bluuebunny/crossref_metadata_2025_split huggingface dataset:
Grafting of GABAergic precursors rescues deficits in hippocampal inhibition
Authors: Calcagnotto Maria E. , Zipancic Ivan , Piquer‐Gil Marina , Mello Luiz E. , Álvarez‐Dolado Manuel 
Published: July 2010

Summaryγ‐Aminobutyric acid (GABA) has an important role in the mechanism of epilepsy. Cell grafts from different sources have been performed to modulate local circuits or increase GABAergic inhibition in animal models of epilepsy. Among the different transplanted cell types, the medial ganglionic eminence (MGE)–derived cells present the best properties to be used in cell‐based therapy. In this work we review previous experiences with these cells. In addition, we present new evidence showing their ability to modulate the levels of inhibition in the host brain of mice with alterations in the GABAergic system, caused by the specific ablation of hippocampal interneurons. Grafted GFP+ MGE–derived cells occupied the area of ablation and differentiated into mature NK‐1‐, SOM‐, PV‐, CR‐, and NPY‐expressing interneurons. Inhibitory postsynaptic current (IPSC) frequency and amplitude on CA1 pyramidal cells of the ablated hippocampus significantly increased after transplantation, reaching levels similar to controls. Our data strongly suggest the suitability of MGE‐derived cells for the treatment of neurologic conditions for which an increase or modulation of synaptic inhibition is required.
Effect of neuronal precursor cells derived from medial ganglionic eminence in an acute epileptic seizure model
Authors: Calcagnotto Maria E. , Ruiz Lorena P. , Blanco Miriam M. , Santos‐Junior Jair G. , Valente Maria F. , Patti Camila , Frussa‐Filho Roberto , Santiago Marcelo F. , Zipancic Ivan , Álvarez‐Dolado Manuel , Mello Luiz E. , Longo Beatriz M. 
Published: July 2010

SummaryMost of the γ‐aminobutyric acid (GABA)ergic interneurons in the cerebral cortex originate from restricted regions of the ventral telencephalon known as the caudal and medial ganglionic eminence (MGE) and from the preoptic area. It is well established that dysfunction of GABAergic interneurons can lead to epilepsy. During the last decade new approaches to prevent, reduce, or reverse the epileptic condition have been studied, including cell‐based therapy from different sources. Recent studies have shown that transplanted neuronal precursor cells derived from MGE have the ability to migrate, differentiate into inhibitory GABAergic interneurons, and integrate into cortical and hippocampal networks, modifying the inhibitory tone in the host brain. Therefore, transplantation of neuronal precursors derived from MGE into the postnatal central nervous system (CNS) could modify the neuronal circuitry in neurologic diseases in which inhibitory synaptic function is altered, such as in epilepsy. Here, we evaluated the seizure susceptibility of mice transplanted with MGE‐derived cells in the maximum electroconvulsive shock (MES) model and we review some data from different studies using GABAergic precursor or GABA‐releasing cell grafts in animal models of seizure and epilepsy.
Possible therapeutic effects of transcutaneous electrical stimulation via concentric ring electrodes
Authors: Besio Walter G. , Gale Karen N. , Medvedev Andrei V. 
Published: July 2010

SummaryEven with the latest advancements in antiepileptic drugs (AEDs) there are still many persons whose seizures are not controlled. There are also side effects reported associated with the AEDs. Electrical stimulation of the brain has shown promise toward controlling seizures. However, most brain stimulation techniques involve invasive procedures to implant electrodes and electronic stimulators. There are no conclusive descriptions of where to place the implanted electrodes to control seizures. Noninvasive electrical stimulation does not require the risks of implantation, and the electrodes can be moved easily as needed to determine where they may be the most effective in reducing seizure activity. Herein we review the progress of our group in the development of noninvasive electrical stimulation via concentric ring electrodes to control seizures in rats induced by penicillin G, pilocarpine, and pentylenetetrazole (PTZ).
In search of models of pharmacoresistant epilepsy
Authors: Wahab Abdul , Albus Klaus , Gabriel Siegrun , Heinemann Uwe 
Published: July 2010

SummaryClinically available anticonvulsant drugs fail to control seizures in approximately 30% of epileptic patients. If hippocampal sclerosis is combined with focal dysplasia or similar developmental alterations, the likelihood of incomplete seizure control may reach >90%. Because only a minority of epilepsy patients benefit from epilepsy surgery, we need more research into the mechanisms of drug refractoriness. In this review we analyze different approaches to study pharmacoresistance and underlying mechanisms using in vitro models. Epileptiform discharges after prolonged application of low Mg2+ artificial cerebrospinal fluid (ACSF) or 4‐aminopyridine (4‐AP), or combined application of these convulsants with bicuculline in acute hippocampal–entorhinal cortex slices reveal pharmacoresistance and point to loss of γ‐aminobutyric acid (GABA)ergic function, in part due to reduced delivery of GABA from presynaptic terminals. Interestingly, epileptiform activity in immature tissue (organotypic hippocampal slice cultures and acute intact hippocampus) is immediately resistant to available antiepileptic drugs, and preliminary evidence points to a role of alterations in Cl− homeostasis. Seizure‐like events can also be induced in dissected tissues from human epileptic patients. Future research on human tissue may provide useful information for understanding the mechanisms underlying pharmacoresistance.
Simultaneous EEG, fMRI, and behavior in typical childhood absence seizures
Authors: Berman Rachel , Negishi Michiro , Vestal Matthew , Spann Marisa , Chung Mi Hae , Bai Xiaoxiao , Purcaro Michael , Motelow Joshua E. , Danielson Nathan , Dix‐Cooper Linda , Enev Miro , Novotny Edward J. , Constable R. T. , Blumenfeld Hal 
Published: July 2010

SummaryPurpose:  Absence seizures cause transient impairment of consciousness. Typical absence seizures occur in children, and are accompanied by 3–4‐Hz spike–wave discharges (SWDs) on electroencephalography (EEG). Prior EEG–functional magnetic resonance imaging (fMRI) studies of SWDs have shown a network of cortical and subcortical changes during these electrical events. However, fMRI during typical childhood absence seizures with confirmed impaired consciousness has not been previously investigated.Methods:  We performed EEG‐fMRI with simultaneous behavioral testing in 37 children with typical childhood absence epilepsy (CAE). Attentional vigilance was evaluated by a continuous performance task (CPT), and simpler motor performance was evaluated by a repetitive tapping task (RTT).Results:  SWD episodes were obtained during fMRI scanning from 9 patients among the 37 studied. fMRI signal increases during SWDs were observed in the thalamus, frontal cortex, primary visual, auditory, somatosensory, and motor cortex, and fMRI decreases were seen in the lateral and medial parietal cortex, cingulate gyrus, and basal ganglia. Omission error rate (missed targets) with SWDs during fMRI was 81% on CPT and 39% on RTT. For those seizure epochs during which CPT performance was impaired, fMRI changes were seen in cortical and subcortical structures typically involved in SWDs, whereas minimal changes were observed for the few epochs during which performance was spared.Discussion:  These findings suggest that typical absence seizures involve a network of cortical–subcortical areas necessary for normal attention and primary information processing. Identification of this network may improve understanding of cognitive impairments in CAE, and may help guide development of new therapies for this disorder.
Decreased Pulmonary Inflammation Following Ethanol and Burn Injury in Mice Deficient in TLR4 but not TLR2 Signaling
Authors: Bird Melanie D. , Zahs Anita , Deburghgraeve Cory , Ramirez Luis , Choudhry Mashkoor A. , Kovacs Elizabeth J. 
Published: July 2010

Background:  Clinical and laboratory evidence suggests that alcohol consumption prior to burn injury leads to dysregulated immune function and subsequent higher rates of morbidity and mortality. Our laboratory previously observed higher levels of pro‐inflammatory cytokines and leukocyte infiltration in the lungs of mice following ethanol and burn injury. To understand the mechanism of the increased inflammatory response, we looked at different signaling initiators of inflammation including toll‐like receptors 2 and 4 (TLR2 and 4) pathways.Methods:  Wild‐type, TLR2, and TLR4 knockout mice were treated with vehicle or a single binge dose of ethanol (1.11 g/kg) and subsequently given a sham or burn injury. Twenty‐four hours postinjury, systemic and pulmonary levels of pro‐inflammatory cytokines were quantified, and differences in neutrophil infiltration were determined by histological examination.Results:  Higher numbers of neutrophils were observed in the lungs of wild‐type mice following the combined insult of ethanol and burn injury relative to either injury alone. This increase in leukocyte accumulation was absent in the TLR4 knockout mice. Circulating levels of IL‐6 and tumor necrosis factor‐α were also elevated in wild‐type mice but not in TLR4 knockout mice. Consistent with these findings, pulmonary levels of KC and IL‐6 were increased in wild‐type mice following burn and ethanol compared to burn injury alone as well as to their TLR4 knockout counterparts. In contrast, TLR2 knockout mice displayed similar levels, to wild‐type mice, of neutrophil infiltration as well as IL‐6 and KC in the lung.Conclusions:  These data suggest that TLR4 signaling is a crucial contributory component in the exuberant inflammation after ethanol and burn injury. However, TLR2 does not appear to play a vital role in the aberrant pulmonary inflammation.
Long‐Term Effects of Conjugated Equine Estrogen Therapies on Domain‐Specific Cognitive Function: Results from the Women's Health Initiative Study of Cognitive Aging Extension
Authors: Espeland Mark A. , Brunner Robert L. , Hogan Patricia E. , Rapp Stephen R. , Coker Laura H. , Legault Claudine , Granek Iris , Resnick Susan M. ,   for the Women's Health Initiative Study of Cognitive Aging Study Group
Published: July 2010

OBJECTIVES: To determine whether small decrements in global cognitive function that conjugated equine estrogen (CEE) therapies have been shown to produce in older women persist after cessation and extend to specific cognitive domains.DESIGN: Randomized controlled clinical trial.SETTING: Fourteen clinical centers of the Women's Health Initiative.PARTICIPANTS: Two thousand three hundred four women aged 65 to 80 free of probable dementia at enrollment.INTERVENTION: CEE 0.625 mg/d with or without medroxyprogesterone acetate (MPA, 10 mg/d) and matching placebos.MEASUREMENTS: Annual administrations of a battery of cognitive tests during and after the trial.RESULTS: Assignment to CEE‐based therapies was associated with small mean relative decrements in global cognitive function and several domain‐specific cognitive functions during the trial, which largely persisted through up to 4 years after the trial. The strongest statistical evidence was for global cognitive function (0.07–standard deviation decrements during (P=.007) and after (P=.01) the trial. For domain‐specific scores, the mean decrements were slightly smaller, were less significant, and tended to be larger for CEE‐alone therapy.CONCLUSION: CEE‐based therapies, when initiated after the age of 65, produce a small broad‐based decrement in cognitive function that persists after their use is stopped, but the differences in cognitive function are small and would not be detectable or have clinical significance for an individual woman. Differences in effects between cognitive domains suggest that more than one mechanism may be involved.
Assessing Dimensionality and Responsiveness of Outcomes Measures for Patients with Low Back Pain
Authors: Cleland Josh , Gillani Rabya , Bienen E. Jay , Sadosky Alesia 
Published: July 2010

AbstractObjective:  To provide a systematic literature review of the responsiveness of patient‐reported health outcomes measures for the evaluation of low back pain (LBP).Methods and Design:  Searches of MEDLINE and EMBASE were performed for articles published in English through June 29, 2009 using the search terms “back pain” or “low back pain” and “questionnaires” or “instrument” or “survey” or “measure” or “patient report outcome.” Information on responsiveness was gathered through additional measure‐specific searches that included the measure name, first author of the original paper, and “respons*” or “sensit*.” Responsiveness was determined based on use of a receiver operating characteristics curve or effect size statistics.Results:  Of 43 identified measures, 31 were reported as being responsive to treatment or clinical change, 25 of which were evaluated for responsiveness using methods considered adequate. When considering both the responsiveness evaluation and the underlying factor structure, 13 measures were identified as being adequately validated for use in evaluating responsiveness in the research or clinical practice setting. The majority of the LBP outcome assessment studies were comprised of patients undergoing physical and interventional therapies from clinical practice and clinical trials. The Roland Morris Disability Questionnaire and the Oswestry Disability Index were the most comprehensively validated measures with respect to responsiveness.Conclusions:  We identified 13 measures of LBP that can be used to evaluate responsiveness to change. Choice of a measure warrants careful evaluation of its construct and responsiveness properties in order to maximize the observed impact on pain and functional improvement in subjects with LBP.
Effects of SPLAT® GM sprayable pheromone formulation on gypsy moth mating success
Authors: Onufrieva Ksenia S. , Thorpe Kevin W. , Hickman Andrea D. , Tobin Patrick C. , Leonard Donna S. , Anderson Roberts E. 
Published: July 2010

AbstractSeveral integrated pest management programs rely on the use of mating disruption tactics to control insect pests. Some programs specifically target non‐native species, such as the gypsy moth, Lymantria dispar (L.) (Lepidoptera: Lymantriidae). We evaluated SPLAT® GM, a new sprayable formulation of the gypsy moth sex pheromone disparlure, for its ability to disrupt gypsy moth mating. The study was conducted in 2006, 2007, and 2008 in forested areas in Virginia, USA. Mating success of gypsy moth females was reduced by >99% and male moth catches in pheromone‐baited traps by >90%, in plots treated with SPLAT® GM at dosages ranging from 15 to 75 g of active ingredient (a.i.) ha−1. Dosage‐response tests conducted in 2008 indicated that SPLAT® GM applied at a dosage of 7.5 g a.i. ha−1 was as effective as a 15 g a.i. ha−1 dosage.
Temperature‐by‐nutrient interactions affecting growth rate in an insect ectotherm
Authors: Lee Kwang Pum , Roh Chris 
Published: July 2010

AbstractTemperature and nutrition are two prominent environmental variables influencing juvenile growth rate in ectotherms. These two factors interact in complex ways. Here, we present a comprehensive analysis of the interactive effects of temperature and nutrition on various components of fitness (growth rate, survival), food intake, and level of energy storage in an insect herbivore, caterpillars of Spodoptera exigua Hübner (Lepidoptera: Noctuidae). In a factorial experimental design, final‐instar caterpillars (i.e., fifth instars) were individually reared at one of three constant temperatures (18, 26, and 34 °C), in which they received one of six diets differing in their ratio of protein and digestible carbohydrate [P:C mixture, expressed as the percentage of diet by dry mass: protein 42%:carbohydrate 0% (42:0), 35:7, 28:14, 21:21, 14:28, and 7:35]. Within the range of test temperatures, larval growth rate increased with rising temperature and was strongly affected by P:C mixture, reaching a maximum on moderate P:C diets at each temperature and falling at very high and low P:C mixtures. There was a significant temperature*diet interaction, such that the difference in growth rates between temperatures was greatest on moderate P:C diets and least on the most extreme diets (42:0 and 7:35). Food intake rate patterns followed a similar trend to growth rate. Rapidly growing animals at high ambient temperature suffered high mortality across all dietary P:C mixtures, but to a greater extent on the extremely unbalanced diets. This suggests that there are developmental and physiological costs associated with fast growth at high temperature, as indicated by high rate of pupation failure and reduced lipid storage efficiency. Our study shows how temperature and nutrition interplay to mediate phenotypic variations in growth rates and energy utilization in an insect ectotherm.
Influence of parasitism and soil compaction on pupation of the green bottle fly, Lucilia sericata
Authors: Cammack Jonathan A. , Adler Peter H. , Tomberlin Jeffery K. , Arai Yuji , Bridges William C. 
Published: July 2010

AbstractThe influence of parasitoids and soil compaction on pupation behavior of blow flies was examined in a host–parasitoid system involving Lucilia sericata (Meigen) (Diptera: Calliphoridae) and Nasonia vitripennis (Walker) (Hymenoptera: Pteromalidae). Larvae of L. sericata were introduced to containers with soil of different compaction levels, with or without parasitoids. Although females of N. vitripennis did not significantly affect the pupation depth of L. sericata, they increased the rate of pupal development by 15.0–23.7 h at 28.4 ± 1.2 °C, and increased the clumping of puparia. Pupation depth of L. sericata was negatively related to soil compaction; mean depth of pupation was 4.4 cm in uncompacted soil and 0.5 cm in high‐compaction soil. In high‐compaction soil, pupal development increased by 10.5–18.8 h at 25.2 ± 0.3 °C, and puparia were clumped. These results provide a framework for locating puparia in forensic investigations and releasing appropriate parasitoids for biological control of blow flies.
Coming to Terms with Separatist Insurgencies
Authors: Harris Albert W. 
Published: July 2010

Although insurgencies may begin their rebellions with expressed desires for outcomes unacceptable to opposing governments, the desired insurgent outcomes sometimes undergo modification, creating conditions that can make governments more amenable to external mediation. In certain separatist conflicts, the likelihood of external mediation increases when the political redefinition of the state insisted upon by the insurgents undergoes a revision, from secession to self‐determination, understood as a variant of autonomy.In the same vein, although it may not happen concurrently, insurgent movements become more amenable to external mediation if and when opposing governments revise the preferred conflict outcome from a military defeat of the insurgents to a containment of the movement. These two developments can serve as objective referents helping external parties to identify a ripe moment in the conflict and initiate mediation.But the implementation of an agreement ending separatist conflict may not occur if the government fails to submit the proposed territorial bounds of autonomy to prior review by constituents. Potential spoilers among government constituents should be identified and recruited to participate in the negotiations so that the likelihood of agreement rejection is reduced. In some states, however, the legal mechanisms and political opportunities for constituents to act as spoilers do not exist.
Role of the metastasis‐promoting protein osteopontin in the tumour microenvironment
Authors: Anborgh Pieter H. , Mutrie Jennifer C. , Tuck Alan B. , Chambers Ann F. 
Published: July 2010

AbstractOsteopontin (OPN) is a secreted protein present in bodily fluids and tissues. It is subject to multiple post‐translational modifications, including phosphorylation, glycosylation, proteolytic cleavage and crosslinking by transglutamination. Binding of OPN to integrin and CD44 receptors regulates signalling cascades that affect processes such as adhesion, migration, invasion, chemotaxis and cell survival. A variety of cells and tissues express OPN, including bone, vasculature, kidney, inflammatory cells and numerous secretory epithelia. Normal physiological roles include regulation of immune functions, vascular remodelling, wound repair and developmental processes. OPN also is expressed in many cancers, and elevated levels in patients’ tumour tissue and blood are associated with poor prognosis. Tumour growth is regulated by interactions between tumour cells and their tissue microenvironment. Within a tumour mass, OPN can be expressed by both tumour cells and cellular components of the tumour microenvironment, and both tumour and normal cells may have receptors able to bind to OPN. OPN can also be found as a component of the extracellular matrix. The functional roles of OPN in a tumour are thus complex, with OPN secreted by both tumour cells and cells in the tumour microenvironment, both of which can in turn respond to OPN. Much remains to be learned about the cross‐talk between normal and tumour cells within a tumour, and the role of multiple forms of OPN in these interactions. Understanding OPN‐mediated interactions within a tumour will be important for the development of therapeutic strategies to target OPN.
Persistence of borrelial DNA in the joints of Borrelia burgdorferi‐infected mice after ceftriaxone treatment
Authors: YRJÄNÄINEN HETA , HYTÖNEN JUKKA , HARTIALA PAULIINA , OKSI JARMO , VILJANEN MATTI K. 
Published: July 2010

Yrjänäinen H, Hytönen J, Hartiala P, Oksi J, Viljanen MK. Persistence of borrelial DNA in the joints of Borrelia burgdorferi‐infected mice after ceftriaxone treatment. APMIS 2010; 118: 665–73.We have earlier shown that Borrelia burgdorferi‐infected and ceftriaxone‐treated mice have viable spirochetes in their body, since immunosuppressive treatment allows B. burgdorferi to be detected by culture. However, the niche of the persisting spirochetes remained unknown. In the present study, we analyzed the tissues of B. burgdorferi‐infected and ceftriaxone‐treated mice by culture and PCR to reveal the foci of persisting spirochetes. C3H/HeN mice were infected via intradermal needle injection with B. burgdorferi s.s. N40. The mice were treated as follows: (i) short (5 days) and (ii) long (18 days) course of ceftriaxone at 2 weeks of infection and killed after either 10 or 30 weeks, or (iii) the mice received ceftriaxone for 5 days at 18 weeks of infection and were killed 21 weeks after the treatment. All samples of ceftriaxone‐treated mice were culture negative, whereas all untreated controls were culture positive. Importantly, B. burgdorferi DNA was detected in the joints of 30–100% of the treated mice. In conclusion, these results combined with earlier results suggest that the joint or a tissue adjacent to the joint is the niche of persisting B. burgdorferi in ceftriaxone‐treated mice.