bluuebunny/crossref_metadata_2025_split huggingface dataset:
GABRB3, Epilepsy, and Neurodevelopment
Authors: Tanaka Miyabi , DeLorey Timothy M. , Delgado-Escueta Antonio V. , Olsen Richard W. 
Published: May 2013

Abstract
Three neurodevelopmental disorders—Angelman syndrome (AS), Rett syndrome (RS), and autism spectrum disorders (ASD)—share several clinical features, most notably neurodevelopmental delay and epilepsy. Here, we ask: what common mechanisms do these three neurodevelopmental disorders share that lead to a decline in cognitive development and epilepsy? Based on our observations concerning the genetic regulation of GABRB3 in childhood absence epilepsy (CAE), we posit that the genetic mutations in these three neurodevelopmental disorders converge on a common disease mechanism involving genetic and epigenetic regulation of GABRB3. We first explain the data on human CAE supporting this hypothesis and show that three different point mutations in an alternative signal sequence (exon 1A) and N terminus (exon 2) in GABRB3 result in hyperglycosylation and decreased gamma-aminobutyric acid (GABA) currents, all of which segregate with CAE. One of the variants of exon 1A, P11S, which is maternally transmitted, links GABRB3 dysfunction with ASD and provides a possible cause of the seizures in this syndrome. In AS, GABRB3 deletion contributes to the severe seizure phenotype. Rett syndrome is caused by mutations in MeCp2. Because MeCp2 epigenetically regulates GABRB3, reduced expression of GABRB3 and epilepsy are considered consequences of MeCp2 mutations. We then review the significance of GABRB3 in embryonic and adult neurogenesis and neuronal development in mammalian brain. We point to a master regulator of neurogenesis, RE1 silencing transcription factor (REST), which binds to repressor element 1 (RE1) in intron 3 and the 5′ region of GABRB3. REST epigenetically regulates tissue and developmental expression of GABRB3. Finally, we chart the future challenges and experiments that could prove or disprove our hypothesis that REST and epigenetic regulation are involved in neurogenesis and epileptogenesis of absence seizures.
Pathophysiology of Epilepsy in Autism Spectrum Disorders
Authors: Stafstrom Carl E. , Hagerman Paul J. , Pessah Isaac N. 
Published: May 2013

Abstract
Why are seizures so common in children with autism? This relatively straightforward question does not, unfortunately, have a straightforward answer. In this chapter, we explore this question from clinical, pathophysiological, and molecular perspectives, using as examples two genetic disorders that share a high prevalence of autism and epilepsy—fragile X syndrome (FXS) and tuberous sclerosis complex (TSC)—with the hope that understanding the pathophysiology of these monogenic conditions will lead to broader understanding of neural hyperexcitability in other autism syndromes. We conclude by discussing cellular and network dysfunctions that might be amenable to targeted treatments in these disorders, with potential wider applicability to idiopathic autism.
Deep Brain Stimulation for Epilepsy
Authors: Graber Kevin D. , Fisher Robert S. 
Published: May 2013

Abstract
Studies of deep brain stimulation in laboratory models of seizures and epilepsy are invaluable for understanding the mechanisms of stimulation and for identifying the best targets and parameters of stimulation. Unfortunately, existing laboratory studies of brain stimulation in epilepsy models present an incomplete and often contradictory picture (Table 79–1). Some efficacy for deep brain stimulation has been documented in labora tory models involving the cerebellar cortex, caudate, hypothalamus, subthalamus, centromedian and midline thalamus, anterior thalamus, hippocampus, and neocortex. However, many studies are empiric in nature and mechanisms, and our understanding of the optimal parameters remains incomplete. Pivotal clinical trials with the ANT and responsive neural stimulation of the hippocampus and neocortex have been effective in reducing seizures. These recent successes in clinical studies may give more impetus to laboratory investigations, which in turn will potentially further our clinical practice.
Strategies for Antiepileptogenesis
Authors: Löscher Wolfgang 
Published: May 2013

Abstract
Epileptogenesis, that is, the process leading to epilepsy, is a common sequel of brain insults such as head trauma, cerebrovascular disease, brain tumors, neurosurgical procedures, neurodegenerative conditions, status epilepticus (SE), and complex febrile seizures.1–3 Following such brain insults, there is a cascade of morphological and functional changes in the injured area over months to years before the occurrence of spontaneous recurrent seizures, that is, the hallmark of epilepsy (Fig. 81–1). This latent (“silent”) period may offer a therapeutic window for the prevention of epileptogenesis and the subsequent development of unprovoked seizures and epilepsy.2
Neural Stem Cell Therapy for Temporal Lobe Epilepsy
Authors: Shetty Ashok K. 
Published: May 2013

Abstract
The major objective of this chapter is to evaluate the contemporary knowledge and to put forward perspectives concerning the NSC grafting therapy for TLE. Since the efficiency of grafting of neural progenitors obtained from the fetal brain or ES cells are covered in other chapters in this book, this chapter is deliberately confined to studies on the efficacy of NSC grafts in TLE prototypes. The first section will focus on the prospects for preventing or minimizing SRS using NSC grafting procedures that are performed shortly after the initial precipitating injury (IPI), such as SE or a direct excitotoxic lesion. The second section will consider the promise of NSC grafting therapy for restraining seizures and easing cognitive dysfunction when applied shortly after or at prolonged periods after the onset of SE- or kindling- induced TLE. Several critical issues that need to be resolved before initiating the clinical application of NSC grafting therapy for TLE are also discussed.
Embryonic Stem Cell Therapy for Intractable Epilepsy
Authors: Naegele Janice R. , Vemuri Mohan C. , Studer Lorenz 
Published: May 2013

Abstract
Envisioning a world in which humans are able to regenerate severed limbs, rewire neural pathways, and enhance sensory perception has been a mainstay of science fiction novels and movies for decades. While human limb regeneration is still not possible, remarkable developments in the fields of stem cell biology and neuroscience are leading the way for stem cell-based therapies to amend brain and spinal cord damage and repair sensory organs. In this chapter, we discuss recent efforts to derive neural stem cells from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) and their applications to treating conditions such as temporal lobe epilepsy (TLE) and neurodegenerative diseases.
Gene Therapy of Focal-Onset Epilepsy Using Adeno-Associated Virus Vector-Mediated Overexpression of Neuropeptide Y
Authors: Noè Francesco M. , Sørensen Andreas T. , Kokaia Merab , Vezzani Annamaria 
Published: May 2013

Abstract
Although various new antiepileptic drugs (AEDs) with diverse mechanisms of action have been developed in the last 15 years with improved tolerability and pharmacokinetic properties,1,2 there has been relatively little improvement in their ability to control pharmacoresistant epilepsies compared to traditional AEDs. Thus, about 30% of patients with epilepsy still have seizures that are resistant to available AEDs. Drug-resistant epileptic patients are considered for surgical resection of the epileptic focus: this invasive procedure, however, is suitable only for a minority of them and results in complete control of epilepsy (seizure freedom without AEDs) in about 30% to 50% of cases, according to a 5- to 10-year follow-up study.3 Additionally, most AEDs provide symptomatic suppression of seizures without apparently interfering with the mechanisms involved in the epileptic process.4,5 Currently, AEDs mainly target neurotransmitter receptors, mechanisms of neurotransmitter release or reuptake, or ion channels.1 There is therefore an urgent need to find novel treatment strategies, particularly for the most refractory forms, such as temporal lobe epilepsy (TLE). 4,6 As an alternative approach to pharmacotherapy, preclinical studies in models of seizures and epilepsy are addressing the possibility of suppressing seizures by inducing the overexpression of neuromodulatory molecules in the area(s) of seizure origin or propagation. This may be achieved using gene therapy that has been developed, and clinically applied, in other neurological disorders.7–12 The intent of experimental studies is to establish the proof-of-concept evidence that gene therapy may be envisioned as a novel therapeutic approach to control drug-resistant seizures in focal-onset epilepsies.
The Social Determinants of Depression in Older Adulthood
Authors: Gilman Stephen E. , Carliner Hannah , Cohen Alex 
Published: May 2013

Abstract
There is longstanding evidence of the impact of social and environmental factors on the development of persistence of depression. This chapter reviews the current evidence on the social determinants of depression in older adulthood. In addition, evidence is reviewed on the social determinants of the receipt and effectiveness of treatments for late-life depression. The social determinants of late-life depression onset and treatment outcomes include socioeconomic and demographic factors (socioeconomic status, gender, race/ethnicity), and factors related to social integration (social networks and social support). Future work in this area is needed to understand the etiological pathways underlying these associations, and modifiable points of intervention to reduce the disproportionate burden of late-life depression among population subgroups at highest risk.
Structural Brain Abnormalities in Bipolar Disorder
Authors: Matsuo Koji , Sanches Marsal , Brambilla Paolo , Soares Jair C. 
Published: May 2013

AbstractStructural brain imaging, particularly using fMRI, provides a means to identify the neuroanatomic substrate for psychiatric conditions, including bipolar disorder. Regional brain volumetric studies suggest enlargement in several key structures that subsume emotional and cognitive control, including striatum (particularly putamen) and possibly amygdala in adult bipolar subjects. Decreased volumes have been observed in prefrontal areas, the cerebellar vermis and white matter structures. Unlike findings in adults, bipolar youth exhibit decreased amygdala volumes, suggestion developmental specificity of abnormalities within this structure. The functional meaning of these abnormalities has been difficult to ascertain, as correlations with clinical data are often inconsistent. Nonetheless, some changes seem to reflect progression related to the number of affective episodes as well as potentially from treatment exposure. In particular, lithium may increase gray matter volumes in some structures (e.g., amygdala) over time. White matter abnormalities have also been relatively consistently demonstrated using various structural imaging techniques in bipolar disorder. These findings support a neuroanatomic model of bipolar disorder involving abnormalities within ventral brain networks that modulate mood.
Neuroimaging in Bipolar Disorder and Schizophrenia
Authors: Whalley Heather C. , Sussmann Jessika E. , McIntosh Andrew M. 
Published: May 2013

AbstractBipolar disorder and schizophrenia are overlapping syndromes that show evidence of shared risk factors, treatments and disease outcomes. Magnetic resonance imaging has been used to address the question of whether these are separate diseases or whether a single category or dimension better explains clinical observations. Evidence from brain imaging has yielded a complex answer. Studies of grey and white matter imaging suggest a degree of overlap, but investigations to date have been too small and infrequent to come to any confident conclusion. Studies using functional MRI on the other hand, suggest that there may be significant differences in task related activation of frontotemporal and limbic brain regions, possibly mirroring the relatively common and distinct clinical phenotypes seen in practice. These findings suggest that imaging may yet prove to have predictive diagnostic value and utility in defining syndromes more closely related to their underlying etiology.
A cohort study of chest pain patients discharged from the emergency department for early outpatient treadmill exercise stress testing
Authors: Paoloni Richard , Ibuowo Razaq 
Published: May 2013

AbstractObjectiveGuidelines on intermediate‐risk chest pain, based on consensus alone, recommend inpatient provocative testing after infarct exclusion. Inpatient testing exceeds capacity in many hospitals, so guidelines concede outpatient testing within 72 h is acceptable. We performed a cohort study of chest pain patients having early outpatient treadmill exercise stress testing (EST).MethodsAll chest pain patients discharged from our emergency with booked outpatient treadmill EST during the 2008 to 2010 calendar years were included. There were no exclusions. The primary outcome was diagnosis of major coronary artery disease among stress test attendees. Secondary outcomes were time to stress test booking, representations with chest pain or death within 30 days.ResultsThe cohort consisted of 657 patients: 59% men, mean age 53.2 years. Time from discharge to stress test averaged 10.6 days and 73% of patients attended. Of patients who attended, 14% had a positive test and 13% an inconclusive result. These patients were older than those with negative results (P < 0.001). Four patients (0.8% of attendees) were diagnosed with major coronary artery disease. There were no representations with acute myocardial infarction and no deaths identified.ConclusionsOutpatient treadmill EST an average of 10 days post‐discharge from emergency with chest pain did not result in adverse events despite reasonably high positive stress test rates. Consensus‐based recommendations for inpatient testing or outpatient testing within 72 h of discharge should be reviewed in light of these data.
Cranofacial osteosarcoma: Single institutional experience in Korea
Authors: Lim Seungtaek , Lee Soohyeon , Rha Sun Young , Rho Jae Kyung 
Published: May 2013

AbstractIntroductionCraniofacial osteosarcoma is a rare disease accounting for only 1% of all head and neck malignancies. Its clinical features and optimal treatments are not yet clearly established.MethodsWe retrospectively analyzed the clinical course of 15 patients with craniofacial osteosarcoma treated in a single institute.ResultsOut of 13 patients who initially underwent primary mass resection, disease recurrence was found in five (36%). Patients with positive surgical margins showed higher recurrence and shorter median recurrence‐free and overall survival. Of three patients who had secondary operation after local recurrence, two survived for 44.6 and 64.2 months, respectively. One patient who underwent repeated lung metastasectomy had a disease‐free survival of 18.4 months from the first recurrence.ConclusionThe current study demonstrates that positive surgical margins are important predictive factors for recurrence and overall survival. Salvage surgery for local recurrence and metastasectomy for systemic recurrence might have a positive impact on survival.
Why are there delays in seeking treatment for childhood diarrhoea in India?
Authors: Malhotra Nisha , Upadhyay Ravi Prakash 
Published: May 2013

AbstractAimTo examine the barriers and facilitating factors for seeking treatment for childhood diarrhoea and to determine the main causes for delay in seeking treatment.MethodsData from Indian Demographic and Health survey 2005–06 (NFHS‐III) were used. Mothers were asked whether their children (<5‐years) had suffered from diarrhoea during the 2 weeks preceding the survey. Data were collected on the time of seeking treatment after start of the illness and days waited to seek treatment after the diarrhoea started. Multivariate logistic regression analysis was performed to find the determinants of seeking treatment at the health facility and the factors responsible for the ‘delay’ in seeking advice/treatment.ResultsOf a sample of 41 287 children, 3890 (9.4%) reportedly had diarrhoea. Sixty percentage of children with diarrhoea were taken to a health facility. Mother's education till higher secondary and above (OR 1.65; 95% CI, 1.08–2.54), richest (OR 1.76; 95% CI, 1.24–2.48) wealth index, and possession of a health card by the mother (OR 1.35; 95% CI, 1.12–1.62) increased the odds of seeking treatment. There was a strong gender bias; a male child had lower odds of experiencing a ‘delay’ in seeking treatment, compared with a female child (OR 0.71; 95% CI, 0.55–0.92). Access to a health facility still remains a major issue: treatment seeking was delayed when distance to a health facility was reported as a ‘major problem’ (OR 1.33; 95% CI, 1.01–1.76).Conclusion(s)Improved care seeking for childhood diarrhoea in India is still constrained by access to a health facility and requires expansion and strengthening of the public health system. The caregivers, especially the mothers need to be educated about the importance of seeking timely treatment and the benefits of oral rehydration solution.
Diagnostic methods used to monitor an outbreak of babesiosis (Babesia bovis) in a herd of feral cattle in New Caledonia
Authors: Hüe T , Graille M , Mortelecque A , Desoutter D , Delathière JM , Marchal C , Teurlai M , Barré N 
Published: May 2013

BackgroundIn December 2007, Babesia bovis was introduced to New Caledonia through the importation of cattle vaccinated with a live tick fever (babesiosis and anaplasmosis) vaccine. Medical measures, acaricide and antiprotozoal treatments, and quarantine restrictions were implemented with success on all the farms involved, but the disease spread to one of the neighbouring properties where feral cattle were present. To circumscribe and eliminate this outbreak, the authorities decided to slaughter all animals on the neighbouring property.ObjectivesTo monitor the spread of babesiosis in naïve cattle and to compare the usefulness of PCR, ELISA and brain smear for disease detection in monitoring this outbreak.MethodsBlood and brain samples of slaughtered animals were analysed over time throughout the eradication campaign using serology, PCR and brain smears. In addition, field numbers of Rhipicephalus microplus tick larvae were assessed and Babesia infection of the larvae analysed using PCR.ResultsThis study showed the natural spread of babesiosis in a naïve herd without pharmacological control measures. Prevalence reached 80% within a year of introduction. ELISA and PCR tests performed similarly in detecting disease in cattle and both were superior to brain smears. Nevertheless, specific tests or combinations of tests may be preferable, depending on the specific requirements of any future disease situation.ConclusionsIn cattle, ELISA and PCR appear to be suitable tools for monitoring the evolution of a babesiosis outbreak, with brain smears as a useful adjunct. PCR was not suitable for detecting infection in tick larvae.
Methicillin‐resistant Staphylococcus aureus: an issue for veterinary hospitals
Authors: Allen JL , Abraham LA , Thompson K , Browning GF 
Published: May 2013

ObjectiveTo investigate the spread of methicillin‐resistant Staphylococcus aureus (MRSA) isolated from a cluster of clinical cases at a veterinary hospital by molecular epidemiological techniques.MethodsAntimicrobial susceptibility testing, spa typing, multilocus sequence typing and pulsed‐field gel electrophoresis were used to compare 16 isolates of MRSA. Four isolates were cultured from clinical cases thought to be involved in the cluster. A single isolate that was unrelated to the cluster and the remaining 10 isolates were obtained from nasal swabs submitted by staff and students during a subsequent survey of MRSA carriage.ResultsIsolates from four clinical cases and an isolate obtained from a staff member were the same strain of MRSA. Some key risk factors associated with transmission of MRSA within veterinary hospitals were identified.ConclusionThe information provided by these techniques was invaluable in developing procedures and identifying risk factors to help reduce the effect of future outbreaks within veterinary hospitals.
Indications, durations and outcomes of mechanical ventilation in dogs and cats with tick paralysis caused byIxodes holocyclus: 61 cases (2008–2011)
Authors: Webster RA , Mills PC , Morton JM 
Published: May 2013

ObjectivesThe primary objectives of this research were to describe the indications for mechanical ventilation, the duration of mechanical ventilation and probability of survival in dogs and cats with respiratory failure induced by the Australian paralysis tick (Ixodes holocyclus).MethodsA retrospective case series and a retrospective single cohort study were conducted using dogs and cats with tick paralysis requiring mechanical ventilation. An index of oxygenating performance of the lung (PFratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen) was derived from arterial blood gas analysis; patients euthanased because of veterinary costs were identified andKaplan‐Meier survival analyses performed.ResultsIn total, 36.6% of patients were ventilated because of hypoxaemia refractory to oxygen therapy, 38.3% because of hypoventilation, 18.3% because of unsustainable respiratory effort and 6.6% because of respiratory arrest. Median duration of mechanical ventilation was 23 h, median time hospitalised was 84 h and 63.9% of all patients requiring mechanical ventilation survived to discharge from the hospital. Survival probability increased to 75% when cases of cost‐based euthanasia were right‐censored rather than treated as deaths. The survival probability of patients ventilated because of hypoxaemia (52.6%) was significantly less than for those ventilated because of hypoventilation (90.5%). The first measuredPFratio after commencing mechanical ventilation was not significantly associated with survival probability.ConclusionsDogs and cats with tick paralysis requiring mechanical ventilation to manage respiratory failure have reasonable survival probability. Dogs and cats requiring mechanical ventilation because of hypoventilation have a higher survival probability than those with oxygenation failure.
Retrospective analysis of complications and outcomes inBoxers andStaffordshireBullTerriers undergoing cranial cruciate ligament surgery
Authors: Levien AS , Brodbelt DC , Arthurs GI 
Published: May 2013

ObjectiveThe aim of this study was to determine whetherBoxers andStaffordshireBullTerriers (SBT) have a higher incidence of complications or a worse outcome after cranial cruciate ligament (CCL) surgery compared with control breeds.DesignThe design was a retrospective cohort study with data reviewed from medical records and outcome assessed by owner questionnaire.ResultsThe cohort included 210 canine stifles comprising 33Boxers, 47SBTsand 130 controls. ForBoxers, the overall complication rate (39.4%), major complication rate (30.3%) and revision surgery rates (18.2%) were significantly higher than those of the control groups (14.6%, 10.8% and 4.6%, respectively). Overall,SBTswere no more likely to suffer complications or repeat surgery than the control group. Considering only lateral fabello‐tibial suture (LFS) stabilisation, bothBoxers (32.0%) andSBTs(23.3%) had higher complication rates than the control group (6.3%). There were no significant differences in outcome among theBoxer,SBTand control groups; median follow‐up time was 2 years (range 0.5–7 years).ConclusionsThe overall complication rate forBoxers undergoingCCLsurgery was higher compared with other breeds of dog. When surgical techniques were analysed separately, theLFSwas associated with a higher complication rate inBoxers andSBTs. Further investigation into breed‐specific surgical techniques is indicated.