The fate of the homoctenids (Tentaculitoidea) during the Frasnian-Famennian mass extinction (Late Devonian)

The homoctenids (Tentaculitoidea) are small, conical-shelled marine animals which are amongst the most abundant and widespread of all Late Devonian fossils. They were a principal casualty of the Frasnian-Famennian (F-F, Late Devonian) mass extinction, and thus provide an insight into the extinction dynamics. Despite their abundance during the Late Devonian, they have been largely neglected by extinction studies. A number of Frasnian-Famennian boundary sections have been studied, in Poland, Germany, France, and the United States. These sections have yielded homoctenids, which allow precise recognition of the timing of the mass extinction. It is clear that the homoctenids almost disappear from the fossil record during the latest Frasnian “Upper Kellwasser Event”. The coincident extinction of this pelagic group, and the widespread development of intense marine anoxia within the water column, provides a causal link between anoxia and the F-F extinction. Most notable is the sudden demise of a group, which had been present in rock-forming densities, during this anoxic event. One new species, belonging to Homoctenus is described, but is not formally named here

Antonio Gramsci’s impact on critical pedagogy

This paper provides an account of Antonio Gramsci’s impact on the area of critical pedagogy. It indicates the Gramscian influence on the thinking of major exponents of the field. It foregrounds Gramsci's ideas and then indicates how they have been taken up by a selection of critical pedagogy exponents who were chosen on the strength of their identification and engagement with Gramsci's ideas, some of them even having written entire essays on Gramsci. The essay concludes with a discussion concerning an aspect of Gramsci's concerns, the question of powerful knowledge, which, in the present author's view, provides a formidable challenge to critical pedagogues.peer-reviewe

Elevated Ratio of Urinary Metabolites of Thromboxane and Prostacyclin Is Associated with Adverse Cardiovascular Events in ADAPT

Results from prevention trials, including the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT), have fueled discussion about the cardiovascular (CV) risks associated with non-steroidal anti-inflammatory drugs (NSAIDs). We tested the hypotheses that (i) adverse CV events reported among ADAPT participants (aged 70 years and older) are associated with increased ratio of urine 11-dehydrothromboxane B2 (Tx-M) to 2′3-donor–6-keto-PGF1 (PGI-M) attributable to NSAID treatments; (ii) coincident use of aspirin (ASA) would attenuate NSAID-induced changes in Tx-M/PGI-M ratio; and (iii) use of NSAIDs and/or ASA would not alter urine or plasma concentrations of F2-isoprostanes (IsoPs), in vivo biomarkers of free radical damage. We quantified urine Tx-M and PGI-M, and urine and plasma F2-IsoPs from 315 ADAPT participants using stable isotope dilution assays with gas chromatography/mass spectrometry, and analyzed these data by randomized drug assignment and self-report compliance as well as ASA use. Adverse CV events were significantly associated with higher urine Tx-M/PGI-M ratio, which seemed to derive mainly from lowered PGI-M. Participants taking ASA alone had reduced urine Tx-M/PGI-M compared to no ASA or NSAID; however, participants taking NSAIDs plus ASA did not have reduced urine Tx-M/PGI-M ratio compared to NSAIDs alone. Neither NSAID nor ASA use altered plasma or urine F2-IsoPs. These data suggest a possible mechanism for the increased risk of CV events reported in ADAPT participants assigned to NSAIDs, and suggest that the changes in the Tx-M/PGI-M ratio was not substantively mitigated by coincident use of ASA in individuals 70 years or older

Rpgrip1 is required for rod outer segment development and ciliary protein trafficking in zebrafish

The authors would like to thank the Royal Society of London, the National Eye Research Centre, the Visual Research Trust, Fight for Sight, the W.H. Ross Foundation, the Rosetrees Trust, and the Glasgow Children’s Hospital Charity for supporting this work. This work was also supported by the Deanship of Scientific Research at King Saud University for funding this research (Research Project) grant number ‘RGP – VPP – 219’.Mutations in the RPGR-interacting protein 1 (RPGRIP1) gene cause recessive Leber congenital amaurosis (LCA), juvenile retinitis pigmentosa (RP) and cone-rod dystrophy. RPGRIP1 interacts with other retinal disease-causing proteins and has been proposed to have a role in ciliary protein transport; however, its function remains elusive. Here, we describe a new zebrafish model carrying a nonsense mutation in the rpgrip1 gene. Rpgrip1homozygous mutants do not form rod outer segments and display mislocalization of rhodopsin, suggesting a role for RPGRIP1 in rhodopsin-bearing vesicle trafficking. Furthermore, Rab8, the key regulator of rhodopsin ciliary trafficking, was mislocalized in photoreceptor cells of rpgrip1 mutants. The degeneration of rod cells is early onset, followed by the death of cone cells. These phenotypes are similar to that observed in LCA and juvenile RP patients. Our data indicate RPGRIP1 is necessary for rod outer segment development through regulating ciliary protein trafficking. The rpgrip1 mutant zebrafish may provide a platform for developing therapeutic treatments for RP patients.Publisher PDFPeer reviewe

Large-scale proteome and metabolome analysis of CSF implicates altered glucose and carbon metabolism and succinylcarnitine in Alzheimer's disease

INTRODUCTION: A hallmark of Alzheimer's disease (AD) is the aggregation of proteins (amyloid beta [A] and hyperphosphorylated tau [T]) in the brain, making cerebrospinal fluid (CSF) proteins of particular interest. METHODS: We conducted a CSF proteome-wide analysis among participants of varying AT pathology (n = 137 participants; 915 proteins) with nine CSF biomarkers of neurodegeneration and neuroinflammation. RESULTS: We identified 61 proteins significantly associated with the AT category (P < 5.46 × 10−5) and 636 significant protein-biomarker associations (P < 6.07 × 10−6). Proteins from glucose and carbon metabolism pathways were enriched among amyloid- and tau-associated proteins, including malate dehydrogenase and aldolase A, whose associations with tau were replicated in an independent cohort (n = 717). CSF metabolomics identified and replicated an association of succinylcarnitine with phosphorylated tau and other biomarkers. DISCUSSION: These results implicate glucose and carbon metabolic dysregulation and increased CSF succinylcarnitine levels with amyloid and tau pathology in AD. HIGHLIGHTS: Cerebrospinal fluid (CSF) proteome enriched for extracellular, neuronal, immune, and protein processing. Glucose/carbon metabolic pathways enriched among amyloid/tau-associated proteins. Key glucose/carbon metabolism protein associations independently replicated. CSF proteome outperformed other omics data in predicting amyloid/tau positivity. CSF metabolomics identified and replicated a succinylcarnitine–phosphorylated tau association

The treatment of migraines and tension-type headaches with intravenous and oral niacin (nicotinic acid): systematic review of the literature

BACKGROUND: Migraine and tension-type headaches impose a tremendous economic drain upon the healthcare system. Intravenous and oral niacin has been employed in the treatment of acute and chronic migraine and tension-type headaches, but its use has not become part of contemporary medicine, nor have there been randomized controlled trials further assessing this novel treatment. We aimed to systematically review the evidence of using intravenous and/or oral niacin as a treatment for migraine headaches, tension-type headaches, and for headaches of other etiologic types. METHODS: We searched English and non-English language articles in the following databases: MEDLINE (1966–February 2004), AMED (1995–February 2004) and Alt HealthWatch (1990–February 2004). RESULTS: Nine articles were found to meet the inclusion criteria and were included in this systematic review. Hypothetical reasons for niacin's effectiveness include its vasodilatory properties, and its ability to improve mitochondrial energy metabolism. Important side effects of niacin include flushing, nausea and fainting. CONCLUSION: Although niacin's mechanisms of action have not been substantiated from controlled clinical trials, this agent may have beneficial effects upon migraine and tension-type headaches. Adequately designed randomized trials are required to determine its clinical implications

Unusual towering elevation of troponin I after ST-elevation myocardial infarction and intensive monitoring with echocardiography post-percutaneous coronary intervention: a case report

<p>Abstract</p> <p>Introduction</p> <p>The elevation of troponin levels directly corresponds to the extent of myocardial injury. Here we present a case of a robust rise in cardiac biomarkers that correspond to extensive damage to the myocardium but did not spell doom for our patient. It is important to note that, to the best of our knowledge, this is the highest level of troponin I ever reported in the literature after a myocardial injury in an acute setting.</p> <p>Case presentation</p> <p>A 53-year-old African American man with an unknown medical history presented to the emergency room of our hospital with chest pain associated with diaphoresis and altered mental status. He required emergency intubation due to acute respiratory failure and circulatory collapse within 10 minutes of his arrival. He was started on heparin and eptifibatide (Integrilin) drips but he was taken immediately for cardiac catheterization, which showed a total occlusion of his proximal left anterior descending, diffuse left circumflex disease and severe left ventricular dysfunction with segmental wall motion abnormality. He remained hypotensive throughout the procedure and an intra-aortic balloon pump was inserted for circulatory support. His urinary toxicology examination result was positive for cocaine metabolites. Serial echocardiograms showed an akinetic apex, a severely hypokinetic septum, and severe systolic dysfunction of his left ventricle. Our patient stayed at the Coronary Care Unit for a total of 15 days before he was finally discharged.</p> <p>Conclusion</p> <p>Studies demonstrate that an increase of 1 ng/ml in the cardiac troponin I level is associated with a significant increase in the risk ratio for death. The elevation of troponin I to 515 ng/ml in our patient is an unusual robust presentation which may reflect a composite of myocyte necrosis and reperfusion but without short-term mortality. Nevertheless, prolonged close monitoring is required for better outcome. We also emphasize the need for the troponin assays to be standardized and have universal cutoffs for comparisons across available data.</p

Predictors of patients’ choices for breast-conserving therapy or mastectomy: a prospective study

A study was undertaken to describe the treatment preferences and choices of patients with breast cancer, and to identify predictors of undergoing breast-conserving therapy (BCT) or mastectomy (MT). Consecutive patients with stage I/II breast cancer were eligible. Information about predictor variables, including socio-demographics, quality of life, patients' concerns, decision style, decisional conflict and perceived preference of the surgeon was collected at baseline, before decision making and surgery. Patients received standard information (n = 88) or a decision aid (n = 92) as a supplement to support decision making. A total of 180 patients participated in the study. In all, 72% decided to have BCT (n = 123); 28% chose MT (n = 49). Multivariate analysis showed that what patients perceived to be their surgeons' preference and the patients' concerns regarding breast loss and local tumour recurrence were the strongest predictors of treatment preference. Treatment preferences in itself were highly predictive of the treatment decision. The decision aid did riot influence treatment choice. The results of this study demonstrate that patients' concerns and their perceptions of the treatment preferences of the physicians are important factors in patients' decision making. Adequate information and communication are essential to base treatment decisions on realistic concerns, and the treatment preferences of patients, (C) 2004 Cancer Research U