani M; Maguire, Mark J; Austin, Lori M; Whetsell, William O; May, James M; Hill, Kristina E; Ebner, Ford F

    2006-06-01

    A short period of combined deficiency of vitamins E and C causes profound central nervous system (CNS) dysfunction in guinea pigs. For this report, CNS histopathology was studied to define the nature and extent of injury caused by this double deficiency. Weanling guinea pigs were fed a vitamin E-deficient or -replete diet for 14 d. Then vitamin C was withdrawn from the diet of some guinea pigs. Four diet groups were thus formed: replete, vitamin E deficient, vitamin C deficient, and both vitamin E and C deficient. From 5 to 11 d after institution of the doubly deficient diet, 9 of 12 guinea pigs developed paralysis, and 2 more were found dead. The remaining guinea pig in the doubly deficient group and all animals in the other 3 groups survived without clinical impairment until the experiment was terminated at 13-15 d. Brains and spinal cords were serially sectioned and stained for examination. Only the combined deficiency produced damage in the CNS. The damage consisted mainly of nerve cell death, axonal degeneration, vascular injury, and associated glial cell responses. The spinal cord and the ventral pons in the brainstem were most severely affected, often exhibiting asymmetric cystic lesions. Several features of the lesions suggest that the primary damage was to blood vessels. These results indicate that the paralysis and death caused by combined deficiency of vitamins E and C in guinea pigs is caused by severe damage in the brainstem and spinal cord.

  6. Severity of depressive symptoms and accuracy of dietary reporting among obese women with major depressive disorder seeking weight loss treatment.

    Science.gov (United States)

    Whited, Matthew C; Schneider, Kristin L; Appelhans, Bradley M; Ma, Yunsheng; Waring, Molly E; DeBiasse, Michele A; Busch, Andrew M; Oleski, Jessica L; Merriam, Philip A; Olendzki, Barbara C; Crawford, Sybil L; Ockene, Ira S; Lemon, Stephenie C; Pagoto, Sherry L

    2014-01-01

    An elevation in symptoms of depression has previously been associated with greater accuracy of reported dietary intake, however this association has not been investigated among individuals with a diagnosis of major depressive disorder. The purpose of this study was to investigate reporting accuracy of dietary intake among a group of women with major depressive disorder in order to determine if reporting accuracy is similarly associated with depressive symptoms among depressed women. Reporting accuracy of dietary intake was calculated based on three 24-hour phone-delivered dietary recalls from the baseline phase of a randomized trial of weight loss treatment for 161 obese women with major depressive disorder. Regression models indicated that higher severity of depressive symptoms was associated with greater reporting accuracy, even when controlling for other factors traditionally associated with reporting accuracy (coefficient  =  0.01 95% CI = 0.01 - 0.02). Seventeen percent of the sample was classified as low energy reporters. Reporting accuracy of dietary intake increases along with depressive symptoms, even among individuals with major depressive disorder. These results suggest that any study investigating associations between diet quality and depression should also include an index of reporting accuracy of dietary intake as accuracy varies with the severity of depressive symptoms.

  7. Damage and loss assessment on rubber trees caused by typhoon based on high-precision remote sensing data and field investigation

    Science.gov (United States)

    Li, Jian; Fang, Weihua; Tan, Chenyan

    2016-04-01

    Forest dynamics are highly relevant to land hydrology, climate, carbon budget and biodiversity. Damage and loss assessment of forest caused by typhoon is essential to the understanding of ecosystem variations. Combination of high-precision remote sensing data and field investigation is critical to the assessment of forest damage loss. In this study, high-precision remote sensing data prior to and after typhoon from IKONOS, QuickBird, unmanned aerial vehicle (UAV) are used for identifying rubber tree disturbance. The ground truth data of rubber tree damage collected through field investigation are used to verify and compare the results. Taken the forest damage induced by typhoon Rammasun (201409) in Hainan as an example, 5 damage types (overthrown, trunk snapped below 2m, trunk snapped above 2m, half-overthrown, and sheared) of rubber trees are clearly interpreted compared with field investigation results. High-precision remote sensing data is then applied to other areas to evaluate the forest damage severity. At last, rubber tree damage severity is investigated with other typhoon hazard factors such as wind, topography, soil and precipitation.

  8. Loss of imprinting at the Dlk1-Gtl2 locus caused by insertional mutagenesis in the Gtl2 5' region

    Directory of Open Access Journals (Sweden)

    Appelbe Oliver K

    2006-10-01

    Full Text Available Abstract Background The Dlk1 and Gtl2 genes define a region of mouse chromosome 12 that is subject to genomic imprinting, the parental allele-specific expression of a gene. Although imprinted genes play important roles in growth and development, the mechanisms by which imprinting is established and maintained are poorly understood. Differentially methylated regions (DMRs, which carry methylation on only one parental allele, are involved in imprinting control at many loci. The Dlk1-Gtl2 region contains three known DMRs, the Dlk1 DMR in the 3' region of Dlk1, the intergenic DMR 15 kb upstream of Gtl2, and the Gtl2 DMR at the Gtl2 promoter. Three mouse models are analyzed here that provide new information about the regulation of Dlk1-Gtl2 imprinting. Results A previously existing insertional mutation (Gtl2lacZ, and a targeted deletion in which the Gtl2 upstream region was replaced by a Neo cassette (Gtl2Δ5'Neo, display partial lethality and dwarfism upon paternal inheritance. Molecular characterization shows that both mutations cause loss of imprinting and changes in expression of the Dlk1, Gtl2 and Meg8/Rian genes. Dlk1 levels are decreased upon paternal inheritance of either mutation, suggesting Dlk1 may be causative for the lethality and dwarfism. Loss of imprinting on the paternal chromosome in both Gtl2lacZ and Gtl2Δ5'Neo mice is accompanied by the loss of paternal-specific Gtl2 DMR methylation, while maternal loss of imprinting suggests a previously unknown regulatory role for the maternal Gtl2 DMR. Unexpectedly, when the Neo gene is excised, Gtl2Δ5' animals are of normal size, imprinting is unchanged and the Gtl2 DMR is properly methylated. The exogenous DNA sequences integrated upstream of Gtl2 are therefore responsible for the growth and imprinting effects. Conclusion These data provide further evidence for the coregulation of the imprinted Dlk1 and Gtl2 genes, and support a role for Dlk1 as an important neonatal growth factor. The

  9. What causes bone loss?

    Science.gov (United States)

    ... bone biology. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology . 13th ed. Philadelphia, PA: Elsevier; 2016:chap 29. Maes C, Kronenberg HM. Bone development and remodeling. In: Jameson JL, ...

  10. Increasing severity of damage caused by floods in the Spanish Mediterranean coast (1960-2014), climate change or vulnerability?

    Science.gov (United States)

    Perez, Alfredo; Gil, Salvador; Lopez, Francisco; Barriendos, Mariano

    2016-04-01

    In recent decades, there has been an increase in physical and economic losses (WMO, CRED and UCL, 2014) that raises serious concerns in society. Climate change projections may explain the rise in flood losses; however, these shouldn't be considered yet (Bouwer, 2011). According to IPCC (2014), there is low confidence in anthropogenic climate change affecting the frequency and magnitude of fluvial floods on a global scale. In other words, this increase in flood events is not completely related to the higher frequency of heavy rainfall. To illustrate the aforementioned, a spatial example can be seen in the study area. In the Spanish Mediterranean coast, we see an increase in economic losses within the last 50 years due to flood events (Gil et al., 2014). It seems that the socio-economic growth and the rise of housing construction (Gaja, 2008) have led to an increase in vulnerability and exposure which are mainly responsible for those losses and the increase in severity of flood events (Pérez et al., 2015). Furthermore, this situation will probably become more precarious if some climate forecasts are met [IPCC, 2014; AEMET, 2015], and if the economic model fails to adopt efficient adaptive measures. Therefore, it is interesting to focus attention on social factors either within the present or future scenario in order to minimise the potential consequences and improve the adaptation. The main objective of this work focuses on the study of the evolution of the severity of the floods in the Spanish Mediterranean coast for the period (1960-2015). To do that, a statistical analysis of the data base [Gil et al., 2014; extended to the entire Spanish Mediterranean coast (MEDIFLOOD)] and a multiscale mapping (local, provincial and regional level) of the frequency of these events will take place in order to make comparisons and show spatiotemporal patterns according to the severity events evolution. Preliminary results show some interesting statistically significant

  11. DNA damage and apoptosis of endometrial cells cause loss of the early embryo in mice exposed to carbon disulfide

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Bingzhen [Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan (China); Shen, Chunzi [Centers for Disease Control and Prevention, Zibo (China); Yang, Liu; Li, Chunhui; Yi, Anji [Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan (China); Wang, Zhiping, E-mail: zhipingw@sdu.edu.cn [Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, Jinan (China)

    2013-12-01

    Carbon disulfide (CS{sub 2}) may lead to spontaneous abortion and very early pregnancy loss in women exposed in the workplace, but the mechanism remains unclear. We designed an animal model in which gestating Kunming strain mice were exposed to CS{sub 2} via i.p. on gestational day 4 (GD4). We found that the number of implanted blastocysts on GD8 was significantly reduced by each dose of 0.1 LD{sub 50} (157.85 mg/kg), 0.2 LD{sub 50} (315.7 mg/kg) and 0.4 LD{sub 50} (631.4 mg/kg). In addition, both the level of DNA damage and apoptosis rates of endometrial cells on GD4.5 were increased, showed definite dose–response relationships, and inversely related to the number of implanted blastocysts. The expressions of mRNA and protein for the Bax and caspase-3 genes in the uterine tissues on GD4.5 were up-regulated, while the expressions of mRNA and protein for the Bcl-2 gene were dose-dependently down-regulated. Our results indicated that DNA damage and apoptosis of endometrial cells were important reasons for the loss of implanted blastocysts induced by CS{sub 2}. - Highlights: • We built an animal model of CS2 exposure during blastocyst implantation. • Endometrial cells were used in the comet assay to detect DNA damage. • CS2 exposure caused DNA damage and endometrial cell apoptosis. • DNA damage and endometrial cell apoptosis were responsible for embryo loss.

  12. Mitochondrial dysfunction due to Leber's hereditary optic neuropathy as a cause of visual loss during assessment for epilepsy surgery.

    Science.gov (United States)

    Niehusmann, Pitt; Surges, Rainer; von Wrede, Randi D; Elger, Christian E; Wellmer, Jörg; Reimann, Jens; Urbach, Horst; Vielhaber, Stefan; Bien, Christian G; Kunz, Wolfram S

    2011-01-01

    Assessment for epilepsy surgery may require invasive measures such as implantation of intracranial electrodes or the Wada test. These investigations are commonly well tolerated. However, complications, including visual disturbances of various etiologies, have been reported. Here we describe two patients with pharmacoresistant temporal lobe epilepsy (TLE) who displayed loss of vision in the context of presurgical assessment and in whom mutations associated with Leber's hereditary optic neuropathy (LHON) were detected. Genetic analysis revealed in one patient the frequent mitochondrial G11778A LHON mutation in ND4. In the second patient, the mitochondrial C4640A mutation in ND2 was detected. This rare LHON mutation enhanced the sensitivity of the patient's muscle and brain tissue to amobarbital, a known blocker of the mitochondrial respiratory chain. Mitochondrial dysfunction has been reported in epilepsy. Thus, the presence of LHON mutations can be a rare cause of visual disturbances in patients with epilepsy and may have predisposed to development of epilepsy.

  13. Surgical treatment of severe chronic venous insufficiency caused by pulsatile varicose veins in a patient with tricuspid regurgitation.

    Science.gov (United States)

    Casian, D; Gutsu, E; Culiuc, V

    2009-04-01

    A case of severe chronic venous insufficiency caused by pulsatile varicose veins in a 46-year-old man with tricuspid regurgitation is presented. Active venous leg ulcer complicated with recurrent venous bleeding and inefficacy of conservative management serve as indications for surgical treatment. This case demonstrates the possibility of radical surgical correction of pathological venous reflux by means of saphenofemoral ligation, foam sclerotherapy and subfascial endoscopic perforator surgery.

  14. Biallelic loss-of-function mutation in NIK causes a primary immunodeficiency with multifaceted aberrant lymphoid immunity.

    Science.gov (United States)

    Willmann, Katharina L; Klaver, Stefanie; Doğu, Figen; Santos-Valente, Elisangela; Garncarz, Wojciech; Bilic, Ivan; Mace, Emily; Salzer, Elisabeth; Conde, Cecilia Domínguez; Sic, Heiko; Májek, Peter; Banerjee, Pinaki P; Vladimer, Gregory I; Haskoloğlu, Sule; Bolkent, Musa Gökalp; Küpesiz, Alphan; Condino-Neto, Antonio; Colinge, Jacques; Superti-Furga, Giulio; Pickl, Winfried F; van Zelm, Menno C; Eibel, Hermann; Orange, Jordan S; Ikincioğulları, Aydan; Boztuğ, Kaan

    2014-11-19

    Primary immunodeficiency disorders enable identification of genes with crucial roles in the human immune system. Here we study patients suffering from recurrent bacterial, viral and Cryptosporidium infections, and identify a biallelic mutation in the MAP3K14 gene encoding NIK (NF-κB-inducing kinase). Loss of kinase activity of mutant NIK, predicted by in silico analysis and confirmed by functional assays, leads to defective activation of both canonical and non-canonical NF-κB signalling. Patients with mutated NIK exhibit B-cell lymphopenia, decreased frequencies of class-switched memory B cells and hypogammaglobulinemia due to impaired B-cell survival, and impaired ICOSL expression. Although overall T-cell numbers are normal, both follicular helper and memory T cells are perturbed. Natural killer (NK) cells are decreased and exhibit defective activation, leading to impaired formation of NK-cell immunological synapses. Collectively, our data illustrate the non-redundant role for NIK in human immune responses, demonstrating that loss-of-function mutations in NIK can cause multiple aberrations of lymphoid immunity.

  15. Organic matter losses in German Alps forest soils since the 1970s most likely caused by warming

    Science.gov (United States)

    Prietzel, Jörg; Zimmermann, Lothar; Schubert, Alfred; Christophel, Dominik

    2016-07-01

    Climate warming is expected to induce soil organic carbon losses in mountain soils that result, in turn, in reduced soil fertility, reduced water storage capacity and positive feedback on climate change. Here we combine two independent sets of measurements of soil organic carbon from forest soils in the German Alps--repeated measurements from 1976 to 2010 and from 1987 to 2011--to show that warming has caused a 14% decline in topsoil organic carbon stocks. The decreases in soil carbon occurred over a period of significant increases in six-month summer temperatures, with the most substantial decreases occurring at sites with large changes in mean annual temperature. Organic carbon stock decreases were largest--on average 32%--in forest soils with initial topsoil organic carbon stocks greater than 8 kg C m-2, which can be found predominantly on calcareous bedrock. However, organic carbon stocks of forest soils with lower initial carbon stocks, as well as soils under pasture or at elevations above 1,150 m, have not changed significantly. We conclude that warming is the most likely reason for the observed losses of soil organic carbon, but that site, land use and elevation may ameliorate the effects of climate change.

  16. Functional mutation of SMAC/DIABLO, encoding a mitochondrial proapoptotic protein, causes human progressive hearing loss DFNA64.

    Science.gov (United States)

    Cheng, Jing; Zhu, Yuhua; He, Sudan; Lu, Yanping; Chen, Jing; Han, Bing; Petrillo, Marco; Wrzeszczynski, Kazimierz O; Yang, Shiming; Dai, Pu; Zhai, Suoqiang; Han, Dongyi; Zhang, Michael Q; Li, Wei; Liu, Xuezhong; Li, Huawei; Chen, Zheng-Yi; Yuan, Huijun

    2011-07-15

    SMAC/DIABLO is a mitochondrial proapoptotic protein that is released from mitochondria during apoptosis and counters the inhibitory activities of inhibitor of apoptosis proteins, IAPs. By linkage analysis and candidate screening, we identified a heterozygous SMAC/DIABLO mutation, c.377C>T (p.Ser126Leu, refers to p.Ser71Leu in the mature protein) in a six-generation Chinese kindred characterized by dominant progressive nonsyndromic hearing loss, designated as DFNA64. SMAC/DIABLO is highly expressed in human embryonic ears and is enriched in the developing mouse inner-ear hair cells, suggesting it has a role in the development and homeostasis of hair cells. We used a functional study to demonstrate that the SMAC/DIABLO(S71L) mutant, while retaining the proapoptotic function, triggers significant degradation of both wild-type and mutant SMAC/DIABLO and renders host mitochondria susceptible to calcium-induced loss of the membrane potential. Our work identifies DFNA64 as the human genetic disorder associated with SMAC/DIABLO malfunction and suggests that mutant SMAC/DIABLO(S71L) might cause mitochondrial dysfunction.

  17. Concurrent posterior semicircular canal benign paroxysmal positional vertigo in patients with ipsilateral sudden sensorineural hearing loss: is it caused by otolith particles?

    Science.gov (United States)

    Kim, Chang-Hee; Shin, Jung Eun; Park, Hong Ju; Koo, Ja-Won; Lee, Jun Ho

    2014-04-01

    The etiology of benign paroxysmal positional vertigo (BPPV) is still elusive even though detached otolith particles from the utricular macula are generally thought to be responsible for the pathogenesis of BPPV. Sudden sensorineural hearing loss (SSNHL), of which the etiology is also idiopathic in most cases, may accompany concurrent BPPV. This uncommon condition of concurrent BPPV with SSNHL has been assumptively explained as selective damage of the cochlea and the utricle due to viral neurolabyrinthitis. Recently, radiological evidences that inner ear hemorrhage is observed in patients with SSNHL accompanied by severe vertigo have been reported. The basic hypothesis for this study is that blood debris in the endolymphatic fluid due to inner ear hemorrhage is one of the causes of concurrent posterior semicircular canal (PSCC) BPPV in patient with ipsilateral SSNHL. In this report, we will outline the clinical findings of 4 patients with PSCC BPPV with SSNHL, and present an experimental results using whole blood in artificial endolymph to evaluate the hypothesis.

  18. [The effect of physical therapy on the most severe forms of knee structral changes caused by osteoarthritis].

    Science.gov (United States)

    Kapidzić-Basić, Nedima; Dzananović, Dzevad; Kapidzić-Duraković, Suada; Kikanović, Sahza; Mulić-Bacić, Suada; Hotić-Hadziefendić, Asja

    2011-01-01

    In the most severe form of structural changes on knee caused by osteoarthritis non-surgical treatment provide minimal results and a question of its purpose is being raised. Aim of the study was to examine the possibilities of physical treatment of patients with the most severe degree of structural changes caused by knee osteoarthritis. Examination was conducted on 60 patients that were on physical treatment because of the knee OA. Structural changes are evaluated by Kellgren-Lawrence scale, functional ability by Lequesne index, and pain by Visual analog scale. Physical treatment lasted for 4 weeks. After the physical treatment there was a significant improvement of functional ability (p = 1.78E-07), but the size of improvement was reduced by the level of structural changes. It was significantly lower in IV class in relation to III and II class (p Physical treatment has lower affect by patients with the most severe form of structural changes caused by knee osteoarthritis, but it still can help patients to ease the appearance of complete dependence on other people's help.

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

    Science.gov (United States)

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

    2016-03-03

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

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

    Science.gov (United States)

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

    2016-01-01

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

  1. Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice

    Science.gov (United States)

    Halim, Danny; Wilson, Michael P.; Oliver, Daniel; Brosens, Erwin; Verheij, Joke B. G. M.; Han, Yu; Nanda, Vivek; Lyu, Qing; Doukas, Michael; Stoop, Hans; Brouwer, Rutger W. W.; van IJcken, Wilfred F. J.; Slivano, Orazio J.; Burns, Alan J.; Christie, Christine K.; de Mesy Bentley, Karen L.; Brooks, Alice S.; Tibboel, Dick; Xu, Suowen; Jin, Zheng Gen; Djuwantono, Tono; Yan, Wei; Alves, Maria M.; Hofstra, Robert M. W.; Miano, Joseph M.

    2017-01-01

    Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a congenital visceral myopathy characterized by severe dilation of the urinary bladder and defective intestinal motility. The genetic basis of MMIHS has been ascribed to spontaneous and autosomal dominant mutations in actin gamma 2 (ACTG2), a smooth muscle contractile gene. However, evidence suggesting a recessive origin of the disease also exists. Using combined homozygosity mapping and whole exome sequencing, a genetically isolated family was found to carry a premature termination codon in Leiomodin1 (LMOD1), a gene preferentially expressed in vascular and visceral smooth muscle cells. Parents heterozygous for the mutation exhibited no abnormalities, but a child homozygous for the premature termination codon displayed symptoms consistent with MMIHS. We used CRISPR-Cas9 (CRISPR-associated protein) genome editing of Lmod1 to generate a similar premature termination codon. Mice homozygous for the mutation showed loss of LMOD1 protein and pathology consistent with MMIHS, including late gestation expansion of the bladder, hydronephrosis, and rapid demise after parturition. Loss of LMOD1 resulted in a reduction of filamentous actin, elongated cytoskeletal dense bodies, and impaired intestinal smooth muscle contractility. These results define LMOD1 as a disease gene for MMIHS and suggest its role in establishing normal smooth muscle cytoskeletal–contractile coupling. PMID:28292896

  2. The use of hearing protection devices with approach risk perception of noise induced hearing loss in several manufacturing industry

    Directory of Open Access Journals (Sweden)

    Behzad Fouladi Deahghi

    2015-06-01

    Full Text Available Background & Objective : Noise is a widespread physical agent and although is a most risk factors in workplaces that workers of health to exposed. Thus, different actions is done for reduce exposure to it in work places, which one of them is use of hearing protection devices. The use of hearing protection devices with approach risk perception of noise induced hearing loss in several manufacturing industry Method: This study was Cross-sectional study and done in five industrial unit with a sound pressure level more of 85 dB-A with the participation of 340 workers. To collect data , individual risk perception and self-investigator questionnaires were used. After collecting data, statistical analysis including Cronbach's alpha and regression were used to analyze the data. Results : Range use of hearing protection devices during shifts work by workers, respectively equal to: 50.4% sometimes, 31.58% never and 18.2% at all times. Also, results indicate significant differences between individual differences and hearing protection devices. Conclusion : Results of this study showed that individual risk perception as an important factor, can do a significant role in predicting the behavior of personals in the use of hearing protection devices, which should be considered in any design and implementation of hearing protection program.

  3. Irvalec inserts into the plasma membrane causing rapid loss of integrity and necrotic cell death in tumor cells.

    Directory of Open Access Journals (Sweden)

    José M Molina-Guijarro

    Full Text Available Irvalec is a marine-derived antitumor agent currently undergoing phase II clinical trials. In vitro, Irvalec induces a rapid loss of membrane integrity in tumor cells, accompanied of a significant Ca(2+ influx, perturbations of membrane conductivity, severe swelling and the formation of giant membranous vesicles. All these effects are not observed in Irvalec-resistant cells, or are significantly delayed by pretreating the cells with Zn(2+. Using fluorescent derivatives of Irvalec it was demonstrated that the compound rapidly interacts with the plasma membrane of tumor cells promoting lipid bilayer restructuration. Also, FRET experiments demonstrated that Irvalec molecules localize in the cell membrane close enough to each other as to suggest that the compound could self-organize, forming supramolecular structures that likely trigger cell death by necrosis through the disruption of membrane integrity.

  4. Trisomy 15 with loss of the paternal 15 as a cause of Prader-Willi syndrome due to maternal disomy

    Energy Technology Data Exchange (ETDEWEB)

    Cassidy, S.B.; Lai, Li-Wen; Erickson, R.P. (Univ. of Arizona College of Medicine, Tucson, AZ (United States)); Magnuson, L.; Thomas, E.; Herrmann, J. (Great Lakes Genetics, Milwaukee, AZ (United States)); Gendron, R. (Great Lakes Genetics, Kingsport, TN (United States))

    1992-10-01

    Uniparental disomy has recently been recognized to cause human disorders, including Prader-Willi syndrome (PWS). The authors describe a particularly instructive case which raises important issues concerning the mechanisms producing uniparental disomy and whose evaluation provides evidence that trisomy may precede uniparental disomy in a fetus. Chorionic villus sampling performed for advanced maternal age revealed trisomy 15 in all direct and cultured cells, though the fetus appeared normal. Chromosome analysis of amniocytes obtained at 15 wk was normal in over 100 cells studied. The child was hypotonic at birth, and high-resolution banding failed to reveal the deletion of 15q11-13, a deletion which is found in 50%-70% of patients with PWS. Over time, typical features of PWS developed. Molecular genetic analysis using probes for chromosome 15 revealed maternal disomy. Maternal nondisjunction with fertilization of a disomic egg by a normal sperm, followed by loss of the paternal 15, is a likely cause of confined placental mosaicism and uniparental disomy in this case of PWS, and advanced maternal age may be a predisposing factor. 38 refs., 3 figs., 2 tabs.

  5. Mutations in CDC14A, Encoding a Protein Phosphatase Involved in Hair Cell Ciliogenesis, Cause Autosomal-Recessive Severe to Profound Deafness.

    Science.gov (United States)

    Delmaghani, Sedigheh; Aghaie, Asadollah; Bouyacoub, Yosra; El Hachmi, Hala; Bonnet, Crystel; Riahi, Zied; Chardenoux, Sebastien; Perfettini, Isabelle; Hardelin, Jean-Pierre; Houmeida, Ahmed; Herbomel, Philippe; Petit, Christine

    2016-06-01

    By genetic linkage analysis in a large consanguineous Iranian family with eleven individuals affected by severe to profound congenital deafness, we were able to define a 2.8 Mb critical interval (at chromosome 1p21.2-1p21.1) for an autosomal-recessive nonsyndromic deafness locus (DFNB). Whole-exome sequencing allowed us to identify a CDC14A biallelic nonsense mutation, c.1126C>T (p.Arg376(∗)), which was present in the eight clinically affected individuals still alive. Subsequent screening of 115 unrelated individuals affected by severe or profound congenital deafness of unknown genetic cause led us to identify another CDC14A biallelic nonsense mutation, c.1015C>T (p.Arg339(∗)), in an individual originating from Mauritania. CDC14A encodes a protein tyrosine phosphatase. Immunofluorescence analysis of the protein distribution in the mouse inner ear showed a strong labeling of the hair cells' kinocilia. By using a morpholino strategy to knockdown cdc14a in zebrafish larvae, we found that the length of the kinocilia was reduced in inner-ear hair cells. Therefore, deafness caused by loss-of-function mutations in CDC14A probably arises from a morphogenetic defect of the auditory sensory cells' hair bundles, whose differentiation critically depends on the proper growth of their kinocilium.

  6. Homozygous EXOSC3 mutation c.92G→C, p.G31A is a founder mutation causing severe pontocerebellar hypoplasia type 1 among the Czech Roma.

    Science.gov (United States)

    Schwabova, Jaroslava; Brozkova, Dana Safka; Petrak, Borivoj; Mojzisova, Mahulena; Pavlickova, Klara; Haberlova, Jana; Mrazkova, Lenka; Hedvicakova, Petra; Hornofova, Ludmila; Kaluzova, Marie; Fencl, Filip; Krutova, Marcela; Zamecnik, Josef; Seeman, Pavel

    2013-12-01

    Pontocerebellar hypoplasia type 1 (PCH1) is characterized by cerebellar and anterior horn motor neuron degeneration and loss, signs of spinal muscular atrophy plus. Patients manifest severe perinatal weakness, hypotonia, and respiratory insufficiency, causing death frequently before the age of 1 year. Recently, causative mutations in EXOSC3 were reported in a majority of PCH1 patients, but the detailed clinical phenotype caused by EXOSC3 mutations, genotype-phenotype correlations, and prevalent mutations in specific ethnic groups is not yet known. Three unrelated Czech Roma patients with PCH1 were investigated clinically, electrophysiologically, neuroradiologically, and neuropathologically (patients 1 and 2). The entire coding region of the EXOSC3 gene, including the adjacent intron sequences, was sequenced in all three patients. The same mutation c.92G→C, p.G31A in EXOSC3 was found in all three affected patients in homozygous state and in heterozygous state in the parents from two of the families. Haplotype analysis with four flanking microsatellite markers showed identical haplotype in 9 out of 11 haplotypes carrying the c.92G→C, p.G31A mutation. Furthermore, four heterozygotes for this mutation were found in anonymous DNA samples from 90 unrelated Roma individuals. All four of these samples shared the same haplotype. No heterozygous sample was found among 120 anonymous DNA samples from Czech non-Roma individuals with no familial relation. It may therefore be concluded that EXOSC3 c.92G→C, p.G31A mutation is a founder mutation with high prevalence among the Czech Roma causing a similar and particularly severe phenotype of PCH1. These observations from the Czech Roma may have consequences also for other Roma from other countries. PCH1 caused by EXOSC3 founder mutation c.92G→C, p.G31A extends the list of autosomal recessive disorders rare among the general population but more frequent among Roma at least in the Czech Republic.

  7. [Causes of moderate to severe visual impairment and blindness in population aged 50 years or more in rural Shandong province].

    Science.gov (United States)

    Li, Yun; Bi, Hong-sheng; Wang, Li-hua; Wang, Ting; Yang, Shao-yuan; Liu, Li-ping; Zhou, Cheng-chao

    2013-02-01

    To investigate the etiological spectrum of moderate to severe visual impairment and blindness in population aged 50 years or more in rural Shandong province, China. A population based, random cluster sampling was used to screening the adults aged 50 years or more living in rural Shandong Province from April to July 2008. Three counties and one suburb representing the different levels of socioeconomic development within Shandong area were selected as the investigated areas. Geographically defined cluster sampling was used in randomly selecting a cross-section of residents aged ≥ 50 years from each county. Best corrected visual acuity and intra-ocular pressure were evaluated in those with presenting visual acuity ≤ 0.5 and suspected glaucoma respectively. The major causes of visual impairment and blindness were diagnosed in those with presenting visual acuity ≤ 0.3. According to the results of presenting visual acuity and best corrected visual acuity, the etiology constituent ratios of the moderate to severe visual impairment and blindness were analyzed respectively. According to the number of people, the first three principal causes for blindness based on the presenting visual acuity were cataract (59.8%, 168/281), fundus disease (12.1%, 34/281) and corneal opacity (4.3%, 12/281) or ametropia (4.3%, 12/281). The first three principal causes for moderate to severe visual impairment and blindness were cataract (55.2%, 844/1530), uncorrected refractive error (18.2%, 278/1530) and fundus disease (11.9%, 182/1530). Based on the best corrected visual acuity, the first three principal causes for blindness were cataract (64.6%, 153/237), fundus disease (10.5%, 25/237) and corneal opacity (4.7%, 11/237), respectively. The first three principal causes for moderate to severe visual impairment and blindness were cataract (66.4%, 590/889), fundus disease (16.0%, 142/889) and optic nerve atrophy (3.0%, 27/889). According to number of the eyes, proportion of cataract in

  8. Novel mutations in NEB cause abnormal nebulin expression and markedly impaired muscle force generation in severe nemaline myopathy

    Directory of Open Access Journals (Sweden)

    Lawlor Michael W

    2011-06-01

    Full Text Available Abstract Background Nemaline myopathy (NM is a congenital muscle disease associated with weakness and the presence of nemaline bodies (rods in muscle fibers. Mutations in seven genes have been associated with NM, but the most commonly mutated gene is nebulin (NEB, which is thought to account for roughly 50% of cases. Results We describe two siblings with severe NM, arthrogryposis and neonatal death caused by two novel NEB mutations: a point mutation in intron 13 and a frameshift mutation in exon 81. Levels of detectable nebulin protein were significantly lower than those in normal control muscle biopsies or those from patients with less severe NM due to deletion of NEB exon 55. Mechanical studies of skinned myofibers revealed marked impairment of force development, with an increase in tension cost. Conclusions Our findings demonstrate that the mechanical phenotype of severe NM is the consequence of mutations that severely reduce nebulin protein levels and suggest that the level of nebulin expression may correlate with the severity of disease.

  9. Prevalence, seasonality and severity of disease caused by pathogenic Escherichia coli in children with diarrhoea in Bolivia.

    Science.gov (United States)

    Gonzales, Lucia; Joffre, Enrique; Rivera, Rosario; Sjöling, Åsa; Svennerholm, Ann-Mari; Iñiguez, Volga

    2013-11-01

    The prevalence of infection caused by different categories of diarrhoeagenic E. coli (DEC) strains, including enteroaggregative (EAEC), enteropathogenic (EPEC), enterotoxigenic (ETEC), enteroinvasive (EIEC) and enterohaemorrhagic (EHEC) E. coli, in children who suffered from diarrhoea (n = 3943) or did not have diarrhoea (n = 1026) were analysed in two areas in Bolivia over a period of 4 years. We also analysed the seasonality of DEC infections and severity of diarrhoea in children with DEC infection and compared antibiotic resistance in DEC strains isolated from children with and without diarrhoea. Stool samples were analysed for the presence of DEC by culturing followed by PCR. The most prevalent DEC categories in samples from the children were: EAEC (11.2 %); ETEC (6.6 %); EPEC (5.8 %); and EIEC and EHEC (<1 %). DEC strains were isolated significantly more often from diarrhoea cases (21.6 %) than from controls (17.6 %; P = 0.002). The number of children with diarrhoea associated with EAEC, EPEC and ETEC infections peaked in the Bolivian winter (April-September), although the proportion of DEC-positive stool samples was higher during the warm rainy season (October-March). High levels of antibiotic resistance were detected among the DEC strains. In particular, resistance to tetracycline and sulfamethoxazole-trimethoprim was significantly higher in strains isolated from individuals with diarrhoea than in samples from controls. The severity of disease in children infected with EAEC, EPEC and ETEC varied from mild to severe diarrhoea, although disease severity did not differ significantly between the different DEC categories. ETEC, EPEC and EAEC are commonly found in Bolivia and may cause severe disease in children.

  10. Disturbed mitochondrial and peroxisomal dynamics due to loss of MFF causes Leigh-like encephalopathy, optic atrophy and peripheral neuropathy.

    Science.gov (United States)

    Koch, Johannes; Feichtinger, René G; Freisinger, Peter; Pies, Mechthild; Schrödl, Falk; Iuso, Arcangela; Sperl, Wolfgang; Mayr, Johannes A; Prokisch, Holger; Haack, Tobias B

    2016-04-01

    Mitochondria are dynamic organelles which undergo continuous fission and fusion to maintain their diverse cellular functions. Components of the fission machinery are partly shared between mitochondria and peroxisomes, and inherited defects in two such components (dynamin-related protein (DRP1) and ganglioside-induced differentiation-associated protein 1 (GDAP1)) have been associated with human disease. Deficiency of a third component (mitochondrial fission factor, MFF) was recently reported in one index patient, rendering MFF another candidate disease gene within the expanding field of mitochondrial and peroxisomal dynamics. Here we investigated three new patients from two families with pathogenic mutations in MFF. The patients underwent clinical examination, brain MRI, and biochemical, cytological and molecular analyses, including exome sequencing. The patients became symptomatic within the first year of life, exhibiting seizures, developmental delay and acquired microcephaly. Dysphagia, spasticity and optic and peripheral neuropathy developed subsequently. Brain MRI showed Leigh-like patterns with bilateral changes of the basal ganglia and subthalamic nucleus, suggestive of impaired mitochondrial energy metabolism. However, activities of mitochondrial respiratory chain complexes were found to be normal in skeletal muscle. Exome sequencing revealed three different biallelic loss-of-function variants in MFF in both index cases. Western blot studies of patient-derived fibroblasts indicated normal content of mitochondria and peroxisomes, whereas immunofluorescence staining revealed elongated mitochondria and peroxisomes. Furthermore, increased mitochondrial branching and an abnormal distribution of fission-mediating DRP1 were observed. Our findings establish MFF loss of function as a cause of disturbed mitochondrial and peroxisomal dynamics associated with early-onset Leigh-like basal ganglia disease. We suggest that, even if laboratory findings are not indicative of

  11. Fatal neonatal encephalopathy and lactic acidosis caused by a homozygous loss-of-function variant in COQ9.

    Science.gov (United States)

    Danhauser, Katharina; Herebian, Diran; Haack, Tobias B; Rodenburg, Richard J; Strom, Tim M; Meitinger, Thomas; Klee, Dirk; Mayatepek, Ertan; Prokisch, Holger; Distelmaier, Felix

    2016-03-01

    Coenzyme Q10 (CoQ10) has an important role in mitochondrial energy metabolism by way of its functioning as an electron carrier in the respiratory chain. Genetic defects disrupting the endogenous biosynthesis pathway of CoQ10 may lead to severe metabolic disorders with onset in early childhood. Using exome sequencing in a child with fatal neonatal lactic acidosis and encephalopathy, we identified a homozygous loss-of-function variant in COQ9. Functional studies in patient fibroblasts showed that the absence of the COQ9 protein was concomitant with a strong reduction of COQ7, leading to a significant accumulation of the substrate of COQ7, 6-demethoxy ubiquinone10. At the same time, the total amount of CoQ10 was severely reduced, which was reflected in a significant decrease of mitochondrial respiratory chain succinate-cytochrome c oxidoreductase (complex II/III) activity. Lentiviral expression of COQ9 restored all these parameters, confirming the causal role of the variant. Our report on the second COQ9 patient expands the clinical spectrum associated with COQ9 variants, indicating the importance of COQ9 already during prenatal development. Moreover, the rescue of cellular CoQ10 levels and respiratory chain complex activities by CoQ10 supplementation points to the importance of an early diagnosis and immediate treatment.

  12. Did Eucalyptus contribute to environment degradation? Implications from a dispute on causes of severe drought in Yunnan and Guizhou, China

    Directory of Open Access Journals (Sweden)

    WenJun Zhang

    2012-06-01

    Full Text Available Various viewpoints were proposed to explain the causes of recent years' severe drought occurred in Yunnan and Guizhou, China. In general there are two parties of viewpoints, the Eucalyptus cause and climate change cause. I think Yunnan-Guizhou drought has been mainly caused by abnormal climate change. Eucalyptus was not significant in the formation of Yunnan-Guizhou drought. However, the forestation effect of Eucalyptus in China was not good. Environment quality and biodiversity in Eucalyptus plantation forests has been degrading in last decades. Enhancement of alleopathy of Eucalyptus trees under drought conditions would partly contribute to biodiversity reduction and environment degradation in Eucalyptus plantation forests. For existing Eucalyptus plantation forests of Yunnan, I suggest that some improvement measures should be adopted. Artificial weeding and cleaning in Eucalyptus plantation forests should be banned. Density of Eucalyptus trees needs to be reduced. Biodiversity should be artificially improved in Eucalyptus plantation forests. In the future, the mountains and lands with better vegetation cover must not be reclaimed for Eucalyptus planting. Eucalyptus plantation forests should be made in barren mountains and lands with poor biodiversity.

  13. Mutations in SLC33A1 cause a lethal autosomal-recessive disorder with congenital cataracts, hearing loss, and low serum copper and ceruloplasmin

    DEFF Research Database (Denmark)

    Huppke, Peter; Brendel, Cornelia; Kalscheuer, Vera

    2012-01-01

    , hearing loss, and severe developmental delay. Cerebral MRI showed pronounced cerebellar hypoplasia and hypomyelination. Homozygosity mapping was performed and displayed a region of commonality among three families at chromosome 3q25. Deep sequencing and conventional sequencing disclosed homozygous...

  14. Diarrheagenic Escherichia coli carrying supplementary virulence genes are an important cause of moderate to severe diarrhoeal disease in Mexico.

    Science.gov (United States)

    Patzi-Vargas, Sandra; Zaidi, Mussaret Bano; Perez-Martinez, Iza; León-Cen, Magda; Michel-Ayala, Alba; Chaussabel, Damien; Estrada-Garcia, Teresa

    2015-03-01

    Diarrheagenic Escherichia coli (DEC) cause acute and persistent diarrhoea worldwide, but little is known about their epidemiology in Mexico. We determined the prevalence of bacterial enteropathogens in 831 children with acute diarrhoea over a four-year period in Yucatan, Mexico. Six DEC supplementary virulence genes (SVG), mainly associated with enteroaggregative E. coli (EAEC), were sought in 3100 E. coli isolates. DEC was the most common bacterial enteropathogen (28%), surpassing Salmonella (12%) and Shigella (9%). Predominant DEC groups were diffusely adherent E. coli (DAEC) (35%), EAEC (24%), and enteropathogenic E. coli (EPEC) (19%). Among children with DEC infections, 14% had severe illness mainly caused by EPEC (26%) and DAEC (18%); 30% had moderate diarrhoea mainly caused by DAEC (36%), mixed DEC infections (33%) and EAEC (32%). DAEC was most prevalent during spring, while ETEC, EAEC and EPEC predominated in summer. EAEC was more frequent in children 6-24 months old than in those younger than 6 months of age (P = 0.008, OR = 4.2, 95% CI, 1.3-13.9). The presence of SVG dispersin, (aatA), dispersin-translocator (aatA), enteroaggregative heat-stable toxin 1 (astA), plasmid encoded toxin (pet), cytolethal distending toxin (cdt) was higher in DEC than non-DEC strains, (36% vs 26%, P DAEC patients had strains with SVG. 54% of EPEC patients carried pet-positive strains alone or in combination with astA; only this DEC group harboured cdt-positive isolates. All ETEC patients carried astA- or astA-aap-positive strains. astA and aap were the most common SVG in DAEC (3% and 2%) and non-DEC strains (21% and 13%). DEC carrying SVG are an important cause of moderate to severe bacterial diarrhoea in Mexican children.

  15. Pregnancy-related severe pelvic girdle pain caused by unilateral noninfectious sacroiliitis. A case report and literature review.

    Science.gov (United States)

    Mahovic, D; Laktasic-Zerjavic, N; Tudor, K I; Mercep, I; Prutki, M; Anic, B

    2014-09-01

    Pelvic girdle pain during and after pregnancy is the clinical syndrome of persistent musculoskeletal pain localized in the posterior and/or anterior aspect of the pelvis originating from sacroiliac joints and/or pubic symphysis due to dynamic instability. We report the case of severe and disabling postpartum pelvic girdle pain caused by unilateral noninfectious sacroiliitis which resolved after 2 months by nonsteroidal anti-inflammatory drug and physical therapy. A short literature review is given on epidemiology, etiology, clinical presentation, therapy, and prognosis of pregnancy-related pelvic girdle pain.

  16. A severe case of esophageal ulcer causing a tight stricture despite long-term D-penicillamine treatment.

    Science.gov (United States)

    Yapali, Suna; Turan, Ilker; Ozutemiz, Omer; Tekesin, Oktay

    2014-12-01

    D-penicillamine has long been used in the management of rheumatic diseases due to the effects on inhibition of collagen synthesis. Herein, we report a severe case of esophageal ulcer causing a tight stricture extending through the distal esophagus despite the long-term D-penicillamine treatment in a patient with Wilson's disease. D-penicillamine would theoretically be expected to contribute to the healing of an esophageal ulcer. However, the drug failed to have a favorable outcome, which is notable and worth reporting.

  17. [Severe dysautonomy as a result of intra-cranial bleeding can cause an electrical storm with auricular fibrillation].

    Science.gov (United States)

    Lindelof, Mette; Jensen, Helene; Vilhjamsson, Asgier Snær; Kemppi, Kajsa; Høst, Ulla

    2015-12-14

    A 69-year-old woman with a medical history of stroke and an ICD device due to torsade de pointes was admitted with a right basal ganglia haemorrhage. In the hours after admission the patient's condition severely declined and she developed fever, hypertension and flushing consistent with autonomic dysfunction with sympathetic storming. ICD interrogation revealed electrical storm with 138 appropriate shocks delivered at the night of admission. We wish to draw attention to the close link between brain and heart, which in predisposed patients with a new stroke can cause malignant arrhythmias.

  18. Hyperbilirubinemia and rapid fatal hepatic failure in severe combined immunodeficiency caused by adenosine deaminase deficiency (ADA-SCID).

    Science.gov (United States)

    Kühl, J S; Schwarz, K; Münch, A; Schmugge, M; Pekrun, A; Meisel, C; Wahn, V; Ebell, W; von Bernuth, H

    2011-03-01

    Adenosin deaminase (ADA) deficiency is the cause for Severe Combined Immunodeficiency (SCID) in about 15% of patients with SCID, often presenting as T (-)B (-)NK (-)SCID. Treatment options for ADA-SCID are enzyme replacement, bone marrow transplantation or gene therapy. We here describe the first patient with ADA-SCID and fatal hepatic failure despite bone marrow transplantation from a 10/10 HLA identical related donor. As patients with ADA-SCID may be at yet underestimated increased risk for rapid hepatic failure we speculate whether hepatitis in ADA-SCID should lead to the immediate treatment with enzyme replacement by pegylated ADA.

  19. Loss of the intestinal mucus layer in the normal rat causes gut injury but not toxic mesenteric lymph nor lung injury.

    Science.gov (United States)

    Sharpe, Susan M; Qin, Xiaofa; Lu, Qi; Feketeova, Eleonora; Palange, David C; Dong, Wei; Sheth, Sharvil U; Lee, Marlon A; Reino, Diego; Xu, Da-Zhong; Deitch, Edwin A

    2010-11-01

    There is substantial evidence that gut barrier failure is associated with distant organ injury and systemic inflammation. After major trauma or stress, the factors and mechanisms involved in gut injury are unknown. Our primary hypothesis is that loss of the intestinal mucus layer will result in injury of the normal gut that is exacerbated by the presence of luminal pancreatic proteases. Our secondary hypothesis is that the injury produced in the gut will result in the production of biologically active mesenteric lymph and consequently distant organ (i.e., lung) injury. To test this hypothesis, five groups of rats were studied: 1) uninstrumented naive rats; 2) control rats in which a ligated segment of distal ileum was filled with saline; 3) rats with pancreatic proteases placed in their distal ileal segments; 4) rats with the mucolytic N-acetylcysteine (NAC) placed in their distal ileal segments; and 5) rats exposed to NAC and pancreatic proteases in their ileal segments. The potential systemic consequences of gut injury induced by NAC and proteases were assessed by measuring the biological activity of mesenteric lymph as well as gut-induced lung injury. Exposure of the normal intestine to NAC, but not saline or proteases, led to increased gut permeability, loss of