bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post‐thrombolytic blood pressure and symptomatic intracerebral hemorrhage
Authors: Waltimo T. , Haapaniemi E. , Surakka I. L. , Melkas S. , Sairanen T. , Sibolt G. , Tatlisumak T. , Strbian D. 
Published: August 2016

Background and purposeMost guidelines for intravenous thrombolysis (IVT) in acute ischaemic stroke patients advise keeping systolic blood pressure (BP) below 180/105 mmHg prior to the bolus injection. Less is known about optimal management of BP thereafter. We assessed temporal changes in post‐thrombolytic systolic BP values and their impact on development of symptomatic intracerebral hemorrhage (sICH).MethodsThe study cohort included 1868 consecutive acute ischaemic stroke patients treated with IVT at the Helsinki University Central Hospital. sICH was defined according to the European Cooperative Acute Stroke Study II (ECASS‐II) (primary outcome), National Institute of Neurological Disorders and Stroke, and Safe Implementation of Thrombolysis in Stroke criteria. We evaluated BP at admission, prior to IVT and at 2, 4, 8, 12, 24 and 48 h after thrombolysis. We used univariate and multivariable models to test the effect of BP at various time‐points on development of post‐thrombolytic sICH.ResultsPrevalence of sICH in the cohort was 5.8% (ECASS‐II). Patients with sICH had significantly higher systolic BP at several time‐points after IVT compared with those without sICH (P < 0.01 at 2 and 4 h; P < 0.05 at 12 and 48 h). The odds ratios for development of sICH per 10 mmHg increase in BP were 1.14 [95% confidence interval (CI), 1.03–1.25], 1.14 (95% CI, 1.03–1.25), 1.12 (95% CI, 1.01–1.23) and 1.12 (95% CI, 1.01–1.23), respectively. At 8 h, we observed a trend (P = 0.07) for ECASS‐II and a significant effect (P < 0.05) for National Institute of Neurological Disorders and Stroke, and Safe Implementation of Thrombolysis in Stroke criteria. Thus, the only time‐point with no difference observed was 24 h.ConclusionsPatients with post‐thrombolytic sICH have significantly higher systolic BP at several time‐points compared with patients without sICH.
Genetic risk factors for antiepileptic drug–induced hypersensitivity reactions in Israeli populations
Authors: Israel Shoshana , Maggio Nicola , Ekstein Dana , Zaid Huda , Firer Maria , Bederovsky Yana , Noyman Iris , Gandelman‐Marton Revital , Blatt Ilan , Brautbar Chaim , Marom Eli , Nahlieli Dil Dorit , Berman Erez , Sabag David , Ingber Arieh , Eyal Sara 
Published: August 2016

SummaryThe human leukocyte antigen (HLA) alleles B*15:02 and A*31:01 have been identified as predictive markers of adverse cutaneous effects of carbamazepine and phenytoin in Asian and North European populations, respectively. Our aim was to estimate the distribution of these alleles in Jewish and Arab populations in Israel. The HLA‐B*15:02 and HLA‐A*31:01 carrier rate was estimated based on data from the Hadassah Bone Marrow Registry. Data on Stevens‐Johnson syndrome (SJS)– and toxic epidermal necrolysis (TEN)–related hospitalizations were obtained from the Israeli Ministry of Health (MOH) registries and from four Israeli medical centers. Of 83,705 Jewish and Arab‐Muslim donors, 81 individuals of known origin carried the HLA‐B*15:02. Among them, 66 were Jews of India‐Cochin descent. Of the Cochin Jewish donors, 12.7% were B*15:02 carriers. HLA‐A*31:01 carrier incidence among Arab and Jewish Israeli populations (3.5% and 2.2%, respectively) was within the range reported in other countries. We did not identify SJS‐ or TEN‐related hospitalizations of Jews of Indian descent. Yet, this population should be considered at greater risk for antiepileptic drug–induced SJS and TEN. Until further data on actual risk are available, such patients should be typed for HLA‐B before treatment with carbamazepine or phenytoin.
Continuous spike‐waves during slow‐wave sleep in a mouse model of focal cortical dysplasia
Authors: Sun Qian‐Quan , Zhou Chen , Yang Weiguo , Petrus Daniel 
Published: August 2016

SummaryObjectiveTo examine if mice with focal cortical dysplasia (FCD) develop spontaneous epileptic seizures and, if so, determine the key electroencephalography (EEG) features.MethodsUnilateral single freeze lesions to the S1 region (SFLS1R) were made in postnatal day 0–1 pups to induce a neocortical microgyrus in the right cortical hemisphere. Continuous 24‐h recordings with intracranialEEGelectrodes and behavioral tests were performed in adultSFLS1R and sham‐control mice to assess neurologic status.ResultsA high percentage of adultSFLS1R animals (89%, 40/45) exhibited at least one or more spontaneous nonconvulsive seizure events over the course of 24 h. Of these animals, 60% (27/45) presented with a chronic seizure state that was persistent throughout the recording session, consisting of bursts of rhythmic high‐amplitude spike‐wave activities and primarily occurring during periods of slow‐wave sleep. In comparison, none of the control, age‐matched, mice (0/12) developed seizures. The epileptic discharge pattern closely resembled a pattern of continuous spike‐waves during slow‐wave sleep (CSWS) of the human syndrome described as an electrical status epilepticus during slow‐wave sleep (ESES). Key findings in theSFLS1R model indicated that the observedCSWS(1) were more prevalent in female (18/23) versus male (9/22, p < 0.05), (2) were strongest in the right S1 region although generalized to other brain regions, (3) were associated with significant cognitive and behavioral deficits, (4) were temporarily alleviated by ethosuximide treatment or optogenetic activation of cortical γ‐aminobutyric acid (GABA)ergic neurons, and (5) theta and alpha band rhythms may play a key role in the generalization of spike‐wave activities.SignificanceThis is the first report of an in vivo animalFCDmodel that induces chronic spontaneous electrographic brain seizures. Further characterization of the abnormal oscillations in this mouse model may lead to a better understanding of the mechanisms ofCSWS/ESES.
Neurodegeneration in equine grass sickness is not attributable to niacin deficiency
Authors: McGorum B. C. , Jago R. C. , Cillan‐Garcia E. , Pirie R. S. , Keen J. A. , Reardon R. J. M. , Saffu P. Y. , Miller N. J. 
Published: August 2016

SummaryBackgroundThe aetiology of equine grass sickness (EGS) is currently unknown. We hypothesised that an acute deficiency of niacin (vitamin B3), which plays a key role in neural homeostasis, may contribute to neurodegeneration inEGS. Niacin deficiency can potentially result from ingestion of niacin antagonists produced by pasture mycotoxigenic fungi.ObjectivesTo compare the niacin status ofEGSand control grazing horses. A secondary objective was to compare blood concentrations of vitamins B1, B2 and B6 inEGSand control grazing horses to determine if the status of these vitamins was altered inEGS.Study designCase–control study.MethodsIndices of niacin status, namely the erythrocyte nicotinamide adenine dinucleotide:nicotinamide adenine dinucleotide phosphate ratio (NAD:NADPratio) and erythrocyte concentrations ofNADandNADP, were compared in blood collected fromEGSand healthy control grazing horses. Blood concentrations of vitamins B1, B2 and B6 were also compared.ResultsThere was no significant intergroup difference in theNAD:NADPratio, the main index of functional niacin status (control group: median 2.1, interquartile range [IQR] 1.8–2.6;EGSgroup: median 2.1,IQR1.9–2.6).EGShorses had significantly higher (median value increased by 25%) concentrations ofNADP. There were no intergroup differences in blood concentrations of vitamins B1, B2 and B6.Main limitationsThe interpretation of data was limited by the lack of previously defined equine reference ranges for many of the analytes. Sample size was low.ConclusionsNiacin deficiency does not contribute toEGSneurodegeneration.
Hopanoids play a role in stress tolerance and nutrient storage in the cyanobacterium Nostoc punctiforme
Authors: Ricci J. N. , Morton R. , Kulkarni G. , Summers M. L. , Newman D. K. 
Published: August 2016

AbstractHopanes are abundant in ancient sedimentary rocks at discrete intervals in Earth history, yet interpreting their significance in the geologic record is complicated by our incomplete knowledge of what their progenitors, hopanoids, do in modern cells. To date, few studies have addressed the breadth of diversity of physiological functions of these lipids and whether those functions are conserved across the hopanoid‐producing bacterial phyla. Here, we generated mutants in the filamentous cyanobacterium, Nostoc punctiforme, that are unable to make all hopanoids (shc) or 2‐methylhopanoids (hpnP). While the absence of hopanoids impedes growth of vegetative cells at high temperature, the shc mutant grows faster at low temperature. This finding is consistent with hopanoids acting as membrane rigidifiers, a function shared by other hopanoid‐producing phyla. Apart from impacting fitness under temperature stress, hopanoids are dispensable for vegetative cells under other stress conditions. However, hopanoids are required for stress tolerance in akinetes, a resting survival cell type. While 2‐methylated hopanoids do not appear to contribute to any stress phenotype, total hopanoids and to a lesser extent 2‐methylhopanoids were found to promote the formation of cyanophycin granules in akinetes. Finally, although hopanoids support symbiotic interactions between Alphaproteobacteria and plants, they do not appear to facilitate symbiosis between N. punctiforme and the hornwort Anthoceros punctatus. Collectively, these findings support interpreting hopanes as general environmental stress biomarkers. If hopanoid‐mediated enhancement of nitrogen‐rich storage products turns out to be a conserved phenomenon in other organisms, a better understanding of this relationship may help us parse the enrichment of 2‐methylhopanes in the rock record during episodes of disrupted nutrient cycling.
Medication appropriateness tool for co‐morbid health conditions in dementia: consensus recommendations from a multidisciplinary expert panel
Authors: Page A. T. , Potter K. , Clifford R. , McLachlan A. J. , Etherton‐Beer C. 
Published: August 2016

BackgroundMedication management for people living with dementia is a complex task as it is unclear what constitutes optimal medication management in this population due to the shifting focus of health priorities and the balance between the benefits and harms of medications.AimThis study sought expert opinion to create a consensus list to define appropriate medication management of co‐morbidities for people with dementia.MethodsThis study used the Delphi technique. We invited multidisciplinary experts in geriatric therapeutics including pharmacists, doctors, nurse practitioners, a patient advocate and a psychologist to participate. Participants were asked to engage into three or more rounds of questioning. Round 1 was a questionnaire comprised of one question defining dementia and seven open‐ended questions about appropriate management of co‐morbidities in people with dementia. Two investigators qualitatively analysed the responses to questions from Round 1 using thematic analysis. The results of this analysis were provided to participants as statements in the Round 2 survey. The participants were asked to rate their agreement with each statement on a 5‐point Likert scale. The median and interquartile range (IQR) were calculated for the responses to each statement. Consensus was pre‐specified as an IQR less than or equal to 1. Statements where consensus was not achieved were presented to participants in Round 3. The Round 2 median and IQR values were provided and participants were again asked to rate their agreement with each statement on a 5‐point Likert scale. The statements where participants agreed or strongly agreed were included in the Medication Appropriateness Tool for Co‐morbid Health conditions in Dementia criteria.ResultsFifty‐seven experts agreed to participate in the study, of whom 58% were pharmacists and 36% were medical practitioners. Fifty‐five participants completed the Round 1 (95% response rate). A total of 128 statements was included in the Round 2 survey. Consensus was reached on 93 statements in Round 2 (n = 48 responders, 84% response rate) and on 18 statements in Round 3 (n = 43 responders, 75% response rate). The participants reached consensus on 111 of 128 statements. Of these statements, 67 statements were included in the Medication Appropriateness Tool for Co‐morbid Health conditions in Dementia criteria. The statements were in the broad themes of preventative medication, symptom management, disease progression, psychoactive medication, treatment goals, principles of medication use, side‐effects and medication reviews.DiscussionThis research provides consensus‐based guidance for clinicians who manage co‐morbid health conditions in people with dementia.
Return to sender: the need to re‐address patient antibiotic allergy labels in Australia and New Zealand
Authors: Trubiano J. A. , Worth L. J. , Urbancic K. , Brown T. M. , Paterson D. L. ,   on behalf of the Australasian Society for Infectious Diseases Clinical Research Network, Lucas M. ,   on behalf of the Australasian Society of Clinical Immunology and Allergy, Phillips E. 
Published: August 2016

Background/AimAntibiotic allergies are frequently reported and have significant impacts upon appropriate prescribing and clinical outcomes. We surveyed infectious diseases physicians, allergists, clinical immunologists and hospital pharmacists to evaluate antibiotic allergy knowledge and service delivery in Australia and New Zealand.MethodsAn online multi‐choice questionnaire was developed and endorsed by representatives of the Australasian Society of Clinical Immunology and Allergy (ASCIA) and the Australasian Society of Infectious Diseases (ASID). The 37‐item survey was distributed in April 2015 to members of ASCIA, ASID, the Society of Hospital Pharmacists of Australia and the Royal Australasian College of Physicians.ResultsOf 277 respondents, 94% currently use or would utilise antibiotic allergy testing (AAT) and reported seeing up to 10 patients/week labelled as antibiotic‐allergic. Forty‐two per cent were not aware of or did not have AAT available. Most felt that AAT would aid antibiotic selection, antibiotic appropriateness and antimicrobial stewardship (79, 69 and 61% respectively). Patients with the histories of immediate hypersensitivity were more likely to be referred than those with delayed hypersensitivities (76 vs 41%, P = 0.0001). Lack of specialist physicians (20%) and personal experience (17%) were barriers to service delivery. A multidisciplinary approach was a preferred AAT model (53%). Knowledge gaps were identified, with the majority overestimating rates of penicillin/cephalosporin (78%), penicillin/carbapenem (57%) and penicillin/monobactam (39%) cross‐reactivity.ConclusionsA high burden of antibiotic allergy labelling and demand for AAT is complicated by a relative lack availability or awareness of AAT services in Australia and New Zealand. Antibiotic allergy education and deployment of AAT, accessible to community and hospital‐based clinicians, may improve clinical decisions and reduce antibiotic allergy impacts. A collaborative approach involving infectious diseases physicians, pharmacists and allergists/immunologists is required.
New P–T constraints on the Tamayen glaucophane‐bearing rocks, eastern Taiwan: Perple_X modelling results and geodynamic implications
Authors: Baziotis I. , Tsai C.‐H. , Ernst W. G. , Jahn B.‐M. , Iizuka Y. 
Published: August 2016

AbstractNew pseudosection modelling was applied to better constrain the P–T conditions and evolution of glaucophane‐bearing rocks in the Tamayen block of the Yuli belt, recognized as the world's youngest known blueschist complex. Based on the predominant clinoamphibole, textural relationships, and mineral compositions, these glaucophane‐bearing high‐P rocks can be divided into four types. We focused on the three containing garnet. The chief phase assemblages are (in decreasing mode): amphibole + quartz + epidote + garnet + chlorite + rutile/titanite (Type‐I), phengite + amphibole + quartz + garnet + chlorite + epidote + titanite + biotite + magnetite (Type‐II), and amphibole + quartz + albite + epidote + garnet + rutile + hematite + titanite (Type‐III). Amphibole exhibits compositional zoning from core to rim as follows: glaucophane → pargasitic amphibole → actinolite (Type‐I), barroisite → Mg‐katophorite/taramite → Fe‐glaucophane (Type‐II), glaucophane → winchite (Type‐III). Using petrographic data, mineral compositions and Perple_X modelling (pseudosections and superimposed isopleths), peak P–T conditions were determined as 13 ± 1 kbar and 550 ± 40 °C for Type‐I, 10.5 ± 0.5 kbar and 560 ± 30 °C for Type‐II (thermal peak) and 11 ± 1 kbar and 530 ± 30 °C for Type‐III. The calculations yield higher pressures and temperatures than previously thought; the difference is ~1–6 kbar and 50–200 °C. The three rock types record similar P–T retrograde paths with clockwise trajectories; all rocks followed trajectories with substantial pressure decrease under near‐isothermal conditions (Type‐I and Type‐III), with the probable exception of Type‐II where decompression followed colder geotherms. The P–T paths suggest a tectonic environment in which the rocks were exhumed from maximum depths of ~45 km within a subduction channel along a relative cold geothermal gradient of ~11–14 °C km−1.
Mapping the alterations in glutamate with GluCEST MRI in a mouse model of dopamine deficiency
Authors: Bagga Puneet , Crescenzi Rachelle , Krishnamoorthy Guruprasad , Verma Gaurav , Nanga Ravi Prakash Reddy , Reddy Damodar , Greenberg Joel , Detre John A. , Hariharan Hari , Reddy Ravinder 
Published: August 2016

AbstractGlutamate chemical exchange saturation transfer (GluCEST) MRI was used to measure metabolic changes in mice treated with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) by mapping regional cerebral glutamate. The GluCEST contrast following MPTP treatment was correlated with 1H‐MR spectroscopy, motor function, and immunohistochemical measures. The GluCEST contrast was found to be significantly higher in the striatum and motor cortex of mice treated with MPTP than in controls (p < 0.001), which was confirmed by localized 1H‐MR spectroscopy. Elevated striatal GluCEST was positively associated with local astrogliosis measured by immunohistochemistry for glial fibrillary acidic protein. Additionally, a negative correlation was found between motor function, measured by the four‐limb grip strength test, and GluCEST of the striatum (R = −0.705, p < 0.001) and the motor cortex (R = −0.617, p < 0.01), suggesting a role of elevated glutamate in the abnormal cerebral motor function regulation. The GluCEST contrast and glial fibrillary acidic protein immunostaining were unaltered in the thalamus indicating glutamate elevation was localized to the striatum and the motor cortex. These findings suggest that in addition to measuring spatial changes in glutamate, GluCEST may serve as an in vivo biomarker of metabolic and functional changes that may be applied to the assessment of a broad range of neuropathologies.
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Pathogenic mechanisms of prion protein, amyloid‐β and α‐synuclein misfolding: the prion concept and neurotoxicity of protein oligomers
Authors: Ugalde Cathryn L. , Finkelstein David I. , Lawson Victoria A. , Hill Andrew F. 
Published: August 2016

AbstractProteinopathies represent a group of diseases characterized by the unregulated misfolding and aggregation of proteins. Accumulation of misfolded protein in the central nervous system (CNS) is associated with neurodegenerative diseases, such as the transmissible spongiform encephalopathies (or prion diseases), Alzheimer's disease, and the synucleinopathies (the most common of which is Parkinson's disease). Of these, the pathogenic mechanisms of prion diseases are particularly striking where the transmissible, causative agent of disease is the prion, or proteinaceous infectious particle. Prions are composed almost exclusively of PrPSc; a misfolded isoform of the normal cellular protein, PrPC, which is found accumulated in the CNS in disease. Today, mounting evidence suggests other aggregating proteins, such as amyloid‐β (Aβ) and α‐synuclein (α‐syn), proteins associated with Alzheimer's disease and synucleinopathies, respectively, share similar biophysical and biochemical properties with PrPSc that influences how they misfold, aggregate, and propagate in disease. In this regard, the definition of a ‘prion’ may ultimately expand to include other pathogenic proteins. Unifying knowledge of folded proteins may also reveal common mechanisms associated with other features of disease that are less understood, such as neurotoxicity. This review discusses the common features Aβ and α‐syn share with PrP and neurotoxic mechanisms associated with these misfolded proteins.
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Several proteins are known to misfold and accumulate in the central nervous system causing a range of neurodegenerative diseases, such as Alzheimer's, Parkinson's, and the prion diseases. Prions are transmissible misfolded conformers of the prion protein, PrP, which seed further generation of infectious proteins. Similar effects have recently been observed in proteins associated with Alzheimer's disease and the synucleinopathies, leading to the proposition that the definition of a ‘prion’ may ultimately expand to include other pathogenic proteins. Unifying knowledge of misfolded proteins may also reveal common mechanisms associated with other features of disease that are less understood, such as neurotoxicity.
Heterologous regulation of the cannabinoid type 1 receptor by angiotensin II in astrocytes of spontaneously hypertensive rats
Authors: Haspula Dhanush , Clark Michelle A. 
Published: August 2016

AbstractBrainstem and cerebellar astrocytes have critical roles to play in hypertension and attention‐deficit hyperactivity disorder, respectively. Angiotensin (Ang) II, via the astroglial Ang type 1 receptor (AT1R), has been demonstrated to elevate pro‐inflammatory mediators in the brainstem and the cerebellum. The activation of astroglial cannabinoid type 1 receptor (CB1R), a master regulator of homeostasis, has been shown to neutralize inflammatory states. Factors that drive disease progression are known to alter the expression of CB1Rs. In this study, we investigated the role of Ang II in regulating CB1R protein and mRNA expression in astrocytes isolated from the brainstem and the cerebellum of spontaneously hypertensive rats (SHRs). The results were then compared with their normotensive counterpart, Wistar rats. Not only was the basal expression of CB1R protein and mRNA significantly lower in SHR brainstem astrocytes, but treatment with Ang II resulted in lowering it further in the initial 12 h. In the case of cerebellum, Ang II up‐regulated the CB1R protein and mRNA in SHR astrocytes. While the effect of Ang II on CB1R protein was predominantly mediated via the AT1R in SHR brainstem; both AT1R‐ and AT2R‐mediated Ang II's effect in the SHR cerebellum. These data are strongly indicative of a potential new mode of cross‐talk between components of the renin angiotensin system and the endocannabinoid system in astrocytes. The consequence of such a cross‐talk could be a potential reduced endocannabinoid tone in brainstem in hypertensive states, but not in the cerebellum under the same conditions.
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