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Other Publications (200)
- American Journal of Epidemiology
- American Journal of Epidemiology
- American Journal of Epidemiology
- American Journal of Epidemiology
- American Journal of Epidemiology
- Hypertension
- BMC Bioinformatics
- Medical Care
- Journal of Animal Science
- Physiological Genomics
- G3 (Bethesda, Md.)
- Experimental Lung Research
- Biochimica Et Biophysica Acta
- Lancet Neurology
- Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer
- Frontiers of Medicine
- Annals of Behavioral Medicine : a Publication of the Society of Behavioral Medicine
- PloS One
- PloS One
- Dermatologic Surgery : Official Publication for American Society for Dermatologic Surgery [et Al.]
- Journal of Neurotrauma
- Journal of the International Neuropsychological Society : JINS
- Microscopy and Microanalysis : the Official Journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada
- Journal of Wildlife Diseases
- Canadian Respiratory Journal : Journal of the Canadian Thoracic Society
- Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology
- American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
- Cell Reports
- Heart Rhythm : the Official Journal of the Heart Rhythm Society
- AJNR. American Journal of Neuroradiology
- The Journal of Bone and Joint Surgery. American Volume
- Canadian Family Physician Médecin De Famille Canadien
- Journal of Neurological Surgery. Part A, Central European Neurosurgery
- Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A
- Women & Health
- Dalton Transactions (Cambridge, England : 2003)
- PloS One
- Sports Biomechanics / International Society of Biomechanics in Sports
- The Journal of Physician Assistant Education : the Official Journal of the Physician Assistant Education Association
- The New Phytologist
- Behavioural Processes
- Journal of Analytical Toxicology
- Cochrane Database of Systematic Reviews (Online)
- Influenza and Other Respiratory Viruses
- Journal of Neurotrauma
- Public Health Nursing (Boston, Mass.)
- Clinical Oncology (Royal College of Radiologists (Great Britain))
- American Journal of Preventive Medicine
- American Journal of Preventive Medicine
- Eye (London, England)
- Cytometry. Part A : the Journal of the International Society for Analytical Cytology
- PloS One
- Case Reports in Hematology
- The Practising Midwife
- The Medical Journal of Malaysia
- The Southeast Asian Journal of Tropical Medicine and Public Health
- Aging & Mental Health
- Tissue Engineering. Part A
- The Journal of Rural Health : Official Journal of the American Rural Health Association and the National Rural Health Care Association
- Psychiatry Research
- Gastrointestinal Endoscopy Clinics of North America
- Journal of Pediatric Surgery
- The Urologic Clinics of North America
- The Journal of Pediatrics
- Breast Cancer Research and Treatment
- Genetics
- Cerebellum (London, England)
- Frontiers in Neuroscience
- Environmental Science & Technology
- Journal of Strength and Conditioning Research / National Strength & Conditioning Association
- Prevention Science : the Official Journal of the Society for Prevention Research
- Cancer Management and Research
- The Spine Journal : Official Journal of the North American Spine Society
- Foot and Ankle Surgery : Official Journal of the European Society of Foot and Ankle Surgeons
- PM & R : the Journal of Injury, Function, and Rehabilitation
- Journal of Genetic Counseling
- The Journal of Clinical Endocrinology and Metabolism
- Chronic Illness
- Proceedings of the National Academy of Sciences of the United States of America
- Expert Opinion on Pharmacotherapy
- Rural and Remote Health
- Gerontology & Geriatrics Education
- ISRN Neurology
- Revista Panamericana De Salud Pública = Pan American Journal of Public Health
- Science Translational Medicine
- Collegian (Royal College of Nursing, Australia)
- Collegian (Royal College of Nursing, Australia)
- Collegian (Royal College of Nursing, Australia)
- Journal of the American Academy of Child and Adolescent Psychiatry
- Journal of Clinical Anesthesia
- Physical Review Letters
- The Orthopedic Clinics of North America
- Theriogenology
- Journal of Emergency Nursing: JEN : Official Publication of the Emergency Department Nurses Association
- Nature Neuroscience
- Journal of Hepatology
- Journal of Neurochemistry
- Molecular Ecology
- NeuroImage
- PLoS Biology
- PloS One
- BMC Public Health
- Academic Medicine : Journal of the Association of American Medical Colleges
- Arthritis and Rheumatism
- Gastrointestinal Cancer Research : GCR
- Scandinavian Journal of Infectious Diseases
- Ecology Letters
- European Journal of Applied Physiology
- PloS One
- ACS Nano
- Accounts of Chemical Research
- BMC Research Notes
- Leukemia Research
- Journal of Neurology, Neurosurgery, and Psychiatry
- Journal of Analytical Toxicology
- Expert Review of Clinical Pharmacology
- Sociology of Health & Illness
- International Journal of Language & Communication Disorders / Royal College of Speech & Language Therapists
- Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases
- Eating Behaviors
- Eating Behaviors
- Drug and Alcohol Dependence
- Proteomics
- Risk Analysis : an Official Publication of the Society for Risk Analysis
- Micron (Oxford, England : 1993)
- Chemical Communications (Cambridge, England)
- Pediatrics
- Health Affairs (Project Hope)
- Anaesthesia
- Annals of the Royal College of Surgeons of England
- Current Opinion in Gastroenterology
- International Journal of Epidemiology
- Multiple Sclerosis (Houndmills, Basingstoke, England)
- PLoS Genetics
- Molecular Plant-microbe Interactions : MPMI
- Clinical Orthopaedics and Related Research
- Journal of Community Health Nursing
- Journal of Community Health Nursing
- Metallomics : Integrated Biometal Science
- The International Journal of Artificial Organs
- Emergency Medicine Journal : EMJ
- Circulation Research
- Child Abuse & Neglect
- Cell
- Journal of Microbiological Methods
- Contemporary Clinical Trials
- Archives of Disease in Childhood
- Nature Structural & Molecular Biology
- Radiology
- Emergency Medicine Journal : EMJ
- Carcinogenesis
- BMC Pulmonary Medicine
- British Journal of Haematology
- Medical Teacher
- The Journal of Allergy and Clinical Immunology
- Annals of Epidemiology
- Journal of Psychiatric Research
- The Journal of Trauma and Acute Care Surgery
- Journal of Pediatric Orthopedics
- Psychiatry Research
- Journal of the Mechanical Behavior of Biomedical Materials
- Midwifery
- Molecular and Cellular Biology
- Neurosurgery
- Drug Metabolism and Disposition: the Biological Fate of Chemicals
- Proceedings of the National Academy of Sciences of the United States of America
- Journal of Psychopharmacology (Oxford, England)
- Toxicological Sciences : an Official Journal of the Society of Toxicology
- Health Promotion International
- Irish Medical Journal
- Irish Medical Journal
- Journal of Advanced Nursing
- Fertility and Sterility
- Biomaterials
- Structure (London, England : 1993)
- Acta Biomaterialia
- Biomechanics and Modeling in Mechanobiology
- Cancer Genomics & Proteomics
- Cellular Logistics
- Conservation Biology : the Journal of the Society for Conservation Biology
- Alimentary Pharmacology & Therapeutics
- Journal of Psychiatric and Mental Health Nursing
- Gastrointestinal Endoscopy
- Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society
- Natural Product Reports
- The Journal of Cell Biology
- Endocrine Research
- Journal of Advanced Nursing
- Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine
- Seminars in Fetal & Neonatal Medicine
- Behaviour Research and Therapy
- BMC Genomics
- Plant Biotechnology Journal
- The Journal of Bone and Joint Surgery. American Volume
- G3 (Bethesda, Md.)
- Joint Commission Journal on Quality and Patient Safety / Joint Commission Resources
- American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
- Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc
- BMJ Case Reports
- Cytokine
Articles by Conor W. Kelly in JoVE
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Et let, Hovedtelefoner-baseret system til at manipulere Auditiv Feedback i Songbirds
Lukas A. Hoffmann1,2, Conor W. Kelly1,3, David A. Nicholson1,2, Samuel J. Sober1
1Department of Biology, Emory University, 2Neuroscience Graduate Program, Emory University, 3Program in Neuroscience and Behavioral Biology, Emory University
Vi beskriver design og montage af miniaturiserede hovedtelefoner egnet til at erstatte en sangfugl naturlige auditive feedback med et manipuleret akustisk signal. Online lydbehandling hardware bruges til at manipulere sang output, introducere real-time fejl i auditiv feedback via hovedtelefonerne, og køre vokal motorisk indlæring.
Other articles by Conor W. Kelly on PubMed
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Dietary Protein Intake and Blood Pressure: a Meta-analysis of Randomized Controlled Trials
American Journal of Epidemiology.
Oct, 2012 |
Pubmed ID: 23035142 The authors conducted a meta-analysis of randomized controlled trials to evaluate the association of dietary protein intake with blood pressure. To identify articles published before April 2011, the authors searched electronic databases, conducted a manual bibliography review, and consulted experts in the field. Forty trials (including 3,277 participants in total) met the eligibility criteria and were included. Using a standardized form, 2 investigators independently abstracted data on study design, participant characteristics, and treatment outcomes. Net change estimates were pooled across trials using random-effects models. Compared with carbohydrate, dietary protein intake was associated with significant changes in mean systolic and diastolic blood pressure of -1.76 mm Hg (95% confidence interval (CI): -2.33, -1.20) and -1.15 mm Hg (95% CI: -1.59, -0.71), respectively (both P 's < 0.001). Both vegetable protein and animal protein were associated with significant blood pressure changes of -2.27 mm Hg (95% CI: -3.36, -1.18) and -2.54 mm Hg (95% CI: -3.55, -1.53), respectively, for systolic blood pressure (both P 's < 0.001) and -1.26 mm Hg (95% CI: -2.26, -0.26) and -0.95 mm Hg (95% CI: -1.72, -0.19), respectively, for diastolic blood pressure (both P 's = 0.014). Blood pressure reduction was not significantly different when vegetable protein was compared directly with animal protein. These findings indicate that partially replacing dietary carbohydrate with protein may be important for the prevention and treatment of hypertension.
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Effects of Low-carbohydrate Diets Versus Low-fat Diets on Metabolic Risk Factors: a Meta-analysis of Randomized Controlled Clinical Trials
American Journal of Epidemiology.
Oct, 2012 |
Pubmed ID: 23035144 The effects of low-carbohydrate diets (≤45% of energy from carbohydrates) versus low-fat diets (≤30% of energy from fat) on metabolic risk factors were compared in a meta-analysis of randomized controlled trials. Twenty-three trials from multiple countries with a total of 2,788 participants met the predetermined eligibility criteria (from January 1, 1966 to June 20, 2011) and were included in the analyses. Data abstraction was conducted in duplicate by independent investigators. Both low-carbohydrate and low-fat diets lowered weight and improved metabolic risk factors. Compared with participants on low-fat diets, persons on low-carbohydrate diets experienced a slightly but statistically significantly lower reduction in total cholesterol (2.7 mg/dL; 95% confidence interval: 0.8, 4.6), and low density lipoprotein cholesterol (3.7 mg/dL; 95% confidence interval: 1.0, 6.4), but a greater increase in high density lipoprotein cholesterol (3.3 mg/dL; 95% confidence interval: 1.9, 4.7) and a greater decrease in triglycerides (-14.0 mg/dL; 95% confidence interval: -19.4, -8.7). Reductions in body weight, waist circumference and other metabolic risk factors were not significantly different between the 2 diets. These findings suggest that low-carbohydrate diets are at least as effective as low-fat diets at reducing weight and improving metabolic risk factors. Low-carbohydrate diets could be recommended to obese persons with abnormal metabolic risk factors for the purpose of weight loss. Studies demonstrating long-term effects of low-carbohydrate diets on cardiovascular events were warranted.
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Maternal History of Hypertension and Blood Pressure Response to Potassium Intake: The GenSalt Study
American Journal of Epidemiology.
Oct, 2012 |
Pubmed ID: 23035145 The relation between parental history of hypertension and blood pressure response to potassium intake is unknown. A 7-day high-sodium followed by a 7-day high-sodium plus potassium dietary-feeding study was conducted from 2003 to 2005 among 1,871 Chinese participants. Those with a maternal history of hypertension had larger systolic blood pressure responses to potassium compared with those without: -4.31 (95% confidence interval (CI): -4.99, -3.62) mm Hg versus -3.35 (95% CI: -4.00, -2.70) mm Hg, respectively (P(difference) = 0.002). A consistent trend was observed for diastolic blood pressure responses: -1.80 (95% CI: -2.41, -1.20) mm Hg versus -1.35 (95% CI: -1.95, -0.74) mm Hg, respectively (P = 0.07). Stronger associations between early onset maternal hypertension and blood pressure responses were noted, with systolic blood pressure decreases of -4.80 (95% CI: -5.65, -3.95) mm Hg versus -3.55 (95% CI: -4.17, -2.93) mm Hg and diastolic blood pressure decreases of -2.25 (95% CI: -3.01, -1.50) mm Hg versus -1.42 (95% CI: -1.99, -0.85) mm Hg among those with early onset maternal hypertension versus those without, respectively (P = 0.001 and 0.009, respectively). Odds ratios for high potassium sensitivity were 1.36 (95% CI: 0.96, 1.92) and 1.60 (95% CI: 1.08, 2.36) for those with maternal hypertension and early onset maternal hypertension, respectively (P = 0.08 and 0.02, respectively). Potassium supplementation could help to reduce blood pressure among those with a maternal history of hypertension.
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Reproducibility of Blood Pressure Response to the Cold Pressor Test: The GenSalt Study
American Journal of Epidemiology.
Oct, 2012 |
Pubmed ID: 23035148 An elevated blood pressure (BP) response to the cold pressor test (CPT) is associated with increased risk of hypertension and cardiovascular disease. However, it is still unclear whether BP response to the CPT is a stable and reproducible trait over time. Using the same study protocol, the authors repeated the CPT 4.5 years after initial administration among 568 Han Chinese in rural northern China (2003-2005 and 2008-2009). BP was measured using a standard mercury sphygmomanometer prior to and 0, 1, 2, and 4 minutes after the participants immersed their hand in ice water (3°C-5°C) for 1 minute. Absolute BP levels and BP responses during the CPT in the initial and repeated administrations were highly correlated. For example, the correlation coefficients were 0.67, 0.73, 0.71, and 0.72 for absolute systolic BP levels at 0, 1, 2, and 4 minutes after ice-water immersion (all P 's < 0.0001). The correlation coefficients for systolic BP response were 0.41 at 0 minutes, 0.37 at 1 minute, 0.42 for maximum response, and 0.39 for the area under the curve during CPT (all P 's < 0.0001). These data indicate that BP response to the CPT is a long-term reproducible and stable characteristic in the general population.
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Lower Mortality in Magnet Hospitals
Medical Care.
Oct, 2012 |
Pubmed ID: 23047129 BACKGROUND:: Although there is evidence that hospitals recognized for nursing excellence-Magnet hospitals-are successful in attracting and retaining nurses, it is uncertain whether Magnet recognition is associated with better patient outcomes than non-Magnets, and if so why. OBJECTIVES:: To determine whether Magnet hospitals have lower risk-adjusted mortality and failure-to-rescue compared with non-Magnet hospitals, and to determine the most likely explanations. METHOD AND STUDY DESIGN:: Analysis of linked patient, nurse, and hospital data on 56 Magnet and 508 non-Magnet hospitals. Logistic regression models were used to estimate differences in the odds of mortality and failure-to-rescue for surgical patients treated in Magnet versus non-Magnet hospitals, and to determine the extent to which differences in outcomes can be explained by nursing after accounting for patient and hospital differences. RESULTS:: Magnet hospitals had significantly better work environments and higher proportions of nurses with bachelor's degrees and specialty certification. These nursing factors explained much of the Magnet hospital effect on patient outcomes. However, patients treated in Magnet hospitals had 14% lower odds of mortality (odds ratio 0.86; 95% confidence interval, 0.76-0.98; P=0.02) and 12% lower odds of failure-to-rescue (odds ratio 0.88; 95% confidence interval, 0.77-1.01; P=0.07) while controlling for nursing factors as well as hospital and patient differences. CONCLUSIONS:: The lower mortality we find in Magnet hospitals is largely attributable to measured nursing characteristics but there is a mortality advantage above and beyond what we could measure. Magnet recognition identifies existing quality and stimulates further positive organizational behavior that improves patient outcomes.
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Expression of Key Genes of the Somatotropic Axis in Longissimus Dorsi Muscle of Beef Heifers Phenotypically Divergent for Residual Feed Intake
Journal of Animal Science.
Oct, 2012 |
Pubmed ID: 23048153 This study evaluated the effect of residual feed intake (RFI) on the expression of constituent genes of the somatotropic axis in skeletal muscle across 2 diverse dietary regimes. Beef heifers (n = 86; initial BW = 191.8 kg [SD = 37]) fed a low-forage (LF) total mixed ration comprised of 70:30 concentrate:corn silage (11.0 MJ ME/kg DM) were ranked on RFI. The 10 highest- (high RFI) and 10 lowest- (low RFI) ranking animals were selected for the current study. Biopsies of the M. longissimus dorsi were harvested at the end of LF dietary period and again following a 6-wk period during which heifers were offered a high-forage (HF) grass silage only diet (9.7MJ ME/kg DM). Real-time PCR was used to quantify mRNA transcripts of 11 genes including IGF-1, IGF-2, their receptors (IGF-1R; IGF-2R), 6 IGFBP, and GH receptor (GHR). There was no evidence of a RFI phenotype × diet interaction (P > 0.10) for any of the genes examined. An effect (P = 0.02) of RFI phenotype was evident for the abundance of GHR mRNA, with 2-fold greater expression levels detected in the low-RFI compared with the high-RFI phenotype. Additionally, mRNA expression of IGF-1R was up-regulated (1.7 fold; P = 0.04) for the low-RFI compared to high-RFI heifers. Residual feed intake was negatively associated with IGF-1R (r = -0.41; P < 0.05) and GHR (r = -0.50; P < 0.05) mRNA. Moderate negative correlation coefficients were also observed between feed conversion ratio (F:G) and gene expression levels for IGF-1R (r = -0.61; P < 0.01), as well as for GHR (r = - 0.49; P < 0.05). Moreover, associations were detected between DMI with IGF-1R (r = -0.42; P =0.07) and IGF-2R (r = 0.40; P = 0.07). The IGF-1R mRNA was positively correlated with IGF-1 (r = 0.34; P < 0.05) and IGF-2 (r = 0.71; P < 0.001) mRNA. Associations between IGF-1R and IGF-2R with IGFBP5 and GHR were positive (ranging from, r = 0.32 to 0.49). These data suggest that components of the somatotropic axis expressed within muscle tissue may be involved in the 3 regulation of feed efficiency in beef cattle. This effect is apparently consistent across contrasting dietary regimes.
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EXERCISE AND DIET AFFECT QUANTITATIVE TRAIT LOCI FOR BODY WEIGHT AND COMPOSITION TRAITS IN AN ADVANCED INTERCROSS POPULATION OF MICE
Physiological Genomics.
Oct, 2012 |
Pubmed ID: 23048196 Driven by the recent obesity epidemic, there is much interest in understanding the complex genetic and environmental basis of body weight and composition. We investigated this by searching for quantitative trait loci (QTLs) affecting a number of weight and adiposity traits in a G(10) advanced intercross population produced from crosses of mice in inbred strain C57BL/6J with those in a strain selected for high voluntary wheel running. The mice in this population were fed either a high-fat or a control diet throughout the study, and also measured for four exercise traits prior to sacrifice, allowing us to test for pre- and post-exercise QTLs as well as QTL by diet and QTL by exercise interactions. Our genome scan uncovered a number of QTLs, of which 40% replicated QTLs previously found for similar traits in an earlier (G(4)) generation. For those replicated QTL, the confidence intervals were reduced from an average of 19 Mb in the G(4) to 8 Mb in the G(10). Four QTLs on chromosomes 3, 8, 13, and 18 were especially prominent in affecting the percentage of fat in the mice. About 1/3 of all QTLs showed interactions with diet, exercise, or both, their genotypic effects on the traits showing a variety of patterns depending on the diet or level of exercise. It was concluded that the indirect effects of these QTLs provide an underlying genetic basis for the considerable variability in weight or fat loss typically found among individuals on the same diet and/or exercise regimen.
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Multiple Pathways Regulate Minisatellite Stability During Stationary Phase in Yeast
G3 (Bethesda, Md.).
Oct, 2012 |
Pubmed ID: 23050229 Alterations in minisatellite DNA repeat tracts in humans have been correlated with a number of serious disorders, including cancer. Despite their importance for human health, the genetic factors that influence minisatellite stability are not well understood. Previously, we identified mutations in the Saccharomyces cerevisiae zinc homeostasis genes ZRT1 and ZAP1 that significantly increase the frequency of minisatellite alteration specifically during stationary phase. In this work, we identified mutants of END3, PKC1, and RAD27 that increase minisatellite instability during stationary phase. Genetic analysis reveals that these genes, along with ZRT1 and ZAP1, comprise multiple pathways regulating minisatellite stability during stationary phase. Minisatellite alterations generated by perturbation of any of these pathways occur via homologous recombination. We present evidence that suggests formation of ssDNA or ssDNA breaks may play a primary role in stationary phase instability. Finally, we examined the roles of these pathways in the stability of a human minisatellite tract associated with the HRAS1 oncogene and found that loss of RAD27, but not END3 or PKC1, destabilizes the HRAS1 minisatellite in stationary phase yeast. This result indicates that the genetic control of stationary phase minisatellite stability is dependent on the sequence composition of the minisatellite itself.
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Use of a Drug Eluting Pleural Catheter for Pleurodesis
Experimental Lung Research.
Nov, 2012 |
Pubmed ID: 23050934 ABSTRACT Purpose: Repeated administration of low-dose silver nitrate (SN) has been shown to be effective in creating pleurodesis. This study aimed to determine the effectiveness of a SN-eluting pleural catheter for pleurodesis. Methods: Catheters with a chitosan-SN-hyaluronic acid hydrogel coating designed to release SN over 14Â days, or placebo uncoated catheters, were inserted in rabbit and lamb pleurodesis models. Pleurodesis was assessed at 28Â days according to a 1-8 point scoring system and pleural fibrosis and inflammation assessed histologically on a 0-4 point scale. Results: In the rabbit model, pleurodesis scores were significantly increased in both the 24Â mg and 50Â mg SN catheters versus control animals as well as compared to the contralateral untreated pleural space (median-treated side scores were 5, 8, and 1, respectively, median score for contralateral side was 1 in all groups). In the lamb model, pleurodesis scores were significantly increased in both the 750Â mg and 1000Â mg catheter groups versus control animals as well as compared to the contralateral untreated pleural space (median-treated side scores were 7, 7, and 1, respectively, median score for contralateral pleural space was 1 in all groups). Catheters appeared well tolerated, although higher than expected mortality was seen in the 50Â mg catheter rabbit group. Conclusions: A catheter designed to deliver SN to the pleural space over 14Â days appears to be effective in creating pleurodesis. Further investigations to determine in-vivo catheter pharmacokinetics, toxicity, dose and optimal coating methods are warranted.
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Safety and Efficacy of NA-1 in Patients with Iatrogenic Stroke After Endovascular Aneurysm Repair (ENACT): a Phase 2, Randomised, Double-blind, Placebo-controlled Trial
Lancet Neurology.
Nov, 2012 |
Pubmed ID: 23051991 BACKGROUND: Neuroprotection with NA-1 (Tat-NR2B9c), an inhibitor of postsynaptic density-95 protein, has been shown in a primate model of stroke. We assessed whether NA-1 could reduce ischaemic brain damage in human beings. METHODS: For this double-blind, randomised, controlled study, we enrolled patients aged 18 years or older who had a ruptured or unruptured intracranial aneurysm amenable to endovascular repair from 14 hospitals in Canada and the USA. We used a computer-generated randomisation sequence to allocate patients to receive an intravenous infusion of either NA-1 or saline control at the end of their endovascular procedure (1:1; stratified by site, age, and aneurysm status). Both patients and investigators were masked to treatment allocation. The primary outcome was safety and primary clinical outcomes were the number and volume of new ischaemic strokes defined by MRI at 12-95 h after infusion. We used a modified intention-to-treat (mITT) analysis. This trial is registered with ClinicalTrials.gov, number NCT00728182. FINDINGS: Between Sept 16, 2008, and March 30, 2011, we randomly allocated 197 patients to treatment-12 individuals did not receive treatment because they were found to be ineligible after randomisation, so the mITT population consisted of 185 individuals, 92 in the NA-1 group and 93 in the placebo group. Two minor adverse events were adjudged to be associated with NA-1; no serious adverse events were attributable to NA-1. We recorded no difference between groups in the volume of lesions by either diffusion-weighted MRI (adjusted p value=0·120) or fluid-attenuated inversion recovery MRI (adjusted p value=0·236). Patients in the NA-1 group sustained fewer ischaemic infarcts than did patients in the placebo group, as gauged by diffusion-weighted MRI (adjusted incidence rate ratio 0·53, 95% CI 0·38-0·74) and fluid-attenuated inversion recovery MRI (0·59, 0·42-0·83). INTERPRETATION: Our findings suggest that neuroprotection in human ischaemic stroke is possible and that it should be investigated in larger trials. FUNDING: NoNO Inc and Arbor Vita Corp.
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Severe Adhesive Small Bowel Obstruction
Frontiers of Medicine.
Oct, 2012 |
Pubmed ID: 23054502 Adhesive small bowel obstruction is a frequent cause of hospital admission. Water soluble contrast studies may have diagnostic and therapeutic value and avoid challenging demanding surgical operations, but if bowel ischemia is suspected, prompt surgical intervention is mandatory. A 58-year-old patient was operated for extensive adhesive small bowel obstruction after having had two previous laparotomies for colorectal surgery, and had a complex clinical course with multiple operations and several complications. Different strategies of management have been adopted, including non-operative management with the use of hyperosmolar water soluble contrast medium, multiple surgical procedures, total parenteral nutrition (TPN) support, and finally use of anti-adherences icodextrin solution. After 2 years follow-up the patient was doing well without presenting recurrent episodes of adhesive small bowel obstruction. For patients admitted several times for adhesive small bowel obstruction, the relative risk of recurring obstruction increases in relation to the number of prior episodes. Several strategies for non-operative conservative management of adhesive small bowel obstruction have already addressed diagnostic and therapeutic value of hyperosmolar water soluble contrast. According to the most recent evidence-based guidelines, open surgery is the preferred method for surgical treatment of strangulating adhesive small bowel obstruction as well as after failed conservative management. Research interest and clinical evidence are increasing in adhesions prevention. Hyaluronic acid-carboxycellulose membrane and icodextrin may reduce incidence of adhesions.
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Evolutionary Conserved Role of C-Jun-N-Terminal Kinase in CO(2)-Induced Epithelial Dysfunction
PloS One.
2012 |
Pubmed ID: 23056407 Elevated CO(2) levels (hypercapnia) occur in patients with respiratory diseases and impair alveolar epithelial integrity, in part, by inhibiting Na,K-ATPase function. Here, we examined the role of c-Jun N-terminal kinase (JNK) in CO(2) signaling in mammalian alveolar epithelial cells as well as in diptera, nematodes and rodent lungs. In alveolar epithelial cells, elevated CO(2) levels rapidly induced activation of JNK leading to downregulation of Na,K-ATPase and alveolar epithelial dysfunction. Hypercapnia-induced activation of JNK required AMP-activated protein kinase (AMPK) and protein kinase C-ζ leading to subsequent phosphorylation of JNK at Ser-129. Importantly, elevated CO(2) levels also caused a rapid and prominent activation of JNK in Drosophila S2 cells and in C. elegans. Paralleling the results with mammalian epithelial cells, RNAi against Drosophila JNK fully prevented CO(2)-induced downregulation of Na,K-ATPase in Drosophila S2 cells. The importance and specificity of JNK CO(2) signaling was additionally demonstrated by the ability of mutations in the C. elegans JNK homologs, jnk-1 and kgb-2 to partially rescue the hypercapnia-induced fertility defects but not the pharyngeal pumping defects. Together, these data provide evidence that deleterious effects of hypercapnia are mediated by JNK which plays an evolutionary conserved, specific role in CO(2) signaling in mammals, diptera and nematodes.
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Fusion Toxin BLyS-Gelonin Inhibits Growth of Malignant Human B Cell Lines In Vitro and In Vivo
PloS One.
2012 |
Pubmed ID: 23056634 B lymphocyte stimulator (BLyS) is a member of the TNF superfamily of cytokines. The biological activity of BLyS is mediated by three cell surface receptors: BR3/BAFF-R, TACI and BCMA. The expression of these receptors is highly restricted to B cells, both normal and malignant. A BLyS-gelonin fusion toxin (BLyS-gel) was generated consisting of the recombinant plant-derived toxin gelonin fused to the N-terminus of BLyS and tested against a large and diverse panel of B-NHL cell lines. Interestingly, B-NHL subtypes mantle cell lymphoma (MCL), diffuse large B cell lymphoma (DLBCL) and B cell precursor-acute lymphocytic leukemia (BCP-ALL) were preferentially sensitive to BLyS-gel mediated cytotoxicity, with low picomolar EC(50) values. BLyS receptor expression did not guarantee sensitivity to BLyS-gel, even though the construct was internalized by both sensitive and resistant cells. Resistance to BLyS-gel could be overcome by treatment with the endosomotropic drug chloroquine, suggesting BLyS-gel may become trapped within endosomal/lysosomal compartments in resistant cells. BLyS-gel induced cell death was caspase-independent and shown to be at least partially mediated by the "ribotoxic stress response." This response involves activation of p38 MAPK and JNK/SAPK, and BLyS-gel mediated cytotoxicity was inhibited by the p38/JNK inhibitor SB203580. Finally, BLyS-gel treatment was shown to localize to sites of disease, rapidly reduce tumor burden, and significantly prolong survival in xenograft mouse models of disseminated BCP-ALL, DLBCL, and MCL. Together, these findings suggest BLyS has significant potential as a targeting ligand for the delivery of cytotoxic "payloads" to malignant B cells.
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Incidence, Clinical Course, and Predictors of Prolonged Recovery Time Following Sport-Related Concussion in High School and College Athletes
Journal of the International Neuropsychological Society : JINS.
Oct, 2012 |
Pubmed ID: 23058235 Sport-related concussion (SRC) is typically followed by clinical recovery within days, but reports of prolonged symptoms are common. We investigated the incidence of prolonged recovery in a large cohort (n = 18,531) of athlete seasons over a 10-year period. A total of 570 athletes with concussion (3.1%) and 166 controls who underwent pre-injury baseline assessments of symptoms, neurocognitive functioning and balance were re-assessed immediately, 3 hr, and 1, 2, 3, 5, 7, and 45 or 90 days after concussion. Concussed athletes were stratified into typical (within 7 days) or prolonged (> 7 days) recovery groups based on symptom recovery time. Ten percent of athletes (n = 57) had a prolonged symptom recovery, which was also associated with lengthier recovery on neurocognitive testing (p < .001). At 45-90 days post-injury, the prolonged recovery group reported elevated symptoms, without deficits on cognitive or balance testing. Prolonged recovery was associated with unconsciousness [odds ratio (OR), 4.15; 95% confidence interval (CI) 2.12-8.15], posttraumatic amnesia (OR, 1.81; 95% CI, 1.00-3.28), and more severe acute symptoms (p < .0001). These results suggest that a small percentage of athletes may experience symptoms and functional impairments beyond the typical window of recovery after SRC, and that prolonged recovery is associated with acute indicators of more severe injury. (JINS, 2012, 18, 1-12).
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On the Use of Simulated Field-evaporated Specimen Apex Shapes in Atom Probe Tomography Data Reconstruction
Microscopy and Microanalysis : the Official Journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada.
Oct, 2012 |
Pubmed ID: 23058657 The ability to accurately reconstruct original spatial positions of field-evaporated ions emitted from a surface is fundamental to the success of atom probe tomography. As such, a clear understanding of the evolution of specimen shape and the resultant ions' trajectories during field evaporation plays an important role in improving reconstruction accuracy. To further this understanding, field-evaporation simulations of a bilayer specimen composed of two materials having an evaporation field difference of 20% were performed. The simulated field-evaporation patterns qualitatively compare favorably with experimental data, which provides confidence in the accuracy of specimen shapes predicted by the simulation. Correlations of known original atom positions with detector hit positions as a function of lateral detector position and evaporated depth were derived from the simulation. These correlations are contrasted with the current state-of-the-art reconstruction method thus outlining limitations of the current methodology. A pair of transformations are defined that take into account field-evaporated specimen shapes, and the resulting radial magnifications, to relate recorded ion positions in detector space to reconstructed atomic positions in specimen space. This novel process, when applied to simulated data, results in approximately a factor of 2 improvement in accuracy for reconstructions of interfaces with unequal fields (most general interfaces). This method is not constrained by the fundamental assumption of a hemispherical specimen shape.
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Detection of Mycobacterium Avium Subspecies Paratuberculosis in Several Herds of Arctic Caribou (Rangifer Tarandus Ssp.)
Journal of Wildlife Diseases.
Oct, 2012 |
Pubmed ID: 23060493 Mycobacterium avium subspecies paratuberculosis (MAP) is a common pathogen in domestic ruminants that causes granulomatous inflammation of the small intestine leading to emaciation and wasting. Clinical disease (Johne's disease) is also reported for several wild ruminant species. Between 2007 and 2009 we collected 561 fecal samples from caribou (Rangifer tarandus ssp.) representing 10 herds of migratory caribou, two herds of caribou from Greenland, and three populations of boreal woodland caribou. Feces were tested for MAP by bacterial culture and PCR targeting the IS900 insertion sequence. In total, 31 samples from eight different populations representing all three ecotypes were found positive for MAP by PCR, with one sample from the Rivière-aux-Feuilles herd also being culture positive for the type II (cattle) strain. The proportion of positive animals was particularly high in the Akia-Maniitsoq herd in Greenland, and Rivière-aux-Feuilles and Riviè re-George herds in northeastern Canada (23.4, 11.5, and 10.0%, respectively). Our results indicate that MAP is present in several caribou herds of different ecotypes in northern Canada and Greenland and that MAP circulates within wildlife populations that do not have ongoing contact with domestic livestock. The epidemiology, pathogenicity, and effects on the health of caribou in northern ecosystems remain unknown.
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Obesity Results in Progressive Atrial Structural and Electrical Remodeling: Implications for Atrial Fibrillation
Heart Rhythm : the Official Journal of the Heart Rhythm Society.
Sep, 2012 |
Pubmed ID: 23063864 BACKGROUND: Obesity is associated with atrial fibrillation (AF); however, the mechanisms by which it induces AF are unknown. OBJECTIVE: To examine the effect of progressive weight gain on the substrate for AF. METHODS: Thirty sheep were studied at baseline, 4 months, and 8 months, following a high-calorie diet. Ten sheep were sampled at each time point for cardiac magnetic resonance imaging and hemodynamic studies. High-density multisite biatrial epicardial mapping was used to quantify effective refractory period, conduction velocity, and conduction heterogeneity index at 4 pacing cycle lengths and AF inducibility. Histology was performed for atrial fibrosis, inflammation, and intramyocardial lipidosis, and molecular analysis was performed for endothelin-A and -B receptors, endothelin-1 peptide, platelet-derived growth factor, transforming growth factor β1, and connective tissue growth factor. RESULTS: Increasing weight was associated with increasing left atrial volume (P = .01), fibrosis (P = .02), inflammatory infiltrates (P = .01), and lipidosis (P = .02). While there was no change in the effective refractory period (P = .2), there was a decrease in conduction velocity (P
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Pipeline Embolization Device in Aneurysmal Subarachnoid Hemorrhage
AJNR. American Journal of Neuroradiology.
Oct, 2012 |
Pubmed ID: 23064594 BACKGROUND AND PURPOSE:The PED is an FDS designed for the treatment of intracranial aneurysms. Data regarding the use of this device in acute or subacute aSAH is limited to a few case reports or small series. We aimed to demonstrate the feasibility of using an FDS, the PED, for the treatment of ruptured intracranial aneurysms with challenging morphologies.MATERIALS AND METHODS:We conducted a retrospective review of all known patients treated with the PED for aSAH at 4 institutions between June 2008 and January 2012. Pertinent clinical and radiologic information was submitted by individual centers for central collation. The decision to treat with the PED was made on a case-by-case basis by a multidisciplinary team under compassionate use.RESULTS:Twenty patients (15 women; median age, 54.5 years; IQR, 8.0 years) were found. There were 8 blister, 8 dissecting or dysplastic, 2 saccular, and 2 giant aneurysms. Median time to treatment was 4 days (range, 1-90 days; IQR, 12.75 days) from rupture. Three patients had previous failed treatment. Procedure-related symptomatic morbidity and mortality were 15%, with 1 (5%) procedure-related death. Two patients died relative to medical complications, and 1 patient was lost to follow-up. Sixteen patients were available for follow-up, 81% had a GOS of 5, and 13% had a GOS of 4 attributed to a poorer initial clinical presentation. One patient died of urosepsis at 4 months. Occlusion rates were 75% and 94% at 6 months and 12 months, respectively. There were 3 delayed complications (1 silent perforator infarct, 2 moderate asymptomatic in-stent stenoses). No symptomatic delayed complications or rehemorrhages occurred.CONCLUSIONS:The FDS may be a feasible treatment option in the acute or subacute setting of selected ruptured aneurysms, especially blister aneurysms. Ruptured giant aneurysms remain challenging for both surgical and endovascular techniques; at this stage, FDSs should be used with caution in this aneurysm subtype.
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Hemostasis Management During Completely Endoscopic Removal of a Highly Vascular Intraparenchymal Brain Tumor: Technique Assessment
Journal of Neurological Surgery. Part A, Central European Neurosurgery.
Oct, 2012 |
Pubmed ID: 23065778 Background Recently, stereotactic-guided removal of intraparenchymal lesions using endoscopic visualization through a brain port has been successfully reported. Although endoneurosurgical tumor resection uses the same principles as those used in microneurosurgery, the ability to control bleeding through the port requires an adapted technique.Material and Methods We present a patient that underwent a completely endoscopic resection of a vascular brain tumor through a brain port and describe the hemostatic technique.Results A 68 year-old female presented with progressive gait difficulties. She had been previously treated for a breast cancer. Magnetic resonance imaging (MRI) showed a right subcortical solitary cerebellar lesion that homogeneously enhanced. The patient underwent an endoscopic brain port removal of a supposed brain metastasis. After port cannulation, the tumor partly delivered itself into the port. Following initial tumor biopsy, active bleeding occurred. Irrigation and application of Surgifoam allowed to control the bleeding. Coagulation with an adapted bipolar and removal of coagulated tissue with the side-cutting aspiration device were sequentially repeated. Once the tumor was resected, the suction served as counter-traction elongating the vessels whereas the bipolar cauterized them over a long segment. Hemostasis was performed circumferentially along the cavity's walls from deep to superficial, benefiting from the endoscope's dynamic properties and magnification. Pathology confirmed intraoperative suspicion of hemangioblastoma.Conclusion Removal of vascular tumors is feasible through the brain port, despite a relatively narrow corridor of 11.5 mm. However, specific hemostasis techniques are required and adapted instruments are needed to ensure hemostasis through these small corridors.
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Day-case Laparoscopic Nissen Fundoplication: a Default Pathway or is Selection the Key?
Journal of Laparoendoscopic & Advanced Surgical Techniques. Part A.
Nov, 2012 |
Pubmed ID: 23067070 Abstract Background: In recent years, day-case laparoscopic Nissen fundoplication (LNF) has became popular. Our study aims to evaluate the effect of patient factors and severity of gastroesophageal reflux disease measured by DeMeester score on the success of day-case LNF. Subjects and Methods: We conducted a retrospective case series review of patient demographics (age, gender, body mass index [BMI], and smoking status) and DeMeester score over a 5-year period. Between 2005 and 2010, 112 patients had day-case LNF. Same-day discharge was achieved in 80.3%. Twenty-two patients (19.7%) required postoperative admission ("failed day-case surgery"), with a resultant mean length of stay of 1.41 days. Univariate analysis showed that female gender had a significantly higher incidence of postsurgical admission (30.76% females versus 13.69% males, P=.03 by Mann-Whitney U test). Compared with the same-day discharge group, the failed day-case group has a higher mean DeMeester score (50.89 versus 36.03, P=.021 by t test) and BMI (28.71±0.778 kg/m(2) versus 26.79±0.3737 kg/m(2), P=.023). Age and smoking status were not significant determining factors in postoperative admission rates. Using multivariable analysis and logistical regression, we derived a model based on gender, BMI, and DeMeester score to predict the probability of admission following day-case LNF. Conclusions: We conclude that day-case LNF is a safe, feasible procedure in the appropriately selected patient population. Our novel finding of higher admission rates in females, high DeMeester score, and high BMI should be used in planning perioperative hospitalization in this cohort.
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Prenatal HIV Testing: The Compartmentalization of Women's Sexual Risk Exposure and the Return of the Maternal Fetal Conflict
Women & Health.
Oct, 2012 |
Pubmed ID: 23067153 The purpose of the researchers in this study was to investigate how women who were being tested for HIV during their pregnancies were evaluating, conceptualizing, and negotiating their risk of infection. The study included two focus groups and 20 in-depth interviews with 30 patients, ages 17-38 years, from diverse ethnic/racial, social, and economic backgrounds. Qualitative analyses of the interview transcripts revealed support for the idea that pregnant women have a responsibility to minimize risks to their fetus, with all interviewees describing actions to minimize those risks while pregnant. Two sub-themes emerged that were related to the presence of differences in how interviewees conceptualized risk depending on the type of risk being discussed. In the case of diet and lifestyle influences, interviewees framed their health and the health of the fetus as connected. In contrast, when the issue of HIV risk and testing was raised, the interviewees described the risk of HIV to themselves and their fetuses as separate concerns and, with few exceptions, reported no effort to reduce the risk of becoming infected while pregnant (beyond consenting to HIV screening while receiving prenatal care). Findings suggest the importance of developing HIV prevention messages that counter the compartmentalization of risk during pregnancy.
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Nitric Oxide Generated by the Rice Blast Fungus Magnaporthe Oryzae Drives Plant Infection
The New Phytologist.
Oct, 2012 |
Pubmed ID: 23072575 Plant-derived nitric oxide (NO) triggers defence, priming the onset of the hypersensitive response and restricting pathogen ingress during incompatibility. However, little is known about the role of pathogen-produced NO during pre-infection development and infection. We sought evidence for NO production by the rice blast fungus during early infection. NO production was measured using fluorescence of DAR-4M and the role of NO assessed using NO scavengers. The synthesis of NO was investigated by targeted knockout of genes potentially involved in NO synthesis, including nitric oxide synthase-like genes (NOL2 and NOL3) and nitrate (NIA1) and nitrite reductase (NII1), generating single and double Δnia1Δnii1, Δnia1Δnol3, and Δnol2Δnol3 mutants. We demonstrate that Magnaporthe oryzae generates NO during germination and in early development. Removal of NO delays germling development and reduces disease lesion numbers. NO is not generated by the candidate proteins tested, nor by other arginine-dependent NO systems, by polyamine oxidase activity or non-enzymatically by low pH. Furthermore, we show that, while NIA1 and NII1 are essential for nitrate assimilation, NIA1, NII1, NOL2 and NOL3 are all dispensable for pathogenicity. Development of M. oryzae and initiation of infection are critically dependent on fungal NO synthesis, but its mode of generation remains obscure.
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Tolerance to Effects of High-Dose Oral {Delta}9-Tetrahydrocannabinol and Plasma Cannabinoid Concentrations in Male Daily Cannabis Smokers
Journal of Analytical Toxicology.
Oct, 2012 |
Pubmed ID: 23074216 Oral cannabinoids are taken for medicinal or recreational purposes, yet little is known about tolerance to their effects after high-dose extended exposure. The development of tolerance to effects of around-the-clock oral synthetic Δ9-tetrahydrocannabinol (THC) (20 mg every 3.5-6 h) was evaluated in 13 healthy male daily cannabis smokers residing on a secure research unit: 40 mg on Day 1; 100 mg on Days 2-4; 120 mg on Days 5-6. Systolic and diastolic blood pressure (BP), heart rate, and symptoms of subjective intoxication (100 mm visual-analogue scales, VAS) were assessed the morning of Day 1 (before any oral THC), and on Days 2, 4 and 6, every 30 min for 3 h after the first morning THC dose. Morning subjective intoxication ratings increased from Days 1 to 2, and then declined on Days 4 and 6. The morning THC dose increased intoxication ratings on Day 2, but had less effect on Days 4 and 6, a pattern consistent with tolerance. THC lowered BP and increased heart rate over the six days. Plasma THC and 11-OH-THC concentrations increased significantly over the first five days of dosing. Six days of around-the-clock, oral THC produced tolerance to subjective intoxication, but not to cardiovascular effects.
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Systematic Review of Clinical Research on Biomarkers for Pediatric Traumatic Brain Injury
Journal of Neurotrauma.
Oct, 2012 |
Pubmed ID: 23078348 The objective was to systematically review the medical literature and comprehensively summarize clinical research done on biomarkers for pediatric traumatic brain injury (TBI) and to summarize the studies that have assessed serum biomarkers acutely in determining intracranial lesions on CT in children with TBI. The search strategy included a literature search of PubMed®, MEDLINE® and the Cochrane Database from 1966 to August 2011, as well as a review of reference lists of identified studies. Search terms used included pediatrics, children, traumatic brain injury, and biomarkers. Any article with biomarkers of traumatic brain injury as a primary focus and containing a pediatric population was included. The search initially identified 167 articles. Of these, 49 met inclusion and exclusion criteria and were critically reviewed. The median sample size was 58 [IQR 31-101]. The majority of the articles exclusively studied children 36 (74%) and 13 (26%) were studies that included both children and adults in different proportions. There were 99 different biomarkers measured in these 49 studies and the five most frequently examined biomarkers were S100B (27 studies), NSE (15 studies), IL-6 (7 studies), MBP (6 studies), and IL-8 (6 studies). There were 6 studies that assessed the relationship between serum markers and CT lesions. Two studies found that NSE levels ≥ 15 ng/ml within 24 hours of TBI was associated with intracranial lesions. Four studies using serum S100B were conflicting: 2 studies found no association with intracranial lesions and 2 studies found a weak association. The flurry of research in the area over the last decade is encouraging but is limited by small sample sizes, variable practices in sample collection, inconsistent biomarker-related data elements and disparate outcome measures. Future studies of biomarkers for pediatric TBI will require rigorous and more uniform research methodology, common data elements, and consistent performance measures.
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Adverse Ophthalmic Reaction in Poppers Users: Case Series of 'poppers Maculopathy'
Eye (London, England).
Nov, 2012 |
Pubmed ID: 23079752 BackgroundPoppers are a recreational substance of abuse belonging to the alkyl nitrite family of compounds. In the United Kingdom, where they are legal to purchase but illegal to sell for human consumption, 10% of the general population have tried them. They are considered low risk to physical and mental health. Two recent case series from France demonstrated foveal pathology in individuals associated with poppers use.MethodA case series of seven patients presenting to four hospitals in the United Kingdom with visual impairment and maculopathy associated with inhalation of poppers.ResultsAll patients experienced visual symptoms associated with poppers use. The majority had impaired visual acuity, central scotomata, distortion, or phosphenes. Clinical signs on fundoscopy ranged from normal foveal appearance to yellow, dome-shaped lesions at the foveola. Spectral domain optical coherence tomography (SD-OCT) showed varying degrees of disruption of the presumed inner segment/outer segment (IS/OS) junction.DiscussionAlthough poppers have been in use for several decades, in 2007, following legislative changes, there was a change in the most commonly used compound from isobutyl nitrite to isopropyl nitrite. There were no reports of 'poppers maculopathy' before this. Poppers maculopathy may be missed if patients are not directly questioned about their use. The disruption or loss of the presumed IS/OS junction on SD-OCT are a characteristic feature. Further study of maculopathy in poppers users is now needed. Raising public awareness of the ocular risks associated with their use may be necessary.
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Assessment of Self-reported Negative Affect in the NIH Toolbox
Psychiatry Research.
Oct, 2012 |
Pubmed ID: 23083918 We report on the selection of self-report measures for inclusion in the NIH Toolbox that are suitable for assessing the full range of negative affect including sadness, fear, and anger. The Toolbox is intended to serve as a "core battery" of assessment tools for cognition, sensation, motor function, and emotional health that will help to overcome the lack of consistency in measures used across epidemiological, observational, and intervention studies. A secondary goal of the NIH Toolbox is the identification of measures that are flexible, efficient, and precise, an agenda best fulfilled by the use of item banks calibrated with models from item response theory (IRT) and suitable for adaptive testing. Results from a sample of 1763 respondents supported use of the adult and pediatric item banks for emotional distress from the Patient-Reported Outcomes Measurement Information System (PROMIS(®)) as a starting point for capturing the full range of negative affect in healthy individuals. Content coverage for the adult Toolbox was also enhanced by the development of a scale for somatic arousal using items from the Mood and Anxiety Symptom Questionnaire (MASQ) and scales for hostility and physical aggression using items from the Buss-Perry Aggression Questionnaire (BPAQ).
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Nondietary Therapies for Celiac Disease
Gastrointestinal Endoscopy Clinics of North America.
Oct, 2012 |
Pubmed ID: 23083995 Currently, the only available therapy for celiac disease is strict lifelong adherence to a gluten-free diet (GFD). Although safe and effective, the GFD is not ideal. It is frequently expensive, of limited nutritional value, and not readily available in many countries. Consequently, a need exists for novel, nondietary therapies for celiac disease. Based on the current understanding of celiac disease pathogenesis, several potential targets of therapeutic intervention exist. These novel strategies provide promise of alternative, adjunctive treatment options but also raise important questions regarding safety, efficacy, and monitoring of long-term treatment effect.
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Multicenter Study on Season of Birth and Celiac Disease: Evidence For a New Theoretical Model of Pathogenesis
The Journal of Pediatrics.
Oct, 2012 |
Pubmed ID: 23084709 OBJECTIVE: To investigate whether season of birth is associated with celiac disease (CD). STUDY DESIGN: We performed a medical record review of 1964 patients with biopsy-proven CD at 3 teaching hospitals (2 pediatric centers and 1 adult center) between 2000 and 2010. The first positive small intestinal biopsy result defined age of diagnosis. The observed proportions of births in each season (spring [March-May], summer [June-August], fall [September-November], and winter [December-February]) were compared with the expected proportions using binomial probability tests. RESULTS: The mean age at diagnosis was 9.8 ± 5.0 years in the 2 pediatric centers and 43.6 ± 15.8 years in the adult center. The cohort was predominately female (69%). Overall, more patients were born in spring (27%) than in any other season: summer (25%), fall (25%), and winter (23%). In patients diagnosed before age 15 years, the spring birth excess was present in boys (33%; P = .0005), but not in girls (26%; P = .43). The sex difference in season of birth was less striking in patients with CD diagnosed at age ≥15 years. CONCLUSION: Season of birth is an environmental risk factor for CD, particularly in boys diagnosed before age 15 years. The results are consistent with a new theoretical model that integrates potential environmental factors (eg, gluten introduction, ultraviolet-B exposure, vitamin D status) and acute viral gastrointestinal infections in early childhood.
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Dispensable, Redundant, Complementary and Cooperative Roles of Dopamine, Octopamine and Serotonin in Drosophila Melanogaster
Genetics.
Oct, 2012 |
Pubmed ID: 23086220 To investigate the regulation of Drosophila melanogaster behavior by biogenic amines, we have exploited the broad requirement of the vesicular monoamine transporter (VMAT) for the vesicular storage and exocytotic release of all monoamine neurotransmitters. We used the Drosophila VMAT (dVMAT) null mutant to globally ablate exocytotic amine release, and then restored DVMAT activity in either individual or multiple aminergic systems using transgenic rescue techniques. We find that larval survival, larval locomotion, and female fertility rely predominantly on octopaminergic circuits with little apparent input from the vesicular release of serotonin or dopamine. In contrast, male courtship and fertility can be rescued by expressing DVMAT in octopaminergic or dopaminergic neurons, suggesting potentially redundant circuits. Rescue of major aspects of adult locomotion and startle behavior required octopamine, but a complementary role was observed for serotonin. Interestingly, adult circadian behavior could not be rescued by expression of DVMAT in a single subtype of aminergic neurons, but required at least two systems, suggesting the possibility of unexpected cooperative interactions. Further experiments using this model will help determine how multiple aminergic systems may contribute to the regulation of other behaviors. Our data also highlight potential differences between behaviors regulated by standard exocytotic release versus other mechanisms.
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HLA-DR3-DQ2 Mice Do Not Develop Ataxia in the Presence of High Titre Anti-gliadin Antibodies
Cerebellum (London, England).
Oct, 2012 |
Pubmed ID: 23086706 Recently, it has been suggested that anti-gliadin antibodies (αGAb) may produce "gluten ataxia", even in the absence of celiac disease enteropathy. αGAb are reportedly present in 12-50 % of patients with sporadic ataxia, but also in 12 % of the general population, such that the importance of αGAb as a cause of sporadic ataxia is not conclusively settled. We aimed to determine whether mice transgenic for HLA-DR3-DQ2 and immunised with gliadin to achieve high titres of αGAb would develop ataxia and/or cerebellar damage. From 6 weeks of age, HLA-DR3-DQ2 transgenic mice were immunised fortnightly with gliadin (n = 10) or a saline control (n = 6) in adjuvant. Serum titres were measured by αGAb enzyme-linked immunosorbent assay. At 24 weeks of age, mice were tested for locomotor function using the accelerating rotarod, ledged beam, ink-paw gait, and several neurological severity score subtests. Brains were then collected and processed for immunohistochemistry. Sections were analysed for lymphocytic infiltration, changes in morphology and Purkinje cell (PC) dendritic volume and the number of PCs counted via unbiased stereology. Gliadin-immunised mice developed high αGAb titres while controls did not. There was no statistically significant difference between the gliadin and sham-immunised HLA-DR3-DQ2 mice on any of the tests of motor coordination, in lymphocytic infiltration, PC number or in dendritic volume. High levels of αGAb are not sufficient to produce ataxia or cerebellar damage in HLA-DR3-DQ2 transgenic mice.
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The NKI-Rockland Sample: A Model for Accelerating the Pace of Discovery Science in Psychiatry
Frontiers in Neuroscience.
2012 |
Pubmed ID: 23087608 The National Institute of Mental Health strategic plan for advancing psychiatric neuroscience calls for an acceleration of discovery and the delineation of developmental trajectories for risk and resilience across the lifespan. To attain these objectives, sufficiently powered datasets with broad and deep phenotypic characterization, state-of-the-art neuroimaging, and genetic samples must be generated and made openly available to the scientific community. The enhanced Nathan Kline Institute-Rockland Sample (NKI-RS) is a response to this need. NKI-RS is an ongoing, institutionally centered endeavor aimed at creating a large-scale (N > 1000), deeply phenotyped, community-ascertained, lifespan sample (ages 6-85 years old) with advanced neuroimaging and genetics. These data will be publically shared, openly, and prospectively (i.e., on a weekly basis). Herein, we describe the conceptual basis of the NKI-RS, including study design, sampling considerations, and steps to synchronize phenotypic and neuroimaging assessment. Additionally, we describe our process for sharing the data with the scientific community while protecting participant confidentiality, maintaining an adequate database, and certifying data integrity. The pilot phase of the NKI-RS, including challenges in recruiting, characterizing, imaging, and sharing data, is discussed while also explaining how this experience informed the final design of the enhanced NKI-RS. It is our hope that familiarity with the conceptual underpinnings of the enhanced NKI-RS will facilitate harmonization with future data collection efforts aimed at advancing psychiatric neuroscience and nosology.
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Fitness Profiling of Elite Level Adolescent Gaelic Football Players
Journal of Strength and Conditioning Research / National Strength & Conditioning Association.
Oct, 2012 |
Pubmed ID: 23090319 ABSTRACT: The purpose of this study was to evaluate the anthropometric characteristics and fitness levels of elite level under 18 (U-18) Gaelic football players in order to establish normative centile scores for selected fitness parameters, and to compare the physical and fitness characteristics relative to each playing position. A total of 265 male U-18 Gaelic football players (age: 16.96 ± 0.7 yr.; height: 178.11 ± 6.27 cm; weight: 72.07 ± 8.68 kg) participated in the study. According to positional roles, players were categorized as goalkeepers (n=13), defenders (n=113), midfielders (n=30) and forwards (n=109). Height, and weight were measured, and skinfolds were taken before participants sequentially performed a sit and reach test (S&R), countermovement jump (CMJ), standing long jump (SLJ), 5 m and 20 m speed test and the Yo-Yo Intermittent Recovery Test Level 1 (YYIRT1). The percentage body fat was higher (p < 0.01) in goalkeepers than each of the other playing positions. Goalkeepers had a higher BMI than defenders (p < 0.05) and forward players (p < 0.01). Midfield players and goalkeepers were taller (p < 0.01) and heavier (p < 0.01) than defenders and forward players. The total distance covered in the YYIRT1 was significantly lower (p < 0.01) in goalkeepers than the other playing positions. There was no significant positional difference in the performance scores in the S&R test, CMJ, SLJ and 5 m and 20 m running speed. The study findings indicate minimal differences in the anthropometric and physiological characteristics between playing positions in elite youth level Gaelic football players. The norm-referenced percentile scores will enable conditioning coaches to benchmark elite performance and design training programmes.
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The Personal and National Costs of Early Retirement Because of Spinal Disorders: Impacts on Income, Taxes, and Government Support Payments
The Spine Journal : Official Journal of the North American Spine Society.
Oct, 2012 |
Pubmed ID: 23092718 BACKGROUND CONTEXT: Spinal disorders can reduce an individual's ability to participate in the labor force, and this can lead to considerable impacts on both the individual and the state. PURPOSE: This study was aimed to quantify the personal cost of lost income and the cost to the state from lost income taxation, increased benefits payments, and lost gross domestic product (GDP) as a result of early retirement because of spinal disorders in Australians aged 45 to 64 years in 2009. METHODS: This was done using cross-sectional analysis of the base population of Health&WealthMOD, a microsimulation model built on data from the Australian Bureau of Statistics' Survey of Disability, Ageing and Carers, and STINMOD, an income and savings microsimulation model. Linear regression models were used to examine the relationship between spinal disorders, labor force participation, income, taxation, and government support payments. RESULTS: It was found that individuals aged 45 to 64 years who have retired early because of spinal disorders have significantly lower income (79% less; 95% confidence interval [CI], -84.7, -71.1; p
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Counseling Customers: Emerging Roles for Genetic Counselors in the Direct-to-Consumer Genetic Testing Market
Journal of Genetic Counseling.
Oct, 2012 |
Pubmed ID: 23093333 Individuals now have access to an increasing number of internet resources offering personal genomics services. As the direct-to-consumer genetic testing (DTC GT) industry expands, critics have called for pre- and post-test genetic counseling to be included with the product. Several genetic testing companies offer genetic counseling. There has been no examination to date of this service provision, whether it meets critics' concerns and implications it may have for the genetic counseling profession. Considering the increasing relevance of genetics in healthcare, the complexity of genetic information provided by DTC GT, the mediating role of the internet in counseling, and potential conflicts of interest, this is a topic which deserves further attention. In this paper we offer a discourse analysis of ways in which genetic counseling is represented on DTC GT websites, blogs and other online material. This analysis identified four types of genetic counseling represented on the websites: the integrated counseling product; discretionary counseling; independent counseling; and product advice. Genetic counselors are represented as having the following roles: genetics educator; mediator; lifestyle advisor; risk interpreter; and entrepreneur. We conclude that genetic counseling as represented on DTC GT websites demonstrates shifting professional roles and forms of expertise in genetic counseling. Genetic counselors are also playing an important part in how the genetic testing market is taking shape. Our analysis offers important and timely insights into recent developments in the genetic counseling profession, which have relevance for practitioners, researchers and policy makers concerned with the evolving field of personal genomics.
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Optic Neuropathy in McCune-Albright Syndrome: Effects of Early Diagnosis and Treatment of Growth Hormone Excess
The Journal of Clinical Endocrinology and Metabolism.
Oct, 2012 |
Pubmed ID: 23093488 Context:GH excess is a serious complication of McCune-Albright syndrome (MAS) and has been associated with craniofacial morbidity.Objective:The aim of the study was to determine whether early diagnosis and treatment of MAS-associated GH excess prevents optic neuropathy and hearing impairment, the major morbidities associated with GH excess.Design and Setting:A retrospective cross-sectional analysis was conducted at a clinical research center.Patients:Twenty-two subjects with MAS-associated GH excess and 21 control MAS subjects without GH excess were included in the study.Intervention:Biochemical testing included random GH, nadir GH after glucose load, nadir GH on frequent sampling, and IGF-I Z-score. Subjects underwent imaging, ophthalmological, audiological, and otolaryngological assessment. Treatment included octreotide, pegvisomant, transphenoidal surgery, and/or radiotherapy as indicated.Main Outcome Measure:Association of optic neuropathy and hearing impairment to age at GH excess diagnosis/treatment was measured.Results:Of 129 MAS subjects, 26 (20%) were diagnosed with GH excess based on elevation of two measures of GH function. Of these, 22 subjects were candidates for pharmacological intervention. Optic neuropathy was significantly correlated with intervention status, with no cases in the early intervention group (diagnosed/treated before age 18) or the control group, and four of seven (57%) in the late intervention group (diagnosed/treated after age 18) (Fisher's exact test; odds ratio, 0.027; P = 0.0058). Early diagnosis/intervention was not associated with reduction in hearing deficits (odds ratio, 1.25; P = 1.00). Mean head circumference sd score was significantly higher in the late (6.08; range, 2.70 to 22.56) than the early intervention (2.67; range, -0.65 to 6.72) or control groups (2.13; range, -2.06 to 7.79) (P = 0.003).Conclusions:Early diagnosis/treatment of GH excess in MAS is important to prevent optic neuropathy and craniofacial expansion. The relationship between hearing deficits and GH excess remains less clear and requires further study.
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Treatment Burden Among People with Chronic Illness: What Are Consumer Health Organizations Saying?
Chronic Illness.
Oct, 2012 |
Pubmed ID: 23093542 OBJECTIVES: To explore the perspectives of consumer health organizations about the burden of chronic illness and multiple treatment regimens experienced by the consumers they represent. METHODS: In-depth interviews (n = 15) were conducted with senior representatives from peak Australian consumer health organizations representing diabetes, asthma, cardiovascular disease, cancer, musculoskeletal illness and mental health. RESULTS: Medication burden, which included aspects such as multiple medications, side effects, stigma and adverse events resulting from medication use, emerged as the most significant and prevalent theme. Carer burden and the negative impact of financial burden was widely discussed, particularly for low-income earners with claims that these consumers were forced to prioritise medications according to how effective they perceived them to be. Time taken to learn about treatment, administer, and monitor or travel to obtain treatment also emerged as being burdensome, however, difficulty accessing treatment was considered to be particularly burdensome. The disjointed nature of care among healthcare services was thought to create a sense of confusion and distress. DISCUSSION: Many of the issues discussed by participants corroborated existing research, underscoring the complementary provider, and advocacy role of these organisations in mitigating treatment burden for people with chronic illness.
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Fibroblast Growth Factor 10 Gene Regulation in the Second Heart Field by Tbx1, Nkx2-5, and Islet1 Reveals a Genetic Switch for Down-regulation in the Myocardium
Proceedings of the National Academy of Sciences of the United States of America.
Nov, 2012 |
Pubmed ID: 23093675 During cardiogenesis, Fibroblast Growth Factor (Fgf10) is expressed in the anterior second heart field. Together with Fibroblast growth factor 8 (Fgf8), Fgf10 promotes the proliferation of these cardiac progenitor cells that form the arterial pole of the heart. We have identified a 1.7-kb region in the first intron of Fgf10 that is necessary and sufficient to direct transgene expression in this cardiac context. The 1.7-kb sequence is directly controlled by T-box transcription factor 1 (Tbx1) in anterior second heart field cells that contribute to the outflow tract. It also responds to both NK2 transcription factor related, locus 5 (Nkx2-5) and ISL1 transcription factor, LIM/homeodomain (Islet1), acting through overlapping sites. Mutation of these sites reduces transgene expression in the anterior second heart field where the Fgf10 regulatory element is activated by Islet1 via direct binding in vivo. Analysis of the response to Nkx2-5 loss- and Isl1 gain-of-function genetic backgrounds indicates that the observed up-regulation of its activity in Nkx2-5 mutant hearts, reflecting that of Fgf10, is due to the absence of Nkx2-5 repression and to up-regulation of Isl1, normally repressed in the myocardium by Nkx2-5. ChIP experiments show strong binding of Nkx2-5 in differentiated myocardium. Molecular and genetic analysis of the Fgf10 cardiac element therefore reveals how key cardiac transcription factors orchestrate gene expression in the anterior second heart field and how genes, such as Fgf10, normally expressed in the progenitor cell population, are repressed when these cells enter the heart and differentiate into myocardium. Our findings provide a paradigm for transcriptional mechanisms that underlie the changes in regulatory networks during the transition from progenitor state to that of the differentiated tissue.
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Recent Developments in Home Sleep-monitoring Devices
ISRN Neurology.
2012 |
Pubmed ID: 23097718 Improving our understanding of sleep physiology and pathophysiology is an important goal for both medical and general wellness reasons. Although the gold standard for assessing sleep remains the laboratory polysomnogram, there is an increasing interest in portable monitoring devices that provide the opportunity for assessing sleep in real-world environments such as the home. Portable devices allow repeated measurements, evaluation of temporal patterns, and self-experimentation. We review recent developments in devices designed to monitor sleep-wake activity, as well as monitors designed for other purposes that could in principle be applied in the field of sleep (such as cardiac or respiratory sensing). As the body of supporting validation data grows, these devices hold promise for a variety of health and wellness goals. From a clinical and research standpoint, the capacity to obtain longitudinal sleep-wake data may improve disease phenotyping, individualized treatment decisions, and individualized health optimization. From a wellness standpoint, commercially available devices may allow individuals to track their own sleep with the goal of finding patterns and correlations with modifiable behaviors such as exercise, diet, and sleep aids.
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Clinical Simulation in Australia and New Zealand: Through the Lens of an Advisory Group
Collegian (Royal College of Nursing, Australia).
2012 |
Pubmed ID: 23101352 Across Australia, innovations in simulation to enhance learning in nursing have been occurring for three decades and nursing is, and needs to be, a leading player in simulation knowledge diffusion. However, expertise is unevenly distributed across health services and education providers. Rather than build on the expertise and achievements of others, there is a tendency for resource duplication and for trial and error problem solving, in part related to a failure to communicate achievements for the benefits of the professional collective. For nursing to become a Leader in the use of simulation and drive ongoing development, as well as conducting high quality research and evaluation, academics need to collaborate, aggregate best practice in simulation learning, and disseminate that knowledge to educators working in health services and higher education sectors across the whole of Australia and New Zealand. To achieve this strategic intent, capacity development principles and committed action are necessary. In mid 2010 the opportunity to bring together nurse educators with simulation learning expertise within Australia and New Zealand became a reality. The Council of Deans of Nursing and Midwifery (CDNM) Australia and New Zealand decided to establish an expert reference group to reflect on the state of Australian nursing simulation, to pool expertise and to plan ways to share best practice knowledge on simulation more widely. This paper reflects on the achievements of the first 18 months since the group's establishment and considers future directions for the enhancement of simulation learning practice, research and development in Australian nursing.
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Regulation of Sheep Oocyte Maturation Using CAMP Modulators
Theriogenology.
Oct, 2012 |
Pubmed ID: 23102843 Physical removal of mammalian cumulus-oocyte complexes (COCs) from ovarian follicles results in spontaneous resumption of meiosis, largely because of a decrease in cAMP concentrations, causing asynchrony between cytoplasmic and nuclear maturation and decreased oocyte developmental competence. The aim of this study was to modulate cAMP concentrations within ovine COCs to delay spontaneous nuclear maturation and improve developmental competence. Abattoir-derived sheep COCs were cultured for 2 hours (pre-IVM) in 100 μM forskolin (FSK) plus 500 μM 3-isobutyl-1-methylxanthine (IBMX). Pre-IVM (100 μM FSK and 500 μM IBMX) culture increased COC cAMP concentrations 10-fold compared with controls (P < 0.05). With regard to nuclear maturation, with FSK and IBMX and/or with FSH and cilostamide delayed completion of meiosis (metaphase II) by 3 to 4 hours compared with standard IVM (FSH-stimulated induction of meiosis). In this study, pre-IVM (with FSK and IBMX) followed by IVM (with FSH and cilostamide), increased ovine COC cAMP concentrations and delayed, but did not inhibit, completion of nuclear maturation. This did not affect embryo development rates, but increased total cell number of blastocysts compared with IVM with FSH alone (103 ± 6 vs. 66 ± 4 cells, respectively; mean ± SEM; P < 0.05). We inferred that regulation of ovine oocyte cAMP concentrations during IVM improved embryo quality compared with embryos produced by standard IVM methods.
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A Case of Hepatopulmonary Syndrome Solved by Mycophenolate Mofetil (An Inhibitor Of Angiogenesis and Nitric Oxid Production)
Journal of Hepatology.
Oct, 2012 |
Pubmed ID: 23104163 BACKGROUND: The autoimmune lymphoproliferative syndrome (ALPS) is a rare, multi-systemic disease, caused by an inherited defect in the Fas apoptotic pathway, characterized by a chronic non-malignant lymphoid accumulation, and autoimmune manifestations. Lung, kidney, liver, and gut infiltration is described in severe, multi-systemic cases; so far there is no description of hepatopulmonary syndrome (HPS), for which orthotopic liver transplantation (OLT) is currently the only known effective treatment. CASE REPORT: A Teenage boy, diagnosed with ALPS at 4 years old (lymph nodes enlargement, splenomegaly, immune cytopenias), was stable until 13 years old when he developed insidiously hypoxemia (PaO2 = 46.7 mmHg). He was diagnosed with HPS on the basis of hypoxemia, non-cirrhotic liver disease with portal hypertension, and pulmonary vascular dilatation (intra-pulmonary shunt = 45%). He was treated with oxygen (maximum 6 liters/minute), prednisolone and sirolimus. There was significant regression of all manifestations of ALPS, except the pulmonary symptoms, so, after evaluation in referral centers in England, OLT was proposed. Since he was to be submitted to major surgery, sirolimus, which has wound healing problems, was switched for mycophenolate mofetil (MMF). Following this change, we observed an enormous improvement of the pulmonary symptoms and reduction of oxygen needs. The intra-pulmonary shunt decreased from 45% to 0% in less than a year, and remains so until today (18 months after complete normalization), on continued treatment with MMF. Indication for OLT was suspended. In the last year lymphoid proliferation increased again, with huge splenomegaly, but no recurrence of HPS. The addition of sirolimus to MMF produced again a rapid resolution of lymphoid proliferation. CONCLUSION: The dramatic and unexpected regression of HPS may have been due to inhibition of angiogenesis and nitric oxide (NO) production by MMF (both important pathways/mediators in the HPS pathogenesis). Therefore, we propose the conduct of clinical trials with MMF, and/or other angiogenesis and NO inhibitors, in a long-term treatment basis, to confirm their potential as a valid alternative for medical treatment of HPS.
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Identification of Phosphorylation Sites in the COOH-terminal Tail of the μ-opioid Receptor
Journal of Neurochemistry.
Oct, 2012 |
Pubmed ID: 23106126 Phosphorylation is considered a key event in the signalling and regulation of the μ opioid receptor (MOPr). Here we used mass spectroscopy to determine the phosphorylation status of the C-terminal tail of the rat MOPr expressed in HEK-293 cells. Under basal conditions, MOPr is phosphorylated on Ser(363) and Thr(370) , while in the presence of morphine or [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO), the COOH-terminus is phosphorylated at three additional residues, Ser(356) , Thr(357) , and Ser(375) . Using N-terminal Glutathione S Transferase (GST) fusion proteins of the cytoplasmic, C-terminal tail of MOPr and point mutations of the same, we show that, in vitro, purified G protein-coupled receptor kinase 2 (GRK2) phosphorylates Ser(375) , PKC phosphorylates Ser(363) whilst CaMKII phosphorylates Thr(370) . Phosphorylation of the GST fusion protein of the C-terminal tail of MOPr enhanced its ability to bind arrestin-2 and -3. Hence, our study identifies both the basal and agonist-stimulated phospho-acceptor sites in the C-terminal tail of MOPr, and suggests that the receptor is subject to phosphorylation and hence regulation by multiple protein kinases. © 2012 International Society for Neurochemistry, J. Neurochem. (2012) 10.1111/jnc.12071.
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The Effects of Altered Intrathoracic Pressure on Resting Cerebral Blood Flow and Its Response to Visual Stimulation
NeuroImage.
Oct, 2012 |
Pubmed ID: 23108273 Investigating how intrathoracic pressure changes affect cerebral blood flow (CBF) is important for a clear interpretation of neuroimaging data in patients with abnormal respiratory physiology, intensive care patients receiving mechanical ventilation and in research paradigms that manipulate intrathoracic pressure. Here, we investigated the effect of experimentally increased and decreased intrathoracic pressures upon CBF and the stimulus-evoked CBF response to visual stimulation. Twenty healthy volunteers received intermittent inspiratory and expiratory loads (plus or minus 9cmH(2)O for 270s) and viewed an intermittent 2Hz flashing checkerboard, while maintaining stable end-tidal CO(2). CBF was recorded with transcranial Doppler sonography (TCD) and whole-brain pseudo-continuous arterial spin labeling magnetic resonance imaging (PCASL MRI). Application of inspiratory loading (negative intrathoracic pressure) showed an increase in TCD-measured CBF of 4% and a PCASL-measured increase in grey matter CBF of 5%, but did not alter mean arterial pressure (MAP). Expiratory loading (positive intrathoracic pressure) did not alter CBF, while MAP increased by 3%. Neither loading condition altered the perfusion response to visual stimulation in the primary visual cortex. In both loading conditions localized CBF increases were observed in the somatosensory and motor cortices, and in the cerebellum. Altered intrathoracic pressures, whether induced experimentally, therapeutically or through a disease process, have possible significant effects on CBF and should be considered as a potential systematic confound in the interpretation of perfusion-based neuroimaging data.
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NAD+ Biosynthesis Ameliorates a Zebrafish Model of Muscular Dystrophy
PLoS Biology.
Oct, 2012 |
Pubmed ID: 23109907 Muscular dystrophies are common, currently incurable diseases. A subset of dystrophies result from genetic disruptions in complexes that attach muscle fibers to their surrounding extracellular matrix microenvironment. Cell-matrix adhesions are exquisite sensors of physiological conditions and mediate responses that allow cells to adapt to changing conditions. Thus, one approach towards finding targets for future therapeutic applications is to identify cell adhesion pathways that mediate these dynamic, adaptive responses in vivo. We find that nicotinamide riboside kinase 2b-mediated NAD+ biosynthesis, which functions as a small molecule agonist of muscle fiber-extracellular matrix adhesion, corrects dystrophic phenotypes in zebrafish lacking either a primary component of the dystrophin-glycoprotein complex or integrin alpha7. Exogenous NAD+ or a vitamin precursor to NAD+ reduces muscle fiber degeneration and results in significantly faster escape responses in dystrophic embryos. Overexpression of paxillin, a cell adhesion protein downstream of NAD+ in this novel cell adhesion pathway, reduces muscle degeneration in zebrafish with intact integrin receptors but does not improve motility. Activation of this pathway significantly increases organization of laminin, a major component of the extracellular matrix basement membrane. Our results indicate that the primary protective effects of NAD+ result from changes to the basement membrane, as a wild-type basement membrane is sufficient to increase resilience of dystrophic muscle fibers to damage. The surprising result that NAD+ supplementation ameliorates dystrophy in dystrophin-glycoprotein complex- or integrin alpha7-deficient zebrafish suggests the existence of an additional laminin receptor complex that anchors muscle fibers to the basement membrane. We find that integrin alpha6 participates in this pathway, but either integrin alpha7 or the dystrophin-glycoprotein complex is required in conjunction with integrin alpha6 to reduce muscle degeneration. Taken together, these results define a novel cell adhesion pathway that may have future therapeutic relevance for a broad spectrum of muscular dystrophies.
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Social Support and Age Influence Distress Outcomes Differentially Across Urban, Regional and Remote Australia: an Exploratory Study
BMC Public Health.
Oct, 2012 |
Pubmed ID: 23110446 ABSTRACT: BACKGROUND: The variation of determinants of mental health with remoteness has rarely been directly examined. The current research aims to examine whether the association of psychosocial factors with psychological distress outcomes varies with increasing remoteness. METHODS: Participants were persons aged 55 and over from two community cohorts sampling from across rural and urban New South Wales (N = 4219; mean age = 69.00 years; 46.1% male). Measures of social support from these studies were calibrated to facilitate comparison across the sample. Remoteness was assessed using a continuous measure, the Accessibility/Remoteness Index of Australia. The association between demographic characteristics, social support, remoteness, and their interactions with remoteness in the prediction of high psychological distress (cut-off > 21 on the Kessler 10) were examined using logistic regression. RESULTS: Not being in a married or defacto relationship (OR 0.69; 99% CI 0.51-0.94), lower education (OR 0.52; 99% CI 0.38-0.71) and decreased social support (OR 0.36; 99% CI 0.31-0.42) significantly predicted psychological distress. There was a significant interaction of age and remoteness (OR 0.84; 99% CI 0.67-1.00), indicating that as remoteness increases, older persons are less likely to be highly distressed, as well as a significant interaction of social support and remoteness (OR 1.22; 99% CI 1.04-1.44), indicating that as remoteness decreases, persons with low levels of social support are more likely to be highly distressed. CONCLUSIONS: Remoteness may moderate the influence of social support and age on psychological distress outcomes.
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Effects of a Competitive Wrestling Season on Body Composition, Endocrine Markers, and Anaerobic Exercise Performance in NCAA Collegiate Wrestlers
European Journal of Applied Physiology.
Oct, 2012 |
Pubmed ID: 23114663 Few data exist examining the body composition, endocrine, and anaerobic exercise performance changes over a competitive wrestling season. Eighteen NCAA wrestlers were tested for endocrine markers, body composition, hydration, grip strength, and power on four occasions: prior to pre-season training (T1); after pre-season training 3 days prior to the first seasonal meet (T2); mid-season one day prior to a meet (T3); and at the end of the season 2-3 days following the last meet (T4). Body mass, percent body fat (BF %), and fat mass were significantly lower (P ≤ 0.05) at T2 and T3 compared to T1 but were not different between T1 and T4. Lean body mass was significantly reduced at T2 only. Urine specific gravity was significantly elevated at T3 compared to T1, T2, and T4. Resting cortisol concentrations did not change but resting testosterone concentrations were significantly reduced at T2, T3, and T4. Maximal grip strength was significantly reduced at T2. Vertical jump peak power was significantly reduced at T2, T3, and T4. Wingate peak power was significantly reduced at T2 and T3. However, Wingate average power and total work did not significantly change. Fatigue rate during the Wingate test was significantly improved at T2, T3, and T4 compared to T1. In conclusion, body mass, BF %, and measures of peak force and power were reduced for most of the competitive wrestling season. Competitive wrestling reduces resting total testosterone concentrations throughout the entire season.
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Synthesis of Soluble Graphite and Graphene
Accounts of Chemical Research.
Nov, 2012 |
Pubmed ID: 23116420 Because of graphene's anticipated applications in electronics and its thermal, mechanical, and optical properties, many scientists and engineers are interested in this material. Graphene is an isolated layer of the π-stacked hexagonal allotrope of carbon known as graphite. The interlayer cohesive energy of graphite, or exfoliation energy, that results from van der Waals attractions over the interlayer spacing distance of 3.34 Å (61 meV/C atom) is many times weaker than the intralayer covalent bonding. Since graphene itself does not occur naturally, scientists and engineers are still learning how to isolate and manipulate individual layers of graphene. Some researchers have relied on the physical separation of the sheets, a process that can sometimes be as simple as peeling of sheets from crystalline graphite using Scotch tape. Other researchers have taken an ensemble approach, where they exploit the chemical conversion of graphite to the individual layers. The typical intermediary state is graphite oxide, which is often produced using strong oxidants under acidic conditions. Structurally, researchers hypothesize that acidic functional groups functionalize the oxidized material at the edges and a network of epoxy groups cover the sp(2)-bonded carbon network. The exfoliated material formed under these conditions can be used to form dispersions that are usually unstable. However, more importantly, irreversible defects form in the basal plane during oxidation and remain even after reduction of graphite oxide back to graphene-like material. As part of our interest in the dissolution of carbon nanomaterials, we have explored the derivatization of graphite following the same procedures that preserve the sp(2) bonding and the associated unique physical and electronic properties in the chemical processing of single-walled carbon nanotubes. In this Account, we describe efficient routes to exfoliate graphite either into graphitic nanoparticles or into graphene without resorting to oxidation. Our exfoliation process involves the intercalation of lithium into bulk graphite to yield graphene sheets reduced by the lithium. We can alkylate the resulting graphite salt reductively using solubilizing dodecyl groups. By probe microscopy, we show that these groups are attached covalently only at the graphitic edges.
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Intravaginal Practices and Microbicide Acceptability in Papua New Guinea: Implications for HIV Prevention in a Moderate-prevalence Setting
BMC Research Notes.
Nov, 2012 |
Pubmed ID: 23116431 ABSTRACT: BACKGROUND: The acceptability of female-controlled biomedical prevention technologies has not been established in Papua New Guinea, the only country in the Pacific region experiencing a generalised, moderate-prevalence HIV epidemic. Socio-cultural factors likely to impact on future product uptake and effectiveness, such as women's ability to negotiate safer sexual choices, and intravaginal hygiene and menstrual practices (IVP), remain unclear in this setting. METHODS: A mixed-method qualitative study was conducted among women and men attending a sexual health clinic in Port Moresby. During in-depth interviews, participants used copies of a hand-drawn template to indicate how they wash/clean the vulva and/or vagina. Interviewers pre-filled commercially available vaginal applicators with 2-3mL KY Jelly(R) to create a surrogate vaginal microbicide product, which was demonstrated to study participants. RESULTS: A total of 28 IDIs were conducted (women=16; men=12). A diverse range of IVP were reported. The majority of women described washing the vulva only with soap and water as part of their daily routine; in preparation for sex; and following sexual intercourse. Several women described cleaning inside the vagina using fingers and soap at these same times. Others reported cleaning inside the vagina using a hose connected to a tap; using vaginal inserts, such as crushed garlic; customary menstrual 'steaming' practices; and the use of material fragments, cloth and newspaper to absorb menstrual blood. Unprotected sex during menstruation was common. The majority of both women and men said that they would use a vaginal microbicide gel for HIV/STI protection, should a safe and effective product become available. Microbicide use was considered most appropriate in 'high-risk' situations, such as sex with non-regular, transactional or commercial partners. Most women felt confident that they would be able to negotiate vaginal microbicide use with male sexual partners but if necessary would be prepared to use product covertly. CONCLUSIONS: Notional acceptability of a vaginal microbicide gel for HIV/STI prevention was high among both women and men. IVP were diverse in nature, socio-cultural dimensions and motivators. These factors are likely to impact on the future acceptability and uptake of vaginal microbicides and other biomedical HIV prevention technologies in this setting.
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Phosphorylated Neurofilament Heavy Subunit (pNF-H) in Peripheral Blood and CSF As a Potential Prognostic Biomarker in Amyotrophic Lateral Sclerosis
Journal of Neurology, Neurosurgery, and Psychiatry.
Oct, 2012 |
Pubmed ID: 23117489 BACKGROUND: The phosphorylated neurofilament heavy subunit (pNF-H), a major structural component of motor axons, is a promising putative biomarker in amyotrophic lateral sclerosis (ALS) but has been studied mainly in CSF. We examined pNF-H concentrations in plasma, serum and CSF as a potential biomarker for disease progression and survival in ALS. METHODOLOGY: We measured pNF-H concentration by monoclonal sandwich ELISA in plasma (n=43), serum and CSF (n=20) in ALS patients collected at the Mayo Clinic Florida and Emory University. We included plasma from an ALS cohort (n=20) from an earlier pilot study in order to evaluate baseline pNF-H levels in relation to disease progression using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), survival and anatomical region of ALS onset. RESULTS: Higher pNF-H levels in plasma, serum and CSF showed evidence of association with faster decline in ALSFRS-R. There was evidence for a relationship of higher serum and plasma pNF-H levels with shorter survival, although evidence was weaker for CSF. pNF-H concentration in plasma (n=62) may be higher in patients with bulbar onset than in patients with spinal onset. CONCLUSIONS: In ALS, increased pNF-H concentration in plasma, serum and CSF appears to be associated with faster disease progression. Factors affecting pNF-H levels or their detection in serum and plasma in relation to disease course may differ from those in CSF. Data raising the possibility that site of ALS onset (bulbar vs spinal) may influence pNF-H levels in peripheral blood seems noteworthy but requires confirmation. These data support further study of pNF-H in CSF, serum and plasma as a potential ALS biomarker.
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Validation of LC-TOF-MS Screening for Drugs, Metabolites, and Collateral Compounds in Forensic Toxicology Specimens
Journal of Analytical Toxicology.
Nov, 2012 |
Pubmed ID: 23118149 Liquid chromatography time-of-flight mass spectrometry (LC-TOF-MS) analysis provides an expansive technique for identifying many known and unknown analytes. This study developed a screening method that utilizes automated solid-phase extraction to purify a wide array of analytes involving stimulants, benzodiazepines, opiates, muscle relaxants, hypnotics, antihistamines, antidepressants and newer synthetic "Spice/K2" cannabinoids and cathinone "bath salt" designer drugs. The extract was applied to LC-TOF-MS analysis, implementing a 13 min chromatography gradient with mobile phases of ammonium formate and methanol using positive mode electrospray. Several common drugs and metabolites can share the same mass and chemical formula among unrelated compounds, but they are structurally different. In this method, the LC-TOF-MS was able to resolve many isobaric compounds by accurate mass correlation within 15 ppm mass units and a narrow retention time interval of less than 10 s of separation. Drug recovery yields varied among spiked compounds, but resulted in overall robust area counts to deliver an average match score of 86 when compared to the retention time and mass of authentic standards. In summary, this method represents a rapid, enhanced screen for blood and urine specimens in postmortem, driving under the influence, and drug facilitated sexual assault forensic toxicology casework.
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The Living with Dysarthria Group: Implementation and Feasibility of a Group Intervention for People with Dysarthria Following Stroke and Family Members
International Journal of Language & Communication Disorders / Royal College of Speech & Language Therapists.
Nov, 2012 |
Pubmed ID: 23121529 Background: The broad life implications of acquired dysarthria are recognized, but they have received little attention in stroke management. Reports of group therapy, which may be a suitable approach to intervention, are not available for stroke-related dysarthria. Aims: To examine the operational feasibility of and response to a new eight-session weekly group intervention programme, Living with Dysarthria, designed for people with chronic dysarthria following stroke and their main communication partners. Methods & Procedures: The target participation was for programme completion by two groups of eight people with dysarthria (PWD) and available family members (FMs) or carers. An active recruitment strategy was undertaken from the speech and language therapy case records for the previous 6 years in two hospitals with combined annual stroke admissions of over 500 people. Twelve PWD and seven FMs were recruited (group 1: seven PWD and four FMs; group 2: five PWD and three FMs). Speech intelligibility, communication effectiveness, general well-being, quality of communication life, and knowledge of stroke and dysarthria were assessed pre- and post-programme. Each PWD and FM also set an individual goal and rated their achievement of this on a 0-10 scale. Outcomes & Results: Recruitment to the programme was lower than anticipated and below target. The 12 PWD were recruited from 62 initial contacts, which was the total number who according to available information met the criteria. The programme was viable: it ran to plan, with only minor content alterations, in community accommodation, and with good participant engagement. Group median score changes were in a positive direction for all measures and effect sizes ranged from 0.17 (quality of communication life) to 0.46 (intelligibility). Significant post-programme changes were present for intelligibility and knowledge of stroke and dysarthria (p= 0.05). Participants' ratings of goal achievements ranged from 6 (some change) to 10 (a lot of change). Conclusions & Implications: The recruitment experience revealed a take-up rate of around 20% from PWD following stroke, informing future planning. The participant engagement and performance results from the piloting of the programme indicate that the Living with Dysarthria programme is viable and has potential for effecting positive change. Further testing is justified.
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Can We Identify Patients at High Risk of Recurrent Clostridium Difficile Infection?
Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases.
Dec, 2012 |
Pubmed ID: 23121551 Although most patients with Clostridium difficile infection (CDI) can be managed effectively with discontinuation of prescribed antibiotics and additional treatment with oral metronidazole or vancomycin, up to 25% experience disease recurrence, usually within 30 days of treatment. Failure to mount a systemic anti-toxin antibody response differentiates patients with CDI and recurrent CDI from symptomless carriers of toxinogenic C. difficile. The immunological senescence that accompanies ageing may lead to impaired immune responses to C. difficile and contribute to the significant association between advancing age and increased risk of CDI recurrence. Inadequate immunity may also explain why previous episodes of recurrence constitute a significant risk factor for further CDI recurrences. Other risk factors for recurrent CDI include concurrent use of antibiotics for non-C. difficile infections (which perpetuate the loss of colonization resistance), proton-pump inhibitors, and other gastric acid anti-secretory medications, prolonged hospitalization, and severe underlying illness (as reflected by a high Horn index score). Prominent risk factors have been examined to develop and validate a clinical prediction tool for recurrent CDI, with three factors (age >65 years, severe underlying disease (by the Horn index score), and continued use of antibiotics for non-CDI infections) being highly predictive of CDI recurrence. Such simple clinical prediction rules have the potential to identify patients at high risk of recurrent CDI, and can alert the treating physician to the need for prompt recognition, confirmatory diagnosis and treatment with regimens ideally designed to mitigate the risk of subsequent recurrences.
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Emerging Adults' Treatment Outcomes in Relation to 12-step Mutual-help Attendance and Active Involvement
Drug and Alcohol Dependence.
Oct, 2012 |
Pubmed ID: 23122600 BACKGROUND: Participation in Alcoholics Anonymous (AA) and Narcotics Anonymous (NA) during and following treatment has been found to confer recovery-related benefit among adults and adolescents, but little is known about emerging adults (18-24years). This transitional life-stage is distinctive for greater distress, higher density of psychopathology, and poorer treatment and continuing care compliance. Greater knowledge would inform the utility of treatment referrals to 12-step organizations for this age-group. METHODS: Emerging adults (N=303; 18-24years; 26% female; 95% White; 51% comorbid [SCID-derived] axis I disorders) enrolled in a naturalistic study of residential treatment effectiveness assessed at intake, 3, 6, and 12 months on 12-step attendance and involvement and treatment outcomes (percent days abstinent [PDA]; percent days heavy drinking [PDHD]). Lagged hierarchical linear models (HLMs) tested whether attendance and involvement conferred recovery benefits, controlling for a variety of confounds. RESULTS: The percentage attending 12-step meetings prior to treatment (36%) rose sharply at 3 months (89%), was maintained at 6 months (82%), but declined at 12 months (76%). Average attendance peaked at about 3 times per week at 3 months dropping to just over once per week at 12 months. Initially high, but similarly diminishing, levels of active 12-step involvement were also observed. Lagged HLMs found beneficial effects for attendance, but stronger effects, which increased over time, for active involvement. Several active 12-step involvement indices were associated individually with outcome benefits. CONCLUSIONS: Ubiquitous 12-step organizations may provide a supportive recovery context for this high-risk population at a developmental stage where non-using/sober peers are at a premium.
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A Quantitative Assessment of the Prion Risk Associated with Wastewater from Carcase-Handling Facilities
Risk Analysis : an Official Publication of the Society for Risk Analysis.
Nov, 2012 |
Pubmed ID: 23126436 Wastewater from facilities processing livestock that may harbor transmissible spongiform encephalopathies (TSEs) infectivity is permitted under license for application to land where susceptible livestock may have access. Several previous risk assessments have investigated the risk of bovine spongiform encephalopathy (BSE) associated with wastewater effluents; however, the risk of exposure to classical scrapie and atypical scrapie has not been assessed. With the prevalence of certain TSEs (BSE in cattle and classical scrapie in sheep) steadily in decline, and with considerable changes in the structure of carcase-processing industries in Great Britain, a reappraisal of the TSE risk posed by wastewater is required. Our results indicate that the predicted number of new TSE infections arising from the spreading of wastewater on pasture over one year would be low, with a mean of one infection every 1,000 years for BSE in cattle (769, 555,556), and one infection every 30 years (16, 2,500), and 33 years (16, 3,333) for classical and atypical scrapie, respectively. It is assumed that the values and assumptions used in this risk assessment remain constant. For BSE in cattle the main contributors are abattoir and rendering effluent, contributing 35% and 22% of the total number of new BSE infections. For TSEs in sheep, effluent from small incinerators and rendering plants are the major contributors (on average 32% and 31% of the total number of new classical scrapie and atypical scrapie infections). This is a reflection of the volume of carcase material and Category 1 material flow through such facilities.
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Atomic Force Microscopy Characterization of Collagen 'nanostraws' in Human Costal Cartilage
Micron (Oxford, England : 1993).
Oct, 2012 |
Pubmed ID: 23127510 Costal cartilage, a type of hyaline cartilage that bridges the bony ribs and sternum, is relatively understudied compared to the load bearing cartilages. Deformities of costal cartilage can result in deformation of the chest wall, where the sternum is largely pushed toward or away from the spine, pectus excavatum and pectus carinatum, respectively, with each condition having significant clinical impact. In the absence of extensive literature describing morphological features of costal cartilage, we characterized a sample from the costal margin immunohistologically and through atomic force microscopy. We had previously observed the presence of collagen 'nanostraws' running the length of costal cartilage. Hypothesizing that these structures may be responsible for fluid flow within this thick, avascular tissue, and prior to microfluidic analysis, we estimated the diameters and measured Young's modulus of elasticity of the collagen nanostraws. We found significant differences in results between treatment type and fixation. Significant differences in nanostraw elasticity and diameter obviously affect nano-fluidic transport calculations, and therefore, we consider these results of importance to the scientific community relying upon measurements in the nanoscale.
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Cohort Profile: The Caerphilly Health and Social Needs Electronic Cohort Study (E-CATALyST)
International Journal of Epidemiology.
Nov, 2012 |
Pubmed ID: 23132614 The Caerphilly Health and Social Needs study was established to inform and support collaborative multiagency working on reducing inequalities in health and to investigate neighbourhood influences on mental health. Initially, we collated a robust small-area multiagency dataset of contextual health determinants and outcomes from routine sources and sharing of data between the National Health Service and Caerphilly county borough council. These data were widely used in local joint planning to improve health and reduce health inequalities. Secondly, we carried out a baseline population questionnaire survey, collecting data from 10 892 (60.6%) respondents aged 18-74 years on a wide range of socio-economic, lifestyle, health and housing factors and perceptions of the local neighbourhood, including access to services, social cohesion and neighbourhood quality. We carried out wave 2 of the survey after 7 years with responses from 4558 (50.2%) participants to the same range of questions. We developed the study into an electronic cohort, linking all 17 979 sampled participants aged 18-74 years to mortality and hospital admission records with 10-year follow-up and full recording of migration both within and out of the borough. Readers with an interest in collaborative use of the data should contact Professor David Fone, Principal Investigator.
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Comparative Genomics Suggests an Independent Origin of Cytoplasmic Incompatibility in Cardinium Hertigii
PLoS Genetics.
Oct, 2012 |
Pubmed ID: 23133394 Terrestrial arthropods are commonly infected with maternally inherited bacterial symbionts that cause cytoplasmic incompatibility (CI). In CI, the outcome of crosses between symbiont-infected males and uninfected females is reproductive failure, increasing the relative fitness of infected females and leading to spread of the symbiont in the host population. CI symbionts have profound impacts on host genetic structure and ecology and may lead to speciation and the rapid evolution of sex determination systems. Cardinium hertigii, a member of the Bacteroidetes and symbiont of the parasitic wasp Encarsia pergandiella, is the only known bacterium other than the Alphaproteobacteria Wolbachia to cause CI. Here we report the genome sequence of Cardinium hertigii cEper1. Comparison with the genomes of CI-inducing Wolbachia pipientis strains wMel, wRi, and wPip provides a unique opportunity to pinpoint shared proteins mediating host cell interaction, including some candidate proteins for CI that have not previously been investigated. The genome of Cardinium lacks all major biosynthetic pathways but harbors a complete biotin biosynthesis pathway, suggesting a potential role for Cardinium in host nutrition. Cardinium lacks known protein secretion systems but encodes a putative phage-derived secretion system distantly related to the antifeeding prophage of the entomopathogen Serratia entomophila. Lastly, while Cardinium and Wolbachia genomes show only a functional overlap of proteins, they show no evidence of laterally transferred elements that would suggest common ancestry of CI in both lineages. Instead, comparative genomics suggests an independent evolution of CI in Cardinium and Wolbachia and provides a novel context for understanding the mechanistic basis of CI.
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The Effect of Copper(ii), Iron(ii) Sulphate, and Vitamin C Combinations on the Weak Antimicrobial Activity of (+)-catechin Against Staphylococcus Aureus and Other Microbes
Metallomics : Integrated Biometal Science.
Nov, 2012 |
Pubmed ID: 23138340 Few attempts have been made to improve the activity of plant compounds with low antimicrobial efficacy. (+)-Catechin, a weak antimicrobial tea flavanol, was combined with putative adjuncts and tested against different species of bacteria. Copper(ii) sulphate enhanced (+)-catechin activity against Pseudomonas aeruginosa but not Staphylococcus aureus, Proteus mirabilis or Escherichia coli. Attempts to raise the activity of (+)-catechin against two unresponsive species, S. aureus and E. coli, with iron(ii) sulphate, iron(iii) chloride, and vitamin C, showed that iron(ii) enhanced (+)-catechin against S. aureus, but not E. coli; neither iron(iii) nor combined iron(ii) and copper(ii), enhanced (+)-catechin activity against either species. Vitamin C enhanced copper(ii) containing combinations against both species in the absence of iron(ii). Catalase or EDTA added to active samples removed viability effects suggesting that active mixtures had produced H(2)O(2)via the action of added metal(ii) ions. H(2)O(2) generation by (+)-catechin plus copper(ii) mixtures and copper(ii) alone could account for the principal effect of bacterial growth inhibition following 30 minute exposures as well as the antimicrobial effect of (+)-catechin-iron(ii) against S. aureus. These novel findings about a weak antimicrobial flavanol contrast with previous knowledge of more active flavanols with transition metal combinations. Weak antimicrobial compounds like (+)-catechin within enhancement mixtures may therefore be used as efficacious agents. (+)-Catechin may provide a means of lowering copper(ii) or iron(ii) contents in certain crop protection and other products.
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Identifying Older People at High Risk of Future Falls: Development and Validation of a Screening Tool for Use in Emergency Departments
Emergency Medicine Journal : EMJ.
Nov, 2012 |
Pubmed ID: 23139096 BACKGROUND: Hospital emergency departments (EDs) treat a high proportion of older people, many as a direct consequence of falling. OBJECTIVE: To develop and externally validate a fall risk screening tool for use in hospital EDs and to compare the tool's predictive ability to existing screening tools. METHODS: This prospective cohort study involved two hospital EDs in Sydney, Australia. Potential participants were people aged 70+ years who presented to the ED after falling or with a history of 2+ falls in the previous year and were subsequently discharged. 219 people participated in the tool development study and 178 people participated in the external validation study. Study measures included number of fallers during the 6-month follow-up period, and physical status, medical history, fall history and community service use. RESULTS: 31% and 35% of participants fell in the development and external validation samples, respectively. The developed two-item screening tool included: 2+ falls in the past year (OR 4.18, 95% CI 2.61 to 6.68) and taking 6+ medications (OR 1.89, CI 1.18 to 3.04). The area under the receiver operating characteristic curve (AUC) was 0.70 (0.64-0.76). This represents significantly better predictive ability than the measure of 2+ previous falls alone (AUC 0.67, 0.62-0.72, p=0.02) and similar predictive ability to the FROP-Com (AUC 0.73, 0.67-0.79, p=0.25) and PROFET screens (AUC 0.70, 0.62-0.78, p=0.5). CONCLUSIONS: A simple, two-item screening tool demonstrated good external validity and accurately discriminated between fallers and non-fallers. This tool could identify high risk individuals who may benefit from onward referral or intervention after ED discharge.
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Primary Prevention of Pediatric Abusive Head Trauma: A Cost Audit and Cost-utility Analysis
Child Abuse & Neglect.
Nov, 2012 |
Pubmed ID: 23141137 OBJECTIVES: To obtain comprehensive, reliable data on the direct cost of pediatric abusive head trauma in New Zealand, and to use this data to evaluate the possible cost-benefit of a national primary prevention program. METHODS: A 5 year cohort of infants with abusive head trauma admitted to hospital in Auckland, New Zealand was reviewed. We determined the direct costs of hospital care (from hospital and Ministry of Health financial records), community rehabilitation (from the Accident Compensation Corporation), special education (from the Ministry of Education), investigation and child protection (from the Police and Child Protective Services), criminal trials (from the Police, prosecution and defence), punishment of offenders (from the Department of Corrections) and life-time care for moderate or severe disability (from the Accident Compensation Corporation). Analysis of the possible cost-utility of a national primary prevention program was undertaken, using the costs established in our cohort, recent New Zealand national data on the incidence of pediatric abusive head trauma, international data on quality of life after head trauma, and published international literature on prevention programs. RESULTS: There were 52 cases of abusive head trauma in the sample. Hospital costs totaled $NZ2,433,340, child protection $NZ1,560,123, police investigation $NZ1,842,237, criminal trials $NZ3,214,020, punishment of offenders $NZ4,411,852 and community rehabilitation $NZ2,895,848. Projected education costs for disabled survivors were $NZ2,452,148, and the cost of projected lifetime care was $NZ33,624,297. Total costs were $NZ52,433,864, averaging $NZ1,008,344 per child. Cost-utility analysis resulted in a strongly positive economic argument for primary prevention, with expected case scenarios showing lowered net costs with improved health outcomes. CONCLUSIONS: Pediatric abusive head trauma is very expensive, and on a conservative estimate the costs of acute hospitalization represent no more than 4% of lifetime direct costs. If shaken baby prevention programs are effective, there is likely to be a strong economic argument for their implementation. This study also provides robust data for future cost-benefit analysis in the field of abusive head trauma prevention.
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LIBER8 Design and Methods: An Integrative Intervention for Loss of Control Eating Among African American and White Adolescent Girls
Contemporary Clinical Trials.
Nov, 2012 |
Pubmed ID: 23142669 Loss of control (LOC) eating affects a significant number of adolescents of all racial and ethnic backgrounds and is associated with numerous psychosocial problems, including depression, anxiety, low self-esteem, body dissatisfaction, and weight concerns. However, empirically validated, culturally sensitive treatments for adolescents with these disordered eating behaviors are not available. This pilot project involved designing a developmentally and culturally appropriate treatment for LOC eating for adolescent girls. We intend to conduct multiple focus groups with adolescent girls who engage in LOC eating, and their primary caregivers. Data from these groups will inform the subsequent creation of a manualized treatment protocol. We will then evaluate the efficacy of this intervention (LIBER8-Linking Individuals Being Emotionally Real) to reduce LOC eating. This intervention will integrate components of dialectical behavior therapy, such as mindfulness and distress tolerance skills training, and cognitive-behavioral therapy. We will also integrate text-messaging, a key adolescent communication strategy, as a means of self-monitoring. Participants meeting study criteria will be offered participation in this 12-week randomized controlled trial comparing LIBER8 to a weight management control condition (2BFit). We hypothesize that this intervention will serve to reduce LOC eating, as well as improve psychosocial functioning as evidenced by decreased depression, anxiety, eating disorder cognitions, emotional eating, impulsivity, and improved quality of life. The feasibility and acceptability of this intervention will be extensively evaluated with the explicit intent of informing a subsequent larger randomized controlled trial.
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Community-acquired Neonatal and Infant Sepsis in Developing Countries: Efficacy of WHO's Currently Recommended Antibiotics--systematic Review and Meta-analysis
Archives of Disease in Childhood.
Nov, 2012 |
Pubmed ID: 23142784 OBJECTIVE: To review the aetiology and antibiotic resistance patterns of community-acquired sepsis in developing countries in infants where no clear focus of infection is clinically identified. To estimate the likely efficacy of WHO's recommended treatment for infant sepsis. DESIGN: A systematic review of the literature describing the aetiology of community-acquired neonatal and infant sepsis in developing countries. Using meta-analytical methods, susceptibility was determined to the antibiotic combinations recommended by WHO: (1) benzylpenicillin/ampicillin and gentamicin, (2) chloramphenicol and benzylpenicillin, and (3) third-generation cephalosporins. RESULTS: 19 studies were identified from 13 countries, with over 4000 blood culture isolates. Among neonates, Staphylococcus aureus, Klebsiella spp. and Escherichia coli accounted for 55% (39-70%) of culture positive sepsis on weighted prevalence. In infants outside the neonatal period, the most prevalent pathogens were S aureus, E coli, Klebsiella spp., Streptococcus pneumoniae and Salmonella spp., which accounted for 59% (26-92%) of culture positive sepsis. For neonates, penicillin/gentamicin had comparable in vitro coverage to third-generation cephalosporins (57% vs 56%). In older infants (1-12 months), in vitro susceptibility to penicillin/gentamicin, chloramphenicol/penicillin and third-generation cephalosporins was 63%, 47% and 64%, respectively. CONCLUSIONS: The high rate of community-acquired resistant sepsis-especially that caused by Klebsiella spp. and S aureus-is a serious global public health concern. In vitro susceptibility data suggest that third-generation cephalosporins are not more effective in treating sepsis than the currently recommended antibiotics, benzylpenicillin and gentamicin; however, with either regimen a significant proportion of bacteraemia is not covered. Revised recommendations for effective second-line antibiotics in neonatal and infant sepsis in developing countries are urgently needed.
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Digital Breast Tomosynthesis Versus Supplemental Diagnostic Mammographic Views for Evaluation of Noncalcified Breast Lesions
Radiology.
Nov, 2012 |
Pubmed ID: 23143023 Purpose:To compare the diagnostic performance of breast tomosynthesis versus supplemental mammography views in classification of masses, distortions, and asymmetries.Materials and Methods:Eight radiologists who specialized in breast imaging retrospectively reviewed 217 consecutively accrued lesions by using protocols that were HIPAA compliant and institutional review board approved in 182 patients aged 31-60 years (mean, 50 years) who underwent diagnostic mammography and tomosynthesis. The lesions in the cohort included 33% (72 of 217) cancers and 67% (145 of 217) benign lesions. Eighty-four percent (182 of 217) of the lesions were masses, 11% (25 of 217) were asymmetries, and 5% (10 of 217) were distortions that were initially detected at clinical examination in 8% (17 of 217), at mammography in 80% (173 of 217), at ultrasonography (US) in 11% (25 of 217), or at magnetic resonance imaging in 1% (2 of 217). Histopathologic examination established truth in 191 lesions, US revealed a cyst in 12 lesions, and 14 lesions had a normal follow-up. Each lesion was interpreted once with tomosynthesis and once with supplemental mammographic views; both modes included the mediolateral oblique and craniocaudal views in a fully crossed and balanced design by using a five-category Breast Imaging Reporting and Data System (BI-RADS) assessment and a probability-of-malignancy score. Differences between modes were analyzed with a generalized linear mixed model for BI-RADS-based sensitivity and specificity and with modified Obuchowski-Rockette approach for probability-of-malignancy-based area under the receiver operating characteristic (ROC) curve.Results:Average probability-of-malignancy-based area under the ROC curve was 0.87 for tomosynthesis versus 0.83 for supplemental views (P < .001). With tomosynthesis, the false-positive rate decreased from 85% (989 of 1160) to 74% (864 of 1160) (P < .01) for cases that were rated BI-RADS category 3 or higher and from 57% (663 of 1160) to 48% (559 of 1160) for cases rated BI-RADS category 4 or 5 (P < .01), without a meaningful change in sensitivity. With tomosynthesis, more cancers were classified as BI-RADS category 5 (39% [226 of 576] vs 33% [188 of 576]; P = .017) without a decrease in specificity.Conclusion:Tomosynthesis significantly improved diagnostic accuracy for noncalcified lesions compared with supplemental mammographic views.© RSNA, 2012.
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A Review of Blood Component Usage in a Large UK Emergency Department After Implementation of Simple Measures
Emergency Medicine Journal : EMJ.
Nov, 2012 |
Pubmed ID: 23144079 OBJECTIVES: To review clinical indications and demographics of transfusion and the patterns of blood component ordering, transfusion, wastage and traceability, before (2007) and after (2011) implementation of simple improvement strategies. METHODS: Retrospective case note review of all patients presenting to the Royal Infirmary of Edinburgh (RIE) Emergency Department (ED) for whom a blood component was requested and historic comparison. Improvement measures implemented between 2007 and 2011 included (1) formal staff education, (2) use of e-learning Module One Safe Transfusion Practice (traceability update, Medicines and Healthcare products Regulatory Agency (MHRA) traceability regulations and importance of returning completed blood component tags), (3) an ED resuscitation room blood fridge, (4) introduction of a dedicated ED transfusion consultant and ED transfusion link nurse and (5) the presence of an ED consultant on the Hospital Transfusion Group. RESULTS: Between 1st January and 31st December 2011, blood components were requested for 255 patient episodes, totalling 1034 individual units. 687 units (66.4%) of blood component were transfused, 248 components (24.0%) were recycled, 90 components (8.7%) were discarded and nine units (0.9%) were unaccounted for. There was a 64% reduction in blood component ordering (3209 vs 1034 units), a 39% reduction in blood component transfusion (1131 vs 687 units) and a 96% reduction in unaccounted units (214 vs 9 units) between 2007 and 2011. There was a rise in the median age of the patient for whom a transfusion request was made from 63.9 years in 2007 to 67.0 years in 2011. CONCLUSIONS: Blood component ordering, usage and traceability within the ED have improved significantly since 2007 following implementation of simple strategies. The age of ED transfusion recipients is increasing.
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Suppression of Wnt1-induced Mammary Tumor Growth and Lower Serum Insulin in Offspring Exposed to Maternal Blueberry Diet Suggest Early Dietary Influence on Developmental Programming
Carcinogenesis.
Nov, 2012 |
Pubmed ID: 23144318 Despite the well-accepted notion that early maternal influences persist beyond fetal life and may underlie many adult diseases, the risks imposed by the maternal environment on breast cancer development and underlying biological mechanisms remain poorly understood. In this study, we investigated whether early exposure to blueberry (BB) via maternal diet alters oncogene Wnt1-induced mammary tumorigenesis in offspring. Wnt1-transgenic female mice were exposed to maternal Casein (CAS, control) or blueberry-supplemented (CAS + 3%BB) diets throughout pregnancy and lactation. Offspring were weaned to CAS and mammary tumor development was followed until age 8 months. Tumor incidence and latency were similar for both groups; however, tumor weight at killing and tumor volume within 2 weeks of initial detection were lower (by 50 and 60%, respectively) in offspring of BB- versus control-fed dams. Dietary BB exposure beginning at weaning did not alter mammary tumor parameters. Tumors from maternal BB-exposed offspring showed higher tumor suppressor (Pten and Cdh1) and lower proproliferative (Ccnd1), anti-apoptotic (Bcl2) and proangiogenic (Figf, Flt1 and Ephb4) transcript levels, and displayed attenuated microvessel density. Expression of Pten and Cdh1 genes was also higher in mammary tissues of maternal BB-exposed offspring. Mammary tissues and tumors of maternal BB-exposed offspring showed increased chromatin-modifying enzyme Dnmt1 and Ezh2 transcript levels. Body weight, serum insulin and serum leptin/adiponectin ratio were lower for maternal BB-exposed than control tumor-bearing offspring. Tumor weights and serum insulin were positively correlated. Results suggest that dietary influences on the maternal environment contribute to key developmental programs in the mammary gland to modify breast cancer outcome in adult progeny.
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The Association Between Early Life and Adult Body Mass Index and Physical Activity with Risk of Non-Hodgkin Lymphoma: Impact of Gender
Annals of Epidemiology.
Nov, 2012 |
Pubmed ID: 23146413 PURPOSE: To evaluate the association of body mass index (BMI) and physical activity (PA) during adulthood and at the age of 18 years with risk of non-Hodgkin lymphoma (NHL). METHODS: We enrolled 950 newly diagnosed NHL patients and 1146 frequency-matched clinic-based controls. Height, weight, and PA (recent adult and at the age of 18 years) were self-reported. Odds ratios (ORs), 95% confidence intervals, and tests for trend were estimated using unconditional logistic regression adjusted for age, gender, and residence. RESULTS: BMI at the age of 18 years was associated with an increased NHL risk (OR, 1.38 for highest vs. lowest quartile; p-trend = .0012), which on stratified analysis was specific to females (OR, 1.90; p-trend = .00025). There was no association of adult BMI with NHL risk. Higher PA in adulthood (OR, 1.03; p-trend = .85) or at the age of 18 years (OR, 0.88; 95% confidence interval, 0.72-1.07) was not associated with risk, but there was an inverse association for adult PA that was specific to females (OR, 0.71; p-trend = .039). Only BMI at the age of 18 years remained significantly associated with NHL risk when modeled together with PA in adulthood or at the age of 18 years. There was little evidence for heterogeneity in these results for the common NHL subtypes. CONCLUSIONS: Early adult BMI may be of greatest relevance to NHL risk, particularly in females.
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Cannabis Withdrawal in Chronic Cannabis Users with Schizophrenia
Journal of Psychiatric Research.
Nov, 2012 |
Pubmed ID: 23146560 BACKGROUND: Chronic users of cannabis often report withdrawal symptoms after abstinence from use, but little is known about cannabis withdrawal in people with schizophrenia. METHODS: Cannabis use patterns and withdrawal symptoms in adults with schizophrenia who had at least weekly cannabis use before attempting to quit without formal treatment were assessed with the Marijuana Quit Questionnaire (MJQQ), a 176-item, semi-structured questionnaire. RESULTS: 120 participants, predominantly African-American (62.5%) and male (76.7%), met inclusion criteria. 20.1% reported that their first regular cannabis use (median age 15 years [range 8-48]) preceded their age at first psychotic symptoms (20 [4-50] years). Twenty (16.7%) participants met lifetime criteria for cannabis abuse; 98 (81.7%) met surrogate criteria for lifetime cannabis dependence. Withdrawal symptoms were reported by 113 (94.2%) participants, with 74.2% reporting ≥4 symptoms. The most frequently reported withdrawal symptoms were craving for cannabis (59.2%), feeling anxious (52.57%), feeling bored (47.5%), feeling sad or depressed (45.8%), feeling irritable or jumpy (45.0%), feeling restless (43.3%), and trouble failing asleep (33.3%). One hundred-and-four (92.0%) participants took some action to relieve at least one of their withdrawal symptoms during their index-quit attempt, including 26 (23.0%) participants who reported resuming cannabis use. CONCLUSION: Cannabis withdrawal is a clinically significant feature of cannabis use among people with schizophrenia, may serve as a negative reinforcer for relapse, and deserves greater attention in treatment and research. Clinical Trials registration NCT00679016.
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Patterns of Structural Head Injury in Children Younger Than 3 Years: A 10-year Review of 519 Patients
The Journal of Trauma and Acute Care Surgery.
Nov, 2012 |
Pubmed ID: 23147184 BACKGROUND: Abusive head injury is a major contributor to morbidity and mortality in infants and toddlers, but data comparing patterns of injury in corroborated accidental trauma and confessed child abuse are scarce. METHODS: This is a retrospective review of head injuries with abnormal neuroimaging in children younger than 3 years during a 10-year period in Auckland, New Zealand. Histories were assumed to be true. Results were analyzed for incongruity then compared with data on confessed abuse and corroborated accidental injury. RESULTS: Five hundred nineteen cases were analyzed. Most cases were congruent with the history, and their pattern was consistent with the literature on accidental head trauma in childhood. However, a spike of subdural hemorrhage was seen in the first 6 months of life, explained neither by mechanism nor by published data on birth trauma. The age distribution of retinal hemorrhage was also inconsistent with published data on birth trauma. In infants younger than 6 months, retinal and subdural hemorrhages were associated with the absence of a history of trauma. In older children (6 months-3 years), subdural hemorrhage was more common after minor falls (2 m, 20%) (p = 0.002). CONCLUSION: We conclude that when a young child (particularly an infant younger than 6 months) presents with traumatic intracranial pathology and either no history of trauma or a history of a minor fall, it must be seriously considered that the history is false. LEVEL OF EVIDENCE: Observational study, case series, level III.
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Novel Checkpoint Pathway Organization Promotes Genome Stability in Stationary Phase Yeast Cells
Molecular and Cellular Biology.
Nov, 2012 |
Pubmed ID: 23149941 Most DNA alterations occur during DNA replication in S phase of the cell cycle. However, the majority of eukaryotic cells exist in a non-dividing, quiescent state. Little is known about the factors involved in preventing DNA instability within this stationary-phase cell population. Previously, we utilized a unique assay system to identify mutations that increased minisatellite alterations specifically in quiescent cells in Saccharomyces cerevisiae. Here, we conducted a modified version of the Synthetic Genetic Array analysis to determine if checkpoint signaling components play a role in stabilizing minisatellites in stationary phase yeast cells. Our results revealed that a subset of checkpoint components, specifically MRC1, CSM3, TOF1, DDC1, RAD17, MEC3, TEL1, MEC1 and RAD53, prevent stationary-phase minisatellite alterations within the quiescent cell subpopulation of stationary phase cells. Pathway analysis revealed at least three pathways, with MRC1, CSM3 and TOF1 acting in a pathway independent of MEC1 and RAD53. Overall, our data indicate that some well-characterized checkpoint components maintain minisatellite stability in stationary-phase cells, but are regulated differently in those cells compared to actively growing cells. For the MRC1-dependent pathway, the checkpoint itself may not be the important element, but rather loss of the checkpoint proteins' other functions that contribute to DNA instability.
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Bacteria of the Human Gut Microbiome Catabolize Red Seaweed Glycans with Carbohydrate-active Enzyme Updates from Extrinsic Microbes
Proceedings of the National Academy of Sciences of the United States of America.
Nov, 2012 |
Pubmed ID: 23150581 Humans host an intestinal population of microbes-collectively referred to as the gut microbiome-which encode the carbohydrate active enzymes, or CAZymes, that are absent from the human genome. These CAZymes help to extract energy from recalcitrant polysaccharides. The question then arises as to if and how the microbiome adapts to new carbohydrate sources when modern humans change eating habits. Recent metagenome analysis of microbiomes from healthy American, Japanese, and Spanish populations identified putative CAZymes obtained by horizontal gene transfer from marine bacteria, which suggested that human gut bacteria evolved to degrade algal carbohydrates-for example, consumed in form of sushi. We approached this hypothesis by studying such a polysaccharide utilization locus (PUL) obtained by horizontal gene transfer by the gut bacterium Bacteroides plebeius. Transcriptomic and growth experiments revealed that the PUL responds to the polysaccharide porphyran from red algae, enabling growth on this carbohydrate but not related substrates like agarose and carrageenan. The X-ray crystallographic and biochemical analysis of two proteins encoded by this PUL, BACPLE_01689 and BACPLE_01693, showed that they are β-porphyranases belonging to glycoside hydrolase families 16 and 86, respectively. The product complex of the GH86 at 1.3 Å resolution highlights the molecular details of porphyran hydrolysis by this new porphyranase. Combined, these data establish experimental support for the argument that CAZymes and associated genes obtained from extrinsic microbes add new catabolic functions to the human gut microbiome.
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In Vivo Tungsten Exposure Alters B Cell Development and Increases DNA Damage in Murine Bone Marrow
Toxicological Sciences : an Official Journal of the Society of Toxicology.
Nov, 2012 |
Pubmed ID: 23152188 High environmental tungsten levels were identified near the site of a childhood pre-B acute lymphoblastic leukemia (preB-ALL) cluster, however a causal link between tungsten and leukemogenesis has not been established. The major site of tungsten deposition is bone, the site of B cell development. In addition, our in vitro data suggest that developing B lymphocytes are susceptible to tungsten-induced DNA damage and growth inhibition. To extend these results, we assessed whether tungsten exposure altered B-cell development and induced DNA damage in vivo. Wild-type mice were exposed to tungsten in their drinking water for up to 16 weeks. Tungsten concentration in bone was analyzed by inductively coupled plasma mass spectrometry (ICP-MS), and correlated with B-cell development and DNA damage within the bone marrow. Tungsten exposure resulted in a rapid deposition within the bone following one week, and continued to accumulate thereafter, albeit at a decreased rate. Flow cytometric analyses revealed a transient increase in mature IgD(+) B-cells in the first 8 weeks of treatment, in animals of the highest and intermediate exposure groups. Following 16 weeks exposure, all tungsten groups had a significantly greater percentage of cells in the late pro/large preB developmental stages. DNA damage was increased in both whole marrow and isolated B-cells, most notably at the lowest tungsten concentration tested. These findings confirm an immunological effect of tungsten exposure, and suggest that tungsten could act as a tumor promoter, providing leukemic "hits" in multiple forms to developing B lymphocytes within the bone marrow.
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A Mixed-method Examination of Food Marketing Directed Towards Children in Australian Supermarkets
Health Promotion International.
Nov, 2012 |
Pubmed ID: 23154998 The purpose of this study was to determine the prevalence of children's food requests, and parents' experiences of food marketing directed towards children, in the supermarket environment. A mixed-method design was used. Firstly, intercept interviews were conducted with parents accompanied by a child/children on exiting supermarkets (sampled from a large regional centre in Australia). Parents were asked about the prevalence and types of food requests by child/children during their supermarket visit and whether they purchased these foods. Secondly, focus groups (n = 13) and telephone interviews (n = 3) were conducted exploring parents' experiences of supermarket shopping with children and the impact of child-directed marketing. Of the 158 intercept survey participants (30% response rate), 73% reported a food request during the supermarket visit. Most requested food items (88%) were unhealthy foods, with chocolate/confectionery being the most common food category requested (40%). Most parents (70%) purchased at least one food item requested during the shopping trip. Qualitative interviews identified four themes associated with food requests and prompts in the supermarket: parents' experience of pester power in the supermarket; prompts for food requests in the supermarket; parental responses to pestering in the supermarket environment, and; strategies to manage pestering and minimize requests for food items. Food requests from children are common during supermarket shopping. Despite the majority of the requests being unhealthy, parents often purchase these foods. Parents reported difficulties dealing with constant requests and expressed desire for environmental changes including confectionery-free checkouts, minimization of child friendly product placement and reducing children's exposure to food marketing.
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Legitimacy in Legacy: a Discussion Paper of Historical Scholarship Published in the Journal of Advanced Nursing, 1976-2011
Journal of Advanced Nursing.
Nov, 2012 |
Pubmed ID: 23157468 AIMS: This paper presents a discussion of historical scholarship published in the Journal of Advanced Nursing. BACKGROUND: The Journal of Advanced Nursing provides a forum for disseminating high-quality research and scholarship. For over 35Â years, scholars have used the Journal of Advanced Nursing to disseminate research into aspects of nursing, including nursing history. DATA SOURCES: The data source was Wiley Online electronic database for the Journal of Advanced Nursing for the period 1976-December 2011. DISCUSSION: Relative to other academic concerns, nursing history represents a topic of limited concern to nursing scholars, as evidenced in published scholarship in the Journal of Advanced Nursing. The trends in historical scholarship in the journal have been on disciplinary development, the place and context of practice, and gendered relationships. While these are legitimate academic concerns, they suggest a lack of attention to clinical practice in historical research, that which confers social legitimacy on the discipline. IMPLICATIONS FOR NURSING: Nursing derives its social legitimacy, in part, through its history, including reliable accounts of the legacy of nursing work in the development of healthcare systems. Disciplinary development in nursing is advanced by giving greater prominence to nursing history in nursing scholarship, including the history of nursing practice CONCLUSIONS: Relative to other academic concerns, nursing scholarship affords little prominence to the topic of nursing history and less still to the history of practice, as evidenced in the outputs of one of nursing's major organs of scholarship. Not to assign due importance to the history of nursing and its practice demonstrates nursing's lack of disciplinary maturity.
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Effects of Pregnancy Planning, Fertility, and Assisted Reproductive Treatment on Child Behavioral Problems at 5 and 7 Years: Evidence from the Millennium Cohort Study
Fertility and Sterility.
Nov, 2012 |
Pubmed ID: 23158833 OBJECTIVE: To examine the effects of pregnancy planning, time to conception (TTC), and assisted reproductive technologies (ART) on child behavior. DESIGN: Prospective cohort study. SETTING: Not applicable. PATIENT(S): A total of 12,380 singletons recruited at 9 months and followed-up at 5 and 7 years. Conceptions were divided into "unplanned" (unplanned, unhappy), "mistimed" (unplanned, happy), "planned" (planned, TTC
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Fire Mosaics and Reptile Conservation in a Fire-Prone Region
Conservation Biology : the Journal of the Society for Conservation Biology.
Nov, 2012 |
Pubmed ID: 23163245 Fire influences the distribution of fauna in terrestrial biomes throughout the world. Use of fire to achieve a mosaic of vegetation in different stages of succession after burning (i.e., patch-mosaic burning) is a dominant conservation practice in many regions. Despite this, knowledge of how the spatial attributes of vegetation mosaics created by fire affect fauna is extremely scarce, and it is unclear what kind of mosaic land managers should aim to achieve. We selected 28 landscapes (each 12.6 km(2) ) that varied in the spatial extent and diversity of vegetation succession after fire in a 104,000 km(2) area in the semiarid region of southeastern Australia. We surveyed for reptiles at 280 sites nested within the 28 landscapes. The landscape-level occurrence of 9 of the 22 species modeled was associated with the spatial extent of vegetation age classes created by fire. Biogeographic context and the extent of a vegetation type influenced 7 and 4 species, respectively. No species were associated with the diversity of vegetation ages within a landscape. Negative relations between reptile occurrence and both extent of recently burned vegetation (≤10 years postfire, n = 6) and long unburned vegetation (>35 years postfire, n = 4) suggested that a coarse-grained mosaic of areas (e.g. >1000 ha) of midsuccessional vegetation (11-35 years postfire) may support the fire-sensitive reptile species we modeled. This age class coincides with a peak in spinifex cover, a keystone structure for reptiles in semiarid and arid Australia. Maintaining over the long term a coarse-grained mosaic of large areas of midsuccessional vegetation in mallee ecosystems will need to be balanced against the short-term negative effects of large fires on many reptile species and a documented preference by species from other taxonomic groups, particularly birds, for older vegetation. Mosaicos de Fuego y la Conservación de Reptiles en una Región Propensa al Fuego.
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Larazotide Acetate in Patients with Coeliac Disease Undergoing a Gluten Challenge: a Randomised Placebo-controlled Study
Alimentary Pharmacology & Therapeutics.
Nov, 2012 |
Pubmed ID: 23163616 BACKGROUND: Coeliac disease, an autoimmune disorder triggered by gluten ingestion, is managed by a gluten-free diet (GFD), which is difficult for many patients. Larazotide acetate is a first-in-class oral peptide that prevents tight junction opening, and may reduce gluten uptake and associated sequelae. AIM: To evaluate the efficacy and tolerability of larazotide acetate during gluten challenge. METHODS: This exploratory, double-blind, randomised, placebo-controlled study included 184 patients maintaining a GFD before and during the study. After a GFD run-in, patients were randomised to larazotide acetate (1, 4, or 8Â mg three times daily) or placebo and received 2.7 grams of gluten daily for 6Â weeks. Outcomes included an experimental biomarker of intestinal permeability, the lactulose-to-mannitol (LAMA) ratio and clinical symptoms assessed by Gastrointestinal Symptom Rating Scale (GSRS) and anti-transglutaminase antibody levels. RESULTS: No significant differences in LAMA ratios were observed between larazotide acetate and placebo groups. Larazotide acetate 1-mg limited gluten-induced symptoms measured by GSRS (PÂ =Â 0.002 vs. placebo). Mean ratio of anti-tissue transglutaminase IgA levels over baseline was 19.0 in the placebo group compared with 5.78 (PÂ =Â 0.010), 3.88 (PÂ =Â 0.005) and 7.72 (PÂ =Â 0.025) in the larazotide acetate 1-, 4-, and 8-mg groups, respectively. Adverse event rates were similar between larazotide acetate and placebo groups. CONCLUSIONS: Larazotide acetate reduced gluten-induced immune reactivity and symptoms in patients with coeliac disease undergoing gluten challenge and was generally well tolerated; however, no significant difference in LAMA ratios between larazotide acetate and placebo was observed. Results and design of this exploratory study can inform the design of future studies of pharmacological interventions in patients with coeliac disease.
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Expression of the Inflammatory Regulator A20 Correlates with Lung Function in Patients with Cystic Fibrosis
Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society.
Nov, 2012 |
Pubmed ID: 23164641 BACKGROUND: A20 and TAX1BP1 interact to negatively regulate NF-κB-driven inflammation. A20 expression is altered in F508del/F508del patients. Here we explore the effect of CFTR and CFTR genotype on A20 and TAX1BP1 expression. The relationship with lung function is also assessed. METHODS: Primary nasal epithelial cells (NECs) from CF patients (F508del/F508del, n=7, R117H/F508del, n=6) and controls (age-matched, n=8), and 16HBE14o- cells were investigated. A20 and TAX1BP1 gene expression was determined by qPCR. RESULTS: Silencing of CFTR reduced basal A20 expression. Following LPS stimulation A20 and TAX1BP1 expression was induced in control NECs and reduced in CF NECs, broadly reflecting the CF genotype: F508del/F508del had lower expression than R117H/F508del. A20, but not TAX1BP1 expression, was proportional to FEV(1) in all CF patients (r=0.968, p
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Effect of Testosterone on Inflammatory Markers in the Development of Early Atherogenesis in the Testicular-Feminized Mouse Model
Endocrine Research.
Nov, 2012 |
Pubmed ID: 23167461 Background. Low levels of serum testosterone in men are associated with cardiovascular disease. Clinical studies show that testosterone replacement therapy (TRT) can improve symptoms of cardiovascular disease and reduce the inflammatory burden evident in atherosclerosis. Aim. We used an in vivo animal model to determine whether testosterone influences mediators of vascular inflammation as part of its beneficial effects on atherogenesis. Methods. Testicular-feminized (Tfm) mice, which express low endogenous testosterone and a non-functional androgen receptor (AR), were used to assess the effect of androgen status on atheroma formation, serum lipids, and inflammatory mediators. Tfm mice were fed a high-cholesterol diet, received saline or physiological (TRT), and were compared to saline-treated XY littermates. Results. A total of 28 weeks of high-cholesterol diet caused fatty streak formation in the aortic root of XY littermates and Tfm mice, an effect significantly amplified in Tfm mice. Tfm mice on normal diet showed elevated serum tumor necrosis factor-α (TFN-α) and interleukin-6 compared to XY littermates. High-cholesterol diet induced increased monocyte chemoattractant protein-1 (MCP-1) in Tfm mice, and TFN-α and MCP-1 in XY littermates. TRT reduced fatty streak formation and serum interleukin-6 in Tfm mice but had no significant effects on lipid profiles. Monocyte/macrophage staining indicated local inflammation in aortic root fatty streak areas of all mice, with TRT reducing local inflammation through plaque reduction in Tfm mice. Fractalkine (CX(3)CL1) and its receptor (CX(3)CR1) were present in fatty streaks of all mice fed a high-cholesterol diet, independent of androgen status. Conclusion. These results are consistent with AR-dependent and AR-independent anti-inflammatory actions of testosterone in atheroprotection, although the local anti-inflammatory mechanisms via which testosterone acts remain unknown.
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Experiences of Carers Supporting Dying Renal Patients Managed Without Dialysis
Journal of Advanced Nursing.
Nov, 2012 |
Pubmed ID: 23167619 AIM: To explore the impact of being a family carer to patients with stage 5 chronic kidney disease managed without dialysis. BACKGROUND: Increasing numbers of patients with renal disease worldwide are making the decision not to embark on dialysis. This group has significant physical and psychological symptom burdens similar to or greater than those in advanced cancer patients. Little is known about the impact on family carers. DESIGN: Exploratory, qualitative design. METHODS: The study was undertaken with 19 carers caring for patients managed in a Renal Supportive Care Service in the UK between 2006-2008. Sixty-one semi-structured interviews and detailed field notes inform the analysis. FINDINGS: 'Caring from diagnosis to death' was the overarching theme illustrated by three sub-themes: (i) Caregiver's plight - making sense of the disease and potential deterioration; (ii) Having to care indefinitely; and (iii) Avoiding talk of death. 'Caring from diagnosis to death' coincides with an original concept analysis of renal supportive care, which is considered an adjunct to the management of patients with renal disease at all stages of their illness. CONCLUSION: There is a clear need for further research internationally and theory-based nursing interventions to support carers of patients managed without dialysis. The development of a holistic, integrated care pathway based on carer perspectives, which includes identification of information needs related to original diagnosis, associated comorbidities, treatment options, prognosis, and assistance in developing strategies to manage communication with patients as the end of life approaches, is required.
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Effects of Tic Suppression: Ability to Suppress, Rebound, Negative Reinforcement, and Habituation to the Premonitory Urge
Behaviour Research and Therapy.
Oct, 2012 |
Pubmed ID: 23168328 The comprehensive behavioral intervention for tics (CBIT) represents a safe, effective non-pharmacological treatment for Tourette's disorder that remains underutilized as a treatment option. Contributing factors include the perceived negative consequences of tic suppression and the lack of a means through which suppression results in symptom improvement. Participants (n = 12) included youth ages 10-17 years with moderate-to-marked tic severity and noticeable premonitory urges who met Tourette's or chronic tic disorder criteria. Tic frequency and urge rating data were collected during an alternating sequence of tic freely or reinforced tic suppression periods. Even without specific instructions regarding how to suppress tics, youth experienced a significant, robust (72%), stable reduction in tic frequency under extended periods (40 min) of contingently reinforced tic suppression in contrast to periods of time when tics were ignored. Following periods of prolonged suppression, tic frequency returned to pre-suppression levels. Urge ratings did not show the expected increase during the initial periods of tic suppression, nor a subsequent decline in urge ratings during prolonged, effective tic suppression. Results suggest that environments conducive to tic suppression result in reduced tic frequency without adverse consequences. Additionally, premonitory urges, underrepresented in the literature, may represent an important enduring etiological consideration in the development and maintenance of tic disorders.
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SAGA Complex Components and Acetate Repression in Aspergillus Nidulans
G3 (Bethesda, Md.).
Nov, 2012 |
Pubmed ID: 23173087 Alongside the well-established carbon catabolite repression by glucose and other sugars, acetate causes repression in Aspergillus nidulans. Mutations in creA, encoding the transcriptional repressor involved in glucose repression, also affect acetate repression, but mutations in creB or creC, encoding components of a deubiquitination system, do not. To understand the effects of acetate, we used a mutational screen that was similar to screens that uncovered mutations in creA, creB, and creC, except that glucose was replaced by acetate to identify mutations that were affected for repression by acetate but not by glucose. We uncovered mutations in acdX, homologous to the yeast SAGA component gene SPT8, which in growth tests showed derepression for acetate repression but not for glucose repression. We also made mutations in sptC, homologous to the yeast SAGA component gene SPT3, which showed a similar phenotype. We found that acetate repression is complex, and analysis of facA mutations (lacking acetyl CoA synthetase) indicates that acetate metabolism is required for repression of some systems (proline metabolism) but not for others (acetamide metabolism). Although plate tests indicated that acdX- and sptC-null mutations led to derepressed alcohol dehydrogenase activity, reverse-transcription quantitative real-time polymerase chain reaction showed no derepression of alcA or aldA but rather elevated induced levels. Our results indicate that acetate repression is due to repression via CreA together with metabolic changes rather than due to an independent regulatory control mechanism.
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Effects of Short-term Dietary Nitrate Supplementation on Blood Pressure, O2 Uptake Kinetics, and Muscle and Cognitive Function in Older Adults
American Journal of Physiology. Regulatory, Integrative and Comparative Physiology.
Nov, 2012 |
Pubmed ID: 23174856 Dietary nitrate (NO(3)(-)) supplementation has been shown to reduce resting blood pressure and alter the physiological response to exercise in young adults. We investigated whether these effects might also be evident in older adults. In a double-blind, randomized, crossover study, twelve healthy, older (60-70 yrs) adults supplemented their diet for three days with either nitrate-rich concentrated beetroot juice (BR; 2 x 70 ml•d(-1), ~9.6 mmol•d(-1) NO(3)(-)) or a nitrate-depleted beetroot juice placebo (PL; 2 x70 ml•d(-1), ~0.01 mmol•d(-1) NO(3)(-)). Before and after the intervention periods, resting blood pressure and plasma [nitrite] were measured and subjects completed a battery of physiological and cognitive tests. Nitrate supplementation significantly increased plasma [nitrite] and reduced resting systolic (BR:115 ± 9 vs. PL:120 ± 6 mmHg; P
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SDHA Mutations in Adult and Pediatric Wild-type Gastrointestinal Stromal Tumors
Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc.
Nov, 2012 |
Pubmed ID: 23174939 Most gastrointestinal stromal tumors (GISTs) harbor oncogenic mutations in KIT or platelet-derived growth factor receptor-α. However, a small subset of GISTs lacks such mutations and is termed 'wild-type GISTs'. Germline mutation in any of the subunits of succinate dehydrogenase (SDH) predisposes individuals to hereditary paragangliomas and pheochromocytomas. However, germline mutations of the genes encoding SDH subunits A, B, C or D (SDHA, SDHB, SDHC or SDHD; collectively SDHx) are also identified in GISTs. SDHA and SDHB immunohistochemistry are reliable techniques to identify pheochromocytomas and paragangliomas with mutations in SDHA, SDHB, SDHC and SDHD. In this study, we investigated if SDHA immunohistochemistry could also identify SDHA-mutated GISTs. Twenty-four adult wild-type GISTs and nine pediatric/adolescent wild-type GISTs were analyzed with SDHB, and where this was negative, then with SDHA immunohistochemistry. If SDHA immunohistochemistry was negative, sequencing analysis of the entire SDHA coding sequence was performed. All nine pediatric/adolescent GISTs and seven adult wild-type GISTs were negative for SDHB immunohistochemistry. One pediatric GIST and three SDHB-immunonegative adult wild-type GISTs were negative for SDHA immunohistochemistry. In all four SDHA-negative GISTs, a germline SDHA c.91C>T transition was found leading to a nonsense p.Arg31X mutation. Our results demonstrate that SDHA immunohistochemistry on GISTs can identify the presence of an SDHA germline mutation. Identifying GISTs with deficient SDH activity warrants additional genetic testing, evaluation and follow-up for inherited disorders and paragangliomas.Modern Pathology advance online publication, 23 November 2012; doi:10.1038/modpathol.2012.186.
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