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Find video protocols related to scientific articles indexed in Pubmed.
Valuing Stillbirths.
Bioethics
PUBLISHED: 11-15-2014
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Estimates of the burden of disease assess the mortality and morbidity that affect a population by producing summary measures of health such as quality-adjusted life years (QALYs) and disability-adjusted life years (DALYs). These measures typically do not include stillbirths (fetal deaths occurring during the later stages of pregnancy or during labor) among the negative health outcomes they count. Priority-setting decisions that rely on these measures are therefore likely to place little value on preventing the more than three million stillbirths that occur annually worldwide. In contrast, neonatal deaths, which occur in comparable numbers, have a substantial impact on burden of disease estimates and are commonly seen as a pressing health concern. In this article we argue in favor of incorporating unintended fetal deaths that occur late in pregnancy into estimates of the burden of disease. Our argument is based on the similarity between late-term fetuses and newborn infants and the assumption that protecting newborns is important. We respond to four objections to counting stillbirths: (1) that fetuses are not yet part of the population and so their deaths should not be included in measures of population health; (2) that valuing the prevention of stillbirths will undermine women's reproductive rights; (3) that including stillbirths implies that miscarriages (fetal deaths early in pregnancy) should also be included; and (4) that birth itself is in fact ethically significant. We conclude that our proposal is ethically preferable to current practice and, if adopted, is likely to lead to improved decisions about health spending.
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Extensive Phenotyping of Individuals At-risk for Familial Interstitial Pneumonia Reveals Clues to the Pathogenesis of Interstitial Lung Disease.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 11-13-2014
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Introduction: Asymptomatic relatives of patients with Familial Interstitial Pneumonia (FIP), the inherited form of Idiopathic Interstitial Pneumonia (IIP), carry increased risk for developing interstitial lung disease. Studying these at-risk individuals provides a unique opportunity to investigate early stages of FIP pathogenesis and develop predictive models of disease onset. Methods: Seventy-five asymptomatic first-degree relatives of FIP patients (mean age 50.8 years) underwent blood sampling and high-resolution chest CT (HRCT) scan in an ongoing cohort study; 72 consented to bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsies. Twenty-seven healthy individuals were used as controls. Results: Eleven of 75 at-risk subjects (14%) had evidence of interstitial changes by HRCT while 35.2% had abnormalities on transbronchial biopsies. No differences were noted in inflammatory cells in BAL between at-risk individuals and controls. At-risk subjects had increased herpesvirus DNA in cell-free BAL and evidence of herpesvirus antigen expression in alveolar epithelial cells (AECs), which correlated with expression of endoplasmic reticulum stress markers in AECs. Peripheral blood mononuclear cell and AEC telomere length were shorter in at-risk individuals than healthy controls. The minor allele frequency of the Muc5B rs35705950 promoter polymorphism was increased in at-risk subjects. Levels of several plasma biomarkers differed between at-risk subjects and controls, and correlated with abnormal HRCT scans. Conclusions: Evidence of lung parenchymal remodeling and epithelial dysfunction were identified in asymptomatic individuals at-risk for FIP. Together, these findings offer new insights into the early pathogenesis of IIP and provide an ongoing opportunity to characterize presymptomatic abnormalities that predict progression to clinical disease.
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Clarifying substituted judgement: the endorsed life approach.
J Med Ethics
PUBLISHED: 11-01-2014
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A primary goal of clinical practice is to respect patient autonomy. To promote this goal for patients who have lost the ability to make their own decisions, commentators recommend that surrogates make their treatment decisions based on the substituted judgment standard. This standard is commonly interpreted as directing surrogates to make the decision the patient would have made in the circumstances, if the patient were competent. However, recent commentators have argued that this approach-attempting to make the decision the patient would have made if competent-is theoretically problematic, practically infeasible, and ignores the interests of the patient's family and loved ones. These commentators conclude that the substituted judgment standard should be revised significantly, or abandoned altogether. While this response would avoid the cited problems, it also would require substantial changes to clinical practice and would raise significant problems of its own. The present paper thus considers the possibility that the criticisms do not point to problems with the substituted judgment standard itself; instead, they point to problems with the way it is most commonly interpreted. This analysis suggests that the substituted judgment standard need not be dramatically revised or abandoned. Instead, it should be interpreted in a way that effectively promotes respect for the autonomy of incompetent patients. The 'endorsed life' interpretation described here helps clinicians and surrogates to achieve this important goal. To clarify this approach, we explain how it differs from three other recently proposed alternatives to the standard interpretation of the substituted judgment standard.
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Is Linear Advancement Related to Relapse in Unilateral Cleft Lip and Palate Orthognathic Surgery?
Cleft Palate Craniofac. J.
PUBLISHED: 09-27-2014
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Objective :? To investigate the stability of major versus minor Le Fort I maxillary advancements in unilateral cleft lip and palate (UCLP) patients. Design :? A retrospective longitudinal study was undertaken on 30 nonsyndromic UCLP patients treated with the same protocol at The Hospital for Sick Children, Toronto, Canada. Patients were grouped into major and minor movement groups based on planned surgical advancement. Standard lateral cephalometric radiographs were taken preoperatively (T1), immediately postoperatively (T2), and at least 1 year postoperatively (T3). Skeletal and dental variables were measured using cephalometric analysis. Stability was compared between groups using repeated-measures analysis of variance. Linear regression analysis was used to assess the relationship between advancement and relapse for the entire study population. Results :? A mean maxillary advancement of 9.8 mm and 4.9 mm was seen for the major (n = 10) and minor (n = 20) movement groups, respectively. The mean skeletal horizontal relapse was 1.8 mm (18%) for the major advancement group and 1.5 mm (31%) for the minor advancement group. There was no significant difference in skeletal horizontal relapse between the groups (P > .05). The correlation coefficient (r) between linear horizontal advancement and relapse was calculated to be .31 (P > .05). Dental horizontal relapse was not significant for either the major or minor groups, and no significant difference was found between the groups (P > .05). Conclusion :? Skeletal and dental relapse was found to be unrelated to the amount of maxillary linear advancement using conventional Le Fort I osteotomies in UCLP.
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Replication stress by Py-Im polyamides induces a non-canonical ATR-dependent checkpoint response.
Nucleic Acids Res.
PUBLISHED: 09-23-2014
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Pyrrole-imidazole polyamides targeted to the androgen response element were cytotoxic in multiple cell lines, independent of intact androgen receptor signaling. Polyamide treatment induced accumulation of S-phase cells and of PCNA replication/repair foci. Activation of a cell cycle checkpoint response was evidenced by autophosphorylation of ATR, the S-phase checkpoint kinase, and by recruitment of ATR and the ATR activators RPA, 9-1-1, and Rad17 to chromatin. Surprisingly, ATR activation was accompanied by only a slight increase in single-stranded DNA, and the ATR targets RPA2 and Chk1, a cell cycle checkpoint kinase, were not phosphorylated. However, ATR activation resulted in phosphorylation of the replicative helicase subunit MCM2, an ATR effector. Polyamide treatment also induced accumulation of monoubiquitinated FANCD2, which is recruited to stalled replication forks and interacts transiently with phospho-MCM2. This suggests that polyamides induce replication stress that ATR can counteract independently of Chk1 and that the FA/BRCA pathway may also be involved in the response to polyamides. In biochemical assays, polyamides inhibit DNA helicases, providing a plausible mechanism for S-phase inhibition.
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A Novel SHOC2 Variant in Rasopathy.
Hum. Mutat.
PUBLISHED: 09-11-2014
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Rasopathies are a group of genetic disorders caused by germline mutations in multiple genes of the Extracellular signal-Regulated Kinases 1 and 2 (ERK1/2) pathway. The only previously identified missense mutation in SHOC2, a scaffold protein of the ERK1/2 pathway, led to Noonan-like syndrome with loose anagen hair. Here, we report a novel mutation in SHOC2(c.519G>A; p.M173I) that leads to a Rasopathy with clinical features partially overlapping those occurring in Noonan and cardiofaciocutaneous syndromes. Studies to clarify the significance of this SHOC2 variant revealed that the mutant protein has impaired capacity to interact with protein phosphatase 1c (PP1c), leading to insufficient activation of RAF-1 kinase. This SHOC2 variant thus is unable to fully rescue ERK1/2 activity in cells depleted of endogenous SHOC2. We conclude that SHOC2 mutations can cause a spectrum of Rasopathy phenotypes in heterozygous individuals. Importantly, our work suggests that individuals with mild Rasopathy symptoms may be underdiagnosed.
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Cephalometric outcomes of orthognathic surgery in hemifacial microsomia.
J Craniofac Surg
PUBLISHED: 09-10-2014
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Hemifacial microsomia is a hypoplastic disorder of the first and second branchial arches that significantly impacts on the development of the jaws, leading to malocclusion and facial asymmetry. There is little in the literature regarding the application of orthodontic/orthognathic approaches to the correction of these deformities and the stability of the surgical results. To address this, a retrospective chart review of 10 patients with complete orthodontic records and greater than 1 year of follow-up was performed. Posteroanterior cephalograms were assessed by modified Grummons analysis to determine mandibular offset (deviation of the chin point from the skeletal midline) and occlusal cant. These measurements were performed at 3 time points (T1: preoperative, T2: immediate postoperative, T3: follow-up) to elucidate the surgical movement (T2-T1), the postoperative relapse (T3-T2), and the net gain movement (T3-T1). Maxillary movements were quantified, and the occlusal cant was expressed as a ratio between vertical heights of the maxilla at the first molar on each side. One sample t test demonstrated statistically significant surgical movement and net gain. Relapse was statistically insignificant. Repeated-measures analysis of variance demonstrated similar results for chin point position relative to the putative midline. Our results suggest that a combined orthodontic/orthognathic approach at skeletal maturity delivers improved occlusal outcomes in the long term as assessed by chin point deviation and occlusal cant, but secondary surgery rates are higher than those for orthognathic surgery in other patient groups. We advocate limiting surgery to skeletal maturity whenever possible to achieve stable long-term results while limiting morbidity and number of procedures.
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TMEM14C is required for erythroid mitochondrial heme metabolism.
J. Clin. Invest.
PUBLISHED: 08-26-2014
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The transport and intracellular trafficking of heme biosynthesis intermediates are crucial for hemoglobin production, which is a critical process in developing red cells. Here, we profiled gene expression in terminally differentiating murine fetal liver-derived erythroid cells to identify regulators of heme metabolism. We determined that TMEM14C, an inner mitochondrial membrane protein that is enriched in vertebrate hematopoietic tissues, is essential for erythropoiesis and heme synthesis in vivo and in cultured erythroid cells. In mice, TMEM14C deficiency resulted in porphyrin accumulation in the fetal liver, erythroid maturation arrest, and embryonic lethality due to profound anemia. Protoporphyrin IX synthesis in TMEM14C-deficient erythroid cells was blocked, leading to an accumulation of porphyrin precursors. The heme synthesis defect in TMEM14C-deficient cells was ameliorated with a protoporphyrin IX analog, indicating that TMEM14C primarily functions in the terminal steps of the heme synthesis pathway. Together, our data demonstrate that TMEM14C facilitates the import of protoporphyrinogen IX into the mitochondrial matrix for heme synthesis and subsequent hemoglobin production. Furthermore, the identification of TMEM14C as a protoporphyrinogen IX importer provides a genetic tool for further exploring erythropoiesis and congenital anemias.
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COMQ-12 scores in adult patients without chronic middle ear disease.
Clin Otolaryngol
PUBLISHED: 08-20-2014
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To determine the COMQ-12 score in an adult population without active COM STUDY DESIGN: Analysis of COMQ-12 scores in participants without active COM SETTING: East Anglia, United Kingdom PARTICIPANTS: 70 healthy volunteers recruited from two local hospitals RESULTS: The median COMQ-12 score overall was 2 and the modal score was 0 with 27(39%) participants achieving this score.
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Cephalometric Outcomes of Orthognathic Surgery in Hemifacial Microsomia.
J Craniofac Surg
PUBLISHED: 07-30-2014
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Hemifacial microsomia is a hypoplastic disorder of the first and second branchial arches that significantly impacts on the development of the jaws, leading to malocclusion and facial asymmetry. There is little in the literature regarding the application of orthodontic/orthognathic approaches to the correction of these deformities and the stability of the surgical results. To address this, a retrospective chart review of 10 patients with complete orthodontic records and greater than 1 year of follow-up was performed. Posteroanterior cephalograms were assessed by modified Grummons analysis to determine mandibular offset (deviation of the chin point from the skeletal midline) and occlusal cant. These measurements were performed at 3 time points (T1: preoperative, T2: immediate postoperative, T3: follow-up) to elucidate the surgical movement (T2-T1), the postoperative relapse (T3-T2), and the net gain movement (T3-T1). Maxillary movements were quantified, and the occlusal cant was expressed as a ratio between vertical heights of the maxilla at the first molar on each side. One sample t test demonstrated statistically significant surgical movement and net gain. Relapse was statistically insignificant. Repeated-measures analysis of variance demonstrated similar results for chin point position relative to the putative midline. Our results suggest that a combined orthodontic/orthognathic approach at skeletal maturity delivers improved occlusal outcomes in the long term as assessed by chin point deviation and occlusal cant, but secondary surgery rates are higher than those for orthognathic surgery in other patient groups. We advocate limiting surgery to skeletal maturity whenever possible to achieve stable long-term results while limiting morbidity and number of procedures.
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Acute Porphyrias in the USA: Features of 108 Subjects from Porphyria Consortium.
Am. J. Med.
PUBLISHED: 06-23-2014
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Recent descriptions of the clinical and laboratory features of subjects with acute porphyrias in the US are lacking. Our aim was to describe clinical, biochemical and genetic features of 108 subjects.
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RNAi-mediated silencing of hepatic Alas1 effectively prevents and treats the induced acute attacks in acute intermittent porphyria mice.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 05-12-2014
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The acute hepatic porphyrias are inherited disorders of heme biosynthesis characterized by life-threatening acute neurovisceral attacks. Factors that induce the expression of hepatic 5-aminolevulinic acid synthase 1 (ALAS1) result in the accumulation of the neurotoxic porphyrin precursors 5-aminolevulinic acid (ALA) and porphobilinogen (PBG), which recent studies indicate are primarily responsible for the acute attacks. Current treatment of these attacks involves i.v. administration of hemin, but a faster-acting, more effective, and safer therapy is needed. Here, we describe preclinical studies of liver-directed small interfering RNAs (siRNAs) targeting Alas1 (Alas1-siRNAs) in a mouse model of acute intermittent porphyria, the most common acute hepatic porphyria. A single i.v. dose of Alas1-siRNA prevented the phenobarbital-induced biochemical acute attacks for approximately 2 wk. Injection of Alas1-siRNA during an induced acute attack significantly decreased plasma ALA and PBG levels within 8 h, more rapidly and effectively than a single hemin infusion. Alas1-siRNA was well tolerated and a therapeutic dose did not cause hepatic heme deficiency. These studies provide proof-of-concept for the clinical development of RNA interference therapy for the prevention and treatment of the acute attacks of the acute hepatic porphyrias.
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The grab-and-drop protocol: a novel strategy for membrane protein isolation and reconstitution from single cells.
Analyst
PUBLISHED: 04-08-2014
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We present a rapid and robust technique for the sampling of membrane-associated proteins from the surface of a single, live cell and their subsequent deposition onto a solid-supported lipid bilayer. As a proof of principle, this method has been used to extract green fluorescent protein (EGFP) labelled K-ras proteins located at the inner leaflet of the plasma membrane of colon carcinoma cells and to transfer them to an S-layer supported lipid bilayer system. The technique is non-destructive, meaning that both the cell and proteins are intact after the sampling operation, offering the potential for repeated measurements of the same cell of interest. This system provides the ideal tool for the investigation of cellular heterogeneity, as well as a platform for the investigation of rare cell types such as circulating tumour cells.
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Cohort Profile: the Health and Retirement Study (HRS).
Int J Epidemiol
PUBLISHED: 03-25-2014
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The Health and Retirement Study (HRS) is a nationally representative longitudinal survey of more than 37 000 individuals over age 50 in 23 000 households in the USA. The survey, which has been fielded every 2 years since 1992, was established to provide a national resource for data on the changing health and economic circumstances associated with ageing at both individual and population levels. Its multidisciplinary approach is focused on four broad topics-income and wealth; health, cognition and use of healthcare services; work and retirement; and family connections. HRS data are also linked at the individual level to administrative records from Social Security and Medicare, Veteran's Administration, the National Death Index and employer-provided pension plan information. Since 2006, data collection has expanded to include biomarkers and genetics as well as much greater depth in psychology and social context. This blend of economic, health and psychosocial information provides unprecedented potential to study increasingly complex questions about ageing and retirement. The HRS has been a leading force for rapid release of data while simultaneously protecting the confidentiality of respondents. Three categories of data-public, sensitive and restricted-can be accessed through procedures described on the HRS website (hrsonline.isr.umich.edu).
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Functional prostacyclin synthase promoter polymorphisms. Impact in pulmonary arterial hypertension.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 03-11-2014
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Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated pulmonary artery pressure, vascular remodeling, and ultimately right ventricular heart failure. PAH can have a genetic component (heritable PAH), most often through mutations of bone morphogenetic protein receptor 2, and idiopathic and associated forms. Heritable PAH is not completely penetrant within families, with approximately 20% concurrence of inactivating bone morphogenetic protein receptor 2 mutations and delayed onset of PAH disease. Because one of the treatment options is using prostacyclin analogs, we hypothesized that prostacyclin synthase promoter sequence variants associated with increased mRNA expression may play a protective role in the bone morphogenetic protein receptor 2 unaffected carriers.
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A mesoscale connectome of the mouse brain.
Nature
PUBLISHED: 02-27-2014
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Comprehensive knowledge of the brain's wiring diagram is fundamental for understanding how the nervous system processes information at both local and global scales. However, with the singular exception of the C. elegans microscale connectome, there are no complete connectivity data sets in other species. Here we report a brain-wide, cellular-level, mesoscale connectome for the mouse. The Allen Mouse Brain Connectivity Atlas uses enhanced green fluorescent protein (EGFP)-expressing adeno-associated viral vectors to trace axonal projections from defined regions and cell types, and high-throughput serial two-photon tomography to image the EGFP-labelled axons throughout the brain. This systematic and standardized approach allows spatial registration of individual experiments into a common three dimensional (3D) reference space, resulting in a whole-brain connectivity matrix. A computational model yields insights into connectional strength distribution, symmetry and other network properties. Virtual tractography illustrates 3D topography among interconnected regions. Cortico-thalamic pathway analysis demonstrates segregation and integration of parallel pathways. The Allen Mouse Brain Connectivity Atlas is a freely available, foundational resource for structural and functional investigations into the neural circuits that support behavioural and cognitive processes in health and disease.
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Dosimetric consequences of interobserver variability in delineating the organs at risk in gynecologic interstitial brachytherapy.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 02-26-2014
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To investigate the dosimetric variability associated with interobserver organ-at-risk delineation differences on computed tomography in patients undergoing gynecologic interstitial brachytherapy.
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Transcriptional landscape of the prenatal human brain.
Nature
PUBLISHED: 02-26-2014
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The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development.
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A new health-related quality of life measure for active chronic otitis media (COMQ-12): development and initial validation.
Otol. Neurotol.
PUBLISHED: 02-13-2014
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To develop and document for clinical use a new HRQoL questionnaire for the assessment of active chronic otitis media.
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Single Versus Segmental Maxillary Osteotomies and Long-Term Stability in Unilateral Cleft Lip and Palate Related Malocclusion.
J. Oral Maxillofac. Surg.
PUBLISHED: 02-09-2014
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To investigate the stability of single-piece versus segmental (2-piece) maxillary advancement in patients with unilateral cleft lip and palate (UCLP) treated using conventional Le Fort I orthognathic surgery.
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A novel dyskerin (DKC1) mutation is associated with familial interstitial pneumonia.
Chest
PUBLISHED: 02-08-2014
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Short telomeres are frequently identified in patients with idiopathic pulmonary fibrosis (IPF) and its inherited form, familial interstitial pneumonia (FIP). We identified a kindred with FIP with short telomeres who did not carry a mutation in known FIP genes TERT or hTR . We performed targeted sequencing of other telomere-related genes to identify the genetic basis of FIP in this kindred. The proband was a 69 year-old man with dyspnea, restrictive pulmonary function test results, and reticular changes on high-resolution CT scan. An older male sibling had died from IPF. The proband had markedly shortened telomeres in peripheral blood and undetectably short telomeres in alveolar epithelial cells. Polymerase chain reaction-based sequencing of NOP10 , TINF2 , NHP2 , and DKC1 revealed that both affected siblings shared a novel A to G 1213 transition in DKC1 near the hTR binding domain that is predicted to encode a Thr405Ala amino acid substitution. hTR levels were decreased out of proportion to DKC1 expression in the T405A DKC1 proband, suggesting this mutation destabilizes hTR and impairs telomerase function. This DKC1 variant represents the third telomere-related gene identified as a genetic cause of FIP. Further investigation into the mechanism by which dyskerin contributes to the development of lung fibrosis is warranted.
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Trans-oral brush biopsies and quantitative PCR for EBV DNA detection and screening of nasopharyngeal carcinoma.
Otolaryngol Head Neck Surg
PUBLISHED: 01-31-2014
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To evaluate a newly developed noninvasive ambulatory, quantitative polymerase chain reaction (Q-PCR) Epstein-Barr virus (EBV) DNA detection and screening system (NP Screen™) for nasopharyngeal carcinoma (NPC).
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Improving reliability and absolute quantification of human brain microarray data by filtering and scaling probes using RNA-Seq.
BMC Genomics
PUBLISHED: 01-30-2014
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High-throughput sequencing is gradually replacing microarrays as the preferred method for studying mRNA expression levels, providing nucleotide resolution and accurately measuring absolute expression levels of almost any transcript, known or novel. However, existing microarray data from clinical, pharmaceutical, and academic settings represent valuable and often underappreciated resources, and methods for assessing and improving the quality of these data are lacking.
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Isolation, structure elucidation and antibacterial activity of a new tetramic acid, ascosetin.
J. Antibiot.
PUBLISHED: 01-25-2014
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The ever-increasing bacterial resistance to clinical antibiotics is making many drugs ineffective and creating significant treatment gaps. This can be only circumvented by the discovery of antibiotics with new mechanisms of action. We report here the identification of a new tetramic acid, ascosetin, from an Ascomycete using the Staphylococcus aureus fitness test screening method. The structure was elucidated by spectroscopic methods including 2D NMR and HRMS. Relative stereochemistry was determined by ROESY and absolute configuration was deduced by comparative CD spectroscopy. Ascosetin inhibited bacterial growth with 2-16 ?g ml(-1) MIC values against Gram-positive strains including methicillin-resistant S. aureus. It also inhibited the growth of Haemophilus influenzae with a MIC value of 8 ?g ml(-1). It inhibited DNA, RNA, protein and lipid synthesis with similar IC50 values, suggesting a lack of specificity; however, it produced neither bacterial membrane nor red blood cell lysis. It showed selectivity for bacterial growth inhibition compared with fungal but not mammalian cells. The isolation, structure and biological activity of ascosetin have been detailed here.
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The effect of differing Gleason scores at biopsy on the odds of upgrading and the risk of death from prostate cancer.
Clin Genitourin Cancer
PUBLISHED: 01-24-2014
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The GS is an established prostate cancer prognostic factor. Whether the presence of differing GSs at biopsy (eg, 4+3 and 3+3), which we term ComboGS, improves the prognosis that would be predicted based on the highest GS (eg, 4+3) because of decreased upgrading is unknown. Therefore, we evaluated the odds of upgrading at time of radical prostatectomy (RP) and the risk of PCSM when ComboGS was present versus absent.
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Greatest percentage of involved core length and the risk of death from prostate cancer in men with highest Gleason score ? 7.
Clin Genitourin Cancer
PUBLISHED: 01-17-2014
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Men with highest GS ? 7 and a differing, lower GS core (ComboGS) have decreased PC-specific mortality (PCSM) risk after RT or RT and androgen deprivation therapy (ADT). Whether the greatest percentage of involved core length (GPC) modulates this risk is unknown.
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Dose to the inferior pharyngeal constrictor predicts prolonged gastrostomy tube dependence with concurrent intensity-modulated radiation therapy and chemotherapy for locally-advanced head and neck cancer.
Radiother Oncol
PUBLISHED: 01-16-2014
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To determine if dose and/or dose-volume parameters to anatomic swallowing structures are predictive of gastrostomy tube (PEG) dependence from chemotherapy-intensity modulated radiotherapy (IMRT) in locally advanced head and neck cancer (LAHNC).
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Mutations in PGAP3 impair GPI-anchor maturation, causing a subtype of hyperphosphatasia with mental retardation.
Am. J. Hum. Genet.
PUBLISHED: 01-16-2014
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Glycosylphophatidylinositol (GPI)-anchored proteins play important roles in many biological processes, and mutations affecting proteins involved in the synthesis of the GPI anchor are reported to cause a wide spectrum of intellectual disabilities (IDs) with characteristic additional phenotypic features. Here, we describe a total of five individuals (from three unrelated families) in whom we identified mutations in PGAP3, encoding a protein that is involved in GPI-anchor maturation. Three siblings in a consanguineous Pakistani family presented with profound developmental delay, severe ID, no speech, psychomotor delay, and postnatal microcephaly. A combination of autozygosity mapping and exome sequencing identified a 13.8 Mb region harboring a homozygous c.275G>A (p.Gly92Asp) variant in PGAP3 region 17q11.2-q21.32. Subsequent testing showed elevated serum alkaline phosphatase (ALP), a GPI-anchored enzyme, in all three affected children. In two unrelated individuals in a cohort with developmental delay, ID, and elevated ALP, we identified compound-heterozygous variants c.439dupC (p.Leu147Profs(?)16) and c.914A>G (p.Asp305Gly) and homozygous variant c.314C>G (p.Pro105Arg). The 1 bp duplication causes a frameshift and nonsense-mediated decay. Further evidence supporting pathogenicity of the missense mutations c.275G>A, c.314C>G, and c.914A>G was provided by the absence of the variants from ethnically matched controls, phylogenetic conservation, and functional studies on Chinese hamster ovary cell lines. Taken together with recent data on PGAP2, these results confirm the importance of the later GPI-anchor remodelling steps for normal neuronal development. Impairment of PGAP3 causes a subtype of hyperphosphatasia with ID, a congenital disorder of glycosylation that is also referred to as Mabry syndrome.
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Isolation, structure elucidation, and biological activity of altersolanol P using Staphylococcus aureus fitness test based genome-wide screening.
J. Nat. Prod.
PUBLISHED: 01-15-2014
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Bacteria continue to evade existing antibiotics by acquiring resistance by various mechanisms, leading to loss of antibiotic effectiveness. To avoid an epidemic from infections of incurable drug-resistant bacteria, new antibiotics with new modes of action are desperately needed. Using a genome-wide mechanism of action-guided whole cell screening approach based on antisense Staphylococcus aureus fitness test technology, we report herein the discovery of altersolanol P (1), a new tetrahydroanthraquinone from an unknown fungus from the Hypocreales isolated from forest litter collected in Puerto Rico. The structure was elucidated by high-resolution mass spectrometry and 2D NMR spectroscopy. Relative stereochemistry was established by NOESY correlations, and absolute configuration was deduced by the application of MPA ester-based methodology. Observed (1)H and (13)C NMR shifts were well aligned with the corresponding chemical shifts predicted by DFT calculations. Altersolanol P exhibited Gram-positive antibacterial activity (MIC range 1-8 ?g/mL) and inhibited the growth of Gram-negative Haemophilus influenzae (MIC 2 ?g/mL). The isolation, structure elucidation, and antibacterial activity of altersolanol P are described.
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Mother-infant mutual eye gaze supports emotion regulation in infancy during the Still-Face paradigm.
Infant Behav Dev
PUBLISHED: 01-14-2014
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This study was designed to examine the sequential relationship between mother-infant synchrony and infant affect using multilevel modeling during the Still Face paradigm. We also examined self-regulatory behaviors that infants use during the Still-Face paradigm to modulate their affect, particularly during stressors where their mothers are not available to help them co-regulate. There were 84 mother-infant dyads, of healthy full term 4 month old infants. Second-by-second coding of infant self-regulation and infant affect was done, in addition to mother-infant mutual eye gaze. Using multilevel modeling, we found that infant affect became more positive when mutual gaze had occurred the previous second, suggesting that the experience of synchronicity was associated with observable shifts in affect. We also found a positive association between self-regulatory behaviors and increases in positive affect only during the Still-Face episode (episode 2). Our study provides support for the role of mother-infant synchronicity in emotion regulation as well as support for the role of self-regulatory behaviors in emotion regulation that can have important implication for intervention.
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Upper urinary tract urothelial carcinoma with intratubular spread.
Am J Clin Exp Urol
PUBLISHED: 01-01-2014
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Upper urinary tract urothelial cell carcinomas (UUT-UCs) are uncommon and are defined as urothelial carcinoma involving the urinary tract from the renal calyces, renal pelvis to the distal ureter. One well-known an peculiar histopathological finding in UUT-UC is urothelial carcinoma with intratubular spread (retrograde spread within renal tubules). However, this special feature has not been systematically studied. We therefore collected a total of 53 consecutive cases of upper urinary tract urothelial carcinomas (UUT-UCs), and studied the clinical and pathological features of intratubular spread (IS). A cocktail stain comprised of antibodies PAX8 and p63 together with PAS was validated and employed to facilitate the study of intratubular spread. Seventeen cases (31.5%) showed intratubular spread demonstrated by either H&E stain and/or the cocktail stain. All of the 17 cases wit intratubular spread had tumor involvement of the renal calyx; the majority of these (14/17, 82.4%) were high grade urothelial carcinoma and the remainder (3/17, 17.6%) were low grade. 4 of 17cases (23.5%) were non-invasive. We classified intratubular spread into 4 different types, based on histopathological patterns: pagetoid, typical, florid, and secondary invasion from intratubular spread. In conclusion, study shows intratubular spread of urothelial carcinoma is fairly common phenomenon in UUT-UC and is associated with a variety of clinical-pathological features. High grade UUT-UC tends to have more extensive intratubular spread and secondary invasion into renal parenchyma. Distinct morphological characteristics as well as the staining pattern from a unique cocktail stain help to identify and evaluate intratubular spread of urothelial carcinoma. Recognizing these different types of intratubular spreading (IS) is crucial for accurate staging of some upper urinary tract urothelial carcinomas (UUT-UCs).
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Variable expressivity and clinical heterogeneity can complicate the diagnosis and management of Pfeiffer syndrome.
J Craniofac Surg
PUBLISHED: 09-17-2013
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We report here a newborn female infant with striking features consistent with severe Pfeiffer syndrome (PS). Pfeiffer syndrome is a rare craniofacial disorder that has an autosomal dominant mode of inheritance (OMIM 101600). Our patient had unexpected differences between her clinical features and those predicted from her genetic tests. The following clinical features were noted: severe exophthalmos, syndactyly, upper extremity contractures, and relative macroglossia. A head computed tomography with three-dimensional reconstruction showed that she did not have craniosynostosis. Genetic tests included a normal 46,XX karyotype and a chromosomal microarray that revealed a copy number gain at 14q23.1 as well as a copy number loss at 16p13.2. FGFR2 sequencing revealed a c.870G>T transversion in exon 8, which is predicted to encode a Trp290Cys substitution.The clinical features of severe exophthalmos and other features typical of PS without craniosynostosis were most consistent with a diagnosis of PS type III. However, her Trp290Cys FGFR2 mutation is reported to be associated with PS type II that includes kleeblatschädel (or "cloverleaf") skull anomalies as a cardinal feature. Our patients lack of craniosynostosis predicted from this mutation is a striking example of variable expressivity. Such discrepancies between the physical findings (phenotype) and the mutation identified (genotype) and the association of different findings with different mutations in the same gene (clinical heterogeneity) can present difficulties in case management. Clinicians should be guided by careful phenotyping rather than by genotypic predictions alone.
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SHC2 gene copy number in multiple system atrophy (MSA).
Clin. Auton. Res.
PUBLISHED: 09-04-2013
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Multiple system atrophy (MSA) is a sporadic, late onset, rapidly progressing neurodegenerative disorder, which is characterized by autonomic failure, together with Parkinsonian, cerebellar, and pyramidal motor symptoms. The pathologic hallmark is the glial cytoplasmic inclusion with ?-synuclein aggregates. MSA is thus an ?-synucleinopathy. Recently, Sasaki et al. reported that heterozygosity for copy number loss of Src homology 2 domain containing-transforming protein 2 (SHC2) genes (heterozygous SHC2 gene deletions) occurred in DNAs from many Japanese individuals with MSA. Because background copy number variation can be distinct in different human populations, we assessed SHC2 allele copy number in DNAs from a US cohort of individuals with MSA, to determine the contribution of SHC2 gene copy number variation in an American cohort followed at a US referral center for MSA. Our cohort included 105 carefully phenotyped individuals with MSA.
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Fate of Shiga toxin-producing O157:H7 and non-O157:H7 Escherichia coli cells within refrigerated, frozen, or frozen then thawed ground beef patties cooked on a commercial open-flame gas or a clamshell electric grill.
J. Food Prot.
PUBLISHED: 09-03-2013
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Both high-fat and low-fat ground beef (percent lean:fat = ca. 70:30 and 93:7, respectively) were inoculated with a 6-strain cocktail of non-O157:H7 Shiga toxin-producing Escherichia coli (STEC) or a five-strain cocktail of E. coli O157:H7 (ca. 7.0 log CFU/g). Patties were pressed (ca. 2.54 cm thick, ca. 300 g each) and then refrigerated (4°C, 18 to 24 h), or frozen (-18°C, 3 weeks), or frozen (-18°C, 3 weeks) and then thawed (4°C for 18 h or 21°C for 10 h) before being cooked on commercial gas or electric grills to internal temperatures of 60 to 76.6°C. For E. coli O157:H7, regardless of grill type or fat level, cooking refrigerated patties to 71.1 or 76.6°C decreased E. coli O157:H7 numbers from an initial level of ca. 7.0 log CFU/g to a final level of ?1.0 log CFU/g, whereas decreases to ca. 1.1 to 3.1 log CFU/g were observed when refrigerated patties were cooked to 60.0 or 65.5°C. For patties that were frozen or freeze-thawed and cooked to 71.1 or 76.6°C, E. coli O157:H7 numbers decreased to ca. 1.7 or ?0.7 log CFU/g. Likewise, pathogen numbers decreased to ca. 0.7 to 3.7 log CFU/g in patties that were frozen or freeze-thawed and cooked to 60.0 or 65.5°C. For STEC, regardless of grill type or fat level, cooking refrigerated patties to 71.1 or 76.6°C decreased pathogen numbers from ca. 7.0 to ?0.7 log CFU/g, whereas decreases to ca. 0.7 to 3.6 log CFU/g were observed when refrigerated patties were cooked to 60.0 or 65.5°C. For patties that were frozen or freeze-thawed and cooked to 71.1 or 76.6°C, STEC numbers decreased to a final level of ca. 1.5 to ?0.7 log CFU/g. Likewise, pathogen numbers decreased from ca. 7.0 to ca. 0.8 to 4.3 log CFU/g in patties that were frozen or freeze-thawed and cooked to 60.0 or 65.5°C. Thus, cooking ground beef patties that were refrigerated, frozen, or freeze-thawed to internal temperatures of 71.1 and 76.6°C was effective for eliminating ca. 5.1 to 7.0 log CFU of E. coli O157:H7 and STEC per g.
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Use of a palladium(II)-catalyzed oxidative kinetic resolution in synthetic efforts toward bielschowskysin.
Tetrahedron
PUBLISHED: 08-06-2013
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Progress toward the cyclobutane core of bielshowskysin is reported. The core was thought to arise from a cyclopropane intermediate via a furan-mediated cyclopropane fragmentation, followed by a 1,4-Michael addition. The synthesis of the cyclopropane intermediate utilizes a Suzuki coupling reaction, an esterification with 2-diazoacetoacetic acid, and a copper catalyzed cyclopropanation. An alcohol intermediate within the synthetic route was obtained in high enantiopurity via a highly selective palladium(II)-catalyzed oxidative kinetic resolution (OKR).
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Creating an epiphany with Martha e. Rogers.
Nurs Sci Q
PUBLISHED: 07-03-2013
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Creating an epiphany or integral manifestation with Martha Rogers is discussed in the context of her science of unitary human beings, Barretts power theory, and yinyang. It is shown how Marthas science is related to an epiphany with her. Questions are raised and speculations are made about an epiphany with Martha living in the universe and about gender.
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Endovascular treatment of complex aneurysms at the vertebrobasilar junction with flow-diverting stents: initial experience.
Neurosurgery
PUBLISHED: 06-22-2013
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Large or giant complex vertebrobasilar junction aneurysms have a dismal natural history and are often challenging to treat with standard endovascular or neurosurgical techniques.
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Hyperbaric oxygen as an adjuvant treatment for malignant otitis externa.
Cochrane Database Syst Rev
PUBLISHED: 06-04-2013
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Malignant, or necrotising, otitis externa is a potentially fatal infection of the external ear canal and surrounding soft tissue and bone. It may be complicated by involvement of cranial nerves, principally the facial nerves and the contents of the jugular foramen. It is an uncommon condition mainly found in the elderly or in diabetics.
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Development of low cost medium for ethanol production from syngas by Clostridium ragsdalei.
Bioresour. Technol.
PUBLISHED: 05-21-2013
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The development of a low cost medium for ethanol production is critical for process feasibility. Ten media were formulated for Clostridium ragsdalei by reduction, elimination and replacement of expensive nutrients. Cost analysis and effects of medium components on growth and product formation were investigated. Fermentations were performed in 250 mL bottles using syngas (20% CO, 15% CO2, 5% H2 and 60% N2). The standard medium M1 cost is $9.83/L, of which 93% is attributed to morpholinoethane sulfonic acid (MES) buffer. Statistical analysis of the results showed that MES removal did not affect cell growth and ethanol production (P>0.05). Based on cells elemental composition, a minimal mineral concentration medium M7 was formulated, which provided 29% higher ethanol yield from CO at 3% of the cost compared to medium M1. Ethanol yield from CO in the completely defined medium M9 was 36% higher than while at 5% the cost of medium M1.
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Growth of a pYV-bearing Yersinia pestis KIM5 in retail raw ground pork.
Foodborne Pathog. Dis.
PUBLISHED: 05-01-2013
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Yersinia pestis can cause oropharyngeal plague as a result of consumption or handling of meat from infected animals. Thus, food naturally or intentionally contaminated can have a role in the dissemination of oropharyngeal plague. The growth of a conditionally virulent pYV-bearing rifampicin-resistant Y. pestis KIM5 (rif-Y. pestis KIM5) in retail raw ground pork (RGP) was studied at temperatures ranging from 4 to 30°C. At 4°C, rif-Y. pestis KIM5 did not grow but survived. In RGP, rif-Y. pestis KIM5 grew at refrigerated temperatures of 10 and 15°C with growth rates of 0.05 and 0.16 log(10) colony-forming units (CFU)/h. The growth rates at abusive temperatures of 20, 25, and 30°C were 0.26, 0.30, and 0.77 log(10) CFU/h. The growth rate was increased 15.4-fold with the increase of storage temperatures from 10°C to 30°C. The maximum population density ranged from 6.76 to 8.66 log(10) CFU/g. Furthermore, there was no detectable loss of pYV in surviving rif-Y. pestis KIM5 at any of the temperatures tested in retail RGP. This suggests that under these conditions, Y. pestis could cause oropharyngeal plague if the meat was not properly cooked. The individual infected by Y. pestis in food is a potential reservoir who can infect others, leading to outbreaks of plague.
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Enhanced optomotor efficiency by expression of the human gene superoxide dismutase primarily in Drosophila motorneurons.
J. Neurogenet.
PUBLISHED: 04-18-2013
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Mutation of the human gene superoxide dismutase (hSOD1) triggers the fatal neurodegenerative motorneuron disorder, familial amyotrophic lateral sclerosis (ALS or Lou Gehrigs disease). Broad expression of this gene in Drosophila has no effect on longevity or functional senescence. We show here that restricting expression of human SOD1 primarily to motorneurons of Drosophila has significant effects on optomotor efficiency during in-flight tracking of rapidly moving visual targets. Under high-stress workloads with a recursive visual-motion stimulus cycle, young isogenic controls failed to track rapidly changing visual cues, whereas their same-aged hSOD1-activated progeny maintained coordinated in-flight tracking of the target by phase locking to the dynamic visual movement patterns. Several explanations are considered for the observed effects, including antioxidant intervention in motorneurons, changes in signal transduction pathways that regulate patterns of gene expression in other cell types, and expression of hSOD1 in a small set of neurons in the central brain. That hSOD1 overexpression improves sensorimotor coordination in young organisms may suggest possible therapeutic strategies for early-onset ALS in humans.
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Fate of E. coli O157:H7, Salmonella spp. and potential surrogate bacteria on apricot fruit, following exposure to UV-C light.
Int. J. Food Microbiol.
PUBLISHED: 04-17-2013
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Some soft fruit, such as tree-ripened apricots, cannot be washed with aqueous sanitizers, due to their innate softness and delicate surfaces. In this study, ultraviolet-C (UV-C) light was investigated for its efficacy in inactivating 4-5 individual strains of Escherichia coli O157:H7 and Salmonella spp. on apricots, in addition to a four-strain composite of Shiga toxin-negative E. coli O157:H7 and a cocktail of three attenuated strains of Salmonella Typhimurium and Salmonella Typhimurium LT2. Also, the survival of E. coli O157:H7 and Salmonella spp. after exposure to 74 and 442 mJ/cm² of UV-C was evaluated during post-UV storage at 2 and 20 °C. The fruit was spot inoculated and the areas (ca. 1.5 cm²) of fruit surface with the inoculated bacteria were exposed to UV-C at 7.4 mW/cm². E. coli O157:H7 and Salmonella spp. populations decreased rapidly (1-2 logs) (P<0.05) with increasing UV-C doses of 0 to 74 mJ/cm². Further increases in UV-C dosage achieved only limited additional reductions in bacterial populations. Shiga toxin-negative bacteria and attenuated S. Typhimurium strains, along with S. Typhimurium LT2, responded similarly to corresponding pathogenic E. coli O157:H7 and Salmonella spp. During storage at 2 or 20 °C, populations of pathogenic E. coli O157:H7 and Salmonella spp. on untreated fruit decreased slowly; however, populations on fruit treated with 442 mJ/cm² decreased rapidly at both temperatures. After 8 days at 20 °C or 21 days at 2 °C, E. coli O157:H7 and Salmonella spp. populations on UV-C treated fruit were at least 2 log CFU/g lower than on non-treated controls. Our results suggest that surface-inoculated bacteria survived poorly following UV-C treatment of apricots.
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Influence of periodic vs continuous daily bright light exposure on development of experimental myopia in the chick.
Ophthalmic Physiol Opt
PUBLISHED: 04-09-2013
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In children, time spent outdoors has a protective effect against myopia development. In animal models, bright light reduces the development of experimental myopia. This study investigates how an increase in daily light exposure, presented either continuously during the day or periodically at different times of day, influences the development of experimental myopia in the chick.
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Commercial thermal process for inactivating Salmonella Poona on surfaces of whole fresh cantaloupes.
J. Food Prot.
PUBLISHED: 03-07-2013
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Outbreaks of salmonellosis by Salmonella Poona and listeriosis by Listeria monocytogenes have been associated with the consumption of cantaloupes. Commercial washing processes for cantaloupes are limited in their ability to inactivate and/or remove this human pathogen. Our objective was to develop a commercial-scale surface pasteurization process for enhancing microbiological safety of cantaloupes. Whole cantaloupes, surface inoculated with Salmonella Poona RM 2350, were stored at 32°C for 24 h prior to processing. Temperature-penetration profiles indicated that the surface temperature of the whole cantaloupe was 26 and 30°C below that of the hot water temperature after 2 min of immersion at 82 and 92°C, respectively. Hot water treatments at 92°C for 60 and 90 s reduced Salmonella Poona populations in excess of 5 log CFU/g of rind. Cantaloupes that were treated and stored at 4°C for 9 days retained their firmness quality and maintained nondetectable levels of Salmonella Poona as compared with the controls. Also, levels of Salmonella Poona on fresh-cut cantaloupe prepared from hot water-treated cantaloupes and stored for 9 days at 4°C were nondetectable as compared with the controls. These results indicate that surface pasteurization at 92°C for 90 s will enhance the microbiological safety of cantaloupes and will extend the shelf life of this commodity as well. The process parameter of 90 s or less falls within the commercial requirements of the whole-cantaloupe processor-packer industry.
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Use of a light-dependent magnetic compass for y-axis orientation in European common frog (Rana temporaria) tadpoles.
J. Comp. Physiol. A Neuroethol. Sens. Neural. Behav. Physiol.
PUBLISHED: 03-06-2013
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We provide evidence for the use of a magnetic compass for y-axis orientation (i.e., orientation along the shore-deep water axis) by tadpoles of the European common frog (Rana temporaria). Furthermore, our study provides evidence for a wavelength-dependent effect of light on magnetic compass orientation in amphibians. Tadpoles trained and then tested under full-spectrum light displayed magnetic compass orientation that coincided with the trained shore-deep water axes of their training tanks. Conversely, tadpoles trained under long-wavelength (?500 nm) light and tested under full-spectrum light, and tadpoles trained under full-spectrum light and tested under long-wavelength (?500 nm) light, exhibited a 90° shift in magnetic compass orientation relative to the trained y-axis direction. Our results are consistent with earlier studies showing that the observed 90° shift in the direction of magnetic compass orientation under long-wavelength (?500 nm) light is due to a direct effect of light on the underlying magnetoreception mechanism. These findings also show that wavelength-dependent effects of light do not compromise the function of the magnetic compass under a wide range of natural lighting conditions, presumably due to a large asymmetry in the relatively sensitivity of antagonistic short- and long-wavelength inputs to the light-dependent magnetic compass.
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Expression of zinc-deficient human superoxide dismutase in Drosophila neurons produces a locomotor defect linked to mitochondrial dysfunction.
Neurobiol. Aging
PUBLISHED: 03-03-2013
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More than 130 different mutations in the Cu/Zn superoxide dismutase (SOD1) gene have been associated with amyotrophic lateral sclerosis but the mechanism of this toxicity remains controversial. To gain insight into the importance of the zinc site in the pathogenesis of SOD1 in vivo, we generated a Drosophila model with transgenic expression of a zinc-deficient human SOD1. Expression of zinc-deficient SOD1 in Drosophila resulted in a progressive movement defect with associated mitochondrial cristae vacuolization and reductions in adenosine triphosphate (ATP) levels. Furthermore, these flies are sensitized to mitochondrial toxins, paraquat, and zinc. Importantly, we show that the zinc-deficient SOD1-induced motor defect can be ameliorated by supplementing the endogenous fly respiratory chain machinery with the single-subunit NADH-ubiquinone oxidoreductase from yeast (NADH is nicotinamide adenine dinucleotide, reduced form.). These results demonstrate that zinc-deficient SOD1 is neurotoxic in vivo and suggest that mitochondrial dysfunction plays a critical role in this toxicity. The robust behavioral, pathological, and biochemical phenotypes conferred by zinc-deficient SOD1 in Drosophila have general implications for the role of the zinc ion in familial and sporadic amyotrophic lateral sclerosis.
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Magnetic compass orientation in the European eel.
PLoS ONE
PUBLISHED: 02-12-2013
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European eel migrate from freshwater or coastal habitats throughout Europe to their spawning grounds in the Sargasso Sea. However, their route (~ 6000 km) and orientation mechanisms are unknown. Several attempts have been made to prove the existence of magnetoreception in Anguilla sp., but none of these studies have demonstrated magnetic compass orientation in earth-strength magnetic field intensities. We tested eels in four altered magnetic field conditions where magnetic North was set at geographic North, South, East, or West. Eels oriented in a manner that was related to the tank in which they were housed before the test. At lower temperature (under 12°C), their orientation relative to magnetic North corresponded to the direction of their displacement from the holding tank. At higher temperatures (12-17°C), eels showed bimodal orientation along an axis perpendicular to the axis of their displacement. These temperature-related shifts in orientation may be linked to the changes in behavior that occur between the warm season (during which eels are foraging) and the colder fall and winter (during which eels undertake their migrations). These observations support the conclusion that 1. eels have a magnetic compass, and 2. they use this sense to orient in a direction that they have registered moments before they are displaced. The adaptive advantage of having a magnetic compass and learning the direction in which they have been displaced becomes clear when set in the context of the eels seaward migration. For example, if their migration is halted or blocked, as it is the case when environmental conditions become unfavorable or when they encounter a barrier, eels would be able to resume their movements along their old bearing when conditions become favorable again or when they pass by the barrier.
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Loss-of-function ferrochelatase and gain-of-function erythroid-specific 5-aminolevulinate synthase mutations causing erythropoietic protoporphyria and x-linked protoporphyria in North American patients reveal novel mutations and a high prevalence of X-lin
Mol. Med.
PUBLISHED: 01-23-2013
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Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are inborn errors of heme biosynthesis with the same phenotype but resulting from autosomal recessive loss-of-function mutations in the ferrochelatase (FECH) gene and gain-of-function mutations in the X-linked erythroid-specific 5-aminolevulinate synthase (ALAS2) gene, respectively. The EPP phenotype is characterized by acute, painful, cutaneous photosensitivity and elevated erythrocyte protoporphyrin levels. We report the FECH and ALAS2 mutations in 155 unrelated North American patients with the EPP phenotype. FECH sequencing and dosage analyses identified 140 patients with EPP: 134 with one loss-of-function allele and the common IVS3-48T>C low expression allele, three with two loss-of-function mutations and three with one loss-of-function mutation and two low expression alleles. There were 48 previously reported and 23 novel FECH mutations. The remaining 15 probands had ALAS2 gain-of-function mutations causing XLP: 13 with the previously reported deletion, c.1706_1709delAGTG, and two with novel mutations, c.1734delG and c.1642C>T(p.Q548X). Notably, XLP represented ~10% of EPP phenotype patients in North America, two to five times more than in Western Europe. XLP males had twofold higher erythrocyte protoporphyrin levels than EPP patients, predisposing to more severe photosensitivity and liver disease. Identification of XLP patients permits accurate diagnosis and counseling of at-risk relatives and asymptomatic heterozygotes.
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A comparison of mass transfer coefficients between trickle-bed, hollow fiber membrane and stirred tank reactors.
Bioresour. Technol.
PUBLISHED: 01-21-2013
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Trickle-bed reactor (TBR), hollow fiber membrane reactor (HFR) and stirred tank reactor (STR) can be used in fermentation of sparingly soluble gasses such as CO and H2 to produce biofuels and bio-based chemicals. Gas fermenting reactors must provide high mass transfer capabilities that match the kinetic requirements of the microorganisms used. The present study compared the volumetric mass transfer coefficient (K(tot)A/V(L)) of three reactor types; the TBR with 3 mm and 6 mm beads, five different modules of HFRs, and the STR. The analysis was performed using O2 as the gaseous mass transfer agent. The non-porous polydimethylsiloxane (PDMS) HFR provided the highest K(tot)A/V(L) (1062 h(-1)), followed by the TBR with 6mm beads (421 h(-1)), and then the STR (114 h(-1)). The mass transfer characteristics in each reactor were affected by agitation speed, and gas and liquid flow rates. Furthermore, issues regarding the comparison of mass transfer coefficients are discussed.
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Salmonella and Escherichia coli O157:H7 survival in soil and translocation into leeks (Allium porrum) as influenced by an arbuscular mycorrhizal fungus (Glomus intraradices).
Appl. Environ. Microbiol.
PUBLISHED: 01-11-2013
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A study was conducted to determine the influence of arbuscular mycorrhizal (AM) fungi on Salmonella and enterohemorrhagic Escherichia coli O157:H7 (EHEC) in autoclaved soil and translocation into leek plants. Six-week-old leek plants (with [Myc+] or without [Myc-] AM fungi) were inoculated with composite suspensions of Salmonella or EHEC at ca. 8.2 log CFU/plant into soil. Soil, root, and shoot samples were analyzed for pathogens on days 1, 8, 15, and 22 postinoculation. Initial populations (day 1) were ca. 3.1 and 2.1 log CFU/root, ca. 2.0 and 1.5 log CFU/shoot, and ca. 5.5 and 5.1 CFU/g of soil for Salmonella and EHEC, respectively. Enrichments indicated that at days 8 and 22, only 31% of root samples were positive for EHEC, versus 73% positive for Salmonella. The mean Salmonella level in soil was 3.4 log CFU/g at day 22, while EHEC populations dropped to ? 0.75 log CFU/g by day 15. Overall, Salmonella survived in a greater number of shoot, root, and soil samples, compared with the survival of EHEC. EHEC was not present in Myc- shoots after day 8 (0/16 samples positive); however, EHEC persisted in higher numbers (P = 0.05) in Myc+ shoots (4/16 positive) at days 15 and 22. Salmonella, likewise, survived in statistically higher numbers of Myc+ shoot samples (8/8) at day 8, compared with survival in Myc- shoots (i.e., only 4/8). These results suggest that AM fungi may potentially enhance the survival of E. coli O157:H7 and Salmonella in the stems of growing leek plants.
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Surgical outcomes in craniosynostosis reconstruction: The use of prefabricated templates in cranial vault remodelling.
J Plast Reconstr Aesthet Surg
PUBLISHED: 01-03-2013
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Cranio-orbital reshaping for anterior cranial-vault deformities associated with craniosynostosis traditionally relies on the surgeons subjective estimate of the shape and appearance of a normal forehead. Computer-aided design/computer-aided manufacture (CAD/CAM) bandeau templates to guide reconstruction were introduced in our centre to eliminate this subjectivity and to effect more reproducible surgical results. The aim of this study was to compare two groups of patients (template, n = 14 vs. no template, n = 23) to measure surgical outcomes. The virtual, computational version of the template was used as an outcome assessment tool. It was used to calculate an intervening area under the curve (AUC) between the normative template and the patients reconstructed supra-orbital bar on a representative computed tomography (CT) axial section. A comprehensive chart review was conducted of patients in both groups to examine the preoperative and postoperative variables. Based on the analysis performed on the immediate postoperative CT scans, in the template group - as compared to the control, no-template group - the use of the bandeau template led to a greater reduction in AUC (74% vs. 56%, p = 0.016), indicating a better conformity between the reconstructed supra-orbital bar and the ideal, normal bandeau shape. The duration of operation was significantly reduced with the use of the template (212 vs. 258 min, p < 0.001). The application of prefabricated templates in cranio-orbital reshaping is highly useful for accurate preoperative planning; reproducible and efficient intra-operative correction of dysmorphology; and objective surgical outcomes assessment.
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Rapid learning of magnetic compass direction by C57BL/6 mice in a 4-armed plus water maze.
PLoS ONE
PUBLISHED: 01-01-2013
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Magnetoreception has been demonstrated in all five vertebrate classes. In rodents, nest building experiments have shown the use of magnetic cues by two families of molerats, Siberian hamsters and C57BL/6 mice. However, assays widely used to study rodent spatial cognition (e.g. water maze, radial arm maze) have failed to provide evidence for the use of magnetic cues. Here we show that C57BL/6 mice can learn the magnetic direction of a submerged platform in a 4-armed (plus) water maze. Naïve mice were given two brief training trials. In each trial, a mouse was confined to one arm of the maze with the submerged platform at the outer end in a predetermined alignment relative to magnetic north. Between trials, the training arm and magnetic field were rotated by 180(°) so that the mouse had to swim in the same magnetic direction to reach the submerged platform. The directional preference of each mouse was tested once in one of four magnetic field alignments by releasing it at the center of the maze with access to all four arms. Equal numbers of responses were obtained from mice tested in the four symmetrical magnetic field alignments. Findings show that two training trials are sufficient for mice to learn the magnetic direction of the submerged platform in a plus water maze. The success of these experiments may be explained by: (1) absence of alternative directional cues (2), rotation of magnetic field alignment, and (3) electromagnetic shielding to minimize radio frequency interference that has been shown to interfere with magnetic compass orientation of birds. These findings confirm that mice have a well-developed magnetic compass, and give further impetus to the question of whether epigeic rodents (e.g., mice and rats) have a photoreceptor-based magnetic compass similar to that found in amphibians and migratory birds.
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High-altitude pulmonary hypertension in cattle (brisket disease): Candidate genes and gene expression profiling of peripheral blood mononuclear cells.
Pulm Circ
PUBLISHED: 12-30-2011
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High-altitude pulmonary hypertension (HAPH) is a consequence of chronic alveolar hypoxia, leading to hypoxic vasoconstriction and remodeling of the pulmonary circulation. Brisket disease in cattle is a naturally occurring animal model of hypoxic pulmonary hypertension. Genetically susceptible cattle develop severe pulmonary hypertension and right heart failure at altitudes >7,000 ft. No information currently exists regarding the identity of the pathways and gene(s) responsible for HAPH or influencing severity. We hypothesized that initial insights into the pathogenesis of the disease could be discovered by a strategy of (1) sequencing of functional candidates revealed by single nucleotide polymorphism (SNP) analysis and (2) gene expression profiling of affected cattle compared with altitude-matched normal controls, with gene set enrichment analysis (GSEA) and Ingenuity pathway analysis (IPA). We isolated blood from a single herd of Black Angus cattle of both genders, aged 12-18 months, by jugular vein puncture. Mean pulmonary arterial pressures were 85.6±13 mmHg STD in the 10 affected and 35.3±1.2 mmHg STD in the 10 resistant cattle, P<0.001. From peripheral blood mononuclear cells, DNA was hybridized to an Affymetrix 10K Gene Chip SNP, and RNA was used to probe an Affymetrix Bovine genome array. SNP loci were remapped using the Btau 4.0 bovine genome assembly. mRNA data was analyzed by the Partek software package to identify sets of genes with an expression that was statistically different between the two groups. GSEA and IPA were conducted on the refined expression data to identify key cellular pathways and to generate networks and conduct functional analyses of the pathways and networks. Ten SNPs were identified by allelelic association and four candidate genes were sequenced in the cohort. Neither endothelial nitric oxide synthetase, NADH dehydrogenase, TG-interacting factor-2 nor BMPR2 were different among affected and resistant cattle. A 60-gene mRNA signature was identified that differentiated affected from unaffected cattle. Forty-six genes were overexpressed in the affected and 14 genes were downregulated in the affected cattle by at least 20%. GSEA and Ingenuity analysis identified respiratory diseases, inflammatory diseases and pathways as the top diseases and disorders (P<5.14×10(-14)), cell development and cell signaling as the top cellular functions (P<1.20×10(-08)), and IL6, TREM, PPAR, NFkB cell signaling (P<8.69×10(-09)) as the top canonical pathways associated with this gene signature. This study provides insights into differences in RNA expression in HAPH at a molecular level, and eliminates four functional gene candidates. Further studies are needed to validate and refine these preliminary findings and to determine the role of transcribed genes in the development of HAPH.
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17q24.2 microdeletions: a new syndromal entity with intellectual disability, truncal obesity, mood swings and hallucinations.
Eur. J. Hum. Genet.
PUBLISHED: 12-14-2011
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Although microdeletions of the long arm of chromosome 17 are being reported with increasing frequency, deletions of chromosome band 17q24.2 are rare. Here we report four patients with a microdeletion encompassing chromosome band 17q24.2 with a smallest region of overlap of 713 kb containing five Refseq genes and one miRNA. The patients share the phenotypic characteristics, such as intellectual disability (4/4), speech delay (4/4), truncal obesity (4/4), seizures (2/4), hearing loss (3/4) and a particular facial gestalt. Hallucinations and mood swings were also noted in two patients. The PRKCA gene is a very interesting candidate gene for many of the observed phenotypic features, as this gene plays an important role in many cellular processes. Deletion of this gene might explain the observed truncal obesity and could also account for the hallucinations and mood swings seen in two patients, whereas deletion of a CACNG gene cluster might be responsible for the seizures observed in two patients. In one of the patients, the PRKAR1A gene responsible for Carney Complex and the KCNJ2 gene causal for Andersen syndrome are deleted. This is the first report of a patient with a whole gene deletion of the KCNJ2 gene.
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Identification of plasma biomarkers of TBI outcome using proteomic approaches in an APOE mouse model.
J. Neurotrauma
PUBLISHED: 12-07-2011
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The current lack of diagnostic and prognostic biomarkers for traumatic brain injury (TBI) confounds treatment and management of patients and is of increasing concern as the TBI population grows. We have generated plasma proteomic profiles from mice receiving TBI by controlled cortical impact at either 1.3 mm or 1.8 mm depth, comparing these against those of sham injured-animals to identify plasma biomarkers specific to mild or severe TBI at 24 hours, 1 month, or 3 months post-injury. To identify possible prognostic biomarkers, we used apolipoprotein E (APOE)3 and APOE4 transgenic mice, which demonstrate relatively favorable and unfavorable outcomes respectively, following TBI. Using a quantitative proteomics approach (isobaric tagging for relative and absolute quantitation--iTRAQ) we have identified proteins that are significantly modulated as a function of TBI and also in response to the TBI*APOE genotype interaction, the latter representing potential prognostic biomarkers. These preliminary data clearly demonstrate plasma protein changes that are not only injury dependent but also interaction dependent. Importantly, these results demonstrate the presence of TBI-dependent and interaction-dependent plasma proteins at a 3-month time point, which is a considerable time post-injury in the mouse model, and will potentially be of significance for combat veterans receiving assessment at extended periods post-injury. Furthermore, our identification of clusters of functionally related proteins indicates disturbance of particular biological modules, which potentially increases their value beyond that of solitary biomarkers.
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Genetic approach to evaluation of hearing loss.
Otolaryngol. Clin. North Am.
PUBLISHED: 11-01-2011
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Information on the genetic basis of and testing for disorders with hearing loss is increasing rapidly. In this review, the authors explain genetic terminology, the principles of inheritance, and the types of genetic variation and the genetic basis of selected disorders of hearing loss. The authors also review how information on genetics and genetic testing can be obtained, outline a genetic approach to the diagnosis of hearing loss, and discuss how otologists and geneticists can work together to strengthen the clinical applications of genetics to individuals and families who have hearing loss.
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Repetitive transcranial magnetic stimulation for tinnitus.
Cochrane Database Syst Rev
PUBLISHED: 10-07-2011
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Tinnitus is the perception of sound, in the ear or in the head, in the absence of any external acoustic stimulation. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive means of inducing electrical currents in the brain, and has received increasing attention in recent years for the treatment of many neuropsychiatric disorders, including tinnitus.
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Application of CAD/CAM prefabricated age-matched templates in cranio-orbital remodeling in craniosynostosis.
J Craniofac Surg
PUBLISHED: 10-01-2011
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Infants with craniosynostosis involving the metopic and coronal sutures require cranio-orbital reshaping to correct craniofacial dysmorphologic feature and to improve facial balance. Currently, surgical techniques to create a balanced fronto-orbital region are based on the surgeons subjective approach and artistic vision in creating a normal shape to the forehead. To date, the use of age-matched templates and computer-assisted design/computer-assisted manufacturing techniques in optimizing the outcomes of surgical intervention in this area have not been explored. The aim of this article was to describe the process of template generation and application based on age-matched controls using computer-assisted design/computer-assisted manufacturing technology and to present this application in 2 cases.
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Evaluating the effect of temperature on microbial growth rate--the Ratkowsky and a B?lehrádek-type models.
J. Food Sci.
PUBLISHED: 09-19-2011
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The objective of this paper to conduct a parallel comparison of a new B?lehrádek-type growth rate (with an exponent of 1.5, or the Huang model), Ratkowsky square-root, and Ratkowsky square equations as secondary models for evaluating the effect of temperature on the growth of microorganisms. Growth rates of psychrotrophs and mesophiles were selected from the literature, and independently analyzed with the 3 models using nonlinear regression. Analysis of variance (ANOVA) was used to compare the means of growth rate (?), estimated minimum temperature (T(min) ), approximate standard errors (SE) of T(min) , model mean square errors (MSE), accuracy factor (A(f) ), bias factor (B(f) ), relative residual errors (?), Akaike information criterion (AICc), and Bayesian information criterion (BIC). Based on the estimated T(min) values, the Huang model distinctively classified the bacteria into 2 groups (psychrotrophs and mesophiles). No significant difference (P > 0.05) was observed among the means of the ? values reported in the literature or estimated by the 3 models, suggesting that all 3 models were suitable for curve fitting. Nor was there any significant difference in MSE, SE, ?, A(f) , B(f) , AICc, and BIC. The T(min) values estimated by the Huang model were significantly higher than those estimated by the Ratkowsky models, but were in closer agreement with the biological minimum temperatures for both psychrotrophs and mesophiles. The T(min) values estimated by the Ratkowsky models systematically underestimated the minimum growth temperatures. In addition, statistical estimation showed that the mean exponent for the new B?lehrádek-type growth rate model may indeed be 1.5, further supporting the validity of the Huang model.
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Effect of temperature on microbial growth rate-mathematical analysis: the Arrhenius and Eyring-Polanyi connections.
J. Food Sci.
PUBLISHED: 09-19-2011
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The objective of this work is to develop a mathematical model for evaluating the effect of temperature on the rate of microbial growth. The new mathematical model is derived by combination and modification of the Arrhenius equation and the Eyring-Polanyi transition theory. The new model, suitable for both suboptimal and the entire growth temperature ranges, was validated using a collection of 23 selected temperature-growth rate curves belonging to 5 groups of microorganisms, including Pseudomonas spp., Listeria monocytogenes, Salmonella spp., Clostridium perfringens, and Escherichia coli, from the published literature. The curve fitting is accomplished by nonlinear regression using the Levenberg-Marquardt algorithm. The resulting estimated growth rate (?) values are highly correlated to the data collected from the literature (R(2) = 0.985, slope = 1.0, intercept = 0.0). The bias factor (B(f) ) of the new model is very close to 1.0, while the accuracy factor (A(f) ) ranges from 1.0 to 1.22 for most data sets. The new model is compared favorably with the Ratkowsky square root model and the Eyring equation. Even with more parameters, the Akaike information criterion, Bayesian information criterion, and mean square errors of the new model are not statistically different from the square root model and the Eyring equation, suggesting that the model can be used to describe the inherent relationship between temperature and microbial growth rates. The results of this work show that the new growth rate model is suitable for describing the effect of temperature on microbial growth rate. Practical Application:? Temperature is one of the most significant factors affecting the growth of microorganisms in foods. This study attempts to develop and validate a mathematical model to describe the temperature dependence of microbial growth rate. The findings show that the new model is accurate and can be used to describe the effect of temperature on microbial growth rate in foods.
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Comparison of cerebral volume in children aged 18-22 and 36-47 months born preterm and term.
J. Child Neurol.
PUBLISHED: 09-13-2011
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Studies investigating differences in regional brain volumes in children born preterm and term during early childhood are limited. Neuroimaging could help understand patterns of deficit in children born preterm and target areas of development associated with these regions. The goal of this study was to identify differences in regional brain volume at 2 different ages using magnetic resonance imaging in preterm and term children. Magnetic resonance imaging and developmental testing occurred in children 18 to 22 months old (16 preterm and 10 term children) and 36 to 47 month old (12 preterm and 10 term children). There were significant differences between the 4 groups in the parietal region, cerebral white matter, third ventricle, and lateral ventricle. Correlations between regional cerebral volume and developmental testing were explored for the third and lateral ventricles. Our findings indicate that in young children differences in regional cerebral volume are due to both maturation and prematurity.
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Sampangine inhibits heme biosynthesis in both yeast and human.
Eukaryotic Cell
PUBLISHED: 09-09-2011
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The azaoxoaporphine alkaloid sampangine exhibits strong antiproliferation activity in various organisms. Previous studies suggested that it somehow affects heme metabolism and stimulates production of reactive oxygen species (ROS). In this study, we show that inhibition of heme biosynthesis is the primary mechanism of action by sampangine and that increases in the levels of reactive oxygen species are secondary to heme deficiency. We directly demonstrate that sampangine inhibits heme synthesis in the yeast Saccharomyces cerevisiae. It also causes accumulation of uroporphyrinogen and its decarboxylated derivatives, intermediate products of the heme biosynthesis pathway. Our results also suggest that sampangine likely works through an unusual mechanism-by hyperactivating uroporhyrinogen III synthase-to inhibit heme biosynthesis. We also show that the inhibitory effect of sampangine on heme synthesis is conserved in human cells. This study also reveals a surprising essential role for the interaction between the mitochondrial ATP synthase and the electron transport chain.
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Pediatric facial fractures and potential long-term growth disturbances.
Craniomaxillofac Trauma Reconstr
PUBLISHED: 09-07-2011
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Fractures of the pediatric craniofacial skeleton can be challenging to manage. The initial injury and subsequent treatment can cause long-term growth disturbances yielding problematic secondary deformities. This review considers the normal growth of the craniofacial skeleton and typical facial fracture presentations in children and discusses the potential long-term sequelae from these injuries and their management.
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Cost-effective evaluation of the vestibular patient.
Curr Opin Otolaryngol Head Neck Surg
PUBLISHED: 08-19-2011
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There is in existence a large array of sophisticated equipment to assess patients with complaints of dizziness and imbalance. Many vestibular tests are expensive to administer. In an era of evidence-based medicine and economic austerity, the appropriate utilization of such tests is of paramount importance. This review examines the clinical value together with costs involved in performing the various components of the vestibular assessment battery.
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Advances in percutaneous therapy for upper extremity arterial disease.
Cardiol Clin
PUBLISHED: 08-02-2011
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Upper extremity arteries are affected by occlusive diseases from diverse causes, with atherosclerosis being the most common. Although the overriding principle in managing patients with upper extremity arterial occlusive disease should be cardiovascular risk reduction by noninvasive and pharmacologic means, when target organ ischemia produces symptoms or threatens the patients well-being, revascularization is necessary. Given their minimally invasive nature and successful outcomes, percutaneous catheter-based therapies are preferred to surgical approaches. The fact that expertise in these techniques resides in not one but several disciplines (vascular surgery, radiology, cardiology, vascular medicine) makes this an area ripe for multidisciplinary collaboration to the benefit of patients.
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Uroporphyria in the Cyp1a2-/- mouse.
Blood Cells Mol. Dis.
PUBLISHED: 07-14-2011
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Cytochrome P4501A2 (Cyp1a2) is important in the development of uroporphyria in mice, a model of porphyria cutanea tarda in humans. Heretofore, mice homozygous for the Cyp1a2-/- mutation do not develop uroporphyria with treatment regimens that result in uroporphyria in wild-type mice. Here we report uroporphyria development in Cyp1a2-/- mice additionally null for both alleles of the hemochromatosis (Hfe) gene and heterozygous for deletion of the uroporphyrinogen decarboxylase (Urod) gene (genotype: Cyp1a2-/-;Hfe-/-;Urod+/-), demonstrating that upon adding porphyria-predisposing genetic manipulations, Cyp1a2 is not essential. Cyp1a2-/-;Hfe-/-;Urod+/- mice were treated with various combinations of an iron-enriched diet, parenteral iron-dextran, drinking water containing ?-aminolevulinic acid and intraperitoneal Aroclor 1254 (a polychlorinated biphenyl mixture) and analyzed for uroporphyrin accumulation. Animals fed an iron-enriched diet alone did not develop uroporphyria but uroporphyria developed with all treatments that included iron supplementation and ?-aminolevulinic acid, even with a regimen without Aroclor 1254. Hepatic porphyrin levels correlated with low UROD activity and high levels of an inhibitor of UROD but marked variability in the magnitude of the porphyric response was present in all treatment groups. Gene expression profiling revealed no major differences between genetically identical triple cross mice exhibiting high and low magnitude porphyric responses from iron-enriched diet and iron-dextran supplementation, and ?-aminolevulinic acid. Even though the variation in porphyric response did not parallel the hepatic iron concentration, the results are compatible with the presence of a Cyp1a2-independent, iron-dependent pathway for the generation of uroporphomethene, the UROD inhibitor required for the expression of uroporphyria in mice and PCT in humans.
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Intratympanic steroids for Ménières disease or syndrome.
Cochrane Database Syst Rev
PUBLISHED: 07-08-2011
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Ménières disease is a disorder characterised by hearing loss, tinnitus and disabling vertigo. The use of intratympanic steroids to reduce the severity of these symptoms has been gaining popularity.
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The underestimation of egocentric distance: evidence from frontal matching tasks.
Atten Percept Psychophys
PUBLISHED: 07-08-2011
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There is controversy over the existence, nature, and cause of error in egocentric distance judgments. One proposal is that the systematic biases often found in explicit judgments of egocentric distance along the ground may be related to recently observed biases in the perceived declination of gaze (Durgin & Li, Attention, Perception, & Psychophysics, in press), To measure perceived egocentric distance nonverbally, observers in a field were asked to position themselves so that their distance from one of two experimenters was equal to the frontal distance between the experimenters. Observers placed themselves too far away, consistent with egocentric distance underestimation. A similar experiment was conducted with vertical frontal extents. Both experiments were replicated in panoramic virtual reality. Perceived egocentric distance was quantitatively consistent with angular bias in perceived gaze declination (1.5 gain). Finally, an exocentric distance-matching task was contrasted with a variant of the egocentric matching task. The egocentric matching data approximate a constant compression of perceived egocentric distance with a power function exponent of nearly 1; exocentric matches had an exponent of about 0.67. The divergent pattern between egocentric and exocentric matches suggests that they depend on different visual cues.
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Pharmacologic correction of dominant-negative GH1 deficiency causing mutations.
Clin Transl Sci
PUBLISHED: 06-29-2011
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Dominant-negative growth hormone gene (GH1) mutations cause familial isolated growth hormone deficiency type II (IGHD II), which is characterized by GH deficiency, occasional multiple anterior pituitary hormone deficiencies, and anterior pituitary hypoplasia. We have previously shown that 17.5-/22-kDa GH1 transcript ratios correlate with the severity of the IGHD II phenotype. We hypothesized that different pharmaceutical agents could affect the GH1 transcript ratio by modulating alternative splicing.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.