bluuebunny/crossref_metadata_2025 huggingface dataset:
Thoracic ultrasound prior to medical thoracoscopy improves pleural access and predicts fibrous septation
Authors: MEDFORD Andrew R.L. , AGRAWAL Sanjay , BENNETT Jonathan A. , FREE Catherine M. , ENTWISLE James J.
Published: April 2010

Background and objective: Medical thoracoscopy (MT) is indicated for the investigation of unexplained pleural exudates. Not all MT units create artificial pneumothoraces because of time. Difficult pleural space access and thick fibrous adhesions may prevent MT and pleurodesis, respectively. The potential role of thoracic ultrasound (TUS) pre‐MT has not been fully evaluated. We hypothesized TUS would reduce failure to access the pleural space and enable detection of thick fibrous adhesions.

Methods: Thirty patients underwent single port MT consecutively for investigation of pleural exudates without pre‐MT TUS over a 6‐month period. Over the following 6 months, 30 consecutive patients underwent TUS immediately prior to MT. Pleural access rate and thick fibrous adhesionn detection at both MT and TUS were recorded.

Results: In the non‐TUS cohort, pleural space access failure occurred in 16.7% (leading to five extra procedures), versus no failures in the TUS cohort (P = 0.0522). There were no differences in prevalence of MT fibrous adhesions between cohorts. TUS identified all cases of fibrous septation versus only 12.5% identified by CT in the non‐TUS cohort (P = 0.001). All identified cases of thick fibrous septation on TUS did not receive pleurodesis at MT. TUS detected useful ancillary features in 43% of cases.

Conclusions: A strong trend to reduction in single port MT pleural access failure was noted with pre‐MT TUS thus reducing extra procedures and the need for artificial pneumothoraces. Pre‐MT TUS also reliably detects thick fibrous adhesions at MT. TUS may also detect useful ancillary features. This study provides a rationale for ultrasound‐guided single port MT if a pneumothorax is not created.
Clinical guidelines for nocturia
Authors:   The Committee for Establishment of the Clinical Guidelines for Nocturia of the Neurogenic Bladder Society
Published: April 2010

Nocturia is a bothersome condition, defined as a complaint whereby the individual has to wake one or more times per night in order to void. Nocturia that occurs twice or more per night can have a substantial adverse effect on the patient's quality of life (QOL), and in many cases treatment may be required.

These guidelines provide a treatment algorithm for use by primary care physicians.

The initial assessment is conducted through a history taking interview. With a clear understanding of symptoms, patients can be classified into three broad categories: (1) nocturia only, (2) nocturia and diurnal pollakisuria without other lower urinary tract symptoms, and (3) nocturia and diurnal pollakisuria accompanying other lower urinary tract symptoms.

For treatment, the literature supporting each form of drug therapy was ranked and a recommendation grade was determined for each form of therapy. A grade of ‘F (pending)’ was applied to any drug not currently approved for use in Japan or for which the efficacy and safety in Japanese patients was unconfirmed at the time of evaluation.

We recommend instruction and guidance on water intake that will generally result in 24‐h urine volume of 20 to 25 mL/kg. This corresponds to a daily water intake of 2.0% to 2.5% of body weight. In Japan, desmopressin is indicated for central diabetes insipidus and nocturnal enuresis, but not indicated for nocturia.

The therapeutic mechanism of the anticholinergic drugs for nocturia may depend on the action of the sensory nerve mediated by the muscarinic receptors.
Analysis of the complications after radical hysterectomy for stage IB, IIA and IIB uterine cervical cancer patients
Authors: Kashima Katsunori , Yahata Tetsuro , Fujita Kazuyuki , Tanaka Kenichi
Published: April 2010

Aim:  This study was undertaken to assess whether radical hysterectomy and pelvic lymphadenectomy could be carried out within acceptable complications in uterine cervical cancer patients.

Material & Methods:  One hundred and forty‐six patients of the International Federation of Gynecology and Obstetrics stage IB, IIA and IIB cervical cancer treated by radical hysterectomy or combined with postoperative radiation therapy were enrolled in this study. The study population was 41 women over the age of 60 and 105 women under the age of 59. Complications after the treatment of all patients were examined.

Results:  The complications were significantly high with the patients over the age of 60 (53.7%) in comparison with the patients under the age of 59 (24.8%). Especially, the cases combined with radiation therapy had higher complication rate. The most commonly recorded complications were lymphedema (13.7%) and small bowel obstruction (8.2%).

Conclusion:  We conclude that the complications influenced on the quality of life were more frequent in patients over the age of 60.
Successful treatment of a heterotopic tubal pregnancy by gasless laparoscopic surgery
Authors: Phupong Vorapong , Bunyavejchevin Suvit
Published: April 2010

Heterotopic pregnancy is a rare event and management is by either laparotomy or laparoscopic surgery to remove the extrauterine pregnancy. As there has been no report detailing the use of gasless laparoscopy for management of heterotopic pregnancy, the authors herein report a case of heterotopic pregnancy that was successfully managed by gasless laparoscopic surgery. The subsequent antenatal course was unremarkable. The intrauterine pregnancy carried to term with uneventful maternal and fetal outcomes. Thus, gasless laparoscopy can be used as an alternative method for the management of heterotopic pregnancy.
The availability of vaginal hysterectomy in benign gynecologic diseases: A prospective, non‐randomized trial
Authors: Guvenal Tevfik , Ozsoy A. Zeki , Kilcik M. Ali , Yanik Ali
Published: April 2010

Objective:  To determine whether vaginal hysterectomy can be performed in patients with benign gynecologic diseases regardless of uterine size, uterine mobility and previous pelvic surgery and to compare with abdominal hysterectomy.

Study Design:  Between 2003 and 2008, we compared 47 vaginal hysterectomies (VH) with 61 abdominal hysterectomies (AH). We excluded from the study the clinical conditions that mandate abdominal exploration and standard indications for VH such as uterovaginal prolapse. Large, immobile uterus and previous pelvic surgery were not accepted as a contraindication for VH. Demographic characteristics, primary diagnosis, uterine weight, operation time, intraoperative blood loss, complications, and hospital stay and cost in both groups were compared.

Results:  Groups were similar with respect to demographic features and primary indications. Mean uterine weight and mean operation time were similar in VH and AH groups (258.0 g vs 293.9 g and 93.7 min vs 101.4 min, respectively). Oopherectomy was performed in 44.7% of VH and in 83.6% of AH. Colporrhaphies and/or anti‐incontinence surgery were performed in 15 patients in the VH group (31.9%). The intraoperative blood loss was lower in the VH group than the AH group (245.0 mL vs 408.6 mL, P < 0.001). Perioperative complications were increased with AHs. The mean hospital stay and operation cost in the VH group were significantly less than the AH group (P < 0.001).

Conclusion:  This study indicates that vaginal hysterectomy could be performed with less morbidity in patients with benign gynecologic diseases even in large, immobile uterus and previous pelvic surgery
Clinical characteristics of perforated pyometra and impending perforation: Specific issues in gynecological emergency
Authors: Ou Yu‐Che , Lan Kuo‐Chung , Lin Hao , Tsai Ching‐Chou , ChangChien Chan‐Chao
Published: April 2010

Objective:  To evaluate the clinical characteristics of pyometra and the differences between perforated pyometra and early‐drained pyometra in order to prevent morbidity.

Material and Methods:  Retrospective study of 14 patients diagnosed between 1998 and 2008 with early‐drainage pyometra and six patients with perforated pyometra were included. In addition, a review of the literature yielded another 30 perforated pyometra cases for comparison.

Results:  Of 20 women with pyometra, the main presented symptoms at admission were abdominal pain (80%), fever (45%) and vaginal discharge (25%). The majority of organisms isolated were Bacteroides fragilis (seven cases), Streptococcus species (six cases) and Escherichia coli (five cases). Of the 36 cases with spontaneous uterine perforation to date, 35 cases (97%) had abdominal pain, 11 cases (31%) had fever, and 10 cases (27%) had vomiting. Hypoalbuminemia was found in seven patients (five cases in the perforation group and two cases in the drainage group).

Conclusion:  Early diagnosis of pyometra before perforation can avoid surgical exploration and decrease morbidity and mortality. Perforated pyometra should be considered as a differential diagnosis in women with pneumoperitoneum and fever. Hypoalbuminemia should be considered as a predisposing factor for pyometra perforation.
The Process is the Reality: Perceptions of Procedural Fairness and Participatory Democracy
Authors: Carman Christopher
Published: April 2010

To (re)connect and (re-)engage citizens with their governing institutions, many advanced industrial democracies have adopted innovative reforms designed to ‘transform’ the way citizens interact with public institutions. This article assesses the extent to which the Scottish Parliament's petitioning system, a reform designed to connect the Scottish public with its parliament, influences broader trust in the political system. Using structural equations to model data from a survey of Scottish Parliament petitioners, the article finds that process evaluations far exceed outcome evaluations in influencing petitioner trust in political institutions. Hence simply adopting reforms that allow for ‘civic engagement’ is not enough to improve public support for the political system. Great care must be taken in adopting transformative reforms to ensure that those members of the public who do choose to ‘engage’ with political institutions see procedures as fair and politically neutral.
Democracy and Nature: Speaking and Listening
Authors: Dobson Andrew
Published: April 2010

This article is about the nature of democracy in environmental politics, with special reference to the issue of representation, and to the issues of speaking and listening. It is argued that politics has always been regarded as concerned with ‘speechifying’, and that this has created problems for politicising environmental issues, many of which have to do with ‘dumb nature’. The work of Bruno Latour is examined in this context as a way of including nature in politics without resorting to extravagant claims about ‘nature speaking’. Latour's epistemological approach to ‘politicising nature’ is discussed, and attention is focused on the importance for the political (and especially democratic) process of ‘listening’ as well as ‘speaking’.
Choice of Estimators Based on Different Observations: Modified AIC and LCV Criteria
Authors: LIQUET BENOIT , COMMENGES DANIEL
Published: April 2010

Abstract.  It is quite common in epidemiology that we wish to assess the quality of estimators on a particular set of information, whereas the estimators may use a larger set of information. Two examples are studied: the first occurs when we construct a model for an event which happens if a continuous variable is above a certain threshold. We can compare estimators based on the observation of only the event or on the whole continuous variable. The other example is that of predicting the survival based only on survival information or using in addition information on a disease. We develop modified Akaike information criterion (AIC) and Likelihood cross‐validation (LCV) criteria to compare estimators in this non‐standard situation. We show that a normalized difference of AIC has a bias equal to o(n−1) if the estimators are based on well‐specified models; a normalized difference of LCV always has a bias equal to o(n−1). A simulation study shows that both criteria work well, although the normalized difference of LCV tends to be better and is more robust. Moreover in the case of well‐specified models the difference of risks boils down to the difference of statistical risks which can be rather precisely estimated. For ‘compatible’ models the difference of risks is often the main term but there can also be a difference of mis‐specification risks.
THE SUBURBANISATION OF POLITICAL REPRESENTATION IN A CONTEXT OF PROPORTIONAL REPRESENTATION: THE CASE OF BELGIUM
Authors: DE MAESSCHALCK FILIP
Published: April 2010

Research on political representation of population groups is mostly based upon individual characteristics such as class, race and gender. This paper explicitly focuses on place characteristics. In particular, it deals with the changing places of residence of the Belgian members of parliaments in historical perspective, emphasising the suburbanisation of representation in a system of proportional representation. Spatial representation is analysed on both the municipality and neighbourhood levels, and a pronounced suburbanisation of political representation is identified, although the poorest central city neighbourhoods have never been well represented. However, there are significant differences between the political parties; while suburbanisation has been evident for all political parties since the 1970s, in recent years a distinction is developing between suburban parties and re‐urbanising parties which is consistent with the development of the respective party ideologies.
EXAMINING ACCOUNTABILITY DIMENSIONS IN STATE‐OWNED ENTERPRISES
Authors: Luke Belinda
Published: April 2010

This paper examines accountability in the context of New Zealand's state‐owned enterprises (SOEs), and considers an accountability framework which extends beyond traditional (upward and outward) dimensions. While traditional accountability dimensions are clearly detailed in the legislation, less clear are the dilemmas and contradictions faced by SOEs, balancing multiple interests, and at times, conflicting objectives. These issues are explored through interviews conducted in two phases over a two year period with senior executives from 12 of the then 17 SOEs operating in New Zealand. Findings reveal a number of dimensions of accountability that extend beyond current conceptualisations of accountability in the public sector, often including multiple directions of accountability. Implications suggest the need for a more explicit framework of accountability relevant to the SOE context, which may serve useful in identifying potential pathways to conflict mitigation.
CHINESE PUBLIC FINANCE FRAMEWORK: A CONTEXTUAL ANALYSIS
Authors: Yang ChunLei , Scapens Robert W.
Published: April 2010

This paper explores the complexities of government financial management in China and examines the nature of the recent Public Finance Framework (PFF) reform in that country. We argue that this reform is not just the latest instalment in a centrally dominated reform agenda (and a logical and strategic development in the process of social, political and economic transformation), but that it reflects the Central Government's struggle to fine‐tune central‐local financial relationships and to grapple with the consequences of the previously misplaced delegation of government budgets. In so doing, the paper challenges the prescriptive research which often pervades policy studies in China. Instead, it analyses the historical and contemporary contexts which are shaping government administration in China, and sheds new light on the background, implementation and future prospects of Chinese public sector financial reform. Overall, our contextual analysis provides a starting point for more critical research into the changes in government financial administration at both policy and organisational levels in China.
MULTILEVEL FRAMING: AN ALTERNATIVE UNDERSTANDING OF BUDGET CONTROL IN PUBLIC ENTERPRISES
Authors: Fallan Lars , Pettersen Inger Johanne , Stemsrudhagen Jan Ivar
Published: April 2010

This paper addresses the question as to why there tends to be recurring budget deviations in public sector service organizations. In the public sector, budgets and actuals are loosely coupled, and budgets may serve other institutional functions than control purposes. However, little research has addressed how the framing of budget information may explain the different functions of the budgets as control devices. The paper argues that the valence of budget deviations varies between organizations, and that organizations that have a positively oriented valence towards budget surpluses have a propensity to underspend the budgets. Consequently, organizations that have a positively oriented valence towards budget deficits tend to overspend the budgets. The empirical part analyses the budget situations in the Central Bank of Norway and in a large university hospital in Norway. In the case of the Bank, it was found that underspending of budgets was framed as performance measures indicating high organizational efficiency. The Hospital, on the other hand, showed a different picture as budget deficits were the situation during all years studied. One main finding was the key actors’ roles as translators of the society's expectations as to the fulfilling of the organizations’ missions. These translators function as mediators between the institutional context and pressures, the organizations’ goals and the internal budget processes. The conventional wisdom that the budget also acts as a means of communication and as symbols and ritual acts that reflect the institutional contingencies of the organizations, is further developed by describing how organizations’ goals valence the role of budgets.
A novel MRI‐biomarker candidate for Alzheimer’s disease composed of regional brain volume and perfusion variables
Authors: Luckhaus C. , Jänner M. , Cohnen M. , Flüß M. O. , Teipel S. J. , Grothe M. , Hampel H. , Kornhuber J. , Rüther E. , Peters O. , Supprian T. , Gaebel W. , Mödder U. , Wittsack H.‐J.
Published: April 2010

Background:  Earlier evidence indicates that regional cerebral volume (rVOL) and blood flow (rCBF) variables carry independent information on incipient and early Alzheimer’s disease (AD) and combining these modalities may increase discriminant performance. We compared single variables and combinations regarding their power for optimizing diagnostic accuracy.

Methods:  Twelve cognitively normal elderly controls (CN), 30 subjects with mild cognitive impairment (MCI) and 15 with mild AD were examined by structural and perfusion‐weighted magnetic resonance imaging (MRI) in single sessions at 1.5 Tesla. rVOLs were measured by manual volumetry, and rCBFs were calculated with a ROI‐based co‐localization technique.

Results:  Applying single MRI variables for the differentiation of AD versus CN, the area under curve (AUC) of receiver operating characteristic curves (ROCCs) was highest for rVOL variables (maximum of 0.972 for right amygdala). A composite marker selected and weighted by logistic regression containing left amygdalar rCBF, left hippocampal and right amygdalar rVOLs gave a diagnostic accuracy for AD versus CN of 100%. Internal cross‐validation revealed a reliability of 88.9%.

Conclusions:  Whilst external revalidation is mandatory employing a naturalistic sample containing disease controls, our phase I/II findings demonstrate that deducing composite markers from multimodal MRI acquisitions can optimize diagnostic accuracy for AD.
The value of agri‐environment schemes for macro‐invertebrate feeders: hedgehogs on arable farms in Britain
Authors: Hof A. R. , Bright P. W.
Published: April 2010

Agri‐environment schemes have been introduced in countries throughout the world in an attempt to reverse the negative impacts of agricultural intensification on biodiversity and the environment. There have been some investigations into the effectiveness of such schemes, which show mixed outcomes but little is known with regard to mammals. The hedgehog is a generalist predator and preys on, among others, an array of macro‐invertebrates, prey important for many other taxa. For a non‐volant species, it is highly mobile in the environment and should thus be less susceptible to negative effects of habitat fragmentation caused by agricultural intensification. However, it has recently been included in the UK Biodiversity Action Plan, as a result of evidence of a significant decline. We studied the importance of agri‐environment schemes for hedgehogs using radio‐tracking on arable farms. Both agri‐environment field margins and hedgerows appear to be very valuable for hedgehogs. Both habitat types were intensively utilized by hedgehogs; higher food availability/accessibility on agri‐environment field margins and higher food or nest site availability along edges and/or lower predation risk by badgers in arable areas may explain these preferences. Badger predation of hedgehogs was high in the study site and the main cause of death. Our study emphasizes the importance of natural habitat in an agricultural landscape and shows that agri‐environment schemes can be beneficial to this generalist macro‐invertebrate feeder. The implementation of agri‐environment schemes that include wide field margins and dense, well‐established hedgerows on farmland could significantly contribute to the viability of hedgehog populations in intensive arable‐farming landscapes, and by implication benefit other macro‐invertebrate feeders.
DNA barcoding of arbuscular mycorrhizal fungi
Authors: Stockinger Herbert , Krüger Manuela , Schüßler Arthur
Published: April 2010

Commentary p 265
Excitotoxicity of TNFα derived from KA activated microglia on hippocampal neurons in vitro and in vivo
Authors: Zhu Wei , Zheng Honghua , Shao Xinli , Wang Wei , Yao Qing , Li Zhengli
Published: April 2010

J. Neurochem. (2010) 114, 386–396.

Highly activated microglia and followed excessive expression of inflammatory cytokines are associated with neuroexcitotoxic injuries. We use electrophysiological techniques, ELISA, western‐blot, RT‐PCR assay and TUNEL method to explore whether over‐produced tumor necrosis factor alpha (TNFα) released from activated microglia results in neuronal injuries, and further causes apoptosis through increasing excitotoxicity of hippocampal neurons. Our data showed that kainic acid (KA) activated microglia highly expressed TNFα, mRNA and protein. KA activated microglia conditioned media ((KA‐MCM) significantly enhanced the amplitude of the population spike at rat’s hippocampal CA3 region. It also increased the Ca2+ current amplitude and density in cultured hippocampal neurons, as well as the high expression of NMDAR1, iNOS, and caspase 3 mRNA and protein at both hippocampal neurons and tissues. KA‐MCM also increased TUNEL‐positive cells in hippocampal neurons, whereas addition of anti‐TNFα to the KA‐MCM before its application significantly reduced those effects. These studies suggest that TNFα derived from KA activated microglia increases excitotoxicity of hippocampal neurons, and might induce neuronal apoptosis in vitro and in vivo.
Acetyl‐l‐carnitine ameliorates mitochondrial dysfunction following contusion spinal cord injury
Authors: Patel Samir P. , Sullivan Patrick G. , Lyttle Travis S. , Rabchevsky Alexander G.
Published: April 2010

J. Neurochem. (2010) 114, 291–301.

In the present study, we evaluated the therapeutic efficacy of acetyl‐l‐carnitine (ALC) administration on mitochondrial dysfunction following tenth thoracic level contusion spinal cord injury (SCI) in rats. Initial results from experiments in vitro with naïve mitochondria showed that, in the absence of pyruvate, ALC can be used as an alternative substrate for mitochondrial respiration. Additionally, when added in vitro to mitochondria isolated from 24 h injured cords, ALC restored respiration rates to normal levels. For administration studies in vivo, injured rats were given i.p. injections of saline (vehicle) or ALC (300 mg/kg) at 15, 30 or 60 min post‐injury, followed by one booster after 6 h. Mitochondria were isolated 24 h post‐injury and assessed for respiration rates, activities of NADH dehydrogenase, cytochrome c oxidase and pyruvate dehydrogenase. SCI significantly (p < 0.05) decreased respiration rates and activities of all enzyme complexes, but ALC treatment significantly (p < 0.05) maintained mitochondrial respiration and enzyme activities compared with vehicle treatment. Critically, ALC administration in vivo at 15 min and 6 h post‐injury versus vehicle, followed once daily for 7 days, significantly (p < 0.05) spared gray matter. In summary, ALC treatment maintains mitochondrial bioenergetics following contusion SCI and, thus, holds great potential as a neuroprotective therapy for acute SCI.
Induction of FosB/ΔFosB in the brain stress system‐related structures during morphine dependence and withdrawal
Authors: Núñez Cristina , Martín Fátima , Földes Anna , Luisa Laorden M. , Kovács Krisztina J. , Victoria Milanés M.
Published: April 2010

J. Neurochem.(2010)114, 475–487.

The transcription factor ΔFosB is induced in the nucleus accumbens (NAc) by drugs of abuse. This study was designed to evaluate the possible modifications in FosB/ΔFosB expression in both hypothalamic and extrahypothalamic brain stress system during morphine dependence and withdrawal. Rats were made dependent on morphine and, on day 8, were injected with saline or naloxone. Using immunohistochemistry and western blot, the expression of FosB/ΔFosB, tyrosine hydroxylase (TH), corticotropin‐releasing factor (CRF) and pro‐dynorphin (DYN) was measured in different nuclei from the brain stress system in morphine‐dependent rats and after morphine withdrawal. Additionally, we studied the expression of FosB/ΔFosB in CRF‐, TH‐ and DYN‐positive neurons. FosB/ΔFosB was induced after chronic morphine administration in the parvocellular part of the hypothalamic paraventricular nucleus (PVN), NAc‐shell, bed nucleus of the stria terminalis, central amygdala and A2noradrenergic part of the nucleus tractus solitarius (NTS‐A2). Morphine dependence and withdrawal evoked an increase in FosB/ΔFosB‐TH and FosB/ΔFosB‐CRF double labelling in NTS‐A2and PVN, respectively, besides an increase in TH levels in NTS‐A2and CRF expression in PVN. These data indicate that neuroadaptation to addictive substances, observed as accumulation of FosB/ΔFosB, is not limited to the reward circuits but may also manifest in other brain regions, such as the brain stress system, which have been proposed to be directly related to addiction.
VEGF protects spinal motor neurons against chronic excitotoxic degeneration in vivo by activation of PI3‐K pathway and inhibition of p38MAPK
Authors: Tovar‐y‐Romo Luis B. , Tapia Ricardo
Published: April 2010

J. Neurochem. (2010) 115, 1090–1101.

Vascular endothelial growth factor (VEGF) protects spinal motor neurons in models of familial amyotrophic lateral sclerosis. We previously demonstrated that VEGF also prevents motor neuron death and hindlimb paralysis in rats subjected to α‐amino‐3‐hydroxy‐5‐isoxazolepropionate (AMPA)‐induced chronic excitotoxic motor neuron degeneration. Here, we show that tyrosine kinase receptor‐2 for VEGF (VEGFR2) is expressed in spinal motor neurons of the adult rat, and that its blockade impedes the VEGF‐mediated protection against motor neuron death and paralysis. In addition, inhibition of phosphatidyl‐inositol‐3‐kinase, which is activated by VEGFR2, completely prevented this protection, whereas blockade of mitogen‐activated protein kinase kinases resulted only in a partial prevention. We show as well that AMPA induces an increased p38 mitogen‐activated protein kinase (p38MAPK) phosphorylation and that VEGF blocks this effect. Furthermore, inhibition of p38MAPK prevents the paralysis induced by AMPA. These results shed light into the mechanisms of the protective effect of VEGF against excitotoxic motor neuron death in vivo and suggest that VEGFR2 and activation of phosphatidyl‐inositol‐3‐kinase or inhibition of p38MAPK might be important therapeutic targets for amyotrophic lateral sclerosis.
Acute spinal cord injury persistently reduces R/G RNA editing of AMPA receptors
Authors: Barbon Alessandro , Fumagalli Fabio , Caracciolo Luca , Madaschi Laura , Lesma Elena , Mora Cristina , Carelli Stephana , Slotkin Theodore A. , Racagni Giorgio , Di Giulio Anna Maria , Gorio Alfredo , Barlati Sergio
Published: April 2010

J. Neurochem.(2010)114, 397–407.

Spinal cord injury (SCI) triggers a complex ischemic and inflammatory reaction, involving activation of neurotransmitter systems, in particular glutamate, culminating in cell death. We hypothesized that SCI might lead to alteration in the RNA editing of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA) receptors that govern critical determinants of neuronal survival. To this end, we examined the molecular changes set in motion by SCI that affect the channel properties of AMPA receptors. SCI strongly reduced the level of AMPA receptor R/G editing, involving not only the site of the lesion but also adjacent areas of the cord spared by the lesion. The effects, with changes for some subunits and loci, were observed as long as 30 days after lesioning and may correlate with a partial decrease in enzymatic activity of adenosine deaminase acting on RNA 2 (ADAR2), as deduced from the analysis of ADAR2 self‐editing. The reduced editing at the R/G site of glutamate receptor subunits (GluRs) is likely to reduce post‐synaptic excitatory responses to glutamate, thus limiting the progression of cell death; however, prolonged suppression of GluR function in later stages may hinder synaptic plasticity. These observations provide the first direct evidence of the potential contribution of RNA editing to excitatory neural injury and recovery after SCI.
Pre‐synaptic defects of NPC1‐deficient hippocampal neurons are not directly related to plasma membrane cholesterol
Authors: Hawes Cory M. , Wiemer Hana , Krueger Stefan R. , Karten Barbara
Published: April 2010

J. Neurochem. (2010) 114, 311–332.

Imbalances in brain cholesterol homeostasis have been observed in several neurodegenerative diseases. In Niemann‐Pick Type C (NPC) disease, mutations in NPC1 or NPC2 lead to endosomal cholesterol accumulation, neuronal dysfunction and death. Cholesterol in synaptic plasma membranes influences membrane fluidity, curvature, and protein function, and its depletion may adversely affect synaptic vesicle cycling. We have investigated pre‐synaptic function in primary hippocampal neurons with altered cholesterol distribution because of NPC1 deficiency or cyclodextrin treatment. In NPC1‐deficient neurons grown in serum‐free medium, plasma membrane cholesterol was reduced and total synaptic vesicle release during prolonged stimulation was attenuated. In NPC1‐deficient neurons cultured in the presence of high‐density lipoproteins, plasma membrane cholesterol markedly increased, but the defects in synaptic vesicle release in NPC1‐deficient neurons were exacerbated. Treatment with 1 mM methyl‐β‐cyclodextrin acutely depleted plasma membrane cholesterol in wild‐type neurons to levels below those in NPC1 deficiency, but did not alter synaptic vesicle exo‐ or endocytosis. Defects only became apparent when higher methyl‐β‐cyclodextrin concentrations were used. Our data indicate that synaptic vesicle release can tolerate some degree of plasma membrane cholesterol depletion and suggest that the pre‐synaptic defects in NPC1‐deficient neurons are not solely caused by a reduction of plasma membrane cholesterol.
Dyrk1A‐mediated phosphorylation of Presenilin 1: a functional link between Down syndrome and Alzheimer’s disease
Authors: Ryu Young Shin , Park So Young , Jung Min‐Su , Yoon Song‐Hee , Kwen Mi‐Yang , Lee Sun‐Young , Choi Sun‐Hee , Radnaabazar Chinzorig , Kim Mi‐Kyoung , Kim Hangun , Kim Kwonseop , Song Woo‐Joo , Chung Sul‐Hee
Published: April 2010

J. Neurochem. (2010) 115, 574–584.

The dual‐specificity tyrosine(Y)‐phosphorylation‐regulated kinase 1A (Dyrk1A) gene is located on human chromosome 21 and encodes a proline‐directed protein kinase that might be responsible for mental retardation and early onset of Alzheimer’s disease (AD) in Down syndrome (DS) patients. Presenilin 1 (PS1) is a key component of the γ‐secretase complex in the generation of β‐amyloid (Aβ), an important trigger protein in the pathogenesis of AD. Increased Dyrk1A expression has been reported in human AD and DS brains. We previously showed that Dyrk1A increased Aβ production in mammalian cells and transgenic mice that over‐express Dyrk1A. In this study, we describe a potential mechanism by which Aβ is increased in Dyrk1A‐over‐expressing DS and AD brains. First, we show that PS1 is phosphorylated by the Dyrk1A at Thr354 and that this phosphorylation increases γ‐secretase activity. Then, using transgenic mice that over‐express human Dyrk1A, we demonstrate that phospho‐Thr354‐PS1 (pT354‐PS1) expression is enhanced when Dyrk1A level is increased. We also show that pT354‐PS1 is more stable than the unphosphorylated form of PS1. These results reveal a potential regulatory link between Dyrk1A and PS1 in the Aβ pathway of DS and AD brains, suggesting that up‐regulated Dyrk1A may accelerate AD pathogenesis through PS1 phosphorylation.
17β‐Estradiol protects Schwann cells against H2O2‐induced cytotoxicity and increases transplanted Schwann cell survival in a cervical hemicontusion spinal cord injury model
Authors: Siriphorn Akkradate , Chompoopong Supin , Floyd Candace L.
Published: April 2010

J. Neurochem. (2010) 115, 864–872.

Schwann cell (SC) transplantation is a promising repair strategy after spinal cord injury (SCI); however, a large number of SCs do not survive following transplantation. Previous studies have shown that 17β‐estradiol (E2) protects several cell types against cytotoxicity. Thus, this study evaluated the protective potential of E2 on SCs in vitro and investigated the effect of E2 on transplanted SC survival in a rat model of SCI. Primary SC cultures were found to robustly express estrogen receptors (ER) and incubation with E2 protected SCs against hydrogen peroxide‐induced cell death. This protection was not inhibited by the ER antagonist ICI 182,780, suggesting that genomic signaling is not necessary for protection. In a subsequent experiment, cervical hemicontusion SCI was induced in male rats followed by sustained administration of E2 or placebo. Eight days after SCI, SCs were transplanted into the injury epicenter. E2 treatment significantly increased the number of surviving labeled transplanted SCs evaluated 7 days after transplantation. These data demonstrate that E2 protects SCs against oxidative stress and improves transplanted SC survival, which suggests that E2 administration may be an intervention of choice for enhancing survival of transplanted SCs after SCI.
Manganese chelation therapy extends survival in a mouse model of M1000 prion disease
Authors: Brazier Marcus W. , Volitakis Irene , Kvasnicka Magda , White Anthony R. , Underwood John R. , Green Jason E. , Han Sen , Hill Andrew F. , Masters Colin L. , Collins Steven J.
Published: April 2010

J. Neurochem. (2010) 114, 440–451.

Previous in vitro and in vivo investigations have suggested manganese (Mn2+) may play a role in pathogenesis through facilitating refolding of the normal cellular form of the prion protein into protease resistant, pathogenic isoforms (PrPSc), as well as the subsequent promotion of higher order aggregation of these abnormal conformers. To further explore the role of Mn2+ in pathogenesis, we undertook a number of studies, including an assessment of the disease modifying effects of chelation therapy in a well‐characterized mouse model of prion disease. The di‐sodium, calcium derivative of the chelator, cyclohexanediaminetetraacetic acid (Na2CaCDTA), was administered intraperitoneally to mice inoculated intra‐cerebrally with either high or low‐dose inocula, with treatment beginning early (shortly after inoculation) or late (at the usual mid‐survival point of untreated mice). Analyses by inductively coupled plasma‐mass spectrometry demonstrated brain Mn2+ levels were selectively reduced by up to 50% in treated mice compared with untreated controls, with copper, iron, zinc and cobalt levels unchanged. In mice administered high‐dose inocula, none of the treatment groups displayed an increase in survival although western blot analyses of early intensively treated mice showed reduced brain PrPSc levels; mice infected using low‐dose inocula however, showed a significant prolongation of survival (p = 0.002). Although our findings support a role for Mn2+ in prion disease, further studies are required to more precisely delineate the extent of pathogenic involvement.
The microbe–mineral environment and gypsum neogenesis in a weathered polar evaporite
Authors: COCKELL C. S. , OSINSKI G. R. , BANERJEE N. R. , HOWARD K. T. , GILMOUR I. , WATSON J. S.
Published: April 2010

Evaporitic deposits are a globally widespread habitat for micro‐organisms. The microbe–mineral environment in weathered and remobilized gypsum from exposed mid‐Ordovician marine evaporite beds in the polar desert of Devon Island, Nunavut, Canadian High Arctic was examined. The gypsum is characterized by internal green zones of cyanobacterial colonization (dominated by Gloeocapsa/Aphanothece and Chroococcidiopsis spp. morphotypes) and abundant black zones, visible from the surface, that contain pigmented cyanobacteria and fungi. Bioessential elements in the gypsum are primarily provided by allochthonous material from the present‐day polar desert. The disruption, uplift and rotation of the evaporite beds by the Haughton meteorite impact 39 Ma have facilitated gypsum weathering and its accessibility as a habitat. No cultured cyanobacteria, bacteria and fungi were halophilic consistent with the expectation that halophily is not required to persist in gypsum habitats. Heterotrophic bacteria from the evaporite were slightly or moderately halotolerant, as were heterotrophs isolated from soil near the gypsum outcrop showing that halotolerance is common in arctic bacteria in this location. Psychrotolerant Arthrobacter species were isolated. No psychrophilic organisms were isolated. Two Arthrobacter isolates from the evaporite were used to mediate gypsum neogenesis in the laboratory, demonstrating a potential role for microbial biomineralization processes in polar environments.
Surface wetness and mire development during the late Holocene in central Sweden
Authors: ANDERSSON SOFIA , SCHONING KRISTIAN
Published: April 2010

Andersson, S. & Schoning, K. 2010: Surface wetness and mire development during the late Holocene in central Sweden. Boreas, Vol. 39, pp. 749–760. 10.1111/j.1502‐3885.2010.00157.x. ISSN 0300‐9483.

Late Holocene mire development and surface wetness changes have been studied in a small mixed mire located in central Sweden. Today the mire is characterized by a mainly ombrotrophic centre dominated by Sphagnum mosses, with Carex content increasing towards the more minerotrophic mire margins. Two peat sequences extracted from the central ombrotrophic part were investigated for stratigraphy, humification, testate amoebae analysis, C/N ratio and δ13C and δ15N stable isotopes. Three main stages of mire development are identified, with the first stage, between c. 4200 and 2600 cal. yr BP, characterized by water‐logged conditions, suggesting a minerotrophic fen stage. The second stage, between c. 2600 and 1000 cal. yr BP, is characterized by more ombrotrophic conditions and Sphagnum‐dominated vegetation. The onset of the prominent change at c. 2600 cal. yr BP could have been initiated by climate change coincident with a change in solar activity. The last stage, between c. 1000 and 50 cal. yr BP, is dominated by more ombrotrophic conditions, suggesting increased precipitation. This study shows that the response of hydrological proxies in a mixed mire during its development towards more ombrotrophic conditions might result in conflicting results, a finding that needs to be considered in palaeoenvironmental reconstructions from mires that change between ombrotrophic and minerotrophic settings.
Patterns of Citations of Open Access and Non‐Open Access Conservation Biology Journal Papers and Book Chapters
Authors: CALVER MICHAEL C. , BRADLEY J. STUART
Published: April 2010

Abstract:  Open access (OA) publishing, whereby authors, their institutions, or their granting bodies pay or provide a repository through which peer‐reviewed work is available online for free, is championed as a model to increase the number of citations per paper and disseminate results widely, especially to researchers in developing countries. We compared the number of citations of OA and non‐OA papers in six journals and four books published since 2000 to test whether OA increases number of citations overall and increases citations made by authors in developing countries. After controlling for type of paper (e.g., review or research paper), length of paper, authors’ citation profiles, number of authors per paper, and whether the author or the publisher released the paper in OA, OA had no statistically significant influence on the overall number of citations per journal paper. Journal papers were cited more frequently if the authors had published highly cited papers previously, were members of large teams of authors, or published relatively long papers, but papers were not cited more frequently if they were published in an OA source. Nevertheless, author‐archived OA book chapters accrued up to eight times more citations than chapters in the same book that were not available through OA, perhaps because there is no online abstracting service for book chapters. There was also little evidence that journal papers or book chapters published in OA received more citations from authors in developing countries relative to those journal papers or book chapters not published in OA. For scholarly publications in conservation biology, only book chapters had an OA citation advantage, and OA did not increase the number of citations papers or chapters received from authors in developing countries.
Quantifying Purported Competition with Individual‐ and Population‐Level Metrics
Authors: WALTERS ERIC L. , JAMES FRANCES C.
Published: April 2010

Abstract:  Competitive species interactions may contribute to population declines. Purportedly, Red‐bellied Woodpeckers (Melanerpes carolinus), a common species, and Red‐cockaded Woodpeckers (Picoides borealis), an endangered species, compete for roosting and nesting cavities in living pine trees. To determine whether behavioral interactions measured at the individual level manifest themselves at the population level, we conducted field experiments designed to test whether the presence of Red‐bellied Woodpeckers resulted in a decrease in fitness to Red‐cockaded Woodpeckers. As part of a 4‐year study examining the nature of interspecific interactions in two populations of Red‐cockaded Woodpeckers (one stable, the Apalachicola Ranger District; one declining, the Wakulla Ranger District) in the Apalachicola National Forest, Florida, we conducted a set of Red‐bellied Woodpecker removal experiments. Paradoxically, following the removal of Red‐bellied Woodpeckers, we observed decreases in Red‐cockaded Woodpecker group size, proportion of nests that were successful, and proportion of individuals remaining on territories. Removal of Red‐bellied Woodpeckers may have exaggerated the immigration rate of Red‐bellied Woodpeckers to Red‐cockaded Woodpecker territories. The Red‐cockaded Woodpeckers in the Apalachicola Ranger District likely can withstand pressure from immigrating Red‐bellied Woodpeckers given that their population has remained relatively stable despite the presence of Red‐bellied Woodpeckers. A major factor of population persistence in the Wakulla Ranger District was the high turnover rate of adult female Red‐cockaded Woodpeckers, a phenomenon that was exacerbated by removal of Red‐bellied Woodpeckers. Relying solely on observations of apparently competitive interactions between individuals may not necessarily provide information about population‐level outcomes. Paradoxically, removing species that appear to be competitors may harm species of concern.
Long‐Term, Open‐Label Safety Study of Oral Almotriptan 12.5 mg for the Acute Treatment of Migraine in Adolescents
Authors: Berenson Frank , Vasconcellos Elza , Pakalnis Ann , Mao Lian , Biondi David M. , Armstrong Robert B.
Published: April 2010

(Headache 2010;50:795‐807)

Objectives.— This study evaluated the long‐term safety of oral almotriptan 12.5 mg for the treatment of multiple migraine episodes in adolescents over a 12‐month period. Efficacy outcomes were assessed as a secondary objective.

Methods.— Adolescent migraineurs aged 12‐17 years were enrolled in this 12‐month, open‐label study (Study ID CR002827). Patients were instructed to record their assessments on paper headache records whenever they experienced a migraine headache that they treated with study medication. Safety was assessed descriptively and assessments included adverse event (AE) recording, change in laboratory values, vital signs, and electrocardiogram parameters. Efficacy outcomes were assessed descriptively and outcomes included rates for 2‐ and 24‐hour pain relief and sustained pain relief, 2‐ and 24‐hour pain‐free and sustained pain‐free, and presence of migraine‐associated symptoms of photophobia, phonophobia, nausea and vomiting.

Results.— Overall, 67.1% of patients reported ≥1 AE over the course of the trial, 7.6% had an AE judged by the study investigator to be related to treatment with almotriptan, 2.4% discontinued because of an AE, and 1.9% reported serious AEs. The most commonly reported treatment‐related AEs (occurring in ≥1% of patients) were nausea (1.4%) and somnolence (1.4%). Pain relief responses for treated migraines of moderate or severe intensity at baseline were 61.7% and 68.6%, at 2 and 24 hours, respectively; the sustained pain relief rate was 55.5%. Pain‐free responses were reported for 40.5% of all treated migraines at 2 hours and 65.9% of treated migraines at 24 hours; the sustained pain‐free rate was 38.4%. The proportion of migraines that achieved the pain relief, sustained pain relief, pain‐free and sustained pain‐free endpoints were similar in the 12‐ to 14‐year and 15‐ to 17‐year age groups. Treating with almotriptan 12.5 mg when headache pain was mild was associated with higher rates of pain relief and pain‐free at 2 and 24 hours, and sustained pain relief and sustained pain‐free, compared with treatment initiated when pain was severe.

Conclusions.— Almotriptan 12.5 mg was well tolerated in this adolescent population over a 12‐month period. No unexpected safety or tolerability concerns were revealed over the course of this study. The results are consistent with almotriptan 12.5 mg being effective for the acute treatment of pain and symptoms associated with migraine in both younger and older adolescents.
The Lack of Peripheral Pathology in Migraine Headache
Authors: Lambert Geoffrey A.
Published: April 2010

This article reviews the baffling problem of the pathophysiology behind a peripheral genesis of migraine pain – or more particularly the baffling problem of its absence. I examine a number of pathophysiological states and the effector mechanisms for these states and find most of them very plausible and that they are all supported by abundant evidence. However, this evidence is mostly indirect; to date the occurrence of any of the presumed pathological states has not been convincingly demonstrated. Furthermore, there is little evidence of increased trigeminal sensory traffic into the central nervous system during a migraine attack. The article also examines a number of observations and experimental programs used to bolster a theory of peripheral pathology and suggests reasons why they may in fact not bolster it. I suggest that a pathology, if one exists, may be in the brain and even that it may not be a pathology at all. Migraine headache might just happen because of random noise in an exquisitely sensitive and complex network. The article suggests an experimental program to resolve these issues.