bluuebunny/crossref_metadata_2025_split huggingface dataset:
MELAS: A Multigenerational Impact of the MTTL1 A3243G MELAS Mutation
Authors: Prasad M. , Narayan B. , Prasad A.N. , Rupar C.A. , Levin S. , Kronick J. , Ramsay D. , Tay K.Y. , Prasad C. 
Published: December 2014

Background:the maternally inherited MTTL1 A3243G mutation in the mitochondrial genome causes MelaS (Mitochondrial encephalopathy lactic acidosis with Stroke-like episodes), a condition that is multisystemic but affects primarily the nervous system. Significant intra-familial variation in phenotype and severity of disease is well recognized.Methods:retrospective and ongoing study of an extended family carrying the MTTL1 A3243G mutation with multiple symptomatic individuals. tissue heteroplasmy is reviewed based on the clinical presentations, imaging studies, laboratory findings in affected individuals and pathological material obtained at autopsy in two of the family members.Results:there were seven affected individuals out of thirteen members in this three generation family who each carried the MTTL1 A3243G mutation. the clinical presentations were varied with symptoms ranging from hearing loss, migraines, dementia, seizures, diabetes, visual manifestations, and stroke like episodes. three of the family members are deceased from MelaS or to complications related to MelaS.Conclusions:the results of the clinical, pathological and radiological findings in this family provide strong support to the current concepts of maternal inheritance, tissue heteroplasmy and molecular pathogenesis in MelaS. neurologists (both adult and paediatric) are the most likely to encounter patients with MelaS in their practice. genetic counselling is complex in view of maternal inheritance and heteroplasmy. newer therapeutic options such as arginine are being used for acute and preventative management of stroke like episodes.
N Alpha Methyl Histamine Versus Propranolol in Migraine Prophylaxis
Authors: Millán-Guerrero R.O. , Isais-Millán R. , Guzmán-Chávez B. , Castillo-Varela G. 
Published: December 2014

Objectives:To compare the efficacy and tolerability of the subcutaneous administration of N alpha methyl histamine versus oral propranolol in the treatment of migraine prophylaxis.Background:N alpha methyl histamine has a selective affinity for H3 receptors and could constitute a new therapeutic drug in migraine prophylaxis.Methods:Sixty patients with migraine were selected and enrolled in a 12-week double-blind controlled clinical trial to evaluate the efficacy of subcutaneous administration of N-alpha methyl histamine (1 to 3 ug twice a week ) n=30, compared to administration of 120 mg/day of oral propranolol n=30. the variables were: headache intensity, frequency of attacks, duration of migraine attacks and analgesic intake.Results:fifty five patients completed the study. the data collected during the 4th week of treatment revealed that N alpha methyl histamine and propranolol caused a significantly (p<0.01) greater reduction between the basal values and final values of every variable studied.Conclusions:Both N alpha methyl histamine and propranolol are similarly effective in reducing or eliminating the headache in migraine prophylaxis. low doses of N-alpha methyl histamine injected subcutaneously may represent a novel and effective therapeutic alternative in migraine patients and may lay the clinical and pharmacological groundwork for the use of H3 receptor agonist in migraine prophylaxis.
MSTMP, a Stilbene Derivative, Protects SH-SY5Y Cells Against Oxidative Stress
Authors: Liu Wei-Guo , Zhao Jun-Yi , Zhang Hao , Liu Xin-Yong , Guo Xiu-Li 
Published: December 2014

Objective:The protective effects of a novel stilbene derivative, (E)-2-(3,4,5-trimethoxystyryl)-3,5,6-trimethylpyrazine (MSTMP), on hydrogen peroxide (H2O2)-induced human derived neuroblastoma cell (SH-SY5Y) damage and its molecular mechanisms were investigated.Methods:SH-SY5Y cells were exposed to 200 μmol·L−1 H2O2 for 12 h. The effect of MSTMP on cell viability and apoptosis was assessed by 3-(4,5-dimethyl- thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry method. The activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD) and nitric oxide synthetase (NOS) and the content of malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) in cells were determined by commercial kits. The expressions of pro-apoptotic factor caspase-3, caspase-9 and inducible NOS (iNOS) were detected by Western blotting. Intracellular formation of reactive oxygen species (ROS) was assessed using 6-carboxy-2',7'-dichlorofluorescin diacetate (DCFH-DA) fluorescent probe.Results:MSTMP increased the SH-SY5Y cell viability by inhibition of cell apoptosis induced by H2O2. These effects were accompanied by an increase of SOD activity, GSH level, and a decrease of MDA content. Moreover, MSTMP showed stronger effects on inhibition of LDH leakage, apoptotic cells, intracellular ROS level and the expression of caspase-3 and caspase-9 than TMP. Furthermore, MSTMP induced a decrease of NO level and the activity of iNOS, tNOS in a time-dependent manner.Conclusions:MSTMP prevents H2O2-induced cell injury through anti-oxidation and anti-apoptosis via ROS-NO pathway.
Trends in Hospitalization Associated with TBI in an Urban Level 1 Trauma Centre
Authors: de Guise Elaine , LeBlanc Joanne , Dagher Jehane , Tinawi Simon , Lamoureux Julie , Marcoux Judith , Maleki Mohammed , Feyz Mitra 
Published: December 2014

Objective:Traumatic brain injury (TBI) is the single largest cause of death and disability following injury worldwide. The aim of this study was to determine the demographic, clinical, medical and accident related trends for patients with TBI hospitalized in an urban level 1 Trauma Centre.Methods:Data were retrospectively collected on individuals (n = 5,642) who were admitted to the Traumatic Brain Injury Program of the McGill University Health Centre - Montreal General Hospital from 2000 to 2011.Results:Regression analysis showed a significant upward trend in the yearly number of cases as well as an upward trending by year in the proportion of TBI cases aged 70-years-old or more. The Injury Severity Scale scores were positively associated with year indicating a slight increase in injury severity over the years and there was an increase in patient psychological, social and medical premorbid complexity. In addition, the Extended Glasgow Outcome Scale score tended to become more severe over the years. There was a slight decrease in the proportion of discharges home and in the proportion of deaths.Conclusions:These results will help to understand the impact of TBI in an urban Canadian level 1 Trauma Centre. This information should be used to develop public prevention strategies and to educate the community about the risk of TBI especially the risk of falls in the ageing population. These findings can also provide information to help health policy makers plan for future resources.
Expression of Urotensin II During Focal Cerebral Ischemic in Diabetic Rats
Authors: Tian Lin , Li Yunqian , Hua Wei , Jia Ying , Zhou Min , Gu Yunhe , Qi Jiping 
Published: December 2014

Background:The objective of this study was to explore the expression of urotensin II (UII), its receptor (GPR14), and vascular endothelial growth factor (VEGF), as well as their associations in the ischaemic brains of rats with focal cerebral ischaemia, under normal and diabetic conditions.Methods:Diabetes mellitus (DM) was induced by injection of streptozotocin (STZ) into Sprague—Dawley rats. Focal cerebral ischaemia was induced by middle cerebral artery occlusion (MCAO) four weeks after DM onset by STZ. Rats (n=80) were divided into four groups: normal control, DM, MCAO, and DM/MCAO. Immunohistochemistry and reverse-transcriptase-polymerase chain reaction (RT-PCR) were used to detect the expression of UII, GPR14 and VEGF in the diabetic and ischaemic brain.Results:Expression of UII and GPR14 was increased at mRNA and protein levels in the DM and MCAO group compared with controls. In the DM/MCAO group, expression of UII and GPR14 was increased significantly in the ischaemic brain, and was accompanied by a significantly increased VEGF expression.Conclusion:Diabetes mellitus was seen to aggravate brain lesions after ischaemia, and UII may have an important role.
Typhoid fever acquired in the United States, 1999–2010: epidemiology, microbiology, and use of a space–time scan statistic for outbreak detection
Authors: IMANISHI M. , NEWTON A. E. , VIEIRA A. R. , GONZALEZ-AVILES G. , KENDALL SCOTT M. E. , MANIKONDA K. , MAXWELL T. N. , HALPIN J. L. , FREEMAN M. M. , MEDALLA F. , AYERS T. L. , DERADO G. , MAHON B. E. , MINTZ E. D. 
Published: November 2014

SUMMARYAlthough rare, typhoid fever cases acquired in the United States continue to be reported. Detection and investigation of outbreaks in these domestically acquired cases offer opportunities to identify chronic carriers. We searched surveillance and laboratory databases for domestically acquired typhoid fever cases, used a space–time scan statistic to identify clusters, and classified clusters as outbreaks or non-outbreaks. From 1999 to 2010, domestically acquired cases accounted for 18% of 3373 reported typhoid fever cases; their isolates were less often multidrug-resistant (2%vs. 15%) compared to isolates from travel-associated cases. We identified 28 outbreaks and two possible outbreaks within 45 space–time clusters of ⩾2 domestically acquired cases, including three outbreaks involving ⩾2 molecular subtypes. The approach detected seven of the ten outbreaks published in the literature or reported to CDC. Although this approach did not definitively identify any previously unrecognized outbreaks, it showed the potential to detect outbreaks of typhoid fever that may escape detection by routine analysis of surveillance data. Sixteen outbreaks had been linked to a carrier. Every case of typhoid fever acquired in a non-endemic country warrants thorough investigation. Space–time scan statistics, together with shoe-leather epidemiology and molecular subtyping, may improve outbreak detection.
An unusually long-lasting outbreak of community-acquired Legionnaires' disease, 2005–2008, Italy
Authors: SCATURRO M. , FONTANA S. , CRIPPA S. , CAPORALI M. G. , SEYLER T. , VESCHETTI E. , VILLA G. , ROTA M. C. , RICCI M. L. 
Published: November 2014

SUMMARYAn unusually long-lasting community-acquired outbreak of Legionnaires’ disease (LD) occurred in the inhabitants of a town in northern Italy from 2005 to 2008. Overall, 43 cases were diagnosed including five deaths. Hundreds of water samples were collected forLegionellaisolation but only two clinical samples were obtained. Clinical strains were ST23 as were environmental isolates detected in mostLegionella-positive patients' homes and those from a public fountain. Although noLegionellawas found in the municipal water mains, a continuous chlorination was applied in 2008. This action resulted in a halving of cases, although incidence remained tenfold higher than the Italian average incidence until the end of 2013, when it dropped to the expected rate. Retrospective analyses of prevalent wind direction suggested that a hidden cooling tower could have been the main cause of this uncommon outbreak, highlighting the importance of implementation of cooling tower registers in supporting LD investigations.
Outbreaks ofSalmonellainfections attributed to beef – United States, 1973–2011
Authors: LAUFER A. S. , GRASS J. , HOLT K. , WHICHARD J. M. , GRIFFIN P. M. , GOULD L. H. 
Published: November 2014

SUMMARYNon-typhoidalSalmonellais estimated to be the most common bacterial cause of foodborne illness in the United States, causing an estimated one million domestically acquired foodborne illnesses annually. Recent, large outbreaks have highlighted the importance of ground beef as an important source of multidrug-resistantSalmonella. We analysed the epidemiology of salmonellosis outbreaks that were attributed to beef in the United States reported to the Centers for Disease Control and Prevention (CDC) from 1973 to 2011. During 1973–2011, of the 1965 outbreaks ofSalmonellawhere a food vehicle was implicated, 96 were attributed to beef, accounting for 3684 illnesses. We observed a shift in the type of beef implicated in salmonellosis outbreaks, from roast to ground beef. Delicatessen-style roast beef cooked in commercial processing establishments was the predominant type during the 1970s and early 1980s; regulations on cooking and processing essentially eliminated this problem by 1987. Ground beef emerged as an important vehicle in the 2000s; it was implicated in 17 (45%) of the 38 beef-attributed outbreaks reported during 2002–2011. Although this emergence was likely due in part to increased participation in CDC's PulseNet, which was established in 1996, and proactive decisions by the United States Department of Agriculture's Food Safety and Inspection Service, stronger measures are needed to decrease contamination of ground beef withSalmonella.
Multilocus genotypic characterization of Escherichia coli O157:H7 recovered from food sources
Authors: ELHADIDY M. M. , ELKHATIB W. F. 
Published: November 2014

SUMMARYEscherichia coli O157:H7 strains (n = 33) recovered from different food sources in Egypt were characterized using molecular assays to identify strain genotypes associated with various levels of pathogenic potential. Genotypic characterization included: lineage-specific polymorphism assay (LSPA-6), Shiga-toxin-encoding bacteriophage insertion site assay (SBI), clade 8 typing, Tir (A255 T) polymorphism, and variant analysis of Shiga toxin 2 gene (Stx2a and Stx2c), and anti-terminator Q genes (Q933 and Q21). Genotypes LI/II (76%), SBI 1 (60·6%), clade 8 (69·7%), Tir (255 T) (72·7%) and Stx2c (45·5%) were found to be significantly more frequent compared to other genetic markers in the strains analysed. Multivariable analysis revealed a significant association between LPSA-6 and clade types as well as Tir (A255 T). To the best of our knowledge, this is the first study to report the characterization of these genetic markers in E. coli O157:H7 strains in the Middle East and Africa.
COMPLETENESS OF ÅQVIST’S SYSTEMSEANDF
Authors: PARENT XAVIER 
Published: November 2014

AbstractThis paper tackles an open problem posed by Åqvist. It is the problem of whether his dyadic deontic systemsEandFare complete with respect to their intended Hanssonian preference-based semantics. It is known that there are two different ways of interpreting what it means for a world to be best or top-ranked among alternatives. This can be understood as saying that it is optimal among them, or maximal among them. First, it is established that, under either the maximality rule or the optimality rule,Eis sound and complete with respect to the class of all preference models, the class of those in which the betterness relation is reflexive, and the class of those in which it is total. Next, an analogous result is shown to hold forF. That is, it is established that, under either rule,Fis sound and complete with respect to the class of preference models in which the betterness relation is limited, the class of those in which it is limited and reflexive, and the class of those in which it is limited and total.
Lessons from Regulating Carbon Offset Markets
Authors: Arup Christopher , Zhang Hao 
Published: December 2014

AbstractTo support carbon markets, regulators must engage in a continuous process of learning. This article explores offsets regulation in the compliance markets of Europe, the United States and China, alongside the Clean Development Mechanism, to identify what has been learnt since offsets were initiated. We argue that offsets regulation must learn to work with demands for commercial viability, environmental sustainability and political legitimacy. We find that the learning here recommends greater control of the shares, sectors, sources and standards of offsets than was initially chosen. The findings provide some cautious optimism about the scope for improvements to such market mechanisms.
Ionizing radiations sustain glioblastoma cell dedifferentiation to a stem-like phenotype through survivin: possible involvement in radioresistance
Authors: Dahan P , Martinez Gala J , Delmas C , Monferran S , Malric L , Zentkowski D , Lubrano V , Toulas C , Cohen-Jonathan Moyal E , Lemarie A 
Published: November 2014

AbstractGlioblastomas (GBM) are some bad prognosis brain tumors despite a conventional treatment associating surgical resection and subsequent radio-chemotherapy. Among these heterogeneous tumors, a subpopulation of chemo- and radioresistant GBM stem-like cells appears to be involved in the systematic GBM recurrence. Moreover, recent studies showed that differentiated tumor cells may have the ability to dedifferentiate and acquire a stem-like phenotype, a phenomenon also called plasticity, in response to microenvironment stresses such as hypoxia. We hypothesized that GBM cells could be subjected to a similar dedifferentiation process after ionizing radiations (IRs), then supporting the GBM rapid recurrence after radiotherapy. In the present study we demonstrated that subtoxic IR exposure of differentiated GBM cells isolated from patient resections potentiated the long-term reacquisition of stem-associated properties such as the ability to generate primary and secondary neurospheres, the expression of stemness markers and an increased tumorigenicity. We also identified during this process an upregulation of the anti-apoptotic protein survivin and we showed that its specific downregulation led to the blockade of the IR-induced plasticity. Altogether, these results demonstrated that irradiation could regulate GBM cell dedifferentiation via a survivin-dependent pathway. Targeting the mechanisms associated with IR-induced plasticity will likely contribute to the development of some innovating pharmacological strategies for an improved radiosensitization of these aggressive brain cancers.
Acute focal brain damage alters mitochondrial dynamics and autophagy in axotomized neurons
Authors: Cavallucci V , Bisicchia E , Cencioni M T , Ferri A , Latini L , Nobili A , Biamonte F , Nazio F , Fanelli F , Moreno S , Molinari M , Viscomi M T , D'Amelio M 
Published: November 2014

AbstractMitochondria are key organelles for the maintenance of life and death of the cell, and their morphology is controlled by continual and balanced fission and fusion dynamics. A balance between these events is mandatory for normal mitochondrial and neuronal function, and emerging evidence indicates that mitochondria undergo extensive fission at an early stage during programmed cell death in several neurodegenerative diseases. A pathway for selective degradation of damaged mitochondria by autophagy, known as mitophagy, has been described, and is of particular importance to sustain neuronal viability. In the present work, we analyzed the effect of autophagy stimulation on mitochondrial function and dynamics in a model of remote degeneration after focal cerebellar lesion. We provided evidence that lesion of a cerebellar hemisphere causes mitochondria depolarization in axotomized precerebellar neurons associated with PTEN-induced putative kinase 1 accumulation and Parkin translocation to mitochondria, block of mitochondrial fusion by Mfn1 degradation, increase of calcineurin activity and dynamin-related protein 1 translocation to mitochondria, and consequent mitochondrial fission. Here we suggest that the observed neuroprotective effect of rapamycin is the result of a dual role: (1) stimulation of autophagy leading to damaged mitochondria removal and (2) enhancement of mitochondria fission to allow their elimination by mitophagy. The involvement of mitochondrial dynamics and mitophagy in brain injury, especially in the context of remote degeneration after acute focal brain damage, has not yet been investigated, and these findings may offer new target for therapeutic intervention to improve functional outcomes following acute brain damage.
Disruption of SF3B1 results in deregulated expression and splicing of key genes and pathways in myelodysplastic syndrome hematopoietic stem and progenitor cells
Authors: Dolatshad H , Pellagatti A , Fernandez-Mercado M , Yip B H , Malcovati L , Attwood M , Przychodzen B , Sahgal N , Kanapin A A , Lockstone H , Scifo L , Vandenberghe P , Papaemmanuil E , Smith C W J , Campbell P J , Ogawa S , Maciejewski J P , Cazzola M , Savage K I , Boultwood J 
Published: November 2014

Abstract
The splicing factor SF3B1 is the most commonly mutated gene in the myelodysplastic syndrome (MDS), particularly in patients with refractory anemia with ring sideroblasts (RARS). We investigated the functional effects of SF3B1 disruption in myeloid cell lines: SF3B1 knockdown resulted in growth inhibition, cell cycle arrest and impaired erythroid differentiation and deregulation of many genes and pathways, including cell cycle regulation and RNA processing. MDS is a disorder of the hematopoietic stem cell and we thus studied the transcriptome of CD34+ cells from MDS patients with SF3B1 mutations using RNA sequencing. Genes significantly differentially expressed at the transcript and/or exon level in SF3B1 mutant compared with wild-type cases include genes that are involved in MDS pathogenesis (ASXL1 and CBL), iron homeostasis and mitochondrial metabolism (ALAS2, ABCB7 and SLC25A37) and RNA splicing/processing (PRPF8 and HNRNPD). Many genes regulated by a DNA damage-induced BRCA1–BCLAF1–SF3B1 protein complex showed differential expression/splicing in SF3B1 mutant cases. This is the first study to determine the target genes of SF3B1 mutation in MDS CD34+ cells. Our data indicate that SF3B1 has a critical role in MDS by affecting the expression and splicing of genes involved in specific cellular processes/pathways, many of which are relevant to the known RARS pathophysiology, suggesting a causal link.
Inverse design and implementation of a wavelength demultiplexing grating coupler
Authors: Piggott Alexander Y. , Lu Jesse , Babinec Thomas M. , Lagoudakis Konstantinos G. , Petykiewicz Jan , Vučković Jelena 
Published: November 2014

AbstractNanophotonics has emerged as a powerful tool for manipulating light on chips. Almost all of today's devices, however, have been designed using slow and ineffective brute-force search methods, leading in many cases to limited device performance. In this article, we provide a complete demonstration of our recently proposed inverse design technique, wherein the user specifies design constraints in the form of target fields rather than a dielectric constant profile and in particular we use this method to demonstrate a new demultiplexing grating. The novel grating, which has not been developed using conventional techniques, accepts a vertical-incident Gaussian beam from a free-space and separates O-band (1300 nm) and C-band (1550 nm) light into separate waveguides. This inverse design concept is simple and extendable to a broad class of highly compact devices including frequency filters, mode converters and spatial mode multiplexers.