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Find video protocols related to scientific articles indexed in Pubmed.
"The stress will kill you": prisoner reentry as experienced by family members and the urgent need for support services.
J Health Care Poor Underserved
PUBLISHED: 08-19-2014
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The role of incarceration and community reentry after incarceration has been studied extensively for individual and community health; however, little attention has been given to the experiences of individuals who provide support to those in reentry. Through a community-academic partnership, seven focus groups were conducted with 39 individuals supporting a family member in reentry in the summer of 2012. The primary objectives of the focus groups were to explore community experiences and perspectives regarding providing support during a family member's reentry from a period of incarceration and any desired support for themselves during this time. Five themes emerged under a metatheme of stress, indicating that family members experience acute stress as a result of family reentry that adds to the chronic stress they already endure. Programs that acknowledge the difficult role of family members as supporters during an individual's reentry and provide support to them are desperately needed.
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Increased Brain Gray Matter in the Primary Somatosensory Cortex is Associated with Increased Pain and Mood Disturbance in Interstitial Cystitis/Painful Bladder Syndrome Patients.
J. Urol.
PUBLISHED: 08-14-2014
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Interstitial cystitis (IC) is a highly prevalent pain condition, estimated to affect 3-6% of women in the United States. Emerging data suggests there are central neurobiological components to the etiology of this disease. Here we report the first brain structural imaging findings from the Multidisciplinary Approach to Pelvic Pain (MAPP) network, with data on over 300 participants.
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Age-dependent metabolic dysregulation in cancer and Alzheimer's disease.
Biogerontology
PUBLISHED: 07-30-2014
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Age is the main risk factor for cancer and neurodegeneration; two radically divergent diseases. Yet selective pressure to meet cellular metabolic needs may provide a common mechanism linking these two disorders. The exclusive use of glycolysis, despite the presence of oxygen, is commonly referred to as aerobic glycolysis and is the primary metabolic pathway of cancer cells. Recent evidence suggests that aerobic glycolysis is also a key regulator of synaptic plasticity in the brain that may positively influence cognition. Elevated aerobic glycolysis is a contributing factor to the development of cancer as increased glycolytic flux plays an important role in the biosynthesis of macromolecules and promotes proliferation. In contrast, decreased aerobic glycolysis in the brain occurs with age and could lead to a loss of cell survival mechanisms that counter pathogenic processes underlying neurodegeneration. In this review we discuss the recent findings from epidemiological studies demonstrating an inverse comorbidity of cancer and Alzheimer's disease. We summarize evidence linking the two diseases through changes in metabolism over the course of normal aging. We discuss the key steps and regulatory mechanisms of aerobic glycolysis and mitochondrial oxidative phosphorylation which could be exploited for the development of novel therapies. In addition, we outline the regulation of aerobic glycolysis at the transcriptional level by HIF-1? and Pin1 and their roles in cancer and neurodegeneration. Finally, we provide a possible explanation for metabolic dysregulation that occurs with age, and how it may be a contributing factor to age-related diseases. Determining how metabolism becomes dysregulated over time could lead to the development of effective interventions for ensuring metabolic homeostasis and healthy aging.
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Changes in clinical pain in fibromyalgia patients correlate with changes in brain activation in the cingulate cortex in a response inhibition task.
Pain Med
PUBLISHED: 07-04-2014
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The primary symptom of fibromyalgia is chronic, widespread pain; however, patients report additional symptoms including decreased concentration and memory. Performance-based deficits are seen mainly in tests of working memory and executive functioning. It has been hypothesized that pain interferes with cognitive performance; however, the neural correlates of this interference are still a matter of debate. In a previous, cross-sectional study, we reported that fibromyalgia patients (as compared with healthy controls) showed a decreased blood oxygen level dependent (BOLD) response related to response inhibition (in a simple Go/No-Go task) in the anterior/mid cingulate cortex, supplementary motor area, and right premotor cortex.
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Excitatory and Inhibitory Brain Metabolites as Targets and Predictors of Effective Motor Cortex tDCS Therapy in Fibromyalgia.
PUBLISHED: 06-06-2014
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Objective. Transcranial direct current stimulation (tDCS) has been shown to improve pain symptoms in fibromyalgia (FM), a central pain syndrome; the underlying mechanisms are not well understood. Our objective was to explore the neurochemical action of tDCS in the FM brain using proton magnetic resonance spectroscopy ((1) H-MRS). Methods. Twelve patients with FM underwent sham tDCS over the left motor (anode) and contralateral supraorbital cortices (cathode) (M1-SO) for 5 consecutive days, a 7 day washout period, and then active M1-SO tDCS for 5 consecutive days. The subjects had clinical pain assessment and (1) H-MRS testing at baseline, the week following post-sham tDCS trial, and the week following post-active tDCS trial. Results. There was a significant decrease in clinical pain scores between baseline and active tDCS time-points (P=0.04). There was a significant decrease in Glx (glutamate and glutamine) in the anterior cingulate (P=0.013) and a trend towards decreased Glx in the thalami (P=0.056) for the sham-active tDCS comparison. For the baseline-sham tDCS comparison, there was a significant increase in N-acetylaspartate (NAA) levels in the posterior insula (P=0.015). There was a trend towards increased ?-aminobutyric acid (GABA) in the anterior insula for the baseline-active tDCS comparison (P=0.064). There were significant linear regression coefficients between anterior cingulate Glx levels at baseline and the clinical pain scale changes between the baseline-sham tDCS comparison (?1 =1.31;P<0.001) and the baseline-active tDCS comparison (?1 =1.87;P<0.001). Conclusion. Our findings suggest that GABA, Glx and NAA play an important role in the pathophysiology of FM and its modulation by tDCS. © 2014 American College of Rheumatology.
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Comprehensive analysis of pathogenic deletion variants in fanconi anemia genes.
Hum. Mutat.
PUBLISHED: 05-02-2014
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Fanconi anemia (FA) is a rare recessive disease resulting from mutations in one of at least 16 different genes. Mutation types and phenotypic manifestations of FA are highly heterogeneous and influence the clinical management of the disease. We analyzed 202 FA families for large deletions, using high-resolution comparative genome hybridization arrays, single-nucleotide polymorphism arrays, and DNA sequencing. We found pathogenic deletions in 88 FANCA, seven FANCC, two FANCD2, and one FANCB families. We find 35% of FA families carry large deletions, accounting for 18% of all FA pathogenic variants. Cloning and sequencing across the deletion breakpoints revealed that 52 FANCA deletion ends, and one FANCC deletion end extended beyond the gene boundaries, potentially affecting neighboring genes with phenotypic consequences. Seventy-five percent of the FANCA deletions are Alu-Alu mediated, predominantly by AluY elements, and appear to be caused by nonallelic homologous recombination. Individual Alu hotspots were identified. Defining the haplotypes of four FANCA deletions shared by multiple families revealed that three share a common ancestry. Knowing the exact molecular changes that lead to the disease may be critical for a better understanding of the FA phenotype, and to gain insight into the mechanisms driving these pathogenic deletion variants.
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Brain regions involved in processing facial identity and expression are differentially selective for surface and edge information.
Neuroimage
PUBLISHED: 04-05-2014
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Although different brain regions are widely considered to be involved in the recognition of facial identity and expression, it remains unclear how these regions process different properties of the visual image. Here, we ask how surface-based reflectance information and edge-based shape cues contribute to the perception and neural representation of facial identity and expression. Contrast-reversal was used to generate images in which normal contrast relationships across the surface of the image were disrupted, but edge information was preserved. In a behavioural experiment, contrast-reversal significantly attenuated judgements of facial identity, but only had a marginal effect on judgements of expression. An fMR-adaptation paradigm was then used to ask how brain regions involved in the processing of identity and expression responded to blocks comprising all normal, all contrast-reversed, or a mixture of normal and contrast-reversed faces. Adaptation in the posterior superior temporal sulcus--a region directly linked with processing facial expression--was relatively unaffected by mixing normal with contrast-reversed faces. In contrast, the response of the fusiform face area--a region linked with processing facial identity--was significantly affected by contrast-reversal. These results offer a new perspective on the reasons underlying the neural segregation of facial identity and expression in which brain regions involved in processing invariant aspects of faces, such as identity, are very sensitive to surface-based cues, whereas regions involved in processing changes in faces, such as expression, are relatively dependent on edge-based cues.
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Verbal redundancy aids memory for filmed entertainment dialogue.
J Psychol
PUBLISHED: 04-02-2014
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Three studies investigated the effects of presentation modality and redundancy of verbal content on recognition memory for entertainment film dialogue. U.S. participants watched two brief movie clips and afterward answered multiple-choice questions about information from the dialogue. Experiment 1 compared recognition memory for spoken dialogue in the native language (English) with subtitles in English, French, or no subtitles. Experiment 2 compared memory for material in English subtitles with spoken dialogue in English, French, or no sound. Experiment 3 examined three control conditions with no spoken or captioned material in the native language. All participants watched the same video clips and answered the same questions. Performance was consistently good whenever English dialogue appeared in either the subtitles or sound, and best of all when it appeared in both, supporting the facilitation of verbal redundancy. Performance was also better when English was only in the subtitles than when it was only spoken. Unexpectedly, sound or subtitles in an unfamiliar language (French) modestly improved performance, as long as there was also a familiar channel. Results extend multimedia research on verbal redundancy for expository material to verbal information in entertainment media.
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Alterations in resting state oscillations and connectivity in sensory and motor networks in women with interstitial cystitis/painful bladder syndrome.
J. Urol.
PUBLISHED: 03-10-2014
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The pathophysiology of interstitial cystitis/painful bladder syndrome remains incompletely understood but is thought to involve central disturbance in the processing of pain and viscerosensory signals. We identified differences in brain activity and connectivity between female patients with interstitial cystitis/painful bladder syndrome and healthy controls to advance clinical phenotyping and treatment efforts for interstitial cystitis/painful bladder syndrome.
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Preliminary structural MRI based brain classification of chronic pelvic pain: A MAPP network study.
Pain
PUBLISHED: 02-25-2014
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Neuroimaging studies have shown that changes in brain morphology often accompany chronic pain conditions. However, brain biomarkers that are sensitive and specific to chronic pelvic pain (CPP) have not yet been adequately identified. Using data from the Trans-MAPP Research Network, we examined the changes in brain morphology associated with CPP. We used a multivariate pattern classification approach to detect these changes and to identify patterns that could be used to distinguish participants with CPP from age-matched healthy controls. In particular, we used a linear support vector machine (SVM) algorithm to differentiate gray matter images from the 2 groups. Regions of positive SVM weight included several regions within the primary somatosensory cortex, pre-supplementary motor area, hippocampus, and amygdala were identified as important drivers of the classification with 73% overall accuracy. Thus, we have identified a preliminary classifier based on brain structure that is able to predict the presence of CPP with a good degree of predictive power. Our regional findings suggest that in individuals with CPP, greater gray matter density may be found in the identified distributed brain regions, which are consistent with some previous investigations in visceral pain syndromes. Future studies are needed to improve upon our identified preliminary classifier with integration of additional variables and to assess whether the observed differences in brain structure are unique to CPP or generalizable to other chronic pain conditions.
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Altered resting state connectivity of the insular cortex in individuals with fibromyalgia.
J Pain
PUBLISHED: 02-17-2014
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The insular cortex (IC) and cingulate cortex (CC) are critically involved in pain perception. Previously we demonstrated that fibromyalgia (FM) patients have greater connectivity between the insula and default mode network at rest, and that changes in the degree of this connectivity were associated with changes in the intensity of ongoing clinical pain. In this study we more thoroughly evaluated the degree of resting-state connectivity to multiple regions of the IC in individuals with FM and healthy controls. We also investigated the relationship between connectivity, experimental pain, and current clinical chronic pain. Functional connectivity was assessed using resting-state functional magnetic resonance imaging in 18 FM patients and 18 age- and sex-matched healthy controls using predefined seed regions in the anterior, middle, and posterior IC. FM patients exhibited greater connectivity between 1) right mid IC and right mid/posterior CC and right mid IC, 2) right posterior IC and left CC, and 3) right anterior IC and left superior temporal gyrus. Healthy controls displayed greater connectivity between left anterior IC and bilateral medial frontal gyrus/anterior cingulate cortex; and left posterior IC and right superior frontal gyrus. Within the FM group, greater connectivity between the IC and CC was associated with decreased pressure-pain thresholds.
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Disrupted brain circuitry for pain-related reward/punishment in fibromyalgia.
PUBLISHED: 01-23-2014
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While patients with fibromyalgia (FM) are known to exhibit hyperalgesia, the central mechanisms contributing to this altered pain processing are not fully understood. This study was undertaken to investigate potential dysregulation of the neural circuitry underlying cognitive and hedonic aspects of the subjective experience of pain, such as anticipation of pain and anticipation of pain relief.
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Dynamic stimuli demonstrate a categorical representation of facial expression in the amygdala.
Neuropsychologia
PUBLISHED: 01-07-2014
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Face-selective regions in the amygdala and posterior superior temporal sulcus (pSTS) are strongly implicated in the processing of transient facial signals, such as expression. Here, we measured neural responses in participants while they viewed dynamic changes in facial expression. Our aim was to explore how facial expression is represented in different face-selective regions. Short movies were generated by morphing between faces posing a neutral expression and a prototypical expression of a basic emotion (either anger, disgust, fear, happiness or sadness). These dynamic stimuli were presented in block design in the following four stimulus conditions: (1) same-expression change, same-identity, (2) same-expression change, different-identity, (3) different-expression change, same-identity, and (4) different-expression change, different-identity. So, within a same-expression change condition the movies would show the same change in expression whereas in the different-expression change conditions each movie would have a different change in expression. Facial identity remained constant during each movie but in the different identity conditions the facial identity varied between each movie in a block. The amygdala, but not the posterior STS, demonstrated a greater response to blocks in which each movie morphed from neutral to a different emotion category compared to blocks in which each movie morphed to the same emotion category. Neural adaptation in the amygdala was not affected by changes in facial identity. These results are consistent with a role of the amygdala in category-based representation of facial expressions of emotion.
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Variable clinical presentation of Shwachman-Diamond syndrome: update from the North American Shwachman-Diamond Syndrome Registry.
J. Pediatr.
PUBLISHED: 01-07-2014
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To investigate the range of clinical presentations for Shwachman-Diamond syndrome (SDS) with the long-term goal of improving diagnosis.
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Pregabalin rectifies aberrant brain chemistry, connectivity, and functional response in chronic pain patients.
Anesthesiology
PUBLISHED: 12-18-2013
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Chronic pain remains a significant challenge for modern health care as its pathologic mechanisms are largely unknown and preclinical animal models suffer from limitations in assessing this complex subjective experience. However, human brain neuroimaging techniques enable the assessment of functional and neurochemical alterations in patients experiencing chronic pain and how these factors may dynamically change with pharmacologic treatment.
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Preliminary differences in peripheral immune markers and brain metabolites between fatigued and non-fatigued breast cancer survivors: a pilot study.
Brain Imaging Behav
PUBLISHED: 11-14-2013
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Persistent cancer-related fatigue (PCRF) is one of the most troubling side-effects of breast cancer (BC) treatment. One explanatory model for PCRF is sickness behavior, which is a set of adaptive responses including sleepiness and depressed mood in reaction to an inflammatory trigger. Prior research has investigated differences in inflammatory cytokines between fatigued and non-fatigued BC survivors, but no study has examined differences in brain metabolites. Differences in inflammatory markers, and brain metabolites using proton magnetic resonance spectroscopy were evaluated within 16 fatigued and 13 non-fatigued BC survivors. Fatigued BC survivors had significantly higher ratios of two markers derived from brain metabolites; namely (a) creatine, normalized to total creatine (creatine + phosphocreatine (Cr/tCr)) ratio (P?=?0.03) and (b) glutamate + glutamine (Glx) to N-acetyl-aspartate (NAA) ratio (P?=?0.01) in the posterior insula compared to non-fatigued breast cancer survivor. Further, serum IL-6 was increased in fatigued women compared to non-fatigued women (P?=?0.03), Using receiver operator curves (ROC) we determined that the posterior insula Glx/NAA ratio was the best predictor of fatigue with an overall area under the receiver operating characteristic curve (AUROC) of 79 %, with a sensitivity of 81 % and a specificity of 69 %. However, posterior insula Glx/NAA, Cr/tCr and serum IL-6 were not significantly correlated with one another implying the possibility of independent biological mechanisms for PCRF rather than an interrelated mechanism as represented by the sickness behavior model. This study provides novel preliminary evidence of several distinct neurobiological changes in the posterior insula associated with PCRF in BC survivors. Future, longitudinal studies are needed to explore these distinct biological phenomena where changes through time in peripheral immune markers and brain metabolites are examined to determine if they correlate with changes in fatigue.
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Increased pressure pain sensitivity in women with chronic pelvic pain.
Obstet Gynecol
PUBLISHED: 10-10-2013
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To determine whether women with chronic pelvic pain and variable degrees of endometriosis demonstrate altered pain sensitivity relative to pain-free healthy women in a control group and whether such differences are related to the presence or severity of endometriosis or comorbid pain syndromes.
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Alterations in endogenous opioid functional measures in chronic back pain.
J. Neurosci.
PUBLISHED: 09-13-2013
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The absence of consistent end organ abnormalities in many chronic pain syndromes has led to a search for maladaptive CNS mechanisms that may explain their clinical presentations and course. Here, we addressed the role of brain regional ?-opioid receptor-mediated neurotransmission, one of the best recognized mechanisms of pain regulation, in chronic back pain in human subjects. We compared ?-opioid receptor availability in vivo at baseline, during pain expectation, and with moderate levels of sustained pain in 16 patients with chronic nonspecific back pain (CNBP) and in 16 age- and gender-matched healthy control subjects, using the ?-opioid receptor-selective radioligand [(11)C]carfentanil and positron emission tomography. We found that CNBP patients showed baseline increases in thalamic ?-opioid receptor availability, contrary to a previously studied sample of patients diagnosed with fibromyalgia. During both pain expectation and sustained pain challenges, CNBP patients showed regional reductions in the capacity to activate this neurotransmitter system compared with their control sample, further associated with clinical pain and affective state ratings. Our results demonstrate heterogeneity in endogenous opioid system functional measures across pain conditions, and alterations in both receptor availability and endogenous opioid function in CNBP that are relevant to the clinical presentation of these patients and the effects of opioid analgesics on ?-opioid receptors.
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A winged helix domain in human MUS81 binds DNA and modulates the endonuclease activity of MUS81 complexes.
Nucleic Acids Res.
PUBLISHED: 08-27-2013
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The MUS81-EME1 endonuclease maintains metazoan genomic integrity by cleaving branched DNA structures that arise during the resolution of recombination intermediates. In humans, MUS81 also forms a poorly characterized complex with EME2. Here, we identify and determine the structure of a winged helix (WH) domain from human MUS81, which binds DNA. WH domain mutations greatly reduce binding of the isolated domain to DNA and impact on incision activity of MUS81-EME1/EME2 complexes. Deletion of the WH domain reduces the endonuclease activity of both MUS81-EME1 and MUS81-EME2 complexes, and incisions made by MUS81-EME2 are made closer to the junction on substrates containing a downstream duplex, such as fork structures and nicked Holliday junctions. WH domain mutation or deletion in Schizosaccharomyces pombe phenocopies the DNA-damage sensitivity of strains deleted for mus81. Our results indicate an important role for the WH domain in both yeast and human MUS81 complexes.
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The Effect of Dialect on Speech Audiometry Testing.
Am J Audiol
PUBLISHED: 07-05-2013
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This study examined the validity of using materials from two non-regional yet mutually intelligible dialects to evaluate an individuals speech recognition threshold (SRT) and word-recognition (WR) abilities, and whether a speaker of one dialect could accurately administer and score materials in the other dialect.
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Oxygen exposure and toxicity in recreational technical divers.
Diving Hyperb Med
PUBLISHED: 07-02-2013
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Central nervous system oxygen toxicity is a recognised risk in recreational open-circuit scuba diving with the use of nitrox (oxygen-enriched air mixtures), but other forms of oxygen toxicity in other diving settings are poorly understood. However, divers using constant partial pressure of oxygen closed-circuit rebreathers (CCRs) for multi-day, multi-dive expeditions could potentially experience cumulative oxygen exposures above the current recommended limits.
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Examination of the association of diet and persistent cancer-related fatigue: a pilot study.
Oncol Nurs Forum
PUBLISHED: 06-14-2013
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To examine associations between diet and persistent cancer-related fatigue (PCRF) in cancer survivors.
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Reduced Insular Glutamine and N-acetylaspartate in systemic lupus erythematosus: a single-voxel (1)H-MR spectroscopy study.
Acad Radiol
PUBLISHED: 05-30-2013
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To investigate for differences in metabolic concentrations and ratios between patients with systemic lupus erythematosus (SLE) without (group SLE) and those with neurological symptoms (group NPSLE) compared to a healthy control (group HC) in three normal-appearing brain regions: the frontal white matter, right insula (RI), and occipital gray matter and whether changes in any of the metabolites or metabolic ratios are correlated to disease activity and other clinical parameters.
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Conformational Properties of Peptides Corresponding to the Ebolavirus GP2 Membrane-Proximal External Region in the Presence of Micelle-Forming Surfactants and Lipids.
Biochemistry
PUBLISHED: 05-07-2013
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Ebola virus and Sudan virus are members of the family Filoviridae of nonsegmented negative-strand RNA viruses ("filoviruses") that cause severe hemorrhagic fever with fatality rates as high as 90%. Infection by filoviruses requires membrane fusion between the host and the virus; this process is facilitated by the two subunits of the envelope glycoprotein, GP1 (the surface subunit) and GP2 (the transmembrane subunit). The membrane-proximal external region (MPER) is a Trp-rich segment that immediately precedes the transmembrane domain of GP2. In the analogous glycoprotein for HIV-1 (gp41), the MPER is critical for membrane fusion and is the target of several neutralizing antibodies. However, the role of the MPER in filovirus GP2 and its importance in membrane fusion have not been established. Here, we characterize the conformational properties of peptides representing the GP MPER segments of Ebola virus and Sudan virus in the presence of micelle-forming surfactants and lipids, at pH 7 and 4.6. Circular dichroism spectroscopy and tryptophan fluorescence indicate that the GP2 MPER peptides bind to micelles of sodium dodecyl sulfate and dodecylphosphocholine (DPC). Nuclear magnetic resonance spectroscopy of the Sudan virus MPER peptide revealed that residues 644-651 interact directly with DPC, and that this interaction enhances the helical conformation of the peptide. The Sudan virus MPER peptide was found to moderately inhibit cell entry by a GP-pseudotyped vesicular stomatitis virus but did not induce leakage of a fluorescent molecule from a large unilammellar vesicle comprised of 1-palmitoyl-2-oleoylphosphatidylcholine or cause hemolysis. Taken together, this analysis suggests the filovirus GP2 MPER binds and inserts shallowly into lipid membranes.
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Oxandrolone for the treatment of bone marrow failure in Fanconi anemia.
Pediatr Blood Cancer
PUBLISHED: 05-03-2013
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A majority of Fanconi anemia (FA) patients will experience bone marrow failure (BMF) and androgen therapy (most often oxymetholone) may be utilized as a treatment to improve BMF-related cytopenias. However, oxymetholone is associated with toxicities making identification of other agents of interest. In this study we aimed to evaluate the toxicity profile and hematologic response in patients with FA who are treated with low-dose oxandrolone, a synthetic non-fluorinated anabolic steroid, similar to oxymetholone, with known dosing thresholds for virilization.
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The modified Brown-Peterson task: a tool to directly compare children and adults working memory.
J Genet Psychol
PUBLISHED: 03-29-2013
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The study had 2 major purposes. First, it showed that the same task (Brown-Peterson task) can be used to test the memory abilities of both young children and adults, given an appropriate distracter task. Second, it illustrated that children can perform as accurately as adults on working memory tasks when prompted to use memory techniques such as rehearsal. Specifically, a modified version of the Brown-Peterson task (typically used with adults), tested working memory of adults and children aged 5-6 years. The modification was reciting the pledge of allegiance as the distracter task, as the pledge is at a level where young children are just learning it, and thus they know it, but not exceptionally well. Adults would have previously overlearned it as children but may not have recited it recently. This allows for the use of the same distracter task, thus allowing for a direct comparison of children and adults. Under experimental conditions, both groups showed a typical Brown-Peterson decay curve, with children showing a steeper decay than adults. With no distracter, adults performed at ceiling level, but only when rehearsal was encouraged did the accuracy of recalling the trigrams in the Brown-Peterson task improve for children, resulting in similar performance as adults.
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Application of the anthropogenic allee effect model to trophy hunting as a conservation tool.
Conserv. Biol.
PUBLISHED: 03-28-2013
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Trophy hunting can provide economic incentives to conserve wild species, but it can also involve risk when rare species are hunted. The anthropogenic Allee effect (AAE) is a conceptual model that seeks to explain how rarity may spread the seeds of further endangerment. The AAE model has increasingly been invoked in the context of trophy hunting, increasing concerns that such hunting may undermine rather than enhance conservation efforts. We question the appropriateness of uncritically applying the AAE model to trophy hunting for 4 reasons. First, the AAE assumes an open-access resource, which is a poor characterization of most trophy-hunting programs and obscures the potential for state, communal, or private-property use rights to generate positive incentives for conservation. Second, study results that show the price of hunting increases as the rarity of the animal increases are insufficient to indicate the presence of AAE. Third, AAE ignores the existence of biological and behavioral factors operating in most trophy-hunting contexts that tend to regulate the effect of hunting. We argue that site-specific data, rather than aggregated hunting statistics, are required to demonstrate that patterns of unsustainable exploitation can be well explained by an AAE model. Instead, we suggest that conservation managers seeking to investigate and identify constraints that limit the potential conservation role of trophy hunting, should focus on the critical governance characteristics that shape the potential conservation role of trophy hunting, such as corruption, insecure property rights, and inadequate sharing of benefits with local people.
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Attenuation of LDHA expression in cancer cells leads to redox-dependent alterations in cytoskeletal structure and cell migration.
Cancer Lett.
PUBLISHED: 03-28-2013
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Aerobic glycolysis, the preferential use of glycolysis even in the presence of oxygen to meet cellular metabolic demands, is a near universal feature of cancer. This unique type of metabolism is thought to protect cancer cells from damaging reactive oxygen species (ROS) produced in the mitochondria. Using the cancer cell line MDA-MB-435 it is shown that shRNA mediated knockdown of lactate dehydrogenase A (LDHA), a key mediator of aerobic glycolysis, results in elevated mitochondrial ROS production and a concomitant decrease in cell proliferation and motility. Redox-sensitive proteins affected by oxidative stress associated with LDHA knockdown were identified by Redox 2D-PAGE and mass spectrometry. In particular, tropomyosin (Tm) isoforms Tm4, Tm5NM1 and Tm5NM5, proteins involved in cell migration and cytoskeletal dynamics, exhibited changes in disulfide bonding and co-localized with peri-nuclear actin aggregates in LDHA knockdown cells. In contrast, treatment with the thiol-based antioxidant N-acetylcysteine promoted the relocalization of Tms to cortical actin microfilaments and partially rescued the migration defects associated with attenuated LDHA expression. These results suggest that aerobic glycolysis and reduced mitochondrial ROS production create an environment conducive to cytoskeletal remodeling; key events linked to the high cell motility associated with cancer.
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Provisional report on diving-related fatalities in Australian waters 2008.
Diving Hyperb Med
PUBLISHED: 03-20-2013
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An individual case review of diving-related deaths, reported as occurring in Australia in 2008, was conducted as part of the DAN Asia-Pacific dive fatality reporting project.
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Augmented central pain processing in vulvodynia.
J Pain
PUBLISHED: 01-15-2013
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Vulvodynia (VVD) is a chronic pain disorder wherein women display sensitivity to evoked stimuli at the vulva and/or spontaneous vulvar pain. Our previous work suggests generalized hyperalgesia in this population; however, little is known about central neurobiological factors that may influence pain in VVD. Here we investigated local (vulvar) and remote (thumb) pressure-evoked pain processing in 24 VVD patients compared to 13 age-matched, pain-free healthy controls (HCs). As a positive control we also examined thumb pressure pain in 24 fibromyalgia patients. The VVD and fibromyalgia patients displayed overlapping insular brain activations that were greater than HCs in response to thumb stimulation (P < .005 corrected). Compared to HCs, VVD participants displayed greater levels of activation during thumb stimulation within the insula, dorsal midcingulate, posterior cingulate, and thalamus (P < .005 corrected). Significant differences between VVD subgroups (primary versus secondary and provoked versus unprovoked) were seen within the posterior cingulate with thumb stimulation and within the precuneus region with vulvar stimulation (provoked versus unprovoked only). The augmented brain activation in VVD patients in response to a stimulus remote from the vulva suggests central neural pathology in this disorder. Moreover, differing central activity between VVD subgroups suggests heterogeneous pathologies within this diagnosis.
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Understanding housing and health through the lens of transitional housing members in a high-incarceration Baltimore City neighborhood: the GROUP Ministries Photovoice Project to promote community redevelopment.
Health Place
PUBLISHED: 01-11-2013
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In this study we used photovoice to better understand transitional housing residents perceptions of housing and health at the individual and community levels. Discussion sessions were recorded, transcribed, and analyzed through a modified constant comparison approach. The results demonstrate that participants had a rich understanding of the complex connections between housing, neighborhood, and health that were intimately tied to the spatial concentration of incarceration in their community. The men identified social and physical sources of stress that manifest in a community-wide sense of hopelessness; however, utilization of community social networks and social capital provide opportunities for addressing these issues locally.
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Endocrine evaluation of children with and without Shwachman-Bodian-Diamond syndrome gene mutations and Shwachman-Diamond syndrome.
J. Pediatr.
PUBLISHED: 01-08-2013
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To characterize the endocrine phenotype of patients with Shwachman-Diamond syndrome (SDS).
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Backbone (1)H, (13)C, (15)N NMR assignments of yeast OMP synthase in unliganded form and in complex with orotidine 5-monophosphate.
Biomol NMR Assign
PUBLISHED: 01-04-2013
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The type I phosphoribosyltransferase OMP synthase (EC 2.4.2.10) is involved in de novo synthesis of pyrimidine nucleotides forming the UMP precursor orotidine 5-monophosphate (OMP). The homodimeric enzyme has a Rossman ?/? core topped by a base-enclosing "hood" domain and a flexible domain-swapped catalytic loop. High-resolution X-ray structures of the homologous Salmonella typhimurium and yeast enzymes show that a general compacting of the core as well as movement of the hood and a major disorder-to-order transition of the loop occur upon binding of ligands MgPRPP and orotate. Here we present backbone NMR assignments for the unliganded yeast enzyme (49 kDa) and its complex with product OMP. We were able to assign 212-213 of the 225 non-proline backbone (15)N and amide proton resonances. Significant difference in chemical shifts of the amide cross peaks occur in regions of the structure that undergo movement upon ligand occupancy in the S. typhimurium enzyme.
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Promoting smoke-free environments and tobacco cessation in residential treatment facilities for mental health and substance addictions, Oregon, 2010.
Prev Chronic Dis
PUBLISHED: 12-15-2011
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We assessed tobacco-related policies and procedures at all state-funded, community-based residential mental health and substance addiction treatment facilities before implementation of new state policy requirements. We conducted telephone interviews with 162 of 166 (98%) facility administrators. Only 15% had voluntarily implemented 100% smoke-free campus policies, and 47% offered cessation resources at patient discharge; however, less than 10% expressed opposition to these future requirements. Smoking bans and cessation support in residential treatment facilities can reduce tobacco-related disparities among people with mental illness and addictions, but states may need to be the catalyst for policy implementation.
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Masking level difference in an adaptive procedure for clinical investigation.
Int J Audiol
PUBLISHED: 07-01-2011
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Masking level difference (MLD) tests are an established component of auditory processing test batteries; however, normative data for these tests vary according to procedure. The purpose of this study was to establish a standardized procedure for clinical use in the measurement of the MLD.
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Impaired immune function in children with Fanconi anaemia.
Br. J. Haematol.
PUBLISHED: 05-04-2011
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Fanconi anaemia is an autosomal recessive or X-linked disease characterized by progressive bone marrow failure, variable congenital abnormalities and a predisposition to malignancy. Reports of immune function in this population are limited, and include only specific areas of immune performance, showing variable defects. We report a cross-sectional immunological assessment in 10 children with FA. Absolute numbers of B cells and natural killer (NK) cells were reduced compared to controls (P = 0·048 and P = 0·0002, respectively), while absolute number of T cells were within normal range. Perforin and granzyme content of NK cells was reduced (P < 0·00001 and P = 0·0057, respectively) along with the NK cell cytotoxicity (P < 0·001). Antigen proliferation in response to tetanus was decreased (P = 0·008) while responses to candida and phytohaemagglutinin were not. Cytotoxic T cell function was also reduced (P < 0·0001). Immunoglobulin G levels were normal in those evaluated. Our series represents the first attempt at a comprehensive quantitative and functional evaluation of immune function in this rare group of patients and demonstrates a significant deficit in the NK cell compartment, a novel quantitative B cell defect, along with abnormal cytotoxic function. These findings may be especially relevant in this patient population with known predisposition to DNA damage and malignancy.
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Activated ERK2 is a monomer in vitro with or without divalent cations and when complexed to the cytoplasmic scaffold PEA-15.
Biochemistry
PUBLISHED: 05-04-2011
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The extracellular signal-regulated protein kinase, ERK2, fully activated by phosphorylation and without a His(6) tag, shows little tendency to dimerize with or without either calcium or magnesium ions when analyzed by light scattering or analytical ultracentrifugation. Light scattering shows that ~90% of ERK2 is monomeric. Sedimentation equilibrium data (obtained at 4.8-11.2 ?M ERK2) with or without magnesium (10 mM) are well described by an ideal one-component model with a fitted molar mass of 40180 ± 240 Da (without Mg(2+) ions) or 41290 ± 330 Da (with Mg(2+) ions). These values, close to the sequence-derived mass of 41711 Da, indicate that no significant dimerization of ERK2 occurs in solution. Analysis of sedimentation velocity data for a 15 ?M solution of ERK2 with an enhanced van Holde-Weischet method determined the sedimentation coefficient (s) to be ~3.22 S for activated ERK2 with or without 10 mM MgCl(2). The frictional coefficient ratio (f/f(0)) of 1.28 calculated from the sedimentation velocity and equilibrium data is close to that expected for an ~42 kDa globular protein. The translational diffusion coefficient of ~8.3 × 10(-7) cm(2) s(-1) calculated from the experimentally determined molar mass and sedimentation coefficient agrees with the value determined by dynamic light scattering in the absence and presence of calcium or magnesium ions and a value determined by NMR spectrometry. ERK2 has been proposed to homodimerize and bind only to cytoplasmic but not nuclear proteins [Casar, B., et al. (2008) Mol. Cell 31, 708-721]. Our light scattering data show, however, that ERK2 forms a strong 1:1 complex of ~57 kDa with the cytoplasmic scaffold protein PEA-15. Thus, ERK2 binds PEA-15 as a monomer. Our data provide strong evidence that ERK2 is monomeric under physiological conditions. Analysis of the same ERK2 construct with the nonphysiological His(6) tag shows substantial dimerization under the same ionic conditions.
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Role of ?7 nicotinic acetylcholine receptors in regulating tumor necrosis factor-? (TNF-?) as revealed by subtype selective agonists.
J. Neuroimmunol.
PUBLISHED: 04-03-2011
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Immunological responses to protect against excessive inflammation can be regulated by the central nervous system through the cholinergic anti-inflammatory pathway wherein acetylcholine released from vagus nerves can inhibit inflammatory cytokines. Although a role for the ?7 nicotinic acetylcholine receptor (?7 nAChR) in mediating this pathway has been suggested, pharmacological modulation of the pathway by selective agonists remains to be further elucidated. In this study, the role of ?7 nAChRs in the regulation of TNF-? release was investigated using high affinity and selective ?7 nAChR agonists in mouse peritoneal macrophage and human whole blood in vitro, and in mouse serum in vivo. In mouse peritoneal macrophages, LPS-induced TNF-? release in vitro was inhibited by a selective ?7 nAChR agonist, A-833834 (5-[6-(5-Methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-pyridazin-3-yl]-1H-indole), and that effect was attenuated by ?7 nAChR antagonist methyllycaconitine. The inhibitory effect of A-833834 on LPS-induced TNF-? release was also observed in human whole blood in vitro. I.v. LPS-induced TNF-? release in mouse serum was attenuated following i.p. administration of A-833834. Similarly, i.v. LPS-induced TNF-? release in mouse serum was also attenuated following i.p. administration of A-585539, another ?7 nAChR agonist with limited brain penetration, suggesting that these effects are mediated by peripheral ?7 nAChRs. A-833834 was also efficacious in suppressing TNF-? release in mouse serum following oral administration in zymosan-induced peritonitis. These studies collectively demonstrate that selectively targeting ?7 nAChRs could offer a novel therapeutic modality to treat acute and chronic inflammatory disease states.
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Fibromyalgia: an afferent processing disorder leading to a complex pain generalized syndrome.
Pain Physician
PUBLISHED: 03-18-2011
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Fibromyalgia is a condition which appears to involve disordered central afferent processing. The major symptoms of fibromyalgia include multifocal pain, fatigue, sleep disturbances, and cognitive or memory problems. Other symptoms may include psychological distress, impaired functioning, and sexual dysfunction. The pathophysiology of fibromyalgia remains uncertain but is believed to be largely central in nature. In 1990 the American College of Rheumatology (ACR) published diagnostic research criteria for fibromyalgia. The criteria included a history of chronic and widespread pain and the presence of 11 or more out of 18 tender points. Pain was considered chronic widespread when all of the following are present: pain in the left side of the body; pain in the right side of the body; pain above the waist; pain below the waist. In addition, axial skeletal pain must be present and the duration of pain must be more than 3 months. A tender point is considered positive when pain can be elicited by pressures of 4 kg/cm2 or less. For tender points to be considered positive, the patient must perceive the palpation as painful; tenderness to palpation is not sufficient. However, over the next 20 years it became increasingly appreciated that the focus on tender points was not justified. In 2010 a similar group of investigators performed a multicenter study of 829 previously diagnosed fibromyalgia patients and controls using physician physical and interview examinations, including a widespread pain index (WPI), a measure of the number of painful body regions. Random forest and recursive partitioning analyses were used to guide the development of a case definition of fibromyalgia, to develop new preliminary ACR diagnostic criteria, and to construct a symptom severity (SS) scale. The most important diagnostic variables were WPI and categorical scales for cognitive symptoms, un-refreshed sleep, fatigue, and number of somatic symptoms. The categorical scales were summed to create an SS scale. The investigators combined the SS scale and the WPI to recommend a new case definition of fibromyalgia: (WPI > or = 7 AND SS > or = 5). Although there is no known cure for fibromyalgia, multidisciplinary team efforts using combined treatment approaches, including patient education, aerobic exercise, cognitive behavioral therapy, and pharmacologic therapies (serotonin norepinephrine reuptake inhibitors [e.g., duloxetine, milnacipran] and alpha 2-delta receptor ligands [e.g., pregabalin]) might improve symptoms as well as function in patients with fibromyalgia.
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The development of psychometrically equivalent Cantonese speech audiometry materials.
Int J Audiol
PUBLISHED: 02-16-2011
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The aim of this study was to develop and psychometrically evaluate speech audiometry materials that can be used to measure word recognition (WR) and speech recognition testing (SRT) in quiet for native speakers of Cantonese.
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The clinical phenotype of children with Fanconi anemia caused by biallelic FANCD1/BRCA2 mutations.
Pediatr Blood Cancer
PUBLISHED: 01-29-2011
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Fanconi anemia (FA) is characterized by progressive marrow failure, congenital anomalies, and predisposition to malignancy. Biallelic FANCD1/BRCA2 mutations are the genetic basis of disease in a small proportion of children with FA with earlier onset and increased incidence of leukemia and solid tumors. Patients with FA have increased sensitivity to chemotherapy and radiation, and upon development of a solid tumor, require modification of these therapies. We report clinical and molecular features of three patients with FA associated with FANCD1/BRCA2 mutations, including two novel mutations, and discuss treatment of malignancy and associated side effects in this particularly vulnerable group.
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The talk of the town: kit manufacturers negotiate the building industry, 1905-1929.
J Urban Hist
PUBLISHED: 12-15-2010
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Urban historical scholars have neglected smaller urban centers, including their residential environments and the forces that shaped them. For a time, one of these forces was the mail-order kit home. Kit manufacturers sold houses to families throughout the United States and Canada but enjoyed their greatest success in small towns where detached single-family homes were the norm. They worked to insert themselves into local building industries: They challenged lumber dealers and ignored architects but strove to mollify the contractors on whom they and their customers depended. They attracted considerable attention and met with initial success: Emerging rapidly after 1905, they had hit their stride by 1914 and enjoyed a heyday in the 1920s. They were stricken by, and failed to recover from, the Depression in large part because lumber dealers had learned how to compete with them.
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The impact of conservation on the status of the worlds vertebrates.
Michael Hoffmann, Craig Hilton-Taylor, Ariadne Angulo, Monika Böhm, Thomas M Brooks, Stuart H M Butchart, Kent E Carpenter, Janice Chanson, Ben Collen, Neil A Cox, William R T Darwall, Nicholas K Dulvy, Lucy R Harrison, Vineet Katariya, Caroline M Pollock, Suhel Quader, Nadia I Richman, Ana S L Rodrigues, Marcelo F Tognelli, Jean-Christophe Vié, John M Aguiar, David J Allen, Gerald R Allen, Giovanni Amori, Natalia B Ananjeva, Franco Andreone, Paul Andrew, Aida Luz Aquino Ortiz, Jonathan E M Baillie, Ricardo Baldi, Ben D Bell, S D Biju, Jeremy P Bird, Patricia Black-Decima, J Julian Blanc, Federico Bolaños, Wilmar Bolivar-G, Ian J Burfield, James A Burton, David R Capper, Fernando Castro, Gianluca Catullo, Rachel D Cavanagh, Alan Channing, Ning Labbish Chao, Anna M Chenery, Federica Chiozza, Viola Clausnitzer, Nigel J Collar, Leah C Collett, Bruce B Collette, Claudia F Cortez Fernandez, Matthew T Craig, Michael J Crosby, Neil Cumberlidge, Annabelle Cuttelod, Andrew E Derocher, Arvin C Diesmos, John S Donaldson, J W Duckworth, Guy Dutson, S K Dutta, Richard H Emslie, Aljos Farjon, Sarah Fowler, Jörg Freyhof, David L Garshelis, Justin Gerlach, David J Gower, Tandora D Grant, Geoffrey A Hammerson, Richard B Harris, Lawrence R Heaney, S Blair Hedges, Jean-Marc Hero, Baz Hughes, Syed Ainul Hussain, Javier Icochea M, Robert F Inger, Nobuo Ishii, Djoko T Iskandar, Richard K B Jenkins, Yoshio Kaneko, Maurice Kottelat, Kit M Kovacs, Sergius L Kuzmin, Enrique La Marca, John F Lamoreux, Michael W N Lau, Esteban O Lavilla, Kristin Leus, Rebecca L Lewison, Gabriela Lichtenstein, Suzanne R Livingstone, Vimoksalehi Lukoschek, David P Mallon, Philip J K McGowan, Anna McIvor, Patricia D Moehlman, Sanjay Molur, Antonio Muñoz Alonso, John A Musick, Kristin Nowell, Ronald A Nussbaum, Wanda Olech, Nikolay L Orlov, Theodore J Papenfuss, Gabriela Parra-Olea, William F Perrin, Beth A Polidoro, Mohammad Pourkazemi, Paul A Racey, James S Ragle, Mala Ram, Galen Rathbun, Robert P Reynolds, Anders G J Rhodin, Stephen J Richards, Lily O Rodriguez, Santiago R Ron, Carlo Rondinini, Anthony B Rylands, Yvonne Sadovy de Mitcheson, Jonnell C Sanciangco, Kate L Sanders, Georgina Santos-Barrera, Jan Schipper, Caryn Self-Sullivan, Yichuan Shi, Alan Shoemaker, Frederick T Short, Claudio Sillero-Zubiri, Débora L Silvano, Kevin G Smith, Andrew T Smith, Jos Snoeks, Alison J Stattersfield, Andrew J Symes, Andrew B Taber, Bibhab K Talukdar, Helen J Temple, Rob Timmins, Joseph A Tobias, Katerina Tsytsulina, Denis Tweddle, Carmen Ubeda, Sarah V Valenti, Peter Paul van Dijk, Liza M Veiga, Alberto Veloso, David C Wege, Mark Wilkinson, Elizabeth A Williamson, Feng Xie, Bruce E Young, H Resit Akçakaya, Leon Bennun, Tim M Blackburn, Luigi Boitani, Holly T Dublin, Gustavo A B da Fonseca, Claude Gascon, Thomas E Lacher, Georgina M Mace, Susan A Mainka, Jeffery A McNeely, Russell A Mittermeier, Gordon McGregor Reid, Jon Paul Rodríguez, Andrew A Rosenberg, Michael J Samways, Jane Smart, Bruce A Stein, Simon N Stuart.
Science
PUBLISHED: 10-26-2010
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Using data for 25,780 species categorized on the International Union for Conservation of Nature Red List, we present an assessment of the status of the worlds vertebrates. One-fifth of species are classified as Threatened, and we show that this figure is increasing: On average, 52 species of mammals, birds, and amphibians move one category closer to extinction each year. However, this overall pattern conceals the impact of conservation successes, and we show that the rate of deterioration would have been at least one-fifth again as much in the absence of these. Nonetheless, current conservation efforts remain insufficient to offset the main drivers of biodiversity loss in these groups: agricultural expansion, logging, overexploitation, and invasive alien species.
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Elevated excitatory neurotransmitter levels in the fibromyalgia brain.
Arthritis Res. Ther.
PUBLISHED: 10-01-2010
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Consistent brain imaging findings demonstrate that neurobiological factors may contribute to the pathology of central pain states such as fibromyalgia (FM). Studies using proton magnetic resonance spectroscopy suggest that glutamate (Glu), a key excitatory neurotransmitter, may be present in higher concentrations within the brains of FM patients. This neurotransmitter imbalance is present in multiple brain regions that have been implicated in processing pain information. However, it is unknown if elevated Glu is acting at the synapse. New investigations are needed to investigate the molecular action of Glu in FM and to investigate these findings during treatment that modulates glutamatergic neurotransmission.
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Optimization of therapy for severe aplastic anemia based on clinical, biologic, and treatment response parameters: conclusions of an international working group on severe aplastic anemia convened by the Blood and Marrow Transplant Clinical Trials Network,
Biol. Blood Marrow Transplant.
PUBLISHED: 09-17-2010
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Although recent advances in therapy offer the promise for improving survival in patients with severe aplastic anemia (SAA), the small size of the patient population, lack of a mechanism in North America for longitudinal follow-up of patients, and inadequate cooperation among hematologists, scientists, and transplant physicians remain obstacles to conducting large studies that would advance the field. To address this issue, the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) convened a group of international experts in March 2010 to define the most important questions in the basic science, immunosuppressive therapy (IST), and bone marrow transplantation (BMT) of SAA and propose initiatives to facilitate clinical and biologic research. Key conclusions of the working group were: (1) new patients should obtain accurate, expert diagnosis and early identification of biologic risk; (2) a population-based SAA outcomes registry should be established in North America to collect data on patients longitudinally from diagnosis through and after treatment; (3) a repository of biologic samples linked to the clinical data in the outcomes registry should be developed; (4) innovative approaches to unrelated donor BMT that decrease graft-versus-host disease are needed; and (5) alternative donor transplantation approaches for patients lacking HLA-matched unrelated donors must be improved. A partnership of BMT, IST, and basic science researchers will develop initiatives and partner with advocacy and funding organizations to address these challenges. Collaboration with similar study groups in Europe and Asia will be pursued.
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Before the measurement of prejudice: early psychological and sociological papers on prejudice.
J Hist Behav Sci
PUBLISHED: 07-13-2010
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Given its renown, many psychologists and sociologists likely consider the publication of Gordon Allports (1954/1979) seminal book The Nature of Prejudice as the inauguration of the psychological study of prejudice. However, we have uncovered rarely-cited, published papers (starting in 1830) that provide a wealth of speculation on prejudice even before psychologists/sociologists attempted to measure it (circa 1925). Thus, this paper intends to discuss early published work on prejudice in psychology and sociology by focusing on three key questions: a) when did psychologists/sociologists recognize prejudice as a psychological phenomenon, b) when did psychologists/sociologists recognize prejudice as a phenomenon in need of study, and c) what were the historical and personal conditions that gave rise to the interest in prejudice? In short, the seeds of prejudice research were maturing for some time before Allports seminal book and the first attitudinal studies on prejudice, although these earlier works are seldom cited.
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Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity.
Arthritis Rheum.
PUBLISHED: 05-28-2010
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Fibromyalgia (FM) is considered to be the prototypical central chronic pain syndrome and is associated with widespread pain that fluctuates spontaneously. Multiple studies have demonstrated altered brain activity in these patients. The objective of this study was to investigate the degree of connectivity between multiple brain networks in patients with FM, as well as how activity in these networks correlates with the level of spontaneous pain.
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Increased anterior brain activation to correct responses on high-conflict Stroop task in obsessive-compulsive disorder.
Clin Neurophysiol
PUBLISHED: 05-25-2010
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An abnormally increased activation in anterior brain networks, accompanied by normal task performance, has been reported in studies on biological mechanisms of obsessive-compulsive disorder (OCD). We test a hypothesis, that this phenomenon, deemed specific to OCD, will be compromised by a very difficult task, which may lead to reduced cortical information processing and erroneous performance, as found in other disorders such as schizophrenia.
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Autologous peripheral blood stem cell transplantation in children with refractory or relapsed lymphoma: results of Childrens Oncology Group study A5962.
Biol. Blood Marrow Transplant.
PUBLISHED: 05-12-2010
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This prospective study was designed to determine the safety and efficacy of cyclophosphamide, BCNU, and etoposide (CBV) conditioning and autologous peripheral blood stem cell transplant (PBSCT) in children with relapsed or refractory Hodgkin and non-Hodgkin lymphoma (HL and NHL). Patients achieving complete remission (CR) or partial remission (PR) after 2 to 4 courses of reinduction underwent a granulocyte-colony stimulating factor (G-CSF) mobilized PBSC apheresis with a target collection dose of 5 × 10? CD34(+)/kg. Those eligible to proceed received autologous PBSCT after CBV (7200 mg/m², 450-300 mg/m², 2400 mg/m²). Forty-three of 69 patients (30/39 HL, 13/30 NHL) achieved a CR/PR after reinduction. Thirty-eight patients (28 HL, 10 NHL) underwent PBSCT. All initial 6 patients who received BCNU at 450 mg/m² experienced grade III or IV pulmonary toxicity compared to none of the subsequent 32 receiving 300 mg/m² (P < .0001). The probability of overall survival (OS) at 3 years for all patients is 51% and for transplanted patients is 64%. The 3-year event-free survival (EFS) is 38% (45% for HL; 30% NHL). The 3-year EFS in transplanted patients is 66% (65% HL; 70% NHL). Initial duration of remission of ?12 versus <12 months was associated with a significant increase in OS (3 years OS 70% versus 34%) (P = .003). BCNU at 300 mg/m(2) in a CBV regimen prior to PBSCT is well tolerated in relapsed or refractory pediatric lymphoma patients. A short duration (<12 months) of initial remission is associated with a poorer prognosis. Last, a high percentage of patients achieving a CR/PR after reinduction therapy can be salvaged with CBV and autologlous PBSCT.
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Backbone 1H, 13C, 15N NMR assignments of the unliganded and substrate ternary complex forms of mevalonate diphosphate decarboxylase from Streptococcus pneumoniae.
Biomol NMR Assign
PUBLISHED: 05-11-2010
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Mevalonate diphosphate decarboxylase (MDD) catalyzes the ATP-dependent decarboxylation of diphosphomevalonate (DPM) to produce isopentenyl diphosphate (IPP), the molecular "building block" for more than 25,000 distinct isoprenoids, including cholesterol, steroid hormones and terpenoids. Here, we present the first backbone assignment of Streptococcus pneumoniae MDD in the unliganded state and in a ternary complex with DPM and AMPPCP--a nucleotide analogue unable to transfer the ?-phosphoryl group. The secondary chemical shifts for the unliganded form are in good agreement with the crystal structure of Streptococcus pyogenes (~70% sequence identity). The addition of substrate and nucleotide to the enzyme results in chemical shift changes of cross peaks that correspond to residues in the binding pocket.
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Catechol O-methyltransferase haplotype predicts immediate musculoskeletal neck pain and psychological symptoms after motor vehicle collision.
J Pain
PUBLISHED: 04-17-2010
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Genetic variations in the catechol-O-methyltransferase (COMT) gene have been associated with experimental pain and risk of chronic pain development, but no studies have examined genetic predictors of neck pain intensity and other patient characteristics after motor vehicle collision (MVC). We evaluated the association between COMT genotype and acute neck pain intensity and other patient characteristics in 89 Caucasian individuals presenting to the emergency department (ED) after MVC. In the ED in the hours after MVC, individuals with a COMT pain vulnerable genotype were more likely to report moderate-to-severe musculoskeletal neck pain (76 versus 41%, RR = 2.11 (1.33-3.37)), moderate or severe headache (61 versus 33%, RR = 3.15 (1.05-9.42)), and moderate or severe dizziness (26 versus 12%, RR = 1.97 (1.19-3.21)). Individuals with a pain vulnerable genotype also experienced more dissociative symptoms in the ED, and estimated a longer time to physical recovery (median 14 versus 7 days, P = .002) and emotional recovery (median 8.5 versus 7 days, P = .038). These findings suggest that genetic variations affecting stress response system function influence the somatic and psychological response to MVC, and provide the first evidence of genetic risk for clinical symptoms after MVC.
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Alcohol-related emergency department attendances: is preloading a risk factor? Cross-sectional survey.
Int J Emerg Med
PUBLISHED: 04-12-2010
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Preloading is a phenomenon where people drink alcohol at a private residence before going out. We aimed to identify whether preloading is a risk factor for alcohol-related emergency department attendance. We also wanted to identify where people became injured or unwell.
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Paradoxes in acupuncture research: strategies for moving forward.
Evid Based Complement Alternat Med
PUBLISHED: 04-05-2010
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In November 2007, the Society for Acupuncture Research (SAR) held an international symposium to mark the 10th anniversary of the 1997 NIH Consensus Development Conference on Acupuncture. The symposium presentations revealed the considerable maturation of the field of acupuncture research, yet two provocative paradoxes emerged. First, a number of well-designed clinical trials have reported that true acupuncture is superior to usual care, but does not significantly outperform sham acupuncture, findings apparently at odds with traditional theories regarding acupuncture point specificity. Second, although many studies using animal and human experimental models have reported physiological effects that vary as a function of needling parameters (e.g., mode of stimulation) the extent to which these parameters influence therapeutic outcomes in clinical trials is unclear. This White Paper, collaboratively written by the SAR Board of Directors, identifies gaps in knowledge underlying the paradoxes and proposes strategies for their resolution through translational research. We recommend that acupuncture treatments should be studied (1) "top down" as multi-component "whole-system" interventions and (2) "bottom up" as mechanistic studies that focus on understanding how individual treatment components interact and translate into clinical and physiological outcomes. Such a strategy, incorporating considerations of efficacy, effectiveness and qualitative measures, will strengthen the evidence base for such complex interventions as acupuncture.
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1H, 13C, 15N backbone NMR assignments of the Staphylococcus aureus small multidrug-resistance pump (Smr) in a functionally active conformation.
Biomol NMR Assign
PUBLISHED: 03-23-2010
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The plasmid-encoded small multidrug resistance pump from S. aureus transports a variety of quaternary ammonium and other hydrophobic compounds, enhancing the bacterial hosts resistance to common hospital disinfectants. The protein folds as a homo-dimer of four transmembrane helices each, and appears to be fully functional only in lipid bilayers. Here we report the backbone resonance assignments and implied secondary structure for (2)H(13)C(15)N Smr reconstituted into lipid bicelles. Significant changes were observed between the chemical shifts of the protein in lipid bicelles compared to those in detergent micelles.
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Relaxation acupressure reduces persistent cancer-related fatigue.
Evid Based Complement Alternat Med
PUBLISHED: 02-17-2010
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Persistent cancer-related fatigue (PCRF) is a symptom experienced by many cancer survivors. Acupressure offers a potential treatment for PCRF. We investigated if acupressure treatments with opposing actions would result in differential effects on fatigue and examined the effect of different "doses" of acupressure on fatigue. We performed a trial of acupressure in cancer survivors experiencing moderate to severe PCRF. Participants were randomized to one of three treatment groups: relaxation acupressure (RA), high-dose stimulatory acupressure (HIS), and low-dose stimulatory acupressure (LIS). Participants performed acupressure for 12-weeks. Change in fatigue as measured by the Brief Fatigue Inventory (BFI) was our primary outcome. Secondary outcomes were assessment of blinding and compliance to treatment. Fatigue was significantly reduced across all treatment groups (mean ± SD reduction in BFI: RA 4.0 ± 1.5, HIS 2.2 ± 1.6, LIS 2.7 ± 2.2), with significantly greater reductions in the RA group. In an adjusted analysis, RA resulted in significantly less fatigue after controlling for age, cancer type, cancer stage, and cancer treatments. Self-administered RA caused greater reductions in fatigue compared to either HIS or LIS. The magnitude of the reduction in fatigue was clinically relevant and could represent a viable alternative for cancer survivors with PCRF.
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Numerical chromosomal changes and risk of development of myelodysplastic syndrome--acute myeloid leukemia in patients with Fanconi anemia.
Cancer Genet. Cytogenet.
PUBLISHED: 01-14-2010
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Fanconi Anemia (FA) is an inherited bone marrow failure syndrome characterized by congenital abnormalities, progressive marrow failure and predisposition to myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and solid tumors. The most common acquired chromosomal aberrations in FA patients are trisomy of 1q and monosomy of chromosome 7; the latter is known to be associated with poor prognosis. A few reports also suggest that gains of 3q are associated with progression to MDS-AML and overall poor prognosis. It is not uncommon for patients with Fanconi anemia to have easily detectable (oligoclonal) chromosomal alterations in their still normal (nonmalignant) marrow, which makes it even more challenging to determine the import of such alterations. We conducted a retrospective longitudinal analysis of fluorescent in situ hybridization (FISH) analysis for gains in 1q and 3q and for monosomy 7 and 7q deletions on 212 bone marrow samples from 77 children with FA treated at our institution between 1987 and 2007. Given the baseline increased chromosomal instability and defective DNA repair in patients with FA, which leads to unbalanced chromosomal aberrations such as deletions, insertions, and translocations, for the purpose of this analysis an abnormal clone was defined as ?10% abnormal cells. Chromosome 3 and 7 aberrations were associated with increased risk of developing MDS-AML (P = 0.019 and P < 0.001 respectively), although the significance of chromosome 3 aberrations disappeared when different observation times were accounted for. Gain of 1q alone did not predict development of MDS-AML. In conclusion, children with FA should be followed closely with FISH analyses, because some of the clonal chromosomal abnormalities may be early indicators of progression toward MDS-AML and thus also of the need for hematopoietic stem cell transplantation.
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SCY-635, a novel nonimmunosuppressive analog of cyclosporine that exhibits potent inhibition of hepatitis C virus RNA replication in vitro.
Antimicrob. Agents Chemother.
PUBLISHED: 11-23-2009
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SCY-635 is a novel nonimmunosuppressive cyclosporine-based analog that exhibits potent suppression of hepatitis C virus (HCV) replication in vitro. SCY-635 inhibited the peptidyl prolyl isomerase activity of cyclophilin A at nanomolar concentrations but showed no detectable inhibition of calcineurin phosphatase activity at concentrations up to 2 microM. Metabolic studies indicated that SCY-635 did not induce the major cytochrome P450 enzymes 1A2, 2B6, and 3A4. SCY-635 was a weak inhibitor and a poor substrate for P-glycoprotein. Functional assays with stimulated Jurkat cells and stimulated human peripheral blood mononuclear cells indicated that SCY-635 is a weaker inhibitor of interleukin-2 secretion than cyclosporine. A series of two-drug combination studies was performed in vitro. SCY-635 exhibited synergistic antiviral activity with alpha interferon 2b and additive antiviral activity with ribavirin. SCY-635 was shown to be orally bioavailable in multiple animal species and produced blood and liver concentrations of parent drug that exceeded the 50% effective dose determined in the bicistronic con1b-derived replicon assay. These results suggest that SCY-635 warrants further investigation as a novel therapeutic agent for the treatment of individuals who are chronically infected with HCV.
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Radiographic assessment of biomechanical parameters following hip resurfacing and cemented total hip arthroplasty.
Hip Int
PUBLISHED: 11-06-2009
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Resurfacing hip arthroplasty and total hip replacement both aim to restore anatomical parameters.Leg length and offset discrepancy can result in altered joint reaction forces, and are associated with increased wear, dislocation, and decreased patient satisfaction. This study assesses the accuracy of leg length and offset restoration after either a Birmingham Hip Resurfacing (BHR) or a cemented total hip replacement (THR).Standardised antero-posterior radiography was performed on two groups of 30 patients with unilateral primary osteoarthritis undergoing either a cemented total hip or resurfacing. The normal contra-lateral hip was used as the control. Leg length and offset were measured pre-operatively with no significant difference between the two groups.Cup offset, femoral offset, total offset and leg length of the prosthesis and normal side were measured by two observers and mean measurements were analysed by a paired t test.Leg lengths in each group did not differ significantly from the normal side, THR 0.53 mm (95% CI -2.4 to 3.4 mm) but BHR implantation did result in mean leg shortening of -1.9 mm (95% CI -4.5 mm to 0.6mm). Cup offset differed significantly from normal anatomy in both groups, as did femoral and total offset for the total hip replacement group. However, femoral offset was restored in the Birmingham resurfacing group. When the THR group was compared against the BHR group we found no difference between restoration of leg lengths (p = 0.21) and cup offset (p = 0.30) but femoral (p = 0.0063) and total offset (p = 0.03) were restored more accurately with a BHR.
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Elevated insular glutamate in fibromyalgia is associated with experimental pain.
Arthritis Rheum.
PUBLISHED: 10-01-2009
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Central pain augmentation resulting from enhanced excitatory and/or decreased inhibitory neurotransmission is a proposed mechanism underlying the pathophysiology of functional pain syndromes such as fibromyalgia (FM). Multiple functional magnetic resonance imaging studies implicate the insula as a region of heightened neuronal activity in this condition. Since glutamate (Glu) is a major cortical excitatory neurotransmitter that functions in pain neurotransmission, we undertook this study to test our hypothesis that increased levels of insular Glu would be present in FM patients and that the concentration of this molecule would be correlated with pain report.
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Genitourinary infection and barotrauma as complications of P-valve use in drysuit divers.
Diving Hyperb Med
PUBLISHED: 06-19-2009
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Drysuits are commonly worn by divers undertaking long exposures in cold water. The need to urinate during such dives leads to the use of a variety of devices to conduct urine from the diver to the ambient water. The final common pathway to the water is via a suit bulkhead known as a P-valve. Use of the various urinary devices and P-valve can lead to a number of complications including urogenital sepsis, pneumaturia and genital squeeze. The urinary devices in current use are described, then four clinical cases that illustrate the complications are presented. Recommendations for prevention of these complications are made.
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Solution structure and phylogenetics of Prod1, a member of the three-finger protein superfamily implicated in salamander limb regeneration.
PLoS ONE
PUBLISHED: 06-17-2009
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Following the amputation of a limb, newts and salamanders have the capability to regenerate the lost tissues via a complex process that takes place at the site of injury. Initially these cells undergo dedifferentiation to a state competent to regenerate the missing limb structures. Crucially, dedifferentiated cells have memory of their level of origin along the proximodistal (PD) axis of the limb, a property known as positional identity. Notophthalmus viridescens Prod1 is a cell-surface molecule of the three-finger protein (TFP) superfamily involved in the specification of newt limb PD identity. The TFP superfamily is a highly diverse group of metazoan proteins that includes snake venom toxins, mammalian transmembrane receptors and miscellaneous signaling molecules.
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Characterization of phospholipase C gamma enzymes with gain-of-function mutations.
J. Biol. Chem.
PUBLISHED: 06-16-2009
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Phospholipase C gamma isozymes (PLC gamma 1 and PLC gamma 2) have a crucial role in the regulation of a variety of cellular functions. Both enzymes have also been implicated in signaling events underlying aberrant cellular responses. Using N-ethyl-N-nitrosourea (ENU) mutagenesis, we have recently identified single point mutations in murine PLC gamma 2 that lead to spontaneous inflammation and autoimmunity. Here we describe further, mechanistic characterization of two gain-of-function mutations, D993G and Y495C, designated as ALI5 and ALI14. The residue Asp-993, mutated in ALI5, is a conserved residue in the catalytic domain of PLC enzymes. Analysis of PLC gamma 1 and PLC gamma 2 with point mutations of this residue showed that removal of the negative charge enhanced PLC activity in response to EGF stimulation or activation by Rac. Measurements of PLC activity in vitro and analysis of membrane binding have suggested that ALI5-type mutations facilitate membrane interactions without compromising substrate binding and hydrolysis. The residue mutated in ALI14 (Tyr-495) is within the spPH domain. Replacement of this residue had no effect on folding of the domain and enhanced Rac activation of PLC gamma 2 without increasing Rac binding. Importantly, the activation of the ALI14-PLC gamma 2 and corresponding PLC gamma 1 variants was enhanced in response to EGF stimulation and bypassed the requirement for phosphorylation of critical tyrosine residues. ALI5- and ALI14-type mutations affected basal activity only slightly; however, their combination resulted in a constitutively active PLC. Based on these data, we suggest that each mutation could compromise auto-inhibition in the inactive PLC, facilitating the activation process; in addition, ALI5-type mutations could enhance membrane interaction in the activated state.
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A follow up audit of pharyngeal pouch surgery using endoscopic stapling.
Eur Arch Otorhinolaryngol
PUBLISHED: 04-20-2009
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The aim of this study is to assess patient satisfaction, success at controlling symptoms and conversion rates to open surgery in patients undergoing pharyngeal pouch surgery using an endoscopic stapler in a second cycle of audit. The design consisted of a review of patient records augmented by an electronic search of operation codes in the hospitals theatre records. The setting was in Worcester Royal Hospital, BUPA Southbank Hospital and Hereford Hospital, UK. Participants include all patients with pharyngeal pouches undergoing endoscopic pharyngeal pouch repair by the senior author between July 2002 and July 2007. The total number of participants was 31. All patients were undergoing treatment for the first time. The main outcome measures were pre- and postoperative symptom prevalence, conversion rates to open surgery, patient satisfaction. Endoscopic pharyngeal pouch surgery was successful in the vast majority of cases, with 97% of patients being satisfied with the result. The conversion rate to open surgery was 9.7%. These figures are improved from the last round of audit. In conclusion, endoscopic surgery to treat pharyngeal pouches is safe, effective and patient selection is improving. A modified method of endoscopy using a Negus scope rather than a Baldwin scope has allowed more patients to be treated via endoscopic methods. Open surgery is still required in some patients.
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Health status, not head injury, predicts concussion symptoms after minor injury.
Am J Emerg Med
PUBLISHED: 04-18-2009
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Postconcussion (PC) syndrome etiology remains poorly understood. We sought to examine predictors of persistent PC symptoms after minor injury.
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Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on mu-opioid receptors (MORs).
Neuroimage
PUBLISHED: 04-10-2009
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Controversy remains regarding the mechanisms of acupuncture analgesia. A prevailing theory, largely unproven in humans, is that it involves the activation of endogenous opioid antinociceptive systems and mu-opioid receptors (MORs). This is also a neurotransmitter system that mediates the effects of placebo-induced analgesia. This overlap in potential mechanisms may explain the lack of differentiation between traditional acupuncture and either non-traditional or sham acupuncture in multiple controlled clinical trials. We compared both short- and long-term effects of traditional Chinese acupuncture (TA) versus sham acupuncture (SA) treatment on in vivo MOR binding availability in chronic pain patients diagnosed with fibromyalgia (FM). Patients were randomized to receive either TA or SA treatment over the course of 4 weeks. Positron emission tomography (PET) with (11)C-carfentanil was performed once during the first treatment session and then repeated a month later following the eighth treatment. Acupuncture therapy evoked short-term increases in MOR binding potential, in multiple pain and sensory processing regions including the cingulate (dorsal and subgenual), insula, caudate, thalamus, and amygdala. Acupuncture therapy also evoked long-term increases in MOR binding potential in some of the same structures including the cingulate (dorsal and perigenual), caudate, and amygdala. These short- and long-term effects were absent in the sham group where small reductions were observed, an effect more consistent with previous placebo PET studies. Long-term increases in MOR BP following TA were also associated with greater reductions in clinical pain. These findings suggest that divergent MOR processes may mediate clinically relevant analgesic effects for acupuncture and sham acupuncture.
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Brain encoding of acupuncture sensation--coupling on-line rating with fMRI.
Neuroimage
PUBLISHED: 04-08-2009
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Acupuncture-induced sensations have historically been associated with clinical efficacy. These sensations are atypical, arising from sub-dermal receptors, and their neural encoding is not well known. In this fMRI study, subjects were stimulated at acupoint PC-6, while rating sensation with a custom-built, MR-compatible potentiometer. Separate runs included real (ACUP) and sham (SHAM) acupuncture, the latter characterized by non-insertive, cutaneous stimulation. FMRI data analysis was guided by the on-line rating timeseries, thereby localizing brain correlates of acupuncture sensation. Sensation ratings correlated with stimulation more (p<0.001) for SHAM (r=0.63) than for ACUP (r=0.32). ACUP induced stronger and more varied sensations with significant persistence into no-stimulation blocks, leading to more run-time spent rating low and moderate sensations compared to SHAM. ACUP sensation correlated with activation in regions associated with sensorimotor (SII, insula) and cognitive (dorsomedial prefrontal cortex (dmPFC)) processing, and deactivation in default-mode network (DMN) regions (posterior cingulate, precuneus). Compared to SHAM, ACUP yielded greater activity in both anterior and posterior dmPFC and dlPFC. In contrast, SHAM produced greater activation in sensorimotor (SI, SII, insula) and greater deactivation in DMN regions. Thus, brain encoding of ACUP sensation (more persistent and varied, leading to increased cognitive load) demonstrated greater activity in both cognitive/evaluative (posterior dmPFC) and emotional/interoceptive (anterior dmPFC) cortical regions. Increased cognitive load and dmPFC activity may be a salient component of acupuncture analgesia--sensations focus attention and accentuate bodily awareness, contributing to enhanced top-down modulation of any nociceptive afference and central pain networks. Hence, acupuncture may function as a somatosensory-guided mind-body therapy.
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Behavioral profile of P2X7 receptor knockout mice in animal models of depression and anxiety: relevance for neuropsychiatric disorders.
Behav. Brain Res.
PUBLISHED: 03-31-2009
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The purinergic P2X(7) receptor is a ligand-gated ion channel found on peripheral macrophages and microglia in the nervous system. Activation of P2X(7) receptors results in the rapid release of interleukin-1 beta (IL-1 beta). Cytokines like IL-1 beta are suggested to be involved in the pathophysiology of depression. The aim of this study was to behaviorally profile P2X(7) receptor knockout (KO) mice in behavioral models of depression- and anxiety-like behaviors. P2X(7) receptor KO and wild type (WT) mice were tested in multiple models including; forced swim test, tail suspension test, elevated plus maze, novelty suppressed feeding, spontaneous locomotor activity, and food intake. P2X(7) receptor KO mice exhibited an antidepressant-like profile in tail suspension test and forced swim test; an effect that was not associated with changes in spontaneous locomotor activity. In addition, P2X(7) receptor KO mice showed higher responsivity to a subefficacious dose of the antidepressant drug imipramine (15 mg/kg) in forced swim test. No significant differences between genotypes were observed in models of anxiety. These data support the relevance of pro-inflammatory cytokines in depressive-like states, and suggest that P2X(7) receptor antagonists could be of potential interest for the treatment of affective disorders.
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Time-variant fMRI activity in the brainstem and higher structures in response to acupuncture.
Neuroimage
PUBLISHED: 03-23-2009
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Acupuncture modulation of activity in the human brainstem is not well known. This structure is plagued by physiological artifact in neuroimaging experiments. In addition, most studies have used short (<15 min) block designs, which miss delayed responses following longer duration stimulation. We used brainstem-focused cardiac-gated fMRI and evaluated time-variant brain response to longer duration (>30 min) stimulation with verum (VA, electro-stimulation at acupoint ST-36) or sham point (SPA, non-acupoint electro-stimulation) acupuncture. Our results provide evidence that acupuncture modulates brainstem nuclei important to endogenous monoaminergic and opioidergic systems. Specifically, VA modulated activity in the substantia nigra (SN), nucleus raphe magnus, locus ceruleus, nucleus cuneiformis, and periaqueductal gray (PAG). Activation in the ventrolateral PAG was greater for VA compared to SPA. Linearly decreasing time-variant activation, suggesting classical habituation, was found in response to both VA and SPA in sensorimotor (SII, posterior insula, premotor cortex) brain regions. However, VA also produced linearly time-variant activity in limbic regions (amygdala, hippocampus, and SN), which was bimodal and not likely habituation--consisting of activation in early blocks, and deactivation by the end of the run. Thus, acupuncture induces different brain response early, compared to 20-30 min after stimulation. We attribute the fMRI differences between VA and SPA to more varied and stronger psychophysical response induced by VA. Our study demonstrates that acupuncture modulation of brainstem structures can be studied non-invasively in humans, allowing for comparison to animal studies. Our protocol also demonstrates a fMRI approach to study habituation and other time-variant phenomena over longer time durations.
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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.