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Sample records for function induces severe

  1. Postnatal weight gain modifies severity and functional outcome of oxygen-induced proliferative retinopathy.

    Science.gov (United States)

    Stahl, Andreas; Chen, Jing; Sapieha, Przemyslaw; Seaward, Molly R; Krah, Nathan M; Dennison, Roberta J; Favazza, Tara; Bucher, Felicitas; Löfqvist, Chatarina; Ong, Huy; Hellström, Ann; Chemtob, Sylvain; Akula, James D; Smith, Lois E H

    2010-12-01

    In clinical studies, postnatal weight gain is strongly associated with retinopathy of prematurity (ROP). However, animal studies are needed to investigate the pathophysiological mechanisms of how postnatal weight gain affects the severity of ROP. In the present study, we identify nutritional supply as one potent parameter that affects the extent of retinopathy in mice with identical birth weights and the same genetic background. Wild-type pups with poor postnatal nutrition and poor weight gain (PWG) exhibit a remarkably prolonged phase of retinopathy compared to medium weight gain or extensive weight gain pups. A high (r(2) = 0.83) parabolic association between postnatal weight gain and oxygen-induced retinopathy severity is observed, as is a significantly prolonged phase of proliferative retinopathy in PWG pups (20 days) compared with extensive weight gain pups (6 days). The extended retinopathy is concomitant with prolonged overexpression of retinal vascular endothelial growth factor in PWG pups. Importantly, PWG pups show low serum levels of nonfasting glucose, insulin, and insulin-like growth factor-1 as well as high levels of ghrelin in the early postoxygen-induced retinopathy phase, a combination indicative of poor metabolic supply. These differences translate into visual deficits in adult PWG mice, as demonstrated by impaired bipolar and proximal neuronal function. Together, these results provide evidence for a pathophysiological correlation between poor postnatal nutritional supply, slow weight gain, prolonged retinal vascular endothelial growth factor overexpression, protracted retinopathy, and reduced final visual outcome.

  2. Functional Limitations in Severe Haemophilia

    NARCIS (Netherlands)

    Genderen, F.R. van

    2006-01-01

    This thesis aims to describe the Disablement Process (DP) in Dutch adult patients with severe haemophilia, with specific focus on the domain of “Functional Limitations”. Four main questions underlie this thesis: How can Functional Limitations in severe haemophilia be investigated? Can the

  3. Constraint-Induced Movement Therapy Combined with Transcranial Direct Current Stimulation over Premotor Cortex Improves Motor Function in Severe Stroke: A Pilot Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Suellen M. Andrade

    2017-01-01

    Full Text Available Objective. We compared the effects of transcranial direct current stimulation at different cortical sites (premotor and motor primary cortex combined with constraint-induced movement therapy for treatment of stroke patients. Design. Sixty patients were randomly distributed into 3 groups: Group A, anodal stimulation on premotor cortex and constraint-induced movement therapy; Group B, anodal stimulation on primary motor cortex and constraint-induced movement therapy; Group C, sham stimulation and constraint-induced movement therapy. Evaluations involved analysis of functional independence, motor recovery, spasticity, gross motor function, and muscle strength. Results. A significant improvement in primary outcome (functional independence after treatment in the premotor group followed by primary motor group and sham group was observed. The same pattern of improvement was highlighted among all secondary outcome measures regarding the superior performance of the premotor group over primary motor and sham groups. Conclusions. Premotor cortex can contribute to motor function in patients with severe functional disabilities in early stages of stroke. This study was registered in ClinicalTrials.gov database (NCT 02628561.

  4. Convex trace functions of several variables

    DEFF Research Database (Denmark)

    Hansen, Frank

    2002-01-01

    We prove that the function (x1,...,xk)¿Tr(f(x1,...,xk)), defined on k-tuples of symmetric matrices of order (n1,...,nk) in the domain of f, is convex for any convex function f of k variables. The matrix f(x1,...,xk) is defined by the functional calculus for functions of several variables, and it ...

  5. Stimulus induced bursts in severe postanoxic encephalopathy.

    Science.gov (United States)

    Tjepkema-Cloostermans, Marleen C; Wijers, Elisabeth T; van Putten, Michel J A M

    2016-11-01

    To report on a distinct effect of auditory and sensory stimuli on the EEG in comatose patients with severe postanoxic encephalopathy. In two comatose patients admitted to the Intensive Care Unit (ICU) with severe postanoxic encephalopathy and burst-suppression EEG, we studied the effect of external stimuli (sound and touch) on the occurrence of bursts. In patient A bursts could be induced by either auditory or sensory stimuli. In patient B bursts could only be induced by touching different facial regions (forehead, nose and chin). When stimuli were presented with relatively long intervals, bursts persistently followed the stimuli, while stimuli with short intervals (encephalopathy can be induced by external stimuli, resulting in stimulus-dependent burst-suppression. Stimulus induced bursts should not be interpreted as prognostic favourable EEG reactivity. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  6. Hepatitis E-induced severe myositis.

    Science.gov (United States)

    Mengel, Annerose M; Stenzel, Werner; Meisel, Andreas; Büning, Carsten

    2016-02-01

    Hepatitis E virus (HEV) is endemic in Asian and African countries but is rarely reported in Western countries. Although there are some prominent neurological manifestations, HEV is rarely recognized by neurologists. This is a case report of myositis induced by HEV. We report the life-threatening case of a 57-year-old man with flaccid tetraparesis due to myositis, acute hepatitis, and renal failure caused by HEV infection. Muscle biopsy revealed scattered myofiber necrosis with a diffuse, mild lymphomonocytic infiltrate in the endomysium and perimysium. Because the patient suffered from an acute HEV infection with a rapidly progressive course of severe myopathy, we started ribavirin treatment. He recovered partially within 3 weeks and recovered fully within 6 months. This case highlights a neurological manifestation of endemic HEV infection with severe myositis in a patient with alcoholic chronic liver disease. Ribavirin treatment is effective in severe HEV infection and may also lead to rapid neurological recovery. © 2015 Wiley Periodicals, Inc.

  7. PEG-asparaginase induced severe hypertriglyceridemia.

    Science.gov (United States)

    Galindo, Rodolfo J; Yoon, Justin; Devoe, Craig; Myers, Alyson K

    2016-04-01

    Asparaginase (ASP) is an effective chemotherapy agent extensively used in children with acute lymphocytic leukemia (ALL). There has been a recent interest in using ASP in adults with ALL, particularly the less toxic pegylated (PEG) formulation. Hypertriglyceridemia (HTG) is a rare complication of PEG-ASP therapy. We report two cases of obese patients who developed severe HTG after receiving PEG for ALL. Both patients were incidentally found to have severe HTG (TG of 4,330 and 4,420 mg/dL). In both patients, there was no personal or family history of dyslipidemia or hypothyroidism. There was no evidence of pancreatitis or skin manifestations of HTG. Both patients were treated with PEG cessation, low-fat diet and pharmacotherapy. Both patients were re-challenged with PEG, with subsequent increase in TG but no associated complications. TG returned to baseline after discontinuing PEG and while on therapy for HTG. A literature review of PEG-induced HTG in adults demonstrated similar results: asymptomatic presentation despite very severe HTG. HTG is a rare but clinically important adverse effect of PEG. Underlying obesity and/or diabetes may represent risk factors. Clinicians should monitor TG levels during PEG therapy to avoid TG-induced pancreatitis.

  8. Development and validation of a questionnaire to measure the severity of functional limitations and reduction of sports ability in German-speaking patients with exercise-induced leg pain.

    Science.gov (United States)

    Nauck, Tanja; Lohrer, Heinz; Padhiar, Nat; King, John B

    2015-01-01

    Currently, there is no generally agreed measure available to quantify a subject's perceived severity of exercise-induced leg pain symptoms. The aim of this study was to develop and validate a questionnaire that measures the severity of symptoms that impact on function and sports ability in patients with exercise-induced leg pain. The exercise-induced leg pain questionnaire for German-speaking patients (EILP-G) was developed in five steps: (1) initial item generation, (2) item reduction, (3) pretesting, (4) expert meeting and (5) validation. The resulting EILP-G was tested for reliability, validity and internal consistency in 20 patients with exercise-induced leg pain, 20 asymptomatic track and field athletes serving as a population at risk and 33 asymptomatic sport students. The patient group scored the EILP-G questionnaire significantly lower than both control groups (each psports ability in patients with exercise-induced leg pain. It can be recommended as a robust tool for measuring the subjectively perceived severity in German-speaking patients with exercise-induced leg pain. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  9. Eating disorder severity and functional impairment

    DEFF Research Database (Denmark)

    Davidsen, Annika Helgadóttir; Hoyt, William T.; Poulsen, Stig Bernt

    2017-01-01

    Purpose: The aim was to examine duration of illness and body mass index as possible moderators of the relationship between eating disorder severity and functional impairment, as well as psychological distress as a possible mediator of this relationship. Methods: The study included 159 patients...... was measured with the Sheehan Disability Scale, and psychological distress was measured with the Symptom Check List-90-R. Duration of illness and body mass index were assessed clinically. Results: Duration of illness significantly moderated the relationship between eating disorder severity and functional...... impairment; the relationship was strongest for patients with a shorter duration of illness. Psychological distress partly mediated the relationship between eating disorder severity and functional impairment. Duration of illness significantly moderated the relationship between psychological distress...

  10. Kiss-induced severe anaphylactic reactions

    Directory of Open Access Journals (Sweden)

    Atanasković-Marković Marina

    2010-01-01

    Full Text Available Introduction. Ingestion is the principal route for food allergens to trigger allergic reaction in atopic persons. However, in some highly sensitive patients severe symptoms may develop upon skin contact and by inhalation. The clinical spectrum ranges from mild facial urticaria and angioedema to life-threatening anaphylactic reactions. Outline of Cases. We describe cases of severe anaphylactic reactions by skin contact, induced by kissing in five children with prior history of severe anaphylaxis caused by food ingestion. These cases were found to have the medical history of IgE mediated food allergy, a very high total and specific serum IgE level and very strong family history of allergy. Conclusion. The presence of tiny particles of food on the kisser's lips was sufficient to trigger an anaphylactic reaction in sensitized children with prior history of severe allergic reaction caused by ingestion of food. Allergic reaction provoked with food allergens by skin contact can be a risk factor for generalized reactions. Therefore, extreme care has to be taken in avoiding kissing allergic children after eating foods to which they are highly allergic. Considering that kissing can be a cause of severe danger for the food allergic patient, such persons should inform their partners about the risk factor for causing their food hypersensitivity.

  11. Analytic functions of several complex variables

    CERN Document Server

    Gunning, Robert C

    2009-01-01

    The theory of analytic functions of several complex variables enjoyed a period of remarkable development in the middle part of the twentieth century. After initial successes by Poincaré and others in the late 19th and early 20th centuries, the theory encountered obstacles that prevented it from growing quickly into an analogue of the theory for functions of one complex variable. Beginning in the 1930s, initially through the work of Oka, then H. Cartan, and continuing with the work of Grauert, Remmert, and others, new tools were introduced into the theory of several complex variables that resol

  12. Severe excessive daytime sleepiness induced by hydroxyurea.

    Science.gov (United States)

    Revol, Bruno; Joyeux-Faure, Marie; Albahary, Marie-Victoire; Gressin, Remy; Mallaret, Michel; Pepin, Jean-Louis; Launois, Sandrine H

    2017-06-01

    Excessive daytime sleepiness (EDS) has been reported with many drugs, either as an extension of a hypnotic effect (e.g. central nervous system depressants) or as an idiosyncratic response of the patient. Here, we report unexpected and severe subjective and objective EDS induced by hydroxyurea therapy, with a favorable outcome after withdrawal. Clinical history, sleep log, polysomnography, and multiple sleep latency tests confirming the absence of other EDS causes are presented. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  13. Function theory of several complex variables

    CERN Document Server

    Krantz, Steven G

    2001-01-01

    The theory of several complex variables can be studied from several different perspectives. In this book, Steven Krantz approaches the subject from the point of view of a classical analyst, emphasizing its function-theoretic aspects. He has taken particular care to write the book with the student in mind, with uniformly extensive and helpful explanations, numerous examples, and plentiful exercises of varying difficulty. In the spirit of a student-oriented text, Krantz begins with an introduction to the subject, including an insightful comparison of analysis of several complex variables with th

  14. Pazopanib-Induced Severe Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Kazumichi Kawakubo

    2015-08-01

    Full Text Available Pazopanib is an oral angiogenesis inhibitor targeting vascular endothelial growth factor receptors, platelet-derived growth factor receptors, and c-Kit approved for the treatment of renal cell carcinoma and soft tissue sarcoma. Nonselective kinase inhibitors, such as sunitinib and sorafenib, are known to be associated with acute pancreatitis. There are few case reports of severe acute pancreatitis induced by pazopanib treatment. We present a case of severe acute pancreatitis caused by pazopanib treatment for cutaneous angiosarcoma. The patient was an 82-year-old female diagnosed with cutaneous angiosarcoma. She had been refractory to docetaxel treatment and began pazopanib therapy. Three months after pazopanib treatment, CT imaging of the abdomen showed the swelling of the pancreas and surrounding soft tissue inflammation without abdominal pain. After she continued pazopanib treatment for 2 months, she presented with nausea and appetite loss. Abdominal CT showed the worsening of the surrounding soft tissue inflammation of the pancreas. Serum amylase and lipase levels were 296 and 177 IU/l, respectively. She was diagnosed with acute pancreatitis induced by pazopanib treatment and was managed conservatively with discontinuation of pazopanib, but the symptoms did not improve. Subsequently, an abdominal CT scan demonstrated the appearance of a pancreatic pseudocyst. She underwent endoscopic ultrasound-guided pseudocyst drainage using a flared-end fully covered self-expandable metallic stent. Then, the symptoms resolved without recurrence. Due to the remarkable progress of molecular targeted therapy, the oncologist should know that acute pancreatitis was recognized as a potential adverse event of pazopanib treatment and could proceed to severe acute pancreatitis.

  15. Apoptosis-induced lymphopenia in sepsis and other severe injuries.

    Science.gov (United States)

    Girardot, Thibaut; Rimmelé, Thomas; Venet, Fabienne; Monneret, Guillaume

    2017-02-01

    Sepsis and other acute injuries such as severe trauma, extensive burns, or major surgeries, are usually followed by a period of marked immunosuppression. In particular, while lymphocytes play a pivotal role in immune response, their functions and numbers are profoundly altered after severe injuries. Apoptosis plays a central role in this process by affecting immune response at various levels. Indeed, apoptosis-induced lymphopenia duration and depth have been associated with higher risk of infection and mortality in various clinical settings. Therapies modulating apoptosis represent an interesting approach to restore immune competence after acute injury, although their use in clinical practice still presents several limitations. After briefly describing the apoptosis process in physiology and during severe injuries, we will explore the immunological consequences of injury-induced lymphocyte apoptosis, and describe associations with clinically relevant outcomes in patients. Therapeutic perspectives targeting apoptosis will also be discussed.

  16. Severe Hypertriglyceridemia Induced Pancreatitis in Pregnancy

    OpenAIRE

    Gupta, Natasha; Ahmed, Seema; Shaffer, Lemuel; Cavens, Paula; Blankstein, Josef

    2014-01-01

    Acute pancreatitis caused by severe gestational hypertriglyceridemia is a rare complication of pregnancy. Acute pancreatitis has been well associated with gallstone disease, alcoholism, or drug abuse but rarely seen in association with severe hypertriglyceridemia. Hypertriglyceridemia may occur in pregnancy due to normal physiological changes leading to abnormalities in lipid metabolism. We report a case of severe gestational hypertriglyceridemia that caused acute pancreatitis at full term an...

  17. Severe Hypertriglyceridemia Induced Pancreatitis in Pregnancy

    Directory of Open Access Journals (Sweden)

    Natasha Gupta

    2014-01-01

    Full Text Available Acute pancreatitis caused by severe gestational hypertriglyceridemia is a rare complication of pregnancy. Acute pancreatitis has been well associated with gallstone disease, alcoholism, or drug abuse but rarely seen in association with severe hypertriglyceridemia. Hypertriglyceridemia may occur in pregnancy due to normal physiological changes leading to abnormalities in lipid metabolism. We report a case of severe gestational hypertriglyceridemia that caused acute pancreatitis at full term and was successfully treated with postpartum therapeutic plasma exchange. Patient also developed several other complications related to her substantial hypertriglyceridemia including preeclampsia, chylous ascites, retinal detachment, pleural effusion, and chronic pericarditis. This patient had no previous family or personal history of lipid abnormality and had four successful prior pregnancies without developing gestational hypertriglyceridemia. Such a severe hypertriglyceridemia is usually seen in patients with familial chylomicronemia syndromes where hypertriglyceridemia is exacerbated by the pregnancy, leading to fatal complications such as acute pancreatitis.

  18. Severe Acneiform Eruption Induced by Cetuximab (Erbitux?)

    OpenAIRE

    Lee, Jung Eun; Lee, Sang Ju; Lee, Hee Jung; Lee, Ju Hee; Lee, Kwang Hoon

    2008-01-01

    Epidermal growth factor has an important role in the regulation of proliferation and differentiation in epidermal keratinocytes, as well as in the survival, angiogenesis and metastasis of cancer cells. Cetuximab is a chimeric monoclonal antibody selective for the epidermal growth factor receptor that induces a broad range of cellular responses that enhance tumor sensitivity to radiotherapy and chemotherapeutic agents. However, it can cause adverse events in the patient including acneiform eru...

  19. Right ventricular function during acute exacerbation of severe equine asthma.

    Science.gov (United States)

    Decloedt, A; Borowicz, H; Slowikowska, M; Chiers, K; van Loon, G; Niedzwiedz, A

    2017-09-01

    Pulmonary hypertension has been described in horses with severe equine asthma, but its effect on the right ventricle has not been fully elucidated. To evaluate right ventricular structure and function after a 1-week period of pulmonary hypertension secondary to acute exacerbation of severe equine asthma. Prospective study. A clinical episode of severe equine asthma was induced experimentally in six susceptible horses. Examinations in remission and on day 7 of the clinical episode included a physical examination with clinical scoring, echocardiography, arterial blood gas measurements, venous blood sampling for cardiac biomarkers, intracardiac pressure measurements, right ventricular and right atrial myocardial biopsies, airway endoscopy and bronchoalveolar lavage. After 1 month of recovery, physical examination, echocardiography and cardiac biomarker analysis were repeated. Echocardiographic and pressure measurements were compared with those in 10 healthy control horses. All horses developed clinical signs of acute pulmonary obstruction. Right heart pressures increased significantly. Altered right ventricular function could be detected by tissue Doppler and speckle tracking echocardiography. Cardiac troponin concentrations did not increase significantly, but were highly elevated in one horse which exercised in the paddock prior to sampling. Focal neutrophil infiltration was present in two myocardial samples. Even in remission, asthmatic horses showed a thicker right ventricular wall, an increased left ventricular end-systolic eccentricity index at chordal level and decreased right ventricular longitudinal strain compared with controls. The induced clinical episode was rather mild and the number of horses was limited because of the invasive nature of the study. Pulmonary obstruction in asthmatic horses induces pulmonary hypertension with right ventricular structural and functional changes. © 2017 EVJ Ltd.

  20. Functional Recovery After Severe Traumatic Brain Injury

    DEFF Research Database (Denmark)

    Hart, Tessa; Kozlowski, Allan; Whyte, John

    2014-01-01

    recovery was best modeled with linear, cubic, and quadratic components: relatively steep recovery was followed by deceleration of improvement, which attenuated prior to discharge. Slower recovery was associated with older age, longer coma, and interruptions to rehabilitation. Patients admitted at lower...... multi-disciplinary teams were recorded daily in 15-minute units provided to patients and family members, separately. MAIN OUTCOME MEASURES: Motor and Cognitive FIM measured on admission, discharge, and every 2 weeks in between, analyzed with Individual Growth Curve methodology. RESULTS: Inpatient...... functional levels received more treatment and more treatment was associated with slower recovery, presumably because treatment was allocated according to need. Thus, effects of treatment on outcome could not be disentangled from effects of case mix factors. CONCLUSIONS: FIM gain during inpatient recovery...

  1. NKT Cells in the Induced Sputum of Severe Asthmatics

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available To determine whether there was a specific inflammatory process in severe asthmatics, the phenotypic characteristics of induced sputum immune cells were analysed among patients with severe asthma. Twenty-two induced sputa (10 severe asthmatics were studied. Flow cytometric analysis was performed using immune cells of the sputum and monoclonal antibodies to CD3, CD4, CD8, CD56, CD25, and TCRγδ . The number of NKT (CD3 + CD 56+ cells was significantly higher in the sputum of severe asthmatics compared with mild asthmatic and healthy control groups ( p<.05 . CD8+CD 56+ cells were the predominant subtype of the increased NKT cells in severe asthmatics. CD3 +CD56+Vα24 +, TCRγδ CD56+, and CD4+CD25+ T cells were significantly increased in severe asthmatic patients. These results suggest that the immunopathogenesis of severe asthmatics vary between severe and mild asthmatics, and that CD8+ CD 56+ NKT cells may play an important role in the immunopathogenesis of severe asthma.

  2. Gravity induced wave function collapse

    Science.gov (United States)

    Gasbarri, G.; Toroš, M.; Donadi, S.; Bassi, A.

    2017-11-01

    Starting from an idea of S. L. Adler [in Quantum Nonlocality and Reality: 50 Years of Bell's Theorem, edited by M. Bell and S. Gao (Cambridge University Press, Cambridge, England 2016)], we develop a novel model of gravity induced spontaneous wave function collapse. The collapse is driven by complex stochastic fluctuations of the spacetime metric. After deriving the fundamental equations, we prove the collapse and amplification mechanism, the two most important features of a consistent collapse model. Under reasonable simplifying assumptions, we constrain the strength ξ of the complex metric fluctuations with available experimental data. We show that ξ ≥10-26 in order for the model to guarantee classicality of macro-objects, and at the same time ξ ≤10-20 in order not to contradict experimental evidence. As a comparison, in the recent discovery of gravitational waves in the frequency range 35 to 250 Hz, the (real) metric fluctuations reach a peak of ξ ˜10-21.

  3. Capecitabine induced hypertriglyceridaemia: An underreported and potentially severe side effect

    OpenAIRE

    Tabchi S; Joseph K

    2014-01-01

    A 57 year-old-woman, with no previous history of dyslipedemia, developed severe hypertriglyceridemia while being treated with capecitabine for metastatic breast cancer. Capecitabine was not discontinued and serum triglyceride levels were normalized after 4 weeks of treatment with fenofibrate. Capecitabine induced hypertriglyceridemia, as a rare drug-related side effect, seems to be often overlooked by clinicians.

  4. Capecitabine induced hypertriglyceridaemia: An underreported and potentially severe side effect

    Directory of Open Access Journals (Sweden)

    Tabchi S

    2014-05-01

    Full Text Available A 57 year-old-woman, with no previous history of dyslipedemia, developed severe hypertriglyceridemia while being treated with capecitabine for metastatic breast cancer. Capecitabine was not discontinued and serum triglyceride levels were normalized after 4 weeks of treatment with fenofibrate. Capecitabine induced hypertriglyceridemia, as a rare drug-related side effect, seems to be often overlooked by clinicians.

  5. Severe exacerbations and decline in lung function in asthma

    DEFF Research Database (Denmark)

    O'Byrne, Paul M; Pedersen, Søren; Lamm, Carl Johan

    2009-01-01

    RATIONALE: To evaluate the association between asthma exacerbations and the decline in lung function, as well as the potential effects of an inhaled corticosteroid, budesonide, on exacerbation-related decline in patients with asthma. OBJECTIVES: To determine whether severe asthma exacerbations...... with low-dose inhaled budesonide prevents severe asthma-related events (exacerbations requiring hospitalization or emergency treatment) and decline in lung function. MEASUREMENTS AND MAIN RESULTS: There were 315 patients who experienced at least one severe asthma exacerbation, of which 305 were analyzable...... of reduction afforded by budesonide, in patients who experienced at least one severe asthma-related event compared with those who did not, was statistically significant (P = 0.042). CONCLUSIONS: Severe asthma exacerbations are associated with a more rapid decline in lung function. Treatment with low doses...

  6. Down-regulation of Wild-type p53-induced Phosphatase 1 (Wip1) Plays a Critical Role in Regulating Several p53-dependent Functions in Premature Senescent Tumor Cells*

    Science.gov (United States)

    Crescenzi, Elvira; Raia, Zelinda; Pacifico, Francesco; Mellone, Stefano; Moscato, Fortunato; Palumbo, Giuseppe; Leonardi, Antonio

    2013-01-01

    Premature or drug-induced senescence is a major cellular response to chemotherapy in solid tumors. The senescent phenotype develops slowly and is associated with chronic DNA damage response. We found that expression of wild-type p53-induced phosphatase 1 (Wip1) is markedly down-regulated during persistent DNA damage and after drug release during the acquisition of the senescent phenotype in carcinoma cells. We demonstrate that down-regulation of Wip1 is required for maintenance of permanent G2 arrest. In fact, we show that forced expression of Wip1 in premature senescent tumor cells induces inappropriate re-initiation of mitosis, uncontrolled polyploid progression, and cell death by mitotic failure. Most of the effects of Wip1 may be attributed to its ability to dephosphorylate p53 at Ser15 and to inhibit DNA damage response. However, we also uncover a regulatory pathway whereby suppression of p53 Ser15 phosphorylation is associated with enhanced phosphorylation at Ser46, increased p53 protein levels, and induction of Noxa expression. On the whole, our data indicate that down-regulation of Wip1 expression during premature senescence plays a pivotal role in regulating several p53-dependent aspects of the senescent phenotype. PMID:23612976

  7. Sitaxsentan-Induced Acute Severe Hepatitis Treated with Glucocorticoid Therapy

    Directory of Open Access Journals (Sweden)

    Marcus W Chin

    2012-01-01

    Full Text Available Endothelin receptor antagonists are commonly used in the treatment of pulmonary hypertension. Sitaxsentan, a selective endothelin A receptor blocker, induces a mild transaminitis in approximately 3% to 5% of patients, but rarely an acute severe hepatitis. A case involving a 61-year-old female with sitaxsentan-induced acute severe liver failure is presented. Depite withdrawal of therapy, her liver tests failed to improve. After six weeks of monitoring, the patient was administered high-dose corticosteroids, with a good clinical and biochemical response. While endothelin receptor antagonists are postulated to cause hepatitis by inhibition of a bile salt transporter pump, an immune-mediated or idiosyncratic mechanism should be considered.

  8. Severe valproate induced hyperammonemic encephalopathy successfully managed with peritoneal dialysis.

    Science.gov (United States)

    Kumar, Amandeep; Suri, Ashish; Sharma, Bhawani S

    2014-07-01

    Valproic acid (VPA) is a commonly used drug for epilepsy, psychiatric disorders and migraine and is frequently used in neurosurgical intensive care units. Though most of its side-effects are mild and transient, certain idiosyncratic side-effects have been attributed to VPA. Valproate induced hyperammonemia (VIH) is one such side-effect. VIH can produce symptoms of encephalopathy known as valproate induced hyperammonemic encephalopathy (VHE). VIH and VHE usually respond to withdrawal of VPA. However, in some cases VHE can be unresponsive to supportive measures and severe enough to be life-threatening. In such cases, dialysis can be used to rapidly reverse hyperammonemia and VHE and can prove to be a lifesaving measure. We report such a case of VIH and life-threatening VHE in a postoperative neurosurgical patient that was managed successfully with peritoneal dialysis.

  9. Long-term functional health status of severely injured patients

    NARCIS (Netherlands)

    Holtslag, H. R.; Post, M. W.; Lindeman, E.; Van der Werken, Chr.

    Background: Studies of the consequences of major trauma have traditionally focused on mortality rates. The aims of this study were, firstly, to investigate the long-term functional health status in a large, unselected group of severely injured patients and to compare this with normative data, and

  10. Safety of Induced Sputum Collection in Children Hospitalized With Severe or Very Severe Pneumonia.

    Science.gov (United States)

    DeLuca, Andrea N; Hammitt, Laura L; Kim, Julia; Higdon, Melissa M; Baggett, Henry C; Brooks, W Abdullah; Howie, Stephen R C; Deloria Knoll, Maria; Kotloff, Karen L; Levine, Orin S; Madhi, Shabir A; Murdoch, David R; Scott, J Anthony G; Thea, Donald M; Amornintapichet, Tussanee; Awori, Juliet O; Chuananon, Somchai; Driscoll, Amanda J; Ebruke, Bernard E; Hossain, Lokman; Jahan, Yasmin; Kagucia, E Wangeci; Kazungu, Sidi; Moore, David P; Mudau, Azwifarwi; Mwananyanda, Lawrence; Park, Daniel E; Prosperi, Christine; Seidenberg, Phil; Sylla, Mamadou; Tapia, Milagritos D; Zaman, Syed M A; O'Brien, Katherine L

    2017-06-15

    Induced sputum (IS) may provide diagnostic information about the etiology of pneumonia. The safety of this procedure across a heterogeneous population with severe pneumonia in low- and middle-income countries has not been described. IS specimens were obtained as part a 7-country study of the etiology of severe and very severe pneumonia in hospitalized children <5 years of age. Rigorous clinical monitoring was done before, during, and after the procedure to record oxygen requirement, oxygen saturation, respiratory rate, consciousness level, and other evidence of clinical deterioration. Criteria for IS contraindications were predefined and serious adverse events (SAEs) were reported to ethics committees and a central safety monitor. A total of 4653 IS procedures were done among 3802 children. Thirteen SAEs were reported in relation to collection of IS, or 0.34% of children with at least 1 IS specimen collected (95% confidence interval, 0.15%-0.53%). A drop in oxygen saturation that required supplemental oxygen was the most common SAE. One child died after feeding was reinitiated 2 hours after undergoing sputum induction; this death was categorized as "possibly related" to the procedure. The overall frequency of SAEs was very low, and the nature of most SAEs was manageable, demonstrating a low-risk safety profile for IS collection even among severely ill children in low-income-country settings. Healthcare providers should monitor oxygen saturation and requirements during and after IS collection, and assess patients prior to reinitiating feeding after the IS procedure, to ensure patient safety. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  11. Mindfulness-Based Cognitive Therapy for severe Functional Disorders

    DEFF Research Database (Denmark)

    Fjorback, Lone Overby

    MINDFULNESS-BASED COGNITIVE THERAPY FOR FUNCTIONAL DISORDERS- A RANDOMISED CONTROLLED TRIAL   Background: Mindfulness-Based Stress Reduction (MBSR) is a group skills-training program developed by Kabat-Zinn. It is designed to teach patients to become more aware of and relate differently...... to their thoughts, feelings, and bodily sensations. Randomised controlled studies of MBSR have shown mitigation of stress, anxiety, and dysphoria in general population and reduction in total mood disturbance and stress symptoms in a medical population. In Mindfulness Based Cognitive Therapy MBSR is recombined...... with cognitive therapy. Aim: To examine the efficacy of Mindfulness-Based Cognitive Therapy in severe Functional disorders, defined as severe Bodily Distress Disorder. Method: 120 patients are randomised to either Mindfulness Based Cognitive Therapy: a manualized programme with eight weekly 3 ½ hour group...

  12. Mindfulness-Based Cognitive Therapy for severe Functional Disorders

    DEFF Research Database (Denmark)

    Fjorback, Lone Overby

    with cognitive therapy. Aim: To examine the efficacy of Mindfulness-Based Cognitive Therapy in severe Functional disorders, defined as severe Bodily Distress Disorder. Method: 120 patients are randomised to either Mindfulness Based Cognitive Therapy: a manualized programme with eight weekly 3 ½ hour group......MINDFULNESS-BASED COGNITIVE THERAPY FOR FUNCTIONAL DISORDERS- A RANDOMISED CONTROLLED TRIAL   Background: Mindfulness-Based Stress Reduction (MBSR) is a group skills-training program developed by Kabat-Zinn. It is designed to teach patients to become more aware of and relate differently...... to their thoughts, feelings, and bodily sensations. Randomised controlled studies of MBSR have shown mitigation of stress, anxiety, and dysphoria in general population and reduction in total mood disturbance and stress symptoms in a medical population. In Mindfulness Based Cognitive Therapy MBSR is recombined...

  13. Large Eddy Simulations of Severe Convection Induced Turbulence

    Science.gov (United States)

    Ahmad, Nash'at; Proctor, Fred

    2011-01-01

    Convective storms can pose a serious risk to aviation operations since they are often accompanied by turbulence, heavy rain, hail, icing, lightning, strong winds, and poor visibility. They can cause major delays in air traffic due to the re-routing of flights, and by disrupting operations at the airports in the vicinity of the storm system. In this study, the Terminal Area Simulation System is used to simulate five different convective events ranging from a mesoscale convective complex to isolated storms. The occurrence of convection induced turbulence is analyzed from these simulations. The validation of model results with the radar data and other observations is reported and an aircraft-centric turbulence hazard metric calculated for each case is discussed. The turbulence analysis showed that large pockets of significant turbulence hazard can be found in regions of low radar reflectivity. Moderate and severe turbulence was often found in building cumulus turrets and overshooting tops.

  14. Virus-induced Gene Silencing-based Functional Analyses Revealed the Involvement of Several Putative Trehalose-6-Phosphate Synthase/Phosphatase Genes in Disease Resistance against Botrytis cinerea and Pseudomonas syringae pv. tomato DC3000 in Tomato

    Directory of Open Access Journals (Sweden)

    Huijuan Zhang

    2016-08-01

    Full Text Available Trehalose and its metabolism have been demonstrated to play important roles in control of plant growth, development and stress responses. However, direct genetic evidence supporting the functions of trehalose and its metabolism in defense response against pathogens is lacking. In the present study, genome-wide characterization of putative trehalose-related genes identified 11 SlTPSs for trehalose-6-phosphate synthase, 8 SlTPPs for trehalose-6-phosphate phosphatase and one SlTRE1 for trehalase in tomato genome. Nine SlTPSs, 4 SlTPPs and SlTRE1 were selected for functional analyses to explore their involvement in tomato disease resistance. Some selected SlTPSs, SlTPPs and SlTRE1 responded with distinct expression induction patterns to Botrytis cinerea and Pseudomonas syringae pv. tomato (Pst DC3000 as well as to defense signaling hormones (e.g. salicylic acid, jasmonic acid and a precursor of ethylene. Virus-induced gene silencing-mediated silencing of SlTPS3, SlTPS4 or SlTPS7 led to deregulation of ROS accumulation and attenuated the expression of defense-related genes upon pathogen infection and thus deteriorated the resistance against B. cinerea or Pst DC3000. By contrast, silencing of SlTPS5 or SlTPP2 led to an increased expression of the defense-related genes upon pathogen infection and conferred an increased resistance against Pst DC3000. Silencing of SlTPS3, SlTPS4, SlTPS5, SlTPS7 or SlTPP2 affected trehalose level in tomato plants with or without infection of B. cinerea or Pst DC3000. These results demonstrate that SlTPS3, SlTPS4, SlTPS5, SlTPS7 and SlTPP2 play roles in resistance against B. cinerea and Pst DC3000, implying the importance of trehalose and tis metabolism in regulation of defense response against pathogens in tomato.

  15. Allopurinol-induced Severe Hypersensitivity with Acute Renal Failure

    Directory of Open Access Journals (Sweden)

    I-Hung Chen

    2005-05-01

    Full Text Available A 62-year-old male was sent to the emergency room due to a high fever and generalized skin rash after taking allopurinol for 9 days. Physical examination was normal except for the generalized skin rash presenting with erythematous macules. Complete blood count showed leukocytosis with eosinophilia. Blood biochemistry showed impaired renal and hepatic function. Pathologic examination concluded that the skin rash was erythema multiforme. These findings met the diagnostic criteria for allopurinol-induced hypersensitivity syndrome (AHS. Our patient not only had the most common skin lesion but soon developed acute renal failure that required intermittent hemodialysis, despite rapid discontinuation of allopurinol and adequate hydration and steroid therapy. No other causes of acute renal failure were found. Renal impairment was the worst part of the patient's condition and he never completely recovered. AHS should be considered in the differential diagnosis of acute renal and hepatic failure in patients with evidence of allergy and recent use of allopurinol.

  16. Effects of alcoholism severity and smoking on executive neurocognitive function.

    Science.gov (United States)

    Glass, Jennifer M; Buu, Anne; Adams, Kenneth M; Nigg, Joel T; Puttler, Leon I; Jester, Jennifer M; Zucker, Robert A

    2009-01-01

    Neurocognitive deficits in chronic alcoholic men are well documented. Impairments include memory, visual-spatial processing, problem solving and executive function. The cause of impairment could include direct effects of alcohol toxicity, pre-existing cognitive deficits that predispose towards substance abuse, comorbid psychiatric disorders and abuse of substances other than alcohol. Cigarette smoking occurs at higher rates in alcoholism and has been linked to poor cognitive performance, yet the effects of smoking on cognitive function in alcoholism are often ignored. We examined whether chronic alcoholism and chronic smoking have effects on executive function. Alcoholism and smoking were examined in a community-recruited sample of alcoholic and non-alcoholic men (n = 240) using standard neuropsychological and reaction-time measures of executive function. Alcoholism was measured as the average level of alcoholism diagnoses across the study duration (12 years). Smoking was measured in pack-years. Both alcoholism and smoking were correlated negatively with a composite executive function score. For component measures, alcoholism was correlated negatively with a broad range of measures, whereas smoking was correlated negatively with measures that emphasize response speed. In regression analyses, both smoking and alcoholism were significant predictors of executive function composite. However, when IQ is included in the regression analyses, alcoholism severity is no longer significant. Both smoking and alcoholism were related to executive function. However, the effect of alcoholism was not independent of IQ, suggesting a generalized effect, perhaps affecting a wide range of cognitive abilities of which executive function is a component. On the other hand, the effect of smoking on measures relying on response speed were independent of IQ, suggesting a more specific processing speed deficit associated with chronic smoking.

  17. Association Between Functional Dyspepsia And Severity Of Depression

    International Nuclear Information System (INIS)

    Jamil, O.; Sarwar, S.; Hussain, Z.; Fiaz, R. O.; Chaudary, R. D.

    2016-01-01

    Objective: To determine the association between functional dyspepsia and the severity of depression. Study Design: Cross-sectional study. Place and Duration of Study: Department of Medicine, King Edward Medical University/Mayo Hospital, Lahore, from September 2012 till January 2013. Methodology: After taking informed written consent, patients with symptoms of dyspepsia fulfilling the Rome III criteria were included in the study. All patients were evaluated for depression, using Hamilton depression rating scale (HDRS). Upper gastrointestinal endoscopy was done. Fischers' exact test and independent t-test were used for determining significance of association. Result: One hundred and one patients with mean age of 35.81 14.81) years and male to female ratio of 1.41:1 (54/47) were included. Predominant symptoms were early satiety (72.3 percentage), epigastric pain (65.3 percentage), bloating (49.5 percentage), postprandial fullness (40.6 percentage), and regurgitation (40.6 percentage). Alarm symptoms were positive in 44 (43.6 percentage) patients. Dyspepsia were classified as epigastric pain syndrome (EPS, 69.3 percentage), and postprandial distress syndrome (PDS, 30.7 percentage). Significantly more females had PDS (p=0.04), with positive endoscopic findings in EPS (p=0.03). Positive endoscopic findings noted were esophagitis in 21.8 percentage, and gastritis in 48.5 percentage patients. All patients except one had depression, mild in 22.8 percentage, moderate in 33.7 percentage, severe in 31.7 percentage, and very severe in 10.9 percentage patients. Severe depression was seen in 32 (45.7 percentage) patients with EPS and PDS; whereas very severe depression was in 11 (15.7 percentage) patients of EPS, while 11 (35.4 percentage) patients of PDS had severe depression but the difference was not significant. Conclusion: Functional dyspepsia is associated with depression, while positive endoscopic findings are more likely in patients with EPS. Very severe depression

  18. Pheochromocytoma with Markedly Abnormal Liver Function Tests and Severe Leukocytosis

    Directory of Open Access Journals (Sweden)

    Chai Ryoung Eun

    2014-03-01

    Full Text Available Pheochromocytoma is a rare neuroendocrine tumor arising from the medulla of the adrenal glands, which causes an overproduction of catecholamines. The common symptoms are headache, palpitations, and sweating; however, various other clinical manifestations might also be present. Accurate diagnosis of pheochromocytoma is important because surgical treatment is usually successful, and associated clinical problems are reversible if treated early. A 49-year-old man with a history of uncontrolled hypertension and diabetes mellitus presented with chest pain, fever, and sweating. His liver function tests and white blood cell counts were markedly increased and his echocardiography results suggested stress-induced cardiomyopathy. His abdominal computed tomography showed a 5×5-cm-sized tumor in the left adrenal gland, and laboratory tests confirmed catecholamine overproduction. After surgical resection of the left adrenal gland, his liver function tests and white blood cell counts normalized, and echocardiography showed normal cardiac function. Moreover, his previous antihypertensive regimen was deescalated, and his previously uncontrolled blood glucose levels normalized without medication.

  19. Real analysis series, functions of several variables, and applications

    CERN Document Server

    Laczkovich, Miklós

    2017-01-01

    This book develops the theory of multivariable analysis, building on the single variable foundations established in the companion volume, Real Analysis: Foundations and Functions of One Variable. Together, these volumes form the first English edition of the popular Hungarian original, Valós Analízis I & II, based on courses taught by the authors at Eötvös Loránd University, Hungary, for more than 30 years. Numerous exercises are included throughout, offering ample opportunities to master topics by progressing from routine to difficult problems. Hints or solutions to many of the more challenging exercises make this book ideal for independent study, or further reading. Intended as a sequel to a course in single variable analysis, this book builds upon and expands these ideas into higher dimensions. The modular organization makes this text adaptable for either a semester or year-long introductory course. Topics include: differentiation and integration of functions of several variables; infinite numerica...

  20. Sever hepatitis induced by Epstein-Barr virus: case series

    Directory of Open Access Journals (Sweden)

    Roushan Mohammad Reza Hasanjani

    2018-03-01

    Full Text Available Epstein-Barr virus (EBV is a causative agent of infectious mononucleosis syndrome. This infection often resolves over a period of several months without outcomes, but may occasionally be complicated by a great variety of neurologic, hepatic, hematologic and respiratory complications. In the current report, we present the case histories of three patients with acute hepatitis following EBV infection when previously healthy. The patients showed fever, nausea, weakness, as well as yellowing of the skin, and then in the course of examination, sore throat. They were managed supportively and their clinical condition improved. Liver function tests such as ALT, AST, ALP, were undertaken and bilirubin were elevated. The serological tests for EBV infection were consistent with the acute phase of infection. The monospot test was also positive. The patients were managed supportively, and their critical condition was improved.

  1. Functional neurologic recovery in two dogs diagnosed with severe

    Directory of Open Access Journals (Sweden)

    Mônica Vicky Bahr Arias

    2015-04-01

    Full Text Available Traumatic injuries to the vertebral column, spinal cord, and cauda equina nerve roots occur frequently in human and veterinary medicine and lead to devastating consequences. Complications include partial or complete loss of motor, sensory, and visceral functions, which are among the main causes of euthanasia in dogs. The present case report describes neurological functional recovery in two dogs that were treated surgically for severe spinal fracture and vertebral luxation. In the first case, a stray, mixed breed puppy was diagnosed with thoracolumbar syndrome and Schiff-Scherrington posture, as well as a T13 caudal epiphyseal fracture with 100% luxation between vertebrae T13 and L1; despite these injuries, the animal did show deep pain sensation in the pelvic limbs. Decompression through hemilaminectomy and spinal stabilization with vertebral body pins and bone cement were performed, and the treatment was supplemented with physiotherapy and acupuncture . In the second case, a mixed breed dog was diagnosed with a vertebral fracture and severe luxation between L6 and L7 after a vehicular trauma, but maintained nociception and perineal reflex. Surgical stabilization of the spine was performed using a modified dorsal segmental fixation technique Both patients showed significant recovery of neurological function. Complete luxation of the spinal canal observed radiographically does not mean a poor prognosis, and in some cases, motor, sensory, and visceral functions all have the potential for recovery. In the first case the determining factor for good prognosis was the presence of deep pain perception, and in the second case the prognosis was determined by the presence of sensitivity and anal sphincter tone during the initial neurological examination

  2. Brain atrophy in the visual cortex and thalamus induced by severe stress in animal model.

    Science.gov (United States)

    Yoshii, Takanobu; Oishi, Naoya; Ikoma, Kazuya; Nishimura, Isao; Sakai, Yuki; Matsuda, Kenichi; Yamada, Shunji; Tanaka, Masaki; Kawata, Mitsuhiro; Narumoto, Jin; Fukui, Kenji

    2017-10-06

    Psychological stress induces many diseases including post-traumatic stress disorder (PTSD); however, the causal relationship between stress and brain atrophy has not been clarified. Applying single-prolonged stress (SPS) to explore the global effect of severe stress, we performed brain magnetic resonance imaging (MRI) acquisition and Voxel-based morphometry (VBM). Significant atrophy was detected in the bilateral thalamus and right visual cortex. Fluorescent immunohistochemistry for Iba-1 as the marker of activated microglia indicates regional microglial activation as stress-reaction in these atrophic areas. These data certify the impact of severe psychological stress on the atrophy of the visual cortex and the thalamus. Unexpectedly, these results are similar to chronic neuropathic pain rather than PTSD clinical research. We believe that some sensitisation mechanism from severe stress-induced atrophy in the visual cortex and thalamus, and the functional defect of the visual system may be a potential therapeutic target for stress-related diseases.

  3. Polyhexamethyleneguanidine phosphate induces severe lung inflammation, fibrosis, and thymic atrophy.

    Science.gov (United States)

    Song, Jeong Ah; Park, Hyun-Ju; Yang, Mi-Jin; Jung, Kyung Jin; Yang, Hyo-Seon; Song, Chang-Woo; Lee, Kyuhong

    2014-07-01

    Polyhexamethyleneguanidine phosphate (PHMG-P) has been widely used as a disinfectant because of its strong bactericidal activity and low toxicity. However, in 2011, the Korea Centers for Disease Control and Prevention and the Ministry of Health and Welfare reported that a suspicious outbreak of pulmonary disease might have originated from humidifier disinfectants. The purpose of this study was to assess the toxicity of PHMG-P following direct exposure to the lung. PHMG-P (0.3, 0.9, or 1.5 mg/kg) was instilled into the lungs of mice. The levels of proinflammatory markers and fibrotic markers were quantified in lung tissues and flow cytometry was used to evaluate T cell distribution in the thymus. Administration of PHMG-P induced proinflammatory cytokines elevation and infiltration of immune cells into the lungs. Histopathological analysis revealed a dose-dependent exacerbation of both inflammation and pulmonary fibrosis on day 14. PHMG-P also decreased the total cell number and the CD4(+)/CD8(+) cell ratio in the thymus, with the histopathological examination indicating severe reduction of cortex and medulla. The mRNA levels of biomarkers associated with T cell development also decreased markedly. These findings suggest that exposure of lung tissue to PHMG-P leads to pulmonary inflammation and fibrosis as well as thymic atrophy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Extracorporeal Treatment in Severe Hypertriglyceridemia-Induced Pancreatitis.

    Science.gov (United States)

    Zeitler, Heike; Balta, Zeynep; Klein, Burkhard; Strassburg, Christian P

    2015-08-01

    Plasmapheresis is a well-accepted treatment option in severe hypertriglyceridemia-induced pancreatitis (HTGP). The rationale behind this approach is the depletion of triglycerides and the reduction of inflammatory cytokines. The time span between onset of clinical symptoms and start of plasmapheresis might have an important impact on mortality. Hyperviscosity of patients' plasma represents another special challenge for the applied separation technology. The procedures can be performed either by centrifugal device (CFD) or membrane based (MBS) units. The present study reports the outcome of 10 patients suffering from HTG. The expected mortality of the collective was 25%. Plasmapheresis was started after an average 16.3 h (SD ± 6.7 h) after onset of symptoms. No mortality occurred. Apheresis was statistically equally effective with both devices. A median of 3 sessions reduced the TG level to normal and correlated with patients' improvement. During follow up, three patients developed a pancreatic pseudocyst requiring surgical intervention without further complication. © 2015 The Authors. Therapeutic Apheresis and Dialysis © 2015 International Society for Apheresis.

  5. GRAVES’ DISEASE INDUCED REVERSIBLE SEVERE RIGHT HEART FAILURE

    Directory of Open Access Journals (Sweden)

    Kathyayani

    2015-07-01

    Full Text Available A middle aged man presented with evidence of right - sided heart failure in atrial fibrillation (AF and was found to have severe Tricuspid Regurgitation (TR with pulmonary artery hypertension (PAH, with normal left ventricular function. The common possible seconda ry causes of PAH were ruled out, but during investigation he was found to have elevated thyroid function tests compatible with the diagnosis of Graves’ disease. The treatment of Graves’ disease was started with anti - thyroid drugs and associated with a sign ificant reduction in the pulmonary arterial pressure. This case report is presented to highlight one of the rare and underdiagnosed presentations of Graves’ disease. Thyrotoxicosis can present with profound cardiovascular complications. In recent times, th ere have been few reports of secondary PAH with TR in patients with hyperthyroidism. Previously asymptomatic Graves’ disease having the signs and symptoms of right heart failure is a rare presentation and the association could be easily missed. This case p resentation emphasizes that the diagnosis of thyroid heart disease with heart failure secondary to Graves’ disease should be considered in any patient regardless of age, gender with clinical features of heart failure of unknown etiology and timely initiation of anti - thyroid drugs is necessary to treat these reversible cardiac failures.

  6. Assessment of Dengue Fever Severity Through Liver Function Tests

    International Nuclear Information System (INIS)

    Ahmed, A.; Alvi, A. H.; Nawaz, A. A.; Butt, A.; Hanif, A.

    2014-01-01

    Objective: To assess the utility of liver function tests (LFTs) for early recognition and prediction of severity of Dengue fever in hospitalized patients. Study Design: An analytical study. Place and Duration of Study: Services Institute of Medical Science and Fatima Memorial Hospital, Lahore, from September - December 2010. Methodology: Admitted cases of Dengue fever were divided into 3 groups; mild, moderate and severe increases in aminotransferases. Elevation in LFTs was co-related with good or bad outcome i.e. (survival or complication free stay) or (death or complications). Results were analyzed in SPSS version 18. Results: Out of the 353 patients with mean age of 37.12 +- 15.45 years, 245 (69.4%) were males and 108 (30.6%) were females. Seventy five patients (21.2%) had mild elevation of aminotransferases (2 fold increases), 265 patients (75.1%) had moderate increases (3 to 4 fold) and 13 (3.7%) had severe (> 4 fold increase). ALT was statistically higher in patients with septicemia, hepatic and renal failure (p-value 0.05). AST was higher in almost all complications. Prolonged hospital stay was associated with raised LFTs and greater complications and mortality. AST was found to be twice as much raised as ALT. Conclusion: AST and ALT were statistically higher in patients with worse outcome thus can lead to early recognition of high risk cases. (author)

  7. Monocyte function is severely impaired by the fluorochrome calcein acetomethylester

    International Nuclear Information System (INIS)

    Czepluch, Frauke S.; Olieslagers, Serve J.F.; Waltenberger, Johannes

    2007-01-01

    For rapid chemotaxis quantification, cell prelabelling is often performed with the fluorochrome calcein acetomethylester (calcein AM). We investigated whether calcein AM-prelabelling is reliable for monocyte migration analysis. Human monocytes were either preexposed to calcein AM or unlabelled. Monocyte migration towards the potent chemoattractants transforming growth factor-β1 (TGF-β1) and N-formyl-Methionin-Leucin-Phenylalanin (fMLP) was assessed using a 48-well micro-chemotaxis chamber. For quantification, cells were visualized by light microscopy and counted. Surprisingly, random migration of calcein AM-prelabelled cells was significantly impaired compared to the unlabelled control. Accordingly, monocyte chemotaxis towards either TGF-β1 or fMLP dramatically declined. Adherence of calcein AM-labelled monocytes on plastic was also significantly decreased compared to control cells. As adhesion is regarded as an essential component of monocyte migration, the reduced migration observed in calcein AM-labelled monocytes might be explained by a fluorochrome-induced adhesion defect. Therefore, use of the fluorochrome calcein AM cannot be recommended for functional testing of monocytes

  8. Assessing depression related severity and functional impairment: the Overall Depression Severity and Impairment Scale (ODSIS.

    Directory of Open Access Journals (Sweden)

    Masaya Ito

    Full Text Available The Overall Depression Severity and Impairment Scale (ODSIS is a brief, five-item measure for assessing the frequency and intensity of depressive symptoms, as well as functional impairments in pleasurable activities, work or school, and interpersonal relationships due to depression. Although this scale is expected to be useful in various psychiatric and mental health settings, the reliability, validity, and interpretability have not yet been fully examined. This study was designed to examine the reliability, factorial, convergent, and discriminant validity of a Japanese version of the ODSIS, as well as its ability to distinguish between individuals with and without a major depressive disorder diagnosis.From a pool of registrants at an internet survey company, 2830 non-clinical and clinical participants were selected randomly (619 with major depressive disorder, 619 with panic disorder, 576 with social anxiety disorder, 645 with obsessive-compulsive disorder, and 371 non-clinical panelists. Participants were asked to respond to the ODSIS and conventional measures of depression, functional impairment, anxiety, neuroticism, satisfaction with life, and emotion regulation.Exploratory and confirmatory factor analysis of three split subsamples indicated the unidimensional factor structure of ODSIS. Multi-group confirmatory factor analysis showed invariance of factor loadings between non-clinical and clinical subsamples. The ODSIS also showed excellent internal consistency and test-retest intraclass correlation coefficients. Convergence and discriminance of the ODSIS with various measures were in line with our expectations. Receiver operating characteristic curve analyses showed that the ODSIS was able to detect a major depressive syndrome accurately.This study supports the reliability and validity of ODSIS in a non-western population, which can be interpreted as demonstrating cross-cultural validity.

  9. NKT Cells in the Induced Sputum of Severe Asthmatics

    Directory of Open Access Journals (Sweden)

    Agnes Hamzaoui

    2006-01-01

    of the sputum and monoclonal antibodies to CD3, CD4, CD8, CD56, CD25, and TCRγδ. The number of NKT (CD3+CD56+ cells was significantly higher in the sputum of severe asthmatics compared with mild asthmatic and healthy control groups (P<.05. CD8+CD56+ cells were the predominant subtype of the increased NKT cells in severe asthmatics. CD3+CD56+Vα24+, TCRγδ+ CD56+, and CD4+CD25+ T cells were significantly increased in severe asthmatic patients. These results suggest that the immunopathogenesis of severe asthmatics vary between severe and mild asthmatics, and that CD8+CD56+ NKT cells may play an important role in the immunopathogenesis of severe asthma.

  10. Thymus function in drug-induced lupus.

    Science.gov (United States)

    Rubin, R L; Salomon, D R; Guerrero, R S

    2001-01-01

    Autoimmunity develops when a lupus-inducing drug is introduced into the thymus of normal mice, but the relevance of this model to the human disorder is unclear in part because it is widely assumed that the thymus is non-functional in the adult. We compared thymus function in 10 patients with symptomatic procainamide-induced lupus to that in 13 asymptomatic patients who only developed drug-induced autoantibodies. T cell output from the thymus was quantified using a competitive polymerase chain reaction that detects T cell receptor DNA excision circles in peripheral blood lymphocytes. Despite the advanced age of the patient population under study, newly generated T cells were detected in all subjects. Although there was no overall quantitative difference between the symptomatic and asymptomatic patients, we found a positive correlation between the level of T cell receptor excision circles in peripheral lymphocytes and serum IgG anti-chromatin antibody activity in patients with drug-induced lupus. The association between autoantibodies and nascent peripheral T cells supports the requirement for T cells in autoantibody production. Our observations are consistent with findings in mice in which autoreactive T cells derived from drug-induced abnormalities in T cell development in the thymus.

  11. Severe Statin-induced Rhabdomyolysis following Cholestatic Hepatitis induced by Amoxicillin-clavulanate

    Directory of Open Access Journals (Sweden)

    Rachele Rapetti

    2014-05-01

    Full Text Available We report the case of an 86-year-old man with a past history of coronary disease admitted to our internal medicine department for severe asthenia and weakness due to rhabdomyolysis. Three days earlier, he had been discharged from a gastroenterology unit with a diagnosis of amoxicillin–clavulanate-induced acute cholestatic hepatitis. A review of his drugs revealed that he had taken atorvastatin 10 mg daily in the previous six years, without clinical or laboratory signs of myopathy. Atorvastatin was therefore stopped, with gradual improvement of the rhabdomyolysis. All concomitant drug therapy needs to be reassessed in elderly patients, especially when they become acutely ill.

  12. Clozapine-induced severe mixed hyperlipidemia: a case report.

    LENUS (Irish Health Repository)

    Ahmed, Mohamed

    2009-01-01

    To highlight the association between the use of clozapine and the early development of severe mixed hyperlipidemia, a condition that substantially increases the risk of cardiovascular events and other medical complications.

  13. Early plasmapheresis in patients with severe hypertriglyceridemia induced acute pancreatitis

    OpenAIRE

    Nasa, Prashant; Alexander, George; Kulkarni, Amitabh; Juneja, Deven; Sehra, Sudhish; Agarwal, Rajesh; Koul, Kandy

    2015-01-01

    Hypertriglyceridemia can cause severe diseases such as acute pancreatitis (AP) and coronary artery disease. The routine management of hypertriglyceridemia is dietary restriction of fat and lipid-lowering medications to manage the secondary or precipitating causes of hypertriglyceridemia. However, in cases of AP with severe hypertriglyceridemia (SHTG) (triglycerides [TG] >1000 mg/dl) rapid reduction of TG levels to well below 1000 mg/dl can improve outcome and prevent further episodes of pancr...

  14. Correlation of Thyroid Functions with Severity and Outcome of ...

    African Journals Online (AJOL)

    During normal pregnancy, changes in thyroid function are well documented; however, information regarding thyroid function in preeclampsia is scanty. Pregnancy is associated with increased total thyroxine (T4) and, in preeclampsia, biochemical hypothyroidism (raised thyroid‑stimulating hormone [TSH]) occurs.

  15. Differential antibiotic-induced endotoxin release in severe melioidosis

    NARCIS (Netherlands)

    Simpson, A. J.; Opal, S. M.; Angus, B. J.; Prins, J. M.; Palardy, J. E.; Parejo, N. A.; Chaowagul, W.; White, N. J.

    2000-01-01

    Severe melioidosis is a life-threatening, systemic bacterial infection caused by Burkholderia pseudomallei. A prospective, randomized treatment trial was conducted in northeast Thailand to compare ceftazidime (a penicillin-binding protein [PBP]-3-specific agent that causes release of large amounts

  16. Which functional parameters can help differentiate severe asthma from COPD?

    Directory of Open Access Journals (Sweden)

    Ricardo Marques Dias

    2010-03-01

    Full Text Available The aim of this study was to identify the respiratory function parameters that help in the accurate diagnosis of asthma and COPD. We studied 20 asthma and 30 COPD patients who underwent lung function tests including spirometry and plethysmography both with bronchodilator test and diffusion with carbon monoxide (DLCO. The tests were performed according to International Guidelines (ATS/ERS. The asthma patients were younger (mean age = 48 than those in the COPD group (mean age = 59 and this group also had more female patients (65% than the COPD group (40%. The results showed a more severe obstruction in the asthma group: FEV1/FVC = 59% versus 66% for COPD. There was also a greater bronchodilator response as shown by changes in absolute and percentage values for FEV1 in the asthma group. Average DLCO values were normal in the asthma group (103%P and lower in the COPD (69%. In plethysmography the asthma group had a higher residual volume (%P and a higher airway resistance. We concluded that many functional parameters were useful in distinguishing the asthma and COPD groups. In individual analysis, DLCO was the parameter which best aided in an accurate diagnosis in both groups, with a higher specificity for COPD. The bronchodilator response measured by changes in FEV1 showed a higher sensitivity for asthma. Thus, these two tests are highlighted in the differential diagnosis of obstructive diseases. Resumo: Com o objectivo de identificar parâmetros funcionais respiratórios que contribuam para o diagnóstico diferencial entre asma e DPOC, estudámos 20 asmáticos e 30 bronquíticos, com ou sem enfisema, com os exames usuais de função pulmonar: espirografia, pletismografia e DLCO, pré e pós-broncodilatação para os dois primeiros exames. Os grupos apresentam diferenças significativas na sua constituição. Os asmáticos são mais jovens, média de 48 anos, contra 59 anos no grupo com DPOC, e o

  17. Relations among several nuclear and electronic density functional reactivity indexes

    Science.gov (United States)

    Torrent-Sucarrat, Miquel; Luis, Josep M.; Duran, Miquel; Toro-Labbé, Alejandro; Solà, Miquel

    2003-11-01

    An expansion of the energy functional in terms of the total number of electrons and the normal coordinates within the canonical ensemble is presented. A comparison of this expansion with the expansion of the energy in terms of the total number of electrons and the external potential leads to new relations among common density functional reactivity descriptors. The formulas obtained provide explicit links between important quantities related to the chemical reactivity of a system. In particular, the relation between the nuclear and the electronic Fukui functions is recovered. The connection between the derivatives of the electronic energy and the nuclear repulsion energy with respect to the external potential offers a proof for the "Quantum Chemical le Chatelier Principle." Finally, the nuclear linear response function is defined and the relation of this function with the electronic linear response function is given.

  18. Effect of joint traction on functional improvement and quality of life in patients with severe knee osteoarthritis

    OpenAIRE

    Sedigheh Sadat Naeimee; Abbas Rahimi; Mehdi Rezaee; Alireza Akbarzadeh Baghban; Khosro Khademi Kalantari; ُSomayeh Mahmoudi Aghdam

    2012-01-01

    Background and aim: Osteoarthritis (OA) is the most prevalent joint disease in adults around the world and its incidence rises with age. Patients with severe knee osteoarthritis often complain of pain and severe functional disability. Most of conservative treatments used in this group of patients induce poor improvements. This study evaluated the effect of joint traction on quality of life of patients with severe knee osteoarthritis.Materials and Methods: In this clinical trial study, forty f...

  19. Regorafenib induced severe toxic hepatitis: characterization and discussion.

    Science.gov (United States)

    Sacré, Anne; Lanthier, Nicolas; Dano, Hélène; Aydin, Selda; Leggenhager, Daniela; Weber, Achim; Dekairelle, Anne-France; De Cuyper, Astrid; Gala, Jean-Luc; Humblet, Yves; Sempoux, Christine; Van den Eynde, Marc

    2016-11-01

    Regorafenib is the first small-molecule multikinase inhibitor which showed survival benefits in pretreated metastatic colorectal cancer (mCRC) patients. Besides classical adverse events of this drug class, hepatotoxicity has been described as a frequent side effect. Patients with refractory mCRC treated with regorafenib in our institution were reviewed. Severe treatment-related liver toxicity was investigated. Clinical history, liver histology and genetic assessment (sequence analysis) of cytochrome P3A4 (CYP3A4) and uridine diphosphate-glucuronosyltransferase 1A9 (UGT1A9) involved in regorafenib metabolization were here reported for patients with severe hepatotoxicity. Among the 93 reviewed patients, 3 presented severe and icteric toxic hepatitis which was fatal for 1 patient. Histopathological liver lesions were different depending on the onset of hepatotoxicity (acute or subacute): acinar zone 3 necrosis in case of acute symptoms, and portal tract inflammation with porto-central bridging and fibrosis in the delayed presentation. None of the patients had CYP3A4 gene mutations. Similar polymorphisms in UGT1A9 gene promoter region (UGT1A9 variant -118T 9>10 [rs3832043]) were found in both patients who presented acute hepatitis. Moreover, it appears retrospectively that both of them already experienced significant toxicity under irinotecan-based chemotherapy. This is the first report of severe hepatotoxicity with available liver histology and genetic assessment of enzymes involved in regorafenib metabolization. This report also reminds the importance of close liver tests monitoring during regorafenib treatment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Spirometry quality in adults with very severe lung function impairment.

    Science.gov (United States)

    Torre-Bouscoulet, Luis; Velázquez-Uncal, Mónica; García-Torrentera, Rogelio; Gochicoa-Rangel, Laura; Fernández-Plata, Rosario; Enright, Paul; Pérez-Padilla, Rogelio

    2015-05-01

    Some technologists worry that patients with very severe lung disease are unable to complete several spirometry maneuvers, which require considerable effort. We retrospectively selected all spirometry tests with an FEV1 30,000 subjects tested during the 3-y period) had adequate quality spirometry. Subjects with airway obstruction were less likely to meet FVC repeatability goals. A poor spirometry quality grade was associated with a very low FVC and a low body mass index, but not older age. Severe lung disease should not be used as an excuse for not meeting spirometry quality goals. Copyright © 2015 by Daedalus Enterprises.

  1. Improved WKB radial wave functions in several bases

    International Nuclear Information System (INIS)

    Durand, B.; Durand, L.; Department of Physics, University of Wisconsin, Madison, Wisconsin 53706)

    1986-01-01

    We develop approximate WKB-like solutions to the radial Schroedinger equation for problems with an angular momentum barrier using Riccati-Bessel, Coulomb, and harmonic-oscillator functions as basis functions. The solutions treat the angular momentum singularity near the origin more accurately in leading approximation than the standard WKB solutions based on sine waves. The solutions based on Riccati-Bessel and free Coulomb wave functions continue smoothly through the inner turning point and are appropriate for scattering problems. The solutions based on oscillator and bound Coulomb wave functions incorporate both turning points smoothly and are particularly appropriate for bound-state problems; no matching of piecewise solutions using Airy functions is necessary

  2. Baking soda induced severe metabolic alkalosis in a haemodialysis patient.

    Science.gov (United States)

    Solak, Yalcin; Turkmen, Kultigin; Atalay, Huseyin; Turk, Suleyman

    2009-08-01

    Metabolic alkalosis is a rare occurence in hemodialysis population compared to metabolic acidosis unless some precipitating factors such as nasogastric suction, vomiting and alkali ingestion or infusion are present. When metabolic alkalosis develops, it may cause serious clinical consequences among them are sleep apnea, resistent hypertension, dysrhythmia and seizures. Here, we present a 54-year-old female hemodialysis patient who developed a severe metabolic alkalosis due to baking soda ingestion to relieve dyspepsia. She had sleep apnea, volume overload and uncontrolled hypertension due to metabolic alkalosis. Metabolic alkalosis was corrected and the patient's clinical condition was relieved with negative-bicarbonate hemodialysis.

  3. Congenital Zika Virus Infection Induces Severe Spinal Cord Injury.

    Science.gov (United States)

    Ramalho, Fernando S; Yamamoto, Aparecida Y; da Silva, Luis L; Figueiredo, Luiz T M; Rocha, Lenaldo B; Neder, Luciano; Teixeira, Sara R; Apolinário, Letícia A; Ramalho, Leandra N Z; Silva, Deisy M; Coutinho, Conrado M; Melli, Patrícia P; Augusto, Marlei J; Santoro, Ligia B; Duarte, Geraldo; Mussi-Pinhata, Marisa M

    2017-08-15

    We report 2 fatal cases of congenital Zika virus (ZIKV) infection. Brain anomalies, including atrophy of the cerebral cortex and brainstem, and cerebellar aplasia were observed. The spinal cord showed architectural distortion, severe neuronal loss, and microcalcifications. The ZIKV proteins and flavivirus-like particles were detected in cytoplasm of spinal neurons, and spinal cord samples were positive for ZIKV RNA. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  4. From moderately severe to severe hypertriglyceridemia induced acute pancreatitis: circulating miRNAs play role as potential biomarkers.

    Directory of Open Access Journals (Sweden)

    Fangmei An

    Full Text Available The incidence of hypertriglyceridemia induced acute pancreatitis (HTAP continues to rise in China. It has systemic complications and high mortality, making the early assessment of the severity of this disease even more important. Circulating microRNAs (miRNAs could be novel, non-invasive biomarkers for disease progression judgment. This study aimed to identify the potential role of serum miRNAs as novel biomarkers of HTAP progression. HTAP patients were divided into two groups: moderately severe (HTMSAP and severe (HTSAP, healthy people were used as control group. The serum miRNA expression profiles of these three groups were determined by microarray and verified by qRT-PCR. The functions and pathways of the targeted genes of deregulated miRNAs were predicted, using bioinformatics analysis; miRNA-mRNA network was generated. Moreover, the correlation between miR-181a-5p and pancreatitis metabolism related substances were studied and the serum concentration of inflammatory cytokines and miRNAs at different time points during the MSAP and SAP were investigated, respectively. Finally, the receiver operating characteristic (ROC curve of miRNAs was studied. Significant changes in the serum concentration of the following miRNAs of HTAP patients (P<0.05 were discovered: miR24-3p, 361-5p, 1246, and 222-3p (constantly upregulated, and 181a-5p (constantly downregulated (P<0.05. Bioinformatics analysis predicted that 13 GOs and 36 pathways regulated by overlap miRNAs were involved in glucose, fat, calcium (Ca++, and insulin metabolism (P<0.001. miRNA-mRNA network revealed that the overlap miRNAs targeted genes participating in pancreas metabolism and miR-181a-5p, the only downregulated miRNA, had good negative correlation with triglyceride (TG, total cholesterol (TC, and fast blood glucose (FBG, but a positive correlation with Ca++. When compared with inflammatory cytokines, the changes of all five overlap miRNAs were more stable. It was found that when

  5. A reliable, practical, and economical protocol for inducing diarrhea and severe dehydration in the neonatal calf.

    Science.gov (United States)

    Walker, P G; Constable, P D; Morin, D E; Drackley, J K; Foreman, J H; Thurmon, J C

    1998-07-01

    Fifteen healthy, colostrum-fed, male dairy calves, aged 2 to 7 d were used in a study to develop a diarrhea protocol for neonatal calves that is reliable, practical, and economical. After instrumentation and recording baseline data, diarrhea and dehydration were induced by administering milk replacer [16.5 mL/kg of body weight (BW), PO], sucrose (2 g/kg in a 20% aqueous solution, p.o.), spironolactone and hydrochlorothiazide (1 mg/kg, PO) every 8 h, and furosemide (2 mg/kg, i.m., q6h). Calves were administered sucrose and diuretic agents for 48 h to induce diarrhea and severe dehydration. Clinical changes after 48 h were severe watery diarrhea, severe depression, and marked dehydration (mean, 14% BW loss). Cardiac output, stroke volume, mean central venous pressure, plasma volume, thiocyanate space, blood pH and bicarbonate concentration, base excess, serum chloride concentration, and fetlock temperature were decreased. Plasma lactate concentration, hematocrit, and serum potassium, creatinine, phosphorus, total protein and albumin concentrations were increased. This non-infectious calf diarrhea protocol has a 100% response rate, while providing a consistent and predictable hypovolemic state with diarrhea that reflects most of the clinicopathologic changes observed in osmotic/maldigestive diarrhea caused by infection with rotavirus, coronavirus or cryptosporidia. Limitations of the protocol, when compared to infectious diarrhea models, include failure to induce a severe metabolic acidosis, absence of hyponatremia, renal instead of enteric loss of chloride, renal as well as enteric loss of free water, absence of profound clinical depression and suspected differences in the morphologic and functional effect on intestinal epithelium. Despite these differences, the sucrose/diuretic protocol should be useful in the initial screening of new treatment modalities for calf diarrhea. To confirm their efficacy, the most effective treatment methods should then be examined in

  6. Isolated medulla oblongata function after severe traumatic brain injury

    OpenAIRE

    Wijdicks, E; Atkinson, J; Okazaki, H

    2001-01-01

    The objective was to report the first pathologically confirmed case of partly functionally preserved medulla oblongata in a patient with catastrophic traumatic brain injury.
A patient is described with epidural haematoma with normal breathing and blood pressure and a retained coughing reflex brought on only by catheter suctioning of the carina. Multiple contusions in the thalami and pons were found but the medulla oblongata was spared at necropsy. 
In conclusion, medulla oblong...

  7. Effect of respiratory function training on respiratory function of patients with severe cerebrovascular disease

    Directory of Open Access Journals (Sweden)

    Ming GUO

    2017-07-01

    Full Text Available Objective To investigate the effect of respiratory function training on respiratory function and conscious state of patients with severe cerebrovascular disease (SCVD.  Methods A total of 27 patients with SCVD were divided into control group (N = 17 and observation group (N = 10. Control group received routine drug and rehabilitation treatment, and observation group was added respiratory function training based on routine treatment. The respiratory rate, tidal volume (TV, heart rate, blood pressure and artery oxygen saturation (SaO2 of patients were monitored by breathing machine before and after 4-week treatment. Meanwhile, arterial blood gas analysis was used to detect arterial partial pressure of oxygen (PaO2, oxygenation index, partial pressure of carbon dioxide (PaCO2 and pH value. At the same time, Glasgow Coma Scale (GCS was used to evaluate the conscious state of patients.  Results All patients successfully completed 4-week rehabilitation training, without asphyxia, arrhythmia or other adverse events. Compared with before training, the respiratory rate (P = 0.006 and pH value (P = 0.010 were significantly decreased, while SaO2 (P = 0.001, oxygenation index (P = 0.000 and GCS scores (P = 0.004, 0.017 were significantly increased in both groups of patients after training. There was no statistically significant difference between 2 groups on respiratory function indexes and GCS scores after training (P > 0.05, for all. Conclusions Respiratory function training did not significantly improve the respiratory function and conscious state of patients with SCVD, yet to be further studied. Randomized controlled clinical trials with larger, layered samples and long-term prognosis observation are needed. Examination method of respiratory function of SCVD patients is also a topic to be explored.  DOI: 10.3969/j.issn.1672-6731.2017.04.007

  8. Severe non-anion gap metabolic acidosis induced by topiramate: a case report.

    Science.gov (United States)

    Shiber, Joseph R

    2010-05-01

    A non-anion gap acidosis can be induced by topiramate, causing symptomatic dyspnea and confusion. Discuss the pathophysiology of the hyperchloremic metabolic acidosis caused by topiramate, the typical clinical presentation, and the recommended treatment. This case presents a young woman with a clinically significant non-anion gap metabolic acidosis believed to be caused by topiramate. She had been taking the medication for several months without prior adverse effects. Once she began having dyspnea as a respiratory response to the renal tubule acidosis, she had decreased oral intake of food and fluids, which induced a pre-renal acute renal failure that worsened her acidemia. In the Emergency Department, she received intravenous fluids and sodium bicarbonate, and later was intubated for mechanical ventilation due to respiratory fatigue. With the topiramate withdrawn, the patient had a full recovery of her renal function and metabolic acid-base status over the next 72 h. This case serves to increase awareness of this possible adverse effect and the recommended treatment as topiramate becomes more widely used. Topiramate can induce a renal tubule acidosis resulting in a hyperchloremic metabolic acidosis. Recognition of the underlying cause is crucial so that the drug can be withdrawn while supportive care is provided. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  9. Age and Adaptive Functioning in Children and Adolescents with ASD: The Effects of Intellectual Functioning and ASD Symptom Severity.

    Science.gov (United States)

    Hill, Trenesha L; Gray, Sarah A O; Kamps, Jodi L; Enrique Varela, R

    2015-12-01

    The present study examined the moderating effects of intellectual functioning and ASD symptom severity on the relation between age and adaptive functioning in 220 youth with autism spectrum disorder (ASD). Regression analysis indicated that intellectual functioning and ASD symptom severity moderated the relation between age and adaptive functioning. For younger children with lower intellectual functioning, higher ASD symptom severity was associated with better adaptive functioning than that of those with lower ASD symptom severity. Similarly, for older children with higher intellectual functioning, higher ASD symptom severity was associated with better adaptive functioning than that of those with lower ASD symptom severity. Analyses by subscales suggest that this pattern is driven by the Conceptual subscale. Clinical and research implications are discussed.

  10. Evaluation of the field relevance of several injury risk functions.

    Science.gov (United States)

    Prasad, Priya; Mertz, Harold J; Dalmotas, Danius J; Augenstein, Jeffrey S; Diggs, Kennerly

    2010-11-01

    An evaluation of the four injury risk curves proposed in the NHTSA NCAP for estimating the risk of AIS>= 3 injuries to the head, neck, chest and AIS>=2 injury to the Knee-Thigh-Hip (KTH) complex has been conducted. The predicted injury risk to the four body regions based on driver dummy responses in over 300 frontal NCAP tests were compared against those to drivers involved in real-world crashes of similar severity as represented in the NASS. The results of the study show that the predicted injury risks to the head and chest were slightly below those in NASS, and the predicted risk for the knee-thigh-hip complex was substantially below that observed in the NASS. The predicted risk for the neck by the Nij curve was greater than the observed risk in NASS by an order of magnitude due to the Nij risk curve predicting a non-zero risk when Nij = 0. An alternative and published Nte risk curve produced a risk estimate consistent with the NASS estimate of neck injury. Similarly, an alternative and published chest injury risk curve produced a risk estimate that was within the bounds of the NASS estimates. No published risk curve for femur compressive load could be found that would give risk estimates consistent with the range of the NASS estimates. Additional work on developing a femur compressive load risk curve is recommended.

  11. Severe diarrhea-dehydration in infancy permanently alters auditory function.

    Science.gov (United States)

    Todd, N Wendell

    2012-02-01

    Of the myriad etiologies of sensorineural hearing impairment, metabolic stress is rarely considered. I posit that severe dehydration in conjunction with hypoxia, at least during infancy, prompts permanent changes in the cochlea. In a population-based prospective study of otitis media, children without otitis were found to have at age 4-8 years, worse auditory thresholds if as an infant had been hospitalized for diarrhea-dehydration. What is more, stapedius reflex thresholds tended to be lower in children who had been hospitalized for diarrhea-dehydration: that is, less acoustic energy for arousal or to be frightening. The hypothesis that the transient metabolic stress of dehydration with hypoxia prompts permanent sensorineural hearing impairment with reduced uncomfortable loudness thresholds, is both (1) consistent in an evolutionary sense with a subsequent survival advantage, and (2) subject to verification both by descriptive studies of children undergoing ECMO (ExtraCorporeal Membrane Oxygenation) or care for congenital diaphragmatic hernia, and by animal studies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Structural and functional analysis of APOA5 mutations identified in patients with severe hypertriglyceridemia[S

    Science.gov (United States)

    Mendoza-Barberá, Elena; Julve, Josep; Nilsson, Stefan K.; Lookene, Aivar; Martín-Campos, Jesús M.; Roig, Rosa; Lechuga-Sancho, Alfonso M.; Sloan, John H.; Fuentes-Prior, Pablo; Blanco-Vaca, Francisco

    2013-01-01

    During the diagnosis of three unrelated patients with severe hypertriglyceridemia, three APOA5 mutations [p.(Ser232_Leu235)del, p.Leu253Pro, and p.Asp332ValfsX4] were found without evidence of concomitant LPL, APOC2, or GPIHBP1 mutations. The molecular mechanisms by which APOA5 mutations result in severe hypertriglyceridemia remain poorly understood, and the functional impairment/s induced by these specific mutations was not obvious. Therefore, we performed a thorough structural and functional analysis that included follow-up of patients and their closest relatives, measurement of apoA-V serum concentrations, and sequencing of the APOA5 gene in 200 nonhyperlipidemic controls. Further, we cloned, overexpressed, and purified both wild-type and mutant apoA-V variants and characterized their capacity to activate LPL. The interactions of recombinant wild-type and mutated apoA-V variants with liposomes of different composition, heparin, LRP1, sortilin, and SorLA/LR11 were also analyzed. Finally, to explore the possible structural consequences of these mutations, we developed a three-dimensional model of full-length, lipid-free human apoA-V. A complex, wide array of impairments was found in each of the three mutants, suggesting that the specific residues affected are critical structural determinants for apoA-V function in lipoprotein metabolism and, therefore, that these APOA5 mutations are a direct cause of hypertriglyceridemia. PMID:23307945

  13. Hypoxic pretreatment protects against neuronal damage of the rat hippocampus induced by severe hypoxia.

    Science.gov (United States)

    Gorgias, N; Maidatsi, P; Tsolaki, M; Alvanou, A; Kiriazis, G; Kaidoglou, K; Giala, M

    1996-04-01

    The present study investigates whether under conditions of successive hypoxic exposures pretreatment with mild (15% O(2)) or moderate (10% O(2)) hypoxia, protects hippocampal neurones against damage induced by severe (3% O(2)) hypoxia. The ultrastructural findings were also correlated with regional superoxide dismutase (SOD) activity changes. In unpretreated rats severe hypoxia induced ultrastructural changes consistent with the aspects of delayed neuronal death (DND). However, in preexposed animals hippocampal damage was attenuated in an inversely proportional way with the severity of the hypoxic pretreatment. The ultrastructural hypoxic tolerance findings were also closely related to increased regional SOD activity levels. Thus the activation of the endogenous antioxidant defense by hypoxic preconditioning, protects against hippocampal damage induced by severe hypoxia. The eventual contribution of increased endogenous adenosine and/or reduced excitotoxicity to induce hypoxic tolerance is discussed.

  14. Electron Beam Induced Functionalization of Fluoropolymers

    International Nuclear Information System (INIS)

    Lappan, U.

    2006-01-01

    Ionizing radiation affects the properties of polymers by chain scission and cross-linking reactions. One process will usually predominate, depending on the chemical structure of the polymer and the irradiation conditions such as temperature and atmosphere. Poly(tetrafluoroethylene) (PTFE) and the perfluorinated copolymers poly(tetrafluoroethylene-co-hexafluoropropylene) (FEP) and poly(tetrafluoroethylene-co-perfluoropropylvinyl ether) (PFA) undergo predominantly chain scission, if the irradiation is performed at room temperature. This shortcoming is exploited by converting PTFE into low molecular weight micropowders. The irradiation of PTFE in the presence of air results in micropowders functionalized with oxygen-containing groups. The concentration of end groups was investigated by FTIR and 19F solid-state NMR. The data were used to calculate number-average molecular weights. It was demonstrated that PTFE can be cross-linked by irradiation above its crystalline melting temperature in an oxygen-free atmosphere. Evidence for cross-links in PTFE was derived directly from structural information using 19 F solid-state NMR. FEP is understood to undergo cross-linking by irradiation above the glass transition temperature. It was found that also PFA can be branched and cross-linked by irradiation under special conditions. Radiation-induced grafting of styrene into fluoropolymer films and subsequent sulfonation offers an attractive way to prepare proton exchange membranes. Recently, radiation-induced grafting into cross-linked PTFE was reported. Modified FEP, PFA and ETFE films have been used as base material in this study. The modified films have been prepared by irradiation in nitrogen atmosphere at different temperatures up to temperatures above the melting temperature of the fluoropolymer

  15. Hsp72 preserves muscle function and slows progression of severe muscular dystrophy.

    Science.gov (United States)

    Gehrig, Stefan M; van der Poel, Chris; Sayer, Timothy A; Schertzer, Jonathan D; Henstridge, Darren C; Church, Jarrod E; Lamon, Severine; Russell, Aaron P; Davies, Kay E; Febbraio, Mark A; Lynch, Gordon S

    2012-04-04

    Duchenne muscular dystrophy (DMD) is a severe and progressive muscle wasting disorder caused by mutations in the dystrophin gene that result in the absence of the membrane-stabilizing protein dystrophin. Dystrophin-deficient muscle fibres are fragile and susceptible to an influx of Ca(2+), which activates inflammatory and muscle degenerative pathways. At present there is no cure for DMD, and existing therapies are ineffective. Here we show that increasing the expression of intramuscular heat shock protein 72 (Hsp72) preserves muscle strength and ameliorates the dystrophic pathology in two mouse models of muscular dystrophy. Treatment with BGP-15 (a pharmacological inducer of Hsp72 currently in clinical trials for diabetes) improved muscle architecture, strength and contractile function in severely affected diaphragm muscles in mdx dystrophic mice. In dko mice, a phenocopy of DMD that results in severe spinal curvature (kyphosis), muscle weakness and premature death, BGP-15 decreased kyphosis, improved the dystrophic pathophysiology in limb and diaphragm muscles and extended lifespan. We found that the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA, the main protein responsible for the removal of intracellular Ca(2+)) is dysfunctional in severely affected muscles of mdx and dko mice, and that Hsp72 interacts with SERCA to preserve its function under conditions of stress, ultimately contributing to the decreased muscle degeneration seen with Hsp72 upregulation. Treatment with BGP-15 similarly increased SERCA activity in dystrophic skeletal muscles. Our results provide evidence that increasing the expression of Hsp72 in muscle (through the administration of BGP-15) has significant therapeutic potential for DMD and related conditions, either as a self-contained therapy or as an adjuvant with other potential treatments, including gene, cell and pharmacological therapies.

  16. Permanent Pacemaker Lead Induced Severe Tricuspid Regurgitation in Patient Undergoing Multiple Valve Surgery

    Directory of Open Access Journals (Sweden)

    Jung Hee Lee

    2015-04-01

    Full Text Available Severe and permanent tricuspid regurgitation induced by pacemaker leads is rarely reported in the literature. The mechanism of pacemaker-induced tricuspid regurgitation has been identified, but its management has not been well established. Furthermore, debate still exists regarding the proper surgical approach. We present the case of a patient with severe tricuspid regurgitation induced by a pacemaker lead, accompanied by triple valve disease. The patient underwent double valve replacement and tricuspid valve repair without removal of the pre-existing pacemaker lead. The operation was successful and the surgical procedure is discussed in detail.

  17. Permanent pacemaker lead induced severe tricuspid regurgitation in patient undergoing multiple valve surgery.

    Science.gov (United States)

    Lee, Jung Hee; Kim, Tae Ho; Kim, Wook Sung

    2015-04-01

    Severe and permanent tricuspid regurgitation induced by pacemaker leads is rarely reported in the literature. The mechanism of pacemaker-induced tricuspid regurgitation has been identified, but its management has not been well established. Furthermore, debate still exists regarding the proper surgical approach. We present the case of a patient with severe tricuspid regurgitation induced by a pacemaker lead, accompanied by triple valve disease. The patient underwent double valve replacement and tricuspid valve repair without removal of the pre-existing pacemaker lead. The operation was successful and the surgical procedure is discussed in detail.

  18. Exercise-induced changes in left ventricular global longitudinal strain in asymptomatic severe aortic stenosis.

    Science.gov (United States)

    Lech, Agnieszka K; Dobrowolski, Piotr P; Klisiewicz, Anna; Hoffman, Piotr

    2017-01-01

    The management of patients with asymptomatic severe aortic stenosis (ASAS) is still under discussion. Therefore, it is advisable to search for the parameters of early damage to left ventricular (LV) function. The aim of the study was to assess exercise-induced changes in LV global longitudinal strain (GLS) in ASAS. The ASAS group consisted of 50 patients (26 women and 24 men, aged 38.4 ± 18.1 years) meeting the echocardiographic criteria of severe aortic stenosis (AVA 4 m/s, mean aortic gradient > 40 mm Hg), with normal LV ejection fraction (LVEF ≥ 55%) and sinus rhythm on electrocardiogram, and without significant concomitant valvular heart diseases. The control group consisted of 21 people matched for age and sex. Echocardiographic examinations and echocardiographic stress tests with the assessment of GLS using the speckle tracking imaging were performed. The ASAS group was characterised by statistically significantly higher LV mass index (LVMI) and higher LVEF. GLS values at rest in both groups were within normal limits but were significantly higher in the control group (-18.9 ± 2.4% vs. -20.7 ± 1.7%, p = 0.006). An increase in GLS at peak exercise in both groups was observed, lower in the ASAS group (the difference was not statistically significant: -0.8 ± 3.0% vs. -2.2 ± 3.1%, p = 0.086). Changes in GLS during exercise (ΔGLS) did not correlate with the parameters of the severity of aortic stenosis. In the multivariate model, LVMI proved to be a factor associated with GLS at rest and during exercise. In patients with ASAS, GLS is a non-invasive marker of an early stage of LV myocardial damage associated with myocardial hypertrophy. An increase in GLS during exercise in the ASAS group, smaller than in the control group, indicates a preserved functional reserve of the LV myocardium but smaller than in healthy individuals. The assessment of the clinical usefulness of exercise-induced changes in GLS requires further research.

  19. Management and outcomes in patients with moderate or severe functional mitral regurgitation and severe left ventricular dysfunction

    DEFF Research Database (Denmark)

    Samad, Zainab; Shaw, Linda K; Phelan, Matthew

    2015-01-01

    AIMS: The management and outcomes of patients with functional moderate/severe mitral regurgitation and severe left ventricular (LV) systolic dysfunction are not well defined. We sought to determine the characteristics, management strategies, and outcomes of patients with moderate or severe mitral...... fraction ≤ 30% or LV end-systolic diameter > 55 mm). We examined treatment effects in two ways. (i) A multivariable Cox proportional hazards model was used to assess the independent relationship of different treatment strategies and long-term event (death, LV assist device, or transplant)-free survival...... [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.42-0.76] and CABG with MV surgery (HR 0.58, 95% CI 0.44-0.78) were associated with long-term, event-free survival benefit. Percutaneous intervention treatment produced a borderline result (HR 0.78, 95% CI 0.61-1.00). However, the relationship...

  20. Blood eosinophil counts for the prediction of the severity of exercise-induced bronchospasm in asthma.

    Science.gov (United States)

    Koh, Y I; Choi, S

    2002-02-01

    It has been suggested that airway eosinophilic inflammation is associated with the severity of exercise-induced bronchospasm (EIB). Blood eosinophils are known to be an indirect marker of airway inflammation in asthma. The aim of this study is to investigate that a simple and easy blood test for blood eosinphil counts may predict the severity of EIB in asthma. Seventy-seven men with perennial asthma (age range 18-23 years) were included. Lung function test, skin prick test, and blood tests for eosinophils counts and total IgE levels were performed. Methacholine bronchial provocation test and, 24 h later, free running test were carried out. EIB was defined as a 15% reduction or more in post-exercise FEV1 compared with pre-exercise FEV1 value. Atopy score was defined as a sum of mean wheal diameters to allergens. EIB was observed in 60 (78%) of 77 subjects. Asthmatics with EIB showed significantly increased percentages of eosinophils (P 700 microl(-1) (36.9 +/- 12.7%) had significantly greater maximal % fall in FEV1 after exercise than asthmatics with eosinophils of 350 microl(-1) yielded the specificity of 88% and positive predictive value of 93% for the presence of EIB. When a multiple regression analysis of maximal % fall in FEV1 according to log eosinophil counts, log PC20, log IgE and atopy score was performed, only blood eosinophil counts were significant factor contributing to the maximal % fall in FEV1 after exercise. These findings not only suggest that a simple blood test for eosinophils may be useful in the prediction of the severity of EIB, but also reinforce the view that airway eosinophilic inflammation may play a major role in EIB in asthma.

  1. The effectiveness of the treatment of severe exercise-induced asthma in schoolchildren

    Directory of Open Access Journals (Sweden)

    M.N. Garas

    2017-03-01

    Full Text Available Background. Bronchial asthma is one of the most common chronic multifactorial diseases of the lungs. At least 10–12 % of patients with bronchial asthma are suffering from a severe form of the disease. One aspect of inadequate severe asthma control is its phenotypic heterogeneity, interest of experts increases to the problem of exercise-induced asthma. The purpose of the study was to increase efficiency of treatment for severe exercise-induced asthma in schoolchildren based on the analysis of the attack dynamics and to achieve disease control according to main inflammatometric and spirometric indices. Materials and methods. We examined 46 children with severe persistent bronchial asthma, in particular, 15 schoolchildren suffering from severe exercise-induced asthma, the second clinical group (comparison one consisted of 31 children suffering from severe type of the disease, with no signs of exercise-induced bronchoconstriction. Basic therapy effectiveness was determined prospectively by assessing the disease control using AST-test with an interval of 3 months. The severity of bronchial obstruction syndrome in patients on admission to hospital during exacerbation was assessed by score scale. Airway hyperresponsiveness was evaluated according to the results of bronchoprovocation with histamine. Results. Children of I clinical group had more significant manifestations of bronchial obstruction during the week of inpatient treatment than the comparison group of patients, including significantly more severe manifestations of bronchial obstruction were verified on 1st and 7th day of hospitalization. Due to the analysis of basic therapy effectiveness, only a quarter of I clinical group patients and a larger part of schoolchildren in comparison group achieved the partial control after a 3-month course of anti-inflammatory treatment. Eosinophilic inflammation was observed in most children with severe exercise-induced asthma (60.1 % and in 47.2 % of

  2. Eating disorder severity and functional impairment: moderating effects of illness duration in a clinical sample.

    Science.gov (United States)

    Davidsen, Annika Helgadóttir; Hoyt, William T; Poulsen, Stig; Waaddegaard, Mette; Lau, Marianne

    2017-09-01

    The aim was to examine duration of illness and body mass index as possible moderators of the relationship between eating disorder severity and functional impairment, as well as psychological distress as a possible mediator of this relationship. The study included 159 patients diagnosed with bulimia nervosa, binge eating disorder or eating disorder not otherwise specified. Regression analysis was applied to assess the effect of the hypothesized moderators and mediators. Eating disorder severity was measured with the Eating Disorder Examination Questionnaire, functional impairment was measured with the Sheehan Disability Scale, and psychological distress was measured with the Symptom Check List-90-R. Duration of illness and body mass index were assessed clinically. Duration of illness significantly moderated the relationship between eating disorder severity and functional impairment; the relationship was strongest for patients with a shorter duration of illness. Psychological distress partly mediated the relationship between eating disorder severity and functional impairment. Duration of illness significantly moderated the relationship between psychological distress and functional impairment; the strongest relationship was seen for patients with a shorter duration of illness. Body mass index was not a significant moderator of the relationship between ED severity and functional impairment. Overall, this study established a link between ED severity, psychological distress and functional impairment indicating that both eating disorder severity and psychological distress are more strongly related to impaired role functioning for patients with more recent onset of an eating disorder. More research in the complex relationship between ED severity and functional impairment is needed.

  3. A Functional Analysis of Gestural Behaviors Emitted by Young Children with Severe Developmental Disabilities

    Science.gov (United States)

    Ferreri, Summer J.; Plavnick, Joshua B.

    2011-01-01

    Many children with severe developmental disabilities emit idiosyncratic gestures that may function as verbal operants (Sigafoos et al., 2000). This study examined the effectiveness of a functional analysis methodology to identify the variables responsible for gestures emitted by 2 young children with severe developmental disabilities. Potential…

  4. Corrections Regarding the Impedance of Distance Functions for Several g(d) Functions

    Science.gov (United States)

    Beaman, Jay

    1976-01-01

    Five functions were introduced for modeling travel behavior in the Beaman article "Distance and the 'Reaction' to Distance as a Function of Distance" published in Vol. 6, No. 3 of "Journal of Leisure Research" with the graphs of the functions printed incorrectly. This is a corrected version. (MM)

  5. Differential relationship between depression severity and patients' perceived family functioning in women versus in men.

    Science.gov (United States)

    Febres, Jeniimarie; Rossi, Rita; Gaudiano, Brandon A; Miller, Ivan W

    2011-07-01

    Previous research suggests that depression and family functioning are related and that women and men may differ in how they respond to and cope with depression. Significantly less attention has been paid to whether sex moderates the relationship between family functioning and depression. In the current study, the relationship between depression severity and perceived family functioning, both generally and in specific areas, was examined in women and men (N = 117) hospitalized with major depression. The level of depression severity was not significantly different in men and in women. Correlations between depression severity and most domains of family functioning were significant and positive for men only. Furthermore, sex statistically moderated the associations between depression severity and family functioning in the areas of problem solving, communication, affective responsiveness, and behavior control. The implications for the assessment and treatment of family dysfunction in severely depressed patients are discussed.

  6. Virtual continuity of the measurable functions of several variables, and Sobolev embedding theorems

    OpenAIRE

    Vershik, Anatoly; Zatitskiy, Pavel; Petrov, Fedor

    2013-01-01

    Classical Luzin's theorem states that the measurable function of one variable is "almost" continuous. This is not so anymore for functions of several variables. The search of right analogue of the Luzin theorem leads to a notion of virtually continuous functions of several variables. This probably new notion appears implicitly in the statements like embeddings theorems and traces theorems for Sobolev spaces. In fact, it reveals their nature as theorems about virtual continuity. This notion is...

  7. Severe acute cholangitis after endoscopic sphincterotomy induced by barium examination: A case report.

    Science.gov (United States)

    Zhang, Zhen-Hai; Wu, Ya-Guang; Qin, Cheng-Kun; Su, Zhong-Xue; Xu, Jian; Xian, Guo-Zhe; Wu, Shuo-Dong

    2012-10-21

    Endoscopic sphincterotomy (EST) is considered as a possible etiological factor for severe cholangitis. We herein report a case of severe cholangitis after endoscopic sphincterotomy induced by barium examination. An adult male patient presented with epigastric pain was diagnosed as having choledocholithiasis by ultrasonography. EST was performed and the stone was completely cleaned. Barium examination was done 3 d after EST and severe cholangitis appeared 4 h later. The patient was recovered after treated with tienam for 4 d. Barium examination may induce severe cholangitis in patients after EST, although rare, barium examination should be chosen cautiously. Cautions should be also used when EST is performed in patients younger than 50 years to avoid the damage to the sphincter of Oddi.

  8. ESAT6-induced IFNgamma and CXCL9 can differentiate severity of tuberculosis.

    Directory of Open Access Journals (Sweden)

    Zahra Hasan

    Full Text Available BACKGROUND: Protective responses against Mycobacterium tuberculosis are dependent on appropriate T cell and macrophage activation. Mycobacterial antigen six kDa early secreted antigenic target (ESAT6 and culture filtrate protein 10 (CFP10 can detect M. tuberculosis specific IFNgamma responses. However, most studies have been performed in non-endemic regions and to study pulmonary tuberculosis (PTB. We have studied ESAT6 and CFP10 induced cytokine and chemokines responses in PTB and extrapulmonary (EPul TB. METHODOLOGY: IFNgamma, IL10, CXCL9 and CCL2 responses were determined using an ex vivo whole blood assay system in PTB (n = 30 and EPulTB patients with limited (LNTB, n = 24 or severe (SevTB, n = 22 disease, and in healthy endemic controls (ECs. Responses to bacterial LPS were also determined. PRINCIPAL FINDINGS: ESAT6- and CFP10-induced IFNgamma was comparable between ECs and TB patients. Both ESAT6- and CFP10-induced IFNgamma secretion was greater in LNTB than PTB. ESAT6-induced CXCL9 was greater in EPulTB as compared with PTB, with an increase in SevTB as compared with LNTB. CFP10-induced CCL2 was higher in PTB than LNTB patients. LPS-stimulated CXCL9 was greatest in SevTB and LPS-induced CCL2 was increased in PTB as compared with LNTB patients. A positive correlation between ESAT6-induced IFNgamma and CXCL9 was present in all TB patients, but IFNgamma and CCL2 was only correlated in LNTB. ESAT-induced CCL2 and CXCL9 were significantly associated in LNTB while correlation in response to LPS was only present in SevTB. CONCLUSIONS: ESAT6 induced IFNgamma and CXCL9 can differentiate between limited and severe TB infections.

  9. Analysis of 90 cases of antithyroid drug-induced severe hepatotoxicity over 13 years in China.

    Science.gov (United States)

    Yang, Jun; Li, Lin-Fa; Xu, Qin; Zhang, Jun; Weng, Wan-Wen; Zhu, Yang-Jun; Dong, Meng-Jie

    2015-03-01

    Antithyroid drug (ATD)-induced severe hepatotoxicity is a rare but serious complication of ATD therapy. The characteristics of severe hepatotoxicity have been reported in only a small number of patients. Ninety patients with ATD-induced severe hepatotoxicity presenting during a 13 year period (2000-2013) who were about to undergo nuclear medicine therapy with (131)I from a sample of 8864 patients with hyperthyroidism were studied, and the outcomes were evaluated. The mean age of the patients with ATD-induced severe hepatotoxicity was 41.6±12.5 years (mean±standard deviation), and the female to male ratio was 2.2:1. The methimazole (MMI) dose given at the onset was 19.1±7.4 mg/day. The propylthiouracil (PTU) dose given at the onset was 212.8±105.0 mg/day. ATD-induced severe hepatotoxicity occurred in 63.3%, 75.6%, and 81.1% of patients within 4, 8, and 12 weeks of the onset of ATD therapy, respectively. The types of severe hepatotoxicity did not differ significantly between the MMI and PTU groups (p=0.188). The frequency of the cholestatic type in the MMI group (35.3%, 18/51) was higher than that in the PTU group (17.9%, 7/39), but these frequencies were not significantly different (p=0.069). The patients who were treated with (131)I received an average dose of 279.1±86.1 MBq (n=84). Therapy was successful in 60 of the 67 patients (89.6%). The success rate was equivalent (p=0.696) between the groups receiving MMI (91.7%, 33/36) and PTU (87.1%, 27/31). Severe hepatotoxicity tends to occur within the first three months after the onset of ATD therapy. The type of ATD-induced severe hepatotoxicity did not differ between the MMI and PTU groups. (131)I therapy is an effective treatment approach for patients with ATD-induced severe hepatotoxicity.

  10. Prevention of Severe Hypoglycemia-Induced Brain Damage and Cognitive Impairment with Verapamil.

    Science.gov (United States)

    Jackson, David A; Michael, Trevin; Vieira de Abreu, Adriana; Agrawal, Rahul; Bortolato, Marco; Fisher, Simon J

    2018-05-03

    People with insulin-treated diabetes are uniquely at risk for severe hypoglycemia-induced brain damage. Since calcium influx may mediate brain damage, we tested the hypothesis that the calcium channel blocker, verapamil, would significantly reduce brain damage and cognitive impairment caused by severe hypoglycemia. Ten-week-old Sprague-Dawley rats were randomly assigned to one of three treatments; 1) control hyperinsulinemic (200 mU.kg -1 min -1 ) euglycemic (80-100mg/dl) clamps (n=14), 2) hyperinsulinemic hypoglycemic (10-15mg/dl) clamps (n=16), or 3) hyperinsulinemic hypoglycemic clamps followed by a single treatment with verapamil (20mg/kg) (n=11). As compared to euglycemic controls, hypoglycemia markedly increased dead/dying neurons in the hippocampus and cortex, by 16-fold and 14-fold, respectively. Verapamil treatment strikingly decreased hypoglycemia-induced hippocampal and cortical damage, by 87% and 94%, respectively. Morris Water Maze probe trial results demonstrated that hypoglycemia induced a retention, but not encoding, memory deficit (noted by both abolished target quadrant preference and reduced target quadrant time). Verapamil treatment significantly rescued spatial memory as noted by restoration of target quadrant preference and target quadrant time. In summary, a one-time treatment with verapamil following severe hypoglycemia prevented neural damage and memory impairment caused by severe hypoglycemia. For people with insulin treated diabetes, verapamil may be a useful drug to prevent hypoglycemia-induced brain damage. © 2018 by the American Diabetes Association.

  11. Family Functioning in First-Episode and Chronic Psychosis: The Role of Patient's Symptom Severity and Psychosocial Functioning.

    Science.gov (United States)

    Koutra, Katerina; Triliva, Sofia; Roumeliotaki, Theano; Basta, Maria; Lionis, Christos; Vgontzas, Alexandros N

    2016-08-01

    The aim of the present study was to assess the relationship between illness-related characteristics, such as symptom severity and psychosocial functioning, and specific aspects of family functioning both in patients experiencing their first episode of psychosis (FEP) and chronically ill patients. A total of 50 FEP and 50 chronic patients diagnosed with schizophrenia or bipolar disorder (most recent episode manic severe with psychotic features) and their family caregivers participated in the study. Family functioning was evaluated in terms of cohesion and flexibility (FACES IV Package), expressed emotion (FQ), family burden (FBS) and caregivers' psychological distress (GHQ-28). Patients' symptom severity (BPRS) and psychosocial functioning (GAS) were assessed by their treating psychiatrist within 2 weeks from the caregivers' assessment. Increased symptom severity was associated with greater dysfunction in terms of family cohesion and flexibility (β coefficient -0.13; 95 % CI -0.23, -0.03), increased caregivers' EE levels on the form of emotional overinvolvement (β coefficient 1.03; 95 % CI 0.02, 2.03), and psychological distress (β coefficient 3.37; 95 % CI 1.29, 5.45). Family burden was found to be significantly related to both symptom severity (β coefficient 3.01; 95 % CI 1.50, 4.51) and patient's functioning (β coefficient -2.04; 95 % CI -3.55, -0.53). No significant interaction effect of chronicity was observed in the afore-mentioned associations. These findings indicate that severe psychopathology and patient's low psychosocial functioning are associated with poor family functioning. It appears that the effect for family function is significant from the early stages of the illness. Thus, early psychoeducational interventions should focus on patients with severe symptomatology and impaired functioning and their families.

  12. Hippocampal structure and function are maintained despite severe innate peripheral inflammation.

    Science.gov (United States)

    Süß, Patrick; Kalinichenko, Liubov; Baum, Wolfgang; Reichel, Martin; Kornhuber, Johannes; Loskarn, Sandra; Ettle, Benjamin; Distler, Jörg H W; Schett, Georg; Winkler, Jürgen; Müller, Christian P; Schlachetzki, Johannes C M

    2015-10-01

    Chronic peripheral inflammation mediated by cytokines such as TNFα, IL-1β, and IL-6 is associated with psychiatric disorders like depression and anxiety. However, it remains elusive which distinct type of peripheral inflammation triggers neuroinflammation and affects hippocampal plasticity resulting in depressive-like behavior. We hypothesized that chronic peripheral inflammation in the human TNF-α transgenic (TNFtg) mouse model of rheumatoid arthritis spreads into the central nervous system and induces depressive state manifested in specific behavioral pattern and impaired adult hippocampal neurogenesis. TNFtg mice showed severe erosive arthritis with increased IL-1β and IL-6 expression in tarsal joints with highly elevated human TNF-α levels in the serum. Intriguingly, IL-1β and IL-6 mRNA levels were not altered in the hippocampus of TNFtg mice. In contrast to the pronounced monocytosis in joints and spleen of TNFtg mice, signs of hippocampal microgliosis or astrocytosis were lacking. Furthermore, locomotion was impaired, but there was no locomotion-independent depressive behavior in TNFtg mice. Proliferation and maturation of hippocampal neural precursor cells as well as survival of newly generated neurons were preserved in the dentate gyrus of TNFtg mice despite reduced motor activity and peripheral inflammatory signature. We conclude that peripheral inflammation in TNFtg mice is mediated by chronic activation of the innate immune system. However, severe peripheral inflammation, though impairing locomotor activity, does not elicit depressive-like behavior. These structural and functional findings indicate the maintenance of hippocampal immunity, cellular plasticity, and behavior despite peripheral innate inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Mild, moderate, meaningful? Examining the psychological and functioning correlates of DSM-5 eating disorder severity specifiers.

    Science.gov (United States)

    Gianini, Loren; Roberto, Christina A; Attia, Evelyn; Walsh, B Timothy; Thomas, Jennifer J; Eddy, Kamryn T; Grilo, Carlos M; Weigel, Thomas; Sysko, Robyn

    2017-08-01

    This study evaluated the DSM-5 severity specifiers for treatment-seeking groups of participants with anorexia nervosa (AN), the purging form of bulimia nervosa (BN), and binge-eating disorder (BED). Hundred and sixty-two participants with AN, 93 participants with BN, and 343 participants with BED were diagnosed using semi-structured interviews, sub-categorized using DSM-5 severity specifiers and compared on demographic and cross-sectional clinical measures. In AN, the number of previous hospitalizations and the duration of illness increased with severity, but there was no difference across severity groups on measures of eating pathology, depression, or measures of self-reported physical or emotional functioning. In BN, the level of eating concerns increased across the severity groups, but the groups did not differ on measures of depression, self-esteem, and most eating pathology variables. In BN, support was also found for an alternative severity classification scheme based upon number of methods of purging. In BED, levels of several measures of eating pathology and self-reported physical and emotional functioning increased across the severity groups. For BED, however, support was also found for an alternative severity classification scheme based upon overvaluation of shape and weight. Preliminary evidence was also found for a transdiagnostic severity index based upon overvaluation of shape and weight. Overall, these data show limited support for the DSM-5 severity specifiers for BN and modest support for the DSM-5 severity specifiers for AN and BED. © 2017 Wiley Periodicals, Inc.

  14. Plasmodium falciparum-induced severe malaria with acute kidney injury and jaundice: a case report

    Science.gov (United States)

    Baswin, A.; Siregar, M. L.; Jamil, K. F.

    2018-03-01

    P. falciparum-induced severe malaria with life-threatening complications like acute kidney injury (AKI), jaundice, cerebral malaria, severe anemia, acidosis, and acute respiratory distress syndrome (ARDS). A 31-year-old soldier man who works in Aceh Singkil, Indonesia which is an endemic malaria area presented with a paroxysm of fever, shaking chills and sweats over four days, headache, arthralgia, abdominal pain, pale, jaundice, and oliguria. Urinalysis showed hemoglobinuria. Blood examination showed hemolytic anemia, thrombocytopenia, and hyperbilirubinemia. Falciparum malaria was then confirmed by peripheral blood smear, antimalarial medications were initiated, and hemodialysis was performed for eight times. The patient’s condition and laboratory results were quickly normalized. We report a case of P. falciparum-induced severe malaria with AKI and jaundice. The present case suggests that P. falciparum may induce severe malaria with life-threatening complications, early diagnosis and treatment is important to improve the quality of life of patients. Physicians must be alert for correct diagnosis and proper management of imported tropical malaria when patients have travel history in endemic areas.

  15. Low Levels of NDRG1 in Nerve Tissue Are Predictive of Severe Paclitaxel-Induced Neuropathy.

    Directory of Open Access Journals (Sweden)

    Raghav Sundar

    Full Text Available Sensory peripheral neuropathy caused by paclitaxel is a common and dose limiting toxicity, for which there are currently no validated predictive biomarkers. We investigated the relationship between the Charcot-Marie-Tooth protein NDRG1 and paclitaxel-induced neuropathy.Archived mammary tissue specimen blocks of breast cancer patients who received weekly paclitaxel in a single centre were retrieved and NDRG1 immunohistochemistry was performed on normal nerve tissue found within the sample. The mean nerve NDRG1 score was defined by an algorithm based on intensity of staining and percentage of stained nerve bundles. NDRG1 scores were correlated with paclitaxel induced neuropathy.111 patients were studied. 17 of 111 (15% developed severe paclitaxel-induced neuropathy. The mean nerve NDRG1 expression score was 5.4 in patients with severe neuropathy versus 7.7 in those without severe neuropathy (p = 0.0019. A Receiver operating characteristic (ROC curve analysis of the mean nerve NDRG1 score revealed an area under the curve of 0.74 (p = 0.0013 for the identification of severe neuropathy, with a score of 7 being most discriminative. 13/54 (24% subjects with an NDRG1 score 7 (p = 0.017.Low NDRG1 expression in nerve tissue present within samples of surgical resection may identify subjects at risk for severe paclitaxel-induced neuropathy. Since nerve biopsies are not routinely feasible for patients undergoing chemotherapy for early breast cancer, this promising biomarker strategy is compatible with current clinical workflow.

  16. Transcatheter aortic valve implantation: emerging role in poor left ventricular function severe aortic stenosis?

    Directory of Open Access Journals (Sweden)

    K. M. John Chan

    2014-01-01

    Full Text Available Transcatheter aortic valve implantation (TAVI has become an established treatment option for high risk elderly patients with symptomatic severe aortic stenosis. Its role in less high risk patients is being evaluated in clinical trials. Patients with severely impaired left ventricular function may be another group who may benefit from this emerging percutaneous treatment option.

  17. Postural Care for People with Intellectual Disabilities and Severely Impaired Motor Function: A Scoping Review

    Science.gov (United States)

    Robertson, Janet; Baines, Susannah; Emerson, Eric; Hatton, Chris

    2018-01-01

    Background: Poor postural care can have severe and life-threatening complications. This scoping review aims to map and summarize existing evidence regarding postural care for people with intellectual disabilities and severely impaired motor function. Method: Studies were identified via electronic database searches (MEDLINE, CINAHL, PsycINFO and…

  18. Load Carriage Induced Alterations of Pulmonary Function

    Science.gov (United States)

    1989-01-01

    pulmonar , function reductions are directh’ related to the backpack load carried due to the mechanical constraint it imposes on the thoracic cage.2 To...and Fish- man. A.P.. 1965. The regulation of venttlation in diffuse Agostor. E.. D’Angelc, E. and Piolini, M., 1978. Breathing pulmonary fibrosis . J

  19. The extremity function index (EFI), a disability severity measure for neuromuscular diseases : psychometric evaluation

    NARCIS (Netherlands)

    Bos, Isaac; Wynia, Klaske; Drost, Gea; Almansa, Josué; Kuks, Joannes

    2017-01-01

    OBJECTIVE: To adapt and to combine the self-report Upper Extremity Functional Index and Lower Extremity Function Scale, for the assessment of disability severity in patients with a neuromuscular disease and to examine its psychometric properties in order to make it suitable for indicating disease

  20. Continuity in Λ-variation of functions of several variables and convergence of multiple Fourier series

    International Nuclear Information System (INIS)

    Bakhvalov, A N

    2002-01-01

    The behaviour of rectangular partial sums of the Fourier series of functions of several variables having bounded Λ-variation is considered. It is proved that if a continuous function is also continuous in harmonic variation, then its Fourier series uniformly converges in the sense of Pringsheim. On the other hand, it is demonstrated that in dimensions greater than 2 there always exists a continuous function of bounded harmonic variation with Fourier series divergent over cubes at the origin

  1. Effect of joint traction on functional improvement and quality of life in patients with severe knee osteoarthritis

    Directory of Open Access Journals (Sweden)

    Sedigheh Sadat Naeimee

    2012-07-01

    Full Text Available Background and aim: Osteoarthritis (OA is the most prevalent joint disease in adults around the world and its incidence rises with age. Patients with severe knee osteoarthritis often complain of pain and severe functional disability. Most of conservative treatments used in this group of patients induce poor improvements. This study evaluated the effect of joint traction on quality of life of patients with severe knee osteoarthritis.Materials and Methods: In this clinical trial study, forty female patients with severe knee OA were randomly assigned to two following groups; common physiotherapy treatment and common physiotherapy treatment accompanied by knee distraction. Quality of life was evaluated pre- and post-treatment and also one month follow-up using the Knee injury and Osteoarthritis Outcome Score (KOOS questionnaire.Results: Common physiotherapy treatment accompanied by knee distraction resulted in significantly better quality of life post-treatment and at 1month follow-up, compared to common physiotherapy treatment alone (P<0.01.Conclusion: Common physiotherapy treatment accompanied by knee distraction induces significant improvement in quality of life in patients with severe knee osteoarthritis compared to common physiotherapy treatment alone.

  2. Studying the Effects of Fasting during Ramadan on Pulmonary Functioning Test and Asthma Severity

    Directory of Open Access Journals (Sweden)

    Seyyed Hassan Adeli

    2015-03-01

    Full Text Available Background and Objectives: Studies have shown that fasting can have an impact on the course and severity of chronic diseases. There are a few studies on the association of fasting and asthma. Therefore, this study has been conducted with the purpose of examining the effects of fasting on asthma severity and pulmonary functioning tests. Methods: 30 patients with asthma who attended a pulmonology clinic in Qom were enrolled in this study. The severity of patients’ asthma has been studied by questionnaire and spirometry of pulmonary functioning in the month of Shaban, Ramadan and Shawwal. The results of Asthma Control Questionnaire and the pulmonary functioning tests in three months have been compared. Results: The average age of patients was 43.42 years and 43.3% of patients were males. The Average score for asthma severity questionnaire in three months were 20.4, 21 and 20.17 respectively. Statistically, there haven’t been any significant differences between the results of pulmonary functioning test and asthma severity before Ramadan (Shaban, during Ramadan and after that (Shawwal. Conclusion: The findings of this study showed that fasting in patients with asthma has no effect on pulmonary function and asthma severity.

  3. Age-Related Effect of Viral-Induced Wheezing in Severe Prematurity

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    Geovanny F. Perez

    2016-10-01

    Full Text Available Premature children are prone to severe viral respiratory infections in early life, but the age at which susceptibility peaks and disappears for each pathogen is unclear. Methods: A retrospective analysis was performed of the age distribution and clinical features of acute viral respiratory infections in full-term and premature children, aged zero to seven years. Results: The study comprised of a total of 630 hospitalizations (n = 580 children. Sixty-seven percent of these hospitalizations occurred in children born full-term (>37 weeks, 12% in preterm (32–37 weeks and 21% in severely premature children (<32 weeks. The most common viruses identified were rhinovirus (RV; 60% and respiratory syncytial virus (RSV; 17%. Age-distribution analysis of each virus identified that severely premature children had a higher relative frequency of RV and RSV in their first three years, relative to preterm or full-term children. Additionally, the probability of RV- or RSV-induced wheezing was higher overall in severely premature children less than three years old. Conclusions: Our results indicate that the vulnerability to viral infections in children born severely premature is more specific for RV and RSV and persists during the first three years of age. Further studies are needed to elucidate the age-dependent molecular mechanisms that underlie why premature infants develop RV- and RSV-induced wheezing in early life.

  4. Relationship of Renal Function Tests and Electrolyte Levels with Severity of Dehydration in Acute Diarrhea.

    Science.gov (United States)

    Gauchan, E; Malla, K K

    2015-01-01

    Acute diarrheal illness constitutes a major cause of morbidity and mortality in children in developing countries. Most of the complications of diarrhea occur due to excessive fluid and electrolyte loss; adverse complications are seen more with increasing severity of dehydration. This study was conducted to identify the relation of renal function and electrolyte abnormalities in children with varying severity of dehydration. This study was carried out in Manipal Teaching Hospital, Pokhara, Nepal over duration of one year. The aims were to find out the association of renal function and electrolyte disturbances with type of diarrhea, severity of dehydration and their relation to outcome. All children more than one month and less than 15 years with acute diarrhea were included in the study. Data were entered and analyzed by SPSS version 19. Statistical analysis applied was Chi-square test. A p-value of Dehydration was associated more with Acute Watery Diarrhea than with Invasive Diarrhea. Renal function and electrolyte abnormalities were seen more in Acute Watery Diarrhea with increasing levels of blood urea, serum creatinine and abnormal levels of serum sodium seen with increased severity of dehydration. Abnormalities in renal function and electrolytes correlated significantly with severity of dehydration. The outcome of patients correlated with severity of dehydration with mortality occurring in 18.1% of patients with Severe dehydration, 0.8% of Some dehydration with no mortality in the No dehydration group.

  5. Two unusual cases of severe recalcitrant hypocalcemia due to aminoglycoside-induced hypomagnesemia

    Directory of Open Access Journals (Sweden)

    Tarun Varma

    2013-01-01

    Full Text Available Aminoglycoside (AMG-induced renal toxicity is well-known and may manifest with non-oliguric renal failure or renal tubular dysfunction like Fanconi-like syndrome, Barter syndrome-like syndrome or distal renal tubular acidosis (RTA. These phenomena have been described with Gentamycin and Amikacin though rarely with Kanamycin. We present two cases of pulmonary tuberculosis that were treated with Kanamycin and during the course of treatment, developed severe recalcitrant hypocalcemia along with hypomagnesemia.

  6. Association of Body Mass Index with Asthma Severity and Pulmonary Function among Asthmatic Children

    Directory of Open Access Journals (Sweden)

    Rasuol Nasiri Kalmarzi

    2016-09-01

    Full Text Available Background Asthma is a chronic inflammatory disease in respiratory system and obesity is another inflammatory disease which incidence rate is increasing. Although, many studies have been conducted on severity of asthma and its relationship with obesity, but different results have been obtained. This study aimed to determine a relationship between asthma severity, Body Mass Index (BMI and pulmonary function in Kurdistan province, Iran. Materials and Methods: In this cross sectional study 90 asthmatic patients referred to referral hospital in Kurdistan, North West of Iran, were selected by simple random method. BMI was calculated by dividing weight by height.Pulmonary Function Test (PFT and bronchial-stimulation-test were used for confirmation and investigation of asthma severity. Data were analyzed using SPSS-15 and Chi-square and spearman correlation coefficient tests. Results: Relationship between BMI and severity of asthma (mild, medium and severe was evaluated, there was a relationship and positive relationship between them (P

  7. Radiations - induced disorders in ovarian function

    International Nuclear Information System (INIS)

    Saleh, S.; Roushdy, H.M.; Abdel-Aziz, M.T.; Eldenshary, A.E.; Abdel-Khalek, A.; Ramadan, L.A.

    1988-01-01

    The effect of whole body gamma radiation exposure (7.5 and 6.5 Gy) on the secretory activity and the structure of the ovaries was investigated. The parameters studied were serum levels of oestrogen, progesterone, Lh and FSH, beside histopathological studies of the ovaries of femaler rats. These were measured on the next day after radiation exposure and then after one two oestrus cycles. Whole body gamma - irradiation of females rats at two levels of exposure progressively decreased the level of oestrogen and progesterone while increased the level of LH and FSH as compared with the control. moreover, the changes in the ovaries were demonstrated in the histopathological investigation. Keywords: Radiation exposure - ovarian function - hormone radioimmunoassay - oestrogen - progesterone - LH - FSH

  8. Laterality of cerebral hemispheres on CT scan and gross motor function in severely handicapped children

    Energy Technology Data Exchange (ETDEWEB)

    Iwasaki, Nobuaki; Hamano, Kenzo; Nakamoto, Natsue; Okada, Yusuke [Tsukuba Univ., Ibaraki (Japan); Takeya, Toshiki

    1997-06-01

    The relation between brain damage and gross motor function in severely handicapped children (spastic type) was studied. The subjects were fifteen cases with laterality in their cerebral hemisphere CT scans (laterality group) and 28 cases with no laterality (control group). All cases were divided into four groups according to the level of gross motor function. The grade of brain damage was estimated based on CT scan analysis using the following parameters and index: maximum frontal extracerebral space (ES), maximum width of Sylvian fissure (SY), Evans` ratio, and cella media index. In the laterality group, the parameters and index were measured for both cerebral hemispheres, respectively. In the more severely disturbed hemisphere of the laterality group, ES and SY were significantly enlarged compared with those of the cases with the same level of motor function in the control group (p<0.01). In the less severely disturbed hemisphere of the laterality group, the ES, SY, Evans` ratio and cell media index were not significantly enlarged compared to cases with the same level of motor function as the control group. These findings may indicate that gross motor function of severely handicapped children is closely related to the less severely disturbed cerebral hemisphere. (author)

  9. Laterality of cerebral hemispheres on CT scan and gross motor function in severely handicapped children

    International Nuclear Information System (INIS)

    Iwasaki, Nobuaki; Hamano, Kenzo; Nakamoto, Natsue; Okada, Yusuke; Takeya, Toshiki.

    1997-01-01

    The relation between brain damage and gross motor function in severely handicapped children (spastic type) was studied. The subjects were fifteen cases with laterality in their cerebral hemisphere CT scans (laterality group) and 28 cases with no laterality (control group). All cases were divided into four groups according to the level of gross motor function. The grade of brain damage was estimated based on CT scan analysis using the following parameters and index: maximum frontal extracerebral space (ES), maximum width of Sylvian fissure (SY), Evans' ratio, and cella media index. In the laterality group, the parameters and index were measured for both cerebral hemispheres, respectively. In the more severely disturbed hemisphere of the laterality group, ES and SY were significantly enlarged compared with those of the cases with the same level of motor function in the control group (p<0.01). In the less severely disturbed hemisphere of the laterality group, the ES, SY, Evans' ratio and cell media index were not significantly enlarged compared to cases with the same level of motor function as the control group. These findings may indicate that gross motor function of severely handicapped children is closely related to the less severely disturbed cerebral hemisphere. (author)

  10. Oculomotor executive function abnormalities with increased tic severity in Tourette syndrome.

    Science.gov (United States)

    Jeter, Cameron B; Patel, Saumil S; Morris, Jeffrey S; Chuang, Alice Z; Butler, Ian J; Sereno, Anne B

    2015-02-01

    Reports conflict as to whether Tourette syndrome (TS) confers deficits in executive function. This study's aim was to evaluate executive function in youths with TS using oculomotor tasks while controlling for confounds of tic severity, age, medication, and severity of comorbid disorders. Four saccade tasks requiring the executive functions of response generation, response inhibition, and working memory (prosaccade, antisaccade, 0-back, and 1-back) were administered. Twenty youths with TS and low tic severity (TS-low), nineteen with TS and moderate tic severity (TS-moderate), and 29 typically developing control subjects (Controls) completed the oculomotor tasks. There were small differences across groups in the prosaccade task. Controlling for any small sensorimotor differences, TS-moderate subjects had significantly higher error rates than Controls and TS-low subjects in the 0-back and 1-back tasks. In the 1-back task, these patients also took longer to respond than Controls or TS-low subjects. In a highly controlled design, the findings demonstrate for the first time that increased tic severity in TS is associated with impaired response inhibition and impaired working memory and that these executive function deficits cannot be accounted for by differences in age, medication or comorbid symptom severity. © 2014 Association for Child and Adolescent Mental Health.

  11. Winter severity determines functional trait composition of phytoplankton in seasonally ice-covered lakes.

    Science.gov (United States)

    Özkundakci, Deniz; Gsell, Alena S; Hintze, Thomas; Täuscher, Helgard; Adrian, Rita

    2016-01-01

    How climate change will affect the community dynamics and functionality of lake ecosystems during winter is still little understood. This is also true for phytoplankton in seasonally ice-covered temperate lakes which are particularly vulnerable to the presence or absence of ice. We examined changes in pelagic phytoplankton winter community structure in a north temperate lake (Müggelsee, Germany), covering 18 winters between 1995 and 2013. We tested how phytoplankton taxa composition varied along a winter-severity gradient and to what extent winter severity shaped the functional trait composition of overwintering phytoplankton communities using multivariate statistical analyses and a functional trait-based approach. We hypothesized that overwintering phytoplankton communities are dominated by taxa with trait combinations corresponding to the prevailing winter water column conditions, using ice thickness measurements as a winter-severity indicator. Winter severity had little effect on univariate diversity indicators (taxon richness and evenness), but a strong relationship was found between the phytoplankton community structure and winter severity when taxon trait identity was taken into account. Species responses to winter severity were mediated by the key functional traits: motility, nutritional mode, and the ability to form resting stages. Accordingly, one or the other of two functional groups dominated the phytoplankton biomass during mild winters (i.e., thin or no ice cover; phototrophic taxa) or severe winters (i.e., thick ice cover; exclusively motile taxa). Based on predicted milder winters for temperate regions and a reduction in ice-cover durations, phytoplankton communities during winter can be expected to comprise taxa that have a relative advantage when the water column is well mixed (i.e., need not be motile) and light is less limiting (i.e., need not be mixotrophic). A potential implication of this result is that winter severity promotes different

  12. CPAP therapy improves erectile function in patients with severe obstructive sleep apnea.

    Science.gov (United States)

    Schulz, Richard; Bischof, Fabian; Galetke, Wolfgang; Gall, Henning; Heitmann, Jörg; Hetzenecker, Andrea; Laudenburg, Markus; Magnus, Till Jonas; Nilius, Georg; Priegnitz, Christina; Randerath, Winfried; Schröder, Maik; Treml, Marcel; Arzt, Michael

    2018-04-10

    Erectile dysfunction (ED) is highly prevalent in obstructive sleep apnea (OSA), however, the effect of continuous positive airway pressure (CPAP) therapy on erectile function has not yet been thoroughly investigated in these patients. Ninety-four men with severe OSA (ie, with an apnea-hypopnea-index ≥ 30/h of sleep) were prospectively evaluated for the presence and severity of ED before and after 6-12 months of CPAP therapy. The abbreviated version of the International Index of Erectile Function, (the IIEF-5) was used to rate erectile function. Furthermore, all study participants responded to standard questionnaires of daytime sleepiness (Epworth Sleepiness Scale), quality of life (WHO Wellbeing 5 questionnaire) and depression (Major Depression Inventory). ED as defined by an IIEF-5 score of ≤21 was present in 64 patients (68.1%). CPAP treatment significantly improved erectile function in those patients suffering from moderate and severe ED. Additionally, a trend for a correlation between the improvement of erectile function under CPAP and the hours of its use was observed. Finally, this effect was associated with larger improvements of quality of life in affected patients. ED is very frequent in men with severe OSA and can at least partly be reversed by long-term CPAP therapy in most seriously affected patients. The beneficial effect on erectile function may depend on CPAP compliance and is accompanied by improvements of quality of life. Randomized controlled trials are needed to confirm these findings. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Examining the interplay among negative emotionality, cognitive functioning, and attention deficit/hyperactivity disorder symptom severity.

    Science.gov (United States)

    Healey, Dione M; Marks, David J; Halperin, Jeffrey M

    2011-05-01

    Cognition and emotion, traditionally thought of as largely distinct, have recently begun to be conceptualized as dynamically linked processes that interact to influence functioning. This study investigated the moderating effects of cognitive functioning on the relationship between negative emotionality and attention deficit/hyperactivity disorder (ADHD) symptom severity. A total of 216 (140 hyperactive/inattentive; 76 typically developing) preschoolers aged 3-4 years were administered a neuropsychological test battery (i.e., NEPSY). To avoid method bias, child negative emotionality was rated by teachers (Temperament Assessment Battery for Children-Revised), and parents rated symptom severity on the ADHD Rating Scale (ADHD-RS-IV). Hierarchical Linear Regression analyses revealed that both negative emotionality and Perceptual-Motor & Executive Functions accounted for significant unique variance in ADHD symptom severity. Significant interactions indicated that when negative emotionality is low, but not high, neuropsychological functioning accounts for significant variability in ADHD symptoms, with lower functioning predicting more symptoms. Emotional and neuropsychological functioning, both individually and in combination, play a significant role in the expression of ADHD symptom severity.

  14. Loss of the inducible Hsp70 delays the inflammatory response to skeletal muscle injury and severely impairs muscle regeneration.

    Directory of Open Access Journals (Sweden)

    Sarah M Senf

    Full Text Available Skeletal muscle regeneration following injury is a highly coordinated process that involves transient muscle inflammation, removal of necrotic cellular debris and subsequent replacement of damaged myofibers through secondary myogenesis. However, the molecular mechanisms which coordinate these events are only beginning to be defined. In the current study we demonstrate that Heat shock protein 70 (Hsp70 is increased following muscle injury, and is necessary for the normal sequence of events following severe injury induced by cardiotoxin, and physiological injury induced by modified muscle use. Indeed, Hsp70 ablated mice showed a significantly delayed inflammatory response to muscle injury induced by cardiotoxin, with nearly undetected levels of both neutrophil and macrophage markers 24 hours post-injury. At later time points, Hsp70 ablated mice showed sustained muscle inflammation and necrosis, calcium deposition and impaired fiber regeneration that persisted several weeks post-injury. Through rescue experiments reintroducing Hsp70 intracellular expression plasmids into muscles of Hsp70 ablated mice either prior to injury or post-injury, we confirm that Hsp70 optimally promotes muscle regeneration when expressed during both the inflammatory phase that predominates in the first four days following severe injury and the regenerative phase that predominates thereafter. Additional rescue experiments reintroducing Hsp70 protein into the extracellular microenvironment of injured muscles at the onset of injury provides further evidence that Hsp70 released from damaged muscle may drive the early inflammatory response to injury. Importantly, following induction of physiological injury through muscle reloading following a period of muscle disuse, reduced inflammation in 3-day reloaded muscles of Hsp70 ablated mice was associated with preservation of myofibers, and increased muscle force production at later time points compared to WT. Collectively our

  15. Craniopharyngioma presenting with severe hyponatremia, hyponatremia-induced myopathy, and panhypopituitarism: a case report.

    Science.gov (United States)

    Dilrukshi, M D S A; Sandakumari, G V N; Abeysundara, P K; Chang, T

    2017-02-05

    Craniopharyngiomas are rare intracranial tumors commonly presenting with neurological symptoms. Reports of severe hyponatremia as a presenting manifestation of a craniopharyngioma and hyponatremia-induced myopathy are rare. We report the case of a patient with craniopharyngioma presenting with severe hyponatremia, panhypopituitarism, and hyponatremia-induced myopathy. A 52-year-old Sri Lankan man presented with anorexia, nausea, fatigue, generalized muscle weakness, and cramps for 1 week. The onset of his illness had been preceded by vomiting and diarrhea for 1 day which he attributed to food poisoning. On examination, he had an apathetic disposition with a generalized "sallow complexion." He was not dehydrated. Apart from reduced muscle power (4/5) and hyporeflexia, the neurological examination was normal. His serum sodium was 102 mmol/l; potassium 4.1 mmol/l; chloride 63 mmol/l; plasma osmolality 272 mosm/KgH 2 O; urine osmolality 642 mosm/KgH 2 O; and urine sodium 79 mmol/l. His creatine phosphokinase was 12,400 U/l, lactate dehydrogenase 628 U/l, aspartate aminotransferase 360 U/l, and alanine aminotransferase 64 U/l. His hormone profile revealed panhypopituitarism. An electromyogram showed nonspecific abnormalities while a muscle biopsy did not show any pathology. Magnetic resonance imaging of his brain demonstrated a well-defined craniopharyngioma with suprasellar extension. His pituitary gland was compressed and the pituitary stalk was displaced by the tumor. He had marked improvement in muscle power and rapid reduction of serum creatine phosphokinase levels paralleling the correction of severe hyponatremia, even before the initiation of hormone replacement. This case illustrates the rare presentation of severe hyponatremia and hyponatremia-induced myopathy in patients with craniopharyngioma, awareness of which would facilitate early appropriate investigations and treatment.

  16. EEG-Triggered Functional Electrical Stimulation Therapy for Restoring Upper Limb Function in Chronic Stroke with Severe Hemiplegia

    Directory of Open Access Journals (Sweden)

    Cesar Marquez-Chin

    2016-01-01

    Full Text Available We report the therapeutic effects of integrating brain-computer interfacing technology and functional electrical stimulation therapy to restore upper limb reaching movements in a 64-year-old man with severe left hemiplegia following a hemorrhagic stroke he sustained six years prior to this study. He completed 40 90-minute sessions of functional electrical stimulation therapy using a custom-made neuroprosthesis that facilitated 5 different reaching movements. During each session, the participant attempted to reach with his paralyzed arm repeatedly. Stimulation for each of the movement phases (e.g., extending and retrieving the arm was triggered when the power in the 18 Hz–28 Hz range (beta frequency range of the participant’s EEG activity, recorded with a single electrode, decreased below a predefined threshold. The function of the participant’s arm showed a clinically significant improvement in the Fugl-Meyer Assessment Upper Extremity (FMA-UE subscore (6 points as well as moderate improvement in Functional Independence Measure Self-Care subscore (7 points. The changes in arm’s function suggest that the combination of BCI technology and functional electrical stimulation therapy may restore voluntary motor function in individuals with chronic hemiplegia which results in severe upper limb deficit (FMA-UE ≤ 15, a population that does not benefit from current best-practice rehabilitation interventions.

  17. Erdosteine reduces the exercise-induced oxidative stress in patients with severe COPD: Results of a placebo-controlled trial.

    Science.gov (United States)

    Dal Negro, Roberto W; Visconti, Maria

    2016-12-01

    Erdosteine (ER), a multimechanism, mucoactive agent with anti-oxidant and anti-inflammatory properties, has been shown to improve lung function, decrease plasma reactive oxygen species (ROS), and 8-isoprostane levels in patients with chronic obstructive pulmonary disease (COPD). To assess vs. placebo the effect of ER on the exercise-induced oxidative stress by measuring and comparing the release of pro-inflammatory mediators in severe COPD patients. The double blind, placebo controlled study was carried out in 24 severe (GOLD Class III) COPD patients, aged >40 yr, randomized to receive either oral ER (600 mg/day, 8 males, mean age 70.5 yr) or placebo (9 males, mean age 70.8 yr) for 10 days. All patients performed a 6-min walking test (6MWT) before and after both treatments. Mean ROS plasma levels increased significantly, but equally, in each group following the baseline 6MWT (p = ns). At the end of both treatments, a significant difference in mean plasma ROS increase from baseline became clear between the ER (+14.6% ± 2.7) and the placebo group (+24.4% ± 3.8) after the second 6MWT (p release of inflammatory mediators due to the exercise-induced oxidative stress in severe COPD patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Trauma center designation correlates with functional independence after severe but not moderate traumatic brain injury.

    Science.gov (United States)

    Brown, Joshua B; Stassen, Nicole A; Cheng, Julius D; Sangosanya, Ayodele T; Bankey, Paul E; Gestring, Mark L

    2010-08-01

    The mortality of traumatic brain injury (TBI) continues to decline, emphasizing functional outcomes. Trauma center designation has been linked to survival after TBI, but the impact on functional outcomes is unclear. The objective was to determine whether trauma center designation influenced functional outcomes after moderate and severe TBI. Trauma subjects presenting to an American College of Surgeons (ACS) Level I or II trauma center with a Glasgow Coma Score (GCS) independence (FI) defined as a modified functional independence measure (FIM) of 12, and independent expression (IE) defined as a FIM component of 4. These were compared between Level I and Level II centers in subjects with both moderate (GCS 9-12) and severe (GCS severe TBI). After adjusting for covariates, ACS Level I designation was associated with FI (odds ratio: 1.16; confidence interval: 1.07-1.24, p < 0.01) and IE (1.10; 1.03-1.17, p < 0.01) after severe TBI. Trauma center designation was not associated with FI or IE after moderate TBI. ACS trauma center designation is significantly associated with FI and IE after severe, but not moderate TBI. Prospective study is warranted to verify and explore factors contributing to this discrepancy.

  19. Left ventricular diastolic function is associated with symptom status in severe aortic valve stenosis

    DEFF Research Database (Denmark)

    Dahl, Jordi S; Christensen, Nicolaj L; Videbæk, Lars

    2014-01-01

    atrial volume index, and deceleration time were still associated with the presence of symptoms. CONCLUSIONS: The present study demonstrates that symptomatic status in severe AS is associated with impaired diastolic function, LV hypertrophy, concentric remodeling, and left atrial dilatation when corrected...... function, and left atrial dilatation compared with asymptomatic patients. METHODS AND RESULTS: In a retrospective descriptive study, we compared clinical characteristics and echocardiographic parameters in 99 symptomatic and 139 asymptomatic patients with severe AS and LV ejection fraction ≥50.......001), and had a lower prevalence of hypertension (73% versus 40%; Ptime (199±58 versus...

  20. Exercise and cognitive functions in Parkinson's disease: Gender differences and disease severity

    Directory of Open Access Journals (Sweden)

    Claudia Teixeira-Arroyo

    2014-12-01

    Full Text Available This study investigated the effect of a multimodal exercise program on executive functions and memory in people with Parkinson's disease, taking into account disease severity and gender. Twenty-three patients with Parkinson's disease (PD were evaluated before and after a 6-month exercise program to improve executive functions and memory. We observed the effects of the intervention on executive functions (ability to abstract: p = .01, immediate memory (p= .04 and declarative episodic memory (p < .001. Women showed higher scores on declarative episodic memory (p = .03 than men, however there was no interaction between gender and the intervention. Regardless of sex and disease severity, these preliminary results indicate that the multimodal exercise seems to be effective in improving cognitive functions in patients with PD, suggesting that this program can be indicated as a preventive strategy to mitigate progressive cognitive deficits in the later stages of the disease.

  1. Hyperbaric oxygen as sole treatment for severe radiation - induced haemorrhagic cystitis

    Energy Technology Data Exchange (ETDEWEB)

    Dellis, Athanasios, E-mail: aedellis@gmail.com [Department of Surgery, National and Kapodistrian University of Athens, Aretaieion Academic Hospital, Athens (Greece); Papatsoris, Athanasios; Deliveliotis, Charalambos; Skolarikos, Andreas [Department of Urology, University of Athens, Sismanoglio General Hospital, Athens (Greece); Kalentzos, Vasileios [Department of Diving and Hyperbaric Oxygen, Naval and Veterans Hospital, Athens (Greece)

    2017-05-15

    Purpose: To examine the safety and efficacy of hyperbaric oxygen as the primary and sole treatment for severe radiation-induced haemorrhagic cystitis. Materials and methods: Hyperbaric oxygen was prospectively applied as primary treatment in 38 patients with severe radiation cystitis. Our primary endpoint was the incidence of complete and partial response to treatment, while the secondary endpoints included the duration of response, the correlation of treatment success-rate to the interval between the onset of haematuria and initiation of therapy, blood transfusion need and total radiation dose, the number of sessions to success, the avoidance of surgery and the overall survival. Results: All patients completed therapy without complications with a mean follow-up of 29.33 months. Median number of sessions needed was 33. Complete and partial response rate was 86.8% and 13.2%, respectively. All 33 patients with complete response received therapy within 6 months of the haematuria onset. One patient needed cystectomy, while 33 patients were alive at the end of follow-up. Conclusions: Our study suggests the early primary use of hyperbaric oxygen for radiation-induced severe cystitis as an effective and safe treatment option. (author)

  2. Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis

    Science.gov (United States)

    Monin, Leticia; Griffiths, Kristin L.; Lam, Wing Y.; Gopal, Radha; Kang, Dongwan D.; Ahmed, Mushtaq; Rajamanickam, Anuradha; Cruz-Lagunas, Alfredo; Zúñiga, Joaquín; Babu, Subash; Kolls, Jay K.; Mitreva, Makedonka; Rosa, Bruce A.; Ramos-Payan, Rosalio; Morrison, Thomas E.; Murray, Peter J.; Rangel-Moreno, Javier; Pearce, Edward J.; Khader, Shabaana A.

    2015-01-01

    Parasitic helminth worms, such as Schistosoma mansoni, are endemic in regions with a high prevalence of tuberculosis (TB) among the population. Human studies suggest that helminth coinfections contribute to increased TB susceptibility and increased rates of TB reactivation. Prevailing models suggest that T helper type 2 (Th2) responses induced by helminth infection impair Th1 immune responses and thereby limit Mycobacterium tuberculosis (Mtb) control. Using a pulmonary mouse model of Mtb infection, we demonstrated that S. mansoni coinfection or immunization with S. mansoni egg antigens can reversibly impair Mtb-specific T cell responses without affecting macrophage-mediated Mtb control. Instead, S. mansoni infection resulted in accumulation of high arginase-1–expressing macrophages in the lung, which formed type 2 granulomas and exacerbated inflammation in Mtb-infected mice. Treatment of coinfected animals with an antihelminthic improved Mtb-specific Th1 responses and reduced disease severity. In a genetically diverse mouse population infected with Mtb, enhanced arginase-1 activity was associated with increased lung inflammation. Moreover, in patients with pulmonary TB, lung damage correlated with increased serum activity of arginase-1, which was elevated in TB patients coinfected with helminths. Together, our data indicate that helminth coinfection induces arginase-1–expressing type 2 granulomas, thereby increasing inflammation and TB disease severity. These results also provide insight into the mechanisms by which helminth coinfections drive increased susceptibility, disease progression, and severity in TB. PMID:26571397

  3. Simulation of Exercise-Induced Syncope in a Heart Model with Severe Aortic Valve Stenosis

    Directory of Open Access Journals (Sweden)

    Matjaž Sever

    2012-01-01

    Full Text Available Severe aortic valve stenosis (AVS can cause an exercise-induced reflex syncope (RS. The precise mechanism of this syncope is not known. The changes in hemodynamics are variable, including arrhythmias and myocardial ischemia, and one of the few consistent changes is a sudden fall in systemic and pulmonary arterial pressures (suggesting a reduced vascular resistance followed by a decline in heart rate. The contribution of the cardioinhibitory and vasodepressor components of the RS to hemodynamics was evaluated by a computer model. This lumped-parameter computer simulation was based on equivalent electronic circuits (EECs that reflect the hemodynamic conditions of a heart with severe AVS and a concomitantly decreased contractility as a long-term detrimental consequence of compensatory left ventricular hypertrophy. In addition, the EECs model simulated the resetting of the sympathetic nervous tone in the heart and systemic circuit during exercise and exercise-induced syncope, the fluctuating intra-thoracic pressure during respiration, and the passive relaxation of ventricle during diastole. The results of this simulation were consistent with the published case reports of exertional syncope in patients with AVS. The value of the EEC model is its ability to quantify the effect of a selective and gradable change in heart rate, ventricular contractility, or systemic vascular resistance on the hemodynamics during an exertional syncope in patients with severe AVS.

  4. [Severe hypertriglyceridemia induced acute pancreatitis: a case report and review of the literature].

    Science.gov (United States)

    Herrera Del Águila, Dwight Denis; Garavito Rentería, Jorge; Linarez Medina, Karen; Lizarzaburu Rodríguez, Víctor

    2015-01-01

    Hypertriglyceridemia-induced acute pancreatitis occurs in about 1-4% of the cases. It is the third leading cause of pancreatitis after biliary and alcoholic etiology. Hypertriglyceridemia can be caused by primary causes, lipid metabolism disorders and secondary causes. A 32 year old man, born in Huancayo, with a history of diabetes mellitus type 2, severe mixed dyslipidemia with primary hypertriglyceridemia, was admitted to emergency with 10 days of abdominal pain with moderate intensity in epigastrium and left hypochondrium spreading to dorsal region after intake of high-fat meal. 24 hours before admission, pain exacerbates increasing intensity and causing nausea and bilious vomits. Therefore, all laboratory examinations are carried out resulting in hypertriglyceridemia-induced acute pancreatitis. For that reason, an adequate clinical history physical examination associated with laboratory and image examinations are important to consider hypertriglyceridemia as part of the etiology of acute pancreatitis.

  5. Amikacin-induced type 5 Bartter-like syndrome with severe hypocalcemia

    Directory of Open Access Journals (Sweden)

    Chrispal A

    2009-01-01

    Full Text Available Aminoglycoside-induced renal toxicity is well known and may manifest with nonoliguric renal failure or renal tubular dysfunction. Aminoglycoside-induced renal tubular dysfunction could result in diffuse damage or manifest as a Fanconi-like syndrome, Bartter-like syndrome, or distal renal tubular acidosis. We discuss a patient who developed severe renal tubular dysfunction secondary to short-term therapy with Amikacin, resulting in refractory hypokalemia, hypocalcemia, hypomagnesemia, metabolic alkalosis, and polyuria. This constellation of biochemical abnormalities mimic Type 5 Bartter′s syndrome, where there is activating mutation of the calcium sensing receptor in the thick ascending loop of Henle and the distal tubule. In this case this activation of the calcium sensing receptor was triggered by amikacin. This phenomenon has been described with gentamicin though never with amikacin. Recovery of the tubular dysfunction took 15 days following cessation of the offending drug, Amikacin.

  6. Vitamin D Deficiency Is Associated With the Severity of Radiation-Induced Proctitis in Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Ghorbanzadeh-Moghaddam, Amir [Medical Student' s Research Center, Isfahan University of Medical Sciences, Isfahan (Iran, Islamic Republic of); Gholamrezaei, Ali, E-mail: Gholamrezaei@med.mui.ac.ir [Medical Student' s Research Center, Isfahan University of Medical Sciences, Isfahan (Iran, Islamic Republic of); Poursina Hakim Research Institution, Isfahan (Iran, Islamic Republic of); Hemati, Simin [Department of Radiotherapy Oncology, Isfahan University of Medical Sciences, Isfahan (Iran, Islamic Republic of)

    2015-07-01

    Purpose: Radiation-induced injury to normal tissues is a common complication of radiation therapy in cancer patients. Considering the role of vitamin D in mucosal barrier hemostasis and inflammatory responses, we investigated whether vitamin D deficiency is associated with the severity of radiation-induced acute proctitis in cancer patients. Methods and Materials: This prospective observational study was conducted in cancer patients referred for pelvic radiation therapy. Serum concentration of 25-hydroxyvitamin D was measured before radiation therapy. Vitamin D deficiency was defined as 25-hydroxyvitamin D concentrations of <35 nmol/L and <40 nmol/L in male and female patients, respectively, based on available normative data. Acute proctitis was assessed after 5 weeks of radiation therapy (total received radiation dose of 50 Gy) and graded from 0 to 4 using Radiation Therapy Oncology Group (RTOG) criteria. Results: Ninety-eight patients (57.1% male) with a mean age of 62.8 ± 9.1 years were studied. Vitamin D deficiency was found in 57 patients (58.1%). Symptoms of acute proctitis occurred in 72 patients (73.4%) after radiation therapy. RTOG grade was significantly higher in patients with vitamin D deficiency than in normal cases (median [interquartile range] of 2 [0.5-3] vs 1 [0-2], P=.037). Vitamin D deficiency was associated with RTOG grade of ≥2, independent of possible confounding factors; odds ratio (95% confidence interval) = 3.07 (1.27-7.50), P=.013. Conclusions: Vitamin D deficiency is associated with increased severity of radiation-induced acute proctitis. Investigating the underlying mechanisms of this association and evaluating the effectiveness of vitamin D therapy in preventing radiation-induced acute proctitis is warranted.

  7. Vitamin D Deficiency Is Associated With the Severity of Radiation-Induced Proctitis in Cancer Patients

    International Nuclear Information System (INIS)

    Ghorbanzadeh-Moghaddam, Amir; Gholamrezaei, Ali; Hemati, Simin

    2015-01-01

    Purpose: Radiation-induced injury to normal tissues is a common complication of radiation therapy in cancer patients. Considering the role of vitamin D in mucosal barrier hemostasis and inflammatory responses, we investigated whether vitamin D deficiency is associated with the severity of radiation-induced acute proctitis in cancer patients. Methods and Materials: This prospective observational study was conducted in cancer patients referred for pelvic radiation therapy. Serum concentration of 25-hydroxyvitamin D was measured before radiation therapy. Vitamin D deficiency was defined as 25-hydroxyvitamin D concentrations of <35 nmol/L and <40 nmol/L in male and female patients, respectively, based on available normative data. Acute proctitis was assessed after 5 weeks of radiation therapy (total received radiation dose of 50 Gy) and graded from 0 to 4 using Radiation Therapy Oncology Group (RTOG) criteria. Results: Ninety-eight patients (57.1% male) with a mean age of 62.8 ± 9.1 years were studied. Vitamin D deficiency was found in 57 patients (58.1%). Symptoms of acute proctitis occurred in 72 patients (73.4%) after radiation therapy. RTOG grade was significantly higher in patients with vitamin D deficiency than in normal cases (median [interquartile range] of 2 [0.5-3] vs 1 [0-2], P=.037). Vitamin D deficiency was associated with RTOG grade of ≥2, independent of possible confounding factors; odds ratio (95% confidence interval) = 3.07 (1.27-7.50), P=.013. Conclusions: Vitamin D deficiency is associated with increased severity of radiation-induced acute proctitis. Investigating the underlying mechanisms of this association and evaluating the effectiveness of vitamin D therapy in preventing radiation-induced acute proctitis is warranted

  8. The application of a mathematical model linking structural and functional connectomes in severe brain injury

    Directory of Open Access Journals (Sweden)

    A. Kuceyeski

    2016-01-01

    Full Text Available Following severe injuries that result in disorders of consciousness, recovery can occur over many months or years post-injury. While post-injury synaptogenesis, axonal sprouting and functional reorganization are known to occur, the network-level processes underlying recovery are poorly understood. Here, we test a network-level functional rerouting hypothesis in recovery of patients with disorders of consciousness following severe brain injury. This hypothesis states that the brain recovers from injury by restoring normal functional connections via alternate structural pathways that circumvent impaired white matter connections. The so-called network diffusion model, which relates an individual's structural and functional connectomes by assuming that functional activation diffuses along structural pathways, is used here to capture this functional rerouting. We jointly examined functional and structural connectomes extracted from MRIs of 12 healthy and 16 brain-injured subjects. Connectome properties were quantified via graph theoretic measures and network diffusion model parameters. While a few graph metrics showed groupwise differences, they did not correlate with patients' level of consciousness as measured by the Coma Recovery Scale — Revised. There was, however, a strong and significant partial Pearson's correlation (accounting for age and years post-injury between level of consciousness and network diffusion model propagation time (r = 0.76, p < 0.05, corrected, i.e. the time functional activation spends traversing the structural network. We concluded that functional rerouting via alternate (and less efficient pathways leads to increases in network diffusion model propagation time. Simulations of injury and recovery in healthy connectomes confirmed these results. This work establishes the feasibility for using the network diffusion model to capture network-level mechanisms in recovery of consciousness after severe brain injury.

  9. The functions of hospital-based home care for people with severe mental illness in Taiwan.

    Science.gov (United States)

    Huang, Xuan-Yi; Lin, Mei-Jue; Yang, Tuz-Ching; Hsu, Yuan-Shan

    2010-02-01

    The purposes of this study were to understand the functions of hospital-based home care for people with severe mental illness in Taiwan, and the factors that affect functions of professionals who provide hospital-based home care. Hospital-based home care is a service which provides those people with serious mental illnesses who are in crisis and who are candidates for admission to hospital. Home care has been shown to have several advantages over inpatient treatment. However, there is a lack of knowledge about the functions of hospital-based home care for people with severe mental illness in Taiwan. This qualitative study was based on the grounded theory method of Strauss and Corbin. The study was conducted in six different hospital areas in central Taiwan in 2007-2008. Data were collected using semi-structured face-to-face interviews. Constant comparative analysis continued during the open, axial and selective coding processes until data saturation occurred. Participants were selected by theoretical sampling. When theoretical saturation was achieved, 21 clients with mental illness, 19 carers and 25 professionals were interviewed. Several functions were found when these professionals provided hospital-based home care services for people with severe mental illness in Taiwan, including stabilising the clients illness, supplying emergency care services, improving life-coping abilities, employment and welfare assistance, emotional support for both clients and carers, assistance with future and long-term arrangements and assistance with communication between carers and clients. Hospital-based home care provides several important services for helping clients and their families to live in the community. The recommendations based on the findings of this study can be used as a guide to improve the delivery of hospital-based home care services to community-dwelling clients with severe mental illness and their carers.

  10. Vision-Related Functional Burden of Diabetic Retinopathy Across Severity Levels in the United States.

    Science.gov (United States)

    Willis, Jeffrey R; Doan, Quan V; Gleeson, Michelle; Haskova, Zdenka; Ramulu, Pradeep; Morse, Lawrence; Cantrell, Ronald A

    2017-09-01

    Among adults with diabetes in the United States, severe forms of diabetic retinopathy (DR) are significantly associated with a greater vision-related functional burden. To assess the functional burden of DR across severity levels in the United States. This cross-sectional study was based on 1004 participants 40 years or older with diabetes and valid ocular and sociodemographic outcomes in the National Health and Nutrition Examination Surveys (NHANES) (2005-2006 and 2007-2008). Diabetic retinopathy was based on fundus photograph grading, using the Early Treatment Diabetic Retinopathy Study severity scale. The analysis was performed from October 15, 2016, to June 15, 2017. Functional difficulties secondary to vision were assessed during a household questionnaire in which participants self-reported difficulty with reading, visuospatial tasks (ie, close-up work or finding things on a crowded shelf), mobility (ie, walking down steps, stairs, or curbs), and driving. The main outcome measure was vision-related functional burden, which was defined as present for individuals reporting moderate or greater difficulty in any of the aforementioned tasks. Of the 1004 persons with diabetes analyzed for this study (mean age, 65.7 years [95% CI, 64.0-67.3 years]; 51.1% male [95% CI, 47.1-55.2] and 48.9% female [95% CI, 44.8-52.9]), the prevalence was 72.3% for no retinopathy, 25.4% for mild and moderate nonproliferative diabetic retinopathy (NPDR), and 2.3% for severe NPDR or proliferative diabetic retinopathy (PDR). The prevalence of vision-related functional burden was 20.2% (95% CI, 16.3%-24.1%) for those with no retinopathy, 20.4% (95% CI, 15.3%-27.8%) for those with mild and moderate NPDR, and 48.5% (95% CI, 25.6%-71.5%) for those with severe NPDR or PDR (P = .02). In multivariable analysis, the odds of vision-related functional burden were significantly greater among those with severe NPDR or PDR relative to those with no retinopathy (adjusted odds ratio [aOR], 3.59; 95

  11. Tachycardia-Induced Right Heart Failure and Severe Tricuspid Regurgitation That Improved with Medication.

    Science.gov (United States)

    Yang, Young Ae; Yang, Dong Heon; Kim, Hong Nyun; Kwon, Sang Hoon; Jang, Se Young; Bae, Myung Hwan; Lee, Jang Hoon; Chae, Shung Chull

    2015-12-01

    Secondary tricuspid regurgitation (TR) primarily develops due to left heart failure or primary pulmonary diseases. Tricuspid annular dilation, which is commonly caused by right ventricular volume and pressure overload followed by right ventricle dilation, is believed to be the main mechanism underlying secondary TR. It is reported that once the tricuspid annulus is dilated, its size cannot spontaneously return to normal, and it may continue to dilate. These reports also suggest the use of an aggressive surgical approach for secondary TR. In the present report, we describe a case of tachycardia-induced severe TR that was completely resolved without the need for surgery.

  12. Tribulus terrestris-induced severe nephrotoxicity in a young healthy male.

    Science.gov (United States)

    Talasaz, Azita Hajhossein; Abbasi, Mohammad-Reza; Abkhiz, Saeed; Dashti-Khavidaki, Simin

    2010-11-01

    Herbal medications are being progressively utilized all over the world. Nevertheless, herbal remedies are not without hazards and several cases of adverse reactions have been described. Tribulus terrestris is traditionally used because of its aphrodisiac and antiurolithiatic activities with almost complete inhibition of stone formation. We report a case of T. terrestris-induced hepatotoxicity, nephrotoxicity and neurotoxicity in an Iranian male patient who used the plant's extract to prevent kidney stone formation. He presented with seizure and very high serum aminotransferases and creatinine after consuming herbal water for 2 days. Discontinuation of the herbal remedy resulted in improvement in symptoms and normalization of his liver enzymes.

  13. Association between Global Assessment of Functioning scores and indicators of functioning, severity, and prognosis in first-time schizophrenia

    DEFF Research Database (Denmark)

    Köhler-Forsberg, Ole; Horsdal, Henriette Thisted; Baandrup, Lone

    2016-01-01

    are associated with other indicators of functioning, severity, and hospitalization. METHODS: A Danish population-based cohort study of adults (≥18 years) with a recorded GAF-F score at first-time schizophrenia diagnosis during 2004-2011 was performed. The internal validity of GAF-F was evaluated by assessing its...... of schizophrenia with a GAF-F score at first-time diagnosis (73.0% inpatients; 62.6% males). GAF-F was associated with several baseline measures of functioning and illness severity, such as female sex, being in work, and a longer baseline hospitalization. Lower GAF-F scores were associated with higher.......36-3.90), fitting a dose-response relationship (P=0.031). This association was not found in females. CONCLUSION: GAF-F at first-time schizophrenia diagnosis showed good internal validity against other measures of functionality in a Danish hospital setting. Severe impairment (as measured by the GAF-F score) at first...

  14. Association between vitamin D status and physical function in the severely obese.

    LENUS (Irish Health Repository)

    Ahern, T

    2014-07-01

    Mortality is 85% higher in severely obese subjects (body mass index [BMI] > 40 kg\\/m(2)) than in subjects with a healthy BMI; poor physical function may be contributory. Hypovitaminosis D is common in obese subjects and is associated with physical dysfunction in the elderly.

  15. Application of the Mitrofanoff principle in children with severe impairment of bladder function

    NARCIS (Netherlands)

    Heij, H. A.; Ekkelkamp, S.; Moorman-Voestermans, C. G.; Vos, A.

    1997-01-01

    Treatment of children with severe impairment of bladder function requires a large-volume, low-pressure reservoir combined with a continent, easily catheterizable valve. The Mitrofanoff principle (MP) appears to meet these requirements. Between 1986 and 1993, the MP was applied in 15 children (4

  16. Using Functional Analysis Methodology to Evaluate Effects of an Atypical Antipsychotic on Severe Problem Behavior

    Science.gov (United States)

    Danov, Stacy E.; Tervo, Raymond; Meyers, Stephanie; Symons, Frank J.

    2012-01-01

    The atypical antipsychotic medication aripiprazole was evaluated using a randomized AB multiple baseline, double-blind, placebo-controlled design for the treatment of severe problem behavior with 4 children with intellectual and developmental disabilities. Functional analysis (FA) was conducted concurrent with the medication evaluation to…

  17. Long-term psychological functioning of adults with severe congenital facial disfigurement

    NARCIS (Netherlands)

    Passchier, J.; Versnel, S.L.; Plomp, R.G.; Duivenvoorden, H.J.; Mathijssen, I.M.

    2012-01-01

    BACKGROUND: In adults with severe congenital facial disfigurement, assessment of long-term psychological impact remains limited. This study determines the long-term psychological functioning in these patients and evaluates differences compared with patients with acquired facial disfigurement and a

  18. Effect of abnormal thyroid function on the severity of Graves' ophthalmopathy

    NARCIS (Netherlands)

    Prummel, M. F.; Wiersinga, W. M.; Mourits, M. P.; Koornneef, L.; Berghout, A.; van der Gaag, R.

    1990-01-01

    Many clinicians have the impression that treatment of thyroid dysfunction ameliorates ophthalmopathy in Graves' disease. The aim of our study was to relate thyroid function to the severity of Graves' ophthalmopathy. We studied 90 patients with Graves' ophthalmopathy and Graves' hyperthyroidism in

  19. Study on severe accident induced by large break loss of coolant accident for pressureized water reactor

    International Nuclear Information System (INIS)

    Zhang Longfei; Zhang Dafa; Wang Shaoming

    2007-01-01

    Using the best estimate computer code SCDAP/RELAP5/MOD3.2 and taking US Westinghouse corporation Surry nuclear power plant as the reference object, a typical three-loop pressurized water reactor severe accident calculation model was established and 25 cm large break loss of coolant accident (LBLOCA) in cold and hot leg of primary loop induced core melt accident was analyzed. The calculated results show that core melt progression is fast and most of the core material melt and relocated to the lower plenum. The lower head of reactor pressure vessel failed at an early time and the cold leg break is more severe than the hot leg break in primary loop during LBLOCA. (authors)

  20. Functionalized Surface Geometries Induce: “Bone: Formation by Autoinduction”

    Directory of Open Access Journals (Sweden)

    Ugo Ripamonti

    2018-02-01

    Full Text Available The induction of tissue formation, and the allied disciplines of tissue engineering and regenerative medicine, have flooded the twenty-first century tissue biology scenario and morphed into high expectations of a fulfilling regenerative dream of molecularly generated tissues and organs in assembling human tissue factories. The grand conceptualization of deploying soluble molecular signals, first defined by Turing as forms generating substances, or morphogens, stemmed from classic last century studies that hypothesized the presence of morphogens in several mineralized and non-mineralized mammalian matrices. The realization of morphogens within mammalian matrices devised dissociative extractions and chromatographic procedures to isolate, purify, and finally reconstitute the cloned morphogens, found to be members of the transforming growth factor-β (TGF-β supergene family, with insoluble signals or substrata to induce de novo tissue induction and morphogenesis. Can we however construct macroporous bioreactors per se capable of inducing bone formation even without the exogenous applications of the osteogenic soluble molecular signals of the TGF-β supergene family? This review describes original research on coral-derived calcium phosphate-based macroporous constructs showing that the formation of bone is independent of the exogenous application of the osteogenic soluble signals of the TGF-β supergene family. Such signals are the molecular bases of the induction of bone formation. The aim of this review is to primarily describe today's hottest topic of biomaterials' science, i.e., to construct and define osteogenetic biomaterials' surfaces that per se, in its own right, do initiate the induction of bone formation. Biomaterials are often used to reconstruct osseous defects particularly in the craniofacial skeleton. Edentulism did spring titanium implants as tooth replacement strategies. No were else that titanium surfaces require functionalized

  1. Effect of severe anaemia on renal function: a case-control study

    International Nuclear Information System (INIS)

    Kumar, A.; Hentok, P.; Chandrashekar, N.; Thomas, E.J.; Tripathi, M.; Bal, C.S.; Ghosh, A.; Jailkhani, B.L.; Malhotra, O.P.

    2002-01-01

    Aim: Anaemia, if severe, causes multi systemic functional changes. We tried to find out the effect of severe anaemia on renal function. Materials and Methods: A total of 66 patients with severe anemia and 10 healthy controls were recruited in this study. The cases were divided into following groups: group A: patients with Hb≤3 gm/dl (n=33); group B: patients with Hb≤6 but > 3 gm/dl (n=33); group C: healthy controls with normal renal function and Hb>12gm/dl. Out of 66 anaemic patients, 36 had nutritional anaemia (mainly iron deficiency; group A=20, group B=16), 24 patients were suffering from aplastic anaemia (group A=11, group B=13) and rest 6 had megaloblastic anaemia (group A=2, group B=4). No subject had hypertension, diabetes, primary renal dysfunction or any other systemic illness, affecting kidney. Various renal function test parameters and diagnostic renal failure indices were obtained for all subjects. GFR with 2-sample method after injection of 99m-Tc DTPA and ERPF with single sample method after injection of 131-I OIH were also calculated. Results: Fourteen patients had mild to moderate pedal edema (10 in group A and 4 in group B). Out of these patients, 8 had palpable liver and signs of systemic congestion. Signs of raised systemic venous pressure (raised JVP) were found in 7 patients of group A. In about 55% of patients, chest x-ray showed mild to moderately enlarged heart with disturbed cardiophrenic angle. Urine output was >600 ml/day in all cases. Results are presented. All renal functional parameters and indices were significantly reduced in anaemic patients and were suggestive of pre-renal failure. The reduction was correlating well with the severity of anaemia.Conclusion: Severe anaemia leads to renal dysfunction with alteration of minor and major renal failure indices, which can be characterized by sub-clinical and pre-biochemical non-oliguric pre-renal failure

  2. Glutamine granule-supplemented enteral nutrition maintains immunological function in severely burned patients.

    Science.gov (United States)

    Peng, Xi; Yan, Hong; You, Zhongyi; Wang, Pei; Wang, Shiliang

    2006-08-01

    Glutamine is an important energy source for immune cells. It is a necessary nutrient for cell proliferation, and serves as specific fuel for lymphocytes, macrophages, and enterocytes when it is present in appropriate concentrations. The purpose of this clinical study was to observe the effects of enteral nutrition supplemented with glutamine granules on immunologic function in severely burned patients. Forty-eight severely burned patients (total burn surface area 30-75%, full thickness burn area 20-58%) who met the requirements of the protocol joined this double-blind randomized controlled clinical trail. Patients were randomly divided into two groups: burn control group (B group, 23 patients) and glutamine treated group (Gln group, 25 patients). There was isonitrogenous and isocaloric intake in both groups, Gln and B group patents were given glutamine granules or placebo (glycine) at 0.5 g/kgd for 14 days with oral feeding or tube feeding, respectively. The plasma level of glutamine and several indices of immunologic function including lymphocyte transformation ratio, neutrophil phagocytosis index (NPI), CD4/CD8 ratio, the content of immunoglobulin, complement C3, C4 and IL-2 levels were determined. Moreover, wound healing rate of burn area was observed and then hospital stay was recorded. The results showed significantly reduced plasma glutamine and damaged immunological function after severe burn Indices of cellular immunity function were remarkably decreased from normal controls. After taking glutamine granules for 14 days, plasma glutamine concentration was significantly higher in Gln group than that in B group (607.86+/-147.25 micromol/L versus 447.63+/-132.38 micromol/L, P0.05). In addition, wound healing was better and hospital stay days were reduced in Gln group (46.59+/-12.98 days versus 55.68+/-17.36 days, Pburn; supplemented glutamine granules with oral feeding or tube feeding abate the degree of immunosuppression, improve immunological function

  3. Association Between Severe Vitamin D Deficiency, Lung Function and Asthma Control.

    Science.gov (United States)

    Beyhan-Sagmen, Seda; Baykan, Ozgur; Balcan, Baran; Ceyhan, Berrin

    2017-04-01

    To examine the relationship between severe vitamin D deficiency, asthma control, and pulmonary function in Turkish adults with asthma. One hundred six asthmatic patients underwent pulmonary function tests skin prick test, peripheral blood eosinophil counts, IgE, body mass index and vitamin D levels were determined. Patients were divided into 2 subgroups according to vitamin D levels (vitamin D level<10ng/ml and vitamin D level≥10 ng/ml). Asthma control tests were performed. The mean age of subgroup i (vitamin D level<10) was 37±10 and the mean age of subgroup ii (vitamin D level≥10ng/ml) was 34±8. Sixty-six percent of patients had severe vitamin D deficiency (vitamin D level<10 ng/ml). There was a significant trend towards lower absolute FEV 1 (L) values in patients with lower vitamin D levels (P=.001). Asthma control test scores were significantly low in the severe deficiency group than the other group (P=.02). There were a greater number of patients with uncontrolled asthma (asthma control test scores<20) in the severe vitamin D deficiency group (P=.040). Patients with severe vitamin D deficiency had a higher usage of inhaled corticosteroids than the group without severe vitamin D deficiency (P=.015). There was a significant trend towards lower absolute FEV 1 (L) (P=.005, r=.272) values in patients with lower vitamin D levels. Vitamin D levels were inversely related with body mass index (P=.046). The incidence of severe vitamin D deficiency was high in adult Turkish asthmatics. In addition, lower vitamin D levels were associated with poor asthma control and decreased pulmonary function. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. Autoimmune severe hypertriglyceridemia induced by anti-apolipoprotein C-II antibody.

    Science.gov (United States)

    Yamamoto, Hiroyasu; Tanaka, Minoru; Yoshiga, Satomi; Funahashi, Tohru; Shimomura, Iichiro; Kihara, Shinji

    2014-05-01

    Among type V hyperlipoproteinemias, only one-fourth of the patients have genetic defects in lipoprotein lipase (LPL) or in its associated molecules; the exact mechanism in other patients is usually unknown. The aim of the study was to report a case of severe hypertriglyceridemia induced by anti-apolipoprotein (apo) C-II autoantibody and to clarify its pathogenesis. A 29-year-old Japanese woman presented with severe persistent hypertriglyceridemia since the age of 20 years. The past history was negative for acute pancreatitis, eruptive xanthomas, or lipemia retinalis. LPL mass and activities were normal. Plasma apo C-II levels were extremely low, but no mutation was observed in APOC2. Apo C-II protein was detected in the serum by immunoprecipitation and Western blotting. Large amounts of IgG and IgM were incorporated with apo C-II protein coimmunoprecipitated by anti-apo C-II antibody. IgG, but not IgM, purified from the serum prevented interaction of apo C-II with lipid substrate and diminished LPL hydrolysis activity. We identified anti-apo C-II antibody in a myeloma-unrelated severe hypertriglyceridemic patient. In vitro analysis confirmed that the autoantibody disrupted the interaction between apo C-II and lipid substrate, suggesting the etiological role of anti-apo C-II antibody in severe hypertriglyceridemia in this patient.

  5. Intermittent Hypoxia Increases the Severity of Bleomycin-Induced Lung Injury in Mice

    Directory of Open Access Journals (Sweden)

    Thomas Gille

    2018-01-01

    Full Text Available Background. Severe obstructive sleep apnea (OSA with chronic intermittent hypoxia (IH is common in idiopathic pulmonary fibrosis (IPF. Here, we evaluated the impact of IH on bleomycin- (BLM- induced pulmonary fibrosis in mice. Methods. C57BL/6J mice received intratracheal BLM or saline and were exposed to IH (40 cycles/hour; FiO2 nadir: 6%; 8 hours/day or intermittent air (IA. In the four experimental groups, we evaluated (i survival; (ii alveolar inflammation, pulmonary edema, lung oxidative stress, and antioxidant enzymes; (iii lung cell apoptosis; and (iv pulmonary fibrosis. Results. Survival at day 21 was lower in the BLM-IH group (p<0.05. Pulmonary fibrosis was more severe at day 21 in BLM-IH mice, as assessed by lung collagen content (p=0.02 and histology. At day 4, BLM-IH mice developed a more severe neutrophilic alveolitis, (p<0.001. Lung oxidative stress was observed, and superoxide dismutase and glutathione peroxidase expression was decreased in BLM-IH mice (p<0.05 versus BLM-IA group. At day 8, pulmonary edema was observed and lung cell apoptosis was increased in the BLM-IH group. Conclusion. These results show that exposure to chronic IH increases mortality, lung inflammation, and lung fibrosis in BLM-treated mice. This study raises the question of the worsening impact of severe OSA in IPF patients.

  6. Risk assessment of severe accident-induced steam generator tube rupture

    International Nuclear Information System (INIS)

    1998-03-01

    This report describes the basis, results, and related risk implications of an analysis performed by an ad hoc working group of the U.S. Nuclear Regulatory Commission (NRC) to assess the containment bypass potential attributable to steam generator tube rupture (SGTR) induced by severe accident conditions. The SGTR Severe Accident Working Group, comprised of staff members from the NRC's Offices of Nuclear Reactor Regulation (NRR) and Nuclear Regulatory Research (RES), undertook the analysis beginning in December 1995 to support a proposed steam generator integrity rule. The work drew upon previous risk and thermal-hydraulic analyses of core damage sequences, with a focus on the Surry plant as a representative example. This analysis yielded new results, however, derived by predicting thermal-hydraulic conditions of selected severe accident scenarios using the SCDAP/RELAP5 computer code, flawed tube failure modeling, and tube failure probability estimates. These results, in terms of containment bypass probability, form the basis for the findings presented in this report. The representative calculation using Surry plant data indicates that some existing plants could be vulnerable to containment bypass resulting from tube failure during severe accidents. To specifically identify the population of plants that may pose a significant bypass risk would require more definitive analysis considering uncertainties in some assumptions and plant- and design-specific variables. 46 refs., 62 figs., 37 tabs

  7. Accuracy of automated classification of major depressive disorder as a function of symptom severity.

    Science.gov (United States)

    Ramasubbu, Rajamannar; Brown, Matthew R G; Cortese, Filmeno; Gaxiola, Ismael; Goodyear, Bradley; Greenshaw, Andrew J; Dursun, Serdar M; Greiner, Russell

    2016-01-01

    Growing evidence documents the potential of machine learning for developing brain based diagnostic methods for major depressive disorder (MDD). As symptom severity may influence brain activity, we investigated whether the severity of MDD affected the accuracies of machine learned MDD-vs-Control diagnostic classifiers. Forty-five medication-free patients with DSM-IV defined MDD and 19 healthy controls participated in the study. Based on depression severity as determined by the Hamilton Rating Scale for Depression (HRSD), MDD patients were sorted into three groups: mild to moderate depression (HRSD 14-19), severe depression (HRSD 20-23), and very severe depression (HRSD ≥ 24). We collected functional magnetic resonance imaging (fMRI) data during both resting-state and an emotional-face matching task. Patients in each of the three severity groups were compared against controls in separate analyses, using either the resting-state or task-based fMRI data. We use each of these six datasets with linear support vector machine (SVM) binary classifiers for identifying individuals as patients or controls. The resting-state fMRI data showed statistically significant classification accuracy only for the very severe depression group (accuracy 66%, p = 0.012 corrected), while mild to moderate (accuracy 58%, p = 1.0 corrected) and severe depression (accuracy 52%, p = 1.0 corrected) were only at chance. With task-based fMRI data, the automated classifier performed at chance in all three severity groups. Binary linear SVM classifiers achieved significant classification of very severe depression with resting-state fMRI, but the contribution of brain measurements may have limited potential in differentiating patients with less severe depression from healthy controls.

  8. Induced tolerance to nebulized colistin after severe reaction to the drug.

    Science.gov (United States)

    Domínguez-Ortega, J; Manteiga, E; Abad-Schilling, C; Juretzcke, M A; Sánchez-Rubio, J; Kindelan, C

    2007-01-01

    Daily nebulized colistin therapy has been used as maintenance therapy for patients with chronic Pseudomonas aeruginosa infection and in treatment protocols aimed at eradicating early P aeruginosa infection. Colistin-induced nephrotoxicity and mild neurotoxic effects have been described but hypersensitivity reactions are rare. However, bronchial constriction has been reported associated with the inhalation of the antibiotic. We report the case of a 63-year-old man who had been diagnosed with bronchiectasis and bronchopleural fistula and who developed severe bronchospasm when using nebulized colistin. A skin prick test (80 mg/mL) with colistin was performed and was negative. An intradermal test was not performed due to its possible irritant effect. As our patient suffered from a tobramycin-resistant P aeruginosa infection, we started a procedure to induce tolerance to 80 mg colistin (8 mg, 16 mg, 24 mg, 32 mg, 40 mg, 80 mg) nebulized in 30-minutes-intervals. No changes in forced expiratory volume in 1 second values were observed and the patient continues on treatment twice daily after the tolerance induction with no new episodes of bronchospasm. We report the first successful procedure to induce tolerance to colistin after escalating doses of inhaled colistin.

  9. Protective Effect of Tetrandrine on Sodium Taurocholate-Induced Severe Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Xian-lin Wu

    2015-01-01

    Full Text Available Tet is a type of alkaloid extracted from Stephania tetrandra, and it has recently been demonstrated that Tet can protect against inflammation and free radical injury and inhibit the release of inflammatory mediators. The present study was designed to observe the protective effect of Tet on sodium taurocholate-induced severe acute pancreatitis (SAP. The rat model of SAP was induced by retrograde bile duct injection of sodium taurocholate and then treated with Verapamil and Tet. The results showed that Tet can reduce NF-κB activation in pancreas issue, inhibit the SAP cascade, and improve SAP through inducing pancreas acinar cell apoptosis and stabilizing intracellular calcium in the pancreas, thus mitigating the damage to the pancreas. Our study revealed that Tet may reduce systemic inflammatory response syndrome (SIRS and multiple organ dysfunction syndromes (MODS to protect against damage, and these roles may be mediated through the NF-κB pathway to improve the proinflammatory/anti-inflammatory imbalance.

  10. Serum phosphate is an early predictor of outcome in severe acetaminophen-induced hepatotoxicity

    DEFF Research Database (Denmark)

    Schmidt, Lars E; Dalhoff, Kim

    2002-01-01

    Hypophosphatemia is frequently observed in acetaminophen-induced hepatotoxicity and may be involved in the pathogenesis of hepatic failure. The aim of the study was to evaluate the prognostic value of serial measurements of serum phosphate in patients with severe acetaminophen poisoning. Prospect......Hypophosphatemia is frequently observed in acetaminophen-induced hepatotoxicity and may be involved in the pathogenesis of hepatic failure. The aim of the study was to evaluate the prognostic value of serial measurements of serum phosphate in patients with severe acetaminophen poisoning...... Hospital (KCH) criteria. Phosphate concentrations were significantly higher in nonsurvivors than in survivors at 48 to 72 hours after overdose (mean 2.65 +/- 1.18 mmol/L vs. 0.68 +/- 0.22 mmol/L, P L vs. 0.59 +/- 0.23 mmol/L, P ...). A threshold phosphate concentration of 1.2 mmol/L at 48 to 96 hours after overdose had sensitivity 89%, specificity 100%, accuracy 98%, positive predictive value 100%, and negative predictive value 98%. The phosphate criteria had higher sensitivity, accuracy, and positive and negative predictive values than...

  11. Cyclophosphamide-induced symptomatic hyponatremia, a rare but severe side effect: a case report

    Directory of Open Access Journals (Sweden)

    Elazzazy S

    2014-09-01

    Full Text Available Shereen Elazzazy,1 Asmaa Elhassan Mohamed,2 Amaal Gulied1 1Pharmacy Department, 2Oncology Hematology Department, National Center for Cancer Care and Research (NCCCR, Hamad Medical Corporation, Doha, QatarAbstract: Cyclophosphamide is commonly used in the treatment of malignant diseases. Symptomatic severe hyponatremia induced by low-dose cyclophosphamide is very uncommon worldwide. We report a case of severe symptomatic hyponatremia that developed in a female breast cancer patient following the first cycle of chemotherapy containing low-dose cyclophosphamide. Her laboratory test showed serum Na of 112 mmol/L. Her hyponatremia was initially treated with sodium bicarbonate. She completely recovered without neurological deficits after slow correction of the serum Na concentration. Although hyponatremia is a rare toxicity it should always be considered during the usage of cyclophosphamide, even if the dosage is low, especially with concurrent use of other medications that impair water excretion, like chlorthalidone. This report describes the first reported case of cyclophosphamide-induced hyponatremia in Qatar.Keywords: AC protocol, adjuvant chemotherapy, breast cancer, cyclophosphamide, hyponatremia, thiazides

  12. Neutralizing effects of polyvalent antivenom on severe inflammatory response induced by Mesobuthus eupeus scorpion venom

    Directory of Open Access Journals (Sweden)

    Zayerzadeh1 E.

    2014-11-01

    Full Text Available This study evaluated the effects of Mesobuthus eupeus (Me scorpion venom on inflammatory response following injection. Additionally, the present study examined whether immunotherapy at specific time intervals would be effective on inflammatory response after Me venom inoculation. Animals were divided randomly into four groups: the first group received LD50 of venom and the second and third groups of animals; immunotherapy was performed in different time intervals and fourth group was considered as control group. Me venom inoculation is caused respiratory perturbations such as respiratory distress, respiration with open mouth, crepitation and finally respiratory arrest. Me inoculation is resulted in increased pro-inflammatory cytokines including TNF-α and IL-1. Venom injection also induced inflammatory response, characterized by significant increase in serum white blood cells and neutrophils at 30, 60 and 180 min following envenomation. Simultaneous administration of antivenom and venom prevented entirely clinical sings, cytokines and hematological changes. Delayed immunotherapy gradually ameliorated clinical features, cytokines changes and hematological abnormalities related to the envenomation. In conclusion, our observations indicate injection of M. eupeus scorpion venom induces severe inflammatory response which can be one of the causes of clinical complications. Additionally, immunotherapy beyond 1 h after envenomation with appropriate dose and route in victims with severe inflammatory response related to the M.eupeus scorpion envenomation is beneficial.

  13. Overdose pattern and outcome in paracetamol-induced acute severe hepatotoxicity

    Science.gov (United States)

    Craig, Darren G N; Bates, Caroline M; Davidson, Janice S; Martin, Kirsty G; Hayes, Peter C; Simpson, Kenneth J

    2011-01-01

    AIMS Paracetamol (acetaminophen) hepatotoxicity is the commonest cause of acute liver failure (ALF) in the UK. Conflicting data regarding the outcomes of paracetamol-induced ALF resulting from different overdose patterns are reported. METHODS Using prospectively defined criteria, we have analysed the impact of overdose pattern upon outcome in a cohort of 938 acute severe liver injury patients admitted to the Scottish Liver Transplantation Unit. RESULTS Between 1992 and 2008, 663 patients were admitted with paracetamol-induced acute severe liver injury. Of these patients, 500 (75.4%) had taken an intentional paracetamol overdose, whilst 110 (16.6%) had taken an unintentional overdose. No clear overdose pattern could be determined in 53 (8.0%). Unintentional overdose patients were significantly older, more likely to abuse alcohol, and more commonly overdosed on compound narcotic/paracetamol analgesics compared with intentional overdose patients. Unintentional overdoses had significantly lower admission paracetamol and alanine aminotransferase concentrations compared with intentional overdoses. However, unintentional overdoses had greater organ dysfunction at admission, and subsequently higher mortality (unintentional 42/110 (38.2%), intentional 128/500 (25.6%), P paracetamol overdose is associated with increased mortality compared with intentional paracetamol overdose, despite lower admission paracetamol concentrations. Alternative prognostic criteria may be required for unintentional paracetamol overdoses. PMID:21219409

  14. Severe hypoxia induces chemo-resistance in clinical cervical tumors through MVP over-expression.

    Science.gov (United States)

    Lara, Pedro C; Lloret, Marta; Clavo, Bernardino; Apolinario, Rosa M; Henríquez-Hernández, Luis Alberto; Bordón, Elisa; Fontes, Fausto; Rey, Agustín

    2009-08-06

    Oxygen molecule modulates tumour response to radiotherapy. Higher radiation doses are required under hypoxic conditions to induce cell death. Hypoxia may inhibit the non-homologous end-joining DNA repair through down regulating Ku70/80 expression. Hypoxia induces drug resistance in clinical tumours, although the mechanism is not clearly elucidated. Vaults are ribonucleoprotein particles with a hollow barrel-like structure composed of three proteins: major vault protein (MVP), vault poly(ADP-ribose) polymerase, and telomerase associated protein-1 and small untranslated RNA. Over-expression of MVP has been associated with chemotherapy resistance. Also, it has been related to poor outcome in patients treated with radiotherapy alone. The aim of the present study was to assess the relation of Major Vault Protein expression and tumor hypoxia in clinical cervical tumors. MVP, p53 and angiogenesis, together with tumor oxygenation, were determined in forty-three consecutive patients suffering from localized cervix carcinoma. High MVP expression was related to severe hypoxia compared to low MVP expressing tumors (p = 0.022). Tumors over-expressing MVP also showed increased angiogenesis (p = 0.003). Besides it, in this study we show for the first time that severe tumor hypoxia is associated with high MVP expression in clinical cervical tumors. Up-regulation of MVP by hypoxia is of critical relevance as chemotherapy is currently a standard treatment for those patients. From our results it could be suggested that hypoxia not only induces increased genetic instability, oncogenic properties and metastatization, but through the correlation observed with MVP expression, another pathway of chemo and radiation resistance could be developed.

  15. Severe hypoxia induces chemo-resistance in clinical cervical tumors through MVP over-expression

    International Nuclear Information System (INIS)

    Lara, Pedro C; Lloret, Marta; Clavo, Bernardino; Apolinario, Rosa M; Henríquez-Hernández, Luis Alberto; Bordón, Elisa; Fontes, Fausto; Rey, Agustín

    2009-01-01

    Oxygen molecule modulates tumour response to radiotherapy. Higher radiation doses are required under hypoxic conditions to induce cell death. Hypoxia may inhibit the non-homologous end-joining DNA repair through down regulating Ku70/80 expression. Hypoxia induces drug resistance in clinical tumours, although the mechanism is not clearly elucidated. Vaults are ribonucleoprotein particles with a hollow barrel-like structure composed of three proteins: major vault protein (MVP), vault poly(ADP-ribose) polymerase, and telomerase associated protein-1 and small untranslated RNA. Over-expression of MVP has been associated with chemotherapy resistance. Also, it has been related to poor outcome in patients treated with radiotherapy alone. The aim of the present study was to assess the relation of Major Vault Protein expression and tumor hypoxia in clinical cervical tumors. MVP, p53 and angiogenesis, together with tumor oxygenation, were determined in forty-three consecutive patients suffering from localized cervix carcinoma. High MVP expression was related to severe hypoxia compared to low MVP expressing tumors (p = 0.022). Tumors over-expressing MVP also showed increased angiogenesis (p = 0.003). Besides it, in this study we show for the first time that severe tumor hypoxia is associated with high MVP expression in clinical cervical tumors. Up-regulation of MVP by hypoxia is of critical relevance as chemotherapy is currently a standard treatment for those patients. From our results it could be suggested that hypoxia not only induces increased genetic instability, oncogenic properties and metastatization, but through the correlation observed with MVP expression, another pathway of chemo and radiation resistance could be developed

  16. Sodium butyrate protects against severe burn-induced remote acute lung injury in rats.

    Directory of Open Access Journals (Sweden)

    Xun Liang

    Full Text Available High-mobility group box 1 protein (HMGB1, a ubiquitous nuclear protein, drives proinflammatory responses when released extracellularly. It plays a key role as a distal mediator in the development of acute lung injury (ALI. Sodium butyrate, an inhibitor of histone deacetylase, has been demonstrated to inhibit HMGB1 expression. This study investigates the effect of sodium butyrate on burn-induced lung injury. Sprague-Dawley rats were divided into three groups: 1 sham group, sham burn treatment; 2 burn group, third-degree burns over 30% total body surface area (TBSA with lactated Ringer's solution for resuscitation; 3 burn plus sodium butyrate group, third-degree burns over 30% TBSA with lactated Ringer's solution containing sodium butyrate for resuscitation. The burned animals were sacrificed at 12, 24, and 48 h after burn injury. Lung injury was assessed in terms of histologic changes and wet weight to dry weight (W/D ratio. Tumor necrosis factor (TNF-α and interleukin (IL-8 protein concentrations in bronchoalveolar lavage fluid (BALF and serum were measured by enzyme-linked immunosorbent assay, and HMGB1 expression in the lung was determined by Western blot analysis. Pulmonary myeloperoxidase (MPO activity and malondialdehyde (MDA concentration were measured to reflect neutrophil infiltration and oxidative stress in the lung, respectively. As a result, sodium butyrate significantly inhibited the HMGB1 expressions in the lungs, reduced the lung W/D ratio, and improved the pulmonary histologic changes induced by burn trauma. Furthermore, sodium butyrate administration decreased the TNF-α and IL-8 concentrations in BALF and serum, suppressed MPO activity, and reduced the MDA content in the lungs after severe burn. These results suggest that sodium butyrate attenuates inflammatory responses, neutrophil infiltration, and oxidative stress in the lungs, and protects against remote ALI induced by severe burn, which is associated with inhibiting HMGB1

  17. Hydrogen-rich saline ameliorates the severity of L-arginine-induced acute pancreatitis in rats

    International Nuclear Information System (INIS)

    Chen, Han; Sun, Yan Ping; Li, Yang; Liu, Wen Wu; Xiang, Hong Gang; Fan, Lie Ying; Sun, Qiang; Xu, Xin Yun; Cai, Jian Mei; Ruan, Can Ping; Su, Ning; Yan, Rong Lin; Sun, Xue Jun; Wang, Qiang

    2010-01-01

    Molecular hydrogen, which reacts with the hydroxyl radical, has been considered as a novel antioxidant. Here, we evaluated the protective effects of hydrogen-rich saline on the L-arginine (L-Arg)-induced acute pancreatitis (AP). AP was induced in Sprague-Dawley rats by giving two intraperitoneal injections of L-Arg, each at concentrations of 250 mg/100 g body weight, with an interval of 1 h. Hydrogen-rich saline (>0.6 mM, 6 ml/kg) or saline (6 ml/kg) was administered, respectively, via tail vein 15 min after each L-Arg administration. Severity of AP was assessed by analysis of serum amylase activity, pancreatic water content and histology. Samples of pancreas were taken for measuring malondialdehyde and myeloperoxidase. Apoptosis in pancreatic acinar cell was determined with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL). Expression of proliferating cell nuclear antigen (PCNA) and nuclear factor kappa B (NF-κB) were detected with immunohistochemistry. Hydrogen-rich saline treatment significantly attenuated the severity of L-Arg-induced AP by ameliorating the increased serum amylase activity, inhibiting neutrophil infiltration, lipid oxidation and pancreatic tissue edema. Moreover, hydrogen-rich saline treatment could promote acinar cell proliferation, inhibit apoptosis and NF-κB activation. These results indicate that hydrogen treatment has a protective effect against AP, and the effect is possibly due to its ability to inhibit oxidative stress, apoptosis, NF-κB activation and to promote acinar cell proliferation.

  18. Splenectomy attenuates severe thermal trauma-induced intestinal barrier breakdown in rats.

    Science.gov (United States)

    Liu, Xiang-dong; Chen, Zhen-yong; Yang, Peng; Huang, Wen-guang; Jiang, Chun-fang

    2015-12-01

    The severe local thermal trauma activates a number of systemic inflammatory mediators, such as TNF-α, NF-κB, resulting in a disruption of gut barrier. The gastrointestinal tight junction (TJ) is highly regulated by membrane-associated proteins including zonula occludens protein-1 (ZO-1) and occludin, which can be modulated by inflammatory cytokines. As splenectomy has been shown to reduce secretion of cytokines, we hypothesized that (1) severe scald injury up-regulates TNF-α and NF-κB, meanwhile down-regulates expression of ZO-1 and occludin, leading to the increased intestinal permeability, and (2) splenectomy can prevent the burn-induced decrease in ZO-1 and occludin expression, resulting in improved intestinal barrier. Wistar rats undergoing a 30% total body surface area (TBSA) thermal trauma were randomized to receive an accessorial splenectomy meanwhile or not. Intestinal injury was assessed by histological morphological analysis, and serum endotoxin levels, TNF-α, NF-κB, ZO-1 and occludin levels were detected by Western blotting in the terminal ileum mucosal tissue. 30% TBSA burn caused a significant increase in serum endotoxin levels, but NF-κB, and TNF-α, and the average intestinal villus height and mucosal thickness were decreased significantly. Burn injury could also markedly decrease the levels of ZO-1 and occludin in terminal ileum mucosal tissue (all PSplenectomy at 7th day after burn significantly reversed the burn-induced breakdown of ZO-1 and occludin (all PSplenectomy may provide a therapeutic benefit in restoring burn-induced intestinal barrier by decreasing the release of inflammatory cytokines and recovering TJ proteins.

  19. When Is the Optimal Timing of Surgical Intervention for Severe Functional Tricuspid Regurgitation?

    Directory of Open Access Journals (Sweden)

    Nobuhiro Nakanishi

    2017-01-01

    Full Text Available Functional tricuspid regurgitation (TR is a serious pathology to be noted for severe right heart failure (HF and poor prognosis; however, the conventional assessment of TR has some limitations and the optimal timing of surgical intervention remains unclear. A 79-year-old Japanese female was admitted to our hospital to undergo cardiac surgery, because edema gradually got worse despite the increase in diuretics. She had a history of atrial fibrillation (AF and chronic HF due to severe TR and had been treated with a furosemide for leg edema 4 years ago. A transthoracic echocardiogram (TTE, transesophageal echocardiogram, cardiac magnetic resonance imaging, and cardiac pool scintigraphy demonstrated severe functional TR with tricuspid annular dilation, insufficient tricuspid valve coaptation, and reduced right ventricular ejection fraction (EF but preserved left ventricular EF. In addition, Swan-Ganz catheter study showed normal pulmonary arterial wedge pressure and mean pulmonary arterial pressure. Tricuspid ring annuloplasty was performed with MC3 ring. Postoperative TTE showed trivial TR, and she had no edema with normal sinus rhythm two months later. Annuloplasty to severe functional TR caused by tricuspid annular dilation due to AF dramatically improved right HF. Cardiologist should pay strict attention to the optimal timing of surgical intervention for TR.

  20. Mechanochemistry Induced Using Force Exerted by a Functionalized Microscope Tip

    DEFF Research Database (Denmark)

    Zhang, Yajie; Wang, Yongfeng; Lü, Jing-Tao

    2017-01-01

    Atomic-scale mechanochemistry is realized from force exerted by a C60 -functionalized scanning tunneling microscope tip. Two conformers of tin phthalocyanine can be prepared on coinage-metal surfaces. A transition between these conformers is induced on Cu(111) and Ag(100). Density...

  1. Relationship between plasma matrix metalloproteinase levels, pulmonary function, bronchodilator response, and emphysema severity.

    Science.gov (United States)

    Koo, Hyeon-Kyoung; Hong, Yoonki; Lim, Myoung Nam; Yim, Jae-Joon; Kim, Woo Jin

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation in the airway and lung. A protease-antiprotease imbalance has been suggested as a possible pathogenic mechanism for COPD. We evaluated the relationship between matrix metalloproteinase (MMP) levels and COPD severity. Plasma levels of MMP-1, MMP-8, MMP-9, and MMP-12 were measured in 57 COPD patients and 36 normal controls. The relationship between MMP levels and lung function, emphysema index, bronchial wall thickness, pulmonary artery pressure, and quality of life was examined using general linear regression analyses. There were significant associations of MMP-1 with bronchodilator reversibility and of MMP-8 and MMP-9 with lung function. Also, MMP-1, MMP-8, and MMP-9 levels were correlated with the emphysema index, independent of lung function. However, MMP-12 was not associated with lung function or emphysema severity. Associations between MMP levels and bronchial wall thickness, pulmonary artery pressure, and quality of life were not statistically significant. Plasma levels of MMP-1, MMP-8, and MMP-9 are associated with COPD severity and can be used as a biomarker to better understand the characteristics of COPD patients.

  2. Multiple cluster axis II comorbidity and functional outcome in severe patients with borderline personality disorder.

    Science.gov (United States)

    Palomares, Nerea; McMaster, Antonia; Díaz-Marsá, Marina; de la Vega, Irene; Montes, Ana; Carrasco, José Luis

    2016-11-01

    Current literature suggests that personality disorder comorbidity negatively contributes to both the severity and prognosis of other disorders; however, little literature has been devoted to its influence on borderline personality disorder (BPD). The objective of the present work is to study comorbidity with other personality disorders in a severe clinical sample of patients with BPD, and its relationship with global functionality. A sample of 65 patients with severe borderline personality disorder was included in the study. Clinical and functionality measures were applied in order to study comorbidity of BPD with other disorders and its relationship with functionality. Associations with other comorbid PDs were analyzed with t-tests and linear correlations. Most patients (87%) presented comorbidity with other PDs. Almost half of the sample (42%) presented more than two PDs, and cluster A (paranoid) and C (obsessive and avoidant) PD were more frequent than cluster B (histrionic and antisocial). Only the presence of avoidant PD predicted a worse functional outcome in the long term (U Mann Withney ppersonality disorder might negatively predict for prognosis.

  3. Genetic and environmental components of female depression as a function of the severity of the disorder.

    Science.gov (United States)

    Rusby, James S M; Tasker, Fiona; Cherkas, Lynn

    2016-10-01

    Both clinical care and genome-wide studies need to account for levels of severity in the etiology of depression. The purpose of the study is to estimate the genetic and environmental components of female depression as a function of the severity of the disorder. A genetic and environmental model analysis of depression incidence was made using the IOP Depression Severity Measure (IDSM). Details of lifetime depression incidence were obtained by questionnaire from twins on the DTR registry. Data from 1449 matched female twin pairs in the age range 19-85 years in four ordinal categories of increasing severity were employed in the analysis. Estimates of additive and dominance genetic components of 27% and 25% were found when all three levels of depression were included, and near zero and 33% when the recurrent/severe level was excluded. Shared environmental effects were not significant in either case, but the estimate for random environmental effects was greater when the severe level was excluded. These results suggest that the incidence of severe depression is associated with homozygotic alleles and the less severe with heterozygotic alleles. This is in accord with the finding that the hereditary component of severe depression is relatively high and that milder forms are more dependent on life-time environmental factors. Such conclusions have clinical implications for the diagnosis and treatment of the disorder by practicing psychiatrists. They also lead to the importance of focusing future genome-wide and linkage studies on those females with severe levels of depression if progress in identifying genetic risk loci is to be made.

  4. Long-term psychological functioning of adults with severe congenital facial disfigurement.

    Science.gov (United States)

    Versnel, Sarah L; Plomp, Raul G; Passchier, Jan; Duivenvoorden, Hugo J; Mathijssen, Irene M J

    2012-01-01

    In adults with severe congenital facial disfigurement, assessment of long-term psychological impact remains limited. This study determines the long-term psychological functioning in these patients and evaluates differences compared with patients with acquired facial disfigurement and a non-facially disfigured reference group. Also explored is the extent to which psychological functioning of the congenital group is related to satisfaction with facial appearance, fear of negative appearance evaluation by others, self-esteem, and severity of the facial deformity. Fifty-nine adults with severe congenital facial disfigurement, 59 adults with a traumatically acquired facial deformity in adulthood, and 120 non-facially disfigured adults completed standardized psychological, physical, and demographic questionnaires, including the Fear of Negative Appearance Evaluation Scale, the Rosenberg Self-Esteem Scale, the Hospital Anxiety and Depression Scale, the Achenbach Adult Self-Report, the 36-Item Short-Form Health Survey, and a visual analogue scale. Adults with severe congenital facial disfigurement had relatively normal psychological functioning but appeared more prone to internalizing problems than the non-facially disfigured adults. Compared with patients with an acquired facial deformity, the congenital group displayed fewer problems on the physical component score of quality of life only. Satisfaction with facial appearance, fear of negative appearance evaluation, and self-esteem were good predictors of the different aspects of psychological functioning, with the exception of the physical component score of quality of life. Improving satisfaction with facial appearance (by surgery), enhancing self-esteem, or lowering fear of negative appearance evaluation (by psychological support) may enhance long-term psychological functioning. Future research should focus on the individual patient and risk factors for maladjustment. Risk, II.

  5. Cisplatin Therapy Does Not Worsen Renal Function in Severe Antenatal Bartter Syndrome.

    Science.gov (United States)

    Welch, Thomas R; Shaffer, David R; Feldman, Darren R

    2017-01-01

    A 30-year-old man with severe antenatal Bartter syndrome, diagnosed and treated in infancy, developed testicular carcinoma. Despite the known renal complications of cisplatin, this drug was used for his chemotherapy because of its superior antineoplastic effect. Nonsteroidal anti-inflammatory drug administration was continued during cisplatin therapy. Despite an increase in his oral potassium requirement, renal function was maintained following completion of chemotherapy. In spite of its significant associated nephrotoxicity, cisplatin can be used in patients with severe antenatal Bartter syndrome if required for therapy of malignancy.

  6. Severe Food Protein-Induced Enterocolitis Syndrome to Cow’s Milk in Infants

    Directory of Open Access Journals (Sweden)

    Min Yang

    2015-12-01

    Full Text Available Cow’s milk is the most common cause of food-protein-induced enterocolitis syndrome (FPIES. The aim of this study was to examine the clinical features and treatment outcomes of infants with severe FPIES to cow’s milk. We reviewed all infants ≤12 months of age who were hospitalized and diagnosed with severe FPIES to cow’s milk between 1 January 2011 and 31 August 2014 in a tertiary Children’s Medical Center in China. Patients’ clinical features, feeding patterns, laboratory tests, and treatment outcomes were reviewed. A total of 12 infants met the inclusion criteria. All infants presented with diarrhea, edema, and hypoalbuminemia. Other main clinical manifestations included regurgitation/vomiting, skin rashes, low-grade fever, bloody and/or mucous stools, abdominal distention, and failure to thrive. They had clinical remission with resolution of diarrhea and significant increase of serum albumin after elimination of cow’s milk protein (CMP from the diet. The majority of infants developed tolerance to the CMP challenge test after 12 months of avoidance. In conclusion, we reported the clinical experience of 12 infants with severe FPIES to cow’s milk, which resulted in malnutrition, hypoproteinemia, and failure to thrive. Prompt treatment with CMP-free formula is effective and leads to clinical remission of FPIES in infants.

  7. Severe Hypertriglyceridemia Induced by Sirolimus Treated With Medical Management Without Plasmapheresis: A Case Report.

    Science.gov (United States)

    Kido, Kazuhiko; Evans, Rickey A; Gopinath, Anil; Flynn, Jeremy D

    2018-02-01

    Hypertriglyceridemia and hyperlipidemia are the most remarkable metabolic complications seen with long-term sirolimus therapy. We report the case of a 36-year-old woman status post bilateral lung transplantation on a maintenance immunosuppression regimen of sirolimus, tacrolimus, and prednisone who presented with status migrainosus, chest pain, abdominal discomfort, and triglyceride levels greater than 4425 mg/dL. In previously reported cases of severe hypertriglyceridemia that developed on maintenance sirolimus therapy, plasmapheresis has been utilized as an early strategy to rapidly lower triglycerides in order to minimize the risk of acute complications such as pancreatitis, but our case was managed medically without plasmapheresis. The most recent triglyceride was down to 520 mg/dL 2 months after discontinuation of sirolimus. We estimate the probability of this reaction to sirolimus as probable based on a score of 5 points on the Naranjo scale. This is the first case report to our knowledge that highlights the sole use of oral lipid-lowering drug agents to treat severe hypertriglyceridemia secondary to sirolimus without the use of plasmapheresis. Sirolimus-induced severe hypertriglyceridemia can be managed with oral lipid-lowering agents without plasmapheresis. Clinician needs to be aware of the importance of baseline and regular triglyceride monitoring in patients on sirolimus.

  8. Prevalence and severity of plaque-induced gingivitis in a Saudi adult population

    Science.gov (United States)

    Idrees, Majdy M.; Azzeghaiby, Saleh N.; Hammad, Mohammad M.; Kujan, Omar B.

    2014-01-01

    Objectives: To evaluate the prevalence and severity of plaque-induced gingivitis among a Saudi adult population in Riyadh region. Methods: Three hundred and eighty-five eligible participants in this cross-sectional study were recruited from routine dental patients attending the oral diagnosis clinic at Al-Farabi College in Riyadh, Saudi Arabia from June 2013 to December 2013. A clinical examination was performed by 2 dentists to measure the gingival and plaque indices of Löe and Silness for each participant. Results: The prevalence of gingivitis was 100% among adult subjects aged between 18-40 years old. Moreover, the mean gingival index was 1.68±0.31, which indicates a moderate gingival inflammation. In fact, males showed more severe signs of gingival inflammation compared with females (p=0.001). In addition, the mean plaque index was 0.875±0.49, which indicates a good plaque status of the participants. Interestingly, the age was not related either to the gingival inflammation (p=0.13), or to the amount of plaque accumulation (p=0.17). However, males were more affected than females (p=0.005). Conclusion: The results of this study show that plaque accumulation is strongly associated with high prevalence of moderate to severe gingivitis among Saudi subjects. PMID:25399215

  9. Measuring personality functioning in older adults: construct validity of the Severity Indices of Personality Functioning - Short Form (SIPP-SF).

    Science.gov (United States)

    Rossi, Gina; Debast, Inge; van Alphen, S P J

    2017-07-01

    The dimensional personality disorders model in the Diagnostic and Statistical Manual (DSM)-5 section III conceptually differentiates impaired personality functioning (criterion A) from the presence of pathological traits (criterion B). This study is the first to specifically address the measurement of criterion A in older adults. Moreover, the convergent/divergent validity of criterion A and criterion B will be compared in younger and older age groups. The Severity Indices of Personality Functioning - Short Form (SIPP-SF) was administered in older (N = 171) and younger adults (N = 210). The factorial structure was analyzed with exploratory structural equation modeling. Differences in convergent/divergent validity between personality functioning (SIPP-SF) and pathological traits (Personality Inventory for DSM-5; Dimensional Assessment of Personality Pathology-Basic Questionnaire) were examined across age groups. Identity Integration, Relational Capacities, Responsibility, Self-Control, and Social Concordance were corroborated as higher order domains. Although the SIPP-SF domains measured unique variation, some high correlations with pathological traits referred to overlapping constructs. Moreover, in older adults, personality functioning was more strongly related to Psychoticism, Disinhibition, Antagonism and Dissocial Behavior compared to younger adults. The SIPP-SF construct validity was demonstrated in terms of a structure of five higher order domains of personality functioning. The instrument is promising as a possible measure of impaired personality functioning in older adults. As such, it is a useful clinical tool to follow up effects of therapy on levels of personality functioning. Moreover, traits were associated with different degrees of personality functioning across age groups.

  10. Model approach for stress induced steroidal hormone cascade changes in severe mental diseases.

    Science.gov (United States)

    Volko, Claus D; Regidor, Pedro A; Rohr, Uwe D

    2016-03-01

    Stress was described by Cushing and Selye as an adaptation to a foreign stressor by the anterior pituitary increasing ACTH, which stimulates the release of glucocorticoid and mineralocorticoid hormones. The question is raised whether stress can induce additional steroidal hormone cascade changes in severe mental diseases (SMD), since stress is the common denominator. A systematic literature review was conducted in PubMed, where the steroidal hormone cascade of patients with SMD was compared to the impact of increasing stress on the steroidal hormone cascade (a) in healthy amateur marathon runners with no overtraining; (b) in healthy well-trained elite soldiers of a ranger training unit in North Norway, who were under extreme physical and mental stress, sleep deprivation, and insufficient calories for 1 week; and, (c) in soldiers suffering from post traumatic stress disorder (PTSD), schizophrenia (SI), and bipolar disorders (BD). (a) When physical stress is exposed moderately to healthy men and women for 3-5 days, as in the case of amateur marathon runners, only few steroidal hormones are altered. A mild reduction in testosterone, cholesterol and triglycerides is detected in blood and in saliva, but there was no decrease in estradiol. Conversely, there is an increase of the glucocorticoids, aldosterone and cortisol. Cellular immunity, but not specific immunity, is reduced for a short time in these subjects. (b) These changes are also seen in healthy elite soldiers exposed to extreme physical and mental stress but to a somewhat greater extent. For instance, the aldosterone is increased by a factor of three. (c) In SMD, an irreversible effect on the entire steroidal hormone cascade is detected. Hormones at the top of the cascade, such as cholesterol, dehydroepiandrosterone (DHEA), aldosterone and other glucocorticoids, are increased. However, testosterone and estradiol and their metabolites, and other hormones at the lower end of the cascade, seem to be reduced. 1

  11. Olfactory functions are not associated with autism severity in autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Dudova I

    2013-11-01

    Full Text Available Iva Dudova, Michal HrdlickaDepartment of Child Psychiatry, University Hospital Motol, Prague, Czech RepublicBackground: Changes in olfactory functions have been found in many neurodegenerative and psychiatric disorders, including autism spectrum disorders (ASDs. The aim of the present study was to evaluate the relationship between olfactory functions (odor-detection thresholds, odor identification, and odor preference and autism severity and sensory-related behavior in children and adolescents with ASD.Subjects and methods: Our sample consisted of 35 high-functioning patients with ASD (mean age 10.8±3.6 years, 31 boys. Olfactory testing (threshold and identification used the Sniffin' Sticks test. Odor pleasantness was assessed on a 5-point scale using the Identification part of the Sniffin’ Sticks test. The severity of autistic psychopathology was measured using the Childhood Autism Rating Scale (CARS.Results: Using Spearman’s correlation, we found no significant correlations between autism severity (as expressed by total CARS score and odor-detection thresholds (R=0.144, P=0.409, odor identification (R=0.07, P=0.966, or odor pleasantness (R=-0.046, P=0.794. There was also no significant relationship between CARS item 9 (“Taste, smell, and touch response and use” and odor-detection thresholds (R=0.170, P=0.330, odor identification (R=0.282, P=0.100, or odor pleasantness (R=0.017, P=0.923.Conclusion: We did not find any significant relationship between the severity of autistic psychopathology and olfactory functions.Keywords: autism spectrum disorders, psychopathology, Sniffin’ Sticks, odor threshold, odor identification, odor pleasantness

  12. Restoration of Function With Acupuncture Following Severe Traumatic Brain Injury: A Case Report

    OpenAIRE

    Wolf, Jacob; Sparks, Linda; Deng, Yong; Langland, Jeffrey

    2015-01-01

    This case report illustrates the improvement of an acupuncture-treated patient who incurred a severe traumatic brain injury (TBI) from a snowboarding accident. Over 4 years, the patient progressed from initially not being able to walk, having difficulty with speech, and suffering from poor eyesight to where he has now regained significant motor function, speech, and vision and has returned to snowboarding. A core acupuncture protocol plus specific points added to address the patient's ongoing...

  13. The Relationship between Symptom Severity and Cognitive Functions with Obesity in Fibromyalgia Syndrome

    OpenAIRE

    Selçuk Sayılır

    2017-01-01

    Objective: To investigate the relationship between obesity with symptom severity and cognitive functions in Fibromyalgia syndrome (FMS) patients. Materials and Methods: The study comprised 33 FMS patients (mean age 41.21±7.6 years). The patients who have hypertension, hypercholesterolaemia or diabetes, chronic inflammatory disorders, cardiovascular-pulmonary diseases, rheumatological/endocrine diseases, using anticoagulant therapy or have thrombotic disorders, malignancies and pregnant wom...

  14. Onset of Coagulation Function Recovery Is Delayed in Severely Injured Trauma Patients with Venous Thromboembolism.

    Science.gov (United States)

    McCully, Belinda H; Connelly, Christopher R; Fair, Kelly A; Holcomb, John B; Fox, Erin E; Wade, Charles E; Bulger, Eileen M; Schreiber, Martin A

    2017-07-01

    Altered coagulation function after trauma can contribute to development of venous thromboembolism (VTE). Severe trauma impairs coagulation function, but the trajectory for recovery is not known. We hypothesized that enhanced, early recovery of coagulation function increases VTE risk in severely injured trauma patients. Secondary analysis was performed on data from the Pragmatic Randomized Optimal Platelet and Plasma Ratio (PROPPR) trial, excluding patients who died within 24 hours or were on pre-injury anticoagulants. Patient characteristics, adverse outcomes, and parameters of platelet function and coagulation (thromboelastography) were compared from admission to 72 hours between VTE (n = 83) and non-VTE (n = 475) patients. A p value value (48 vs 24 hours), α-angle (no recovery), maximum amplitude (24 vs 12 hours), and clot lysis at 30 minutes (48 vs 12 hours). Platelet function recovery mediated by arachidonic acid (72 vs 4 hours), ADP (72 vs 12 hours), and collagen (48 vs 12 hours) was delayed in VTE patients. The VTE patients had lower mortality (4% vs 13%; p < 0.05), but fewer hospital-free days (0 days [interquartile range 0 to 8 days] vs 10 days [interquartile range 0 to 20 days]; p < 0.05) and higher complication rates (p < 0.05). Recovery from platelet dysfunction and coagulopathy after severe trauma were delayed in VTE patients. Suppressed clot lysis and compensatory mechanisms associated with altered coagulation that can potentiate VTE formation require additional investigation. Copyright © 2017 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  15. A study on quantifying COPD severity by combining pulmonary function tests and CT image analysis

    Science.gov (United States)

    Nimura, Yukitaka; Kitasaka, Takayuki; Honma, Hirotoshi; Takabatake, Hirotsugu; Mori, Masaki; Natori, Hiroshi; Mori, Kensaku

    2011-03-01

    This paper describes a novel method that can evaluate chronic obstructive pulmonary disease (COPD) severity by combining measurements of pulmonary function tests and measurements obtained from CT image analysis. There is no cure for COPD. However, with regular medical care and consistent patient compliance with treatments and lifestyle changes, the symptoms of COPD can be minimized and progression of the disease can be slowed. Therefore, many diagnosis methods based on CT image analysis have been proposed for quantifying COPD. Most of diagnosis methods for COPD extract the lesions as low-attenuation areas (LAA) by thresholding and evaluate the COPD severity by calculating the LAA in the lung (LAA%). However, COPD is usually the result of a combination of two conditions, emphysema and chronic obstructive bronchitis. Therefore, the previous methods based on only LAA% do not work well. The proposed method utilizes both of information including the measurements of pulmonary function tests and the results of the chest CT image analysis to evaluate the COPD severity. In this paper, we utilize a multi-class AdaBoost to combine both of information and classify the COPD severity into five stages automatically. The experimental results revealed that the accuracy rate of the proposed method was 88.9% (resubstitution scheme) and 64.4% (leave-one-out scheme).

  16. Pulmonary function tests and impulse oscillometry in severe chronic obstructive pulmonary disease patients′ offspring

    Directory of Open Access Journals (Sweden)

    Babak Amra

    2015-01-01

    Full Text Available Background: Several studies have showed an increased prevalence of airflow obstruction in first degree relatives of individuals with chronic obstructive pulmonary disease (COPD. Considering no specific research had evaluated airway resistance in offspring of patients with severe COPD, we utilized a spirometry and a impulse oscillometry (IO to evaluate this population. Materials and Methods: In this case control study, from November 2011 to July 2012, we consecutively evaluated 54 offsprings of severe COPD patients (case group admitted in the pulmonary ward, affiliated to the Isfahan University of Medical Sciences and control group. Pulmonary function tests and the IO were obtained for both groups. Student′s t-test was used for inter-group comparisons, and P values below 0.05 were taken as significant. Results: Abnormal increased airway resistance was seen in cases in comparison with controls (R5 Hz [46.29%, P = 0.01], R25 Hz [42.59%, P < 0.001]. Also, considering the spirometry, case group had pulmonary function parameters less than control group (forced vital capacity [FVC]; P = 0.02, forced expiratory volume in 1 st s; P < 0.001, forced expiratory flow (FEF 25-75; P < 0.001, FEF 25-75/FVC; P < 0.001 but they were in normal range. Conclusion: This study demonstrated increased airway resistance among the severe COPD offsprings. The IO may be a sensitive tool for detection of high risk subjects in families with COPD.

  17. Investigating executive functions in children with severe speech and movement disorders using structured tasks

    Directory of Open Access Journals (Sweden)

    Kristine eStadskleiv

    2014-09-01

    Full Text Available Executive functions are the basis for goal-directed activity and include planning, monitoring, and inhibition, and language seems to play a role in the development of these functions. There is a tradition of studying executive function in both typical and atypical populations, and the present study investigates executive functions in children with severe speech and motor impairments who are communicating using communication aids with graphic symbols, letters and/or words. There are few neuropsychological studies of children in this group and little is known about their cognitive functioning, including executive functions. It was hypothesized that aided communication would tax executive functions more than speech. 29 children using communication aids and 27 naturally speaking children participated. Structured tasks resembling everyday activities, where the action goals had to be reached through communication with a partner, were used to get information about executive functions. The children a directed the partner to perform actions like building a Lego tower from a model the partner could not see and b gave information about an object without naming it to a person who had to guess what object it was. The executive functions of planning, monitoring and impulse control were coded from the children’s on-task behavior. Both groups solved most of the tasks correctly, indicating that aided communicators are able to use language to direct another person to do a complex set of actions. Planning and lack of impulsivity was positively related to task success in both groups. The aided group completed significantly fewer tasks, spent longer time and showed more variation in performance than the comparison group. The aided communicators scored lower on planning and showed more impulsivity than the comparison group, while both groups showed an equal degree of monitoring of the work progress. The results are consistent with the hypothesis that aided language

  18. Iodine-induced thyrotoxicosis--a case for subtotal thyroidectomy in severely ill patients.

    Science.gov (United States)

    Köbberling, J; Hintze, G; Becker, H D

    1985-01-02

    Iodine-induced thyrotoxicosis (IIT), due to iodine application in high amounts in patients with circumscript or disseminated thyroid autonomy, is complicated by a prolonged course, mainly due on the body's resistance to conservative therapy with thiourea derivates. Therefore, we decided to perform subtotal thyroidectomy in 16 thyrotoxic patients. This is in contrast to the common opinion that surgery should only be performed after normalization of thyroid hormones. In all 16 patients with severe IIT, including three patients with thyroid storm, hormone levels decreased within a few days after surgery to normal or subnormal values and the clinical picture of thyrotoxicosis disappeared. In the case of thyroid storm the signs of disorientation normalized within 1-3 days. One patient died 5 weeks after surgery due to severe concomitant diseases. One patient exhibited transitory respiration distress and another had postoperative hypocalcaemia. In nine patients L-thyroxine replacement became necessary because of subclinical or clinical hypothyroidism. Only by this procedure will the high intrathyroidal storage of iodine and performed hormone be extracted. Surgery as a treatment for thyrotoxicosis should be reserved for patients with severe IIT, where conservative treatment has been shown to be ineffective. Furthermore, in rare selected cases, when a rapid normalization is required, surgery without preoperative treatment seems to be justified. The effect of surgery was impressive in all our cases and there were only minor perioperative complications. Thus, it could be shown that subtotal thyroidectomy may be a rational and effective treatment in severe IIT which should be carefully considered and weighed against other types of therapy.

  19. Several localized waves induced by linear interference between a nonlinear plane wave and bright solitons

    Science.gov (United States)

    Qin, Yan-Hong; Zhao, Li-Chen; Yang, Zhan-Ying; Yang, Wen-Li

    2018-01-01

    We investigate linear interference effects between a nonlinear plane wave and bright solitons, which are admitted by a pair-transition coupled two-component Bose-Einstein condensate. We demonstrate that the interference effects can induce several localized waves possessing distinctive wave structures, mainly including anti-dark solitons, W-shaped solitons, multi-peak solitons, Kuznetsov-Ma like breathers, and multi-peak breathers. Specifically, the explicit conditions for them are clarified by a phase diagram based on the linear interference properties. Furthermore, the interactions between these localized waves are discussed. The detailed analysis indicates that the soliton-soliton interaction induced phase shift brings the collision between these localized waves which can be inelastic for solitons involving collision and can be elastic for breathers. These characters come from the fact that the profile of solitons depends on the relative phase between bright solitons and a plane wave, and the profile of breathers does not depend on the relative phase. These results would motivate more discussions on linear interference between other nonlinear waves. Specifically, the solitons or breathers obtained here are not related to modulational instability. The underlying reasons are discussed in detail. In addition, possibilities to observe these localized waves are discussed in a two species Bose-Einstein condensate.

  20. LPS-induced systemic inflammation is more severe in P2Y12 null mice.

    Science.gov (United States)

    Liverani, Elisabetta; Rico, Mario C; Yaratha, Laxmikausthubha; Tsygankov, Alexander Y; Kilpatrick, Laurie E; Kunapuli, Satya P

    2014-02-01

    Thienopyridines are a class of antiplatelet drugs that are metabolized in the liver to several metabolites, of which only one active metabolite can irreversibly antagonize the platelet P2Y12 receptor. Possible effects of these drugs and the role of activated platelets in inflammatory responses have also been investigated in a variety of animal models, demonstrating that thienopyridines could alter inflammation. However, it is not clear whether it is caused only by the P2Y12 antagonism or whether off-target effects of other metabolites also intervene. To address this question, we investigated P2Y12 KO mice during a LPS-induced model of systemic inflammation, and we treated these KO mice with a thienopyridine drug (clopidogrel). Contrary to the reported effects of clopidogrel, numbers of circulating WBCs and plasma levels of cytokines were increased in LPS-exposed KO mice compared with WT in this inflammation model. Moreover, both spleen and bone marrow show an increase in cell content, suggesting a role for P2Y12 in regulation of bone marrow and spleen cellular composition. Finally, the injury was more severe in the lungs of KO mice compared with WT. Interestingly, clopidogrel treatments also exerted protective effects in KO mice, suggesting off-target effects for this drug. In conclusion, the P2Y12 receptor plays an important role during LPS-induced inflammation, and this signaling pathway may be involved in regulating cell content in spleen and bone marrow during LPS systemic inflammation. Furthermore, clopidogrel may have effects that are independent of P2Y12 receptor blockade.

  1. Artesunate Protects Against the Organ Injury and Dysfunction Induced by Severe Hemorrhage and Resuscitation.

    Science.gov (United States)

    Sordi, Regina; Nandra, Kiran K; Chiazza, Fausto; Johnson, Florence L; Cabrera, Claudia P; Torrance, Hew D; Yamada, Noriaki; Patel, Nimesh S A; Barnes, Michael R; Brohi, Karim; Collino, Massimo; Thiemermann, Christoph

    2017-02-01

    To evaluate the effects of artesunate on organ injury and dysfunction associated with hemorrhagic shock (HS) in the rat. HS is still a common cause of death in severely injured patients and is characterized by impairment of organ perfusion, systemic inflammatory response, and multiple organ failure. There is no specific therapy that reduces organ injury/dysfunction. Artesunate exhibits pharmacological actions beyond its antimalarial activity, such as anticancer, antiviral, and anti-inflammatory effects. Rats were submitted to HS. Mean arterial pressure was reduced to 30 mm Hg for 90 minutes, followed by resuscitation. Rats were randomly treated with artesunate (2.4 or 4.8 mg/kg i.v.) or vehicle upon resuscitation. Four hours later, parameters of organ injury and dysfunction were assessed. Artesunate attenuated the multiple organ injury and dysfunction caused by HS. Pathway analysis of RNA sequencing provided good evidence to support an effect of artesunate on the Akt-survival pathway, leading to downregulation of interleukin-1 receptor-associated kinase 1. Using Western blot analysis, we confirmed that treatment of HS rats with artesunate enhanced the phosphorylation (activation) of Protein kinase B (Akt) and endothelial nitric oxide synthase and the phosphorylation (inhibition) of glycogen synthase kinase-3β (GSK-3β). Moreover, artesunate attenuated the HS-induced activation of nuclear factor kappa B and reduced the expression of proinflammatory proteins (inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin 6). Artesunate attenuated the organ injury/dysfunction associated with HS by a mechanism that involves the activation of the Akt-endothelial nitric oxide synthase survival pathway, and the inhibition of glycogen synthase kinase-3β and nuclear factor kappa B. A phase II clinical trial evaluating the effects of good manufacturing practice-artesunate in patients with trauma and severe hemorrhage is planned.

  2. Validation of the baseline severity stratification of objective functional impairment in lumbar degenerative disc disease.

    Science.gov (United States)

    Stienen, Martin N; Smoll, Nicolas R; Joswig, Holger; Corniola, Marco V; Schaller, Karl; Hildebrandt, Gerhard; Gautschi, Oliver P

    2017-05-01

    OBJECTIVE The Timed Up and Go (TUG) test is a simple, objective, and standardized method to measure objective functional impairment (OFI) in patients with lumbar degenerative disc disease (DDD). The objective of the current work was to validate the OFI baseline severity stratification (BSS; with levels of "none," "mild," "moderate," and "severe"). METHODS Data were collected in a prospective IRB-approved 2-center study. Patients were assessed with a comprehensive panel of scales for measuring pain (visual analog scale [VAS] for back and leg pain), functional impairment (Roland-Morris Disability Index [RMDI] and Oswestry Disability Index [ODI]), and health-related quality of life (HRQOL; EQ-5D and SF-12). OFI BSS was determined using age- and sex-adjusted cutoff values. RESULTS A total of 375 consecutive patients scheduled for lumbar spine surgery were included. Each 1-step increase on the OFI BSS corresponded to an increase of 0.53 in the back pain VAS score, 0.69 in the leg pain VAS score, 1.81 points in the RMDI, and 5.93 points in the ODI, as well as to a decrease in HRQOL of -0.073 in the EQ-5D, -1.99 in the SF-12 physical component summary (PCS), and -1.62 in the SF-12 mental component summary (MCS; all p measure of functional impairment for use in daily clinical practice. The presence of OFI indicates the presence of significant functional impairment on subjective outcome measures.

  3. Self-focused processing after severe traumatic brain injury: Relationship to neurocognitive functioning and mood symptoms.

    Science.gov (United States)

    Ownsworth, Tamara; Gooding, Kynan; Beadle, Elizabeth

    2018-05-28

    To investigate the impact of neurocognitive functioning on the self-focused processing styles of rumination and reflection, and the relationship to mood symptoms after severe traumatic brain injury (TBI). A cross-sectional design with a between-group component comparing self-focused processing styles and mood symptoms of adults with TBI and age- and gender-matched controls. Fifty-two participants with severe TBI (75% male, M age = 36.56, SD = 12.39) completed cognitive tests of attention, memory, executive functioning and the Awareness Questionnaire, Reflection and Rumination Questionnaire (RRQ), and Depression, Anxiety, and Stress Scales (DASS - 21). Fifty age- and gender-matched controls completed the RRQ and DASS-21. TBI participants reported significantly greater mood symptoms than controls (p levels of rumination and reflection did not significantly differ. TBI participants high on both reflection and rumination had significantly greater mood symptoms than those with high reflection and low rumination (p levels of rumination and reflection were associated with better working memory and immediate and delayed verbal memory (r = .36-.43, p levels of rumination were also associated with greater verbal fluency, self-awareness, and mood symptoms (r = .36-.70, p processing after severe TBI. Reflection without ruminative tendencies is more adaptive for mental health than reflection with rumination. Individuals with severe TBI report more mood symptoms than non-injured controls but do not differ on self-focused processing. Poorer memory function is related to lower levels of rumination and reflection. Reflection without ruminative tendencies is adaptive for mental health after severe TBI. Individuals with greater self-awareness and ruminative tendencies are at increased risk of mental health problems following severe TBI. Rumination and reflection were assessed using a self-report measure which assumes that people with severe TBI are able to reliably report

  4. Severe hyposmia and aberrant functional connectivity in cognitively normal Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Noritaka Yoneyama

    Full Text Available Severe hyposmia is a risk factor of dementia in Parkinson's disease (PD, while the underlying functional connectivity (FC and brain volume alterations in PD patients with severe hyposmia (PD-SH are unclear.We examined voxel-based morphometric and resting state functional magnetic resonance imaging findings in 15 cognitively normal PD-SH, 15 cognitively normal patients with PD with no/mild hyposmia (PD-N/MH, and 15 healthy controls (HCs.Decreased gray matter volume (GMV was observed in the bilateral cuneus, right associative visual area, precuneus, and some areas in anterior temporal lobes in PD-SH group compared to HCs. Both the PD-SH and PD-N/MH groups showed increased GMV in the bilateral posterior insula and its surrounding regions. A widespread significant decrease in amygdala FC beyond the decreased GMV areas and olfactory cortices were found in the PD-SH group compared with the HCs. Above all, decreased amygdala FC with the inferior parietal lobule, lingual gyrus, and fusiform gyrus was significantly correlated with both reduction of Addenbrooke's Cognitive Examination-Revised scores and severity of hyposmia in all participants. Canonical resting state networks exhibited decreased FC in the precuneus and left executive control networks but increased FC in the primary and high visual networks of patients with PD compared with HCs. Canonical network FC to other brain regions was enhanced in the executive control, salience, primary visual, and visuospatial networks of the PD-SH.PD-SH showed extensive decreased amygdala FC. Particularly, decreased FC between the amygdala and inferior parietal lobule, lingual gyrus, and fusiform gyrus were associated with the severity of hyposmia and cognitive performance. In contrast, relatively preserved canonical networks in combination with increased FC to brain regions outside of canonical networks may be related to compensatory mechanisms, and preservation of brain function.

  5. Multidisciplinary Treatment of Severe Osteogenesis Imperfecta: Functional Outcomes at Skeletal Maturity.

    Science.gov (United States)

    Montpetit, Kathleen; Palomo, Telma; Glorieux, Francis H; Fassier, François; Rauch, Frank

    2015-10-01

    To determine the functional outcomes associated with long-term multidisciplinary treatment, intravenous bisphosphonate treatment, orthopedic surgery, and rehabilitation in children with severe osteogenesis imperfecta (OI) (diagnosed clinically as OI types III or IV). Retrospective study where outcomes were measured prospectively. Pediatric orthopedic hospital. Adolescents (N=41; age range, 15-21y) with severe OI (OI type III: n=17; OI type IV: n=24) who had started therapy before the age of 6 years, had received treatment for at least 10 years, and had achieved final height. Intravenous bisphosphonate treatment, orthopedic surgery, and rehabilitation. Pediatric Evaluation of Disability Inventory. At the time of the last available follow-up examination, none of the individuals diagnosed with OI type III (most severely affected group) was able to ambulate without ambulation aids, whereas 20 (83%) patients with OI type IV were able to ambulate without ambulation aids. Regarding self-care, we specifically assessed 8 skills that we deemed essential for living independently (grooming; dressing; toileting; bed, chair, toilet, tub, and car transfers). Only 6 (35%) of the youths with OI type III were able to complete all 8 items, whereas 23 (96%) individuals with OI type IV managed to perform all tasks. Teens with OI type III often needed assistance for the transfer to toilet, tub, and car and for personal hygiene and clothing management associated with toileting, usually because of limitations in upper-extremity function. These observations suggest that further improvements in the functional status of the most severely affected children with OI are contingent on advances in the clinical management of upper-extremity issues. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  6. Abnormal prefrontal cortex resting state functional connectivity and severity of internet gaming disorder.

    Science.gov (United States)

    Jin, Chenwang; Zhang, Ting; Cai, Chenxi; Bi, Yanzhi; Li, Yangding; Yu, Dahua; Zhang, Ming; Yuan, Kai

    2016-09-01

    Internet Gaming Disorder (IGD) among adolescents has become an important public concern and gained more and more attention internationally. Recent studies focused on IGD and revealed brain abnormalities in the IGD group, especially the prefrontal cortex (PFC). However, the role of PFC-striatal circuits in pathology of IGD remains unknown. Twenty-five adolescents with IGD and 21 age- and gender-matched healthy controls were recruited in our study. Voxel-based morphometric (VBM) and functional connectivity analysis were employed to investigate the abnormal structural and resting-state properties of several frontal regions in individuals with online gaming addiction. Relative to healthy comparison subjects, IGD subjects showed significant decreased gray matter volume in PFC regions including the bilateral dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) and the right supplementary motor area (SMA) after controlling for age and gender effects. We chose these regions as the seeding areas for the resting-state analysis and found that IGD subjects showed decreased functional connectivity between several cortical regions and our seeds, including the insula, and temporal and occipital cortices. Moreover, significant decreased functional connectivity between some important subcortical regions, i.e., dorsal striatum, pallidum, and thalamus, and our seeds were found in the IGD group and some of those changes were associated with the severity of IGD. Our results revealed the involvement of several PFC regions and related PFC-striatal circuits in the process of IGD and suggested IGD may share similar neural mechanisms with substance dependence at the circuit level.

  7. Mannose binding lectin (MBL levels predict lung function decline in severe asthma

    Directory of Open Access Journals (Sweden)

    Ilonka. H. van Veen

    2006-12-01

    Full Text Available There is increasing evidence that activation of the complement system in asthma contributes to ongoing inflammation, tissue damage and airway remodeling. Mannose binding lectin (MBL is a pattern recognition molecule that serves as the key mediator of the lectin pathway of complement activation. MBL levels are genetically determined and vary widely amongst individuals. In the present study we hypothesized that high MBL levels in asthma are associated with increased loss of lung function over time, as a consequence of inflammatory tissue damage. We measured serum MBL levels by ELISA in 68 patients with severe asthma and prospectively determined the change in post-bronchodilator (pb FEV1 over a mean period of 5.7 years. The relationship between MBL and change in pbFEV1 (FEV1 was analysed using (multiple regression analysis and corrected for possible confounders (age, sex, age of onset, asthma duration, and pbFEV1. The median (range MBL level was 332 (10.8-3587 ng·ml–1. MBL was significantly associated with FEV1 (p<0.04. Patients with a high MBL level (332 ng·ml–1 had an increased risk of lung function decline compared to those with low MBL levels (OR (CI: 3.16 (1.14-8.79, p = 0.027; the excess decline being 42 ml·yr–1 (p = 0.01. We conclude that a high MBL level is associated with an increased decline in lung function in patients with severe asthma. MBL might provide a clue towards better understanding of the pathophysiology of ongoing inflammation and subsequent decline in lung function of patients with severe asthma.

  8. A case report: pregnancy-induced severe osteoporosis with eight vertebral fractures.

    Science.gov (United States)

    Ofluoglu, Onder; Ofluoglu, Demet

    2008-12-01

    Osteoporosis associated with pregnancy and lactation is a rare condition. The prevalence, etiology and its pathogenesis is unknown. It causes one or more vertebral fractures with severe, prolonged back pain and height loss in affected women. Majority of the cases are seen in the third trimester or just after delivery in primagravid women. In this case report, a 30-year-old woman who had severe pregnancy-induced osteoporosis with 8 vertebral fractures was presented. During last month of her first pregnancy she had moderate back pain. After delivery, the back pain has gotten worse. The radiological examinations have shown that there was 50% in T6, T8 and T10; 30% in L2; 20% in L1 height loss and biconcave vertebral images in L3-5. In the bone mineral density, L2-4 T score was -4.7 and total femoral T score was -3.1. There was no abnormality in the laboratory findings except mild elevation in alkaline phosphates. Although pregnancy-associated osteoporosis is a rare condition, when pain occurs in the last trimester or early postpartum period, it should be considered in differential diagnosis.

  9. Ergovaline does not alter the severity of ryegrass staggers induced by lolitrem B.

    Science.gov (United States)

    Finch, S C; Vlaming, J B; Sutherland, B L; van Koten, C; Mace, W J; Fletcher, L R

    2018-03-01

    To investigate a possible interaction between lolitrem B and ergovaline by comparing the incidence and severity of ryegrass staggers in sheep grazing ryegrass (Lolium perenne) containing lolitrem B or ryegrass containing both lolitrem B and ergovaline. Ninety lambs, aged approximately 6 months, were grazed on plots of perennial ryegrass infected with either AR98 endophyte (containing lolitrem B), standard endophyte (containing lolitrem B and ergovaline) or no endophyte, for up to 42 days from 2 February 2010. Ten lambs were grazed on three replicate plots per cultivar. Herbage samples were collected for alkaloid analysis and lambs were scored for ryegrass staggers (scores from 0-5) weekly during the study. Any animal which was scored ≥4 was removed from the study. Concentrations of lolitrem B did not differ between AR98 and standard endophyte-infected pastures during the study period (p=0.26), and ergovaline was present only in standard endophyte pastures. Ryegrass staggers was observed in sheep grazing both the AR98 and standard endophyte plots, with median scores increasing in the third week of the study. Prior to the end of the 42-day grazing period, 22 and 17 animals were removed from the standard endophyte and AR98 plots, respectively, because their staggers scores were ≥4. The cumulative probability of lambs having scores ≥4 did not differ between animals grazing the two pasture types (p=0.41). There was no evidence for ergovaline increasing the severity of ryegrass staggers induced by lolitrem B. In situations where the severity of ryegrass staggers appears to be greater than that predicted on the basis of concentrations of lolitrem B, the presence of other tremorgenic alkaloids should be investigated.

  10. Investigating executive functions in children with severe speech and movement disorders using structured tasks.

    Science.gov (United States)

    Stadskleiv, Kristine; von Tetzchner, Stephen; Batorowicz, Beata; van Balkom, Hans; Dahlgren-Sandberg, Annika; Renner, Gregor

    2014-01-01

    Executive functions are the basis for goal-directed activity and include planning, monitoring, and inhibition, and language seems to play a role in the development of these functions. There is a tradition of studying executive function in both typical and atypical populations, and the present study investigates executive functions in children with severe speech and motor impairments who are communicating using communication aids with graphic symbols, letters, and/or words. There are few neuropsychological studies of children in this group and little is known about their cognitive functioning, including executive functions. It was hypothesized that aided communication would tax executive functions more than speech. Twenty-nine children using communication aids and 27 naturally speaking children participated. Structured tasks resembling everyday activities, where the action goals had to be reached through communication with a partner, were used to get information about executive functions. The children (a) directed the partner to perform actions like building a Lego tower from a model the partner could not see and (b) gave information about an object without naming it to a person who had to guess what object it was. The executive functions of planning, monitoring, and impulse control were coded from the children's on-task behavior. Both groups solved most of the tasks correctly, indicating that aided communicators are able to use language to direct another person to do a complex set of actions. Planning and lack of impulsivity was positively related to task success in both groups. The aided group completed significantly fewer tasks, spent longer time and showed more variation in performance than the comparison group. The aided communicators scored lower on planning and showed more impulsivity than the comparison group, while both groups showed an equal degree of monitoring of the work progress. The results are consistent with the hypothesis that aided language tax

  11. Examining Profiles of Family Functioning in Pediatric Asthma: Longitudinal Associations With Child Adjustment and Asthma Severity.

    Science.gov (United States)

    Al G Hriwati, Nour; Winter, Marcia A; Everhart, Robin S

    2017-05-01

    Identify profiles of functioning in families of children with asthma and examine whether profile membership predicts subsequent child mental and physical well-being. Primary caregivers and children ( N  = 1,030) from the Childhood Asthma Management Program completed questionnaires assessing family functioning and child adaptation at five time points. Asthma severity was also assessed via spirometry. Latent profile analyses identified a four-profile solution as best fitting the data: cohesive, permissive, controlling/disengaged, and controlling/enmeshed families. Distal outcome analyses using Bolck-Croon-Hagenaars techniques suggested that children from families that were more cohesive had fewer internalizing and externalizing symptoms. These associations remained stable across time. Family profiles did not differ with regards to child asthma severity. Results highlight the importance of looking beyond the effects of distinct components of family functioning and instead using pattern-based approaches. Recommendations for incorporating screenings and services for families in pediatric care settings are provided. © The Author 2016. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  12. Correlation between audiovestibular function tests and hearing outcomes in severe to profound sudden sensorineural hearing loss.

    Science.gov (United States)

    Wang, Chi-Te; Huang, Tsung-Wei; Kuo, Shih-Wei; Cheng, Po-Wen

    2009-02-01

    This study investigated whether audiovestibular function tests, namely auditory brain stem response (ABR) and vestibular-evoked myogenic potential (VEMP) tests were correlated to hearing outcomes after controlling the effects of other potential confounding factors in severe to profound sudden sensorineural hearing loss (SSHL). Eighty-eight patients with severe to profound SSHL were enrolled in this study. Pretreatment hearing levels, results of audiovestibular function tests, and final hearing outcomes were recorded from retrospective chart reviews. Other factors, including age, gender, delay of treatment, vertigo, diabetes mellitus, and hypertension, were collected as well. Comparative analysis between multiple variables and hearing outcomes was conducted using the cumulative logits model in overall subjects. Further, multivariate analysis of prognostic factors was conducted in the stratified groups of severe (70 dB HL 90 dB HL) SSHL. Multivariate analysis showed that pretreatment hearing levels, presence of vertigo, and results of ABR and VEMP testing were significant outcome predictors in the overall subjects. Stratification analysis demonstrated that both the presence of ABR and VEMP waveforms were significantly correlated with better hearing outcomes in the group of severe SSHL [ABR: adjusted odds ratio (aOR) = 14.7, 95% confidence interval (CI) = 1.78 to 122, p = 0.01; VEMP: aOR = 5.91, 95% CI = 1.18 to 29.5, p = 0.03], whereas the presence of vertigo was the only significant negative prognostic factor in the group of profound SSHL (aOR = 0.24, 95% CI = 0.06 to 0.95, p = 0.04). Other variables, including age, gender, diabetes mellitus, hypertension, and delay of treatment, were not significantly related to hearing outcomes in both groups (p > 0.05). A predictive hearing recovery table with the combined ABR and VEMP results was proposed for the group of severe SSHL. ABR and VEMP tests should be included in the battery of neurootological examinations in

  13. Arterial function parameters in patients with metabolic syndrome and severe hypertriglyceridemia.

    Science.gov (United States)

    Rinkūnienė, Egidija; Butkutė, Eglė; Puronaitė, Roma; Petrulionienė, Žaneta; Dženkevičiūtė, Vilma; Kasiulevičius, Vytautas; Laucevičius, Aleksandras

    Hypertriglyceridemia (hTG) is 1 of the dyslipidemia manifestations in patients with metabolic syndrome (MetS). However, for several decades, the role of hTG in cardiovascular risk was not well established. The aim of this study was to assess the parameters of the vascular structure and function in patients with MetS and different degree of hTG. Patients (aged 40-65 years) with MetS were divided into 3 groups by triglyceride (TG) levels according to National Cholesterol Education Program Adult Treatment Panel III Guidelines: severe hTG (TG ≥ 500 mg/dL), moderate hTG (TG 200-499 mg/dL), and a control (TG severe TG was observed in 9.6% (n = 100) of patients. Overall TG concentration was 231.17 ± 184.23 mg/dL; in severe hTG group, TG concentration was 795.36 ± 368.45 mg/dL, in moderate hTG group 285.20 ± 70.86 mg/dL, and 112.48 ± 24.80 mg/dL in control group. AIxHR75 and IMT were the lowest in the severe hTG group (P severe hTG have lower IMT and AIxHR75 and higher PWV and mean arterial pressure. Many factors could affect arterial parameters, and more research are needed to investigate arterial parameters and hTG connection. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  14. The tight junction protein Z O-2 has several functional nuclear export signals

    International Nuclear Information System (INIS)

    Gonzalez-Mariscal, Lorenza; Ponce, Arturo; Alarcon, Lourdes; Jaramillo, Blanca Estela

    2006-01-01

    The tight junction (TJ) protein ZO-2 changes its subcellular distribution according to the state of confluency of the culture. Thus in confluent monolayers, it localizes at the TJ region whereas in sparse cultures it concentrates at the nucleus. The canine sequence of ZO-2 displays four putative nuclear export signals (NES), two at the second PDZ domain (NES-0 and NES-1) and the rest at the GK region (NES-2 and NES-3). The functionality of NES-0 and NES-3 was unknown, hence here we have explored it with a nuclear export assay, injecting into the nucleus of MDCK cells peptides corresponding to the ZO-2 NES sequences chemically coupled to ovalbumin. We show that both NES-0 and NES-3 are functional and sensitive to leptomycin B. We also demonstrate that NES-1, previously characterized as a non functional NES, is rendered capable of nuclear export upon the acquisition of a negative charge at its Ser369 residue. Experiments performed injecting at the nucleus WT and mutated ZO-2-GST fusion proteins revealed the need of both NES-0 and NES-1, and NES-2 and NES-3 for attaining an efficient nuclear exit of the respective amino and middle segments of ZO-2. Moreover, the transfection of MDCK cells with full-length ZO-2 revealed that the mutation of any of the NES present in the molecule was sufficient to induce nuclear accumulation of the protein

  15. The Relationship between Symptom Severity and Cognitive Functions with Obesity in Fibromyalgia Syndrome

    Directory of Open Access Journals (Sweden)

    Selçuk Sayılır

    2017-01-01

    Full Text Available Objective: To investigate the relationship between obesity with symptom severity and cognitive functions in Fibromyalgia syndrome (FMS patients. Materials and Methods: The study comprised 33 FMS patients (mean age 41.21±7.6 years. The patients who have hypertension, hypercholesterolaemia or diabetes, chronic inflammatory disorders, cardiovascular-pulmonary diseases, rheumatological/endocrine diseases, using anticoagulant therapy or have thrombotic disorders, malignancies and pregnant women were excluded from the study. Fibromyalgia Impact Questionnaire (FIQ, Perceived Stress Scale (PSS-10 and Mini Mental State Examination tests were used. The data of FMS patients were recorded by the same physician. Results: There were not statistically significant differences between PSS-10 and MMSE with body mass index (BMI levels. There was a statistically significant difference between FIQ and BMI values. Conclusion: In conclusion, the result of this study showed a statistical relationship between the increased BMI levels and FMS symptom severity that could be beneficial in clinical practice.

  16. Gain-of-function KCNJ6 Mutation in a Severe Hyperkinetic Movement Disorder Phenotype.

    Science.gov (United States)

    Horvath, Gabriella A; Zhao, Yulin; Tarailo-Graovac, Maja; Boelman, Cyrus; Gill, Harinder; Shyr, Casper; Lee, James; Blydt-Hansen, Ingrid; Drögemöller, Britt I; Moreland, Jacqueline; Ross, Colin J; Wasserman, Wyeth W; Masotti, Andrea; Slesinger, Paul A; van Karnebeek, Clara D M

    2018-05-29

    Here, we describe a fourth case of a human with a de novo KCNJ6 (GIRK2) mutation, who presented with clinical findings of severe hyperkinetic movement disorder and developmental delay, similar to the Keppen-Lubinsky syndrome but without lipodystrophy. Whole-exome sequencing of the patient's DNA revealed a heterozygous de novo variant in the KCNJ6 (c.512T>G, p.Leu171Arg). We conducted in vitro functional studies to determine if this Leu-to-Arg mutation alters the function of GIRK2 channels. Heterologous expression of the mutant GIRK2 channel alone produced an aberrant basal inward current that lacked G protein activation, lost K + selectivity and gained Ca 2+ permeability. Notably, the inward current was inhibited by the Na + channel blocker QX-314, similar to the previously reported weaver mutation in murine GIRK2. Expression of a tandem dimer containing GIRK1 and GIRK2(p.Leu171Arg) did not lead to any currents, suggesting heterotetramers are not functional. In neurons expressing p.Leu171Arg GIRK2 channels, these changes in channel properties would be expected to generate a sustained depolarization, instead of the normal G protein-gated inhibitory response, which could be mitigated by expression of other GIRK subunits. The identification of the p.Leu171Arg GIRK2 mutation potentially expands the Keppen-Lubinsky syndrome phenotype to include severe dystonia and ballismus. Our study suggests screening for dominant KCNJ6 mutations in the evaluation of patients with severe movement disorders, which could provide evidence to support a causal role of KCNJ6 in neurological channelopathies. Copyright © 2018. Published by Elsevier Ltd.

  17. Prediction of the survival and functional ability of severe stroke patients after ICU therapeutic intervention

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    Aoun-Bacha Zeina

    2008-06-01

    Full Text Available Abstract Background This study evaluated the benefits and impact of ICU therapeutic interventions on the survival and functional ability of severe cerebrovascular accident (CVA patients. Methods Sixty-two ICU patients suffering from severe ischemic/haemorrhagic stroke were evaluated for CVA severity using APACHE II and the Glasgow coma scale (GCS. Survival was determined using Kaplan-Meier survival tables and survival prediction factors were determined by Cox multivariate analysis. Functional ability was assessed using the stroke impact scale (SIS-16 and Karnofsky score. Risk factors, life support techniques and neurosurgical interventions were recorded. One year post-CVA dependency was investigated using multivariate analysis based on linear regression. Results The study cohort constituted 6% of all CVA (37.8% haemorrhagic/62.2% ischemic admissions. Patient mean(SD age was 65.8(12.3 years with a 1:1 male: female ratio. During the study period 16 patients had died within the ICU and seven in the year following hospital release. The mean(SD APACHE II score at hospital admission was 14.9(6.0 and ICU mean duration of stay was 11.2(15.4 days. Mechanical ventilation was required in 37.1% of cases. Risk ratios were; GCS at admission 0.8(0.14, (p = 0.024, APACHE II 1.11(0.11, (p = 0.05 and duration of mechanical ventilation 1.07(0.07, (p = 0.046. Linear coefficients were: type of CVA – haemorrhagic versus ischemic: -18.95(4.58 (p = 0.007, GCS at hospital admission: -6.83(1.08, (p = 0.001, and duration of hospital stay -0.38(0.14, (p = 0.40. Conclusion To ensure a better prognosis CVA patients require ICU therapeutic interventions. However, as we have shown, where tests can determine the worst affected patients with a poor vital and functional outcome should treatment be withheld?

  18. Preseason Functional Movement Screen Component Tests Predict Severe Contact Injuries in Professional Rugby Union Players.

    Science.gov (United States)

    Tee, Jason C; Klingbiel, Jannie F G; Collins, Robert; Lambert, Mike I; Coopoo, Yoga

    2016-11-01

    Tee, JC, Klingbiel, JFG, Collins, R, Lambert, MI, and Coopoo, Y. Preseason Functional Movement Screen component tests predict severe contact injuries in professional rugby union players. J Strength Cond Res 30(11): 3194-3203, 2016-Rugby union is a collision sport with a relatively high risk of injury. The ability of the Functional Movement Screen (FMS) or its component tests to predict the occurrence of severe (≥28 days) injuries in professional players was assessed. Ninety FMS test observations from 62 players across 4 different time periods were compared with severe injuries sustained during 6 months after FMS testing. Mean composite FMS scores were significantly lower in players who sustained severe injury (injured 13.2 ± 1.5 vs. noninjured 14.5 ± 1.4, Effect Size = 0.83, large) because of differences in in-line lunge (ILL) and active straight leg raise scores (ASLR). Receiver-operated characteristic curves and 2 × 2 contingency tables were used to determine that ASLR (cut-off 2/3) was the injury predictor with the greatest sensitivity (0.96, 95% confidence interval [CI] = 0.79-1.0). Adding the ILL in combination with ASLR (ILL + ASLR) improved the specificity of the injury prediction model (ASLR specificity = 0.29, 95% CI = 0.18-0.43 vs. ASLR + ILL specificity = 0.53, 95% CI = 0.39-0.66, p ≤ 0.05). Further analysis was performed to determine whether FMS tests could predict contact and noncontact injuries. The FMS composite score and various combinations of component tests (deep squat [DS] + ILL, ILL + ASLR, and DS + ILL + ASLR) were all significant predictors of contact injury. The FMS composite score also predicted noncontact injury, but no component test or combination thereof produced a similar result. These findings indicate that low scores on various FMS component tests are risk factors for injury in professional rugby players.

  19. Poor Executive Functions among Children with Moderate-into-Severe Asthma: Evidence from WCST Performance.

    Science.gov (United States)

    Taha, Haitham

    2017-01-01

    Executive functions (EFs) measures of 27 asthmatic children, with general learning difficulties, were tested by using the Wisconsin card sorting test (WCST), and were compared to the performances of 30 non-asthmatic children with general learning difficulties. The results revealed that the asthmatic group has poor performance through all the WCST psychometric parameters and especially the perseverative errors one. The results were discussed in light of the postulation that poor EFs could be associated with the learning difficulties of asthmatic children. Neurophysiological framework has been suggested to explain the etiology of poor EFs among children with moderate into severe asthma.

  20. Restoration of Function With Acupuncture Following Severe Traumatic Brain Injury: A Case Report.

    Science.gov (United States)

    Wolf, Jacob; Sparks, Linda; Deng, Yong; Langland, Jeffrey

    2015-11-01

    This case report illustrates the improvement of an acupuncture-treated patient who incurred a severe traumatic brain injury (TBI) from a snowboarding accident. Over 4 years, the patient progressed from initially not being able to walk, having difficulty with speech, and suffering from poor eyesight to where he has now regained significant motor function, speech, and vision and has returned to snowboarding. A core acupuncture protocol plus specific points added to address the patient's ongoing concerns was used. This case adds to the medical literature by demonstrating the potential role of acupuncture in TBI treatment.

  1. Muscarinic excitation of parvalbumin-positive interneurons contributes to the severity of pilocarpine-induced seizures

    Science.gov (United States)

    Yi, Feng; DeCan, Evan; Stoll, Kurt; Marceau, Eric; Deisseroth, Karl; Lawrence, J. Josh

    2014-01-01

    SUMMARY Objective A common rodent model in epilepsy research employs the muscarinic acetylcholine receptor (mAChR) agonist pilocarpine, yet the mechanisms underlying the induction of pilocarpine-induced seizures (PISs) remain unclear. Global M1 mAChR (M1R) knockout mice are resistant to PISs, implying that M1R activation disrupts excitation/inhibition balance. Parvalbumin-positive (PV) inhibitory neurons express M1 mAChRs, participate in cholinergically-induced oscillations, and can enter a state of depolarization block (DB) during epileptiform activity. Here, we test the hypothesis that pilocarpine activation of M1Rs expressed on PV cells contributes to PISs. Methods CA1 PV cells in PV-CRE mice were visualized with a floxed YFP or hM3Dq-mCherry adeno-associated virus, or by crossing PV-CRE mice with the RosaYFP reporter line. To eliminate M1Rs from PV cells, we generated PV-M1KO mice by crossing PV-CRE and floxed M1 mice. Action potential (AP) frequency was monitored during application of pilocarpine (200 µM). In behavioral experiments, locomotion and seizure symptoms were recorded in WT or PV-M1KO mice during PISs. Results Pilocarpine significantly increased AP frequency in CA1 PV cells into the gamma range. In the continued presence of pilocarpine, a subset (5/7) of PV cells progressed to DB, which was mimicked by hM3Dq activation of Gq-receptor signaling. Pilocarpine-induced depolarization, AP firing at gamma frequency, and progression to DB were prevented in CA1 PV cells of PV-M1KO mice. Finally, compared to WT mice, PV-M1KO mice were associated with reduced severity of PISs. Significance Pilocarpine can directly depolarize PV+ cells via M1R activation but a subset of these cells progress to DB. Our electrophysiological and behavioral results suggest that this mechanism is active during PISs, contributing to a collapse of PV-mediated GABAergic inhibition, dysregulation of excitation/inhibition balance, and increased susceptibility to PISs. PMID:25495999

  2. Assessing the reliability of predictive activity coefficient models for molecules consisting of several functional groups

    Directory of Open Access Journals (Sweden)

    R. P. Gerber

    2013-03-01

    Full Text Available Currently, the most successful predictive models for activity coefficients are those based on functional groups such as UNIFAC. In contrast, these models require a large amount of experimental data for the determination of their parameter matrix. A more recent alternative is the models based on COSMO, for which only a small set of universal parameters must be calibrated. In this work, a recalibrated COSMO-SAC model was compared with the UNIFAC (Do model employing experimental infinite dilution activity coefficient data for 2236 non-hydrogen-bonding binary mixtures at different temperatures. As expected, UNIFAC (Do presented better overall performance, with a mean absolute error of 0.12 ln-units against 0.22 for our COSMO-SAC implementation. However, in cases involving molecules with several functional groups or when functional groups appear in an unusual way, the deviation for UNIFAC was 0.44 as opposed to 0.20 for COSMO-SAC. These results show that COSMO-SAC provides more reliable predictions for multi-functional or more complex molecules, reaffirming its future prospects.

  3. Parenting stress in pediatric IBD: relations with child psychopathology, family functioning, and disease severity.

    Science.gov (United States)

    Gray, Wendy N; Graef, Danielle M; Schuman, Shana S; Janicke, David M; Hommel, Kevin A

    2013-05-01

    Parenting stress in pediatric inflammatory bowel disease (IBD) has been under-examined. Data validating use of the Pediatric Inventory for Parents (PIP), a measure of parenting stress associated with caring for a chronically ill child, in chronic diseases with intermittent, unpredictable disease courses, such as IBD, are needed. This study presents validity data in support of the PIP in pediatric IBD and examines relations between parenting stress and important psychosocial and medical outcomes. Adolescents (N = 130) with IBD and their caregivers across 3 sites completed measures of parenting stress, family functioning, and emotional/behavioral functioning. Disease severity was also assessed for each participant. The PIP demonstrates excellent internal consistency. Parenting stress was significantly higher among those with unhealthy general family functioning and those with children with borderline or clinically elevated internalizing symptoms. Caregiving stress was greater among parents of youth with more active Crohn's disease. Results supported the reliability and validity of the PIP for assessing caregiving stress in pediatric IBD. Routine assessment of parenting stress is recommended, particularly among parents reporting unhealthy family functioning and parents of youth with borderline or clinically elevated internalizing symptoms and more active disease.

  4. Bovine colostrum improves intestinal function following formula-induced gut inflammation in preterm pigs

    DEFF Research Database (Denmark)

    Støy, Ann Cathrine Findal; Heegaard, Peter M. H.; Thymann, Thomas

    2014-01-01

    Background & aims Only few hours of formula feeding may induce proinflammatory responses and predispose to necrotizing enterocolitis (NEC) in preterm pigs. We hypothesized that bovine colostrum, rich in bioactive factors, would improve intestinal function in preterm pigs following an initial...... exposure to formula feeding after some days of total parenteral nutrition (TPN). Methods After receiving TPN for 2 days, preterm pigs were fed formula (FORM, n = 14), bovine colostrum (COLOS, n = 6), or formula (6 h) followed by bovine colostrum (FCOLOS, n = 14). Intestinal lesions, function, and structure...... and FCOLOS pigs, relative to FORM pigs. Intestinal gene expression of serum amyloid A, IL-1β, -6 and -8, and bacterial abundance, correlated positively with NEC severity of the distal small intestine. Conclusions Bovine colostrum restores intestinal function after initial formula-induced inflammation...

  5. Increased physical activity severely induces osteoarthritic changes in knee joints with papain induced sulfate-glycosaminoglycan depleted cartilage.

    Science.gov (United States)

    Siebelt, Michiel; Groen, Harald C; Koelewijn, Stuart J; de Blois, Erik; Sandker, Marjan; Waarsing, Jan H; Müller, Cristina; van Osch, Gerjo J V M; de Jong, Marion; Weinans, Harrie

    2014-01-29

    Articular cartilage needs sulfated-glycosaminoglycans (sGAGs) to withstand high pressures while mechanically loaded. Chondrocyte sGAG synthesis is regulated by exposure to compressive forces. Moderate physical exercise is known to improve cartilage sGAG content and might protect against osteoarthritis (OA). This study investigated whether rat knee joints with sGAG depleted articular cartilage through papain injections might benefit from moderate exercise, or whether this increases the susceptibility for cartilage degeneration. sGAGs were depleted from cartilage through intraarticular papain injections in the left knee joints of 40 Wistar rats; their contralateral joints served as healthy controls. Of the 40 rats included in the study, 20 rats remained sedentary, and the other 20 were subjected to a moderately intense running protocol. Animals were longitudinally monitored for 12 weeks with in vivo micro-computed tomography (μCT) to measure subchondral bone changes and single-photon emission computed tomography (SPECT)/CT to determine synovial macrophage activation. Articular cartilage was analyzed at 6 and 12 weeks with ex vivo contrast-enhanced μCT and histology to measure sGAG content and cartilage thickness. All outcome measures were unaffected by moderate exercise in healthy control joints of running animals compared with healthy control joints of sedentary animals. Papain injections in sedentary animals resulted in severe sGAG-depleted cartilage, slight loss of subchondral cortical bone, increased macrophage activation, and osteophyte formation. In running animals, papain-induced sGAG-depleted cartilage showed increased cartilage matrix degradation, sclerotic bone formation, increased macrophage activation, and more osteophyte formation. Moderate exercise enhanced OA progression in papain-injected joints and did not protect against development of the disease. This was not restricted to more-extensive cartilage damage, but also resulted in pronounced

  6. Increased physical activity severely induces osteoarthritic changes in knee joints with papain induced sulfate-glycosaminoglycan depleted cartilage

    Science.gov (United States)

    2014-01-01

    Introduction Articular cartilage needs sulfated-glycosaminoglycans (sGAGs) to withstand high pressures while mechanically loaded. Chondrocyte sGAG synthesis is regulated by exposure to compressive forces. Moderate physical exercise is known to improve cartilage sGAG content and might protect against osteoarthritis (OA). This study investigated whether rat knee joints with sGAG depleted articular cartilage through papain injections might benefit from moderate exercise, or whether this increases the susceptibility for cartilage degeneration. Methods sGAGs were depleted from cartilage through intraarticular papain injections in the left knee joints of 40 Wistar rats; their contralateral joints served as healthy controls. Of the 40 rats included in the study, 20 rats remained sedentary, and the other 20 were subjected to a moderately intense running protocol. Animals were longitudinally monitored for 12 weeks with in vivo micro-computed tomography (μCT) to measure subchondral bone changes and single-photon emission computed tomography (SPECT)/CT to determine synovial macrophage activation. Articular cartilage was analyzed at 6 and 12 weeks with ex vivo contrast-enhanced μCT and histology to measure sGAG content and cartilage thickness. Results All outcome measures were unaffected by moderate exercise in healthy control joints of running animals compared with healthy control joints of sedentary animals. Papain injections in sedentary animals resulted in severe sGAG-depleted cartilage, slight loss of subchondral cortical bone, increased macrophage activation, and osteophyte formation. In running animals, papain-induced sGAG-depleted cartilage showed increased cartilage matrix degradation, sclerotic bone formation, increased macrophage activation, and more osteophyte formation. Conclusions Moderate exercise enhanced OA progression in papain-injected joints and did not protect against development of the disease. This was not restricted to more-extensive cartilage

  7. Some morphological and physiological features of several dwarf apple sports induced by gamma rays

    International Nuclear Information System (INIS)

    Ikeda, F.; Nishida, T.

    1982-01-01

    Various types of apple mutants have been induced by gamma-ray irradiation since 1962. Using several clones which had attained fruiting in 1975, investigation of the fruit quality was carried out. Desirable mutants were mostly obtained from chronic treatment. As a result of observations of pollen grains, pollen sterility was detected in almost all clones which originated from acute treatment. The characteristics of several mutants with weak growth habit were assessed for their morphological and anatomical characters. Spur-type mutants were characterized by a lesser formation of secondary wood and slightly longer fibre cells in their wood compared with those of the original cultivars. Also, dwarf-type mutants were characterized by weak secondary growth and by shorter fibre cells in the wood. Various morphological mutants were examined by anatomical methods if they arose as peripheral polyploidal chimeras. In comparison with the nuclear volume of each histogenic layer, almost all the original varieties and mutants show a larger nuclear volume in the subepidermal layer, L-2, than in the epidermal layer, L-1. However, a reverse situation was recognized in clone 500-18 which seems to be a polyploidal chimera such as 4-2-2. Clonal differences in the induction of a brown coloured substance developed in fresh leaves with mono-iodoacetic acid were compared with those of their original cultivars. Most mutants with weak growth habit showed a darker colour reaction than that of the original cultivar. Therefore, the colour reaction might be used as an early detection method of a mutation by a chemical procedure in apple. (author)

  8. Unusual Synchronous Methimazole-Induced Agranulocytosis and Severe Hepatotoxicity in Patient with Hyperthyroidism: A Case Report and Review of the Literature

    Science.gov (United States)

    Yang, Jun; Zhang, Jun; Xu, Qin; Sheng, Guo-ping; Weng, Wan-wen; Dong, Meng-jie

    2015-01-01

    Context. To report a patient with hyperthyroidism who developed concurrent occurrence of agranulocytosis and severe hepatotoxicity after taking methimazole (MMI). Case. A 51-year-old Chinese male was diagnosed as hyperthyroidism with normal white blood count and liver function. After 4 weeks' treatment with MMI 20 mg/d, it developed to agranulocytosis and severe cholestatic hepatotoxicity. The patient's symptoms and laboratory abnormalities disappeared after the withdrawal of MMI; his white blood count and liver function recover to normal in 2 weeks and 5 weeks, respectively. 296 MBq dose of 131I was given to the patient 3 weeks after the withdrawal of MMI and his thyroid function was back to normal in 6 months. As we know through literature review, only 5 previous cases reported the synchronous ATD-induced agranulocytosis and severe hepatotoxicity in patients with hyperthyroidism. Methods. Review of the patient's clinical course. Literature review of cases of hyperthyroidism with agranulocytosis and severe hepatotoxicity demonstrated that these complications occurred after taking antithyroid drug (ATD). Conclusions. Patient with hyperthyroidism can have synchronous ATD-induced agranulocytosis and severe hepatotoxicity. This case is extremely rare, but the adverse effects with ATDs is clinically significant. The clinicians need to be careful about this and monitor biochemical of patients who take ATDs. PMID:26060496

  9. Unusual Synchronous Methimazole-Induced Agranulocytosis and Severe Hepatotoxicity in Patient with Hyperthyroidism: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Jun Yang

    2015-01-01

    Full Text Available Context. To report a patient with hyperthyroidism who developed concurrent occurrence of agranulocytosis and severe hepatotoxicity after taking methimazole (MMI. Case. A 51-year-old Chinese male was diagnosed as hyperthyroidism with normal white blood count and liver function. After 4 weeks’ treatment with MMI 20 mg/d, it developed to agranulocytosis and severe cholestatic hepatotoxicity. The patient’s symptoms and laboratory abnormalities disappeared after the withdrawal of MMI; his white blood count and liver function recover to normal in 2 weeks and 5 weeks, respectively. 296 MBq dose of 131I was given to the patient 3 weeks after the withdrawal of MMI and his thyroid function was back to normal in 6 months. As we know through literature review, only 5 previous cases reported the synchronous ATD-induced agranulocytosis and severe hepatotoxicity in patients with hyperthyroidism. Methods. Review of the patient’s clinical course. Literature review of cases of hyperthyroidism with agranulocytosis and severe hepatotoxicity demonstrated that these complications occurred after taking antithyroid drug (ATD. Conclusions. Patient with hyperthyroidism can have synchronous ATD-induced agranulocytosis and severe hepatotoxicity. This case is extremely rare, but the adverse effects with ATDs is clinically significant. The clinicians need to be careful about this and monitor biochemical of patients who take ATDs.

  10. Role of Acute Lesion Topography in Initial Ischemic Stroke Severity and Long-Term Functional Outcomes.

    Science.gov (United States)

    Wu, Ona; Cloonan, Lisa; Mocking, Steven J T; Bouts, Mark J R J; Copen, William A; Cougo-Pinto, Pedro T; Fitzpatrick, Kaitlin; Kanakis, Allison; Schaefer, Pamela W; Rosand, Jonathan; Furie, Karen L; Rost, Natalia S

    2015-09-01

    Acute infarct volume, often proposed as a biomarker for evaluating novel interventions for acute ischemic stroke, correlates only moderately with traditional clinical end points, such as the modified Rankin Scale. We hypothesized that the topography of acute stroke lesions on diffusion-weighted magnetic resonance imaging may provide further information with regard to presenting stroke severity and long-term functional outcomes. Data from a prospective stroke repository were limited to acute ischemic stroke subjects with magnetic resonance imaging completed within 48 hours from last known well, admission NIH Stroke Scale (NIHSS), and 3-to-6 months modified Rankin Scale scores. Using voxel-based lesion symptom mapping techniques, including age, sex, and diffusion-weighted magnetic resonance imaging lesion volume as covariates, statistical maps were calculated to determine the significance of lesion location for clinical outcome and admission stroke severity. Four hundred ninety subjects were analyzed. Acute stroke lesions in the left hemisphere were associated with more severe NIHSS at admission and poor modified Rankin Scale at 3 to 6 months. Specifically, injury to white matter (corona radiata, internal and external capsules, superior longitudinal fasciculus, and uncinate fasciculus), postcentral gyrus, putamen, and operculum were implicated in poor modified Rankin Scale. More severe NIHSS involved these regions, as well as the amygdala, caudate, pallidum, inferior frontal gyrus, insula, and precentral gyrus. Acute lesion topography provides important insights into anatomic correlates of admission stroke severity and poststroke outcomes. Future models that account for infarct location in addition to diffusion-weighted magnetic resonance imaging volume may improve stroke outcome prediction and identify patients likely to benefit from aggressive acute intervention and personalized rehabilitation strategies. © 2015 American Heart Association, Inc.

  11. Loss-of-Function FANCL Mutations Associate with Severe Fanconi Anemia Overlapping the VACTERL Association.

    Science.gov (United States)

    Vetro, Annalisa; Iascone, Maria; Limongelli, Ivan; Ameziane, Najim; Gana, Simone; Della Mina, Erika; Giussani, Ursula; Ciccone, Roberto; Forlino, Antonella; Pezzoli, Laura; Rooimans, Martin A; van Essen, Antoni J; Messa, Jole; Rizzuti, Tommaso; Bianchi, Paolo; Dorsman, Josephine; de Winter, Johan P; Lalatta, Faustina; Zuffardi, Orsetta

    2015-05-01

    The diagnosis of VACTERL syndrome can be elusive, especially in the prenatal life, due to the presence of malformations that overlap those present in other genetic conditions, including the Fanconi anemia (FA). We report on three VACTERL cases within two families, where the two who arrived to be born died shortly after birth due to severe organs' malformations. The suspicion of VACTERL association was based on prenatal ultrasound assessment and postnatal features. Subsequent chromosome breakage analysis suggested the diagnosis of FA. Finally, by next-generation sequencing based on the analysis of the exome in one family and of a panel of Fanconi genes in the second one, we identified novel FANCL truncating mutations in both families. We used ectopic expression of wild-type FANCL to functionally correct the cellular FA phenotype for both mutations. Our study emphasizes that the diagnosis of FA should be considered when VACTERL association is suspected. Furthermore, we show that loss-of-function mutations in FANCL result in a severe clinical phenotype characterized by early postnatal death. © 2015 WILEY PERIODICALS, INC.

  12. Alexithymia, Assertiveness and Psychosocial Functioning in HIV: Implications for Medication Adherence and Disease Severity.

    Science.gov (United States)

    McIntosh, Roger C; Ironson, Gail; Antoni, Michael; Fletcher, Mary Ann; Schneiderman, Neil

    2016-02-01

    Psychosocial function and adherence to antiretroviral regimen are key factors in human immunodeficiency virus (HIV) disease management. Alexithymia (AL) is a trait deficit in the ability to identify and describe feelings, emotions and bodily sensations. A structural equation model was used to test whether high levels of AL indirectly relate to greater non-adherent behavior and HIV disease severity via psychosocial dysfunction. Blood draws for HIV-1 viral load and CD4 T-lymphocyte, along with psychosocial surveys were collected from 439 HIV positive adults aged 18-73 years. The structural model supports significant paths from: (1) AL to non-active patient involvement, psychological distress, and lower social support, (2) psychological distress and non-active involvement to non-adherent behavior, and (3) non-adherence to greater HIV disease severity (CFI = .97, RMSEA = .04, SRMR = .05). A second model confirmed the intermediary effect of greater patient assertiveness on the path from AL to social support and non-active patient involvement (CFI = .94, RMSEA = .04, SRMR = .05). Altogether, AL is indirectly linked with HIV disease management through it's association with poor psychosocial function, however greater patient assertiveness buffers the negative impact of AL on relationship quality with healthcare providers and members of one's social support network.

  13. Plasma Zonulin and its Association with Kidney Function, Severity of Heart Failure, and Metabolic Inflammation.

    Science.gov (United States)

    Dschietzig, Thomas B; Boschann, Felix; Ruppert, Jana; Armbruster, Franz P; Meinitzer, Andreas; Bankovic, Dragic; Mitrovic, Veselin; Melzer, Christoph

    2016-12-01

    The tight junction regulator zonulin has attracted clinical attention as a biomarker of increased gastrointestinal permeability. Recent work also suggests zonulin to represent a general regulator of tissue barriers and a player in metabolic inflammation. Here, we investigated the associations of zonulin with chronic heart failure (CHF), kidney function, and metabolic inflammation. Using multiple linear regression (Generalized Linear Model), this study determined the association of plasma zonulin with different laboratory and clinical parameters in 225 patients carrying automatic implantable cardioverters/defibrillators (AICD) for primary or secondary prevention. In another 115 patients with diastolic or systolic CHF, we investigated a possible relationship between zonulin and CHF severity. In the AICD cohort, zonulin associated inversely with serum creatinine (p = 0.013), carboxymethyl-lysine calprotectin (p zonulin increased significantly with high-sensitivity CRP (p = 0.014). In the CHF cohort, we found a highly significant rise of NT-proBNP, but not of zonulin with NYHA functional classes I-IV or other parameters of CHF severity. The inverse associations of zonulin with creatinine and markers of cardio-vascular risk (high CMLcalprotectin and kynurenine, low homoarginine) are novel findings that need further experimental and clinical clarification. Our study indicates zonulin involvement in metabolic inflammation in T2D, but no association with disease status in CHF.

  14. AWARENESS OF USING RINGER LACTAT SOLUTION IN DENGUE VIRUS INFECTION CASES COULD INDUCE SEVERITY

    Directory of Open Access Journals (Sweden)

    Soegeng Soegijanto

    2013-10-01

    Full Text Available Background:In 2012, serotype ofDengue Virus had changed from Den-2 and Den-3 to Den-1. In 5–10 years ago, serotype ofDen-1 case showed a mild clinical manifestation; but now as a primary case it can also show severe clinical manifestation. One findicator is an increasing liver enzyme, AST and ALT, with level more than 100–200 U/L. Aim: To getting a better solutions for this problem. Method: Obsevasional Study had been done in medical faculty ofAirlangga University (Dr. Soetomo and Soerya hospital Surabaya on Mei–August 2012. There were 10 cases ofdengue virus infection were studied, 5 cases got Ringer Acetate solution (Group A and 5 cases got Ringer Lactate solution (Group B. The diagnosis was based on criteria WHO 2009. Result: Five cases ofDengue Virus Infection had showed a liver damage soon after using Ringer Lactate solution; AST and ALT were increasing more than 100–200 U/L; but the other 5 cases showed better condition. It might be due to use Ringer Acetate that did not have effect for inducing liver damage. By managing carefully, all of the cases had shown full recovery and healthy condition when being discharged. Conclusion: Using Ringer Acetate as fluid therapy in Dengue Virus Infection is better to prevent liver damage than using Ringer Lactate.

  15. Chronic nitrate enrichment decreases severity and induces protection against an infectious disease.

    Science.gov (United States)

    Smallbone, Willow; Cable, Jo; Maceda-Veiga, Alberto

    2016-05-01

    Excessive fertilisation is one of the most pernicious forms of global change resulting in eutrophication. It has major implications for disease control and the conservation of biodiversity. Yet, the direct link between nutrient enrichment and disease remains largely unexplored. Here, we present the first experimental evidence that chronic nitrate enrichment decreases severity and induces protection against an infectious disease. Specifically, this study shows that nitrate concentrations ranging between 50 and 250mgNO3(-)/l reduce Gyrodactylus turnbulli infection intensity in two populations of Trinidadian guppies Poecilia reticulata, and that the highest nitrate concentration can even clean the parasites from the fish. This added to the fact that host nitrate pre-exposure altered the fish epidermal structure and reduced parasite intensity, suggests that nitrate protected the host against the disease. Nitrate treatments also caused fish mortality. As we used ecologically-relevant nitrate concentrations, and guppies are top-consumers widely used for mosquito bio-control in tropical and often nutrient-enriched waters, our results can have major ecological and social implications. In conclusion, this study advocates reducing nitrate level including the legislative threshold to protect the aquatic biota, even though this may control an ectoparasitic disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. A Benchmarking Study of High Energy Carbon Ion Induced Neutron Using Several Monte Carlo Codes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, D. H.; Oh, J. H.; Jung, N. S.; Lee, H. S. [Pohang Accelerator Laboratory, Pohang (Korea, Republic of); Shin, Y. S.; Kwon, D. Y.; Kim, Y. M. [Catholic Univ., Gyeongsan (Korea, Republic of); Oranj, L. Mokhtari [POSTECH, Pohang (Korea, Republic of)

    2014-10-15

    In this study, the benchmarking study was done for the representative particle interaction of the heavy ion accelerator, especially carbon-induced reaction. The secondary neutron is an important particle in the shielding analysis to define the source term and penetration ability of radiation fields. The performance of each Monte Carlo codes were verified for selected codes: MCNPX 2.7, PHITS 2.64 and FLUKA 2011.2b.6. For this benchmarking study, the experimental data of Kurosawa et al. in the SINBAD database of NEA was applied. The calculated results of the differential neutron yield produced from several materials irradiated by high energy carbon beam reproduced the experimental data well in small uncertainty. But the MCNPX results showed large discrepancy with experimental data, especially at the forward angle. The calculated results were lower a little than the experimental and it was clear in the cases of lower incident carbon energy, thinner target and forward angle. As expected, the influence of different model was found clearly at forward direction. In the shielding analysis, these characteristics of each Monte Carlo codes should be considered and utilized to determine the safety margin of a shield thickness.

  17. A Benchmarking Study of High Energy Carbon Ion Induced Neutron Using Several Monte Carlo Codes

    International Nuclear Information System (INIS)

    Kim, D. H.; Oh, J. H.; Jung, N. S.; Lee, H. S.; Shin, Y. S.; Kwon, D. Y.; Kim, Y. M.; Oranj, L. Mokhtari

    2014-01-01

    In this study, the benchmarking study was done for the representative particle interaction of the heavy ion accelerator, especially carbon-induced reaction. The secondary neutron is an important particle in the shielding analysis to define the source term and penetration ability of radiation fields. The performance of each Monte Carlo codes were verified for selected codes: MCNPX 2.7, PHITS 2.64 and FLUKA 2011.2b.6. For this benchmarking study, the experimental data of Kurosawa et al. in the SINBAD database of NEA was applied. The calculated results of the differential neutron yield produced from several materials irradiated by high energy carbon beam reproduced the experimental data well in small uncertainty. But the MCNPX results showed large discrepancy with experimental data, especially at the forward angle. The calculated results were lower a little than the experimental and it was clear in the cases of lower incident carbon energy, thinner target and forward angle. As expected, the influence of different model was found clearly at forward direction. In the shielding analysis, these characteristics of each Monte Carlo codes should be considered and utilized to determine the safety margin of a shield thickness

  18. Trimethoprim/Sulfamethoxazole-Induced Severe Lactic Acidosis: A Case Report and Review of the Literature.

    Science.gov (United States)

    Bulathsinghala, Marie; Keefer, Kimberly; Van de Louw, Andry

    2016-04-01

    Propylene glycol (PG) is used as a solvent in numerous medications, including trimethoprim/sulfamethoxazole (TMP/SMX) and lorazepam, and is metabolized in the liver to lactic acid. Cases of lactic acidosis related to PG toxicity have been described and always involved large doses of benzodiazepines and PG. We present the first case of severe lactic acidosis after a 3-day course of TMP/SMX alone, involving allegedly safe amounts of PG.A 31-year-old female with neurofibromatosis and pilocytic astrocytoma, receiving temozolomide and steroids, was admitted to the intensive care unit for pneumonia and acute respiratory failure requiring intubation. Her initial hemodynamic and acid-base statuses were normal. She was treated with intravenous TMP/SMX for possible Pneumocystis jirovecii pneumonia and was successfully extubated on day 2. On day 3, she developed tachypnea and arterial blood gas analysis revealed a severe metabolic acidosis (pH 7.2, PCO2 19 mm Hg, bicarbonates 8 mEq/L) with anion gap of 25 mEq/L and lactate of 12.1 mmol/L. TMP/SMX was discontinued and the lactate decreased to 2.9 mmol/L within 24 hours while her plasma bicarbonates normalized, without additional intervention. The patient never developed hypotension or severe hypoxia, and her renal and liver functions were normal. No other cause for lactic acidosis was identified and it resolved after TMP/SMX cessation alone, suggesting PG toxicity.Although PG-related lactic acidosis is well recognized after large doses of lorazepam, clinicians should bear in mind that TMP/SMX contains PG as well and should suspect PG toxicity in patients developing unexplained metabolic acidosis while receiving TMP/SMX.

  19. Severe congenital malformations, family functioning and parents' separation/divorce: a longitudinal study.

    Science.gov (United States)

    Brenner, M; Côté, S M; Boivin, M; Tremblay, R E

    2016-01-01

    We aim to explore the association of a severe congenital malformation (SCM) with postnatal family functioning and parents' separation/divorce and to examine if this association might be moderated by birth order of the child and parental level of education. SCM refers to malformations that, without medical intervention, cause handicap or death. Using the Quebec Longitudinal Study of Child Development, an ongoing population-based birth cohort study initiated in 1998, we compared 1675 families of children with and without a SCM to identify if having a child with a SCM was associated with maternal perception of family functioning. We examined if an SCM was associated with parents' separation and examined parents' education level and birth order of the children to evaluate whether these factors had any moderating effect on the results. There were no significant differences in family functioning between families with and without a SCM child at 5 and 17 months. At 5 months, family functioning was significantly better (P = 0.03) for families with a SCM firstborn child than for families with a SCM child that is not firstborn. For parental separation, no significant differences were observed at 5 and 29 months and 4 years. No significant moderating effects were observed for birth order and parental education on parental separation. Families of children with a SCM do not appear to be at higher risk of family dysfunction within the first 17 months after birth nor of parental separation within the first 4 years after birth. Family functioning tends to be worst in families where the child with SCM is the second or subsequent child born. © 2015 John Wiley & Sons Ltd.

  20. Interpersonal traits change as a function of disease type and severity in degenerative brain diseases.

    Science.gov (United States)

    Sollberger, Marc; Neuhaus, John; Ketelle, Robin; Stanley, Christine M; Beckman, Victoria; Growdon, Matthew; Jang, Jung; Miller, Bruce L; Rankin, Katherine P

    2011-07-01

    Different degenerative brain diseases result in distinct personality changes as a result of divergent patterns of brain damage; however, little is known about the natural history of these personality changes throughout the course of each disease. To investigate how interpersonal traits change as a function of degenerative brain disease type and severity. Using the Interpersonal Adjective Scales, informant ratings of retrospective premorbid and current scores for dominance, extraversion, warmth and ingenuousness were collected annually for 1 to 4 years on 188 patients (67 behavioural variant frontotemporal dementia (bvFTD), 40 semantic dementia (SemD), 81 Alzheimer's disease (AD)) and 65 older healthy controls. Using random coefficient models, interpersonal behaviour scores at very mild, mild or moderate-to-severe disease stages were compared within and between patient groups. Group-level changes from premorbid personality occurred as a function of disease type and severity, and were apparent even at a very mild disease stage (Clinical Dementia Rating=0.5) for all three diseases. Decreases in interpersonal traits were associated with emotional affiliation (ie, extraversion, warmth and ingenuousness) and more rigid interpersonal behaviour differentiated bvFTD and SemD patients from AD patients. Specific changes in affiliative interpersonal traits differentiate degenerative brain diseases even at a very mild disease stage, and patterns of personality change differ across bvFTD, SemD and AD with advancing disease. This study describes the typical progression of change of interpersonal traits in each disease, improving the ability of clinicians and caregivers to predict and plan for symptom progression.

  1. Clinical heterogeneity among people with high functioning autism spectrum conditions: evidence favouring a continuous severity gradient

    Directory of Open Access Journals (Sweden)

    Woodbury-Smith Marc

    2008-02-01

    Full Text Available Abstract Background Autism Spectrum Conditions (ASCs are characterized by a high degree of clinical heterogeneity, but the extent to which this variation represents a severity gradient versus discrete phenotypes is unclear. This issue has complicated genetic studies seeking to investigate the genetic basis of the high hereditability observed clinically in those with an ASC. The aim of this study was to examine the possible clustering of symptoms associated with ASCs to determine whether the observed distribution of symptom type and severity supported either a severity or a symptom subgroup model to account for the phenotypic variation observed within the ASCs. Methods We investigated the responses of a group of adults with higher functioning ASCs on the fifty clinical features examined in the Autism Spectrum Quotient, a screening questionnaire used in the diagnosis of higher functioning ASCs. In contrast to previous studies we have used this instrument with no a priori assumptions about any underlying factor structure of constituent items. The responses obtained were analyzed using complete linkage hierarchical cluster analysis. For the members of each cluster identified the mean score on each Autism Spectrum Quotient question was calculated. Results Autism Spectrum Quotient responses from a total of 333 individuals between the ages of 16.6 and 78.0 years were entered into the hierarchical cluster analysis. The four cluster solution was the one that generated the largest number of clusters that did not also include very small cluster sizes, defined as a membership comprising 10 individuals or fewer. Examination of these clusters demonstrated that they varied in total Autism Spectrum Quotient but that the profiles across the symptoms comprising the Autism Spectrum Quotient did not differ independently of this severity factor. Conclusion These results are consistent with a unitary spectrum model, suggesting that the clinical heterogeneity observed

  2. Disengagement from tasks as a function of cognitive load and depressive symptom severity.

    Science.gov (United States)

    Bowie, Christopher R; Milanovic, Melissa; Tran, Tanya; Cassidy, Sarah

    2017-01-01

    Depression is associated with impairment in cognition and everyday functioning. Mechanisms of cognitive dysfunction in depression and the factors that influence strategic deployment of cognitive abilities in complex environments remain elusive. In this study we investigated whether depression symptom severity is associated with disengagement from a working memory task (Paced Auditory Serial Addition Task; PASAT) with parametric adjustment of task difficulty. 235 participants completed the Beck Depression Inventory, low and high cognitive load conditions of the PASAT, and quality of life. Cognitive disengagement was the sum of consecutive items in which participants did not proffer a response to the trial. Individuals with higher depression severity showed more cognitive disengagement on the high but not low cognitive load trial of the PASAT; they did not differ in number of correct responses. Increased disengagement from the low to high cognitive load was associated with more impaired quality of life. Depression severity is associated with increased disengagement from tasks as difficulty increases. These findings suggest the importance of measuring how cognitive skills are avoided in complex environments in addition to considering performance accuracy. Individuals with depressive symptoms might preferentially avoid cognitive tasks that are perceived as more complex in spite of intact ability.

  3. The C-terminal sequence of several human serine proteases encodes host defense functions.

    Science.gov (United States)

    Kasetty, Gopinath; Papareddy, Praveen; Kalle, Martina; Rydengård, Victoria; Walse, Björn; Svensson, Bo; Mörgelin, Matthias; Malmsten, Martin; Schmidtchen, Artur

    2011-01-01

    Serine proteases of the S1 family have maintained a common structure over an evolutionary span of more than one billion years, and evolved a variety of substrate specificities and diverse biological roles, involving digestion and degradation, blood clotting, fibrinolysis and epithelial homeostasis. We here show that a wide range of C-terminal peptide sequences of serine proteases, particularly from the coagulation and kallikrein systems, share characteristics common with classical antimicrobial peptides of innate immunity. Under physiological conditions, these peptides exert antimicrobial effects as well as immunomodulatory functions by inhibiting macrophage responses to bacterial lipopolysaccharide. In mice, selected peptides are protective against lipopolysaccharide-induced shock. Moreover, these S1-derived host defense peptides exhibit helical structures upon binding to lipopolysaccharide and also permeabilize liposomes. The results uncover new and fundamental aspects on host defense functions of serine proteases present particularly in blood and epithelia, and provide tools for the identification of host defense molecules of therapeutic interest. Copyright © 2011 S. Karger AG, Basel.

  4. Functional level during the first 2 years after moderate and severe traumatic brain injury.

    Science.gov (United States)

    Sandhaug, Maria; Andelic, Nada; Langhammer, Birgitta; Mygland, Aase

    2015-01-01

    Long-term outcomes after TBI are examined to a large extent, but longitudinal studies with more than 1-year follow-up time after injury have been fewer in number. The course of recovery may vary due to a number of factors and it is still somewhat unclear which factors are contributing. The aim of this study was to describe the functional level at four time points up to 24 months after traumatic brain injury (TBI) and to evaluate the predictive impact of pre-injury and injury-related factors. A cohort study. Outpatient. Sixty-five patients with moderate (n = 21) or severe (n = 44) TBI. The patients with TBI were examined with Functional Independence Measure (FIM) and Glasgow Outcome Scale Extended (GOSE) at 3 months, 12 months and 24 months after injury. Possible predictors were analysed in a regression model using FIM total score at 24 months as the outcome measure. FIM scores improved significantly from rehabilitation unit discharge to 24 months after injury, with peak levels at 3 and 24 months after injury (p GOSE scores for the whole group and the moderate group improved significantly over time, but the severe group did not. FIM at admission to the rehabilitation unit and GCS score at admission to the rehabilitation unit were closest to being significant predictors of FIM total scores 24 months after injury (B = 0.265 and 2.883, R(2 )= 0.39, p = 0.073, p = 0.081). FIM levels improved during the period from rehabilitation unit discharge to 3 months follow-up; thereafter, there was a 'plateauing' of recovery. In contrast, GOSE 'plateauing' of recovery was at 12 months. The study results may indicate that two of the most used outcome measures in TBI research are more relevant for assessment of the functional recovery in a sub-acute phase than in later stages of TBI recovery.

  5. Application of a simplified definition of diastolic function in severe sepsis and septic shock.

    Science.gov (United States)

    Lanspa, Michael J; Gutsche, Andrea R; Wilson, Emily L; Olsen, Troy D; Hirshberg, Eliotte L; Knox, Daniel B; Brown, Samuel M; Grissom, Colin K

    2016-08-04

    Left ventricular diastolic dysfunction is common in patients with severe sepsis or septic shock, but the best approach to categorization is unknown. We assessed the association of common measures of diastolic function with clinical outcomes and tested the utility of a simplified definition of diastolic dysfunction against the American Society of Echocardiography (ASE) 2009 definition. In this prospective observational study, patients with severe sepsis or septic shock underwent transthoracic echocardiography within 24 h of onset of sepsis (median 4.3 h). We measured echocardiographic parameters of diastolic function and used random forest analysis to assess their association with clinical outcomes (28-day mortality and ICU-free days to day 28) and thereby suggest a simplified definition. We then compared patients categorized by the ASE 2009 definition and our simplified definition. We studied 167 patients. The ASE 2009 definition categorized only 35 % of patients. Random forest analysis demonstrated that the left atrial volume index and deceleration time, central to the ASE 2009 definition, were not associated with clinical outcomes. Our simplified definition used only e' and E/e', omitting the other measurements. The simplified definition categorized 87 % of patients. Patients categorized by either ASE 2009 or our novel definition had similar clinical outcomes. In both definitions, worsened diastolic function was associated with increased prevalence of ischemic heart disease, diabetes, and hypertension. A novel, simplified definition of diastolic dysfunction categorized more patients with sepsis than ASE 2009 definition. Patients categorized according to the simplified definition did not differ from patients categorized according to the ASE 2009 definition in respect to clinical outcome or comorbidities.

  6. Volumetric Nephrogram Represents Renal Function and Complements Aortic Anatomic Severity Grade in Predicting EVAR Outcomes.

    Science.gov (United States)

    Balceniuk, Mark D; Trakimas, Lauren; Aghaie, Claudia; Mix, Doran; Rasheed, Khurram; Seaman, Matthew; Ellis, Jennifer; Glocker, Roan; Doyle, Adam; Stoner, Michael C

    2018-07-01

    Chronic kidney disease (CKD) is a predictor of poor outcomes for patients undergoing endovascular aortic aneurysm repair (EVAR). Anatomic severity grade (ASG) represents a quantitative mechanism for assessing anatomical suitability for endovascular aortic repair. Anatomic severity grade has been correlated with repair outcomes and resource utilization. The purpose of this study was to identify a novel renal perfusion metric as a way to assist ASG with predicting EVAR outcomes. Retrospective review of a prospectively maintained database identified elective infrarenal aortic aneurysm repair cases. Anatomic grading was undertaken by independent reviewers. Using volumetric software, kidney volume, and a novel measure of kidney functional volume, the volumetric nephrogram (VN) was recorded. Systematic evaluation of the relationship of kidney volume and VN to CKD and ASG was undertaken using linear regression and receiver-operator statistical tools. A total of 386 cases with patient and anatomic data were identified and graded. Mean age was 72.9 ± 0.4 years. Renal volume renal volume (AUC = .628; P ≤ .0001) and VN (AUC = .628; P ≤ .0001). Regression analysis demonstrated a strong, inverse relationship between ASG and VN ( R 2 = .95). These data demonstrate that VN is a strong predictor of CKD in a large database of patients undergoing elective aneurysm repair. We demonstrate an inverse relationship between renal function and ASG that has not been previously described in the literature. Additionally, we have shown that VN complements ASG as a model of overall cardiovascular health and atherosclerotic burden. Outcomes in patients with poor renal function may be related to anatomical issues in addition to well-described systemic ramifications.

  7. Esophageal Sensorimotor Function and Psychological Factors Each Contribute to Symptom Severity in Globus Patients.

    Science.gov (United States)

    Rommel, Nathalie; Van Oudenhove, Lukas; Arts, Joris; Caenepeel, Philip; Tack, Jan; Pauwels, Ans

    2016-10-01

    Altered upper esophageal sphincter (UES) and esophageal body (EB) sensorimotor function and psychosocial factors may both be involved in symptom generation in globus, but their common impact is not yet assessed. The aim of the study is (1) to compare UES and EB sensitivity and compliance of globus patients with healthy controls (HC); (2) to study the association of globus symptom severity (GSS) with UES and EB sensitivity and compliance, UES motor function and psychosocial factors. In 58 globus patients, GSS, somatization, and anxiety disorders were determined using validated questionnaires. In 26 HC and 42/58 patients, UES and EB sensitivity and compliance were assessed twice using barostat measurements. UES function of 27 globus patients was evaluated using high-resolution manometry. Bivariate correlations and a general linear model tested the association of these factors with GSS. UES and EB compliance did not differ between globus patients and HC. Upon repeated distension, UES habituation was seen in both groups, whereas EB sensitization (23.3±1.3 vs. 19.5±1.5 mm Hg, Pdisorder (t=3.04, P=0.004), and post-traumatic stress severity (ρ=0.40, P=0.005) were associated with GSS. UES compliance and somatization were independently associated with GSS. A trend (P=0.061) was found for the association of GSS with change in EB compliance. UES compliance, change in EB compliance, and somatization explain 40% of the variance in GSS. This indicates that globus is a complex disorder of the brain-gut axis rather than a "psychosomatic" disorder or a peripheral esophageal disorder.

  8. Clinical presentation of terbinafine-induced severe liver injury and the value of laboratory monitoring: a Critically Appraised Topic.

    Science.gov (United States)

    Kramer, O N; Albrecht, J

    2017-11-01

    Many physicians monitor liver function tests during terbinafine therapy. To evaluate the symptoms of published cases of terbinafine-associated severe drug-induced liver injury (DILI) to assess the utility of laboratory monitoring. We based our search on the LiverTox database of the National Institutes of Health, but we also searched both PubMed and Embase. In addition, we hand searched the references of the papers we found. All reports of patients with DILI on terbinafine and with reported clinical symptoms, or absence thereof, were evaluated. Two independent reviewers (J.A. and O.N.K.) assessed articles for eligibility of inclusion, and collected and evaluated the data. Thirty-eight papers fulfilled the inclusion criteria, with reports of 69 symptomatic patients. The mean duration of terbinafine treatment until onset of symptoms was 30·2 days (range 5-84). Symptoms in order of frequency were jaundice, flu-like symptoms, dark urine and pruritus. Patients experienced symptoms for a mean and median of 14·8 and 16 days, respectively (range 0-42) until seeking medical attention. Patients who had DILI were symptomatic, usually with jaundice, abdominal pain and general malaise, but also with severe pruritus. No asymptomatic patient was identified through laboratory screening. The timeline of DILI onset varies significantly, but most cases occur between 4 and 6 weeks. There was no time point at which monitoring was meaningful, and we do not recommend monitoring of liver function tests on terbinafine; however, patients should be advised to discontinue treatment and look for medical care when symptoms of DILI occur. © 2017 British Association of Dermatologists.

  9. Decannulation and Functional Outcome After Tracheostomy in Patients with Severe Stroke (DECAST): A Prospective Observational Study.

    Science.gov (United States)

    Schneider, Hauke; Hertel, Franziska; Kuhn, Matthias; Ragaller, Maximilian; Gottschlich, Birgit; Trabitzsch, Anne; Dengl, Markus; Neudert, Marcus; Reichmann, Heinz; Wöpking, Sigrid

    2017-08-01

    Tracheostomy is performed in ventilated stroke patients affected by persisting severe dysphagia, reduced level of consciousness, or prolonged mechanical ventilation. The study aim was to determine the frequency and predictors of successful decannulation and long-term functional outcome in tracheotomized stroke patients. A prospective single-center observational study recruited ventilated patients with ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. Follow-up visits were performed at hospital discharge, 3, and 12 months. Competing risk analyses were performed to identify predictors of decannulation. We included 53 ventilated stroke patients who had tracheostomy. One year after tracheostomy, 19 patients were decannulated (median [IQR] time to decannulation 74 [58-117] days), 13 patients were permanently cannulated, and 21 patients died without prior removal of the cannula. Independent predictors for decannulation in our cohort were patient age (HR 0.95 [95% CI: 0.92-0.99] per one year increase, p = 0.003) and absence of sepsis (HR 4.44 [95% CI: 1.33-14.80], p = 0.008). Compared to surviving patients without cannula removal, decannulated patients had an improved functional outcome after one year (median modified Rankin Scale score 4 vs. 5 [p tracheostomy and was associated with better functional outcome compared to patients without decannulation. Further prospective studies with larger sample sizes are needed to confirm our results.

  10. Development and functional demonstration of a wireless intraoral inductive tongue computer interface for severely disabled persons.

    Science.gov (United States)

    N S Andreasen Struijk, Lotte; Lontis, Eugen R; Gaihede, Michael; Caltenco, Hector A; Lund, Morten Enemark; Schioeler, Henrik; Bentsen, Bo

    2017-08-01

    Individuals with tetraplegia depend on alternative interfaces in order to control computers and other electronic equipment. Current interfaces are often limited in the number of available control commands, and may compromise the social identity of an individual due to their undesirable appearance. The purpose of this study was to implement an alternative computer interface, which was fully embedded into the oral cavity and which provided multiple control commands. The development of a wireless, intraoral, inductive tongue computer was described. The interface encompassed a 10-key keypad area and a mouse pad area. This system was embedded wirelessly into the oral cavity of the user. The functionality of the system was demonstrated in two tetraplegic individuals and two able-bodied individuals Results: The system was invisible during use and allowed the user to type on a computer using either the keypad area or the mouse pad. The maximal typing rate was 1.8 s for repetitively typing a correct character with the keypad area and 1.4 s for repetitively typing a correct character with the mouse pad area. The results suggest that this inductive tongue computer interface provides an esthetically acceptable and functionally efficient environmental control for a severely disabled user. Implications for Rehabilitation New Design, Implementation and detection methods for intra oral assistive devices. Demonstration of wireless, powering and encapsulation techniques suitable for intra oral embedment of assistive devices. Demonstration of the functionality of a rechargeable and fully embedded intra oral tongue controlled computer input device.

  11. Analytic function theory of several variables elements of Oka’s coherence

    CERN Document Server

    Noguchi, Junjiro

    2016-01-01

    The purpose of this book is to present the classical analytic function theory of several variables as a standard subject in a course of mathematics after learning the elementary materials (sets, general topology, algebra, one complex variable). This includes the essential parts of Grauert–Remmert's two volumes, GL227(236) (Theory of Stein spaces) and GL265 (Coherent analytic sheaves) with a lowering of the level for novice graduate students (here, Grauert's direct image theorem is limited to the case of finite maps). The core of the theory is "Oka's Coherence", found and proved by Kiyoshi Oka. It is indispensable, not only in the study of complex analysis and complex geometry, but also in a large area of modern mathematics. In this book, just after an introductory chapter on holomorphic functions (Chap. 1), we prove Oka's First Coherence Theorem for holomorphic functions in Chap. 2. This defines a unique character of the book compared with other books on this subject, in which the notion of coherence appear...

  12. Leptin in pediatrics: A hormone from adipocyte that wheels several functions in children

    Directory of Open Access Journals (Sweden)

    Ashraf T Soliman

    2012-01-01

    Full Text Available The protein leptin, a pleiotropic hormone regulates appetite and energy balance of the body and plays important roles in controlling linear growth, pubertal development, cardiovascular function, and immunity. Recent findings in the understanding of the structure, functional roles, and clinical significance of conditions with increased and decreased leptin secretion are summarized. Balance between leptin and other hormones is significantly regulated by nutritional status. This balance influences many organ systems, including the brain, liver, and skeletal muscle, to mediate the essential adaptation process. The aim of this review is to summarize the possible physiological functions of leptin and its signaling pathways during childhood and adolescence including control of food intake, energy regulation, growth and puberty, and immunity. Moreover, its secretion and possible roles in the adaptation process during different disease states (obesity, malnutrition, eating disorders, delayed puberty, congenital heart diseases and hepatic disorders are discussed. The clinical manifestations and the successful management of patients with genetic leptin deficiency and the application of leptin therapy in other diseases including lipodystrophy, states with severe insulin resistance, and diabetes mellitus are discussed.

  13. Leptin in pediatrics: A hormone from adipocyte that wheels several functions in children

    Science.gov (United States)

    Soliman, Ashraf T.; Yasin, Mohamed; Kassem, Ahmed

    2012-01-01

    The protein leptin, a pleiotropic hormone regulates appetite and energy balance of the body and plays important roles in controlling linear growth, pubertal development, cardiovascular function, and immunity. Recent findings in the understanding of the structure, functional roles, and clinical significance of conditions with increased and decreased leptin secretion are summarized. Balance between leptin and other hormones is significantly regulated by nutritional status. This balance influences many organ systems, including the brain, liver, and skeletal muscle, to mediate the essential adaptation process. The aim of this review is to summarize the possible physiological functions of leptin and its signaling pathways during childhood and adolescence including control of food intake, energy regulation, growth and puberty, and immunity. Moreover, its secretion and possible roles in the adaptation process during different disease states (obesity, malnutrition, eating disorders, delayed puberty, congenital heart diseases and hepatic disorders) are discussed. The clinical manifestations and the successful management of patients with genetic leptin deficiency and the application of leptin therapy in other diseases including lipodystrophy, states with severe insulin resistance, and diabetes mellitus are discussed. PMID:23565493

  14. Improvement of Functional Properties by Sever Plastic Deformation on Parts of Titanium Biomaterials

    Science.gov (United States)

    Czán, Andrej; Babík, Ondrej; Daniš, Igor; Martikáň, Pavol; Czánová, Tatiana

    2017-12-01

    Main task of materials for invasive implantology is their biocompatibility with the tissue but also requirements for improving the functional properties of given materials are increasing constantly. One of problems of materials biocompatibility is the impossibility to improve of functional properties by change the percentage of the chemical elements and so it is necessary to find other innovative methods of improving of functional properties such as mechanical action in the form of high deformation process. This paper is focused on various methods of high deformation process such as Equal Channel Angular Pressing (ECAP) when rods with record strength properties were obtained.The actual studies of the deformation process properties as tri-axial compress stress acting on workpiece with high speed of deformation shows effects similar to results obtained using the other methods, but in lower levels of stress. Hydrostatic extrusion (HE) is applying for the purpose of refining the structure of the commercially pure titanium up to nano-scale. Experiments showed the ability to reduce the grain size below 100 nm. Due to the significant change in the performance of the titanium materials by severe plastic deformation is required to identify the processability of materials with respect to the identification of created surfaces and monitoring the surface integrity, where the experimental results show ability of SPD technologies application on biomaterials.

  15. Rethinking platelet function: thrombocytopenia induced immunodeficiency in critical illness

    DEFF Research Database (Denmark)

    Ostrowski, Sisse R; Johansson, Per Ingemar

    2011-01-01

    Thrombocytopenia in critical illness predicts a poor clinical outcome. Apart from its role in microvascular thrombus formation, it is widely anticipated that this association is indirect rather than causal. Emerging evidence however indicates that platelets are also immune competent cells. Like...... per se results in immunodeficiency through loss of platelet-mediated immune functions, and propose that thrombocytopenia induced immunodeficiency in critical illness in part explain the negative predictive value of low or declining platelet count. We propose that rethinking the risks...... of thrombocytopenia to include not only bleeding but also immunodeficiency and immune dysregulation along with the conduct of studies investigating mechanisms contributing to thrombocytopenia induced poor non-hemorrhagic outcome in critical illness, may be means to improve outcome in these patients through...

  16. Intranuclear interactomic inhibition of NF-κB suppresses LPS-induced severe sepsis

    International Nuclear Information System (INIS)

    Park, Sung-Dong; Cheon, So Yeong; Park, Tae-Yoon; Shin, Bo-Young; Oh, Hyunju; Ghosh, Sankar; Koo, Bon-Nyeo; Lee, Sang-Kyou

    2015-01-01

    Suppression of nuclear factor-κB (NF-κB) activation, which is best known as a major regulator of innate and adaptive immune responses, is a potent strategy for the treatment of endotoxic sepsis. To inhibit NF-κB functions, we designed the intra-nuclear transducible form of transcription modulation domain (TMD) of RelA (p65), called nt-p65-TMD, which can be delivered effectively into the nucleus without influencing the cell viability, and work as interactomic inhibitors via disruption of the endogenous p65-mediated transcription complex. nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines, including TNF-α, IL-1β, or IL-6 from BV2 microglia cells stimulated by lipopolysaccharide (LPS). nt-p65-TMD did not inhibit tyrosine phosphorylation of signaling mediators such as ZAP-70, p38, JNK, or ERK involved in T cell activation, but was capable of suppressing the transcriptional activity of NF-κB without the functional effect on that of NFAT upon T-cell receptor (TCR) stimulation. The transduced nt-p65-TMD in T cell did not affect the expression of CD69, however significantly inhibited the secretion of T cell-specific cytokines such as IL-2, IFN-γ, IL-4, IL-17A, or IL-10. Systemic administration of nt-p65-TMD showed a significant therapeutic effect on LPS-induced sepsis model by inhibiting pro-inflammatory cytokines secretion. Therefore, nt-p65-TMD can be a novel therapeutics for the treatment of various inflammatory diseases, including sepsis, where a transcription factor has a key role in pathogenesis, and further allows us to discover new functions of p65 under normal physiological condition without genetic alteration. - Highlights: • The nt-p65-TMD is intra-nuclear interactomic inhibitor of endogenous p65. • The nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines. • The excellent therapeutic potential of nt-p65-TMD was confirmed in sepsis model

  17. Intranuclear interactomic inhibition of NF-κB suppresses LPS-induced severe sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung-Dong [Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Cheon, So Yeong [Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Park, Tae-Yoon; Shin, Bo-Young [Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Oh, Hyunju; Ghosh, Sankar [Department of Microbiology and Immunology, College of Physicians and Surgeons, Columbia University, New York, NY 10032 (United States); Koo, Bon-Nyeo, E-mail: koobn@yuhs.ac [Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Lee, Sang-Kyou, E-mail: sjrlee@yonsei.ac.kr [Translational Research Center for Protein Function Control, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2015-08-28

    Suppression of nuclear factor-κB (NF-κB) activation, which is best known as a major regulator of innate and adaptive immune responses, is a potent strategy for the treatment of endotoxic sepsis. To inhibit NF-κB functions, we designed the intra-nuclear transducible form of transcription modulation domain (TMD) of RelA (p65), called nt-p65-TMD, which can be delivered effectively into the nucleus without influencing the cell viability, and work as interactomic inhibitors via disruption of the endogenous p65-mediated transcription complex. nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines, including TNF-α, IL-1β, or IL-6 from BV2 microglia cells stimulated by lipopolysaccharide (LPS). nt-p65-TMD did not inhibit tyrosine phosphorylation of signaling mediators such as ZAP-70, p38, JNK, or ERK involved in T cell activation, but was capable of suppressing the transcriptional activity of NF-κB without the functional effect on that of NFAT upon T-cell receptor (TCR) stimulation. The transduced nt-p65-TMD in T cell did not affect the expression of CD69, however significantly inhibited the secretion of T cell-specific cytokines such as IL-2, IFN-γ, IL-4, IL-17A, or IL-10. Systemic administration of nt-p65-TMD showed a significant therapeutic effect on LPS-induced sepsis model by inhibiting pro-inflammatory cytokines secretion. Therefore, nt-p65-TMD can be a novel therapeutics for the treatment of various inflammatory diseases, including sepsis, where a transcription factor has a key role in pathogenesis, and further allows us to discover new functions of p65 under normal physiological condition without genetic alteration. - Highlights: • The nt-p65-TMD is intra-nuclear interactomic inhibitor of endogenous p65. • The nt-p65-TMD effectively inhibited the secretion of pro-inflammatory cytokines. • The excellent therapeutic potential of nt-p65-TMD was confirmed in sepsis model.

  18. The early functional outcome of Mau osteotomy for the correction of moderate-severe hallux valgus

    Directory of Open Access Journals (Sweden)

    Tanujan Thangarajah

    2013-11-01

    Full Text Available Hallux valgus is one of the commonest conditions of the foot and has been reported to affect nearly half of the adult population. It is most effectively treated by a corrective osteotomy of which there a numerous subtypes. The Mau osteotomy confers the greatest structural stability but is not thought to provide adequate correction of moderate-severe deformities. Accordingly, complications such as under correction and non-union are common. The aim of this study was to determine the functional outcome in patients with moderate-severe hallux valgus following a Mau osteotomy. A retrospective review of 23 patients with moderate-severe hallux valgus treated by Mau osteotomy was conducted. Patients were assessed clinically by the American Orthopedic Foot and Ankle Society (AOFAS scoring system and radiologically by measuring the first intermetatarsal (IM and hallux abductovalgus angles (HAV. The mean AOFAS score had improved from 47 preoperatively to 92 postoperatively (P<0.01. Additionally, preoperative HAV and IM angles improved from 39° and 15° respectively to 15° and 9° respectively (P<0.01. There were no cases of undercorrection or non-union. In this series, the Mau osteotomy was able to achieve good correction of the IM and HAV angles in patients with moderate-severe hallux valgus. This was reflected in a significantly higher postoperative AOFAS score. Contrary to other studies there were no cases of undercorrection and despite allowing patients to fully weight-bear postoperatively there were no cases of non-union.

  19. Functional Sites Induce Long-Range Evolutionary Constraints in Enzymes.

    Directory of Open Access Journals (Sweden)

    Benjamin R Jack

    2016-05-01

    Full Text Available Functional residues in proteins tend to be highly conserved over evolutionary time. However, to what extent functional sites impose evolutionary constraints on nearby or even more distant residues is not known. Here, we report pervasive conservation gradients toward catalytic residues in a dataset of 524 distinct enzymes: evolutionary conservation decreases approximately linearly with increasing distance to the nearest catalytic residue in the protein structure. This trend encompasses, on average, 80% of the residues in any enzyme, and it is independent of known structural constraints on protein evolution such as residue packing or solvent accessibility. Further, the trend exists in both monomeric and multimeric enzymes and irrespective of enzyme size and/or location of the active site in the enzyme structure. By contrast, sites in protein-protein interfaces, unlike catalytic residues, are only weakly conserved and induce only minor rate gradients. In aggregate, these observations show that functional sites, and in particular catalytic residues, induce long-range evolutionary constraints in enzymes.

  20. Oxidative stress induced inflammation initiates functional decline of tear production.

    Directory of Open Access Journals (Sweden)

    Yuichi Uchino

    Full Text Available Oxidative damage and inflammation are proposed to be involved in an age-related functional decline of exocrine glands. However, the molecular mechanism of how oxidative stress affects the secretory function of exocrine glands is unclear. We developed a novel mev-1 conditional transgenic mouse model (Tet-mev-1 using a modified tetracycline system (Tet-On/Off system. This mouse model demonstrated decreased tear production with morphological changes including leukocytic infiltration and fibrosis. We found that the mev-1 gene encodes Cyt-1, which is the cytochrome b(560 large subunit of succinate-ubiquinone oxidoreductase in complex II of mitochondria (homologous to succinate dehydrogenase C subunit (SDHC in humans. The mev-1 gene induced excessive oxidative stress associated with ocular surface epithelial damage and a decrease in protein and aqueous secretory function. This new model provides evidence that mitochondrial oxidative damage in the lacrimal gland induces lacrimal dysfunction resulting in dry eye disease. Tear volume in Tet-mev-1 mice was lower than in wild type mice and histopathological analyses showed the hallmarks of lacrimal gland inflammation by intense mononuclear leukocytic infiltration and fibrosis in the lacrimal gland of Tet-mev-1 mice. These findings strongly suggest that oxidative stress can be a causative factor for the development of dry eye disease.

  1. Prevention of shockwave induced functional and morphological alterations: an overview.

    Science.gov (United States)

    Sarica, Kemal; Yencilek, Faruk

    2008-03-01

    Experimental as well as clinical findings reported in the literature suggest that treatment with shock wave lithotripsy (SWL) causes renal parenchymal damage mainly by generating free radicals through ischaemia/reperfusion injury mechanism. Although SWL-induced renal damage is well tolerated in the majority of healthy cases with no permanent functional and/or morphologic side effects, a subset of patients with certain risk factors requires close attention on this aspect among which the ones with pre-existing renal disorders, urinary tract infection, previous lithotripsy history and solitary kidneys could be mentioned. It is clear that in such patients lowering the number of shock waves (per session) could be beneficial and has been applied by the physicians as the first practical step of diminishing SWL induced parenchymal damage. On the other hand, taking the injurious effects of high energy shock wave (HESW) induced free radical formation on renal parenchyma and subsequent histopathologic alterations into account, physicians searched for some protective agents in an attempt to prevent or at least to limit the extent of the functional as well as the morphologic alterations. Among these agents calcium channel blocking agents (verapamil and nifedipine), antioxidant agents (allopurinol, vitamin E and selenium) and potassium citrate have been used to minimize these adverse effects. Additionally, therapeutic application of these agents on reducing stone recurrence particularly after SWL will gain more importance in the future in order to limit new stone formation in these cases. Lastly, as experimental and clinical studies have demonstrated, combination of anti-oxidants with free radical scavengers may provide superior renal protection against shock wave induced trauma. However, we believe that further investigations are certainly needed to determine the dose-response relationship between the damaging effects of SWL application and the protective role of these agents.

  2. Structural and functional differences in the cingulate cortex relate to disease severity in anorexia nervosa

    Science.gov (United States)

    Bär, Karl-Jürgen; de la Cruz, Feliberto; Berger, Sandy; Schultz, Carl Christoph; Wagner, Gerd

    2015-01-01

    Background The dysfunction of specific brain areas might account for the distortion of body image in patients with anorexia nervosa. The present study was designed to reveal brain regions that are abnormal in structure and function in patients with this disorder. We hypothesized, based on brain areas of altered activity in patients with anorexia nervosa and regions involved in pain processing, an interrelation of structural aberrations in the frontoparietal–cingulate network and aberrant functional activation during thermal pain processing in patients with the disorder. Methods We determined pain thresholds outside the MRI scanner in patients with anorexia nervosa and matched healthy controls. Thereafter, thermal pain stimuli were applied during fMRI imaging. Structural analyses with high-resolution structural T1-weighted volumes were performed using voxel-based morphometry and a surface-based approach. Results Twenty-six patients and 26 controls participated in our study, and owing to technical difficulties, 15 participants in each group were included in our fMRI analysis. Structural analyses revealed significantly decreased grey matter volume and cortical thickness in the frontoparietal–cingulate network in patients with anorexia nervosa. We detected an increased blood oxygen level–dependent signal in patients during the painful 45°C condition in the midcingulate and posterior cingulate cortex, which positively correlated with increased pain thresholds. Decreased grey matter and cortical thickness correlated negatively with pain thresholds, symptom severity and illness duration, but not with body mass index. Limitations The lack of a specific quantification of body image distortion is a limitation of our study. Conclusion This study provides further evidence for confined structural and functional brain abnormalities in patients with anorexia nervosa in brain regions that are involved in perception and integration of bodily stimuli. The association of

  3. Holonomic functions of several complex variables and singularities of anisotropic Ising n-fold integrals

    Science.gov (United States)

    Boukraa, S.; Hassani, S.; Maillard, J.-M.

    2012-12-01

    Focusing on examples associated with holonomic functions, we try to bring new ideas on how to look at phase transitions, for which the critical manifolds are not points but curves depending on a spectral variable, or even fill higher dimensional submanifolds. Lattice statistical mechanics often provides a natural (holonomic) framework to perform singularity analysis with several complex variables that would, in the most general mathematical framework, be too complex, or simply could not be defined. In a learn-by-example approach, considering several Picard-Fuchs systems of two-variables ‘above’ Calabi-Yau ODEs, associated with double hypergeometric series, we show that D-finite (holonomic) functions are actually a good framework for finding properly the singular manifolds. The singular manifolds are found to be genus-zero curves. We then analyze the singular algebraic varieties of quite important holonomic functions of lattice statistical mechanics, the n-fold integrals χ(n), corresponding to the n-particle decomposition of the magnetic susceptibility of the anisotropic square Ising model. In this anisotropic case, we revisit a set of so-called Nickelian singularities that turns out to be a two-parameter family of elliptic curves. We then find the first set of non-Nickelian singularities for χ(3) and χ(4), that also turns out to be rational or elliptic curves. We underline the fact that these singular curves depend on the anisotropy of the Ising model, or, equivalently, that they depend on the spectral parameter of the model. This has important consequences on the physical nature of the anisotropic χ(n)s which appear to be highly composite objects. We address, from a birational viewpoint, the emergence of families of elliptic curves, and that of Calabi-Yau manifolds on such problems. We also address the question of singularities of non-holonomic functions with a discussion on the accumulation of these singular curves for the non-holonomic anisotropic full

  4. Holonomic functions of several complex variables and singularities of anisotropic Ising n-fold integrals

    International Nuclear Information System (INIS)

    Boukraa, S; Hassani, S; Maillard, J-M

    2012-01-01

    Focusing on examples associated with holonomic functions, we try to bring new ideas on how to look at phase transitions, for which the critical manifolds are not points but curves depending on a spectral variable, or even fill higher dimensional submanifolds. Lattice statistical mechanics often provides a natural (holonomic) framework to perform singularity analysis with several complex variables that would, in the most general mathematical framework, be too complex, or simply could not be defined. In a learn-by-example approach, considering several Picard–Fuchs systems of two-variables ‘above’ Calabi–Yau ODEs, associated with double hypergeometric series, we show that D-finite (holonomic) functions are actually a good framework for finding properly the singular manifolds. The singular manifolds are found to be genus-zero curves. We then analyze the singular algebraic varieties of quite important holonomic functions of lattice statistical mechanics, the n-fold integrals χ (n) , corresponding to the n-particle decomposition of the magnetic susceptibility of the anisotropic square Ising model. In this anisotropic case, we revisit a set of so-called Nickelian singularities that turns out to be a two-parameter family of elliptic curves. We then find the first set of non-Nickelian singularities for χ (3) and χ (4) , that also turns out to be rational or elliptic curves. We underline the fact that these singular curves depend on the anisotropy of the Ising model, or, equivalently, that they depend on the spectral parameter of the model. This has important consequences on the physical nature of the anisotropic χ (n) s which appear to be highly composite objects. We address, from a birational viewpoint, the emergence of families of elliptic curves, and that of Calabi–Yau manifolds on such problems. We also address the question of singularities of non-holonomic functions with a discussion on the accumulation of these singular curves for the non

  5. Diet-induced obesity: dopamine transporter function, impulsivity and motivation.

    Science.gov (United States)

    Narayanaswami, V; Thompson, A C; Cassis, L A; Bardo, M T; Dwoskin, L P

    2013-08-01

    A rat model of diet-induced obesity (DIO) was used to determine dopamine transporter (DAT) function, impulsivity and motivation as neurobehavioral outcomes and predictors of obesity. To evaluate neurobehavioral alterations following the development of DIO induced by an 8-week high-fat diet (HF) exposure, striatal D2-receptor density, DAT function and expression, extracellular dopamine concentrations, impulsivity, and motivation for high- and low-fat reinforcers were determined. To determine predictors of DIO, neurobehavioral antecedents including impulsivity, motivation for high-fat reinforcers, DAT function and extracellular dopamine were evaluated before the 8-week HF exposure. Striatal D2-receptor density was determined by in vitro kinetic analysis of [(3)H]raclopride binding. DAT function was determined using in vitro kinetic analysis of [(3)H]dopamine uptake, methamphetamine-evoked [(3)H]dopamine overflow and no-net flux in vivo microdialysis. DAT cell-surface expression was determined using biotinylation and western blotting. Impulsivity and food-motivated behavior were determined using a delay discounting task and progressive ratio schedule, respectively. Relative to obesity-resistant (OR) rats, obesity-prone (OP) rats exhibited 18% greater body weight following an 8-week HF-diet exposure, 42% lower striatal D2-receptor density, 30% lower total DAT expression, 40% lower in vitro and in vivo DAT function, 45% greater extracellular dopamine and twofold greater methamphetamine-evoked [(3)H]dopamine overflow. OP rats exhibited higher motivation for food, and surprisingly, were less impulsive relative to OR rats. Impulsivity, in vivo DAT function and extracellular dopamine concentration did not predict DIO. Importantly, motivation for high-fat reinforcers predicted the development of DIO. Human studies are limited by their ability to determine if impulsivity, motivation and DAT function are causes or consequences of DIO. The current animal model shows that

  6. Impact of stress-induced diabetes on outcomes in severely burned children.

    Science.gov (United States)

    Finnerty, Celeste C; Ali, Arham; McLean, Josef; Benjamin, Nicole; Clayton, Robert P; Andersen, Clark R; Mlcak, Ronald P; Suman, Oscar E; Meyer, Walter; Herndon, David N

    2014-04-01

    Post-burn hyperglycemia leads to graft failure, multiple organ failure, and death. A hyperinsulinemic-euglycemic clamp is used to keep serum glucose between 60 and 110 mg/dL. Because of frequent hypoglycemic episodes, a less-stringent sliding scale insulin protocol is used to maintain serum glucose levels between 80 and 160 mg/dL after elevations >180 mg/dL. We randomized pediatric patients with massive burns into 2 groups, patients receiving sliding scale insulin to lower blood glucose levels (n = 145) and those receiving no insulin (n = 98), to determine the differences in morbidity and mortality. Patients 0 to 18 years old with burns covering ≥ 30% of the total body surface area and not randomized to receive anabolic agents were included in this study. End points included glucose levels, infections, resting energy expenditure, lean body mass, bone mineral content, fat mass, muscle strength, and serum inflammatory cytokines, hormones, and liver enzymes. Maximal glucose levels occurred within 6 days of burn injury. Blood glucose levels were age dependent, with older children requiring more insulin (p patients not receiving insulin, only in patients who received insulin (p patients receiving insulin (p Burn-induced hyperglycemia develops in a subset of severely burned children. Length of stay was reduced in the no insulin group, and there were no deaths in this group. Administration of insulin positively impacted bone mineral content and muscle strength, but increased resting energy expenditure, hypoglycemic episodes, and mortality. New glucose-lowering strategies might be needed. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  7. Bladder changes after several coverage modalities in the surgically induced model of myelomeningocele in lambs.

    Science.gov (United States)

    Burgos, L; Encinas, J L; García-Cabezas, M Á; Peiró, J L; López-Santamaría, M; Jaureguízar, E

    2014-01-01

    To assess the presence of early bladder abnormalities in a prenatally corrected and uncorrected animal model of Myelomeningocele (MMC). A MMC-like lesion was surgically created in 18 fetal lambs between the 60th and the 80th day of gestation. Eight of them did not undergo fetal repair (group A), three were repaired with an open two-layer closure (group B), three using BioGlue® (groupC) and four fetoscopically (group D). At term, bladders were examined macroscopically and histopathological changes were assessed using H-E and Masson Trichrome. Five animals in group A (5/8, 62%), two in group B (2/3, 66%), one in group C (1/3, 33%) and one in group D (1/4, 25%) survived. Macroscopically bladders in group A were severely dilated and showed thinner walls. Microscopically they showed a thin layer of colagenous tissue (Blue layer. BL) lying immediately subjacent to the urothelium. The muscular layers were thinner. Non compliant pattern with thick wall and low capacity was also found in the non corrected model. Group B and the control showed preservation of muscular layers and absence of BL. Groups C and D presented BL but also preservation of muscular layers. Bladder changes in a surgically-induced model of MMC can be described using histopathological data. Both extremes of bladder changes can be observed in the model. These changes were completely prevented with open fetal surgery and partially with other coverage modalities. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  8. Pilot study of lithium to restore intestinal barrier function in severe graft-versus-host disease.

    Directory of Open Access Journals (Sweden)

    Gideon Steinbach

    Full Text Available Severe intestinal graft-vs-host disease (GVHD after allogeneic hematopoietic cell transplantation (HCT causes mucosal ulceration and induces innate and adaptive immune responses that amplify and perpetuate GVHD and the associated barrier dysfunction. Pharmacological agents to target mucosal barrier dysfunction in GVHD are needed. We hypothesized that induction of Wnt signaling by lithium, an inhibitor of glycogen synthase kinase (GSK3, would potentiate intestinal crypt proliferation and mucosal repair and that inhibition of GSK3 in inflammatory cells would attenuate the deregulated inflammatory response to mucosal injury. We conducted an observational pilot study to provide data for the potential design of a randomized study of lithium. Twenty patients with steroid refractory intestinal GVHD meeting enrollment criteria were given oral lithium carbonate. GVHD was otherwise treated per current practice, including 2 mg/kg per day of prednisone equivalent. Seventeen patients had extensive mucosal denudation (extreme endoscopic grade 3 in the duodenum or colon. We observed that 8 of 12 patients (67% had a complete remission (CR of GVHD and survived more than 1 year (median 5 years when lithium administration was started promptly within 3 days of endoscopic diagnosis of denuded mucosa. When lithium was started promptly and less than 7 days from salvage therapy for refractory GVHD, 8 of 10 patients (80% had a CR and survived more than 1 year. In perspective, a review of 1447 consecutive adult HCT patients in the preceding 6 years at our cancer center showed 0% one-year survival in 27 patients with stage 3-4 intestinal GVHD and grade 3 endoscopic appearance in the duodenum or colon. Toxicities included fatigue, somnolence, confusion or blunted affect in 50% of the patients. The favorable outcomes in patients who received prompt lithium therapy appear to support the future conduct of a randomized study of lithium for management of severe GVHD with

  9. Effects of Temperament, Symptom Severity and Level of Functioning on Maternal Stress in Greek Children and Youth with ASD

    Science.gov (United States)

    Konstantareas, M. Mary; Papageorgiou, Vaya

    2006-01-01

    This study examined the effect of child temperament, symptom severity, verbal ability and level of functioning on maternal stress in 43 Greek mothers of children and young people with autism spectrum disorder. Symptom severity was assessed by the CARS, level of functioning by the PEP, temperament by the Dimensions of Temperament Scale (DOTS-R) and…

  10. Association between Air Pollution Exposure, Cognitive and Adaptive Function, and ASD Severity among Children with Autism Spectrum Disorder

    Science.gov (United States)

    Kerin, Tara; Volk, Heather; Li, Weiyan; Lurmann, Fred; Eckel, Sandrah; McConnell, Rob; Hertz-Picciotto, Irva

    2018-01-01

    Prenatal exposure to air pollution has been associated with autism spectrum disorder (ASD) risk but no study has examined associations with ASD severity or functioning. Cognitive ability, adaptive functioning, and ASD severity were assessed in 327 children with ASD from the Childhood Autism Risks from Genetics and the Environment study using the…

  11. The impairment of MAGMAS function in human is responsible for a severe skeletal dysplasia.

    Directory of Open Access Journals (Sweden)

    Cybel Mehawej

    2014-05-01

    Full Text Available Impairment of the tightly regulated ossification process leads to a wide range of skeletal dysplasias and deciphering their molecular bases has contributed to the understanding of this complex process. Here, we report a homozygous mutation in the mitochondria-associated granulocyte macrophage colony stimulating factor-signaling gene (MAGMAS in a novel and severe spondylodysplastic dysplasia. MAGMAS, also referred to as PAM16 (presequence translocase-associated motor 16, is a mitochondria-associated protein involved in preprotein translocation into the matrix. We show that MAGMAS is specifically expressed in trabecular bone and cartilage at early developmental stages and that the mutation leads to an instability of the protein. We further demonstrate that the mutation described here confers to yeast strains a temperature-sensitive phenotype, impairs the import of mitochondrial matrix pre-proteins and induces cell death. The finding of deleterious MAGMAS mutations in an early lethal skeletal dysplasia supports a key role for this mitochondrial protein in the ossification process.

  12. A functional EGF+61 polymorphism is associated with severity of obstructive sleep apnea.

    Science.gov (United States)

    Ding, Qunli; Cao, Chao; Chen, Zhongbo; Tabusi, Mahebali; Chen, Li; Deng, Zaichun

    2015-05-01

    Involvement of epidermal growth factor (EGF) is reported in diseases caused by hypoxia. Its functional polymorphism may alter its transcription, affecting EGF expression, contributing to obstructive sleep apnea (OSA). The aim of this study was to investigate associations of EGF+61 polymorphism and risk of OSA. Two hundred two participants were enrolled in this case-control study. DNA was extracted from peripheral blood, and EGF 61A/G polymorphism was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. No significant association between EGF 61 A/G polymorphism and risk of OSA was observed in any of the gene models tested (AA vs. GG: OR = 0.97, 95% CI = 0.37-2.55; P = 0.95). However, compared with GG genotype, AG genotype associated with decreased risk of severe OSA (AG vs. GG: OR = 0.32, 95% CI = 0.11-0.94). Our study showed that AG genotype has a protective effect on OSA patients against severe disease, although EGF 61A/G polymorphisms have no role on the risk of the disease. Additional large studies should further validate our findings.

  13. Dexamethasone impairs hypoxia-inducible factor-1 function

    International Nuclear Information System (INIS)

    Wagner, A.E.; Huck, G.; Stiehl, D.P.; Jelkmann, W.; Hellwig-Buergel, T.

    2008-01-01

    Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription-factor composed of α- and β-subunits. HIF-1 is not only necessary for the cellular adaptation to hypoxia, but it is also involved in inflammatory processes and wound healing. Glucocorticoids (GC) are therapeutically used to suppress inflammatory responses. Herein, we investigated whether GC modulate HIF-1 function using GC receptor (GR) possessing (HepG2) and GR deficient (Hep3B) human hepatoma cell cultures as model systems. Dexamethasone (DEX) treatment increased HIF-1α levels in the cytosol of HepG2 cells, while nuclear HIF-1α levels and HIF-1 DNA-binding was reduced. In addition, DEX dose-dependently lowered the hypoxia-induced luciferase activity in a reporter gene system. DEX suppressed the hypoxic stimulation of the expression of the HIF-1 target gene VEGF (vascular endothelial growth factor) in HepG2 cultures. DEX did not reduce hypoxically induced luciferase activity in HRB5 cells, a Hep3B derivative lacking GR. Transient expression of the GR in HRB5 cells restored the susceptibility to DEX. Our study discloses the inhibitory action of GC on HIF-1 dependent gene expression, which may be important with respect to the impaired wound healing in DEX-treated patients

  14. COPD phenotypes on computed tomography and its correlation with selected lung function variables in severe patients

    Directory of Open Access Journals (Sweden)

    da Silva SMD

    2016-03-01

    Full Text Available Silvia Maria Doria da Silva, Ilma Aparecida Paschoal, Eduardo Mello De Capitani, Marcos Mello Moreira, Luciana Campanatti Palhares, Mônica Corso PereiraPneumology Service, Department of Internal Medicine, School of Medical Sciences, State University of Campinas (UNICAMP, Campinas, São Paulo, BrazilBackground: Computed tomography (CT phenotypic characterization helps in understanding the clinical diversity of chronic obstructive pulmonary disease (COPD patients, but its clinical relevance and its relationship with functional features are not clarified. Volumetric capnography (VC uses the principle of gas washout and analyzes the pattern of CO2 elimination as a function of expired volume. The main variables analyzed were end-tidal concentration of carbon dioxide (ETCO2, Slope of phase 2 (Slp2, and Slope of phase 3 (Slp3 of capnogram, the curve which represents the total amount of CO2 eliminated by the lungs during each breath.Objective: To investigate, in a group of patients with severe COPD, if the phenotypic analysis by CT could identify different subsets of patients, and if there was an association of CT findings and functional variables.Subjects and methods: Sixty-five patients with COPD Gold III–IV were admitted for clinical evaluation, high-resolution CT, and functional evaluation (spirometry, 6-minute walk test [6MWT], and VC. The presence and profusion of tomography findings were evaluated, and later, the patients were identified as having emphysema (EMP or airway disease (AWD phenotype. EMP and AWD groups were compared; tomography findings scores were evaluated versus spirometric, 6MWT, and VC variables.Results: Bronchiectasis was found in 33.8% and peribronchial thickening in 69.2% of the 65 patients. Structural findings of airways had no significant correlation with spirometric variables. Air trapping and EMP were strongly correlated with VC variables, but in opposite directions. There was some overlap between the EMP and AWD

  15. Bronchodilator response of advanced lung function parameters depending on COPD severity

    Directory of Open Access Journals (Sweden)

    Jarenbäck L

    2016-11-01

    Full Text Available Linnea Jarenbäck,1 Göran Eriksson,1 Stefan Peterson,2 Jaro Ankerst,1 Leif Bjermer,1 Ellen Tufvesson1 1Respiratory Medicine and Allergology, Department of Clinical Sciences Lund, Lund University, 2Regional Cancer Center South, Skåne University Hospital, Lund, Sweden Background: COPD is defined as partly irreversible airflow obstruction. The response pattern of bronchodilators has not been followed in advanced lung function parameters. Purpose: The aim of this study was to investigate bronchodilator response pattern in advanced lung function parameters in a continuous fashion along forced expiratory volume in 1 second (FEV1 percent predicted (%p in COPD patients and controls. Patients and methods: Eighty-one smokers/ex-smokers (41 controls and 40 COPD performed spirometry, body plethysmography, impulse oscillometry and single-breath helium dilution carbon monoxide diffusion at baseline, after salbutamol inhalation and then after an additional inhalation of ipratropium. Results: Most pulmonary function parameters showed a linear increase in response to decreased FEV1%p. The subjects were divided into groups of FEV1%p <65 and >65, and the findings from continuous analysis were verified. The exceptions to this linear response were inspiratory capacity (IC, forced vital capacity (FVC, FEV1/FVC and expiratory resistance (Rex, which showed a segmented response relationship to FEV1%p. IC and FVC, with break points (BP of 57 and 58 FEV1%p respectively, showed no response above, but an incresed slope below the BP. In addition, in patients with FEV1%p <65 and >65, response of FEV1%p did not correlate to response of volume parameters. Conclusion: Response of several advanced lung function parameters differs depending on patients’ baseline FEV1%p, and specifically response of volume parameters is most pronounced in COPD patients with FEV1%p <65. Volume and resistance responses do not follow the flow response measured with FEV1 and may thus be used as a

  16. Endothelial glycocalyx degradation induces endogenous heparinization in patients with severe injury and early traumatic coagulopathy

    DEFF Research Database (Denmark)

    Ostrowski, Sisse R; Johansson, Pär I

    2012-01-01

    There is emerging evidence that early trauma-induced coagulopathy (TIC) is mechanistically linked to disruption of the vascular endothelium and its glycocalyx, assessed by thrombomodulin and syndecan 1, respectively. This study evaluated if degradation of the endothelial glycocalyx and ensuing...... release of its heparin-like substances induce autoheparinization and thereby contributes to TIC....

  17. Generation of functional podocytes from human induced pluripotent stem cells

    Directory of Open Access Journals (Sweden)

    Osele Ciampi

    2016-07-01

    Full Text Available Generating human podocytes in vitro could offer a unique opportunity to study human diseases. Here, we describe a simple and efficient protocol for obtaining functional podocytes in vitro from human induced pluripotent stem cells. Cells were exposed to a three-step protocol, which induced their differentiation into intermediate mesoderm, then into nephron progenitors and, finally, into mature podocytes. After differentiation, cells expressed the main podocyte markers, such as synaptopodin, WT1, α-Actinin-4, P-cadherin and nephrin at the protein and mRNA level, and showed the low proliferation rate typical of mature podocytes. Exposure to Angiotensin II significantly decreased the expression of podocyte genes and cells underwent cytoskeleton rearrangement. Cells were able to internalize albumin and self-assembled into chimeric 3D structures in combination with dissociated embryonic mouse kidney cells. Overall, these findings demonstrate the establishment of a robust protocol that, mimicking developmental stages, makes it possible to derive functional podocytes in vitro.

  18. Prioritized expression of BTN2 of Saccharomyces cerevisiae under pronounced translation repression induced by severe ethanol stress

    Directory of Open Access Journals (Sweden)

    Yukina Yamauchi

    2016-08-01

    Full Text Available Severe ethanol stress (>9% ethanol, v/v as well as glucose deprivation rapidly induces a pronounced repression of overall protein synthesis in budding yeast Saccharomyces cerevisiae. Therefore, transcriptional activation in yeast cells under severe ethanol stress does not always indicate the production of expected protein levels. Messenger RNAs of genes containing heat shock elements can be intensively translated under glucose deprivation, suggesting that some mRNAs are preferentially translated even under severe ethanol stress. In the present study, we tried to identify the mRNA that can be preferentially translated under severe ethanol stress. BTN2 encodes a v-SNARE binding protein, and its null mutant shows hypersensitivity to ethanol. We found that BTN2 mRNA was efficiently translated under severe ethanol stress but not under mild ethanol stress. Moreover, the increased Btn2 protein levels caused by severe ethanol stress were smoothly decreased with the elimination of ethanol stress. These findings suggested that severe ethanol stress extensively induced BTN2 expression. Further, the BTN2 promoter induced protein synthesis of non-native genes such as CUR1, GIC2, and YUR1 in the presence of high ethanol concentrations, indicating that this promoter overcame severe ethanol stress-induced translation repression. Thus, our findings provide an important clue about yeast response to severe ethanol stress and suggest that the BTN2 promoter can be used to improve the efficiency of ethanol production and stress tolerance of yeast cells by modifying gene expression in the presence of high ethanol concentration.

  19. Saturation of retinol-binding protein correlates closely to the severity of alcohol-induced liver disease

    DEFF Research Database (Denmark)

    Wagnerberger, S.; Schäfer, C.; Bode, C.

    2006-01-01

    Impaired metabolism of retinol has been shown to occur in alcohol-induced liver disease (ALD). The purpose of the present study was to investigate the saturation of retinol-binding protein (RBP) in 6 patients with different stages of ALD. Hospitalized alcohol consumers (n=118) with different stages......: 43.5+/-6.2%; ALD3: 29.0+/-5.1%). The present study indicates that plasma concentrations of retinol and RBP per se do not correlate to severity of ALD, but rather that the retinol/RBP ratio links to the severity of alcohol-induced liver damage. From these results, a reduced availability of retinol...

  20. Sestrin2 induced by hypoxia inducible factor1 alpha protects the blood-brain barrier via inhibiting VEGF after severe hypoxic-ischemic injury in neonatal rats.

    Science.gov (United States)

    Shi, Xudan; Doycheva, Desislava Met; Xu, Liang; Tang, Jiping; Yan, Min; Zhang, John H

    2016-11-01

    Hypoxic ischemic (HI) encephalopathy remains the leading cause of perinatal brain injury resulting in long term disabilities. Stabilization of blood brain barrier (BBB) after HI is an important target, therefore, in this study we aim to determine the role of sestrin2, a stress inducible protein which is elevated after various insults, on BBB stabilization after moderate and severe HI injuries. Rat pups underwent common carotid artery ligation followed by either 150min (severe model) or 100min (moderate model) of hypoxia. 1h post HI, rats were intranasally administered with recombinant human sestrin2 (rh-sestrin2) and sacrificed for infarct area, brain water content, righting reflex and geotaxis reflex. Sestrin2 was silenced using siRNA and an activator/inhibitor of hypoxia inducible factor1α (HIF1α) was used to examine their roles on BBB permeability. Rats subjected to severe HI exhibited larger infarct area and higher sestrin2 expression compared to rats in the moderate HI group. rh-sestrin2 attenuated brain infarct and edema, while silencing sestrin2 reversed these protective effects after severe HI. HIF1α induced sestrin2 activation in severe HI but not in moderate HI groups. A HIF1a agonist was shown to increase permeability of the BBB via vascular endothelial growth factor (VEGF) after moderate HI. However, after severe HI, HIF1α activated both VEGF and sestrin2. But HIF1α dependent sestrin2 activation was the predominant pathway after severe HI which inhibited VEGF and attenuated BBB permeability. rh-sestrin2 attenuated BBB permeability via upregulation of endogenous sestrin2 which was induced by HIF1α after severe HI. However, HIF1α's effects as a prodeath or prosurvival signal were influenced by the severity of HI injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Inducing metabolic suppression in severe hemorrhagic shock: Pilot study results from the Biochronicity Project.

    Science.gov (United States)

    Black, George E; Sokol, Kyle K; Shawhan, Robert R; Eckert, Matthew J; Salgar, Shashikumar; Marko, Shannon T; Hoffer, Zachary S; Keyes, Christopher C; Roth, Mark B; Martin, Matthew J

    2016-12-01

    Suspended animation-like states have been achieved in small animal models, but not in larger species. Inducing metabolic suppression and temporary oxygen independence could enhance survivability of massive injury. Based on prior analyses of key pathways, we hypothesized that phosphoinositol-3-kinase inhibition would produce metabolic suppression without worsening organ injury or systemic physiology. Twenty swine were studied using LY294002 (LY), a nonselective phosphoinositol-3-kinase inhibitor. Animals were assigned to trauma only (TO, n = 3); dimethyl sulfoxide only (DMSO, n = 4), LY drug only (LYO, n = 3), and drug + trauma (LY + T, n = 10) groups. Both trauma groups underwent laparotomy, 35% hemorrhage, severe ischemia/reperfusion injury, and protocolized resuscitation. Laboratory, physiologic, cytokine, and metabolic cart data were obtained. Histology of key end organs was also compared. Baseline values were similar among the groups. Compared with the TO group, the LYO group had reversible decreases in heart rate, mean arterial pressure, cardiac output, oxygen consumption, and carbon dioxide production. Compared with TO, LY + T showed sustained decreases in heart rate (113 vs. 76, p = 0.03), mean arterial pressure (40 vs. 31 mm Hg, p = 0.02), and cardiac output (3.8 vs. 1.9 L/min, p = 0.05) at 6 hours. Metabolic parameters showed profound suppression in the LY + T group. Oxygen consumption in LY + T was lower than both TO (119 vs. 229 mL/min, p = 0.012) and LYO (119 vs. 225 mL/min, p = 0.014) at 6 hours. Similarly, carbon dioxide production was decreased at 6 hours in LY + T when compared with TO (114 vs. 191 mL/min, p = 0.043) and LYO (114 vs. 195 mL/min, p = 0.034) groups. There was no worsening of acidosis (lactate 6.4 vs. 8.3 mmol/L, p = 0.4) or other endpoints. Interleukin 6 (IL-6) showed a significant increase in LY + T when compared with TO at 6 hours (60.5 vs. 2.47, p = 0.043). Tumor necrosis factor α and IL-1β were decreased, and IL-10 increased in

  2. ATM Mutations and the Development of Severe Radiation-Induced Morbidity Following Radiotherapy for Breast Cancer

    National Research Council Canada - National Science Library

    Rosenstein, Barry S

    2005-01-01

    The hypothesis being tested in this project is that a greater proportion of patients who develop radiation-induced subcutaneous late tissue morbidity possess a variant allele in the ATM gene compared...

  3. ATM Mutations and the Development of Severe Radiation-Induced Morbidity Following Radiotherapy for Breast Cancer

    National Research Council Canada - National Science Library

    Rosenstein, Barry S

    2006-01-01

    The hypothesis being tested in this project is that a greater proportion of patients who develop radiation-induced subcutaneous late tissue morbidity possess a variant allele in the ATM gene compared...

  4. Microbial Community Structure and Function Indicate the Severity of Chromium Contamination of the Yellow River

    Directory of Open Access Journals (Sweden)

    Yaxin Pei

    2018-01-01

    Full Text Available The Yellow River is the most important water resource in northern China. In the recent past, heavy metal contamination has become severe due to industrial processes and other anthropogenic activities. In this study, riparian soil samples with varying levels of chromium (Cr pollution severity were collected along the Gansu industrial reach of the Yellow River, including samples from uncontaminated sites (XC, XGU, slightly contaminated sites (LJX, XGD, and heavily contaminated sites (CG, XG. The Cr concentrations of these samples varied from 83.83 mg⋅kg-1 (XGU to 506.58 mg⋅kg-1 (XG. The chromate [Cr (VI] reducing ability in the soils collected in this study followed the sequence of the heavily contaminated > slightly contaminated > the un-contaminated. Common Cr remediation genes chrA and yieF were detected in the XG and CG samples. qRT-PCR results showed that the expression of chrA was up-regulated four and threefold in XG and CG samples, respectively, whereas the expression of yieF was up-regulated 66- and 7-fold in the same samples after 30 min treatment with Cr (VI. The copy numbers of chrA and yieF didn’t change after 35 days incubation with Cr (VI. The microbial communities in the Cr contaminated sampling sites were different from those in the uncontaminated samples. Especially, the relative abundances of Firmicutes and Bacteroidetes were higher while Actinobacteria was lower in the contaminated group than uncontaminated group. Further, potential indicator species, related to Cr such as Cr-remediation genera (Geobacter, PSB-M-3, Flavobacterium, and Methanosarcina; the Cr-sensitive genera (Skermanella, Iamia, Arthrobacter, and Candidatus Nitrososphaera were also identified. These data revealed that Cr shifted microbial composition and function. Further, Cr (VI reducing ability could be related with the expression of Cr remediation genes.

  5. Prevention of acute/severe hypoglycemia-induced neuron death by lactate administration

    OpenAIRE

    Won, Seok Joon; Jang, Bong Geom; Yoo, Byung Hoon; Sohn, Min; Lee, Min Woo; Choi, Bo Young; Kim, Jin Hee; Song, Hong Ki; Suh, Sang Won

    2012-01-01

    Hypoglycemia-induced cerebral neuropathy can occur in patients with diabetes who attempt tight control of blood glucose and may lead to cognitive dysfunction. Accumulating evidence from animal models suggests that hypoglycemia-induced neuronal death is not a simple result of glucose deprivation, but is instead the end result of a multifactorial process. In particular, the excessive activation of poly (ADP-ribose) polymerase-1 (PARP-1) consumes cytosolic nicotinamide adenine dinucleotide (NAD+...

  6. PAI-1-dependent endothelial cell death determines severity of radiation-induced intestinal injury.

    Directory of Open Access Journals (Sweden)

    Rym Abderrahmani

    Full Text Available Normal tissue toxicity still remains a dose-limiting factor in clinical radiation therapy. Recently, plasminogen activator inhibitor type 1 (SERPINE1/PAI-1 was reported as an essential mediator of late radiation-induced intestinal injury. However, it is not clear whether PAI-1 plays a role in acute radiation-induced intestinal damage and we hypothesized that PAI-1 may play a role in the endothelium radiosensitivity. In vivo, in a model of radiation enteropathy in PAI-1 -/- mice, apoptosis of radiosensitive compartments, epithelial and microvascular endothelium was quantified. In vitro, the role of PAI-1 in the radiation-induced endothelial cells (ECs death was investigated. The level of apoptotic ECs is lower in PAI-1 -/- compared with Wt mice after irradiation. This is associated with a conserved microvascular density and consequently with a better mucosal integrity in PAI-1 -/- mice. In vitro, irradiation rapidly stimulates PAI-1 expression in ECs and radiation sensitivity is increased in ECs that stably overexpress PAI-1, whereas PAI-1 knockdown increases EC survival after irradiation. Moreover, ECs prepared from PAI-1 -/- mice are more resistant to radiation-induced cell death than Wt ECs and this is associated with activation of the Akt pathway. This study demonstrates that PAI-1 plays a key role in radiation-induced EC death in the intestine and suggests that this contributes strongly to the progression of radiation-induced intestinal injury.

  7. [Formula: see text]Executive functions and social information processing in adolescents with severe behavior problems.

    Science.gov (United States)

    Van Nieuwenhuijzen, M; Van Rest, M M; Embregts, P J C M; Vriens, A; Oostermeijer, S; Van Bokhoven, I; Matthys, W

    2017-02-01

    One tradition in research for explaining aggression and antisocial behavior has focused on social information processing (SIP). Aggression and antisocial behavior have also been studied from the perspective of executive functions (EFs), the higher-order cognitive abilities that affect other cognitive processes, such as social cognitive processes. The main goal of the present study is to provide insight into the relation between EFs and SIP in adolescents with severe behavior problems. Because of the hierarchical relation between EFs and SIP, we examined EFs as predictors of SIP. We hypothesized that, first, focused attention predicts encoding and interpretation, second, inhibition predicts interpretation, response generation, evaluation, and selection, and third, working memory predicts response generation and selection. The participants consisted of 94 respondents living in residential facilities aged 12-20 years, all showing behavior problems in the clinical range according to care staff. EFs were assessed using subtests from the Amsterdam Neuropsychological Test battery. Focused attention was measured by the Flanker task, inhibition by the GoNoGo task, and working memory by the Visual Spatial Sequencing task. SIP was measured by video vignettes and a structured interview. The results indicate that positive evaluation of aggressive responses is predicted by impaired inhibition and selection of aggressive responses by a combination of impaired focused attention and inhibition. It is concluded that different components of EFs as higher-order cognitive abilities affect SIP.

  8. Psychotherapy use in bipolar disorder: Association with functioning and illness severity.

    Science.gov (United States)

    Sylvia, Louisa G; Thase, Michael E; Reilly-Harrington, Noreen A; Salcedo, Stephanie; Brody, Benjamin; Kinrys, Gustavo; Kemp, David; Shelton, Richard C; McElroy, Susan L; Kocsis, James H; Bobo, William V; Kamali, Masoud; McInnis, Melvin; Friedman, Edward; Tohen, Mauricio; Bowden, Charles L; Ketter, Terence A; Singh, Vivek; Calabrese, Joseph; Nierenberg, Andrew A; Rabideau, Dustin J; Elson, Constance M; Deckersbach, Thilo

    2015-05-01

    This study examines characteristics of individuals with bipolar disorder who sought psychotherapy versus those who did not. Bipolar CHOICE was an 11-site comparative effectiveness study of lithium versus quetiapine in symptomatic outpatients (N = 482) with bipolar disorder. At baseline, participants' psychotherapy use within the past 3 months, mood, functioning, and overall health were assessed. Logistic regressions were used to test whether psychotherapy users and non-users differed on various demographic and clinical variables at baseline. Mixed-effects regression was used to determine whether psychotherapy groups differed on response to treatment over the 6-month study. Kaplan-Meier plots and log-rank tests were employed to test whether there were any differences in time to recovery (CGI-BP ≤ 2 for at least 8 weeks) between the groups. Thirty one percent of participants reported using psychotherapy services. Psychotherapy users reported greater medication side effect burden than non-users and were more likely to have moderate to high suicide risk and at least one anxiety disorder. Participants not utilizing medications or psychotherapy had greater mania symptom severity, were younger, and less educated than medication only users. Medication only users were more likely to be married than the other participants. These data suggest that a minority of individuals with bipolar disorder attend psychotherapy services, and those that do have greater illness burden. © The Royal Australian and New Zealand College of Psychiatrists 2015.

  9. Impaired cardiovascular structure and function in adult survivors of severe acute malnutrition.

    Science.gov (United States)

    Tennant, Ingrid A; Barnett, Alan T; Thompson, Debbie S; Kips, Jan; Boyne, Michael S; Chung, Edward E; Chung, Andrene P; Osmond, Clive; Hanson, Mark A; Gluckman, Peter D; Segers, Patrick; Cruickshank, J Kennedy; Forrester, Terrence E

    2014-09-01

    Malnutrition below 5 years remains a global health issue. Severe acute malnutrition (SAM) presents in childhood as oedematous (kwashiorkor) or nonoedematous (marasmic) forms, with unknown long-term cardiovascular consequences. We hypothesized that cardiovascular structure and function would be poorer in SAM survivors than unexposed controls. We studied 116 adult SAM survivors, 54 after marasmus, 62 kwashiorkor, and 45 age/sex/body mass index-matched community controls who had standardized anthropometry, blood pressure, echocardiography, and arterial tonometry performed. Left ventricular indices and outflow tract diameter, carotid parameters, and pulse wave velocity were measured, with systemic vascular resistance calculated. All were expressed as SD scores. Mean (SD) age was 28.8±7.8 years (55% men). Adjusting for age, sex, height, and weight, SAM survivors had mean (SE) reductions for left ventricular outflow tract diameter of 0.67 (0.16; PMalnutrition survivors are thus likely to develop excess hypertension in later life, especially when exposed to obesity. © 2014 American Heart Association, Inc.

  10. Impact of cognitive function and dysarthria on spoken language and perceived speech severity in multiple sclerosis

    Science.gov (United States)

    Feenaughty, Lynda

    Purpose: The current study sought to investigate the separate effects of dysarthria and cognitive status on global speech timing, speech hesitation, and linguistic complexity characteristics and how these speech behaviors impose on listener impressions for three connected speech tasks presumed to differ in cognitive-linguistic demand for four carefully defined speaker groups; 1) MS with cognitive deficits (MSCI), 2) MS with clinically diagnosed dysarthria and intact cognition (MSDYS), 3) MS without dysarthria or cognitive deficits (MS), and 4) healthy talkers (CON). The relationship between neuropsychological test scores and speech-language production and perceptual variables for speakers with cognitive deficits was also explored. Methods: 48 speakers, including 36 individuals reporting a neurological diagnosis of MS and 12 healthy talkers participated. The three MS groups and control group each contained 12 speakers (8 women and 4 men). Cognitive function was quantified using standard clinical tests of memory, information processing speed, and executive function. A standard z-score of ≤ -1.50 indicated deficits in a given cognitive domain. Three certified speech-language pathologists determined the clinical diagnosis of dysarthria for speakers with MS. Experimental speech tasks of interest included audio-recordings of an oral reading of the Grandfather passage and two spontaneous speech samples in the form of Familiar and Unfamiliar descriptive discourse. Various measures of spoken language were of interest. Suprasegmental acoustic measures included speech and articulatory rate. Linguistic speech hesitation measures included pause frequency (i.e., silent and filled pauses), mean silent pause duration, grammatical appropriateness of pauses, and interjection frequency. For the two discourse samples, three standard measures of language complexity were obtained including subordination index, inter-sentence cohesion adequacy, and lexical diversity. Ten listeners

  11. Study of induced functions by UV in Staphylococcus

    International Nuclear Information System (INIS)

    Silva, B.S. da.

    1982-01-01

    SOS functions induced by ultraviolet (UV) radiation were studied using S. aureus and S. epidermidis. Comparing the results obtained from these two organisms with those described in the literature for E. coli allows us to conclude: the difference in UV sensibility between the lysogenic and non-lysogenic strains of Staphylococcus is extremely large; the dose of UV radiation which results in the maximum induction of the lysogenic strains lead to 99% inactivation of the lysogenic strains; the kinetics of prophage liberation in lysogenic cultures of Staphylococcus is more rapid than those described for E. coli; the dose of UV radiation is much lower than the dose described for E. coli; the maximum W-reactivatio and W-mutagenesis are obtained immediately after the irradiation or within the 15 minutes allowed for the phage adsorption. (author)

  12. Stimulus Over-Selectivity and Extinction-Induced Recovery of Performance as a Product of Intellectual Impairment and Autism Severity

    Science.gov (United States)

    Kelly, Michelle P.; Leader, Geraldine; Reed, Phil

    2015-01-01

    The current experiment investigated the extent to which three variables (autism severity, nonverbal intellectual functioning, and verbal intellectual functioning) are associated with over-selective responding in a group of children with Autism Spectrum Disorder. This paper also analyzed the association of these three variables with the recovery of…

  13. Discrete-Trial Functional Analysis and Functional Communication Training with Three Individuals with Autism and Severe Problem Behavior

    Science.gov (United States)

    Schmidt, Jonathan D.; Drasgow, Erik; Halle, James W.; Martin, Christian A.; Bliss, Sacha A.

    2014-01-01

    Discrete-trial functional analysis (DTFA) is an experimental method for determining the variables maintaining problem behavior in the context of natural routines. Functional communication training (FCT) is an effective method for replacing problem behavior, once identified, with a functionally equivalent response. We implemented these procedures…

  14. Family function and its relationship to injury severity and psychiatric outcome in children with acquired brain injury: a systematized review.

    Science.gov (United States)

    Lax Pericall, Maria Teresa; Taylor, Eric

    2014-01-01

    The psychological and psychiatric outcome of children with acquired brain injury is influenced by many variables. A review was undertaken to clarify the contribution of family function, how it relates to injury severity, and what particular aspects of family function influence psychological outcome in this group. A systematized review of the literature of studies published between 1970 and 2012 from OvidMedline, PsychoInfo, PsycARTICLES, and Cochrane was undertaken focusing on family function, injury severity, and psychiatric outcome. Thirty-six papers met the inclusion criteria. Injury severity was linked to the development of organic personality change. Family function before injury, measured by the Family Assessment Device or the Clinical Rating Scale, had a statistically significant effect on general psychological functioning in six out of eight studies. Family function had a significant effect for oppositional defiant disorder and secondary attention-deficit-hyperactivity disorder. The effects of family function may differ depending on the age of the child and the severity of the injury. Some styles of parenting moderated recovery. After injury, family function was related to the child's contemporaneous psychiatric symptoms. The level of evidence for these papers was 3 or 4 (Oxford Centre for Evidence-based Medicine criteria). Screening for some aspects of family functioning before injury and family function during the rehabilitation phase may identify children at risk of psychiatric disorders. © 2013 Mac Keith Press.

  15. Examining Severe Drought-Induced Vegetation Change and its Influence on Water Resources

    Science.gov (United States)

    White, A. B.; Springer, E. P.; Vivoni, E. R.

    2007-12-01

    A "global-change-type" drought that occurred in the southwestern U.S. from 2000 to 2003, accompanied by increased temperatures and bark beetle infestations, induced large-scale woodland overstory mortality, the consequent redistribution of water, radiation, and nutrients, as well as modification of the ecosystem phenology. Our objectives in this research are to examine these vegetation changes in detail and to determine whether they translated to changes in hydrological processes. We chose the Rio Ojo Caliente, a subbasin of the Rio Grande, as a study site since a significant portion of the woodland ecosystem (piñon-juniper) was affected. Examining a remotely-sensed vegetation index (1-km AVHRR NDVI from 1989 to 2006), there is an increasing trend in the mean NDVI from 1989 to 1998 (pre-drought period), a decreasing trend from 1999 to 2003 (drought period), and a dramatic increasing trend from 2004 to 2006 (post-drought period) in which the mean NDVI rebounds to pre- drought magnitudes. Streamflow records from 1932 to 2006 show the watershed to be primarily spring snowmelt-driven, although monsoonal summer precipitation also plays a significant role. We compare the temporal variability in the streamflow to the NDVI, including the mean, anomalies from the mean, and seasonally- based duration curves, and find significant correlations (correlation coefficient ρ = -0.61) between the streamflow and NDVI at approximately a three-month lag (NDVI lagging streamflow). In analyzing the three phases of the drought, the correlation is slightly stronger during the pre-drought (ρ = -0.64) and drought (ρ = -0.65) periods, yet markedly stronger during the post-drought period (ρ = -0.74). This suggests that the coupling between vegetation water use and streamflow is tighter after the drought. This may be attributable to the reduction in the less-responsive overstory (pinñon mortality) and increase in the more-responsive understory (grasses and shrubs exploiting newly

  16. A review of factors influencing the incidence and severity of plaque-induced gingivitis.

    Science.gov (United States)

    Trombelli, L; Farina, R

    2013-06-01

    An individual variation in the gingival inflammatory response to the dental biofilm has been demonstrated. This variability can be observed between individuals with neither quantitative nor qualitative differences in plaque accumulation. The reported significant differences in gingival inflammatory response under quantitatively and/or qualitatively almost identical bacterial challenge suggest that the gingival response to plaque accumulation may be an individual trait, possibly genetic in origin. The most recent classification of periodontal diseases acknowledges that the clinical expression of plaque-induced gingival inflammation can be substantially modified by systemic factors, either inherent to the host or related to environmental influences. The aim of the present literature review is to describe (i) the factors influencing the development of plaque-induced gingivitis as well as (ii) those metabolic, environmental and systemic factors which have a direct impact on the etiopathogenetic pathway of plaque-induced gingivitis, thus altering the nature or course of the gingival inflammatory response to dental biofilm.

  17. Traditional Chinese medicine, Qing Ying Tang, ameliorates the severity of acute lung injury induced by severe acute pancreatitis in rats via the upregulation of aquaporin-1.

    Science.gov (United States)

    Gao, Zhenming; Xu, Junfeng; Sun, Deguang; Zhang, Rixin; Liang, Rui; Wang, Liming; Fan, Rong

    2014-12-01

    Aquaporin-1 (AQP-1) is expressed in lung endothelial cells and regulates water transport; thus, AQP-1 plays an important role in a number of edema-associated lung diseases. Qing Yin Tang (QYT), a traditional Chinese medicine, has been shown to effectively reduce the mortality rate of acute lung injury (ALI) induced by severe acute pancreatitis (SAP). The current study aimed to investigate the detailed mechanisms underlying the effects of QYT on ALI induced by SAP, particularly the effects on the expression levels of AQP-1 in the lung tissue. ALI was established in Wister rats who were subsequently divided into four groups: SHAM, ALI, dexamethasone (DEX) and QYT groups (n=8 per group). In the QYT group, 20 ml/kg QYT was administered by gavage immediately following the induction of SAP. Blood and lung tissues were collected 8 h following the induction of pancreatitis. The lung wet/dry ratio, as well as the levels of blood gases, serum amylase and tumor necrosis factor-α (TNF-α), were measured at 4, 8 and 12 h following SAP-associated ALI induction surgery. The expression levels of AQP-1 in the lung tissue were detected by quantitative polymerase chain reaction, immunohistochemistry and western blot analysis. No statistically significant differences were observed with regard to the levels of serum amylase, wet/dry ratio, partial pressure of oxygen, serum TNF-α and pathological changes in the pulmonary tissue between the QYT and DEX groups; however, a statistically significant difference was observed when compared with the ALI group. The expression levels of AQP-1 significantly increased (P<0.05) and lung edema was alleviated in the QYT and DEX groups, when compared with ALI group. Therefore, the expression level of AQP-1 is associated with pulmonary edema. QYT protects the lungs from injury induced by SAP via the upregulation of AQP-1, which suppresses TNF-α expression.

  18. Accuracy of automated classification of major depressive disorder as a function of symptom severity

    Directory of Open Access Journals (Sweden)

    Rajamannar Ramasubbu, MD, FRCPC, MSc

    2016-01-01

    Conclusions: Binary linear SVM classifiers achieved significant classification of very severe depression with resting-state fMRI, but the contribution of brain measurements may have limited potential in differentiating patients with less severe depression from healthy controls.

  19. Functional survival after acute care for severe head injury at a designated trauma center in Hong Kong

    Directory of Open Access Journals (Sweden)

    Benedict B.T. Taw

    2012-07-01

    Conclusion: Multidisciplinary neurorehabilitation service is an important component of comprehensive trauma care. Despite significant early mortalities, a proportion of severely head-injured patients who survive acute care may achieve good long-term functional recovery.

  20. The influence of nanostructured features on bacterial adhesion and bone cell functions on severely shot peened 316L stainless steel.

    Science.gov (United States)

    Bagherifard, Sara; Hickey, Daniel J; de Luca, Alba C; Malheiro, Vera N; Markaki, Athina E; Guagliano, Mario; Webster, Thomas J

    2015-12-01

    Substrate grain structure and topography play major roles in mediating cell and bacteria activities. Severe plastic deformation techniques, known as efficient metal-forming and grain refining processes, provide the treated material with novel mechanical properties and can be adopted to modify nanoscale surface characteristics, possibly affecting interactions with the biological environment. This in vitro study evaluates the capability of severe shot peening, based on severe plastic deformation, to modulate the interactions of nanocrystallized metallic biomaterials with cells and bacteria. The treated 316L stainless steel surfaces were first investigated in terms of surface topography, grain size, hardness, wettability and residual stresses. The effects of the induced surface modifications were then separately studied in terms of cell morphology, adhesion and proliferation of primary human osteoblasts (bone forming cells) as well as the adhesion of multiple bacteria strains, specifically Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and ampicillin-resistant Escherichia coli. The results indicated a significant enhancement in surface work hardening and compressive residual stresses, maintenance of osteoblast adhesion and proliferation as well as a remarkable decrease in the adhesion and growth of gram-positive bacteria (S. aureus and S. epidermidis) compared to non-treated and conventionally shot peened samples. Impressively, the decrease in bacteria adhesion and growth was achieved without the use of antibiotics, for which bacteria can develop a resistance towards anyway. By slightly grinding the surface of severe shot peened samples to remove differences in nanoscale surface roughness, the effects of varying substrate grain size were separated from those of varying surface roughness. The expression of vinculin focal adhesions from osteoblasts was found to be singularly and inversely related to grain size, whereas the attachment of gram

  1. Social functioning in youth with anxiety disorders: association with anxiety severity and outcomes from cognitive-behavioral therapy.

    Science.gov (United States)

    Settipani, Cara A; Kendall, Philip C

    2013-02-01

    Social functioning was assessed using the Child Behavior Checklist and Teacher Report Form for children with anxiety disorders who participated in a randomized clinical trial (N = 161, aged 7-14). Significant relationships were found between severity of children's principal anxiety disorder and most measures of social functioning, such that poorer social functioning was associated with more severe anxiety. Among youth who received cognitive-behavioral therapy (n = 111), significant associations were found between parent-reported social competence and both absence of principal anxiety disorder and lower anxiety severity at posttreatment and 1-year follow-up, controlling for the severity of the child's principal anxiety disorder at pretreatment. Findings support a relationship between anxiety severity and social difficulties, and suggest the importance of social competence for a favorable treatment response.

  2. Rescue of the apoptotic-inducing function of mutant p53 by small molecule RITA.

    Science.gov (United States)

    Zhao, Carolyn Y; Grinkevich, Vera V; Nikulenkov, Fedor; Bao, Wenjie; Selivanova, Galina

    2010-05-01

    Expression of mutant p53 correlates with poor prognosis in many tumors, therefore strategies aimed at reactivation of mutant p53 are likely to provide important benefits for treatment of tumors that are resistant to chemotherapy and radiotherapy. We have previously identified and characterized a small molecule RITA which binds p53 and induces a conformational change which prevents the binding of p53 to several inhibitors, including its own destructor MDM2. In this way, RITA rescues the tumor suppression function of wild type p53. Here, we demonstrate that RITA suppressed the growth and induced apoptosis in human tumor cell lines of a diverse origin carrying mutant p53 proteins. RITA restored transcriptional transactivation and transrepression function of several hot spot p53 mutants. The ability of RITA to rescue the activity of different p53 mutants suggests its generic mechanism of action. Thus, RITA is a promising lead for the development of anti-cancer drugs that reactivate the tumor suppressor function of p53 in cancer cells irrespective whether they express mutant or wild type p53.

  3. Prevention of acute/severe hypoglycemia-induced neuron death by lactate administration.

    Science.gov (United States)

    Won, Seok Joon; Jang, Bong Geom; Yoo, Byung Hoon; Sohn, Min; Lee, Min Woo; Choi, Bo Young; Kim, Jin Hee; Song, Hong Ki; Suh, Sang Won

    2012-06-01

    Hypoglycemia-induced cerebral neuropathy can occur in patients with diabetes who attempt tight control of blood glucose and may lead to cognitive dysfunction. Accumulating evidence from animal models suggests that hypoglycemia-induced neuronal death is not a simple result of glucose deprivation, but is instead the end result of a multifactorial process. In particular, the excessive activation of poly (ADP-ribose) polymerase-1 (PARP-1) consumes cytosolic nicotinamide adenine dinucleotide (NAD(+)), resulting in energy failure. In this study, we investigate whether lactate administration in the absence of cytosolic NAD(+) affords neuroprotection against hypoglycemia-induced neuronal death. Intraperitoneal injection of sodium L-lactate corrected arterial blood pH and blood lactate concentration after hypoglycemia. Lactate administered without glucose was not sufficient to promote electroencephalogram recovery from an isoelectric state during hypoglycemia. However, supplementation of glucose with lactate reduced neuronal death by ∼80% in the hippocampus. Hypoglycemia-induced superoxide production and microglia activation was also substantially reduced by administration of lactate. Taken together, these results suggest an intriguing possibility: that increasing brain lactate following hypoglycemia offsets the decrease in NAD(+) due to overactivation of PARP-1 by acting as an alternative energy substrate that can effectively bypass glycolysis and be fed directly to the citric acid cycle to maintain cellular ATP levels.

  4. Common effects of lithium and valproate on mitochondrial functions: protection against methamphetamine-induced mitochondrial damage.

    Science.gov (United States)

    Bachmann, Rosilla F; Wang, Yun; Yuan, Peixiong; Zhou, Rulun; Li, Xiaoxia; Alesci, Salvatore; Du, Jing; Manji, Husseini K

    2009-07-01

    Accumulating evidence suggests that mitochondrial dysfunction plays a critical role in the progression of a variety of neurodegenerative and psychiatric disorders. Thus, enhancing mitochondrial function could potentially help ameliorate the impairments of neural plasticity and cellular resilience associated with a variety of neuropsychiatric disorders. A series of studies was undertaken to investigate the effects of mood stabilizers on mitochondrial function, and against mitochondrially mediated neurotoxicity. We found that long-term treatment with lithium and valproate (VPA) enhanced cell respiration rate. Furthermore, chronic treatment with lithium or VPA enhanced mitochondrial function as determined by mitochondrial membrane potential, and mitochondrial oxidation in SH-SY5Y cells. In-vivo studies showed that long-term treatment with lithium or VPA protected against methamphetamine (Meth)-induced toxicity at the mitochondrial level. Furthermore, these agents prevented the Meth-induced reduction of mitochondrial cytochrome c, the mitochondrial anti-apoptotic Bcl-2/Bax ratio, and mitochondrial cytochrome oxidase (COX) activity. Oligoarray analysis demonstrated that the gene expression of several proteins related to the apoptotic pathway and mitochondrial functions were altered by Meth, and these changes were attenuated by treatment with lithium or VPA. One of the genes, Bcl-2, is a common target for lithium and VPA. Knock-down of Bcl-2 with specific Bcl-2 siRNA reduced the lithium- and VPA-induced increases in mitochondrial oxidation. These findings illustrate that lithium and VPA enhance mitochondrial function and protect against mitochondrially mediated toxicity. These agents may have potential clinical utility in the treatment of other diseases associated with impaired mitochondrial function, such as neurodegenerative diseases and schizophrenia.

  5. Rapidly restoring biological soil crusts and ecosystem functions in a severely disturbed desert ecosystem.

    Science.gov (United States)

    Chiquoine, Lindsay P; Abella, Scott R; Bowker, Matthew A

    2016-06-01

    Restoring biological soil crusts (biocrusts) in degraded drylands can contribute to recovery of ecosystem functions that have global implications, including erosion resistance and nutrient cycling. To examine techniques for restoring biocrusts, we conducted a replicated, factorial experiment on recently abandoned road surfaces by applying biocrust inoculation (salvaged and stored dry for two years), salvaged topsoil, an abiotic soil amendment (wood shavings), and planting of a dominant perennial shrub (Ambrosia dumosa). Eighteen months after treatments, we measured biocrust abundance and species composition, soil chlorophyll a content and fertility, and soil resistance to erosion. Biocrust addition significantly accelerated biocrust recovery on disturbed soils, including increasing lichen and moss cover and cyanobacteria colonization. Compared to undisturbed controls, inoculated plots had similar lichen and moss composition, recovered 43% of total cyanobacteria density, had similar soil chlorophyll content, and exhibited recovery of soil fertility and soil stability. Inoculation was the only treatment that generated lichen and moss cover. Topsoil application resulted in partial recovery of the cyanobacteria community and soil properties. Compared to untreated disturbed plots, topsoil application without inoculum increased cyanobacteria density by 186% and moderately improved soil chlorophyll and ammonium content and soil stability. Topsoil application produced 22% and 51% of the cyanobacteria density g⁻¹ soil compared to undisturbed and inoculated plots, respectively. Plots not treated with either topsoil or inoculum had significantly lower cyanobacteria density, soil chlorophyll and ammonium concentrations, and significantly higher soil nitrate concentration. Wood shavings and Ambrosia had no influence on biocrust lichen and moss species recovery but did affect cyanobacteria composition and soil fertility. Inoculation of severely disturbed soil with native

  6. Edge-Spread Functions Expected for Several Changes in a Commercial Flat-Panel System

    International Nuclear Information System (INIS)

    Schach von Wittenau, A E

    2002-01-01

    The Bldg. 239 radiography facility uses a 9 MeV bremsstrahlung linac and a commercially available fiat-panel detector system. Ref. [1] discusses the facility in detail. Ref. [1] furthermore discusses the imaging quality of the fiat-panel system, and identifies several sources of image blur for the system in question. The maim'' contributors to the imaging blur are radiation scattered from the front cover of the detector housing, radiation scattered from the back cover of the detector housing, and radiation scattered from the aluminum plate that supports the amorphous-Si detector within the detector housing. The manufacturer of one such fiat-panel system seems willing to modify one of their products as requested, if such modifications may be made easily. Easy modifications would include making the detector housing thinner, decreasing the sizes of air gaps inside tile detector system, etc. Removing the aluminum support plate is considered to be a difficult modification. This memo reports the results of a set of Monte Carlo simulations that were performed to predict the changes in imaging quality, compared to that of the current system, if the detector is modified as suggested above. In particular, the edge-spread function (ESF) was calculated for each modification. ESFs were calculated for three photon energies: 100 keV, 450 keV, and 3 MeV. The results suggest that thinning and moving tile front and back covers of the detector housing should result in improved image quality for all of the photon energies considered. Interestingly, the results also suggest that removing the aluminum support plate would improve tim imaging performance at 100 keV and 450 keV, but that removing the plate has no additional benefit for imaging with 3 MeV photons

  7. Ginger extract inhibits LPS induced macrophage activation and function

    Directory of Open Access Journals (Sweden)

    Bruch David

    2008-01-01

    Full Text Available Abstract Background Macrophages play a dual role in host defence. They act as the first line of defence by mounting an inflammatory response to antigen exposure and also act as antigen presenting cells and initiate the adaptive immune response. They are also the primary infiltrating cells at the site of inflammation. Inhibition of macrophage activation is one of the possible approaches towards modulating inflammation. Both conventional and alternative approaches are being studied in this regard. Ginger, an herbal product with broad anti inflammatory actions, is used as an alternative medicine in a number of inflammatory conditions like rheumatic disorders. In the present study we examined the effect of ginger extract on macrophage activation in the presence of LPS stimulation. Methods Murine peritoneal macrophages were stimulated by LPS in presence or absence of ginger extract and production of proinflammatory cytokines and chemokines were observed. We also studied the effect of ginger extract on the LPS induced expression of MHC II, B7.1, B7.2 and CD40 molecules. We also studied the antigen presenting function of ginger extract treated macrophages by primary mixed lymphocyte reaction. Results We observed that ginger extract inhibited IL-12, TNF-α, IL-1β (pro inflammatory cytokines and RANTES, MCP-1 (pro inflammatory chemokines production in LPS stimulated macrophages. Ginger extract also down regulated the expression of B7.1, B7.2 and MHC class II molecules. In addition ginger extract negatively affected the antigen presenting function of macrophages and we observed a significant reduction in T cell proliferation in response to allostimulation, when ginger extract treated macrophages were used as APCs. A significant decrease in IFN-γ and IL-2 production by T cells in response to allostimulation was also observed. Conclusion In conclusion ginger extract inhibits macrophage activation and APC function and indirectly inhibits T cell activation.

  8. Exercise-induced ST-T changes and severity of myocardial ischemia in single-vessel coronary artery disease

    International Nuclear Information System (INIS)

    Shimonagata, Tsuyoshi; Nishimura, Tsunehiko; Uehara, Toshiisa; Hayashida, Kohei; Takamiya, Makoto; Sumiyoshi, Tetsuya; Saito, Muneyasu.

    1986-01-01

    The purpose of this study was to evaluate how exercise-induced ST-T changes reflect the severity of myocardial ischemia in 66 patients with singlevessel disease (SVD) who underwent stress thallium scans. Quantitative assessment of myocardial ischemia was performed with thallium ischemic score (TIS) derived from circumferential profile analysis. Circumferential profiles of the initial and 4 hr redistribution myocardial image were generated for each of three views (ANT, LAO 45, LAO 70) and TIS was obtained as the average of the area between the initial and 4 hr redistribution profile for each view. In 66 patients with SVD, TIS were compared with coronary angiographic findings. TIS was correlated well with the severity of coronary artery stenosis. In addition, TIS was also correlated well with lung thallium uptake in 46 LAD disease. Therefore, these data proved that TIS was useful for the evaluation of the severity of myocardial ischemia. In 46 LAD disease, TIS, being as the indicator of the severity of myocardial ischemia, was compared precisely with results of stress electrocardiograms to evaluate how exercise-induced ST-T changes reflect the severity of myocardial ischemia. Patients with negative U wave had the highest mean TIS and those with horizontal or down sloping ST depression of 1.0 mm or more had higher mean TIS than those with slow upsloping ST depression of 1.5 mm or more, but there were no significant differences between these groups and those without ST-T change and the mean TIS was not different significantly between V 2-6 ST depression group and V 2-6 , II, III, a V F ST depression group. In conclusion, these results indicated that exercise-induced ST-T changes reflect the severity of myocardial ischemia in some degree but also has a limitation in evaluation of the severity of myocardial ischemia. (author)

  9. Child ADHD Severity and Positive and Negative Parenting as Predictors of Child Social Functioning: Evaluation of Three Theoretical Models

    Science.gov (United States)

    Kaiser, Nina M.; McBurnett, Keith; Pfiffner, Linda J.

    2011-01-01

    Objective: Prior research has established links between child social functioning and both parenting and child ADHD severity; however, research examining the way that these variables work together is lacking. The current article aims to test three possible models (main effects, mediation, and moderation) by which ADHD severity and positive and…

  10. Investigating executive functions in children with severe speech and movement disorders using structured tasks

    NARCIS (Netherlands)

    Stadskleiv, K.; Tetzchner, S. von; Batorowicz, B.; Balkom, L.J.M. van; Dahlgren-Sandberg, A.; Renner, G.

    2014-01-01

    Executive functions are the basis for goal-directed activity and include planning, monitoring, and inhibition, and language seems to play a role in the development of these functions. There is a tradition of studying executive function in both typical and atypical populations, and the present study

  11. Social Functioning in Youth with Anxiety Disorders: Association with Anxiety Severity and Outcomes from Cognitive-Behavioral Therapy

    Science.gov (United States)

    Settipani, Cara A.; Kendall, Philip C.

    2013-01-01

    Social functioning was assessed using the Child Behavior Checklist and Teacher Report Form for children with anxiety disorders who participated in a randomized clinical trial (N = 161, aged 7-14). Significant relationships were found between severity of children's principal anxiety disorder and most measures of social functioning, such that poorer…

  12. Teaching a Child with Autism and Severe Language Delays to Reject: Direct and Indirect Effects of Functional Communication Training

    Science.gov (United States)

    Martin, Christian A.; Drasgow, Erik; Halle, James W.; Brucker, Jennifer M.

    2005-01-01

    We used functional communication training to teach Bob, a 10-year-old student with autism and severe language delays, to reject items by touching an icon. Our initial assessment revealed that Bob's behaviours serving a rejecting function consisted of pushing away, yelling, bear hugging-grabbing, and leaving. We used prompting, differential…

  13. [TCD functional test for vertigo induced by ischemic cerebrovascular disorders].

    Science.gov (United States)

    Li, Q; Zhong, N; Xue, X

    1999-04-01

    To diagnose differentially the vetigo induced by some ischemic cerebrovascular disorder. Patients with vertebrobasilar artery transient ischemic vertigo (group A), migraine (group B), hyperventilation syndrome (group C), hypertension (group D) are measured by using TCD functional examination which included blood peak velocity of systolic (Vs) and diastolic (Vd) end-period of vertibrobasilar artery of routine TCD (TCD-R), one minute hyperventilation TCD (TCD-HV) and one minute voluntary apnea TCD (TCD-B) respectively. It showed that the Vs, Vd are decreased under the three conditions in A, B and D groups. The most apparent decrease are obversed in D group. The values of the decrease are similar between group A and B. No changes are found in C group. The abnormal Vs incidences of TCD-B measurement in group A are higher than those in group B and C, but significant lower than those in group D; and in TCD-HV test lower than group D and C, higher than group B; in TCD-R test, lower than group D, and no difference with group B and C. The abnormal incidences of Vd in group A are lower than group D and higher than group B in TCD-B test. In TCD-HV test, the group A abnormol incidences are lower than group D but higher than group B and C. In TCD-R test, the abnormal incidences are lower than group D and no difference between group B and C. The TCD measuremen is useful for differential diagnosis of vertigo induced by ischemic cerebrovascular disorders.

  14. Music-induced changes in functional cerebral asymmetries.

    Science.gov (United States)

    Hausmann, Markus; Hodgetts, Sophie; Eerola, Tuomas

    2016-04-01

    After decades of research, it remains unclear whether emotion lateralization occurs because one hemisphere is dominant for processing the emotional content of the stimuli, or whether emotional stimuli activate lateralised networks associated with the subjective emotional experience. By using emotion-induction procedures, we investigated the effect of listening to happy and sad music on three well-established lateralization tasks. In a prestudy, Mozart's piano sonata (K. 448) and Beethoven's Moonlight Sonata were rated as the most happy and sad excerpts, respectively. Participants listened to either one emotional excerpt, or sat in silence before completing an emotional chimeric faces task (Experiment 1), visual line bisection task (Experiment 2) and a dichotic listening task (Experiment 3 and 4). Listening to happy music resulted in a reduced right hemispheric bias in facial emotion recognition (Experiment 1) and visuospatial attention (Experiment 2) and increased left hemispheric bias in language lateralization (Experiments 3 and 4). Although Experiments 1-3 revealed an increased positive emotional state after listening to happy music, mediation analyses revealed that the effect on hemispheric asymmetries was not mediated by music-induced emotional changes. The direct effect of music listening on lateralization was investigated in Experiment 4 in which tempo of the happy excerpt was manipulated by controlling for other acoustic features. However, the results of Experiment 4 made it rather unlikely that tempo is the critical cue accounting for the effects. We conclude that listening to music can affect functional cerebral asymmetries in well-established emotional and cognitive laterality tasks, independent of music-induced changes in the emotion state. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Changes in physico-chemical characteristics of leukocyte membranes as late effects of low doses of radioactivity and their correlation with several functions of the immune system

    International Nuclear Information System (INIS)

    Kalnina, I.; Meirovics, I.; Bruvere, R.; Heisele, O.; Volrate, A.; Feldmane, G.; Zvagule, T.; Klimkane, L.

    1998-01-01

    Membrane damage is considered to play key role in cell killing by ionising radiation and also in the loss of many different membrane functional properties induced by ionising radiation. The aim of this work was to characterize structural changes of peripheral blood mononuclear cells' (PBMC) membranes and their relationship to several functions of the immune system in Latvia' s residents who have been doing the clean-up work in Chernobyl in 1986. The correlative relationships between the fluorescence intensity and the fluorescence maxima wavelength of ABM in PBMC suspension, and several parameters of the immune state as well as the total anti oxidative activity of serum were determined in 97 clean-up workers. Conclusions: Obtained patterns of spectra suggest that specific and qualitatively different changes of membrane properties are evident in Chernobyl clean-up worker's PBMC. The revealed changes correlates with changes of the immune state of the individuals

  16. A novel hybrid stress-function finite element method immune to severe mesh distortion

    International Nuclear Information System (INIS)

    Cen Song; Zhou Mingjue; Fu Xiangrong

    2010-01-01

    This paper introduces a hybrid stress-function finite element method proposed recently for developing 2D finite element models immune to element shapes. Deferent from the first version of the hybrid-stress element constructed by Pian, the stress function φ of 2D elastic or fracture problem is regarded as the functional variable of the complementary energy functional. Then, the basic analytical solutions of φ are taken as the trial functions for finite element models, and meanwhile, the corresponding unknown stress-function constants are introduced. By using the principle of minimum complementary energy, these unknown stress-function constants can be expressed in terms of the displacements along element edges. Finally, the complementary energy functional can be rewritten in terms of element nodal displacement vector, and thus, the element stiffness matrix of such hybrid-function element can be obtained. As examples, two (8- and 12-node) quadrilateral plane elements and an arbitrary polygonal crack element are constructed by employing different basic analytical solutions of different stress functions. Numerical results show that, the 8- and 12-node plane models can produce the exact solutions for pure bending and linear bending problems, respectively, even the element shape degenerates into triangle and concave quadrangle; and the crack element can also predict accurate results with very low computational cost in analysis of stress-singularity problems.

  17. Neuropsychological predictors of performance-based measures of functional capacity and social skills in individuals with severe mental illness.

    Science.gov (United States)

    Mahmood, Zanjbeel; Burton, Cynthia Z; Vella, Lea; Twamley, Elizabeth W

    2018-04-13

    Neuropsychological abilities may underlie successful performance of everyday functioning and social skills. We aimed to determine the strongest neuropsychological predictors of performance-based functional capacity and social skills performance across the spectrum of severe mental illness (SMI). Unemployed outpatients with SMI (schizophrenia, bipolar disorder, or major depression; n = 151) were administered neuropsychological (expanded MATRICS Consensus Cognitive Battery), functional capacity (UCSD Performance-Based Skills Assessment-Brief; UPSA-B), and social skills (Social Skills Performance Assessment; SSPA) assessments. Bivariate correlations between neuropsychological performance and UPSA-B and SSPA total scores showed that most neuropsychological tests were significantly associated with each performance-based measure. Forward entry stepwise regression analyses were conducted entering education, diagnosis, symptom severity, and neuropsychological performance as predictors of functional capacity and social skills. Diagnosis, working memory, sustained attention, and category and letter fluency emerged as significant predictors of functional capacity, in a model that explained 43% of the variance. Negative symptoms, sustained attention, and letter fluency were significant predictors of social skill performance, in a model explaining 35% of the variance. Functional capacity is positively associated with neuropsychological functioning, but diagnosis remains strongly influential, with mood disorder participants outperforming those with psychosis. Social skill performance appears to be positively associated with sustained attention and verbal fluency regardless of diagnosis; however, negative symptom severity strongly predicts social skills performance. Improving neuropsychological functioning may improve psychosocial functioning in people with SMI. Published by Elsevier Ltd.

  18. Intensive insulin therapy improves insulin sensitivity and mitochondrial function in severely burned children.

    Science.gov (United States)

    Fram, Ricki Y; Cree, Melanie G; Wolfe, Robert R; Mlcak, Ronald P; Qian, Ting; Chinkes, David L; Herndon, David N

    2010-06-01

    To institute intensive insulin therapy protocol in an acute pediatric burn unit and study the mechanisms underlying its benefits. Prospective, randomized study. An acute pediatric burn unit in a tertiary teaching hospital. Children, 4-18 yrs old, with total body surface area burned > or =40% and who arrived within 1 wk after injury were enrolled in the study. Patients were randomized to one of two groups. Intensive insulin therapy maintained blood glucose levels between 80 and 110 mg/dL. Conventional insulin therapy maintained blood glucose patients were included in the data analysis consisting of resting energy expenditure, whole body and liver insulin sensitivity, and skeletal muscle mitochondrial function. Studies were performed at 7 days postburn (pretreatment) and at 21 days postburn (posttreatment). Resting energy expenditure significantly increased posttreatment (1476 +/- 124 to 1925 +/- 291 kcal/m(2) x day; p = .02) in conventional insulin therapy as compared with a decline in intensive insulin therapy. Glucose infusion rate was identical between groups before treatment (6.0 +/- 0.8 conventional insulin therapy vs. 6.8 +/- 0.9 mg/kg x min intensive insulin therapy; p = .5). Intensive insulin therapy displayed a significantly higher glucose clamp infusion rate posttreatment (9.1 +/- 1.3 intensive insulin therapy versus 4.8 +/- 0.6 mg/kg x min conventional insulin therapy, p = .005). Suppression of hepatic glucose release was significantly greater in the intensive insulin therapy after treatment compared with conventional insulin therapy (5.0 +/- 0.9 vs. 2.5 +/- 0.6 mg/kg x min; intensive insulin therapy vs. conventional insulin therapy; p = .03). States 3 and 4 mitochondrial oxidation of palmitate significantly improved in intensive insulin therapy (0.9 +/- 0.1 to 1.7 +/- 0.1 microm O(2)/CS/mg protein/min for state 3, p = .004; and 0.7 +/- 0.1 to 1.3 +/- 0.1 microm O(2)/CS/mg protein/min for state 4, p protocol improves insulin sensitivity and mitochondrial

  19. Inducible indirect defence of plants : from mechanisms to ecological functions

    NARCIS (Netherlands)

    Dicke, M.; Poecke, van R.M.P.; Boer, de J.G.

    2003-01-01

    Inducible defences allow plants to be phenotypically plastic. Inducible indirect defence of plants by attracting carnivorous enemies of herbivorous arthropods can vary with plant species and genotype, with herbivore species or instar and potentially with other environmental conditions. So far,

  20. Alert Regarding Cisplatin-induced Severe Adverse Events in Cancer Patients with Xeroderma Pigmentosum.

    Science.gov (United States)

    Sumiyoshi, Makoto; Soda, Hiroshi; Sadanaga, Noriaki; Taniguchi, Hirokazu; Ikeda, Takaya; Maruta, Hiroshi; Dotsu, Yosuke; Ogawara, Daiki; Fukuda, Yuichi; Mukae, Hiroshi

    2017-01-01

    Xeroderma pigmentosum (XP) is a genetic disease in which DNA repair mechanisms are impaired. Cisplatin (CDDP) exerts cytotoxic effects by forming mainly intrastrand DNA cross-links, and sensitivity to CDDP depends on the DNA repair system. Several in vitro studies have suggested that treatment with CDDP may cause enhanced adverse events as well as anti-tumor activity in cancer patients with XP. This article is the first to describe two cancer patients with XP showing severe adverse events following CDDP-based chemotherapy. Physicians should pay attention when administering CDDP in cancer patients with XP.

  1. Cross-polarization microwave radar return at severe wind conditions: laboratory model and geophysical model function.

    Science.gov (United States)

    Troitskaya, Yuliya; Abramov, Victor; Ermoshkin, Alexey; Zuikova, Emma; Kazakov, Vassily; Sergeev, Daniil; Kandaurov, Alexandr

    2014-05-01

    Satellite remote sensing is one of the main techniques of monitoring severe weather conditions over the ocean. The principal difficulty of the existing algorithms of retrieving wind based on dependence of microwave backscattering cross-section on wind speed (Geophysical Model Function, GMF) is due to its saturation at winds exceeding 25 - 30 m/s. Recently analysis of dual- and quad-polarization C-band radar return measured from satellite Radarsat-2 suggested that the cross-polarized radar return has much higher sensitivity to the wind speed than co-polarized back scattering [1] and conserved sensitivity to wind speed at hurricane conditions [2]. Since complete collocation of these data was not possible and time difference in flight legs and SAR images acquisition was up to 3 hours, these two sets of data were compared in [2] only statistically. The main purpose of this paper is investigation of the functional dependence of cross-polarized radar cross-section on the wind speed in laboratory experiment. Since cross-polarized radar return is formed due to scattering at small-scale structures of the air-sea interface (short-crested waves, foam, sprays, etc), which are well reproduced in laboratory conditions, then the approach based on laboratory experiment on radar scattering of microwaves at the water surface under hurricane wind looks feasible. The experiments were performed in the Wind-wave flume located on top of the Large Thermostratified Tank of the Institute of Applied Physics, where the airflow was produced in the flume with the straight working part of 10 m and operating cross section 0.40?0.40 sq. m, the axis velocity can be varied from 5 to 25 m/s. Microwave measurements were carried out by a coherent Doppler X-band (3.2 cm) scatterometer with the consequent receive of linear polarizations. Experiments confirmed higher sensitivity to the wind speed of the cross-polarized radar return. Simultaneously parameters of the air flow in the turbulent boundary layer

  2. Severe malformations of eelpout (Zoarces viviparus) fry are induced by maternal estrogenic exposure during early embryogenesis

    DEFF Research Database (Denmark)

    Morthorst, Jane Ebsen; Korsgaard, Bodil; Bjerregaard, Poul

    2016-01-01

    Pregnant eelpout were exposed via the water to known endocrine disrupting compounds (EDCs) to clarify if EDCs could be causing the increased eelpout fry malformation frequencies observed in coastal areas receiving high anthropogenic input. The presence of a teratogenic window for estrogen...... induced by EE2 (5.7 and 17.8 ng/L) but not by 4-t-OP and pyrene. A critical period for estrogen-induced fry malformations was identified and closed between 14 and 22 days post fertilization (dpf). Exposure to 17β-estradiol (E2) between 0 and 14 dpf caused severe malformations and severity increased...... the closer exposure start was to fertilization, whereas malformations were absent by exposure starting later than 14 dpf. Data on ovarian fluid volume and larval length supported the suggested teratogenic window. Larval mortality also increased when exposure started right after fertilization....

  3. Willingness to Seek Help as a Function of Self-Disclosure and Problem Severity.

    Science.gov (United States)

    Hinson, Janise A.; Swanson, Jane L.

    1993-01-01

    Examined effects of problem severity, amount of self-disclosure, and self-disclosure flexibility on willingness to seek help for problem. Findings from 101 college students indicated that factors that predicted greatest amount of variance in willingness to seek help were interaction of problem severity with willingness to self-disclose to…

  4. Comparative studies of radiation-induced chromosome aberrations in several mammalian species

    International Nuclear Information System (INIS)

    Muramatsu, S.; Matsuoka, O.

    1976-01-01

    The dose-response relationship for inducing chromosome aberrations in peripheral lymphocytes of five mammalian species - man, cynomolgus monkey, rabbit, domestic cat and beagle dog - were studied comparatively by whole-blood microculture technique following in-vitro exposures at various doses with 200-kVp X rays. The yields of induced chromosome aberrations were dependent on exposure doses between 48 and 480 rads in all the species examined. The relationship between exposure dose (D in rads) and frequency of induced dicentrics per cell (Y) was expressed by: Ysub((man)) = 14.38x10 -6 Dsup(1.94); Ysub((monkey)) = 18.12x10 -6 Dsup(1.86); Ysub((rabbit)) = 1.88x10 -6 Dsup(2.06); Ysub((cat)) = 78.66x10 -6 Dsup(1.35); Ysub((dog)) = 46.13x10 -6 Dsup(1.37). Taking the frequency of dicentrics in man as 1.00, the relative frequency in each species was estimated as 0.79, 0.24, 0.22 and 0.16 in monkey, rabbit, cat and dog, respectively. From these results the consistent relationship could not be discovered between X-ray doses and the dicentric yield based on the arm number effect proposed by Brewen et al., whereas the nuclear DNA contents and the arm number in all the species used are roughly similar to those in man. The authors considered that such interspecies differences may be derived from the cellular and/or physiological features of PHA-responsible lymphocytes (T-cells) in each species, and that may be due to the level of development of each species on the phylogenetic or evolutionary scale. (author)

  5. Efficacy of ginger in alleviating the severe radiation-induced biochemical, histological and embryological impactions pregnant female albino rats

    International Nuclear Information System (INIS)

    Rezk, R.G.; Ibrahim, M.F.; Darwish, M.M.

    2005-01-01

    Ginger (Zingiber officinale), a common part of the diet in many parts of the world, is one of the strongest plant antioxidants that has various pharmacological effects. Accordingly, this study was investigated to clarify the beneficial effect of maternal intake of ginger on radiation-induced maternal and fetal detrimental impacts. Pregnant albino rats were administered ginger tea from gestation day 10 to 14 at a dose rate of 10 ml/kg body weight before being exposed to a single dose of 6 Gy of whole body gamma irradiation at day 15 of gestation, after which they were excised on the 18th day of pregnancy. Maternal ginger pre-treatment before radiation exposure was able to diminish the high levels of malondialdehyde (MDA), glucose, lipids, follicle stimulating hormone (FSH) and luteinizing hormone (LH) recorded in the serum of irradiated mother rats in addition to restoring the histopathological lesions induced in their aorta and uterus tissues. Moreover, ginger intake was found to reduce the severe deleterious symptoms of radiation-induced fetal mortality rate with increased growth in surviving fetuses and remarkable protection against severe morphological deformities.The present study suggests that ginger is an effective agent for improving the affected maternal biochemical and histological studied parameters and reducing the embryonic injuries induced by gamma irradiation

  6. A reliable, practical, and economical protocol for inducing diarrhea and severe dehydration in the neonatal calf.

    OpenAIRE

    Walker, P G; Constable, P D; Morin, D E; Drackley, J K; Foreman, J H; Thurmon, J C

    1998-01-01

    Fifteen healthy, colostrum-fed, male dairy calves, aged 2 to 7 d were used in a study to develop a diarrhea protocol for neonatal calves that is reliable, practical, and economical. After instrumentation and recording baseline data, diarrhea and dehydration were induced by administering milk replacer [16.5 mL/kg of body weight (BW), PO], sucrose (2 g/kg in a 20% aqueous solution, p.o.), spironolactone and hydrochlorothiazide (1 mg/kg, PO) every 8 h, and furosemide (2 mg/kg, i.m., q6h). Calves...

  7. Biological function of activation-induced cytidine deaminase (AID

    Directory of Open Access Journals (Sweden)

    Ritu Kumar

    2014-10-01

    Full Text Available Activation-induced Cytidine Deaminase (AID is an essential regulator of B cell diversification, but its full range of action has until recently been an enigma. Based on homology, it was originally proposed to be an RNA-editing enzyme, but so far, no RNA substrates are known. Rather, it functions by deaminating cytidine, and in this manner, coupled with base-excision repair or mismatch repair machinery, it is a natural mutator. This allows it to play a central role in adaptive immunity, whereby it initiates the processes of class switch recombination and somatic hypermutation to help generate a diverse and high-affinity repertoire of immunoglobulin isotypes. More recently, it has been appreciated that methylated cytidine, already known as a key epigenetic mark on DNA controlling gene expression, can also be a target for AID modification. Coupled with repair machinery, this can facilitate the active removal of methylated DNA. This activity can impact the process of cellular reprogramming, including transition of a somatic cell to pluripotency, which requires major reshuffling of epigenetic memory. Thus, seemingly disparate roles for AID in controlling immune diversity and epigenetic memory have a common mechanistic basis. However, the very activity that is so useful for B cell diversity and cellular reprogramming is dangerous for the integrity of the genome. Thus, AID expression and activity is tightly regulated, and deregulation is associated with diseases including cancer. Here, we review the range of AID functions with a focus on its mechanisms of action and regulation. Major questions remain to be answered concerning how and when AID is targeted to specific loci and how this impacts development and disease.

  8. Inhibition of stress-activated MAP kinases induces clinical improvement in moderate to severe Crohn's disease

    NARCIS (Netherlands)

    Hommes, Daan; van den Blink, Bernt; Plasse, Terry; Bartelsman, Joep; Xu, Cuiping; Macpherson, Bret; Tytgat, Guido; Peppelenbosch, Mailkel; van Deventer, Sander

    2002-01-01

    Background & Aims: We investigated if inhibition of mitogen-activated protein kinases (MAPKs) was beneficial in Crohn's disease. Methods: Inhibition of JNK and p38 MAPK activation with CNI-1493, a guanylhydrazone, was tested in vitro. Twelve patients with severe Crohn's disease (mean baseline, CDAI

  9. Severe Bone Loss induced by Orthodontic Elastic Separator: A Rare Case Report

    Directory of Open Access Journals (Sweden)

    A E Vishwanath

    2013-01-01

    Full Text Available A displaced orthodontic elastic separator was proposed as being the source of a gingival abscess that progressed to severe bone loss and exfoliation in a healthy adolescent patient with sound periodontal status prior to commencement of orthodontic treatment. After 1 year of undergoing orthodontic treatment, the patient presented with dull pain and mobility in the left upper permanent molar for which there was no apparent etiology. On clinical examination, the patient had gingival inflammation, associated with a deep pocket and severe mobility (grade III in relation to the same teeth. Radiographic examination of an orthopantomogram and intraoral periapical radiography (IOPAR revealed a chronic periodontal abscess with severe necrosis of the periodontal ligament and severe alveolar bone loss. A radiopaque mass on the distal surface below the cementoenamel junction (CEJ was also observed. The patient was referred to the department of periodontics for assessment and appropriate treatment. On curettage, it was found that there was orthodontic elastic separator which was displaced subgingivally.

  10. Local anesthetic-induced myotoxicity as a cause of severe trismus after inferior alveolar nerve block.

    Science.gov (United States)

    Smolka, Wenko; Knoesel, Thomas; Mueller-Lisse, Ullrich

    2018-01-01

    A case of a 60-year-old man with severe trismus after inferior alveolar nerve block is presented. MRI scans as well as histologic examination revealed muscle fibrosis and degeneration of the medial part of the left temporal muscle due to myotoxicity of a local anesthetic agent.

  11. Severe Dextran-Induced Anaphylactic Shock during Induction of Hypertension-Hypervolemia-Hemodilution Therapy following Subarachnoid Hemorrhage

    Directory of Open Access Journals (Sweden)

    Tohru Shiratori

    2015-01-01

    Full Text Available Dextran is a colloid effective for volume expansion; however, a possible side effect of its use is anaphylaxis. Dextran-induced anaphylactoid reaction (DIAR is a rare but severe complication, with a small dose of dextran solution sufficient to induce anaphylaxis. An 86-year-old female who underwent clipping for a ruptured cerebral aneurysm was admitted to the intensive care unit. Prophylactic hypertension-hypervolemia-hemodilution therapy was induced for cerebral vasospasm following a subarachnoid hemorrhage. The patient went into severe shock after administration of dextran for volume expansion, and dextran administration was immediately discontinued. The volume administered at that time was only 0.8 mL at the most. After fluid resuscitation with a crystalloid solution, circulatory status began to recover. However, cerebral vasospasm occurred and the patient’s neurological condition deteriorated. Five weeks after the shock, she was diagnosed with hypersensitivity to dextran by a skin test. When severe hypotension occurs after dextran administration, appropriate treatments for shock should be performed immediately with discontinuation of dextran solution. Although colloid administration is recommended in some guidelines and researches, it is necessary to consider concerning the indication for volume expansion as well as the risk of colloid administration.

  12. Subliminally and consciously induced cognitive conflicts interact at several processing levels.

    Science.gov (United States)

    Stock, Ann-Kathrin; Friedrich, Julia; Beste, Christian

    2016-12-01

    Controlled behavior is susceptible to conflicts that can emerge from subliminal or consciously processed information. While research suggests that both sources of conflicting information may interact in their modulation of controlled behavior, it has remained unclear which cognitive sub-processes involved in controlled behavior are affected by this interaction; i.e., at which processing level subliminally and consciously induced response conflicts interact in modulating controlled behavior. Moreover, we investigated whether this interaction of subliminally and consciously induced response conflicts was due to a nexus between the two types of conflict like a common cognitive process or factor. For this, n = 38 healthy young subjects completed a paradigm which combines subliminal primes and consciously perceived flankers while an electroencephalography (EEG) was recorded. We show that the interaction of subliminal and conscious sources of conflict is not restricted to the response selection level (N2) but can already be shown at the earliest stages of perceptual and attentional processing (P1). While the degree of early attentional processing of subliminal information seems to depend on the absence of consciously perceived response conflicts, conflicts during the stage of response selection may be either reduced or enhanced by subliminal priming. Moreover, the results showed that even though the two different sources of conflict interact at the response selection level, they clearly originate from two distinct processes that interact before they detrimentally affect cognitive control. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. MAPK Phosphatase-1 Deficiency Exacerbates the Severity of Imiquimod-Induced Psoriasiform Skin Disease

    Directory of Open Access Journals (Sweden)

    Weiheng Zhao

    2018-03-01

    Full Text Available Persistent activation of mitogen-activated protein kinase (MAPK is believed to be involved in psoriasis pathogenesis. MAPK phosphatase-1 (MKP-1 is an important negative regulator of MAPK activity, but the cellular and molecular mechanisms of MKP-1 in psoriasis development are largely unknown. In this study, we found that the expression of MKP-1 was decreased in the imiquimod (IMQ-induced psoriasiform mouse skin. MKP-1-deficient (MKP-1−/− mice were highly susceptible to IMQ-induced skin inflammation, which was associated with increased production of inflammatory cytokines and chemokines. MKP-1 acted on both hematopoietic and non-hematopoietic cells to regulate psoriasis pathogenesis. MKP-1 deficiency in macrophages led to enhanced p38 activation and higher expression of interleukin (IL-1β, CXCL2, and S100a8 upon R848 stimulation. Moreover, MKP-1 deficiency in the non-hematopoietic compartments led to an enhanced IL-22 receptor signaling and higher expression of CXCL1 and CXCL2 upon IMQ treatment. Collectively, our data suggest a critical role for MKP-1 in the regulation of skin inflammation.

  14. Effects of Functional Mobility Skills Training for Adults with Severe Multiple Disabilities

    Science.gov (United States)

    Whinnery, Stacie B.; Whinnery, Keith W.

    2011-01-01

    This study investigated the effects of a functional mobility program on the functional standing and walking skills of five adults with developmental disabilities. The Mobility Opportunities Via Education (MOVE) Curriculum was implemented using a multiple-baseline across subjects design. Repeated measures were taken during baseline, intervention…

  15. A Functional Assessment of Handmouthing among Persons with Severe and Profound Intellectual Disability

    Science.gov (United States)

    Swender, Stephen L.; Matson, Johnny L.; Mayville, Stephen B.; Gonzalez, Melissa L.; McDowell, Donald

    2006-01-01

    Background: The behavioural function of handmouthing has been assessed across various studies utilising analogue functional analyses. The aim of the current study was to expand upon research on this relatively understudied behaviour by examining the relationship between handmouthing and "Gastro-Esophageal Reflux Disorder" (GERD), and the potential…

  16. Severe Burn-Induced Intestinal Epithelial Barrier Dysfunction Is Associated With Endoplasmic Reticulum Stress and Autophagy in Mice

    Science.gov (United States)

    Huang, Yalan; Feng, Yanhai; Wang, Yu; Wang, Pei; Wang, Fengjun; Ren, Hui

    2018-01-01

    The disruption of intestinal barrier plays a vital role in the pathophysiological changes after severe burn injury, however, the underlying mechanisms are poorly understood. Severe burn causes the disruption of intestinal tight junction (TJ) barrier. Previous studies have shown that endoplasmic reticulum (ER) stress and autophagy are closely associated with the impairment of intestinal mucosa. Thus, we hypothesize that ER stress and autophagy are likely involved in burn injury-induced intestinal epithelial barrier dysfunction. Mice received a 30% total body surface area (TBSA) full-thickness burn, and were sacrificed at 0, 1, 2, 6, 12 and 24 h postburn. The results showed that intestinal permeability was increased significantly after burn injury, accompanied by the damage of mucosa and the alteration of TJ proteins. Severe burn induced ER stress, as indicated by increased intraluminal chaperone binding protein (BIP), CCAAT/enhancer-binding protein homologous protein (CHOP) and inositol-requiring enzyme 1(IRE1)/X-box binding protein 1 splicing (XBP1). Autophagy was activated after burn injury, as evidenced by the increase of autophagy related protein 5 (ATG5), Beclin 1 and LC3II/LC3I ratio and the decrease of p62. Besides, the number of autophagosomes was also increased after burn injury. The levels of p-PI3K(Ser191), p-PI3K(Ser262), p-AKT(Ser473), and p-mTOR were decreased postburn, suggesting that autophagy-related PI3K/AKT/mTOR pathway is involved in the intestinal epithelial barrier dysfunction following severe burn. In summary, severe burn injury induces the ER stress and autophagy in intestinal epithelia, leading to the disruption of intestinal barrier. PMID:29740349

  17. Changes of liver function and serum hepatic fibrosis markers levels in patients with trichloroethylene induced drugrash-like dermatitis

    International Nuclear Information System (INIS)

    Li Senhua; Xie Guoqiang; Zeng Zeming

    2004-01-01

    Objective: To investigate the liver function damage and serum hepatic fibrosis markers levels changes in patients suffering from trichloroethylene induced drugrash-like dermatitis. Methods: Serum hyaluronic acid (HA), laminin (LN), procollagen type III (PC III), type IV collagen ( IV C) levels (with RIA), mono-amine oxidase (MAO) activity (with chemo-colorimetry) and liver function tests (including ALT, AGT, total protein, albumin, total bile acid, with automated biochemical analysis system) were determined in 30 controls and 30 patients with trichloroethylene induced drugrash-like dermatitis. Results: Severe liver function damage was demonstrated in all the patients. The serum hepatic fibrosis markers levels were significantly increased (vs controls, P<0.01) and correlated well with the degree of hepatic damage. Conclusion: Liver damage occurred early in patients with trichloroethylene induced dermatitis, accompanied with laboratory evidence of hepatic fibrosis. (authors)

  18. Assessment of Object Permanence in Severely Handicapped Students as a Function of Motor and Prompting Variables.

    Science.gov (United States)

    Ilmer, Steven; And Others

    1981-01-01

    The study assessed object permanence construct performance in 20 severely handicapped students (4 to 14 years old) who were differentiated by treatment (prompt) condition and motor ability level. Results revealed a trait (motor ability) x treatment interaction. (Author/SB)

  19. Quetiapine Induced Acute Dystonia in a patient with History of severe Head Injury

    OpenAIRE

    Robert G. Bota; Joanne W. Witkowski

    2010-01-01

    A patient with a history of severe head injury 10 years ago regained ability to walk after years of being bound to a wheelchair. During the last psychiatric hospitalization, quetiapine was increased to therapeutic dose using a normal titration. As a result the patient developed dystonia of multiple muscle groups requiring 4 days of hospitalization for remittance of symptoms. In this paper, we take a close look at the literature concerning extrapiramidal symptoms (EPS) in this context, and we ...

  20. Severe Bone Loss induced by Orthodontic Elastic Separator: A Rare Case Report

    OpenAIRE

    A E Vishwanath; B K Sharmada; Sandesh S Pai; Nandini Nelvigi

    2013-01-01

    A displaced orthodontic elastic separator was proposed as being the source of a gingival abscess that progressed to severe bone loss and exfoliation in a healthy adolescent patient with sound periodontal status prior to commencement of orthodontic treatment. After 1 year of undergoing orthodontic treatment, the patient presented with dull pain and mobility in the left upper permanent molar for which there was no apparent etiology. On clinical examination, the patient had gingival inflammation...

  1. Change in Psychiatric Symptomatology after Benfotiamine Treatment in Males is a Function of Lifetime Alcoholism Severity

    Science.gov (United States)

    Manzardo, Ann M.; Pendleton, Tiffany; Poje, Albert; Penick, Elizabeth C.; Butler, Merlin G.

    2015-01-01

    Background Severe alcoholism can be associated with significant nutritional and vitamin deficiency, especially vitamin B1 (thiamine) which is associated with serious illness and neurological deficits that influence mood and cognition. We previously reported reduced alcohol consumption among female but not male alcoholics after supplementation with the high potency thiamine analog benfotiamine (BF). As a follow-up, we have examined the relationship between lifetime alcoholism severity and psychiatric symptoms among the alcohol dependent men from this cohort and their response to BF treatment. Methods Eighty-five adult men (mean age = 48 ± 8 yrs) meeting DSM-IV-TR criteria for current alcohol dependence participated in a randomized, double-blind, placebo-controlled trial of 600 mg BF vs placebo (PL) for 6 months. Psychometric testing included a derived Lifetime Alcoholism Severity Score (AS), Symptom Checklist 90R (SCL-90R), and the Barratt Impulsivity Scale (BIS) at baseline and at 6 months with data analyzed using ANOVA and MANOVA modeling. Results Baseline SCL-90-R scale scores for men with high alcoholism severity (AS ≥ 24; N=46 HAS) were significantly greater than for men with low alcoholism severity (AS < 24; N=39 LAS), but BIS scores did not differ. MANOVA modeling identified a significant treatment effect (F=2.5, df=10, p<0.03) and treatment x alcoholism severity level interaction (F=2.5, dfnum=10, dfden=30, p<0.03) with SCL-90-R scores showing a reduction in symptoms among BF treated, high severity males. Conclustion BF appears to reduce psychiatric distress and may facilitate recovery in severely affected males with lifetime alcohol dependence and should be considered for adjuvant therapy in alcohol rehabilitation. PMID:25908323

  2. Child labor and severe functioning difficulties and disability in Mexican children and adolescents 5-17 years of age

    Directory of Open Access Journals (Sweden)

    Aremis Villalobos

    2017-07-01

    Full Text Available Objective. To describe the characteristics of Mexican children and adolescents 5-17 years with severe functioning difficulties and disability and explore their participation in child labor. Materials and methods. Using data from the National Survey of Boys, Girls and Women in Mexico 2015 we estimated prevalence of functioning difficulties and disability and used logistic regression to explore the association between this condition and child labor. Results. While 11.2% of Mexicans 5-17 years-old has severe functioning difficulties or disability, 13.4% work. The functioning difficulty and disability domains with the highest prevalence are experiencing anxiety (5.4% and depression (1.5% daily. Children and adolescents with severe functioning difficulties and disability are 70% more likely to do child labor [OR=1.7, 95%CI:1.2,2.4]. Educational lag doubles the likelihood of doing child labor [OR=2.2, 95%CI:1.5,3.3]. Conclusions. Guaranteeing educational opportunities and respect for the rights of children with severe functioning difficulties and disability is essential to achieve development of their full potential.

  3. The DSM-5 Levels of Personality Functioning and Severity of Iranian Patients With Antisocial and Borderline Personality Disorders.

    Science.gov (United States)

    Amini, Mehdi; Pourshahbaz, Abbas; Mohammadkhani, Parvaneh; Khodaie Ardakani, Mohammad Reza; Lotfi, Mozhgan

    2015-08-01

    Fundamental problems with Personality Disorders (PD) diagnostic system in the previous version of DSM, led to the revision of DSM. Therefore, a multidimensional system has been proposed for diagnosis of personality disorder features in DSM-5. In the dimensional approach of DSM-5, personality disorders diagnosis is based on levels of personality functioning (Criteria A) and personality trait domains (Criteria B). The purpose of this study was firstly, to examine the DSM-5 levels of personality functioning in antisocial and borderline personality disorders, and second, to explore which levels of personality functioning in patients with antisocial and borderline personality disorders can better predicted severity than others. This study had a cross sectional design. The participants consisted of 252 individuals with antisocial (n = 122) and borderline personality disorders (n = 130). They were recruited from Tehran prisoners, and clinical psychology and psychiatry centers of Razi and Taleghani Hospitals, Tehran, Iran. The sample was selected based on judgmental sampling. The SCID-II-PQ, SCID-II and DSM-5 levels of personality functioning were used to diagnose and assess personality disorders. The data were analyzed by correlation and multiple regression analysis. All statistical analyses were performed using the SPSS 16 software. Firstly, it was found that DSM-5 levels of personality functioning have a strong correlation with antisocial and borderline personality symptoms, specially intimacy and self-directedness (P antisocial personality disorder severity (P personality disorder severity, as well (P personality functioning are a significant predictor of personality disorders severity. The results partially confirm existing studies.

  4. Cognitive tutoring induces widespread neuroplasticity and remediates brain function in children with mathematical learning disabilities.

    Science.gov (United States)

    Iuculano, Teresa; Rosenberg-Lee, Miriam; Richardson, Jennifer; Tenison, Caitlin; Fuchs, Lynn; Supekar, Kaustubh; Menon, Vinod

    2015-09-30

    Competency with numbers is essential in today's society; yet, up to 20% of children exhibit moderate to severe mathematical learning disabilities (MLD). Behavioural intervention can be effective, but the neurobiological mechanisms underlying successful intervention are unknown. Here we demonstrate that eight weeks of 1:1 cognitive tutoring not only remediates poor performance in children with MLD, but also induces widespread changes in brain activity. Neuroplasticity manifests as normalization of aberrant functional responses in a distributed network of parietal, prefrontal and ventral temporal-occipital areas that support successful numerical problem solving, and is correlated with performance gains. Remarkably, machine learning algorithms show that brain activity patterns in children with MLD are significantly discriminable from neurotypical peers before, but not after, tutoring, suggesting that behavioural gains are not due to compensatory mechanisms. Our study identifies functional brain mechanisms underlying effective intervention in children with MLD and provides novel metrics for assessing response to intervention.

  5. Type of Ground Surface during Plyometric Training Affects the Severity of Exercise-Induced Muscle Damage

    Directory of Open Access Journals (Sweden)

    Hamid Arazi

    2016-03-01

    Full Text Available The purpose of this study was to compare the changes in the symptoms of exercise-induced muscle damage from a bout of plyometric exercise (PE; 10 × 10 vertical jumps performed in aquatic, sand and firm conditions. Twenty-four healthy college-aged men were randomly assigned to one of three groups: Aquatic (AG, n = 8, Sand (SG, n = 8 and Firm (FG, n = 8. The AG performed PE in an aquatic setting with a depth of ~130 cm. The SG performed PE on a dry sand surface at a depth of 20 cm, and the FG performed PE on a 10-cm-thick wooden surface. Plasma creatine kinase (CK activity, delayed onset muscle soreness (DOMS, knee range of motion (KROM, maximal isometric voluntary contraction (MIVC of the knee extensors, vertical jump (VJ and 10-m sprint were measured before and 24, 48 and 72 h after the PE. Compared to baseline values, FG showed significantly (p < 0.05 greater changes in CK, DOMS, and VJ at 24 until 48 h. The MIVC decreased significantly for the SG and FG at 24 until 48 h post-exercise in comparison to the pre-exercise values. There were no significant (p > 0.05 time or group by time interactions in KROM. In the 10-m sprint, all the treatment groups showed significant (p < 0.05 changes compared to pre-exercise values at 24 h, and there were no significant (p > 0.05 differences between groups. The results indicate that PE in an aquatic setting and on a sand surface induces less muscle damage than on a firm surface. Therefore, training in aquatic conditions and on sand may be beneficial for the improvement of performance, with a concurrently lower risk of muscle damage and soreness.

  6. DIETOTHERAPY OF FUNCTIONAL DIGESTION DISORDERS IN CHILDREN OF THE FIRST SEVERAL MONTHS OF LIFE

    Directory of Open Access Journals (Sweden)

    T. V. Abramova

    2012-01-01

    Full Text Available The authors discuss the questions of functional digestion disorders dietotherapy with artificial milk formula «CELIA DIGEST» enriched with probiotics in infants. During the study the composition and the properties of afore-mentioned formula as well as the special features of its usage in dietotherapy of functional digestion disorders in children were examined. The results of the clinical evaluation of this formula efficacy in infants at the age from 0 to 2 months old in comparison to the course of functional digestion disorders symptoms in breast-fed children are represented in the article.

  7. Functionalized nanoparticles for AMF-induced gene and drug delivery

    Science.gov (United States)

    Biswas, Souvik

    The properties and broad applications of nano-magnetic colloids have generated much interest in recent years. Specially, Fe3O4 nanoparticles have attracted a great deal of attention since their magnetic properties can be used for hyperthermia treatment or drug targeting. For example, enhanced levels of intracellular gene delivery can be achieved using Fe3O4 nano-vectors in the presence of an external magnetic field, a process known as 'magnetofection'. The low cytotoxicity, tunable particle size, ease of surface functionalization, and ability to generate thermal energy using an external alternating magnetic field (AMF) are properties have propelled Fe3O4 research to the forefront of nanoparticle research. The strategy of nanoparticle-mediated, AMF-induced heat generation has been used to effect intracellular hyperthermia. One application of this 'magnetic hyperthermia' is heat activated local delivery of a therapeutic effector (e.g.; drug or polynucleotide). This thesis describes the development of a magnetic nano-vector for AMF-induced, heat-activated pDNA and small molecule delivery. The use of heat-inducible vectors, such as heat shock protein ( hsp) genes, is a promising mode of gene therapy that would restrict gene expression to a local region by focusing a heat stimulus only at a target region. We thus aimed to design an Fe3O4 nanoparticle-mediated gene transfer vehicle for AMF-induced localized gene expression. We opted to use 'click' oximation techniques to assemble the magnetic gene transfer vector. Chapter 2 describes the synthesis, characterization, and transfection studies of the oxime ether lipid-based nano-magnetic vectors MLP and dMLP. The synthesis and characterization of a novel series of quaternary ammonium aminooxy reagents (2.1--2.4) is described. These cationic aminooxy compounds were loaded onto nanoparticles for ligation with carbonyl groups and also to impart a net positive charge on the nanoparticle surface. Our studies indicated that the

  8. Paranoid Adipsia-induced Severe Hypernatremia and Uremia treated with Hemodialysis

    OpenAIRE

    Choi, Jae-Hyun; Lee, Hee Seung; Kim, Sun Moon; Kim, Hye-young; Kwon, Soon Kil

    2013-01-01

    We describe a patient with severe hypernatremia and uremia caused by paranoid adipsia who was treated successfully with hydration and hemodialysis. A previously healthy 40-year-old woman developed the paranoid idea that her water was poisoned, so she refused to drink any water. On admission, her blood urea nitrogen was 208mg/dL, creatinine 4.90mg/dL, serum osmolality 452mOsm/L, serum sodium 172mEq/L, urine specific gravity ?1.030, urine osmolality 698mOsm/L, and urine sodium/potassium/chlorid...

  9. Development of radiation-induced mutation techniques and functional genomics studies

    International Nuclear Information System (INIS)

    Kim, Dong Sub; Kang, Si Yong; Kim, Jin Baek

    2012-01-01

    This project has been performed to develop plant genetic resources using radiation (gamma-rays, ion-beam, space environments), to conduct functional genomics studies with mutant resources, and to develop new radiation plant breeding techniques using various radiation sources during 3 years. In the first section, we developed flower genetic resources, functional crop resources, and bio-industrial plant resources. In the second section, we cloned several mutated genes and studied mechanisms of gene expression and genetic diversity of mutations induced by gamma-rays. In the third section, we developed new plant breeding techniques using gamma-phytotron, heavy ion-beam, and space environments. Based on these results, a total of 8 cultivars containing Chrysanthemum, Hibiscus, kenaf, rice, and soybean were applied for plant variety protection (PVP) and a total of 4 cultivars were registered for PVP. Also, license agreement for the dwarf type Hibiscus mutant 'Ggoma' was conducted with Supro co. and the manufacturing technology for natural antioxidant pear-grape vinegar was transferred into Enzenic co. Also, 8 gene sequences, such as F3'H and LDOX genes associated with flower color in Chrysanthemum and EPSPS gene from Korean lawn grass, were registered in the database of National Center for Biotechnology Information (NCBI). In the future study, we will develop new radiation mutation breeding techniques through the mutation spectrum induced by various radiation sources, the studies for mechanism of the cellular response to radiation, and the comparative·structural·functional genomics studies for useful traits

  10. Functional promoter variant in zinc finger protein 202 predicts severe atherosclerosis and ischemic heart disease

    DEFF Research Database (Denmark)

    Frikke-Schmidt, R.; Nordestgaard, Børge; Grande, Peer

    2008-01-01

    Objectives This study was designed to test the hypotheses that single nucleotide polymorphisms ( SNPs), in zinc finger protein 202 ( ZNF202), predict severe atherosclerosis and ischemic heart disease ( IHD). Background ZNF202 is a transcriptional repressor controlling promoter elements in genes...... involved in vascular maintenance and lipid metabolism. Methods We first determined genotype association for 9 ZNF202 SNPs with severe atherosclerosis ( ankle brachial index >0.7 vs. ...,998 controls. Finally, we determined whether g. -660A>G altered transcriptional activity of the ZNF202 promoter in vitro. Results Cross-sectionally, ZNF202 g. -660 GG versus AA homozygosity predicted an odds ratio for severe atherosclerosis of 2.01 ( 95% confidence interval [CI]: 1.34 to 3.01). Prospectively...

  11. Variation of several agronomic and biochemical traits in γ-ray induced mutant soybeans

    International Nuclear Information System (INIS)

    Shim, Kyo Moon; Kim, Sun Hyung; Kim, Nam Soo; Son, Hi Sup; Rhee, Hae Ik

    1996-01-01

    Two soybean cultivars(Paldalkong and Bangsakong) were irradiated with gamma-ray to reduce seed size, which is an important trait for soybean sprout and the derived mutant soybeans were analyzed in several agronomic and biochemical traits. There were high levels of variations in quantitative traits among the mutants. Several mutant lines showed higher yield and smaller seed than their parents. Qualitative traits such as seed coat color or pubescent color were also changed in a few lines. Biochemical variations were also observed among the mutants. In seed storage protein analysis, many mutant lines showed reduced intensities in β-subunits in 7S globulin than their parents and an additional band in the acidic subunit at 31KDa. Two mutant lines derived from Paldalkong showed an additional band and a shifted band of protease inhibitor by electrophoretic analysis. Variations in isozymes and RAPD were also observed among the mutants. Six isozymes(Adh, Est, Gdh, Idh, Mdh and Pgm) among eleven isozymes showed some variations and six out of ten primers showed polymorphic amplified DNA fragments among the mutants. (author)

  12. Investigation of severe UF membrane fouling induced by three marine algal species

    KAUST Repository

    Merle, Tony

    2016-02-06

    Reducing membrane fouling caused by seawater algal bloom is a challenge for regions of the world where most of their freshwater is produced by seawater desalination. This study aims to compare ultrafiltration (UF) fouling potential of three ubiquitous marine algal species cultures (i.e., Skeletonena costatum-SKC, Tetraselmis sp.-TET, and Hymenomonas sp.-HYM) sampled at different phases of growth. Results showed that flux reduction and irreversible fouling were more severe during the decline phase as compared to the exponential phase, for all species. SKC and TET were responsible for substantial irreversible fouling but their impact was significantly lower than HYM. The development of a transparent gel layer surrounding the cell during the HYM growth and accumulating in water is certainly responsible for the more severe observed fouling. Chemical backwash with a standard chlorine solution did not recover any membrane permeability. For TET and HYM, the Hydraulically Irreversible Fouling Index (HIFI) was correlated to their biopolymer content but this correlation is specific for each species. Solution pre-filtration through a 1.2 μm membrane proved that cells and particulate algal organic matter (p-AOM) considerably contribute to fouling, especially for HYM for which the HIFI was reduced by a factor of 82.3.

  13. Ultrasonographic Optic Nerve Sheath Diameter as a Surrogate Measure of Raised Intracranial Pressure in Severe Pregnancy-induced Hypertension Patients.

    Science.gov (United States)

    Singh, Shiv Kumar; Bhatia, Kiran

    2018-01-01

    It is a well-known fact that severe pregnancy-induced hypertension (PIH) can be disastrous at times as it can cause a lot of complications to both pregnant women and her baby. Hence, it is always desirable to know the extent of severity by a real-time and easily accessible modality like ultrasound. The aim of the study was to evaluate the incidence of raised intracranial pressure (ICP) in severe preeclampsia and eclampsia patients using ocular ultrasonography with optic nerve sheath diameter (ONSD) measurement. This study design was a prospective and clinically controlled blinded observational study. After taking necessary permissions from the Institution Ethical Committee, 75 patients were enrolled for the study. However, finally, 25 patients in severe preeclampsia and 24 in eclampsia group were compared with 25 normal term antenatal women. Demographic profiles, hemodynamic parameters, laboratory markers for severity of PIH, and ultrasonographic OSND were measured. They were statistically analyzed and compared using one-way ANOVA and Tukey's test. Value of P surrogate marker for raised ICP in severe PIH patients. It is a rapid, bedside, noninvasive, and readily accessible tool and could be a part of a holistic approach for managing such patients.

  14. Metal balance shift induced in small fresh water fish by several environmental stresses

    International Nuclear Information System (INIS)

    Yukawa, Masae; Iso, Hiroyuki; Kodama, Kumiko; Imaseki, Hitoshi; Aoki, Kazuko; Ishikawa, Yuji

    2005-01-01

    Balance of essential elements in organisms might be changed by environmental stresses. Small fresh water fish, Medaka, was burdened with X-ray irradiation (total dose: 17 Gy), keeping in salty water (70% NaCl of sea water) and keeping in metal containing water (10 ppm of Cr and Co). These stresses are not lethal doses. Essential elements in liver, gall bladder, kidney, spleen, heart and brain in the stress-loaded fish were measured by PIXE method and compared with a control fish to determine the effect of the stresses. Various changes of the elemental contents were observed. Effect of X-ray irradiation was the smallest among the stresses. Relatively high content elements such as P, S, Cl and K were hardly affected with the stresses examined in this work. The effect of Cr on the metal balance seems to be larger than the other stresses. As PIXE method can analyze many elements in a small sample simultaneously, change of elemental distribution in small organisms induced by environmental stresses can be determined readily. (author)

  15. Extremely Severe Space Weather and Geomagnetically Induced Currents in Regions with Locally Heterogeneous Ground Resistivity

    Science.gov (United States)

    Fujita, Shigeru; Kataoka, Ryuho; Pulkkinen, Antti; Watari, Shinichi

    2016-01-01

    Large geomagnetically induced currents (GICs) triggered by extreme space weather events are now regarded as one of the serious natural threats to the modern electrified society. The risk is described in detail in High-Impact, Low-Frequency Event Risk, A Jointly-Commissioned Summary Report of the North American Electric Reliability Corporation and the US Department of Energy's November 2009 Workshop, June 2010. For example, the March 13-14,1989 storm caused a large-scale blackout affecting about 6 million people in Quebec, Canada, and resulting in substantial economic losses in Canada and the USA (Bolduc 2002). Therefore, European and North American nations have invested in GIC research such as the Solar Shield project in the USA (Pulkkinen et al. 2009, 2015a). In 2015, the Japanese government (Ministry of Economy, Trade and Industry, METI) acknowledged the importance of GIC research in Japan. After reviewing the serious damages caused by the 2011 Tohoku-Oki earthquake, METI recognized the potential risk to the electric power grid posed by extreme space weather. During extreme events, GICs can be concerning even in mid- and low-latitude countries and have become a global issue.

  16. Programmed cell death in Acanthamoeba castellanii Neff induced by several molecules present in olive leaf extracts.

    Directory of Open Access Journals (Sweden)

    Ines Sifaoui

    Full Text Available Therapy against Acanthamoeba infections such as Granulomatous Amoebic Encephalitis (GAE and Acanthamoeba Keratitis (AK, remains as an issue to be solved due to the existence of a cyst stage which is highly resistant to most chemical and physical agents. Recently, the activity of Olive Leaf Extracts (OLE was demonstrated against Acanthamoeba species. However, the molecules involved in this activity were not identified and/or evaluated. Therefore, the aim of this study was to evaluate the activity of the main molecules which are present in OLE and secondly to study their mechanism of action in Acanthamoeba. Among the tested molecules, the observed activities ranged from an IC50 of 6.59 in the case of apigenine to an IC50 > 100 μg/ml for other molecules. After that, elucidation of the mechanism of action of these molecules was evaluated by the detection of changes in the phosphatidylserine (PS exposure, the permeability of the plasma membrane, the mitochondrial membrane potential and the ATP levels in the treated cells. Vanillic, syringic and ursolic acids induced the higher permeabilization of the plasma membrane. Nevertheless, the mitochondrial membrane was altered by all tested molecules which were also able to decrease the ATP levels to less than 50% in IC90 treated cells after 24 h. Therefore, all the molecules tested in this study could be considered as a future therapeutic alternative against Acanthamoeba spp. Further studies are needed in order to establish the true potential of these molecules against these emerging opportunistic pathogenic protozoa.

  17. A Case of Nivolumab-Induced Severe Mononeuropathy Multiplex and Rhabdomyolysis

    Directory of Open Access Journals (Sweden)

    Katsuya Sakai

    2017-01-01

    Full Text Available We report an 81-year-old man with multiple liver metastases after tumorectomy for primary mediastinal malignant melanoma, who experienced limb weakness and sensory disturbance after nivolumab monotherapy. He was diagnosed with nivolumab-induced mononeuropathy multiplex and rhabdomyolysis based on serologic examination, muscle biopsy, magnetic resonance imaging of the limbs, and a nerve conduction study. A course of intravenous methylprednisolone (mPSL was initiated at 1 g/day for 3 days. After that, oral prednisolone (PSL was started at 1 mg/kg/day and gradually tapered. Limb muscle strength improved, but when PSL was reduced to 0.3 mg/kg/day, the weakness recurred, and a nerve conduction study showed exacerbation of mononeuropathy multiplex. The patient was again administered intravenous mPSL (0.5 g/day for 3 days followed by oral PSL at 0.5 mg/kg/day, and his neurological symptoms improved. Nivolumab, an immune checkpoint inhibitor, is used for the treatment of advanced melanoma and other cancers and causes various immune-related adverse events (irAEs. However, neurological irAEs related to nivolumab are rare. Furthermore, there are no reports of simultaneous nerve and muscle impairment. Unexpected irAEs affecting various organs should be recognized and treated appropriately.

  18. Severe riboflavin deficiency induces alterations in the hepatic proteome of starter Pekin ducks.

    Science.gov (United States)

    Tang, Jing; Hegeman, Maria A; Hu, Jian; Xie, Ming; Shi, Wenbiao; Jiang, Yong; de Boer, Vincent; Guo, Yuming; Hou, Shuisheng; Keijer, Jaap

    2017-11-01

    Suboptimal vitamin B2 status is encountered globally. Riboflavin deficiency depresses growth and results in a fatty liver. The underlying mechanisms remain to be established and an overview of molecular alterations is lacking. We investigated hepatic proteome changes induced by riboflavin deficiency to explain its effects on growth and hepatic lipid metabolism. In all, 360 1-d-old Pekin ducks were divided into three groups of 120 birds each, with twelve replicates and ten birds per replicate. For 21 d, the ducks were fed ad libitum a control diet (CAL), a riboflavin-deficient diet (RD) or were pair-fed with the control diet to the mean daily intake of the RD group (CPF). When comparing RD with CAL and CPF, growth depression, liver enlargement, liver lipid accumulation and enhanced liver SFA (C6 : 0, C12 : 0, C16 : 0, C18 : 0) were observed. In RD, thirty-two proteins were enhanced and thirty-one diminished (>1·5-fold) compared with CAL and CPF. Selected proteins were confirmed by Western blotting. The diminished proteins are mainly involved in fatty acid β-oxidation and the mitochondrial electron transport chain (ETC), whereas the enhanced proteins are mainly involved in TAG and cholesterol biosynthesis. RD causes liver lipid accumulation and growth depression probably by impairing fatty acid β-oxidation and ETC. These findings contribute to our understanding of the mechanisms of liver lipid metabolic disorders due to RD.

  19. Gastroprotective effects of several H2RAs on ibuprofen-induced gastric ulcer in rats.

    Science.gov (United States)

    Liu, Jing; Sun, Dan; He, Jinfeng; Yang, Chengli; Hu, Tingting; Zhang, Lijing; Cao, Hua; Tong, Ai-Ping; Song, Xiangrong; Xie, Yongmei; He, Gu; Guo, Gang; Luo, Youfu; Cheng, Ping; Zheng, Yu

    2016-03-15

    Ibuprofen is the first line of treatment for osteoarthritis and arthritis. The main side effects of ibuprofen especially in long-term treatment include gastric ulcer, duodenal ulcer and indigestion etc. Therefore, screening drugs with effective gastric protective effects and low toxicity for combination therapy with ibuprofen is necessary. The mechanism of gastric damage induced by ibuprofen is still unclear, however, cell damage caused by reactive oxygen species (ROS) is considered as the main reason. Preliminary screening of literature with the criteria of low toxicity led to four histamine-2 receptor antagonists (H2RAs): nizatidine, famotidine, lafutidine, and roxatidine acetate, which were selected for further investigation. These drugs were evaluated systemically by examining the gastric ulcer index, lipid peroxidation (LPO), membrane permeability, toxicity to main organs, and the influence on the activity of antioxidant enzymes, and myeloperoxidase (MPO). Nizatidine was found to be the best gastric protective agent. It exhibited excellent protective effect by increasing antioxidant enzyme activity, decreasing MPO activity, reducing LPO, and membrane permeability. Combination treatment with nizatidine and ibuprofen did not show any significant toxicity. Nizatidine was considered as a good option for combination therapy with ibuprofen especially for diseases that require long-term treatment such as arthritis and osteoarthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Effects of a multimodal exercise program on the functional capacity of Parkinson's disease patients considering disease severity and gender

    Directory of Open Access Journals (Sweden)

    Diego Orcioli-Silva

    2014-03-01

    Full Text Available The purpose of this study was to investigate the effects of a multimodal exercise program (MEP on the functional capacity of patients with Parkinson's disease (PD according to disease severity and gender. Fourteen patients with PD participated in the study and were distributed into groups according to 1 stage of disease and 2 gender. Functional capacity was evaluated before and after 6 months of intervention. The overall PD patient group improved their coordination and strength. Men and women improved in strength performance after exercise. Men also improved on coordination. For severity of disease, the unilateral group improved in strength, while the bilateral group improved in strength, balance, coordination and the UPDRS-functional score. In conclusion, a MEP is efficient in improving components of functional capacity in patients with PD, especially in strength. Gender may be considered in the exercise program. Individuals in the bilateral disease group appeared to benefit more from exercise.

  1. Family functioning in severe brain injuries: correlations with caregivers' burden, perceived social support and quality of life.

    Science.gov (United States)

    Tramonti, Francesco; Bonfiglio, Luca; Di Bernardo, Carolina; Ulivi, Chiara; Virgillito, Alessandra; Rossi, Bruno; Carboncini, Maria Chiara

    2015-01-01

    Severe brain injuries have long-term consequences on functional status and psychosocial functioning. Family life can be greatly influenced as well, and features of high caregiver burden can emerge. Although the data on caregivers' distress are constantly increasing, less information is available about the role of family functioning. Thirty caregivers of hospitalised patients with severe brain injuries received questionnaires for the evaluation of caregiver burden, family functioning and perceived social support. A semi-structured interview was performed for the evaluation of quality of life. Family cohesion and adaptability positively correlated with caregivers' quality of life and perceived social support. Partner caregivers' scores were significantly higher on the time-dependent burden than those of sons and daughters, whereas the latter scored higher on the emotional burden.

  2. Helicobacter pylori: a risk and severity factor of non-steroidal anti-inflammatory drug induced gastropathy.

    Science.gov (United States)

    Heresbach, D; Raoul, J L; Bretagne, J F; Minet, J; Donnio, P Y; Ramée, M P; Siproudhis, L; Gosselin, M

    1992-01-01

    This prospective study aimed to determine the prevalence of Helicobacter pylori infection in relation to the occurrence and severity of NSAIDs induced gastropathy. A total of 111 patients were studied-66 were taking NSAIDs and 45 were control patients. All patients underwent endoscopy during which antral biopsy specimens were taken to determine H pylori status (Gram and Giemsa staining, urease test, and cultures). The NSAID group comprised: group I, patients without mucosal damage (n = 28); group II, patients with gastropathy (n = 26); and group III, patients with bleeding associated with NSAID induced gastropathy (n = 12). Control patients had neither dyspeptic symptoms nor endoscopic lesions. There were no differences in age, sex ratio, or presence of H pylori (26% v 24%) between the NSAID and the control groups. Among patients taking NSAIDs, H pylori infection was more frequently (p gastropathy (groups II and III: 37%) than in those without lesions (group I: 11%). The frequency of H pylori infection increased significantly with the severity of gastropathy (group I = 11%; group II = 31%; group III = 50%; p NSAID induced gastropathy. PMID:1487160

  3. Low concentrations of zinc in gastric mucosa are associated with increased severity of Helicobacter pylori-induced inflammation.

    Science.gov (United States)

    Sempértegui, Fernando; Díaz, Myriam; Mejía, Ricardo; Rodríguez-Mora, Oswaldo G; Rentería, Edgar; Guarderas, Carlos; Estrella, Bertha; Recalde, Ramiro; Hamer, Davidson H; Reeves, Philip G

    2007-02-01

    Chronic Helicobacter pylori infection is the most common cause of gastric cancer. H. pylori induces oxidative stress while zinc deficiency results in increased sensitivity to it. In Ecuador, the prevalence of gastric cancer and zinc deficiency are high. We hypothesized that zinc deficiency in Ecuadorian people would cause increased H. pylori-induced inflammation in the gastric mucosa associated with lower tissue zinc concentrations. Three hundred and fifty-two patients with dyspepsia underwent endoscopy to obtain gastric mucosa biopsies. Diagnosis of H. pylori infection and its severity, histopathology, mucosal zinc concentration, and inflammation intensity were determined. H. pylori-infected patients with non-atrophic chronic gastritis had lower concentrations of zinc in gastric mucosa than uninfected patients with the same type of gastritis (251.3 +/- 225.3 vs. 426.2 +/- 279.9 ng/mg of protein; p = .016). Considering all patients, the more severe the H. pylori infection, the higher the percentage of subjects with infiltration by polymorphonuclear (PMN) cells (p = .0001). Patients with high PMN infiltration had lower mucosal zinc concentrations than patients with low PMN infiltration (35.2 +/- 20.7 vs. 242.9 +/- 191.8 ng/mg of protein; p = .021). The degree of inflammation in H. pylori-induced gastritis appears to be modulated by gastric tissue zinc concentrations.

  4. The limits of adaptation of functional protein synthesis to severe undernutrition

    International Nuclear Information System (INIS)

    Forrester, T.; Jahoor, F.; Reeds, P.

    1996-01-01

    This project was designed to investigate the limits of adaptation of protein metabolism in the stree of severe childhood malnutrition, representing as it does chronic dietary insufficiency of macronutrients and superimposed infection. The tasks included measurement of concentrations and rates of synthesis of nutrient transport proteins and hepatic acute phase proteins inseverely malnourished children during their acute illness and a recovery

  5. Solutions and Hope for Severe Behaviors: The Development of Functional Behavioral Assessment

    Science.gov (United States)

    DeLeon, Iser; Silverman, Wayne

    2008-01-01

    Severe behavior disorders are among the most perplexing conditions encountered by clinicians, and as a front page article in the past Christmas Day's "New York Times" illustrates ("Parents defend school's use of shock therapy"), treatment options remain a topic of contentious debate. Not all that long ago physical restraint was the only option,…

  6. Psychotic reactions to daily life stress and dopamine function in people with severe hearing impairment

    NARCIS (Netherlands)

    Gevonden, M. J.; Myin-Germeys, I.; van den Brink, W.; van Os, J.; Selten, J. P.; Booij, J.

    2015-01-01

    Minor stresses measured in daily life have repeatedly been associated with increased momentary psychotic experiences, both in individuals with psychotic disorders and in persons who are genetically at an increased risk for these disorders. Severe hearing impairment (SHI) is an environmental risk

  7. Visual impairments in people with severe and profound multiple disabilities: An inventory of visual functioning

    NARCIS (Netherlands)

    van den Broek, E.G.C.; Janssen, C.G.C.; van Ramshorst, T.; Deen, L.

    2006-01-01

    Background: The prevalence of visual impairments in people with severe and profound multiple disabilities (SPMD) is the subject of considerable debate and is difficult to assess. Methods: In a typical Dutch care organization, all clients with SPMD (n = 76) participated in the study and specific

  8. Hyperemic stenosis resistance index for evaluation of functional coronary lesion severity

    NARCIS (Netherlands)

    Meuwissen, Martijn; Siebes, Maria; Chamuleau, Steven A. J.; van Eck-Smit, Berthe L. F.; Koch, Karel T.; de Winter, Robbert J.; Tijssen, Jan G. P.; Spaan, Jos A. E.; Piek, Jan J.

    2002-01-01

    Background-Both coronary blood flow velocity reserve (CFVR) and myocardial fractional flow reserve (FFR) are used to evaluate the hemodynamic severity of coronary lesions. However, discordant results between CFVR and FFR have been observed in 25%, to 30% of intermediate coronary lesions. An index of

  9. Nicardipine-induced acute pulmonary edema: a rare but severe complication of tocolysis.

    Science.gov (United States)

    Serena, Claire; Begot, Emmanuelle; Cros, Jérôme; Hodler, Charles; Fedou, Anne Laure; Nathan-Denizot, Nathalie; Clavel, Marc

    2014-01-01

    We report four cases of acute pulmonary edema that occurred during treatment by intravenous tocolysis using nicardipine in pregnancy patients with no previous heart problems. Clinical severity justified hospitalization in intensive care unit (ICU) each time. Acute dyspnea has begun at an average of 63 hours after initiation of treatment. For all patients, the first diagnosis suspected was pulmonary embolism. The patients' condition improved rapidly with appropriate diuretic treatment and by modifying the tocolysis. The use of intravenous nicardipine is widely used for tocolysis in France even if its prescription does not have a marketing authorization. The pathophysiological mechanisms of this complication remain unclear. The main reported risk factors are spontaneous preterm labor, multiple pregnancy, concomitant obstetrical disease, association with beta-agonists, and fetal lung maturation corticotherapy. A better knowledge of this rare but serious adverse event should improve the management of patients. Nifedipine or atosiban, the efficiency of which tocolysis was also studied, could be an alternative.

  10. Quetiapine Induced Acute Dystonia in a patient with History of severe Head Injury

    Directory of Open Access Journals (Sweden)

    Robert G. Bota

    2010-01-01

    Full Text Available A patient with a history of severe head injury 10 years ago regained ability to walk after years of being bound to a wheelchair. During the last psychiatric hospitalization, quetiapine was increased to therapeutic dose using a normal titration. As a result the patient developed dystonia of multiple muscle groups requiring 4 days of hospitalization for remittance of symptoms. In this paper, we take a close look at the literature concerning extrapiramidal symptoms (EPS in this context, and we suggest that in patients with a history of head injury, it is warranted to consider a slower titration of antipsychotic medications, including ones that are considered having a lower risk of EPS such as quetiapine.

  11. Nicardipine-Induced Acute Pulmonary Edema: A Rare but Severe Complication of Tocolysis

    Directory of Open Access Journals (Sweden)

    Claire Serena

    2014-01-01

    Full Text Available We report four cases of acute pulmonary edema that occurred during treatment by intravenous tocolysis using nicardipine in pregnancy patients with no previous heart problems. Clinical severity justified hospitalization in intensive care unit (ICU each time. Acute dyspnea has begun at an average of 63 hours after initiation of treatment. For all patients, the first diagnosis suspected was pulmonary embolism. The patients' condition improved rapidly with appropriate diuretic treatment and by modifying the tocolysis. The use of intravenous nicardipine is widely used for tocolysis in France even if its prescription does not have a marketing authorization. The pathophysiological mechanisms of this complication remain unclear. The main reported risk factors are spontaneous preterm labor, multiple pregnancy, concomitant obstetrical disease, association with beta-agonists, and fetal lung maturation corticotherapy. A better knowledge of this rare but serious adverse event should improve the management of patients. Nifedipine or atosiban, the efficiency of which tocolysis was also studied, could be an alternative.

  12. Urinary C-terminal telopeptide of type II collagen, radiological severity, and functional assessment in knee osteoarthritis: are these related?

    Directory of Open Access Journals (Sweden)

    Hayam M Abdel Ghany

    2016-01-01

    Conclusion This study further confirms that urinary CTX-II is an index of early cartilage degradation in knee OA even before radiological changes occurs. The functional assessment using the WOMAC is an easy inexpensive method in reflecting cartilage degradation. Moreover, this work supports the lack of association between the functional status of knee OA patients assessed using the WOMAC and their radiological severity measured using the Kellgren-Lawrence grading scale.

  13. Surgical treatment is effective in severe cases of exercise-induced laryngeal obstruction: A follow-up study.

    Science.gov (United States)

    Norlander, Katarina; Johansson, Henrik; Jansson, Christer; Nordvall, Lennart; Nordang, Leif

    2015-01-01

    Surgery is an effective treatment in severe cases of supraglottic exercise-induced laryngeal obstruction (E-ILO). Conservatively treated subjects and subjects tested negative for E-ILO, who still experience breathing problems 1-3 years after diagnosis, tend to adjust their physical activity to a greater extent than surgically treated subjects. To investigate how symptoms and level of physical activity change over time in patients with E-ILO who have undergone surgery, patients with E-ILO treated conservatively and patients who tested negative for laryngeal obstruction at continuous laryngoscopy exercise-test (CLE-test). Patients referred for exercise-induced breathing difficulties answered questionnaires at diagnostic CLE-test and at follow-up. Questions regarded exercise-induced breathing problems, current physical activity level, and medical history of asthma and perennial allergy. Out of 84 invited subjects, 59 (70%) answered both questionnaires. Surgically treated subjects had less breathing problems at follow-up compared with conservatively treated subjects and subjects who tested negative (p < 0.001). None of the surgically treated subjects were less physically active or had changed sport due to exercise-induced dyspnoea, whereas 41.7% of the conservatively treated subjects had made such adjustments (p < 0.001).

  14. Initial effect of enalapril on kidney function in patients with moderate to severe chronic nephropathy

    DEFF Research Database (Denmark)

    Kamper, A L; Thomsen, H S; Nielsen, S L

    1990-01-01

    in their renal function. Thirty-one patients were studied, 26 on chronic antihypertensive treatment with drugs other than ACE inhibitors and 5 untreated normotensive. 51Cr-EDTA plasma clearance and renal technetium-99m dimercaptosuccinic acid (99mTc-DMSA) scintigraphy were made before and 24 h after start...

  15. Function assertive community treatment (FACT) and psychiatric service use in patients diagnosed with severe mental illness

    NARCIS (Netherlands)

    Drukker, M.; van Os, J.; Sytema, S.; Driessen, G.; Visser, E.; Delespaul, Ph.

    Aim. Previous work suggests that the Dutch variant of assertive community treatment (ACT), known as Function ACT (FACT), may be effective in increasing symptomatic remission rates when replacing a system of hospital-based care and separate community-based facilities. FACT guidelines propose a

  16. Pharmacokinetics and pharmacodynamics of candesartan cilexetil in patients with normal to severely impaired renal function

    NARCIS (Netherlands)

    Buter, H; Navis, GY; Woittiez, AJJ; de Zeeuw, D; de Jong, PE

    Objective: We studied the pharmacokinetics and pharmacodynamics of single and multiple doses of candesartan cilexetil 8 mg per day in hypertensive patients with different degrees of renal function impairment. Candesartan is an angiotensin II subtype I (AT1) receptor antagonist that is administered

  17. Chronic fatigue syndrome: illness severity, sedentary lifestyle, blood volume and evidence of diminished cardiac function.

    Science.gov (United States)

    Hurwitz, Barry E; Coryell, Virginia T; Parker, Meela; Martin, Pedro; Laperriere, Arthur; Klimas, Nancy G; Sfakianakis, George N; Bilsker, Martin S

    2009-10-19

    The study examined whether deficits in cardiac output and blood volume in a CFS (chronic fatigue syndrome) cohort were present and linked to illness severity and sedentary lifestyle. Follow-up analyses assessed whether differences in cardiac output levels between CFS and control groups were corrected by controlling for cardiac contractility and TBV (total blood volume). The 146 participants were subdivided into two CFS groups based on symptom severity data, severe (n=30) and non-severe (n=26), and two healthy non-CFS control groups based on physical activity, sedentary (n=58) and non-sedentary (n=32). Controls were matched to CFS participants using age, gender, ethnicity and body mass. Echocardiographic measures indicated that the severe CFS participants had 10.2% lower cardiac volume (i.e. stroke index and end-diastolic volume) and 25.1% lower contractility (velocity of circumferential shortening corrected by heart rate) than the control groups. Dual tag blood volume assessments indicated that the CFS groups had lower TBV, PV (plasma volume) and RBCV (red blood cell volume) than control groups. Of the CFS subjects with a TBV deficit (i.e. > or = 8% below ideal levels), the mean+/-S.D. percentage deficit in TBV, PV and RBCV were -15.4+/-4.0, -13.2+/-5.0 and -19.1+/-6.3% respectively. Lower cardiac volume levels in CFS were substantially corrected by controlling for prevailing TBV deficits, but were not affected by controlling for cardiac contractility levels. Analyses indicated that the TBV deficit explained 91-94% of the group differences in cardiac volume indices. Group differences in cardiac structure were offsetting and, hence, no differences emerged for left ventricular mass index. Therefore the findings indicate that lower cardiac volume levels, displayed primarily by subjects with severe CFS, were not linked to diminished cardiac contractility levels, but were probably a consequence of a co-morbid hypovolaemic condition. Further study is needed to address

  18. Hepatobiliary function assessed by 99mTc-mebrofenin cholescintigraphy in the evaluation of severity of steatosis in a rat model

    International Nuclear Information System (INIS)

    Vetelaeinen, Reeta L.; Vliet, Arlene van; Gulik, Thomas M. van; Bennink, Roelof J.; Bruin, Kora de

    2006-01-01

    This study evaluated the utility of non-invasive assessment of hepatobiliary function by 99m Tc-mebrofenin cholescintigraphy in a rat model of diet-induced steatosis. Male Wistar rats (250-300 g) were fed a standard methionine- and choline-deficient (MCD) diet for up to 5 weeks, thereby inducing hepatic fat accumulation, progressive inflammation and fibrogenesis corresponding with clinical steatosis. 99m Tc-mebrofenin pinhole scintigraphy was used to evaluate the hepatocyte mebrofenin uptake rate, the time of maximum hepatic uptake (T peak ) and the time required for peak activity to decrease by 50% (T 1/2peak ). Scintigraphic parameters were correlated with biochemical and serological parameters and with liver histopathology. MCD diet induced mild steatosis after 1 week and severe steatosis with prominent inflammation after 5 weeks. T peak , T 1/2peak prolonged and the uptake rate decreased significantly, while the severity of steatosis increased (p 99m Tc-mebrofenin uptake rate (r 2 =0.83, p 2 =0.82, p 2 =0.72, p 2 =0.52, p=0.001, respectively). The correlation of the uptake rate with hepatocellular damage was weak (AST and ALT, r 2 =0.29 and 0.32, respectively), but correlation with synthetic function was strong (prothrombin time, r 2 =0.70, p 99m Tc-mebrofenin scintigraphy correlates with the extent and progression of steatosis. These results suggest a potential role for mebrofenin scintigraphy as a non-invasive functional follow-up method for disease progression in steatotic patients. (orig.)

  19. [Objective assessment of the functional impact of dry eye severity on the quality of vision by double-pass aberrometry].

    Science.gov (United States)

    Habay, T; Majzoub, S; Perrault, O; Rousseau, C; Pisella, P J

    2014-03-01

    To assess the functional impact of the severity of dry eye on the quality of vision by measuring an Objective Scatter Index (OSI) using double pass aberrometry. Twenty-eight patients (56 eyes) with dry eye syndromes of varying severity participated in this study. A double-pass aberrometer was used to measure the dynamic changes in the OSI for 20 seconds. The mean and standard deviations of the OSI and the number of blinks occurring during the examination were compared as a function of the clinical severity of dry eye disease. The mean OSI increased with the severity of dry eye syndrome with a significant difference for stages 3 (P0.8) or visual acuity (P>0.2). Standard deviation of the OSI also increased with the severity of dry eye disease, with a significant difference for stages 3 (P0.2). The values of the OSI standard deviation represented the dynamic nature of aberrometric changes related to the instability of the tear film. Quality of vision of patients deteriorated in relation to the severity of their dry eye. The analysis of OSI standard deviation appears to be an objective way to assess the intensity of subjective visual disturbances reported by patients with dry eye syndrome. It also provides a new tool to assess the severity of damage to the ocular surface. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  20. Pattern of retinal morphological and functional decay in a light-inducible, rhodopsin mutant mouse.

    Science.gov (United States)

    Gargini, Claudia; Novelli, Elena; Piano, Ilaria; Biagioni, Martina; Strettoi, Enrica

    2017-07-18

    Hallmarks of Retinitis Pigmentosa (RP), a family of genetic diseases, are a typical rod-cone-degeneration with initial night blindness and loss of peripheral vision, followed by decreased daylight sight and progressive visual acuity loss up to legal blindness. Great heterogeneity in nature and function of mutated genes, variety of mutations for each of them, variability in phenotypic appearance and transmission modality contribute to make RP a still incurable disease. Translational research relies on appropriate animal models mimicking the genetic and phenotypic diversity of the human pathology. Here, we provide a systematic, morphological and functional analysis of Rho Tvrm4 /Rho + rhodopsin mutant mice, originally described in 2010 and portraying several features of common forms of autosomal dominant RP caused by gain-of-function mutations. These mice undergo photoreceptor degeneration only when exposed briefly to strong, white light and allow controlled timing of induction of rod and cone death, which therefore can be elicited in adult animals, as observed in human RP. The option to control severity and retinal extent of the phenotype by regulating intensity and duration of the inducing light opens possibilities to exploit this model for multiple experimental purposes. Altogether, the unique features of this mutant make it an excellent resource for retinal degeneration research.

  1. Severe Corticosteroid-Induced Ocular Hypertension Requiring Bilateral Trabeculectomies in a Patient with Takayasu’s Arteritis

    Directory of Open Access Journals (Sweden)

    Anna Maria Gruener

    2016-01-01

    Full Text Available We present a rare case of severe corticosteroid-induced ocular hypertension (OHT after prolonged systemic corticosteroid use in a young woman with Takayasu’s arteritis. As she did not sufficiently respond to ocular antihypertensive therapies, bilateral enhanced trabeculectomies were required to normalize her intraocular pressures. The systemic side effects of corticosteroids are well known, yet steroid-induced OHT and glaucoma remain silent causes of ocular morbidity. This case highlights the importance of IOP-monitoring in visually asymptomatic patients on systemic corticosteroids. It further emphasizes the need to raise awareness of the potential ocular side effects of steroids amongst physicians, in particular those looking after patients with autoimmune and inflammatory diseases.

  2. Study on confinement function of reactor containment during late phase severe accident

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-08-15

    During a severe accident reactor containment integrity is maintained by accident management. However, gas leakage from containment is inevitable after the severe accident. A large amount of hydrogen and rare gases are produced due to core damage or melting. These non-condensable gases cause the containment pressure much higher than atmospheric pressure even after residual heat removal system recovery especially for BWR with smaller containment volume. Besides, iodine confined in water pool is re-evaporated under radiation field. The present study consists of realistic evaluation of fission products source term inside containment, quantitative evaluation of iodine re-evaporation effect and the experimental study of hydrogen treatment in BWR using ammonia production method by catalyst. Activities in fiscal year 2012 are that modification of MELCOR fission product chemical model was done and verified by experimental data, and that effects of CsI on ammonia production rate for Ru catalyst were conducted. (author)

  3. The association of functional oral intake and pneumonia in patients with severe Traumatic Brain Injury

    DEFF Research Database (Denmark)

    Schow, Trine; Larsen, Klaus; Engberg, Aase Worså

    Abstract Objective(s): This study investigates the incidence and onset time of pneumonia for patients with severe Traumatic Brain Injury (TBI) in the early phase of rehabilitation, and identifies parameters associated with the risk of pneumonia. Design: Observational retrospective cohort study....... Setting: A subacute rehabilitation department, university hospital, Denmark. Participants: One-hundred and seventy-three patients aged 16-65 years with severe TBI admitted over a 5-year period. Patients are transferred to the Brain Injury Unit (BIU) as soon as they ventilate spontaneously. Intervention......: None Main Outcome Measure(s): Pneumonia. Results: Twenty-seven percent (27%) of the patients admitted to the BIU were in treatment for pneumonia and 12% developed pneumonia during rehabilitation, all but one within 19 days of admission. Of these patients, 81% received nothing by mouth. Three factors...

  4. A functional analysis of photo-object matching skills of severely retarded adolescents.

    OpenAIRE

    Dixon, L S

    1981-01-01

    Matching-to-sample procedures were used to assess picture representation skills of severely retarded, nonverbal adolescents. Identity matching within the classes of objects and life-size, full-color photos of the objects was first used to assess visual discrimination, a necessary condition for picture representation. Picture representation was then assessed through photo-object matching tasks. Five students demonstrated visual discrimination (identity matching) within the two classes of photo...

  5. Short-range order clustering in BCC Fe-Mn alloys induced by severe plastic deformation

    Science.gov (United States)

    Shabashov, V. A.; Kozlov, K. A.; Sagaradze, V. V.; Nikolaev, A. L.; Lyashkov, K. A.; Semyonkin, V. A.; Voronin, V. I.

    2018-03-01

    The effect of severe plastic deformation, namely, high-pressure torsion (HPT) at different temperatures and ball milling (BM) at different time intervals, has been investigated by means of Mössbauer spectroscopy in Fe100-xMnx (x = 4.1, 6.8, 9) alloys. Deformation affects the short-range clustering (SRC) in BCC lattice. Two processes occur: destruction of SRC by moving dislocations and enhancement of the SRC by migration of non-equilibrium defects. Destruction of SRC prevails during HPT at 80-293 K; whereas enhancement of SRC dominates at 473-573 K. BM starts enhancing the SRC formation at as low as 293 K due to local heating at impacts. The efficiency of HPT in terms of enhancing SRC increases with increasing temperature. The authors suppose that at low temperatures, a significant fraction of vacancies are excluded from enhancing SRC because of formation of mobile bi- and tri-vacancies having low efficiency of enhancing SRC as compared to that of mono vacancies. Milling of BCC Fe100-xMnx alloys stabilises the BCC phase with respect to α → γ transition at subsequent isothermal annealing because of a high degree of work hardening and formation of composition inhomogeneity.

  6. Clozapine-induced severe eosinophilia: report of a case with good outcome

    Directory of Open Access Journals (Sweden)

    Carla R. B. Marcelino

    2013-09-01

    Full Text Available INTRODUCTION: Clozapine is the antipsychotic of choice in the treatment of refractory schizophrenia. However, its side effects, such as eosinophilia, may preclude its use. METHODS: Case report and literature review. RESULTS: Young woman, 19 years old, diagnosed with hebefrenic schizophrenia, admitted at Unicamp's psychiatry ward after psychotic symptoms relapse. Clozapine was started after unsuccessful attempts with risperidon and olanzapine. By the fourth week of clozapine use, eosinophils began to increase. Drug titration was stopped, but eosinophils counts continued to rise up, reaching the mark of 5200/mm³. Due to severity of psychotic symptoms and to the good response obtained with clozapine, we decided to investigate organs involvement before withdrawing the medication. As the patient had no organs involvement, clozapine was maintained and one month after eosinophils peak, it was already normalized. CONCLUSION: Eosinophilia should not necessarily lead to clozapine's withdrawal. Patients who present eosinophilia must be at rigorous observation for organs involvement, and if there is no such involvement, clozapine might be maintained, considering the possible benign and transitory nature of the eosinophils count elevation.

  7. Structural and Functional Analyses of the Severe Acute Respiratory Syndrome Coronavirus Endoribonuclease Nsp15

    Energy Technology Data Exchange (ETDEWEB)

    Bhardwaj, Kanchan; Palaninathan, Satheesh; Alcantara, Joanna Maria Ortiz; Yi, Lillian Li; Guarino, Linda; Sacchettini, James C.; Kao, C. Cheng (TAM)

    2008-03-31

    The severe acute respiratory syndrome (SARS) coronavirus encodes several RNA-processing enzymes that are unusual for RNA viruses, including Nsp15 (nonstructural protein 15), a hexameric endoribonuclease that preferentially cleaves 3' of uridines. We solved the structure of a catalytically inactive mutant version of Nsp15, which was crystallized as a hexamer. The structure contains unreported flexibility in the active site of each subunit. Substitutions in the active site residues serine 293 and proline 343 allowed Nsp15 to cleave at cytidylate, whereas mutation of leucine 345 rendered Nsp15 able to cleave at purines as well as pyrimidines. Mutations that targeted the residues involved in subunit interactions generally resulted in the formation of catalytically inactive monomers. The RNA-binding residues were mapped by a method linking reversible cross-linking, RNA affinity purification, and peptide fingerprinting. Alanine substitution of several residues in the RNA-contacting portion of Nsp15 did not affect hexamer formation but decreased the affinity of RNA binding and reduced endonuclease activity. This suggests a model for Nsp15 hexamer interaction with RNA.

  8. Severe, multimodal stress exposure induces PTSD-like characteristics in a mouse model of single prolonged stress.

    Science.gov (United States)

    Perrine, Shane A; Eagle, Andrew L; George, Sophie A; Mulo, Kostika; Kohler, Robert J; Gerard, Justin; Harutyunyan, Arman; Hool, Steven M; Susick, Laura L; Schneider, Brandy L; Ghoddoussi, Farhad; Galloway, Matthew P; Liberzon, Israel; Conti, Alana C

    2016-04-15

    Appropriate animal models of posttraumatic stress disorder (PTSD) are needed because human studies remain limited in their ability to probe the underlying neurobiology of PTSD. Although the single prolonged stress (SPS) model is an established rat model of PTSD, the development of a similarly-validated mouse model emphasizes the benefits and cross-species utility of rodent PTSD models and offers unique methodological advantages to that of the rat. Therefore, the aims of this study were to develop and describe a SPS model for mice and to provide data that support current mechanisms relevant to PTSD. The mouse single prolonged stress (mSPS) paradigm, involves exposing C57Bl/6 mice to a series of severe, multimodal stressors, including 2h restraint, 10 min group forced swim, exposure to soiled rat bedding scent, and exposure to ether until unconsciousness. Following a 7-day undisturbed period, mice were tested for cue-induced fear behavior, effects of paroxetine on cue-induced fear behavior, extinction retention of a previously extinguished fear memory, dexamethasone suppression of corticosterone (CORT) response, dorsal hippocampal glucocorticoid receptor protein and mRNA expression, and prefrontal cortex glutamate levels. Exposure to mSPS enhanced cue-induced fear, which was attenuated by oral paroxetine treatment. mSPS also disrupted extinction retention, enhanced suppression of stress-induced CORT response, increased mRNA expression of dorsal hippocampal glucocorticoid receptors and decreased prefrontal cortex glutamate levels. These data suggest that the mSPS model is a translationally-relevant model for future PTSD research with strong face, construct, and predictive validity. In summary, mSPS models characteristics relevant to PTSD and this severe, multimodal stress modifies fear learning in mice that coincides with changes in the hypothalamo-pituitary-adrenal (HPA) axis, brain glucocorticoid systems, and glutamatergic signaling in the prefrontal cortex

  9. Mindful creativity matters: trajectories of reported functioning after severe traumatic brain injury as a function of mindful creativity in patients' relatives: a multilevel analysis.

    Science.gov (United States)

    Haller, Chiara S; Bosma, Colin M; Kapur, Kush; Zafonte, Ross; Langer, Ellen J

    2017-04-01

    The objective of the present investigation was to examine the association of mindful creativity with the trajectory of recovery (emotional, interpersonal, cognitive, and total functioning) of patients with severe TBI. This was drawn from a subsample of an adult prospective cohort study on severe TBI in Switzerland; patients and their relatives were assessed at 3, 6, and 12 months (patients N = 176, relatives N = 176). Predictor measures were assessed using Mindful Creativity Scale-short form and time (trajectory of functioning of the patient over time). Outcome measures were assessed using Patient Competency Rating Scale for Neuro-rehabilitation (PCRS-NR; measuring emotional, interpersonal, cognitive, and total functioning post-injury). All measures were assessed at each time point. Mixed linear models were run separately for ages >50 and ≤50 (i.e., bimodal distribution). Patients' mindful creativity showed no significant association with patients' functioning across time in any of the models. In all age groups, interpersonal functioning decreased across time (slope >50  = -4.66, p = .037; slope ≤50  = -7.19, p = .007). Interestingly, in age group ≤50, interpersonal functioning increased when looking at relative mindful creativity by time (slope = 1.69, p = .005). Additionally, relatives mindful creativity was significantly associated with patients' functioning in age group ≤50: (a) patients' total functioning (slope = 0.18, p = .03) and (b) cognitive functioning (slope = 0.72, p = .020). Relatives' mindful creativity was significantly associated with patients' functioning after severe TBI. Implications for treatment and future research are discussed.

  10. Moderate and severe perinatal asphyxia induces differential effects on cocaine sensitization in adult rats.

    Science.gov (United States)

    Galeano, Pablo; Romero, Juan Ignacio; Luque-Rojas, María Jesús; Suárez, Juan; Holubiec, Mariana Inés; Bisagno, Verónica; Santín, Luis Javier; De Fonseca, Fernando Rodríguez; Capani, Francisco; Blanco, Eduardo

    2013-09-01

    Perinatal asphyxia (PA) increases the likelihood of suffering from dopamine-related disorders, such as ADHD and schizophrenia. Since dopaminergic transmission plays a major role in cocaine sensitization, the purpose of this study was to determine whether PA could be associated with altered behavioral sensitization to cocaine. To this end, adult rats born vaginally (CTL), by caesarean section (C+), or by C+ with 15 min (PA15, moderate PA) or 19 min (PA19, severe PA) of global anoxia were repeatedly administered with cocaine (i.p., 15 mg/kg) and then challenged with cocaine (i.p., 15 mg/kg) after a 5-day withdrawal period. In addition, c-Fos, FosB/ΔFosB, DAT, and TH expression were assessed in dorsal (CPu) and ventral (NAcc) striatum. Results indicated that PA15 rats exhibited an increased locomotor sensitization to cocaine, while PA19 rats displayed an abnormal acquisition of locomotor sensitization and did not express a sensitized response to cocaine. c-Fos expression in NAcc, but not in CPu, was associated with these alterations in cocaine sensitization. FosB/ΔFosB expression was increased in all groups and regions after repeated cocaine administration, although it reached lower expression levels in PA19 rats. In CTL, C+, and PA15, but not in PA19 rats, the expression of TH in NAcc was reduced in groups repeatedly treated with cocaine, independently of the challenge test. Furthermore, this reduction was more pronounced in PA15 rats. DAT expression remained unaltered in all groups and regions studied. These results suggest that moderate PA may increase the vulnerability to drug abuse and in particular to cocaine addiction. Copyright © 2013 Wiley Periodicals, Inc.

  11. Low Tidal Volume Reduces Lung Inflammation Induced by Liquid Ventilation in Piglets With Severe Lung Injury.

    Science.gov (United States)

    Jiang, Lijun; Feng, Huizhen; Chen, Xiaofan; Liang, Kaifeng; Ni, Chengyao

    2017-05-01

    Total liquid ventilation (TLV) is an alternative treatment for severe lung injury. High tidal volume is usually required for TLV to maintain adequate CO 2 clearance. However, high tidal volume may cause alveolar barotrauma. We aim to investigate the effect of low tidal volume on pulmonary inflammation in piglets with lung injury and under TLV. After the establishment of acute lung injury model by infusing lipopolysaccharide, 12 piglets were randomly divided into two groups, TLV with high tidal volume (25 mL/kg) or with low tidal volume (6 mL/kg) for 240 min, respectively. Extracorporeal CO 2 removal was applied in low tidal volume group to improve CO 2 clearance and in high tidal volume group as sham control. Gas exchange and hemodynamic status were monitored every 30 min during TLV. At the end of the study, pulmonary mRNA expression and plasmatic concentration of interleukin-6 (IL-6) and interleukin-8 (IL-8) were measured by collecting lung tissue and blood samples from piglets. Arterial blood pressure, PaO 2 , and PaCO 2 showed no remarkable difference between groups during the observation period. Compared with high tidal volume strategy, low tidal volume resulted in 76% reduction of minute volume and over 80% reduction in peak inspiratory pressure during TLV. In addition, low tidal volume significantly diminished pulmonary mRNA expression and plasmatic level of IL-6 and IL-8. We conclude that during TLV, low tidal volume reduces lung inflammation in piglets with acute lung injury without compromising gas exchange. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  12. Imatinib induced severe skin reactions and neutropenia in a patient with gastrointestinal stromal tumor

    International Nuclear Information System (INIS)

    Hwang, Jun-Eul; Yoon, Ju-Young; Bae, Woo-Kyun; Shim, Hyun-Jeong; Cho, Sang-Hee; Chung, Ik-Joo

    2010-01-01

    Imatinib mesylate has been used for the treatment of unresectable or metastatic gastrointestinal stromal tumors (GIST). The current recommended dose of imatinib is 400 mg/day that is increased to 800 mg/day in cases with disease progression. However, imatinib can be associated with diverse adverse events, which has limited its use. We report a case of severe adverse skin reactions with neutropenic fever during imatinib treatment in a patient with GIST. A 71-year-old man was admitted with a one month history of epigastric pain and a palpable mass in the right upper quadrant. An abdominal CT scan revealed a 20 × 19 cm intraabdominal mass with tumor invasion into the peritoneum. Needle biopsy was performed and the results showed spindle shaped tumor cells that were positive for c-KIT. The patient was diagnosed with unresectable GIST. Imatinib 400 mg/day was started. The patient tolerated the first eight weeks of treatment. However, about three months later, the patient developed a grade 4 febrile neutropenia and a grade 3 exfoliative skin rash. The patient recovered from this serious adverse events after discontinuation of imatinib with supportive care. However, the skin lesions recurred whenever the patient received imatinib over 100 mg/day. Therefore, imatinib 100 mg/day was maintained. Despite the low dose imatinib, follow up CT showed a marked partial response without grade 3 or 4 toxicities. The recommended dose of imatinib for the treatment of GIST is 400 mg/day but patients at risk for adverse drug reaction may benefit from lower doses. Individualized treatment is needed for such patients, and we may also try sunitinib as a alternative drug

  13. Effect of doxycycline vs placebo on retinal function and diabetic retinopathy progression in patients with severe nonproliferative or non-high-risk proliferative diabetic retinopathy

    DEFF Research Database (Denmark)

    Scott, Ingrid U; Jackson, Gregory R; Quillen, David A

    2014-01-01

    IMPORTANCE: Inflammation may contribute to the pathogenesis of diabetic retinopathy (DR). OBJECTIVES: To investigate, in a proof-of-concept clinical trial, whether low-dose oral doxycycline monohydrate can (1) slow the deterioration of, or improve, retinal function or (2) induce regression or slow......: We conducted a randomized, double-masked, 24-month proof-of-concept clinical trial. Thirty patients (from hospital-based retina practices) with 1 or more eyes with severe NPDR or PDR less than Early Treatment Diabetic Retinopathy Study-defined high-risk PDR. INTERVENTIONS: Patients were randomized...... adaptation, visual acuity, and quality of life) and anatomic factors (Early Treatment Diabetic Retinopathy Study DR severity level, area of retinal thickening, central macular thickness, macular volume, and retinal vessel diameters). RESULTS: From baseline to month 24, mean FDP foveal sensitivity decreased...

  14. Gastric emptying of water in children with severe functional fecal retention

    Directory of Open Access Journals (Sweden)

    V.P.I. Fernandes

    Full Text Available The objective of this study was to evaluate gastric emptying (GE in pediatric patients with functional constipation. GE delay has been reported in adults with functional constipation. Gastric emptying studies were performed in 22 children with chronic constipation, fecal retention and fecal incontinence, while presenting fecal retention and after resuming regular bowel movements. Patients (18 boys, median age: 10 years; range: 7.2 to 12.7 years were evaluated in a tertiary pediatric gastroenterology clinic. Gastric half-emptying time of water (reference range: 12 ± 3 min was measured using a radionuclide technique immediately after first patient evaluation, when they presented fecal impaction (GE1, and when they achieved regular bowel movements (GE2, 12 ± 5 weeks after GE1. At study admission, 21 patients had reported dyspeptic symptoms, which were completely relieved after resuming regular bowel movements. Medians (and interquartile ranges for GE1 and GE2 were not significantly different [27.0 (16 and 27.5 (21 min, respectively (P = 0.10]. Delayed GE seems to be a common feature among children with chronic constipation and fecal retention. Resuming satisfactory bowel function and improvement in dyspeptic symptoms did not result in normalization of GE data.

  15. Early morphological and functional changes in pancreas following necrosectomy for acute severe necrotizing pancreatitis.

    Science.gov (United States)

    Bavare, Charudatta; Prabhu, Ramkrishna; Supe, Avinash

    2004-01-01

    Morphological and functional changes in the pancreas after surgical pancreatic necrosectomy have not been studied extensively. To study morphological changes in the pancreas, and exocrine and endocrine pancreatic function following pancreatic necrosectomy. Eighteen adult patients surviving at least one month after pancreatic necrosectomy for acute necrotizing pancreatitis were followed up. Contrast-enhanced computed tomography was done every six months. Stool fat was estimated at 3-month intervals, and need for and response to enzyme supplements were recorded. Blood sugar was measured every fortnight; in patients with hyperglycemia, need for oral hypoglycemic agents or insulin was recorded. Additional pancreatic imaging was done in some cases. Six weeks after surgery, nine of 18 patients had exocrine insufficiency. Thirteen patients developed endocrine insufficiency, including 5 who also had exocrine insufficiency. At the end of the study, 13 patients had endocrine insufficiency and 2 had exocrine insufficiency. Pancreatic size was subnormal in all patients at the end of six months. Pancreatography in three cases did not reveal any ductal abnormality. Necrotizing pancreatitis affects pancreatic exocrine or endocrine function in more than half the patients.

  16. Compromised neutrophil function and severe bovine E.coli mastitis: is C5a the missing link?

    Science.gov (United States)

    Around the periparturient period and during early lactation dairy cows have an elevated risk for clinical mastitis. The severity of Gram-negative infections during these periods has been correlated with reduced neutrophil functions. In this review we focus on the potential role of C5a in the develop...

  17. Psychometric Evaluation of the Symptoms and Functioning Severity Scale (SFSS) Short Forms with Out-of-Home Care Youth

    Science.gov (United States)

    Gross, Thomas J.; Duppong Hurley, Kristin; Lambert, Matthew C.; Epstein, Michael H.; Stevens, Amy L.

    2015-01-01

    Background: There is a need for brief progress monitoring measures of behavioral and emotional symptoms for youth in out-of-home care. The Symptoms and Functioning Severity Scale (SFSS; Bickman et al. in Manual of the peabody treatment progress battery. Vanderbilt University, Nashville, 2010) is one measure that has clinician and youth short forms…

  18. Early endocrine alterations reflect prolonged stress and relate to one year functional outcome in patients with severe brain injury

    DEFF Research Database (Denmark)

    Marina, Djordje; Klose, Marianne; Nordenbo, Annette

    2015-01-01

    OBJECTIVE: Severe brain injury poses a risk of developing acute and chronic hypopituitarism. Pituitary hormone alterations developed in the early recovery phase after brain injury may have implications for long-term functional recovery. The objective was to assess the pattern and prevalence...

  19. Hydraulic Function in Australian Tree Species during Drought-Induced Mortality

    Science.gov (United States)

    Tissue, D.; Maier, C.; Creek, D.; Choat, B.

    2016-12-01

    Drought induced tree mortality and decline are key issues facing forest ecology and management. Here, we primarily investigated the hydraulic limitations underpinning drought-induced mortality in three Australian tree species. Using field-based large rainout shelters, three angiosperm species (Casuarina cunninghamiana, Eucalyptus sideroxylon, Eucalyptus tereticornis) were subjected to two successive drought and recovery cycles, prior to a subsequent long and extreme drought to mortality; total duration of experiment was 2.5 years. Leaf gas exchange, leaf and stem hydraulics, and carbon reserves were monitored during the experiment. Trees died as a result of failure in the hydraulic transport system, primarily related to water stress induced embolism. Stomatal closure occurred prior to the induction of significant embolism in the stem xylem of all species. Nonetheless, trees suffered a rapid decline in xylem water potential and increase in embolism during the severe drought treatment. Trees died at water potentials causing greater than 90% loss of hydraulic conductivity in the stem, providing support for the theory that lethal water potential is correlated with complete loss of hydraulic function in the stem xylem of angiosperms.

  20. Lactose Induces Phenotypic and Functional Changes of Neutrophils and Macrophages to Alleviate Acute Pancreatitis in Mice

    Directory of Open Access Journals (Sweden)

    Li-Long Pan

    2018-04-01

    Full Text Available Acute pancreatitis (AP is one common clinical acute abdominal disease, for which specific pharmacological or nutritional therapies remain elusive. Lactose, a macronutrient and an inducer of host innate immune responses, possesses immune modulatory functions. The current study aimed to investigate potential modulatory effects of lactose and the interplay between the nutrient and pancreatic immunity during experimentally induced AP in mice. We found that either prophylactic or therapeutic treatment of lactose time-dependently reduced the severity of AP, as evidenced by reduced pancreatic edema, serum amylase levels, and pancreatic myeloperoxidase activities, as well as by histological examination of pancreatic damage. Overall, lactose promoted a regulatory cytokine milieu in the pancreas and reduced infiltration of inflammatory neutrophils and macrophages. On acinar cells, lactose was able to suppress caerulein-induced inflammatory signaling pathways and to suppress chemoattractant tumor necrosis factor (TNF-α and monocyte chemotactic protein-1 production. Additionally, lactose acted on pancreas-infiltrated macrophages, increasing interleukin-10 and decreasing tumor necrosis factor alpha production. Notably, lactose treatment reversed AP-associated infiltration of activated neutrophils. Last, the effect of lactose on neutrophil infiltration was mimicked by a galectin-3 antagonist, suggesting a potential endogenous target of lactose. Together, the current study demonstrates an immune regulatory effect of lactose to alleviate AP and suggests its potential as a convenient, value-added therapeutic macronutrient to control AP, and lower the risk of its systemic complications.

  1. Communication subjective assessments of patients undergoing compulsory treatment with the severity of negative symptoms and cognitive functioning level

    Directory of Open Access Journals (Sweden)

    Kabanov T.N.

    2015-04-01

    Full Text Available The article presents the results of studies on the relationship of subjective assessments of the mentally ill with the severity of negative symptoms and cognitive functioning level. The features of patients perception of various aspects of compulsory treatment and subjective satisfaction with treatment. In a study of 94 male patients with a diagnosis of organic mental disorder and schizophrenia was used diagnostic system, consisting of patopsihologicheskogo study, formal survey map, the scale of assessment of negative symptoms SANS, questionnaire symptom levels SCL-90, self-existing problems, as well as - in Test authoring tool sheet to treatment and hospital stay (VG Bulygin, Kabanov, TN, 2011. The differences in subjective assessments of aspects of compulsory treatment and social functioning of patients with varying degrees of severity of negative symptoms and dependence of subjective assessments of the level of cognitive functioning.

  2. "Fire Moss" Cover and Function in Severely Burned Forests of the Western United States

    Science.gov (United States)

    Grover, H.; Doherty, K.; Sieg, C.; Robichaud, P. R.; Fulé, P. Z.; Bowker, M.

    2017-12-01

    With wildfires increasing in severity and extent throughout the Western United States, land managers need new tools to stabilize recently burned ecosystems. "Fire moss" consists of three species, Ceratodon purpureus, Funaria hygrometrica, and Bryum argentum. These mosses colonize burned landscapes quickly, aggregate soils, have extremely high water holding capacity, and can be grown rapidly ex-situ. In this talk, I will focus on our efforts to understand how Fire Moss naturally interacts with severely burned landscapes. We examined 14 fires in Arizona, New Mexico, Washington, and Idaho selecting a range of times since fire, and stratified plots within each wildfire by winter insolation and elevation. At 75+ plots we measured understory plant cover, ground cover, Fire Moss cover, and Fire Moss reproductive effort. On plots in the Southwest, we measured a suite of soil characteristics on moss covered and adjacent bare soil including aggregate stability, shear strength, compressional strength, and infiltration rates. Moss cover ranged from 0-75% with a mean of 16% across all plots and was inversely related to insolation (R2 = .32, p = stability and infiltration rates as adjacent bare ground. These results will allow us to model locations where Fire Moss will naturally increase postfire hillslope soil stability, locations for targeting moss restoration efforts, and suggest that Fire Moss could be a valuable tool to mitigate post wildfire erosion.

  3. A COGNITIVE-BEHAVIOURAL GROUP TREATMENT IMPROVED WORK ABILITY IN PATIENTS WITH SEVERE FUNCTIONAL SOMATIC SYNDROMES

    DEFF Research Database (Denmark)

    Schröder, Andreas; Ørnbøl, Eva; Jensen, Jens Søndergaard

    2014-01-01

    Objective: Functional somatic syndromes (FSS) such as fibromyalgia, irritable bowel and chronic fatigue syndrome often disrupt employment and may lead to long-term dependence on social benefits and permanently reduced work ability. Cognitive-behavioural treatments (CBT) relief symptoms and improve...... before to 3 years after treatment by means of random effects modelling allowing individual levels and slopes. Results: Compared with the general population, FSS patients showed a continuous decline in self-support, leading to markedly reduced work ability at trial entry. In the following years, EUC...

  4. The DSM-5 Levels of Personality Functioning and Severity of Iranian Patients With Antisocial and Borderline Personality Disorders

    Science.gov (United States)

    Amini, Mehdi; Pourshahbaz, Abbas; Mohammadkhani, Parvaneh; Khodaie Ardakani, Mohammad Reza; Lotfi, Mozhgan

    2015-01-01

    Background: Fundamental problems with Personality Disorders (PD) diagnostic system in the previous version of DSM, led to the revision of DSM. Therefore, a multidimensional system has been proposed for diagnosis of personality disorder features in DSM-5. In the dimensional approach of DSM-5, personality disorders diagnosis is based on levels of personality functioning (Criteria A) and personality trait domains (Criteria B). Objectives: The purpose of this study was firstly, to examine the DSM-5 levels of personality functioning in antisocial and borderline personality disorders, and second, to explore which levels of personality functioning in patients with antisocial and borderline personality disorders can better predicted severity than others. Patients and Methods: This study had a cross sectional design. The participants consisted of 252 individuals with antisocial (n = 122) and borderline personality disorders (n = 130). They were recruited from Tehran prisoners, and clinical psychology and psychiatry centers of Razi and Taleghani Hospitals, Tehran, Iran. The sample was selected based on judgmental sampling. The SCID-II-PQ, SCID-II and DSM-5 levels of personality functioning were used to diagnose and assess personality disorders. The data were analyzed by correlation and multiple regression analysis. All statistical analyses were performed using the SPSS 16 software. Results: Firstly, it was found that DSM-5 levels of personality functioning have a strong correlation with antisocial and borderline personality symptoms, specially intimacy and self-directedness (P antisocial personality disorder severity (P personality disorder severity, as well (P personality functioning are a significant predictor of personality disorders severity. The results partially confirm existing studies. PMID:26430521

  5. Characterization of Rod Function Phenotypes Across a Range of Age-Related Macular Degeneration Severities and Subretinal Drusenoid Deposits.

    Science.gov (United States)

    Flynn, Oliver J; Cukras, Catherine A; Jeffrey, Brett G

    2018-05-01

    To examine spatial changes in rod-mediated function in relationship to local structural changes across the central retina in eyes with a spectrum of age-related macular degeneration (AMD) disease severity. Participants were categorized into five AMD severity groups based on fundus features. Scotopic thresholds were measured at 14 loci spanning ±18° along the vertical meridian from one eye of each of 42 participants (mean = 71.7 ± 9.9 years). Following a 30% bleach, dark adaptation was measured at eight loci (±12°). Rod intercept time (RIT) was defined from the time to detect a -3.1 log cd/m2 stimulus. RITslope was defined from the linear fit of RIT with decreasing retinal eccentricity. The presence of subretinal drusenoid deposits (SDD), ellipsoid (EZ) band disruption, and drusen at the test loci was evaluated using optical coherence tomography. Scotopic thresholds indicated greater rod function loss in the macula, which correlated with increasing AMD group severity. RITslope, which captures the spatial change in the rate of dark adaptation, increased with AMD severity (P < 0.0001). Three rod function phenotypes emerged: RF1, normal rod function; RF2, normal scotopic thresholds but slowed dark adaptation; and RF3, elevated scotopic thresholds with slowed dark adaptation. Dark adaptation was slowed at all loci with SDD or EZ band disruption, and at 32% of loci with no local structural changes. Three rod function phenotypes were defined from combined measurement of scotopic threshold and dark adaptation. Spatial changes in dark adaptation across the macula were captured with RITslope, which may be a useful outcome measure for functional studies of AMD.

  6. A functional brain-derived neurotrophic factor (BDNF) gene variant increases the risk of moderate-to-severe allergic rhinitis.

    Science.gov (United States)

    Jin, Peng; Andiappan, Anand Kumar; Quek, Jia Min; Lee, Bernett; Au, Bijin; Sio, Yang Yie; Irwanto, Astrid; Schurmann, Claudia; Grabe, Hans Jörgen; Suri, Bani Kaur; Matta, Sri Anusha; Westra, Harm-Jan; Franke, Lude; Esko, Tonu; Sun, Liangdan; Zhang, Xuejun; Liu, Hong; Zhang, Furen; Larbi, Anis; Xu, Xin; Poidinger, Michael; Liu, Jianjun; Chew, Fook Tim; Rotzschke, Olaf; Shi, Li; Wang, De Yun

    2015-06-01

    Brain-derived neurotrophic factor (BDNF) is a secretory protein that has been implicated in the pathogenesis of allergic rhinitis (AR), atopic asthma, and eczema, but it is currently unknown whether BDNF polymorphisms influence susceptibility to moderate-to-severe AR. We sought to identify disease associations and the functional effect of BDNF genetic variants in patients with moderate-to-severe AR. Tagging single nucleotide polymorphisms (SNPs) spanning the BDNF gene were selected from the human HapMap Han Chinese from Beijing (CHB) data set, and associations with moderate-to-severe AR were assessed in 2 independent cohorts of Chinese patients (2216 from Shandong province and 1239 living in Singapore). The functional effects of the BDNF genetic variants were determined by using both in vitro and ex vivo assays. The tagging SNP rs10767664 was significantly associated with the risk of moderate-to-severe AR in both Singapore Chinese (P = .0017; odds ratio, 1.324) and Shandong Chinese populations (P = .039; odds ratio, 1.180). The coding nonsynonymous SNP rs6265 was in perfect linkage with rs10767664 and conferred increased BDNF protein secretion by a human cell line in vitro. Subjects bearing the AA genotype of rs10767664 exhibited increased risk of moderate-to-severe AR and displayed increased BDNF protein and total IgE levels in plasma. Using a large-scale expression quantitative trait locus study, we demonstrated that BDNF SNPs are significantly associated with altered BDNF concentrations in peripheral blood. A common genetic variant of the BDNF gene is associated with increased risk of moderate-to-severe AR, and the AA genotype is associated with increased BDNF mRNA levels in peripheral blood. Together, these data indicate that functional BDNF gene variants increase the risk of moderate-to-severe AR. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. Tobacco Induced Renal Function Alterations in Wistar Rats: An 8 ...

    African Journals Online (AJOL)

    ... pattern was observed for urea and uric acid levels. Over all, the significant increase (P<0.05) in renal function parameters of the test rats (as compared to the control values), suggests that the ingestion of tobacco snuff has harmful effects on kidney functions. Keywords: Tobacco, Snuff, Kidney function, Nicotine substitute.

  8. Dextran sulfate sodium-induced acute colitis impairs dermal lymphatic function in mice.

    Science.gov (United States)

    Agollah, Germaine D; Wu, Grace; Peng, Ho-Lan; Kwon, Sunkuk

    2015-12-07

    To investigate whether dermal lymphatic function and architecture are systemically altered in dextran sulfate sodium (DSS)-induced acute colitis. Balb/c mice were administered 4% DSS in lieu of drinking water ad libitum for 7 d and monitored to assess disease activity including body weight, diarrhea severity, and fecal bleeding. Control mice received standard drinking water with no DSS. Changes in mesenteric lymphatics were assessed following oral administration of a fluorescently-labelled fatty acid analogue, while dermal lymphatic function and architecture was longitudinally characterized using dynamic near-infrared fluorescence (NIRF) imaging following intradermal injection of indocyanine green (ICG) at the base of the tail or to the dorsal aspect of the left paw prior to, 4, and 7 d after DSS administration. We also measured dye clearance rate after injection of Alexa680-bovine serum albumin (BSA). NIRF imaging data was analyzed to reveal lymphatic contractile activity after selecting fixed regions of interest (ROIs) of the same size in fluorescent lymphatic vessels on fluorescence images. The averaged fluorescence intensity within the ROI of each fluorescence image was plotted as a function of imaging time and the lymphatic contraction frequency was computed by assessing the number of fluorescent pulses arriving at a ROI. Mice treated with DSS developed acute inflammation with clinical symptoms of loss of body weight, loose feces/watery diarrhea, and fecal blood, all of which were aggravated as disease progressed to 7 d. Histological examination of colons of DSS-treated mice confirmed acute inflammation, characterized by segmental to complete loss of colonic mucosa with an associated chronic inflammatory cell infiltrate that extended into the deeper layers of the wall of the colon, compared to control mice. In situ intravital imaging revealed that mice with acute colitis showed significantly fewer fluorescent mesenteric lymphatic vessels, indicating impaired

  9. Performance of Several Density Functional Theory Methods on Describing Hydrogen-Bond Interactions.

    Science.gov (United States)

    Rao, Li; Ke, Hongwei; Fu, Gang; Xu, Xin; Yan, Yijing

    2009-01-13

    We have investigated eleven density functionals, including LDA, PBE, mPWPW91, TPSS, B3LYP, X3LYP, PBE0, O3LYP, B97-1, MPW1K, and TPSSh, for their performances on describing hydrogen bond (HB) interactions. The emphasis has been laid not only on their abilities to calculate the intermolecular hydrogen bonding energies but also on their performances in predicting the relative energies of intermolecular H-bonded complexes and the conformer stabilities due to intramolecular hydrogen bondings. As compared to the best theoretical values, we found that although PBE and PBE0 gave the best estimation of HB strengths, they might fail to predict the correct order of relative HB energies, which might lead to a wrong prediction of the global minimum for different conformers. TPSS and TPSSh did not always improve over PBE and PBE0. B3LYP was found to underestimate the intermolecular HB strengths but was among the best performers in calculating the relative HB energies. We showed here that X3LYP and B97-1 were able to give good values for both absolute HB strengths and relative HB energies, making these functionals good candidates for HB description.

  10. Clinical significance of sleep bruxism on several occlusal and functional parameters.

    Science.gov (United States)

    Ommerborn, Michelle A; Giraki, Maria; Schneider, Christine; Fuck, Lars Michael; Zimmer, Stefan; Franz, Matthias; Raab, Wolfgang Hans-michael; Schaefer, Ralf

    2010-10-01

    The aim of this study was to evaluate the association between various functional and occlusal parameters and sleep bruxism. Thirty-nine (39) sleep bruxism patients and 30 controls participated in this investigation. The assessment of sleep bruxism was performed using the Bruxcore Bruxism-Monitoring Device (BBMD) combined with a new computer-based analyzing method. Sixteen functional and/or occlusal parameters were recorded. With a mean slide of 0.95 mm in the sleep bruxism group and a mean slide of 0.42 mm in the control group (Mann Whitney U test; p<0.003), results solely demonstrated a significant group difference regarding the length of a slide from centric occlusion to maximum intercuspation. The results suggest that the slightly pronounced slide could be of clinical importance in the development of increased wear facets in patients with current sleep bruxism activity. Following further evaluation including polysomnographic recordings, the BBMD combined with this new analyzing technique seems to be a clinically feasible instrument that allows the practitioner to quantify abrasion over a short period.

  11. Functional Budd-Chiari Syndrome Associated With Severe Polycystic Liver Disease

    Directory of Open Access Journals (Sweden)

    Precil Diego Miranda de Menezes Neves

    2017-06-01

    Full Text Available A 50-year-old woman with end-stage renal disease secondary to autosomal dominant polycystic kidney disease was referred to a quaternary care center due to significantly increased abdominal girth. Her physical examination revealed tense ascites and abdominal collateral veins. A 10-L paracentesis improved abdominal discomfort and disclosed a transudate, suggestive of portal hypertension. A computed tomographic scan revealed massive hepatomegaly caused by multiple cysts of variable sizes, distributed throughout all hepatic segments. Contrast-enhanced imaging uncovered extrinsic compression of hepatic and portal veins, resulting in functional Budd-Chiari syndrome and portal hypertension. Although image-guided drainage followed by sclerosis of dominant cysts could potentially lead to alleviation of the extrinsic compression, the associated significant risk of cyst hemorrhage and infection precluded this procedure. In this scenario, the decision was to submit the patient to a liver-kidney transplantation. After 1 year of this procedure, the patient maintains normal liver and kidney function and refers significant improvement in quality of life.

  12. Azathioprine-induced Acute Pancreatitis in Patients with Inflammatory Bowel Diseases—A Prospective Study on Incidence and Severity

    Science.gov (United States)

    Mohl, Wolfgang; Bokemeyer, Bernd; Bündgens, Burkhard; Büning, Jürgen; Miehlke, Stephan; Hüppe, Dietrich; Maaser, Christian; Klugmann, Tobias; Kruis, Wolfgang; Siegmund, Britta; Helwig, Ulf; Weismüller, Joseph; Drabik, Attyla; Stallmach, Andreas

    2016-01-01

    Background and Aims: Azathioprine [AZA] is recommended for maintenance of steroid-free remission in inflammatory bowel disease IBD. The aim of this study has been to establish the incidence and severity of AZA-induced pancreatitis, an idiosyncratic and major side effect, and to identify specific risk factors. Methods: We studied 510 IBD patients [338 Crohn’s disease, 157 ulcerative colitis, 15 indeterminate colitis] with initiation of AZA treatment in a prospective multicentre registry study. Acute pancreatitis was diagnosed in accordance with international guidelines. Results: AZA was continued by 324 [63.5%] and stopped by 186 [36.5%] patients. The most common cause of discontinuation was nausea [12.2%]. AZA-induced pancreatitis occurred in 37 patients [7.3%]. Of these: 43% were hospitalised with a median inpatient time period of 5 days; 10% had peripancreatic fluid collections; 24% had vomiting; and 14% had fever. No patient had to undergo nonsurgical or surgical interventions. Smoking was the strongest risk factor for AZA-induced acute pancreatitis [p pancreatitis is a common adverse event in IBD patients, but in this study had a mild course in all patients. Smoking is the most important risk factor. PMID:26468141

  13. Purified rutin and rutin-rich asparagus attenuates disease severity and tissue damage following dextran sodium sulfate-induced colitis.

    Science.gov (United States)

    Power, Krista A; Lu, Jenifer T; Monk, Jennifer M; Lepp, Dion; Wu, Wenqing; Zhang, Claire; Liu, Ronghua; Tsao, Rong; Robinson, Lindsay E; Wood, Geoffrey A; Wolyn, David J

    2016-11-01

    This study investigated the effects of cooked whole asparagus (ASP) versus its equivalent level of purified flavonoid glycoside, rutin (RUT), on dextran sodium sulfate (DSS)-induced colitis and subsequent colitis recovery in mice. C57BL/6 male mice were fed an AIN-93G basal diet (BD), or BD supplemented with 2% cooked ASP or 0.025% RUT for 2 wks prior to and during colitis induction with 2% DSS in water for 7 days, followed by 5 days colitis recovery. In colitic mice, both ASP and RUT upregulated mediators of improved barrier integrity and enhanced mucosal injury repair (e.g. Muc1, IL-22, Rho-A, Rac1, and Reg3γ), increased the proportion of mouse survival, and improved disease activity index. RUT had the greatest effect in attenuating DSS-induced colonic damage indicated by increased crypt and goblet cell restitution, reduced colonic myeloperoxidase, as well as attenuated DSS-induced microbial dysbiosis (reduced Enterobacteriaceae and Bacteroides, and increased unassigned Clostridales, Oscillospira, Lactobacillus, and Bifidobacterium). These findings demonstrate that dietary cooked ASP and its flavonoid glycoside, RUT, may be useful in attenuating colitis severity by modulating the colonic microenvironment resulting in reduced colonic inflammation, promotion of colonic mucosal injury repair, and attenuation of colitis-associated microbial dysbiosis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Vinpocetine inhibits glutamate release induced by the convulsive agent 4-aminopyridine more potently than several antiepileptic drugs.

    Science.gov (United States)

    Sitges, M; Sanchez-Tafolla, B M; Chiu, L M; Aldana, B I; Guarneros, A

    2011-10-01

    4-Aminopyridine (4-AP) is a convulsing agent that in vivo preferentially releases Glu, the most important excitatory amino acid neurotransmitter in the brain. Here the ionic dependence of 4-AP-induced Glu release and the effects of several of the most common antiepileptic drugs (AEDs) and of the new potential AED, vinpocetine on 4-AP-induced Glu release were characterized in hippocampus isolated nerve endings pre-loaded with labelled Glu ([3H]Glu). 4-AP-induced [3H]Glu release was composed by a tetrodotoxin (TTX) sensitive and external Ca2+ dependent fraction and a TTX insensitive fraction that was sensitive to the excitatory amino acid transporter inhibitor, TBOA. The AEDs: carbamazepine, phenytoin, lamotrigine and oxcarbazepine at the highest dose tested only reduced [3H]Glu release to 4-AP between 50-60%, and topiramate was ineffective. Vinpocetine at a much lower concentration than the above AEDs, abolished [3H]Glu release to 4-AP. We conclude that the decrease in [3H]Glu release linked to the direct blockade of presynaptic Na+ channels, may importantly contribute to the anticonvulsant actions of all the drugs tested here (except topiramate); and that the significantly greater vinpocetine effect in magnitude and potency on [3H]Glu release when excitability is exacerbated like during seizures, may involve the increase additionally exerted by vinpocetine in some K+ channels permeability. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity.

    Science.gov (United States)

    Malykhina, Anna P; Lei, Qi; Erickson, Chris S; Epstein, Miles L; Saban, Marcia R; Davis, Carole A; Saban, Ricardo

    2012-12-19

    This work tests the hypothesis that bladder instillation with vascular endothelial growth factor (VEGF) modulates sensory and motor nerve plasticity, and, consequently, bladder function and visceral sensitivity.In addition to C57BL/6J, ChAT-cre mice were used for visualization of bladder cholinergic nerves. The direct effect of VEGF on the density of sensory nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1) and cholinergic nerves (ChAT) was studied one week after one or two intravesical instillations of the growth factor.To study the effects of VEGF on bladder function, mice were intravesically instilled with VEGF and urodynamic evaluation was assessed. VEGF-induced alteration in bladder dorsal root ganglion (DRG) neurons was performed on retrogradly labeled urinary bladder afferents by patch-clamp recording of voltage gated Na+ currents. Determination of VEGF-induced changes in sensitivity to abdominal mechanostimulation was performed by application of von Frey filaments. In addition to an overwhelming increase in TRPV1 immunoreactivity, VEGF instillation resulted in an increase in ChAT-directed expression of a fluorescent protein in several layers of the urinary bladder. Intravesical VEGF caused a profound change in the function of the urinary bladder: acute VEGF (1 week post VEGF treatment) reduced micturition pressure and longer treatment (2 weeks post-VEGF instillation) caused a substantial reduction in inter-micturition interval. In addition, intravesical VEGF resulted in an up-regulation of voltage gated Na(+) channels (VGSC) in bladder DRG neurons and enhanced abdominal sensitivity to mechanical stimulation. For the first time, evidence is presented indicating that VEGF instillation into the mouse bladder promotes a significant increase in peripheral nerve density together with alterations in bladder function and visceral sensitivity. The VEGF pathway is being proposed as a key modulator of neural plasticity in the pelvis and

  16. VEGF induces sensory and motor peripheral plasticity, alters bladder function, and promotes visceral sensitivity

    Directory of Open Access Journals (Sweden)

    Malykhina Anna P

    2012-12-01

    Full Text Available Abstract Background This work tests the hypothesis that bladder instillation with vascular endothelial growth factor (VEGF modulates sensory and motor nerve plasticity, and, consequently, bladder function and visceral sensitivity. In addition to C57BL/6J, ChAT-cre mice were used for visualization of bladder cholinergic nerves. The direct effect of VEGF on the density of sensory nerves expressing the transient receptor potential vanilloid subfamily 1 (TRPV1 and cholinergic nerves (ChAT was studied one week after one or two intravesical instillations of the growth factor. To study the effects of VEGF on bladder function, mice were intravesically instilled with VEGF and urodynamic evaluation was assessed. VEGF-induced alteration in bladder dorsal root ganglion (DRG neurons was performed on retrogradly labeled urinary bladder afferents by patch-clamp recording of voltage gated Na+ currents. Determination of VEGF-induced changes in sensitivity to abdominal mechanostimulation was performed by application of von Frey filaments. Results In addition to an overwhelming increase in TRPV1 immunoreactivity, VEGF instillation resulted in an increase in ChAT-directed expression of a fluorescent protein in several layers of the urinary bladder. Intravesical VEGF caused a profound change in the function of the urinary bladder: acute VEGF (1 week post VEGF treatment reduced micturition pressure and longer treatment (2 weeks post-VEGF instillation caused a substantial reduction in inter-micturition interval. In addition, intravesical VEGF resulted in an up-regulation of voltage gated Na+ channels (VGSC in bladder DRG neurons and enhanced abdominal sensitivity to mechanical stimulation. Conclusions For the first time, evidence is presented indicating that VEGF instillation into the mouse bladder promotes a significant increase in peripheral nerve density together with alterations in bladder function and visceral sensitivity. The VEGF pathway is being proposed as a

  17. Saturation of retinol-binding protein correlates closely to the severity of alcohol-induced liver disease

    DEFF Research Database (Denmark)

    Wagnerberger, S.; Schäfer, C.; Bode, C.

    2006-01-01

    Impaired metabolism of retinol has been shown to occur in alcohol-induced liver disease (ALD). The purpose of the present study was to investigate the saturation of retinol-binding protein (RBP) in 6 patients with different stages of ALD. Hospitalized alcohol consumers (n=118) with different stages...... chromatography and enzyme-linked immunosorbent assay methods, respectively. No differences were noted in daily retinol intake, but subjects with ALD had significantly lower concentrations of retinol in plasma (ALD1: 1.81+/-0.17 micromol/l [mean+/-S.E.M.]; ALD2: 1.95+/-0.24 micromol/l; ALD3: 0.67+/-0.13 micromol......: 43.5+/-6.2%; ALD3: 29.0+/-5.1%). The present study indicates that plasma concentrations of retinol and RBP per se do not correlate to severity of ALD, but rather that the retinol/RBP ratio links to the severity of alcohol-induced liver damage. From these results, a reduced availability of retinol...

  18. HMGB1 and Histones Play a Significant Role in Inducing Systemic Inflammation and Multiple Organ Dysfunctions in Severe Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Runkuan Yang

    2017-01-01

    Full Text Available Severe acute pancreatitis (SAP starts as a local inflammation of pancreatic tissue that induces the development of multiple extrapancreatic organs dysfunction; however, the underlying mechanisms are still not clear. Ischemia-reperfusion, circulating inflammatory cytokines, and possible bile cytokines significantly contribute to gut mucosal injury and intestinal bacterial translocation (BT during SAP. Circulating HMGB1 level is significantly increased in SAP patients and HMGB1 is an important factor that mediates (at least partly gut BT during SAP. Gut BT plays a critical role in triggering/inducing systemic inflammation/sepsis in critical illness, and profound systemic inflammatory response syndrome (SIRS can lead to multiple organ dysfunction syndrome (MODS during SAP, and systemic inflammation with multiorgan dysfunction is the cause of death in experimental SAP. Therefore, HMGB1 is an important factor that links gut BT and systemic inflammation. Furthermore, HMGB1 significantly contributes to multiple organ injuries. The SAP patients also have significantly increased circulating histones and cell-free DNAs levels, which can reflect the disease severity and contribute to multiple organ injuries in SAP. Hepatic Kupffer cells (KCs are the predominant source of circulating inflammatory cytokines in SAP, and new evidence indicates that hepatocyte is another important source of circulating HMGB1 in SAP; therefore, treating the liver injury is important in SAP.

  19. Relation of osteoprotegerin in severe aortic valve stenosis to postoperative outcome and left ventricular function

    DEFF Research Database (Denmark)

    Dahl, Jordi S; Videbæk, Lars; Poulsen, Mikael K

    2013-01-01

    Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily and is known to be among the mediators of the calcification process that has been shown to increase in patients with aortic stenosis (AS). The aim of this study was to characterize the association of OPG with left......, 41 patients died of a presumed cardiovascular cause or remained in New York Heart Association functional class III or IV. The risk of a poor postoperative outcome after AVR increased with increasing OPG tertiles (15% vs 33% vs 51%, p = 0.002). In a multivariate model containing age, ejection fraction......, N-terminal pro-brain natriuretic peptide and left atrial volume index, OPG was still significantly associated with postoperative outcome. In addition, OPG levels associated with cardiovascular mortality during follow-up. In conclusion, OPG is associated with LV and left atrial remodeling in patients...

  20. Function assertive community treatment (FACT) and psychiatric service use in patients diagnosed with severe mental illness.

    Science.gov (United States)

    Drukker, M; van Os, J; Sytema, S; Driessen, G; Visser, E; Delespaul, P

    2011-09-01

    Previous work suggests that the Dutch variant of assertive community treatment (ACT), known as Function ACT (FACT), may be effective in increasing symptomatic remission rates when replacing a system of hospital-based care and separate community-based facilities. FACT guidelines propose a different pattern of psychiatric service consumption compared to traditional services, which should result in different costing parameters than care as usual (CAU). South-Limburg FACT patients, identified through the local psychiatric case register, were matched with patients from a non-FACT control region in the North of the Netherlands (NN). Matching was accomplished using propensity scoring including, among others, total and outpatient care consumption. Assessment, as an important ingredient of FACT, was the point of departure of the present analysis. FACT patients, compared to CAU, had five more outpatient contacts after the index date. Cost-effectiveness was difficult to assess. Implementation of FACT results in measurable changes in mental health care use.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  2. Preservation of beta cell function in adult human pancreatic islets for several months in vitro

    DEFF Research Database (Denmark)

    Brunstedt, J; Andersson, A; Frimodt-Møller, C

    1979-01-01

    Islets of Langerhans were isolated from four human kidney donors, aged 16 to 21 years by the collagenase method described for isolation of rodent islets. So far the human islets have been kept in tissue culture, without attachment, in medium RPMI 1640 supplemented with 10% calf serum for more tha...... technique presents a valuable tool for studying chronic effects of metabolites and hormones on islet function, as well as for islet storage prior to transplantation into humans.......Islets of Langerhans were isolated from four human kidney donors, aged 16 to 21 years by the collagenase method described for isolation of rodent islets. So far the human islets have been kept in tissue culture, without attachment, in medium RPMI 1640 supplemented with 10% calf serum for more than...

  3. SOCS3 Expression Correlates with Severity of Inflammation, Expression of Proinflammatory Cytokines, and Activation of STAT3 and p38 MAPK in LPS-Induced Inflammation In Vivo

    Directory of Open Access Journals (Sweden)

    João Antônio Chaves de Souza

    2013-01-01

    Full Text Available SOCS3 is an inducible endogenous negative regulator of JAK/STAT pathway, which is relevant in inflammatory conditions. We used a model of LPS-induced periodontal disease in rats to correlate SOCS3 expression with the inflammatory status. In vitro we used a murine macrophage cell line to assess the physical interaction between SOCS3 and STAT3 by coimmunoprecipitation. 30 ug of LPS from Escherichia coli were injected in the gingival tissues on the palatal aspect of first molars of the animals 3x/week for up to 4 weeks. Control animals were injected with the vehicle (PBS. The rats were sacrificed at 7, 15, and 30 days. Inflammation and gene expression were assessed by stereometric analysis, immunohistochemistry, RT-qPCR, and western blot. LPS injections increased inflammation, paralleled by an upregulation of SOCS3, of the proinflammatory cytokines IL-1β, IL-6, and TNF-α and increased phosphorylation of STAT3 and p38 MAPK. SOCS3 expression accompanied the severity of inflammation and the expression of proinflammatory cytokines, as well as the activation status of STAT3 and p38 MAPK. LPS stimulation in a macrophage cell line in vitro induced transient STAT3 activation, which was inversely correlated with a dynamic physical interaction with SOCS3, suggesting that this may be a mechanism for SOCS3 regulatory function.

  4. Fentanyl Ameliorates Severe Acute Pancreatitis-Induced Myocardial Injury in Rats by Regulating NF-κB Signaling Pathway.

    Science.gov (United States)

    Wang, Yayun; Chen, Manhua

    2017-07-06

    BACKGROUND Acute pancreatitis (AP) is a sudden inflammation of the pancreas. It results in multiple, severe complications, and 15-20% of patients develop severe acute pancreatitis (SAP) with mortality as high as 30%. Consequently, it is imperative to develop an effective therapy for SAP. MATERIAL AND METHODS We used 30 adult male Sprague Dawley (SD) rats. Rats were randomly divided into 3 groups - sham, SAP, and fentanyl+SAP - with 10 rats in each group. An automatic biochemical analyzer was used to analyze the concentration of creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH). Terminal-deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assay was applied to assess the cell apoptosis rate. Pathological changes in pancreas/heart were detected with hematoxylin and eosin (HE) staining. Western immunoblot assay was used to analyze protein levels of interleukin (IL)-1β, IL-6, and IκB. RESULTS Fentanyl pre-treatment inhibits SAP-induced elevation of CK-MB/LDH concentrations in serum. Compared with the sham group, SAP generates a higher brown/yellow staining rate, which is abated by fentanyl. In the pancreas, SAP generated more serious interstitial edema/hemorrhage and fat necrosis than in the sham group, which are attenuated by fentanyl. Likewise, compared to the sham group, SAP generates swelled/disordered myocardial fibers and congested blood vessels in myocardium, which are ameliorated by fentanyl. In the sham group, there was little IL-1β/IL-6, and fentanyl significantly inhibited SAP-induced up-regulation of IL-1β/IL-6 levels. Compared with the sham group, SAP significantly reduced IκB level, which was rescued by fentanyl. CONCLUSIONS Fentanyl effectively alleviates SAP-induced pancreas and heart injuries through regulating the nuclear factor-κB (NF-κB) signaling pathway.

  5. Mechanisms of Short-Term Training-Induced Reaching Improvement in Severely Hemiparetic Stroke Patients: A TMS Study

    Science.gov (United States)

    Harris-Love, Michelle L.; Morton, Susanne M.; Perez, Monica A.; Cohen, Leonardo G.

    2011-01-01

    Background The neurophysiological mechanisms underlying improved upper-extremity motor skills have been partially investigated in patients with good motor recovery but are poorly understood in more impaired individuals, the majority of stroke survivors. Objective The authors studied changes in primary motor cortex (M1) excitability (motor evoked potentials [MEPs], contralateral and ipsilateral silent periods [CSPs and ISPs] using transcranial magnetic stimulation [TMS]) associated with training-induced reaching improvement in stroke patients with severe arm paresis (n = 11; Upper-Extremity Fugl-Meyer score (F-M) = 27 ± 6). Methods All patients underwent a single session of reaching training focused on moving the affected hand from a resting site to a target placed at 80% of maximum forward reaching amplitude in response to a visual “GO” cue. Triceps contribute primarily as agonist and biceps primarily as antagonist to the trained forward reaching movement. Response times were recorded for each reaching movement. Results Preceding training (baseline), greater interhemispheric inhibition (measured by ISP) in the affected triceps muscle, reflecting inhibition from the nonlesioned to the lesioned M1, was observed in patients with lower F-M scores (more severe motor impairment). Training-induced improvements in reaching were greater in patients with slower response times at baseline. Increased MEP amplitudes and decreased ISPs and CSPs were observed in the affected triceps but not in the biceps muscle after training. Conclusion These results indicate that along with training-induced motor improvements, training-specific modulation of intrahemispheric and interhemispheric mechanisms occurs after reaching practice in chronic stroke patients with substantial arm impairment. PMID:21343522

  6. Hepatobiliary function assessed by {sup 99m}Tc-mebrofenin cholescintigraphy in the evaluation of severity of steatosis in a rat model

    Energy Technology Data Exchange (ETDEWEB)

    Vetelaeinen, Reeta L.; Vliet, Arlene van; Gulik, Thomas M. van [Academic Medical Center, Department of Surgery, Amsterdam (Netherlands); Bennink, Roelof J.; Bruin, Kora de [Academic Medical Center, Department of Nuclear Medicine, Amsterdam (Netherlands)

    2006-10-15

    This study evaluated the utility of non-invasive assessment of hepatobiliary function by {sup 99m}Tc-mebrofenin cholescintigraphy in a rat model of diet-induced steatosis. Male Wistar rats (250-300 g) were fed a standard methionine- and choline-deficient (MCD) diet for up to 5 weeks, thereby inducing hepatic fat accumulation, progressive inflammation and fibrogenesis corresponding with clinical steatosis. {sup 99m}Tc-mebrofenin pinhole scintigraphy was used to evaluate the hepatocyte mebrofenin uptake rate, the time of maximum hepatic uptake (T{sub peak}) and the time required for peak activity to decrease by 50% (T{sub 1/2peak}). Scintigraphic parameters were correlated with biochemical and serological parameters and with liver histopathology. MCD diet induced mild steatosis after 1 week and severe steatosis with prominent inflammation after 5 weeks. T{sub peak}, T{sub 1/2peak} prolonged and the uptake rate decreased significantly, while the severity of steatosis increased (p<0.05). There was a strong, significant correlation between the severity of steatosis (histopathology, hepatic triglyceride content) and the {sup 99m}Tc-mebrofenin uptake rate (r {sup 2}=0.83, p<0.0001 and r {sup 2}=0.82, p<0.0001, respectively). In addition, the uptake rate correlated significantly with the increased inflammation (plasma and hepatic TNF-{alpha}, r {sup 2}=0.72, p<0.0001 and r {sup 2}=0.52, p=0.001, respectively). The correlation of the uptake rate with hepatocellular damage was weak (AST and ALT, r {sup 2}=0.29 and 0.32, respectively), but correlation with synthetic function was strong (prothrombin time, r {sup 2}=0.70, p<0.001). Hepatobiliary function assessed by {sup 99m}Tc-mebrofenin scintigraphy correlates with the extent and progression of steatosis. These results suggest a potential role for mebrofenin scintigraphy as a non-invasive functional follow-up method for disease progression in steatotic patients. (orig.)

  7. Influence of hypothermia combined with erythropoietin on serum neurological function indexes in newborns with severe hypoxic ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Hua Tian

    2017-05-01

    Full Text Available Objective: To study the influence of hypothermia combined with erythropoietin (EPO on serum neurological function indexes in newborns with severe hypoxic ischemic encephalopathy (HIE. Methods: A total of 48 cases of newborns with severe hypoxic ischemic encephalopathy in our hospital were enrolled and divided into control group and observation group according to random number table, 24 cases in each group. On the basis of conventional treatment, patients in control group were treated with mild hypothermia, and those in observation group were treated with mild hypothermia combined with EPO. Serum nerve injury indexes, neurological function indexes and nerve apoptosis indexes were compared between two groups before and after treatment. Results: Before treatment, differences in the levels of nerve injury indexes, neurological function indexes and nerve apoptosis indexes were not statistically significant between two groups. After treatment, serum nerve injury indexes NSE and S-100B levels of observation group were lower than those of control group, neurolocial function indexes BDNF, NGF, IGF-1 and GH levels of observation group were higher than those of control group, and nerve apoptosis indexes sFas and sFasL levels of observation group were lower than those of control group. Conclusion: Mild hypothermia combined with EPO can reduce the neurological damage and inhibit neuronal apoptosis in children with severe HIE.

  8. Evaluation of functional severity of coronary artery disease and fluid dynamics' influence on hemodynamic parameters: A review.

    Science.gov (United States)

    Govindaraju, Kalimuthu; Badruddin, Irfan Anjum; Viswanathan, Girish N; Ramesh, S V; Badarudin, A

    2013-05-01

    Coronary Artery Disease (CAD) is responsible for most of the deaths in patients with cardiovascular diseases. Diagnostic coronary angiography analysis offers an anatomical knowledge of the severity of the stenosis. The functional or physiological significance is more valuable than the anatomical significance of CAD. Clinicians assess the functional severity of the stenosis by resorting to an invasive measurement of the pressure drop and flow. Hemodynamic parameters, such as pressure wire assessment fractional flow reserve (FFR) or Doppler wire assessment coronary flow reserve (CFR) are well-proven techniques to evaluate the physiological significance of the coronary artery stenosis in the cardiac catheterization laboratory. Between the two techniques mentioned above, the FFR is seen as a very useful index. The presence of guide wire reduces the coronary flow which causes the underestimation of pressure drop across the stenosis which leads to dilemma for the clinicians in the assessment of moderate stenosis. In such condition, the fundamental fluid mechanics is useful in the development of new functional severity parameters such as pressure drop coefficient and lesion flow coefficient. Since the flow takes place in a narrowed artery, the blood behaves as a non-Newtonian fluid. Computational fluid dynamics (CFD) allows a complete coronary flow simulation to study the relationship between the pressure and flow. This paper aims at explaining (i) diagnostic modalities for the evaluation of the CAD and valuable insights regarding FFR in the evaluation of the functional severity of the CAD (ii) the role of fluid dynamics in measuring the severity of CAD. Copyright © 2012 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  9. The limits of adaptation of functional protein synthesis to sever undernutrition

    International Nuclear Information System (INIS)

    Jahoor, F.; Bhattiprolu, S.; Reeds, P.; Forrester, T.; Boyne, M.

    1994-01-01

    Our goal is to determine how the stress of infections alters the adaptation to reduced food intake in children. We think that an important element is the need for hepatic synthesis of rapidly turning over acute-phase proteins, a critical factor in overall maintenance of host defenses. When the child's prior intake has been adequate, even though growth may temporarily cease, the presence of adequate amino acid stores in tissues allows the hepatic response to stress to be maintained at the same time as an adequate rate of synthesis of nutrient transport proteins. However, when the immune system is activated in a children whose nutrition is already suboptimal the ability of the liver to synthesize nutrient transport proteins is compromised thereby further impeding nutrient utilization. We will use stable isotope tracer methodology to determine the effects of severe protein energy malnutrition, with and without infection, on the rates of synthesis of nutrient transport proteins and acute-phase proteins in undernourished children at three time points during treatment; in the early resuscitative period, after appetite has returned, and at the end of the catch-up growth phase when normal growth has resumed. (author). 12 refs, 1 fig., 1 tab

  10. The limits of adaptation of functional protein synthesis to sever undernutrition

    Energy Technology Data Exchange (ETDEWEB)

    Jahoor, F; Bhattiprolu, S; Reeds, P [Baylor Coll. of Medicine, Houston, TX (United States). Children` s Nutrition Research Centre; Forrester, T; Boyne, M [West Indies Univ., Mona (Jamaica). Tropical Metabolism Research Unit

    1994-12-31

    Our goal is to determine how the stress of infections alters the adaptation to reduced food intake in children. We think that an important element is the need for hepatic synthesis of rapidly turning over acute-phase proteins, a critical factor in overall maintenance of host defenses. When the child`s prior intake has been adequate, even though growth may temporarily cease, the presence of adequate amino acid stores in tissues allows the hepatic response to stress to be maintained at the same time as an adequate rate of synthesis of nutrient transport proteins. However, when the immune system is activated in a children whose nutrition is already suboptimal the ability of the liver to synthesize nutrient transport proteins is compromised thereby further impeding nutrient utilization. We will use stable isotope tracer methodology to determine the effects of severe protein energy malnutrition, with and without infection, on the rates of synthesis of nutrient transport proteins and acute-phase proteins in undernourished children at three time points during treatment; in the early resuscitative period, after appetite has returned, and at the end of the catch-up growth phase when normal growth has resumed. (author). 12 refs, 1 fig., 1 tab.

  11. A functional analysis of photo-object matching skills of severely retarded adolescents.

    Science.gov (United States)

    Dixon, L S

    1981-01-01

    Matching-to-sample procedures were used to assess picture representation skills of severely retarded, nonverbal adolescents. Identity matching within the classes of objects and life-size, full-color photos of the objects was first used to assess visual discrimination, a necessary condition for picture representation. Picture representation was then assessed through photo-object matching tasks. Five students demonstrated visual discrimination (identity matching) within the two classes of photos and the objects. Only one student demonstrated photo-object matching. The results of the four students who failed to demonstrate photo-object matching suggested that physical properties of photos (flat, rectangular) and depth dimensions of objects may exert more control over matching than the similarities of the objects and images within the photos. An analysis of figure-ground variables was conducted to provide an empirical basis for program development in the use of pictures. In one series of tests, rectangular shape and background were removed by cutting out the figures in the photos. The edge shape of the photo and the edge shape of the image were then identical. The results suggest that photo-object matching may be facilitated by using cut-out figures rather than the complete rectangular photo.

  12. An integrated model of environmental factors in adult asthma lung function and disease severity: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Katz Patricia P

    2010-05-01

    Full Text Available Abstract Background Diverse environmental exposures, studied separately, have been linked to health outcomes in adult asthma, but integrated multi-factorial effects have not been modeled. We sought to evaluate the contribution of combined social and physical environmental exposures to adult asthma lung function and disease severity. Methods Data on 176 subjects with asthma and/or rhinitis were collected via telephone interviews for sociodemographic factors and asthma severity (scored on a 0-28 point range. Dust, indoor air quality, antigen-specific IgE antibodies, and lung function (percent predicted FEV1 were assessed through home visits. Neighborhood socioeconomic status, proximity to traffic, land use, and ambient air quality data were linked to the individual-level data via residential geocoding. Multiple linear regression separately tested the explanatory power of five groups of environmental factors for the outcomes, percent predicted FEV1 and asthma severity. Final models retained all variables statistically associated (p Results Mean FEV1 was 85.0 ± 18.6%; mean asthma severity score was 6.9 ± 5.6. Of 29 variables screened, 13 were retained in the final model of FEV1 (R2 = 0.30; p 2 = 0.16; p 1 as an independent variable to the severity model further increased its explanatory power (R2 = 0.25. Conclusions Multivariate models covering a range of individual and environmental factors explained nearly a third of FEV1 variability and, taking into account lung function, one quarter of variability in asthma severity. These data support an integrated approach to modeling adult asthma outcomes, including both the physical and the social environment.

  13. Functional Data Analysis Applied to Modeling of Severe Acute Mucositis and Dysphagia Resulting From Head and Neck Radiation Therapy

    International Nuclear Information System (INIS)

    Dean, Jamie A.; Wong, Kee H.; Gay, Hiram; Welsh, Liam C.; Jones, Ann-Britt; Schick, Ulrike; Oh, Jung Hun; Apte, Aditya; Newbold, Kate L.; Bhide, Shreerang A.; Harrington, Kevin J.; Deasy, Joseph O.; Nutting, Christopher M.; Gulliford, Sarah L.

    2016-01-01

    Purpose: Current normal tissue complication probability modeling using logistic regression suffers from bias and high uncertainty in the presence of highly correlated radiation therapy (RT) dose data. This hinders robust estimates of dose-response associations and, hence, optimal normal tissue–sparing strategies from being elucidated. Using functional data analysis (FDA) to reduce the dimensionality of the dose data could overcome this limitation. Methods and Materials: FDA was applied to modeling of severe acute mucositis and dysphagia resulting from head and neck RT. Functional partial least squares regression (FPLS) and functional principal component analysis were used for dimensionality reduction of the dose-volume histogram data. The reduced dose data were input into functional logistic regression models (functional partial least squares–logistic regression [FPLS-LR] and functional principal component–logistic regression [FPC-LR]) along with clinical data. This approach was compared with penalized logistic regression (PLR) in terms of predictive performance and the significance of treatment covariate–response associations, assessed using bootstrapping. Results: The area under the receiver operating characteristic curve for the PLR, FPC-LR, and FPLS-LR models was 0.65, 0.69, and 0.67, respectively, for mucositis (internal validation) and 0.81, 0.83, and 0.83, respectively, for dysphagia (external validation). The calibration slopes/intercepts for the PLR, FPC-LR, and FPLS-LR models were 1.6/−0.67, 0.45/0.47, and 0.40/0.49, respectively, for mucositis (internal validation) and 2.5/−0.96, 0.79/−0.04, and 0.79/0.00, respectively, for dysphagia (external validation). The bootstrapped odds ratios indicated significant associations between RT dose and severe toxicity in the mucositis and dysphagia FDA models. Cisplatin was significantly associated with severe dysphagia in the FDA models. None of the covariates was significantly associated with severe

  14. Functional Data Analysis Applied to Modeling of Severe Acute Mucositis and Dysphagia Resulting From Head and Neck Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Dean, Jamie A., E-mail: jamie.dean@icr.ac.uk [Joint Department of Physics, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London (United Kingdom); Wong, Kee H. [Head and Neck Unit, The Royal Marsden NHS Foundation Trust, London (United Kingdom); Gay, Hiram [Department of Radiation Oncology, School of Medicine, Washington University in St Louis, St Louis, Missouri (United States); Welsh, Liam C.; Jones, Ann-Britt; Schick, Ulrike [Head and Neck Unit, The Royal Marsden NHS Foundation Trust, London (United Kingdom); Oh, Jung Hun; Apte, Aditya [Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Newbold, Kate L.; Bhide, Shreerang A.; Harrington, Kevin J. [Head and Neck Unit, The Royal Marsden NHS Foundation Trust, London (United Kingdom); Division of Radiotherapy and Imaging, The Institute of Cancer Research, London (United Kingdom); Deasy, Joseph O. [Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Nutting, Christopher M. [Head and Neck Unit, The Royal Marsden NHS Foundation Trust, London (United Kingdom); Division of Radiotherapy and Imaging, The Institute of Cancer Research, London (United Kingdom); Gulliford, Sarah L. [Joint Department of Physics, The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London (United Kingdom)

    2016-11-15

    Purpose: Current normal tissue complication probability modeling using logistic regression suffers from bias and high uncertainty in the presence of highly correlated radiation therapy (RT) dose data. This hinders robust estimates of dose-response associations and, hence, optimal normal tissue–sparing strategies from being elucidated. Using functional data analysis (FDA) to reduce the dimensionality of the dose data could overcome this limitation. Methods and Materials: FDA was applied to modeling of severe acute mucositis and dysphagia resulting from head and neck RT. Functional partial least squares regression (FPLS) and functional principal component analysis were used for dimensionality reduction of the dose-volume histogram data. The reduced dose data were input into functional logistic regression models (functional partial least squares–logistic regression [FPLS-LR] and functional principal component–logistic regression [FPC-LR]) along with clinical data. This approach was compared with penalized logistic regression (PLR) in terms of predictive performance and the significance of treatment covariate–response associations, assessed using bootstrapping. Results: The area under the receiver operating characteristic curve for the PLR, FPC-LR, and FPLS-LR models was 0.65, 0.69, and 0.67, respectively, for mucositis (internal validation) and 0.81, 0.83, and 0.83, respectively, for dysphagia (external validation). The calibration slopes/intercepts for the PLR, FPC-LR, and FPLS-LR models were 1.6/−0.67, 0.45/0.47, and 0.40/0.49, respectively, for mucositis (internal validation) and 2.5/−0.96, 0.79/−0.04, and 0.79/0.00, respectively, for dysphagia (external validation). The bootstrapped odds ratios indicated significant associations between RT dose and severe toxicity in the mucositis and dysphagia FDA models. Cisplatin was significantly associated with severe dysphagia in the FDA models. None of the covariates was significantly associated with severe

  15. Functional Data Analysis Applied to Modeling of Severe Acute Mucositis and Dysphagia Resulting From Head and Neck Radiation Therapy.

    Science.gov (United States)

    Dean, Jamie A; Wong, Kee H; Gay, Hiram; Welsh, Liam C; Jones, Ann-Britt; Schick, Ulrike; Oh, Jung Hun; Apte, Aditya; Newbold, Kate L; Bhide, Shreerang A; Harrington, Kevin J; Deasy, Joseph O; Nutting, Christopher M; Gulliford, Sarah L

    2016-11-15

    Current normal tissue complication probability modeling using logistic regression suffers from bias and high uncertainty in the presence of highly correlated radiation therapy (RT) dose data. This hinders robust estimates of dose-response associations and, hence, optimal normal tissue-sparing strategies from being elucidated. Using functional data analysis (FDA) to reduce the dimensionality of the dose data could overcome this limitation. FDA was applied to modeling of severe acute mucositis and dysphagia resulting from head and neck RT. Functional partial least squares regression (FPLS) and functional principal component analysis were used for dimensionality reduction of the dose-volume histogram data. The reduced dose data were input into functional logistic regression models (functional partial least squares-logistic regression [FPLS-LR] and functional principal component-logistic regression [FPC-LR]) along with clinical data. This approach was compared with penalized logistic regression (PLR) in terms of predictive performance and the significance of treatment covariate-response associations, assessed using bootstrapping. The area under the receiver operating characteristic curve for the PLR, FPC-LR, and FPLS-LR models was 0.65, 0.69, and 0.67, respectively, for mucositis (internal validation) and 0.81, 0.83, and 0.83, respectively, for dysphagia (external validation). The calibration slopes/intercepts for the PLR, FPC-LR, and FPLS-LR models were 1.6/-0.67, 0.45/0.47, and 0.40/0.49, respectively, for mucositis (internal validation) and 2.5/-0.96, 0.79/-0.04, and 0.79/0.00, respectively, for dysphagia (external validation). The bootstrapped odds ratios indicated significant associations between RT dose and severe toxicity in the mucositis and dysphagia FDA models. Cisplatin was significantly associated with severe dysphagia in the FDA models. None of the covariates was significantly associated with severe toxicity in the PLR models. Dose levels greater than

  16. Cumulative Lung Dose for Several Motion Management Strategies as a Function of Pretreatment Patient Parameters

    International Nuclear Information System (INIS)

    Hugo, Geoffrey D.; Campbell, Jonathon; Zhang Tiezhi; Yan Di

    2009-01-01

    Purpose: To evaluate patient parameters that may predict for relative differences in cumulative four-dimensional (4D) lung dose among several motion management strategies. Methods and Materials: Deformable image registration and dose accumulation were used to generate 4D treatment plans for 18 patients with 4D computed tomography scans. Three plans were generated to simulate breath hold at normal inspiration, target tracking with the beam aperture, and mid-ventilation aperture (control of the target at the mean daily position and application of an iteratively computed margin to compensate for respiration). The relative reduction in mean lung dose (MLD) between breath hold and mid-ventilation aperture (ΔMLD BH ) and between target tracking and mid-ventilation aperture (ΔMLD TT ) was calculated. Associations between these two variables and parameters of the lesion (excursion, size, location, and deformation) and dose distribution (local dose gradient near the target) were also calculated. Results: The largest absolute and percentage differences in MLD were 1.0 Gy and 21.5% between breath hold and mid-ventilation aperture. ΔMLD BH was significantly associated (p TT was significantly associated with excursion, deformation, and local dose gradient. A linear model was constructed to represent ΔMLD vs. excursion. For each 5 mm of excursion, target tracking reduced the MLD by 4% compared with the results of a mid-ventilation aperture plan. For breath hold, the reduction was 5% per 5 mm of excursion. Conclusions: The relative difference in MLD among different motion management strategies varied with patient and tumor characteristics for a given dosimetric target coverage. Tumor excursion is useful to aid in stratifying patients according to appropriate motion management strategies.

  17. Functional polymorphisms of interferon-gamma affect pneumonia-induced sepsis.

    Directory of Open Access Journals (Sweden)

    Ding Wang

    Full Text Available Sepsis is an inflammatory syndrome caused by infection, and both its incidence and mortality are high. Because interferon-gamma (IFN-γ plays an important role in inflammation, this work assessed IFN-γ single nucleotide polymorphism (SNPs that may be associated with sepsis.A total of 196 patients with pneumonia-induced sepsis and 213 age- and sex-matched healthy volunteers participated in our study from July 2012 to July 2013 in Guangzhou, China. Patient clinical information was collected. Clinical pathology was assessed in subgroups defined based on clinical criteria, APACHE II (acute physiology and chronic health evaluation and SOFA (sepsis-related organ failure assessment scores and discharge rate. Four functional SNPs, -1616T/C (rs2069705, -764G/C (rs2069707, +874A/T (rs2430561 and +3234C/T (rs2069718, were genotyped by Snapshot in both sepsis patients and healthy controls. Pearson's chi-square test or Fisher's exact test were used to analyze the distribution of the SNPs, and the probability values (P values, odds ratios (OR and 95% confidence intervals (CIs were calculated.No mutations in the IFN-γ -764G/C SNP were detected among the participants in our study. The +874A/T and +3234C/T SNPs were in strong linkage disequilibrium (LD (r(2 = 0.894. The -1616 TC+TT, +874 AT+AA genotype and the TAC haplotype were significantly associated with sepsis susceptibility, while the CTT haplotype was associated with protection against sepsis incidence. Genotype of -1616 TT wasn't only protective against severity of sepsis, but also against higher APACHE II and SOFA scores as +874 AA and +3234 CC. The TAC haplotype was was protective against progression to severe sepsis either.Our results suggest that functional IFN-γ SNPs and their haplotypes are associated with pneumonia-induced sepsis.

  18. Social functioning as a predictor of the use of mental health resources in patients with severe mental disorder.

    Science.gov (United States)

    Bellido-Zanin, Gloria; Pérez-San-Gregorio, María Ángeles; Martín-Rodríguez, Agustín; Vázquez-Morejón, Antonio J

    2015-12-15

    Previous studies have tried to determine the factors causing greater use of health resources by patients with mental disorders. These studies have essentially focused on socio-economic variables. Nevertheless, many other variables, such as social functioning, have not yet been explored. This study aims to assess the effect of social functioning on mental health service use in a sample of patients with severe mental disorder (schizophrenia, other psychotic disorders or bipolar affective disorder) in an area of Spain. The Social Functioning Scale (SFS) was administered to 172 family members of patients with a severe mental disorder who were receiving care at a community mental health unit. Analysis of bivariate logistic regression identified specific areas as predictors of the use of mental health resources over a 12-month follow-up period. The overall social functioning score predicted need for hospital admissions. In addition, interpersonal behaviour had a major role in the number of outpatient visits, while social isolation significantly predicted the need for hospitalization. These results point out the necessity for including psychosocial variables, such as social functioning in current mental health resource use models. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. How does family functioning effect the outcome of family based treatment for adolescents with severe anorexia nervosa?

    Science.gov (United States)

    Wallis, Andrew; Miskovic-Wheatley, Jane; Madden, Sloane; Rhodes, Paul; Crosby, Ross D; Cao, Li; Touyz, Stephen

    2017-01-01

    The aim of this research was to investigate the relationship between family functioning, adolescent-parent attachment and remission, as well as changes in these variables over time for adolescents with severe anorexia nervosa treated with family based treatment (FBT). Understanding how families respond to treatment is important because the family will be the ongoing context for psychosocial development in the longer term. The relationship between family functioning and outcome is also an important variable because it is potentially modifiable during treatment and this may improve outcome. Fifty-seven female adolescents treated with FBT in a randomised controlled trial were assessed at baseline, FBT session 20 and 12-months post FBT session 20. Data on family functioning and adolescent-parent attachment was collected from patients and their parents at each time point. A series of regression analyses were used to determine the relationship between family functioning and comorbidity at baseline, and the relationship with remission status over time. Repeat measure mixed-effects models were used to assess changes in family functioning and attachment quality over time. Greater adolescent perceived family functioning impairment was positively related to psychiatric comorbidity at the start of treatment. Conversely, better family functioning predicted higher self-esteem and stronger attachment quality. Adolescent's reporting better general family functioning, communication and problem solving were more likely to be remitted at session 20, but not at 12-month follow-up. There was no overall improvement in family functioning for any respondent either during treatment or at follow-up, and no significant relationship between change and remission at either session 20 or follow-up. The adolescent's perspective on family functioning at the start of treatment impacts on a positive outcome. Addressing family issues earlier in FBT may be important for some patients. Further

  20. A Tandem Repeat in Decay Accelerating Factor 1 Is Associated with Severity of Murine Mercury-Induced Autoimmunity

    Directory of Open Access Journals (Sweden)

    David M. Cauvi

    2014-01-01

    Full Text Available Decay accelerating factor (DAF, a complement-regulatory protein, protects cells from bystander complement-mediated lysis and negatively regulates T cells. Reduced expression of DAF occurs in several systemic autoimmune diseases including systemic lupus erythematosus, and DAF deficiency exacerbates disease in several autoimmune models, including murine mercury-induced autoimmunity (mHgIA. Daf1, located within Hmr1, a chromosome 1 locus associated in DBA/2 mice with resistance to mHgIA, could be a candidate. Here we show that reduced Daf1 transcription in lupus-prone mice was not associated with a reduction in the Daf1 transcription factor SP1. Studies of NZB mice congenic for the mHgIA-resistant DBA/2 Hmr1 locus suggested that Daf1 expression was controlled by the host genome and not the Hmr1 locus. A unique pentanucleotide repeat variant in the second intron of Daf1 in DBA/2 mice was identified and shown in F2 intercrosses to be associated with less severe disease; however, analysis of Hmr1 congenics indicated that this most likely reflected the presence of autoimmunity-predisposing genetic variants within the Hmr1 locus or that Daf1 expression is mediated by the tandem repeat in epistasis with other genetic variants present in autoimmune-prone mice. These studies argue that the effect of DAF on autoimmunity is complex and may require multiple genetic elements.

  1. Longitudinal strain predicts left ventricular mass regression after aortic valve replacement for severe aortic stenosis and preserved left ventricular function.

    Science.gov (United States)

    Gelsomino, Sandro; Lucà, Fabiana; Parise, Orlando; Lorusso, Roberto; Rao, Carmelo Massimiliano; Vizzardi, Enrico; Gensini, Gian Franco; Maessen, Jos G

    2013-11-01

    We explored the influence of global longitudinal strain (GLS) measured with two-dimensional speckle-tracking echocardiography on left ventricular mass regression (LVMR) in patients with pure aortic stenosis (AS) and normal left ventricular function undergoing aortic valve replacement (AVR). The study population included 83 patients with severe AS (aortic valve area regression (all P regression in patients with pure AS undergoing AVR. Our findings must be confirmed by further larger studies.

  2. Functional survival after acute care for severe head injury at a designated trauma center in Hong Kong.

    Science.gov (United States)

    Taw, Benedict B T; Lam, Alan C S; Ho, Faith L Y; Hung, K N; Lui, W M; Leung, Gilberto K K

    2012-07-01

    Severe head injury is known to be a major cause of early mortalities and morbidities. Patients' long-term outcome after acute care, however, has not been widely studied. We aim to review the outcome of severely head-injured patients after discharge from acute care at a designated trauma center in Hong Kong. This is a retrospective study of prospectively collected data of patients admitted with severe head injuries between 2004 and 2008. Patients' functional status post-discharge was assessed using the Extended Glasgow Outcome Score (GOSE). Of a total of 1565 trauma patients, 116 had severe head injuries and 41 of them survived acute hospital care. Upon the last follow-up, 23 (56.1%) of the acute-care survivors had improvements in their GOSE, six (11.8%) experienced deteriorations, and 12 (23.5%) did not exhibit any change. The greatest improvement was observed in patients with GOSE of 5 and 6 upon discharge, but two of the 16 patients with GOSE 2 or 3 also had a good recovery. On logistic regression analysis, old age and prolonged acute hospital stay were found to be independent predictors of poor functional outcome after a mean follow-up duration of 42 months. Multidisciplinary neurorehabilitation service is an important component of comprehensive trauma care. Despite significant early mortalities, a proportion of severely head-injured patients who survive acute care may achieve good long-term functional recovery. Copyright © 2012, Asian Surgical Association. Published by Elsevier Taiwan LLC. All rights reserved.

  3. Traumatic Brain Injury Severity, Comorbidity, Social Support, Family Functioning, and Community Reintegration Among Veterans of the Afghanistan and Iraq Wars.

    Science.gov (United States)

    Pugh, Mary Jo; Swan, Alicia A; Carlson, Kathleen F; Jaramillo, Carlos A; Eapen, Blessen C; Dillahunt-Aspillaga, Christina; Amuan, Megan E; Delgado, Roxana E; McConnell, Kimberly; Finley, Erin P; Grafman, Jordan H

    2018-02-01

    To examine the association between traumatic brain injury (TBI) severity; social, family, and community reintegration outcomes; and return to work status among post-9/11 veterans in Department of Veterans Affairs (VA) care. Retrospective observational cohort study. Mail/online survey fielded to a national sample of veterans. Sample of post-9/11 veterans with at least 3 years of VA care stratified according to TBI severity and comorbidities who completed and returned surveys (N=2023). Not applicable. Deployment Risk and Resilience Inventory-2 family functioning and social support subscales; Military to Civilian Questionnaire; and employment status. Bivariate analyses revealed that veterans with every classification of TBI severity reported significantly more difficulty on social, family, and community reintegration outcomes than those with no TBI. In the fully adjusted model, veterans with unclassified and moderate/severe TBI reported significantly more difficulty with community reintegration and were less likely to be employed relative to those with no TBI; those with unclassified TBI also reported significantly more difficulty with family functioning. Veterans with mild TBI also reported significantly more difficulty with community reintegration. This study provides insight into long-term outcomes associated with TBI in post-9/11 veterans and suggests that exposure to TBI has a negative effect on social and family functioning, community reintegration, and return to work even after controlling for comorbidity, deployment experiences, and sociodemographic characteristics. Additional research is required to explicate what appears to be complex interactions among TBI severity, psychosocial well-being, combat exposures, and socioeconomic resources in this population. Published by Elsevier Inc.

  4. Olfactory identification and its relationship to executive functions, memory, and disability one year after severe traumatic brain injury.

    Science.gov (United States)

    Sigurdardottir, Solrun; Andelic, Nada; Skandsen, Toril; Anke, Audny; Roe, Cecilie; Holthe, Oyvor Oistensen; Wehling, Eike

    2016-01-01

    To explore the frequency of posttraumatic olfactory (dys)function 1 year after severe traumatic brain injury (TBI) and determine whether there is a relationship between olfactory identification and neuropsychological test performance, injury severity and TBI-related disability. A population-based multicenter study including 129 individuals with severe TBI (99 males; 16 to 85 years of age) that could accomplish neuropsychological examinations. Olfactory (dys)function (anosmia, hyposmia, normosmia) was assessed by the University of Pennsylvania Smell Identification Test (UPSIT) or the Brief Smell Identification Test (B-SIT). Three tests of the Delis-Kaplan Executive Function System (D-KEFS) were used to assess processing speed, verbal fluency, inhibition and set-shifting, and the California Verbal Learning Test-II was used to examine verbal memory. The Glasgow Outcome Scale-Extended (GOSE) was used to measure disability level. Employing 2 different smell tests in 2 equal-sized subsamples, the UPSIT sample (n = 65) classified 34% with anosmia and 52% with hyposmia, while the B-SIT sample (n = 64) classified 20% with anosmia and 9% with hyposmia. Individuals classified with anosmia by the B-SIT showed significantly lower scores for set-shifting, category switching fluency and delayed verbal memory compared to hyposmia and normosmia groups. Only the B-SIT scores were significantly correlated with neuropsychological performance and GOSE scores. Brain injury severity (Rotterdam CT score) and subarachnoid hemorrhage were related to anosmia. Individuals classified with anosmia demonstrated similar disability as those with hyposmia/normosmia. Different measures of olfaction may yield different estimates of anosmia. Nevertheless, around 1 third of individuals with severe TBI suffered from anosmia, which may also indicate poorer cognitive outcome. (c) 2015 APA, all rights reserved).

  5. Constraint-induced movement therapy promotes brain functional reorganization in stroke patients with hemiplegia

    Science.gov (United States)

    Wang, Wenqing; Wang, Aihui; Yu, Limin; Han, Xuesong; Jiang, Guiyun; Weng, Changshui; Zhang, Hongwei; Zhou, Zhiqiang

    2012-01-01

    Stroke patients with hemiplegia exhibit flexor spasms in the upper limb and extensor spasms in the lower limb, and their movement patterns vary greatly. Constraint-induced movement therapy is an upper limb rehabilitation technique used in stroke patients with hemiplegia; however, studies of lower extremity rehabilitation are scarce. In this study, stroke patients with lower limb hemiplegia underwent conventional Bobath therapy for 4 weeks as baseline treatment, followed by constraint-induced movement therapy for an additional 4 weeks. The 10-m maximum walking speed and Berg balance scale scores significantly improved following treatment, and lower extremity motor function also improved. The results of functional MRI showed that constraint-induced movement therapy alleviates the reduction in cerebral functional activation in patients, which indicates activation of functional brain regions and a significant increase in cerebral blood perfusion. These results demonstrate that constraint-induced movement therapy promotes brain functional reorganization in stroke patients with lower limb hemiplegia. PMID:25337108

  6. Functional outcome and health-related quality of life 10 years after moderate-to-severe traumatic brain injury.

    Science.gov (United States)

    Andelic, N; Hammergren, N; Bautz-Holter, E; Sveen, U; Brunborg, C; Røe, C

    2009-07-01

    To describe the functional outcome and health-related quality of life (HRQL) 10 years after moderate-to-severe traumatic brain injury (TBI). A retrospective, population-based study of 62 survivors of working-age with moderate-to-severe TBI injured in 1995/1996, and hospitalized at the Trauma Referral Center in Eastern Norway. Functional status was measured by the Glasgow Outcome Scale-Extended (GOS-E). HRQL was assessed by the SF-36 questionnaire. The mean current-age was 40.8 years. The frequency of epilepsy was 19% and the depression rate 31%. A majority had good recovery (48%) or moderate disability (44%). Employment rate was 58%. Functional and employment status were associated with initial injury severity in contrast to HRQL. Study patients had significantly lower scores in all SF-36 dimensions when compared with the general Norwegian population. At 10-years follow-up, our study population is still in their most productive years and affected domains should be considered in long-term follow-up and intervention programs.

  7. Frequency of worsening liver function in severe dengue hepatitis patients receiving paracetamol: A retrospective analysis of hospital data

    International Nuclear Information System (INIS)

    Syed, A.A.; Aslam, F.; Hakeem, H.; Siddiqui, F.; Nasir, N.

    2017-01-01

    To determine the frequency of worsening liver function among hospital in-patients with severe dengue hepatitis receiving paracetamol. Methods: This retrospective study was conducted at the Department of Medicine, Aga Khan University Hospital, Karachi, and comprised records of dengue patients with severe hepatitis who received paracetamol for control of fever between June 2007 and December 2014. Alanine aminotransferase at baseline and following paracetamol administration was noted, as well as dosage and duration of paracetamol, along with participants' demographic details. Frequency of patients who developed worsening or improvement of alanine aminotransferase was also noted. SPSS 19 was used for data analysis. Results: Of the 113 subjects, 73(64.6%) were male and 40(35.4%) were female. Overall improvement was observed in subsequent alanine aminotransferase levels (491 units per litre, IQR 356.5 TO 775 vs 151 units per litre, IQR 49.5 to 299.5). Most commonly prescribed dose of paracetamol was 2g (IQR 1 to 5 grams), which was taken for a median duration of 1 day (IQR 1 to 3 days). Moreover, 100(88.5 %) patients showed improvement in alanine aminotransferase. Only 13(11.5 %) patients developed worsening of alanine aminotransferase. Of those with worsening liver function, 8(61.5 %) were discharged home with no clinical deterioration and 5(38.5 %) deaths were observed. However, causes of deaths were unrelated to liver dysfunction. Conclusion: The frequency of worsening liver function following paracetamol administration in patients with severe dengue hepatitis was relatively low. (author)

  8. Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice.

    Science.gov (United States)

    Zhang, Yiqiang; Fischer, Kathleen E; Soto, Vanessa; Liu, Yuhong; Sosnowska, Danuta; Richardson, Arlan; Salmon, Adam B

    2015-06-15

    Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality, leading some to suggest this condition represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging. In female C57BL/6J mice fed a high-fat diet starting in adulthood, mortality was significantly increased as was oxidative damage in vivo. High fat-feeding significantly accelerated the decline in performance in several assays, including activity, gait, and rotarod. However, we also found that obesity had little effect on other markers of function and actually improved performance in grip strength, a marker of muscular function. Together, this first comprehensive assessment of longitudinal, functional changes in high fat-fed mice suggests that obesity may induce segmental acceleration of some of the aging process. Published by Elsevier Inc.

  9. Development of radiation-induced mutation techniques and functional genomics studies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Sub; Kang, Si Yong; Kim, Jin Baek [KAERI, Daejeon (Korea, Republic of); and others

    2012-01-15

    This project has been performed to develop plant genetic resources using radiation (gamma-rays, ion-beam, space environments), to conduct functional genomics studies with mutant resources, and to develop new radiation plant breeding techniques using various radiation sources during 3 years. In the first section, we developed flower genetic resources, functional crop resources, and bio-industrial plant resources. In the second section, we cloned several mutated genes and studied mechanisms of gene expression and genetic diversity of mutations induced by gamma-rays. In the third section, we developed new plant breeding techniques using gamma-phytotron, heavy ion-beam, and space environments. Based on these results, a total of 8 cultivars containing Chrysanthemum, Hibiscus, kenaf, rice, and soybean were applied for plant variety protection (PVP) and a total of 4 cultivars were registered for PVP. Also, license agreement for the dwarf type Hibiscus mutant 'Ggoma' was conducted with Supro co. and the manufacturing technology for natural antioxidant pear-grape vinegar was transferred into Enzenic co. Also, 8 gene sequences, such as F3'H and LDOX genes associated with flower color in Chrysanthemum and EPSPS gene from Korean lawn grass, were registered in the database of National Center for Biotechnology Information (NCBI). In the future study, we will develop new radiation mutation breeding techniques through the mutation spectrum induced by various radiation sources, the studies for mechanism of the cellular response to radiation, and the comparative{center_dot}structural{center_dot}functional genomics studies for useful traits.

  10. Social learning pathways in the relation between parental chronic pain and daily pain severity and functional impairment in adolescents with functional abdominal pain.

    Science.gov (United States)

    Stone, Amanda L; Bruehl, Stephen; Smith, Craig A; Garber, Judy; Walker, Lynn S

    2017-10-06

    Having a parent with chronic pain (CP) may confer greater risk for persistence of CP from childhood into young adulthood. Social learning, such as parental modeling and reinforcement, represents one plausible mechanism for the transmission of risk for CP from parents to offspring. Based on a 7-day pain diary in 154 pediatric patients with functional abdominal CP, we tested a model in which parental CP predicted adolescents' daily average CP severity and functional impairment (distal outcomes) via parental modeling of pain behaviors and parental reinforcement of adolescent's pain behaviors (mediators) and adolescents' cognitive appraisals of pain threat (proximal outcome representing adolescents' encoding of parents' behaviors). Results indicated significant indirect pathways from parental CP status to adolescent average daily pain severity (b = 0.18, SE = 0.08, 95% CI: 0.04, 0.31, p = 0.03) and functional impairment (b = 0.08, SE = 0.04, 95% CI: 0.02, 0.15, p = 0.03) over the 7-day diary period via adolescents' observations of parent pain behaviors and adolescent pain threat appraisal. The indirect pathway through parental reinforcing responses to adolescents' pain did not reach significance for either adolescent pain severity or functional impairment. Identifying mechanisms of increased risk for pain and functional impairment in children of parents with CP ultimately could lead to targeted interventions aimed at improving functioning and quality of life in families with chronic pain. Parental modeling of pain behaviors represents a potentially promising target for family based interventions to ameliorate pediatric chronic pain.

  11. Nephrotic range proteinuria as a strong risk factor for rapid renal function decline during pre-dialysis phase in type 2 diabetic patients with severely impaired renal function.

    Science.gov (United States)

    Kitai, Yuichiro; Doi, Yohei; Osaki, Keisuke; Sugioka, Sayaka; Koshikawa, Masao; Sugawara, Akira

    2015-12-01

    Proteinuria is an established risk factor for progression of renal disease, including diabetic nephropathy. The predictive power of proteinuria, especially nephrotic range proteinuria, for progressive renal deterioration has been well demonstrated in diabetic patients with normal to relatively preserved renal function. However, little is known about the relationship between severity of proteinuria and renal outcome in pre-dialysis diabetic patients with severely impaired renal function. 125 incident dialysis patients with type 2 diabetes were identified. This study was aimed at retrospectively evaluating the impact of nephrotic range proteinuria (urinary protein-creatinine ratio above 3.5 g/gCr) on renal function decline during the 3 months just prior to dialysis initiation. In total, 103 patients (82.4 %) had nephrotic range proteinuria. The median rate of decline in estimated glomerular filtration rate (eGFR) in this study population was 0.98 (interquartile range 0.51-1.46) ml/min/1.73 m(2) per month. Compared to patients without nephrotic range proteinuria, patients with nephrotic range proteinuria showed significantly faster renal function decline (0.46 [0.24-1.25] versus 1.07 [0.64-1.54] ml/min/1.73 m(2) per month; p = 0.007). After adjusting for gender, age, systolic blood pressure, serum albumin, calcium-phosphorus product, hemoglobin A1c, and use of an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker, patients with nephrotic range proteinuria showed a 3.89-fold (95 % CI 1.08-14.5) increased risk for rapid renal function decline defined as a decline in eGFR ≥0.5 ml/min/1.73 m(2) per month. Nephrotic range proteinuria is the predominant renal risk factor in type 2 diabetic patients with severely impaired renal function receiving pre-dialysis care.

  12. Abnormal Intrinsic Functional Hubs in Severe Male Obstructive Sleep Apnea: Evidence from a Voxel-Wise Degree Centrality Analysis.

    Science.gov (United States)

    Li, Haijun; Li, Lan; Shao, Yi; Gong, Honghan; Zhang, Wei; Zeng, Xianjun; Ye, Chenglong; Nie, Si; Chen, Liting; Peng, Dechang

    2016-01-01

    Obstructive sleep apnea (OSA) has been associated with changes in brain structure and regional function in certain brain areas. However, the functional features of network organization in the whole brain remain largely uncertain. The purpose of this study was to identify the OSA-related spatial centrality distribution of the whole brain functional network and to investigate the potential altered intrinsic functional hubs. Forty male patients with newly confirmed severe OSA on polysomnography, and well-matched good sleepers, participated in this study. All participants underwent a resting-state functional MRI scan and clinical and cognitive evaluation. Voxel-wise degree centrality (DC) was measured across the whole brain, and group difference in DC was compared. The relationship between the abnormal DC value and clinical variables was assessed using a linear correlation analysis. Remarkably similar spatial distributions of the functional hubs (high DC) were found in both groups. However, OSA patients exhibited a pattern of significantly reduced regional DC in the left middle occipital gyrus, posterior cingulate cortex, left superior frontal gyrus, and bilateral inferior parietal lobule, and DC was increased in the right orbital frontal cortex, bilateral cerebellum posterior lobes, and bilateral lentiform nucleus, including the putamen, extending to the hippocampus, and the inferior temporal gyrus, which overlapped with the functional hubs. Furthermore, a linear correlation analysis revealed that the DC value in the posterior cingulate cortex and left superior frontal gyrus were positively correlated with Montreal cognitive assessment scores, The DC value in the left middle occipital gyrus and bilateral inferior parietal lobule were negatively correlated with apnea-hypopnea index and arousal index in OSA patients. Our findings suggest that OSA patients exhibited specific abnormal intrinsic functional hubs including relatively reduced and increased DC. This expands

  13. Child and parent perceived food-induced gastrointestinal symptoms and quality of life in children with functional gastrointestinal disorders.

    Science.gov (United States)

    Carlson, Michelle J; Moore, Carolyn E; Tsai, Cynthia M; Shulman, Robert J; Chumpitazi, Bruno P

    2014-03-01

    It is unknown whether children with functional gastrointestinal (GI) disorders identify specific foods that exacerbate their GI symptoms. The objectives of this study were to determine the perceived role of food on GI symptoms and to determine the impact of food-induced symptoms on quality of life (QOL) in children with functional GI disorders. Between August and November 2010, 25 children ages 11 to 17 years old with functional GI disorders and a parent completed a food symptom association questionnaire and validated questionnaires assessing FGID symptoms and QOL. In addition, children completed a 24-hour food recall, participated in focus groups to identify problematic foods and any coping strategies, and discussed how their QOL was affected. Statistical analyses were conducted using χ2, t test, Mann-Whitney U test, Wilcoxon signed rank, and Spearman's ρ. Children identified a median of 11 (range=2 to 25) foods as exacerbating a GI symptom, with the most commonly identified foods being spicy foods, cow's milk, and pizza. Several coping strategies were identified, including consuming smaller portions, modifying foods, and avoiding a median of 8 (range=1 to 20) foods. Children reported that food-induced symptoms interfered with school performance, sports, and social activities. Although the parent's assessment of their child's QOL negatively correlated with the number of perceived symptom-inducing foods in their child, this relationship was not found in the children. Findings suggest that specific foods are perceived to exacerbate GI symptoms in children with functional GI disorders. In addition, despite use of several coping strategies, food-induced symptoms can adversely impact children's QOL in several important areas. Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  14. Altered Brain Functional Activity in Infants with Congenital Bilateral Severe Sensorineural Hearing Loss: A Resting-State Functional MRI Study under Sedation

    Directory of Open Access Journals (Sweden)

    Shuang Xia

    2017-01-01

    Full Text Available Early hearing deprivation could affect the development of auditory, language, and vision ability. Insufficient or no stimulation of the auditory cortex during the sensitive periods of plasticity could affect the function of hearing, language, and vision development. Twenty-three infants with congenital severe sensorineural hearing loss (CSSHL and 17 age and sex matched normal hearing subjects were recruited. The amplitude of low frequency fluctuations (ALFF and regional homogeneity (ReHo of the auditory, language, and vision related brain areas were compared between deaf infants and normal subjects. Compared with normal hearing subjects, decreased ALFF and ReHo were observed in auditory and language-related cortex. Increased ALFF and ReHo were observed in vision related cortex, which suggest that hearing and language function were impaired and vision function was enhanced due to the loss of hearing. ALFF of left Brodmann area 45 (BA45 was negatively correlated with deaf duration in infants with CSSHL. ALFF of right BA39 was positively correlated with deaf duration in infants with CSSHL. In conclusion, ALFF and ReHo can reflect the abnormal brain function in language, auditory, and visual information processing in infants with CSSHL. This demonstrates that the development of auditory, language, and vision processing function has been affected by congenital severe sensorineural hearing loss before 4 years of age.

  15. Abnormal functional connectivity of brain network hubs associated with symptom severity in treatment-naive patients with obsessive-compulsive disorder: A resting-state functional MRI study.

    Science.gov (United States)

    Tian, Lin; Meng, Chun; Jiang, Ying; Tang, Qunfeng; Wang, Shuai; Xie, Xiyao; Fu, Xiangshuai; Jin, Chunhui; Zhang, Fuquan; Wang, Jidong

    2016-04-03

    Abnormal brain networks have been observed in patients with obsessive-compulsive disorder (OCD). However, detailed network hub and connectivity changes remained unclear in treatment-naive patients with OCD. Here, we sought to determine whether patients show hub-related connectivity changes in their whole-brain functional networks. We used resting-state functional magnetic resonance imaging data and voxel-based graph-theoretic analysis to investigate functional connectivity strength and hubs of whole-brain networks in 29 treatment-naive patients with OCD and 29 age- and gender-matched healthy controls. Correlation analysis was applied for potential associations with OCD symptom severity. OCD selectively targeted brain regions of higher functional connectivity strength than the average including brain network hubs, mainly distributed in the cortico-striato-thalamo-cortical (CSTC) circuits and additionally parietal, occipital, temporal and cerebellar regions. Moreover, affected functional connectivity strength in the cerebellum, the medial orbitofrontal cortex and superior occipital cortex was significantly associated with global OCD symptom severity. Our results provide the evidence about OCD-related brain network hub changes, not only in the CSTC circuits but more distributed in whole brain networks. Data suggest that whole brain network hub analysis is useful for understanding the pathophysiology of OCD. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. [Effects of astragalus polysaccharide on intestinal immune function of rats with severe scald injury].

    Science.gov (United States)

    Huang, Cuilan; Zhan, Jianhua; Luo, Jinhua

    2015-02-01

    To observe the effects of astragalus polysaccharide (AP) on the intestinal mucosal morphology, level of secretory IgA (s-IgA) in intestinal mucus, and distribution of T lymphocyte subsets in Peyer's patch in rats with severe scald injury. One hundred and thirty SD rats were divided into sham injury group (SI, sham injured, n = 10), scald group (S, n = 30), low dosage group (LD, n = 30), moderate dosage group (MD, n = 30), and high dosage group (HD, n = 30) according to the random number table. Rats in the latter 4 groups were inflicted with 30% TBSA full-thickness scald on the back. From post injury hour 2, rats in groups LD, MD, and HD were intraperitoneally injected with 0.5 mL AP solution with the dosage of 100, 200, and 300 mg/kg each day respectively, and rats in group S were injected with 0.5 mL normal saline instead. Ten rats from group SI immediately after injury and 10 rats from each of the latter 4 groups on post injury day (PID) 3, 7, 14 were sacrificed, and their intestines were harvested. The morphology of ileal mucosa was examined after HE staining; the level of s-IgA in ileal mucus was determined with double-antibody sandwich ELISA method; the proportions of CD3⁺, CD4⁺, CD8⁺ T lymphocytes in Peyer's patches of intestine were determined with flow cytometer, and the proportion of CD4⁺ to CD8⁺ was calculated. Data were processed with one-way analysis of variance, analysis of variance of factorial design, and SNK test. (1) Villi in normal form and intact villus epithelial cells were observed in rats of group SI immediately after injury, while edema of villi and necrosis and desquamation of an enormous amount of villi were observed in groups with scalded rats on PID 3, with significant infiltration of inflammatory cells. On PID 7, no obvious improvement in intestinal mucosal lesion was observed in groups with scalded rats. On PID 14, the pathology in intestinal mucosa of rats remained nearly the same in group S, and it was alleviated obviously

  17. A numerical investigation of the functionality of coronary bifurcation lesions with respect to lesion configuration and stenosis severity.

    Science.gov (United States)

    Pagiatakis, Catherine; Tardif, Jean-Claude; L'Allier, Philippe L; Mongrain, Rosaire

    2015-09-18

    The intervention of coronary bifurcation lesions is associated with higher rates of peri- and post-procedural clinical events compared to the treatment of isolated lesions. Overall, the factors that influence the dynamics of these types of configurations are still not well understood. A geometric multiscale model, consisting of a 3D representation of the left main coronary artery bifurcation and a 0D representation of the rest of the cardiovascular system, was developed. Computational fluid dynamics simulations of the 3D domain were executed by implementing the multiscale algorithm, in order to characterize the functionality of different multilesional configurations as a function of stenosis severity. The investigation found that coronary branch steal has a significant impact on the functionality of the disease and can render a two-lesion configuration more severe compared to a three-lesion configuration. As a result of the complexity of this phenomenon, it was also suggested that certain lesion configurations could result in false negatives in diagnosis when employing a pullback pressure recording across the tandem lesions. In conclusion, this study showed that coronary bifurcation lesions are subject to intricate haemodynamic interactions which render the characterization of their functionality complex and could have significant clinical implications with regards to their diagnosis and prognosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Genetic Variability in Platelet Integrin α2β1 Density: Possible Contributor to Plasmodium vivax–induced Severe Thrombocytopenia

    Science.gov (United States)

    Campos, Fernanda M. F.; Santos, Marina L. S.; Kano, Flora S.; Fontes, Cor J. F.; Lacerda, Marcus V. G.; Brito, Cristiana F. A.; Carvalho, Luzia H.

    2013-01-01

    Understanding the pathogenesis of Plasmodium vivax malaria is challenging. We hypothesized that susceptibility to P. vivax-induced thrombocytopenia could be associated with polymorphisms on relevant platelet membrane integrins: integrin α2 (C807T), and integrin β3 (T1565C). Although β3 polymorphism was not related with P. vivax malaria, α2 807T carriers, which show high levels of integrin α2β1, had a higher probability for severe thrombocytopenia than wild-type carriers. This evidence of the association of integrin polymorphism and P. vivax morbidity was further demonstrated by a moderate but significant correlation between clinical disease and surface levels of the integrin α2β1. PMID:23249684

  19. Prophylactic Injection of Recombinant Alpha-Enolase Reduces Arthritis Severity in the Collagen-Induced Arthritis Mice Model.

    Directory of Open Access Journals (Sweden)

    Clément Guillou

    Full Text Available To evaluate the ability of the glycolytic enzyme alpha-enolase (ENO1 or its immunodominant peptide (pEP1 to reduce the severity of CIA in DBA/1 mice when injected in a prophylactic way.Mice were treated with mouse ENO1 or pEP1 one day prior to collagen II immunization. Clinical assessment was evaluated using 4 parameters (global and articular scores, ankle thickness and weight. Titers of serum anti-ENO1, anti-cyclic citrullinated peptides (anti-CCP and anti-CII (total IgG and IgG1/IgG2a isotypes antibodies were measured by ELISA at different time-points. Disease activity was assessed by histological analysis of both anterior and hind paws at the end of experimentation.Prophylactic injection of 100 μg of ENO1 reduced severity of CIA. Serum levels of anti-CII antibodies were reduced in ENO1-treated mice. Concordantly, ENO1-treated mice joints presented less severe histological signs of arthritis. ENO1 did not induce a shift toward a Th2 response since IgG1/IgG2a ratio of anti-CII antibodies remained unchanged and IL-4 serum levels were similar to those measured in the control group.Pre-immunization with ENO1 or its immunodominant peptide pEP1 reduces CIA severity at the clinical, immunological and histological levels. Effects of pEP1 were less pronounced. This immunomodulatory effect is associated with a reduction in anti-CII antibodies production but is not due to a Th1/Th2 shift.

  20. Prophylactic Injection of Recombinant Alpha-Enolase Reduces Arthritis Severity in the Collagen-Induced Arthritis Mice Model

    Science.gov (United States)

    Guillou, Clément; Derambure, Céline; Fréret, Manuel; Verdet, Mathieu; Avenel, Gilles; Golinski, Marie-Laure; Sabourin, Jean-Christophe; Loarer, François Le; Adriouch, Sahil; Boyer, Olivier; Lequerré, Thierry; Vittecoq, Olivier

    2015-01-01

    Objective To evaluate the ability of the glycolytic enzyme alpha-enolase (ENO1) or its immunodominant peptide (pEP1) to reduce the severity of CIA in DBA/1 mice when injected in a prophylactic way. Methods Mice were treated with mouse ENO1 or pEP1 one day prior to collagen II immunization. Clinical assessment was evaluated using 4 parameters (global and articular scores, ankle thickness and weight). Titers of serum anti-ENO1, anti-cyclic citrullinated peptides (anti-CCP) and anti-CII (total IgG and IgG1/IgG2a isotypes) antibodies were measured by ELISA at different time-points. Disease activity was assessed by histological analysis of both anterior and hind paws at the end of experimentation. Results Prophylactic injection of 100 μg of ENO1 reduced severity of CIA. Serum levels of anti-CII antibodies were reduced in ENO1-treated mice. Concordantly, ENO1-treated mice joints presented less severe histological signs of arthritis. ENO1 did not induce a shift toward a Th2 response since IgG1/IgG2a ratio of anti-CII antibodies remained unchanged and IL-4 serum levels were similar to those measured in the control group. Conclusions Pre-immunization with ENO1 or its immunodominant peptide pEP1 reduces CIA severity at the clinical, immunological and histological levels. Effects of pEP1 were less pronounced. This immunomodulatory effect is associated with a reduction in anti-CII antibodies production but is not due to a Th1/Th2 shift. PMID:26302382

  1. Test-retest reliability of maximal leg muscle power and functional performance measures in patients with severe osteoarthritis (OA)

    DEFF Research Database (Denmark)

    Villadsen, Allan; Roos, Ewa M.; Overgaard, Søren

    Abstract : Purpose To evaluate the reliability of single-joint and multi-joint maximal leg muscle power and functional performance measures in patients with severe OA. Background Muscle power, taking both strength and velocity into account, is a more functional measure of lower extremity muscle...... and scheduled for unilateral total hip (n=9) or knee (n=11) replacement. Patients underwent a test battery on two occasions separated by approximately one week (range 7 to 11 days). Muscle power was measured using: 1. A linear encoder, unilateral lower limb isolated single-joint dynamic movement, e.g. knee...... flexion 2. A leg extension press, unilateral multi-joint knee and hip extension Functional performance was measured using: 1. 20 m walk usual pace 2. 20 m walk maximal pace 3. 5 times chair stands 4. Maximal number of knee bends/30sec Pain was measured on a VAS prior to and after conducting the entire...

  2. High-throughput identification of off-targets for the mechanistic study of severe adverse drug reactions induced by analgesics

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Jian-Bo [Department of Chemical Biology, College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian 361005 (China); Ji, Nan; Pan, Wen; Hong, Ru [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102 (China); Wang, Hao [Department of Chemical Biology, College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian 361005 (China); Ji, Zhi-Liang, E-mail: appo@xmu.edu.cn [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102 (China); Department of Chemical Biology, College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian 361005 (China)

    2014-01-01

    Drugs may induce adverse drug reactions (ADRs) when they unexpectedly bind to proteins other than their therapeutic targets. Identification of these undesired protein binding partners, called off-targets, can facilitate toxicity assessment in the early stages of drug development. In this study, a computational framework was introduced for the exploration of idiosyncratic mechanisms underlying analgesic-induced severe adverse drug reactions (SADRs). The putative analgesic-target interactions were predicted by performing reverse docking of analgesics or their active metabolites against human/mammal protein structures in a high-throughput manner. Subsequently, bioinformatics analyses were undertaken to identify ADR-associated proteins (ADRAPs) and pathways. Using the pathways and ADRAPs that this analysis identified, the mechanisms of SADRs such as cardiac disorders were explored. For instance, 53 putative ADRAPs and 24 pathways were linked with cardiac disorders, of which 10 ADRAPs were confirmed by previous experiments. Moreover, it was inferred that pathways such as base excision repair, glycolysis/glyconeogenesis, ErbB signaling, calcium signaling, and phosphatidyl inositol signaling likely play pivotal roles in drug-induced cardiac disorders. In conclusion, our framework offers an opportunity to globally understand SADRs at the molecular level, which has been difficult to realize through experiments. It also provides some valuable clues for drug repurposing. - Highlights: • A novel computational framework was developed for mechanistic study of SADRs. • Off-targets of drugs were identified in large scale and in a high-throughput manner. • SADRs like cardiac disorders were systematically explored in molecular networks. • A number of ADR-associated proteins were identified.

  3. High-throughput identification of off-targets for the mechanistic study of severe adverse drug reactions induced by analgesics

    International Nuclear Information System (INIS)

    Pan, Jian-Bo; Ji, Nan; Pan, Wen; Hong, Ru; Wang, Hao; Ji, Zhi-Liang

    2014-01-01

    Drugs may induce adverse drug reactions (ADRs) when they unexpectedly bind to proteins other than their therapeutic targets. Identification of these undesired protein binding partners, called off-targets, can facilitate toxicity assessment in the early stages of drug development. In this study, a computational framework was introduced for the exploration of idiosyncratic mechanisms underlying analgesic-induced severe adverse drug reactions (SADRs). The putative analgesic-target interactions were predicted by performing reverse docking of analgesics or their active metabolites against human/mammal protein structures in a high-throughput manner. Subsequently, bioinformatics analyses were undertaken to identify ADR-associated proteins (ADRAPs) and pathways. Using the pathways and ADRAPs that this analysis identified, the mechanisms of SADRs such as cardiac disorders were explored. For instance, 53 putative ADRAPs and 24 pathways were linked with cardiac disorders, of which 10 ADRAPs were confirmed by previous experiments. Moreover, it was inferred that pathways such as base excision repair, glycolysis/glyconeogenesis, ErbB signaling, calcium signaling, and phosphatidyl inositol signaling likely play pivotal roles in drug-induced cardiac disorders. In conclusion, our framework offers an opportunity to globally understand SADRs at the molecular level, which has been difficult to realize through experiments. It also provides some valuable clues for drug repurposing. - Highlights: • A novel computational framework was developed for mechanistic study of SADRs. • Off-targets of drugs were identified in large scale and in a high-throughput manner. • SADRs like cardiac disorders were systematically explored in molecular networks. • A number of ADR-associated proteins were identified

  4. Regeneration of alveolar type I and II cells from Scgb1a1-expressing cells following severe pulmonary damage induced by bleomycin and influenza.

    Directory of Open Access Journals (Sweden)

    Dahai Zheng

    Full Text Available The lung comprises an extensive surface of epithelia constantly exposed to environmental insults. Maintaining the integrity of the alveolar epithelia is critical for lung function and gaseous exchange. However, following severe pulmonary damage, what progenitor cells give rise to alveolar type I and II cells during the regeneration of alveolar epithelia has not been fully determined. In this study, we have investigated this issue by using transgenic mice in which Scgb1a1-expressing cells and their progeny can be genetically labeled with EGFP. We show that following severe alveolar damage induced either by bleomycin or by infection with influenza virus, the majority of the newly generated alveolar type II cells in the damaged parenchyma were labeled with EGFP. A large proportion of EGFP-expressing type I cells were also observed among the type II cells. These findings strongly suggest that Scgb1a1-expressing cells, most likely Clara cells, are a major cell type that gives rise to alveolar type I and II cells during the regeneration of alveolar epithelia in response to severe pulmonary damage in mice.

  5. Prevotella intermedia induces severe bacteremic pneumococcal pneumonia in mice with upregulated platelet-activating factor receptor expression.

    Science.gov (United States)

    Nagaoka, Kentaro; Yanagihara, Katsunori; Morinaga, Yoshitomo; Nakamura, Shigeki; Harada, Tatsuhiko; Hasegawa, Hiroo; Izumikawa, Koichi; Ishimatsu, Yuji; Kakeya, Hiroshi; Nishimura, Masaharu; Kohno, Shigeru

    2014-02-01

    Streptococcus pneumoniae is the leading cause of respiratory infection worldwide. Although oral hygiene has been considered a risk factor for developing pneumonia, the relationship between oral bacteria and pneumococcal infection is unknown. In this study, we examined the synergic effects of Prevotella intermedia, a major periodontopathic bacterium, on pneumococcal pneumonia. The synergic effects of the supernatant of P. intermedia (PiSup) on pneumococcal pneumonia were investigated in mice, and the stimulation of pneumococcal adhesion to human alveolar (A549) cells by PiSup was assessed. The effects of PiSup on platelet-activating factor receptor (PAFR) transcript levels in vitro and in vivo were analyzed by quantitative real-time PCR, and the differences between the effects of pneumococcal infection induced by various periodontopathic bacterial species were verified in mice. Mice inoculated with S. pneumoniae plus PiSup exhibited a significantly lower survival rate, higher bacterial loads in the lungs, spleen, and blood, and higher inflammatory cytokine levels in the bronchoalveolar lavage fluid (macrophage inflammatory protein 2 and tumor necrosis factor alpha) than those infected without PiSup. In A549 cells, PiSup increased pneumococcal adhesion and PAFR transcript levels. PiSup also increased lung PAFR transcript levels in mice. Similar effects were not observed in the supernatants of Porphyromonas gingivalis or Fusobacterium nucleatum. Thus, P. intermedia has the potential to induce severe bacteremic pneumococcal pneumonia with enhanced pneumococcal adhesion to lower airway cells.

  6. Severity of exercise-induced ischemia with chest pain and recovery from ischemia after the disappearance of chest pain

    International Nuclear Information System (INIS)

    Akutsu, Yasushi; Shinozuka, Akira; Kodama, Yusuke; Li, Hui-Ling; Yamanaka, Hideyuki; Katagiri, Takashi

    2004-01-01

    The severity of exercise-induced painful ischemia and its recovery after the disappearance of pain are unknown. The aim of this study was to investigate the difference in severity of ischemia at both exercise and postexercise between painful ischemia and painless ischemia. After injections of technetium-99m tetrofosmin at peak ergometer exercise and thallium-201 at 3 minutes postexercise, dual-isotope single photon emission tomography was performed in 78 patients with angiographically proven ischemic heart disease. The extent of ischemic areas (the number of areas), the depth of ischemia in the ischemic area (the severity score of ischemia) and the extension of ischemia toward long axis of the left ventricle (the number of left ventricular levels with ischemic areas in apical, middle, and basal levels) at both exercise and postexercise were compared on the basis of the presence of pain and a history of diabetes mellitus (DM). The symptoms improved within 3 minutes postexercise in all painful ischemia patients. Of 59 patients with reversible ischemia, except for 4 painful ischemia patients with DM, the extent and depth of ischemia at postexercise were more severe in 14 painful ischemia patients without DM and 13 painless ischemia patients with DM than 28 painless ischemia patients without DM (extent; 2.9±1.7 areas, 3.5±2.8 areas versus 1.4±1.8 areas, P=0.005, depth; 3.8±3.1 scores, 5.8±5.4 scores versus 1.9±3.0 scores, P=0.0084, respectively) despite a comparable severity of ischemia at peak exercise (extent; 5.4±2.6 areas, 6.0±2.4 areas versus 4.3±3.3 areas, depth; 9.3±5.7 scores, 10.7±7.3 scores and 7.5±8.1 scores, all NS). The extension of ischemia toward long-axis of the left ventricle at both peak exercise and postexercise was more severe in the former 2 groups than the latter group (peak exercise; 2.4±0.6 levels, 2.5±0.7 levels versus 1.9 ±0.8 levels, P=0.0263, postexercise: 1.8±0.7 levels, 1.5±0.9 levels versus 0.8±0.8 levels, P=0

  7. Bifidobacterium breve alters immune function and ameliorates DSS-induced inflammation in weanling rats.

    Science.gov (United States)

    Izumi, Hirohisa; Minegishi, Mario; Sato, Yohei; Shimizu, Takashi; Sekine, Kazunori; Takase, Mitsunori

    2015-10-01

    Bifidobacterium breve M-16V (M16V) is a probiotic bacterial strain with a long tradition of use in neonatal intensive care units in some countries. Previous study showed that the effects of M16V administration on gene expression were greater during the weaning period than in the neonatal period and were greater in the colon than in the small intestine and spleen, suggesting that M16V has anti-inflammatory effects. In this study, we evaluated the effects of inflammation during the weaning period and the effects of M16V on normal and inflammatory conditions. From postnatal day (PD) 21 to 34, weanling rats were administered of 2.5 × 10(9) of M16V daily, and colitis was induced by administration of 2% dextran sulfate sodium from PD28 to 35. Colitis severity, immune function, and microbiota were investigated. Colitis caused a reduction in body weight gain, colon shortening, poor nutritional status, anemia, changes in blood and spleen lymphocyte populations, spleen T-cell malfunctions, and alterations in colon microbiota. M16V administration improved some but not all of the changes induced by colitis. M16V could suppress inflammation and, therefore, can be considered a safe strain to use not only during the neonatal period but also the weaning period.

  8. The impact of depressive and bipolar symptoms on socioeconomic status, core symptoms, function and severity of fibromyalgia.

    Science.gov (United States)

    Gota, Carmen E; Kaouk, Sahar; Wilke, William S

    2017-03-01

    To evaluate the prevalence of depressive and bipolar symptoms in a cohort of consecutive fibromyalgia (FM) patients seen in a tertiary care center and to determine the relationship between depressive and manic symptoms with FM symptoms, socioeconomic status, severity and function. Three hundred and five FM patients were enrolled; demographic, clinical and questionnaire data were collected. Depressive symptoms were measured by the Patient Health Questionnaire (PHQ-9), manic symptoms by the Mood Disorders Questionnaire (MDQ). The FM cohort had the following characteristics: age 43.53 (11.7) years; 86.5% white; 82.7% female; PHQ-9 ≥ 10, 59.7%, mean 11.9 (7.3); no depression 11.4%, mild 29.1%, moderate 27.5%, moderate severe 17.7%, severe 14%; anxiety 41.6%; 21.3% had either an MDQ score ≥ 7 and/or reported a past diagnosis of bipolar disorder (BD). Increasing levels of depression severity, as well as a positive screen for BD were significantly associated with increasing prevalence and severity of FM symptoms, longer duration of morning stiffness, and increased severity of FM. Increasing levels of depression were significantly associated with increase in prevalence of reported past sexual abuse, and a decline in socioeconomic status, including higher disability and unemployment rates. Patients with severe FM disease activity, high load of symptoms, prolonged morning stiffness, increased disability, lower socioeconomic status and those who take a lot of medications for FM should be evaluated for depressive and manic symptoms. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  9. Registration-based assessment of regional lung function via volumetric CT images of normal subjects vs. severe asthmatics

    Science.gov (United States)

    Choi, Sanghun; Hoffman, Eric A.; Wenzel, Sally E.; Tawhai, Merryn H.; Yin, Youbing; Castro, Mario

    2013-01-01

    The purpose of this work was to explore the use of image registration-derived variables associated with computed tomographic (CT) imaging of the lung acquired at multiple volumes. As an evaluation of the utility of such an imaging approach, we explored two groups at the extremes of population ranging from normal subjects to severe asthmatics. A mass-preserving image registration technique was employed to match CT images at total lung capacity (TLC) and functional residual capacity (FRC) for assessment of regional air volume change and lung deformation between the two states. Fourteen normal subjects and thirty severe asthmatics were analyzed via image registration-derived metrics together with their pulmonary function test (PFT) and CT-based air-trapping. Relative to the normal group, the severely asthmatic group demonstrated reduced air volume change (consistent with air trapping) and more isotropic deformation in the basal lung regions while demonstrating increased air volume change associated with increased anisotropic deformation in the apical lung regions. These differences were found despite the fact that both PFT-derived TLC and FRC in the two groups were nearly 100% of predicted values. Data suggest that reduced basal-lung air volume change in severe asthmatics was compensated by increased apical-lung air volume change and that relative increase in apical-lung air volume change in severe asthmatics was accompanied by enhanced anisotropic deformation. These data suggest that CT-based deformation, assessed via inspiration vs. expiration scans, provides a tool for distinguishing differences in lung mechanics when applied to the extreme ends of a population range. PMID:23743399

  10. Impact of Chronic Neonatal Intermittent Hypoxia on Severity of Retinal Damage in a Rat Model of Oxygen-Induced Retinopathy.

    Science.gov (United States)

    Beharry, Kay D; Cai, Charles L; Ahmad, Taimur; Guzel, Sibel; Valencia, Gloria B; Aranda, Jacob V

    2018-01-01

    Neonatal intermittent hypoxia (IH) followed by re-oxygenation in normoxia or supplemental oxygen (IHR) increases the risk for severe retinopathy of prematurity (ROP). The exact timing for the onset of retinal damage which may guide strategic interventions during retinal development, is unknown. We tested the hypothesis that chronic exposure of the immature retina to neonatal IH induces early manifestations of retinal damage that can be utilized as key time points for strategic pharmacologic intervention. Newborn rats were exposed to IH within 2 hours of birth (P0) until P14, or allowed to recover in room air (RA) from P14 to P21 (IHR). Retinal integrity and angiogenesis biomarkers were progressively assessed before (P0), during IH, and post IH (recovery in RA), or IHR, and compared to normoxic age-matched controls. Retinal damage occurred as early as day 3 of neonatal IH, consistent with vascular abnormalities and disturbances in the astrocytic template. These abnormalities worsened during IHR. Pharmacologic and non-pharmacologic interventions to identify, prevent, or minimize neonatal IH should be implemented shortly after birth in high risk preterm newborns. This strategy may lead to a reduction in the outcome of severe ROP requiring later invasive treatments.

  11. Electroacupuncture at Zusanli Prevents Severe Scalds-Induced Gut Ischemia and Paralysis by Activating the Cholinergic Pathway

    Directory of Open Access Journals (Sweden)

    Huan Wang

    2015-01-01

    Full Text Available Severe burn injuries may result in gastrointestinal paralysis, and barrier dysfunction due to gut ischemia and lowered vagus excitability. In this study we investigate whether electroacupuncture (EA at Zusanli (ST36 could prevent severe scalds-induced gut ischemia, paralysis, and barrier dysfunction and whether the protective role of EA at ST36 is related to the vagus nerve. 35% burn area rats were divided into six groups: (a EAN: EA nonchannel acupoints followed by scald injury; (b EA: EA at ST36 after scald injury; (c VGX/EA: vagotomy (VGX before EA at ST36 and scald injury; (d VGX/EAN: VGX before EAN and scald injury; (e atropine/EA: applying atropine before scald injury and then EA at ST36; (f atropine/EAN: applying atropine before scald injury and then EA at nonchannel acupoints. EA at the Zusanli point significantly promoted the intestinal impelling ratio and increased the amount of mucosal blood flow after scald injury. The plasma diamine oxidase (DAO and intestinal permeability decreased significantly after scald injury in the EA group compared with others. However, EA after atropine injection or cervical vagotomy failed to improve intestinal motility and mucosa blood flow suggesting that the mechanism of EA may be related to the activation of the cholinergic nerve pathway.

  12. Integral excitation functions for proton and alpha induced reactions on target elements 22 <= Z <= 28

    International Nuclear Information System (INIS)

    Brinkmann, G.

    1979-01-01

    In the framework of a systematic study which is also important for certain cosmological questions a series of integral excitation functions of p- and α-induced nuclear reactions on target elements 22 [de

  13. High-functioning autism patients share similar but more severe impairments in verbal theory of mind than schizophrenia patients.

    Science.gov (United States)

    Tin, L N W; Lui, S S Y; Ho, K K Y; Hung, K S Y; Wang, Y; Yeung, H K H; Wong, T Y; Lam, S M; Chan, R C K; Cheung, E F C

    2018-06-01

    Evidence suggests that autism and schizophrenia share similarities in genetic, neuropsychological and behavioural aspects. Although both disorders are associated with theory of mind (ToM) impairments, a few studies have directly compared ToM between autism patients and schizophrenia patients. This study aimed to investigate to what extent high-functioning autism patients and schizophrenia patients share and differ in ToM performance. Thirty high-functioning autism patients, 30 schizophrenia patients and 30 healthy individuals were recruited. Participants were matched in age, gender and estimated intelligence quotient. The verbal-based Faux Pas Task and the visual-based Yoni Task were utilised to examine first- and higher-order, affective and cognitive ToM. The task/item difficulty of two paradigms was examined using mixed model analyses of variance (ANOVAs). Multiple ANOVAs and mixed model ANOVAs were used to examine group differences in ToM. The Faux Pas Task was more difficult than the Yoni Task. High-functioning autism patients showed more severely impaired verbal-based ToM in the Faux Pas Task, but shared similar visual-based ToM impairments in the Yoni Task with schizophrenia patients. The findings that individuals with high-functioning autism shared similar but more severe impairments in verbal ToM than individuals with schizophrenia support the autism-schizophrenia continuum. The finding that verbal-based but not visual-based ToM was more impaired in high-functioning autism patients than schizophrenia patients could be attributable to the varied task/item difficulty between the two paradigms.

  14. The Effect of Different Intensities of Treadmill Exercise on Cognitive Function Deficit Following a Severe Controlled Cortical Impact in Rats

    Directory of Open Access Journals (Sweden)

    Xiafeng Shen

    2013-10-01

    Full Text Available Exercise has been proposed for the treatment of traumatic brain injury (TBI. However, the proper intensity of exercise in the early phase following a severe TBI is largely unknown. To compare two different treadmill exercise intensities on the cognitive function following a severe TBI in its early phase, rats experienced a controlled cortical impact (CCI and were forced to treadmill exercise for 14 days. The results revealed that the rats in the low intensity exercise group had a shorter latency to locate a platform and a significantly better improvement in spatial memory in the Morris water maze (MWM compared to the control group (p 0.05. The brain-derived neurotrophic factor (BDNF and p-CREB protein levels in the contralateral hippocampus were increased significantly in the low intensity exercise group. Our results suggest that 2 weeks of low intensity of treadmill exercise is beneficial for improving cognitive function and increasing hippocampal BDNF expression after a severe TBI in its early phase.

  15. Gravity induced corrections to quantum mechanical wave functions

    International Nuclear Information System (INIS)

    Singh, T.P.

    1990-03-01

    We perform a semiclassical expansion in the Wheeler-DeWitt equation, in powers of the gravitational constant. We then show that quantum gravitational fluctuations can provide a correction to the wave-functions which are solutions of the Schroedinger equation for matter. This also implies a correction to the expectation values of quantum mechanical observables. (author). 6 refs

  16. Functional MRI of food-induced brain responses

    NARCIS (Netherlands)

    Smeets, P.A.M.

    2006-01-01

    The ultimate goal of this research was to find central biomarkers of satiety, i.e., physiological measures in the brain that relate to subjectively rated appetite, actual food intake, or both. This thesis describes the changes in brain activity in response to food stimuli as measured by functional

  17. Functional polymeric materials : Complexing amphiphiles as structure-inducing elements

    NARCIS (Netherlands)

    ten Brinke, G.; Ikkala, O.

    2003-01-01

    Self-assembly of polymeric comb-shaped supramolecules is a powerful tool to prepare functional materials. Enhanced conductivity due to hexagonal self-organization of conducting polyaniline and polarized photoluminance in solid-state films of rodlike poly(2,5-pyridinediyl) obtained by removing

  18. Hyperoxia-Induced Proliferative Retinopathy: Early Interruption of Retinal Vascular Development with Severe and Irreversible Neurovascular Disruption.

    Directory of Open Access Journals (Sweden)

    Michelle Lajko

    Full Text Available Bronchopulmonary dysplasia (BPD is a major cause of neonatal morbidity in premature infants, occurring as a result of arrested lung development combined with multiple postnatal insults. Infants with BPD exposed to supplemental oxygen are at risk of retinopathy of prematurity as well. Thus, we studied the effects of hyperoxia on the retinal vasculature in a murine model of BPD. The retinal phenotype of this model, which we termed hyperoxia-induced proliferative retinopathy (HIPR, shows severe disruption of retinal vasculature and loss of vascular patterning, disorganized intra-retinal angiogenesis, inflammation and retinal detachment. Neonatal mice were subjected to 75% oxygen exposure from postnatal day (P0 to P14 to model BPD, then allowed to recover in room air for 1 (P15, 7 (P21, or 14 days (P28. We quantified retinal thickness, protein levels of HIF-1α, NOX2, and VEGF, and examined the cellular locations of these proteins by immunohistochemistry. We examined the retinal blood vessel integrity and inflammatory markers, including macrophages (F4/80 and lymphocytes (CD45R. Compared to controls, normal retinal vascular development was severely disrupted and replaced by a disorganized sheet of intra-retinal angiogenesis in the HIPR mice. At all time-points, HIPR showed persistent hyaloidal vasculature and a significantly thinner central retina compared to controls. HIF-1α protein levels were increased at P15, while VEGF levels continued to increase until P21. Intra-retinal fibrinogen was observed at P21 followed by sub-retinal deposition in at P28. Inflammatory lymphocytes and macrophages were observed at P21 and P28, respectively. This model presents a severe phenotype of disrupted retinal vascular development, intra-retinal angiogenesis inflammation and retinal detachment.

  19. C-Speak Aphasia alternative communication program for people with severe aphasia: importance of executive functioning and semantic knowledge.

    Science.gov (United States)

    Nicholas, Marjorie; Sinotte, Michele P; Helm-Estabrooks, Nancy

    2011-06-01

    Learning how to use a computer-based communication system can be challenging for people with severe aphasia even if the system is not word-based. This study explored cognitive and linguistic factors relative to how they affected individual patients' ability to communicate expressively using C-Speak Aphasia (CSA), an alternative communication computer program that is primarily picture-based. Ten individuals with severe non-fluent aphasia received at least six months of training with CSA. To assess carryover of training, untrained functional communication tasks (i.e., answering autobiographical questions, describing pictures, making telephone calls, describing a short video, and two writing tasks) were repeatedly probed in two conditions: (1) using CSA in addition to natural forms of communication, and (2) using only natural forms of communication, e.g., speaking, writing, gesturing, drawing. Four of the 10 participants communicated more information on selected probe tasks using CSA than they did without the computer. Response to treatment was also examined in relation to baseline measures of non-linguistic executive function skills, pictorial semantic abilities, and auditory comprehension. Only nonlinguistic executive function skills were significantly correlated with treatment response.

  20. Measurements of the proton light output function of the organic liquid scintillator NE213 in several detectors

    Energy Technology Data Exchange (ETDEWEB)

    Hawkes, N.P.; Adams, J.M.; Bond, D.S.; Croft, S; Jarvis, O.N. E-mail: onj@jet.uk; Watkins, N

    2002-01-01

    When using an organic liquid scintillator such as NE213 for neutron spectrometry, the light output as a function of proton energy is needed in order to unfold the neutron spectrum from the scintillator's pulse height distribution. We have measured this function for several detectors over the range 1.5-16 MeV approximately, using monoenergetic neutrons from the Harwell 5 MV Van de Graaff accelerator. Results were obtained for a wide variety of sizes and shapes of the scintillator cell, and were found to be essentially in agreement within errors. The results were also compared with those of several other workers (amongst whom there is considerable disagreement). Below 10 MeV, there is excellent agreement with one worker and moderate or poor agreement with others; above 10 MeV, agreement is moderate in all cases. We conclude that workers wishing to unfold neutron spectra from NE213 pulse height distributions would be advised to make measurements with their own particular detector configuration, rather than use published functions.

  1. C-Speak Aphasia Alternative Communication Program for People with Severe Aphasia: Importance of Executive Functioning and Semantic Knowledge

    Science.gov (United States)

    Nicholas, Marjorie; Sinotte, Michele P.; Helm-Estabrooks, Nancy

    2011-01-01

    Learning how to use a computer-based communication system can be challenging for people with severe aphasia even if the system is not word-based. This study explored cognitive and linguistic factors relative to how they affected individual patients’ ability to communicate expressively using C-Speak Aphasia, (CSA), an alternative communication computer program that is primarily picture-based. Ten individuals with severe non-fluent aphasia received at least six months of training with CSA. To assess carryover of training, untrained functional communication tasks (i.e., answering autobiographical questions, describing pictures, making telephone calls, describing a short video, and two writing tasks) were repeatedly probed in two conditions: 1) using CSA in addition to natural forms of communication, and 2) using only natural forms of communication, e.g., speaking, writing, gesturing, drawing. Four of the ten participants communicated more information on selected probe tasks using CSA than they did without the computer. Response to treatment also was examined in relation to baseline measures of non-linguistic executive function skills, pictorial semantic abilities, and auditory comprehension. Only nonlinguistic executive function skills were significantly correlated with treatment response. PMID:21506045

  2. Improved split renal function after percutaneous nephrostomy in young adults with severe hydronephrosis due to ureteropelvic junction obstruction.

    Science.gov (United States)

    Zhang, Shiwei; Zhang, Qing; Ji, Changwei; Zhao, Xiaozhi; Liu, Guangxiang; Zhang, Shun; Li, Xiaogong; Lian, Huibo; Zhang, Gutian; Guo, Hongqian

    2015-01-01

    We evaluated percutaneous nephrostomy for adult kidneys with severe hydronephrosis due to ureteropelvic junction obstruction and less than 10% split renal function. In this retrospective analysis we included patients who underwent percutaneous nephrostomy for unilateral ureteropelvic junction obstruction of the kidneys with hydronephrosis and less than 10% split renal function at our hospital between May 2009 and January 2012. Adults (age 18 years or greater) were divided into those 35 years or younger (young adults) and older than 35 years (older adults). The percutaneous nephrostomy remained in situ a mean ± SD of 6.62 ± 2.55 weeks and patients underwent repeat renography before pyeloplasty. When there was no significant improvement in split renal function (10% or greater) and drainage (greater than 400 ml per day), nephrectomy was performed. Otherwise pyeloplasty was performed. Patients were followed by renography, ultrasound and contrast computerized tomography at 3 and 6 months, at 1 year and annually thereafter. Of 53 patients 30 (56.6%) showed improvement after percutaneous nephrostomy drainage and urine output greater than 400 ml per day with percutaneous nephrostomy. Pyeloplasty was then performed. Of 29 young adults 24 (82.8%) showed improved split renal function vs 6 of 24 older adults (25%). Nephrectomy of the other 23 kidneys was performed. At a mean followup of 19.27 ± 7.82 months (range 12 to 36), no patient showed hypertension or urinary tract infection. Split renal function detected by renography may not accurately predict recovered, poorly functioning kidneys, especially in young adults. First observing the recoverability of hydronephrotic kidneys by percutaneous nephrostomy drainage and then preserving select kidneys may be an effective method to manage poorly functioning kidneys due to ureteropelvic junction obstruction. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights

  3. Functional cardiotoxicity assessment of cosmetic compounds using human-induced pluripotent stem cell-derived cardiomyocytes.

    Science.gov (United States)

    Chaudhari, Umesh; Nemade, Harshal; Sureshkumar, Poornima; Vinken, Mathieu; Ates, Gamze; Rogiers, Vera; Hescheler, Jürgen; Hengstler, Jan Georg; Sachinidis, Agapios

    2018-01-01

    There is a large demand of a human relevant in vitro test system suitable for assessing the cardiotoxic potential of cosmetic ingredients and other chemicals. Using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), we have already established an in vitro cardiotoxicity assay and identified genomic biomarkers of anthracycline-induced cardiotoxicity in our previous work. Here, five cosmetic ingredients were studied by the new hiPSC-CMs test; kojic acid (KJA), triclosan (TS), triclocarban (TCC), 2,7-naphthalenediol (NPT), and basic red 51 (BR51) based on cytotoxicity as well as ATP assays, beating rate, and genomic biomarkers to determine the lowest observed effect concentration (LOEC) and no observed effect concentration (NOEC). The LOEC for beating rate were 400, 10, 3, >400, and 3 µM for KJA, TS, TCC, NPT, and BR51, respectively. The corresponding concentrations for cytotoxicity or ATP depletion were similar, with the exception of TS and TCC, where the cardiomyocyte-beating assay showed positive results at non-cytotoxic concentrations. Functional analysis also showed that the individual compounds caused different effects on hiPSC-CMs. While exposure to KJA, TS, TCC, and BR51 induced significant arrhythmic beating, NPT slightly decreased cell viability, but did not influence beating. Gene expression studies showed that TS and NPT caused down-regulation of cytoskeletal and cardiac ion homeostasis genes. Moreover, TS and NPT deregulated genomic biomarkers known to be affected also by anthracyclines. The present study demonstrates that hiPSC-CMs can be used to determine LOECs and NOECs in vitro, which can be compared to human blood concentrations to determine margins of exposure. Our in vitro assay, which so far has been tested with several anthracyclines and cosmetics, still requires validation by larger numbers of positive and negative controls, before it can be recommended for routine analysis.

  4. Functional MRI of CO2 induced increase in cerebral perfusion

    DEFF Research Database (Denmark)

    Rostrup, Egill; Larsson, H B; Toft, P B

    1994-01-01

    The sensitivity of MR gradient echo imaging towards CO2 induced changes in cerebral blood flow was investigated in 10 normal subjects. The subjects were inhaling 5% and 7% CO2 and the experiments were carried out at 1.5 T (n = 6) and 2.0 T (n = 5), allowing a comparison of field strengths....... Additional experiments were carried out using a higher spatial resolution. The largest signal increases were noted in areas corresponding to larger vessels, but significant changes were also conspicuous in deeper cortical and central grey matter. The changes appeared linearly related to the arterial CO2...... tension, within the range of PaCO2 studied. In white matter, the changes were not statistically significant....

  5. Functional analysis of chloroplast early light inducible proteins (ELIPs)

    Energy Technology Data Exchange (ETDEWEB)

    Wetzel, Carolyn M

    2005-02-22

    The objectives of this project were to characterize gene expression patterns of early light inducible protein (ELIP) genes in Arabidopsis thaliana and in Lycopersicon esculentum, to identify knock mutants of the 2 ELIP genes in Arabidopsis, and to characterize the effects of the knockouts. Expression in Arabidopsis was studied in response to thylakoid electron transport chain (PETC) capacity, where it was found that there is a signal for expression associated with reduction of the PETC. Expression in response to salt was also studied, with different responses of the two gene copies. Knockout lines for ELIP1 and ELIP2 have been identified and are being characterized. In tomato, it was found that the single-copy ELIP gene is highly expressed in ripening fruit during the chloroplast-to-chromoplast transition. Studies of expression in tomato ripening mutants are ongoing.

  6. Acute Malaria Induces PD1+CTLA4+ Effector T Cells with Cell-Extrinsic Suppressor Function.

    Directory of Open Access Journals (Sweden)

    Maria Sophia Mackroth

    2016-11-01

    Full Text Available In acute Plasmodium falciparum (P. falciparum malaria, the pro- and anti-inflammatory immune pathways must be delicately balanced so that the parasitemia is controlled without inducing immunopathology. An important mechanism to fine-tune T cell responses in the periphery is the induction of coinhibitory receptors such as CTLA4 and PD1. However, their role in acute infections such as P. falciparum malaria remains poorly understood. To test whether coinhibitory receptors modulate CD4+ T cell functions in malaria, blood samples were obtained from patients with acute P. falciparum malaria treated in Germany. Flow cytometric analysis showed a more frequent expression of CTLA4 and PD1 on CD4+ T cells of malaria patients than of healthy control subjects. In vitro stimulation with P. falciparum-infected red blood cells revealed a distinct population of PD1+CTLA4+CD4+ T cells that simultaneously produced IFNγ and IL10. This antigen-specific cytokine production was enhanced by blocking PD1/PDL1 and CTLA4. PD1+CTLA4+CD4+ T cells were further isolated based on surface expression of PD1 and their inhibitory function investigated in-vitro. Isolated PD1+CTLA4+CD4+ T cells suppressed the proliferation of the total CD4+ population in response to anti-CD3/28 and plasmodial antigens in a cell-extrinsic manner. The response to other specific antigens was not suppressed. Thus, acute P. falciparum malaria induces P. falciparum-specific PD1+CTLA4+CD4+ Teffector cells that coproduce IFNγ and IL10, and inhibit other CD4+ T cells. Transient induction of regulatory Teffector cells may be an important mechanism that controls T cell responses and might prevent severe inflammation in patients with malaria and potentially other acute infections.

  7. Autoimmune Pancreatitis Can Transform Into Chronic Features Similar to Advanced Chronic Pancreatitis With Functional Insufficiency Following Severe Calcification.

    Science.gov (United States)

    Kanai, Keita; Maruyama, Masahiro; Kameko, Fumiko; Kawasaki, Kenji; Asano, Junpei; Oguchi, Takaya; Watanabe, Takayuki; Ito, Tetsuya; Muraki, Takashi; Hamano, Hideaki; Matsumoto, Akihiro; Arakura, Norikazu; Kawa, Shigeyuki

    2016-09-01

    Because several studies for autoimmune pancreatitis (AIP) have revealed pancreatic calcification resembling that in chronic pancreatitis (CP), we sought to clarify whether AIP could transform into chronic features similar to advanced CP with severe pancreatic dysfunction. Pancreatic functions of 92 AIP patients, 47 definite CP patients, and 30 healthy controls were assessed by fecal elastase-1 concentration (FEC), fasting immunoreactive insulin (IRI), and homeostatic model assessment (HOMA)-R. The 92 AIP patients included 17 (18%) with severe calcification (SC) and 75 without. The FEC levels in AIP and CP patients were significantly lower than that in controls. Exocrine insufficiency defined as FEC less than 200 μg/g was 39% in AIP without SC, 56% in AIP with SC, and 74% in CP. Fasting IRI and C-peptide reactivity values in CP were significantly lower than those in AIP, with no significant differences between AIP subgroups. The prevalence of endocrine insufficiency according to fasting IRI less than 5.0 μU/mL was 26% in AIP without SC, 31% in AIP with SC, and 59% in CP, respectively. HOMA-R values were significantly higher in all AIP groups than in CP. Autoimmune pancreatitis can transform into a state of pancreatic insufficiency after calcification that is less severe than that in definite CP.

  8. Altered functional brain connectivity in patients with visually induced dizziness

    Directory of Open Access Journals (Sweden)

    Angelique Van Ombergen

    2017-01-01

    Conclusions: We found alterations in the visual and vestibular cortical network in VID patients that could underlie the typical VID symptoms such as a worsening of their vestibular symptoms when being exposed to challenging visual stimuli. These preliminary findings provide the first insights into the underlying functional brain connectivity in VID patients. Future studies should extend these findings by employing larger sample sizes, by investigating specific task-based paradigms in these patients and by exploring the implications for treatment.

  9. Repeated pulse feeding induces functional stability in anaerobic digestion.

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