bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADCK3 mutations with epilepsy, stroke‐like episodes and ataxia: a POLG mimic?
Authors: Hikmat O. , Tzoulis C. , Knappskog P. M. , Johansson S. , Boman H. , Sztromwasser P. , Lien E. , Brodtkorb E. , Ghezzi D. , Bindoff L. A. 
Published: April 2016

Background and purposeDefects of coenzyme Q10 (CoQ10) metabolism cause a variety of disorders ranging from isolated myopathy to multisystem involvement. ADCK3 is one of several genes associated with CoQ10 deficiency that presents with progressive cerebellar ataxia, epilepsy, migraine and psychiatric disorders. Diagnosis is challenging due to the wide clinical spectrum and overlap with other mitochondrial disorders.MethodsA detailed description of three new patients and one previously reported patient from three Norwegian families with novel and known ADCK3 mutations is provided focusing on the epileptic semiology and response to treatment. Mutations were identified by whole exome sequencing and in two measurement of skeletal muscle CoQ10 was performed.ResultsAll four patients presented with childhood‐onset epilepsy and progressive cerebellar ataxia. Three patients had epilepsia partialis continua and stroke‐like episodes affecting the posterior brain. Electroencephalography showed focal epileptic activity in the occipital and temporal lobes. Genetic investigation revealed ADCK3 mutations in all patients including a novel change in exon 15: c.T1732G, p.F578V. There was no apparent genotype−phenotype correlation.ConclusionADCK3 mutations can cause a combination of progressive ataxia and acute epileptic encephalopathy with stroke‐like episodes. The clinical, radiological and electrophysiological features of this disorder mimic the phenotype of polymerase gamma (POLG) related encephalopathy and it is therefore suggested that ADCK3 mutations be considered in the differential diagnosis of mitochondrial encephalopathy with POLG‐like features.
Long‐term prognosis of epilepsy, prognostic patterns and drug resistance: a population‐based study
Authors: Giussani G. , Canelli V. , Bianchi E. , Erba G. , Franchi C. , Nobili A. , Sander J. W. , Beghi E. ,   the EPIRES Group
Published: April 2016

Background and purposeSeizures in most people with epilepsy remit but prognostic markers are poorly understood. There is also little information on the long‐term outcome of people who fail to achieve seizure control despite the use of two antiepileptic drugs (drug resistance).MethodsPeople with a validated diagnosis of epilepsy in whom two antiepileptic drugs had failed were identified from primary care records. All were registered with one of 123 family physicians in an area of northern Italy. Remission (uninterrupted seizure freedom lasting 2 years or longer) and prognostic patterns (early remission, late remission, remission followed by relapse, no remission) were determined.ResultsIn all, 747 individuals (381 men), aged 11 months to 94 years, were followed for 11 045.5 person‐years. 428 (59%) were seizure‐free. The probability of achieving 2‐year remission was 18% at treatment start, 34% at 2 years, 45% at 5, 52% at 10 and 67% at 20 years (terminal remission, 60%). Epilepsy syndrome and drug resistance were the only independent predictors of 2‐ and 5‐year remission. Early remission was seen in 101 people (19%), late remission in 175 (33%), remission followed by relapse in 85 (16%) and no remission in 166 (32%). Treatment response was the only variable associated with differing prognostic patterns.ConclusionThe long‐term prognosis of epilepsy is favourable in most cases. Early seizure remission is not invariably followed by terminal remission and seizure outcome varies according to well‐defined patterns. Prolonged seizure remission and prognostic patterns can be predicted by broad syndromic categories and the failure of two antiepileptic drugs.
The syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis mimicking an acute stroke
Authors: Guillan M. , DeFelipe‐Mimbrera A. , Alonso‐Canovas A. , Matute M. C. , Vera R. , Cruz‐Culebras A. , Garcia‐Barragan N. , Masjuan J. 
Published: April 2016

Background and purposeThe syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL) can present as sudden onset of focal neurological deficits which are clinically and radiologically indistinguishable from an ischaemic stroke. Its diagnosis requires a lumbar puncture (LP), which contraindicates intravenous thrombolytic therapy (IV‐tPA).MethodsAll patients referred to our stroke centre as a stroke code resulting in a final diagnosis of HaNDL syndrome from June 2005 to June 2015 were retrospectively analysed.ResultsNine cases were identified: seven women and two men (mean age 27.6 years, range 15–51). Clinical onset consisted of isolated aphasia (two) and aphasia with right hemiparesis/hemiparaesthesia (seven). All patients had headache in the acute setting, lasting 2–12 h. Cranial computed tomography (CT) and CT angiography (CTA) were normal in all patients. Perfusion CT was performed in seven patients, showing left hemispheric focal hypoperfusion in five cases; the remaining two were normal. Five patients were initially diagnosed as stroke and treated uneventfully with IV‐tPA. Cranial magnetic resonance imaging within 48 h was normal in all cases. LP performed in all patients showed pleocytosis (range 17–351 cells/mm3), high protein levels (range 0.4–1.6 g/l) and normal glucose levels. All cases recovered within 12 h and suffered a second episode within 72 h. Patients were asymptomatic between episodes and after remission.ConclusionsThe decision to thrombolyse or perform an LP in HaNDL patients mimicking a stroke is difficult in the acute setting. Perfusion CT can provide misleading results and CTA may be useful in ruling out occlusion of a cerebral vessel.
Fibulin‐5: a novel biomarker for evaluating severity and predicting prognosis in patients with acute intracerebral haemorrhage
Authors: Hu L. , Dong M.‐X. , Zhao H. , Xu G.‐H. , Qin X.‐Y. 
Published: April 2016

Background and purposeThe aim was to investigate relationships between serum fibulin‐5 concentration and the severity or prognosis in patients with acute intracerebral haemorrhage (ICH).MethodsConsecutive ICH patients and healthy controls were included and clinical data were collected. National Institute of Health Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS) were assessed at admission time within 3 days after bleeding. Cerebral haemorrhage volume was calculated and serum fibulin‐5 concentration was measured at the same time. Multivariate linear regression analyses were performed to determine risk factors for serum fibulin‐5 concentration and Spearman correlation coefficients were obtained to explore the relationships between fibulin‐5 concentration and NIHSS or GCS scores. Patients were followed up for 3 months and the modified Rankin Scale was evaluated for all survivors. Receiver operating characteristic (ROC) curves were obtained to explore fibulin‐5 concentration in predicting prognosis.ResultsSerum fibulin‐5 concentration had increased in ICH patients compared with healthy controls (65.86 ± 26.39 μg/l vs. 40.66 ± 5.03 μg/l, P = 0.00) and was mainly influenced by haemorrhage volume (β = 0.905, P = 0.000) and extension to ventricles (β = 10.173, P = 0.097). Serum fibulin‐5 concentration was positively correlated with NIHSS score (r = 0.511, P = 0.000) but inversely correlated with GCS score (r = −0.585, P = 0.000). Based on the ROC curves, the optimal cut‐off point was 80.68 μg/l for death, and the sensitivity and specificity values of serum fibulin‐5 were 77.8% and 93.2%, whilst the optimal cut‐off point was 48.45 μg/l for poor prognosis and the sensitivity and specificity values were 86.4% and 54.1%, respectively.ConclusionsSerum fibulin‐5 concentration can be regarded as a biomarker for evaluating disease severity and predicting prognosis in ICH patients.
Managing anti‐epileptic drug treatment in adult patients with intellectual disability: a serious conundrum
Authors: Doran Z. , Shankar R. , Keezer M. R. , Dale C. , McLean B. , Kerr M. P. , Devapriam J. , Craig J. , Sander J. W. 
Published: April 2016

Background and purposeAbout a quarter of people with epilepsy have intellectual disability (ID). This group has communication issues, premature mortality, more treatment resistance, difficulties in making informed choices and greater risks of physical and mental health comorbidities. There is no specific prescribing guidance for this large and vulnerable group. The literature on prescribing for epilepsy in this group was reviewed, in particular examining how antiepileptic drugs (AEDs) work regarding their side effect profiles, effects on specific epilepsy syndromes associated with ID and their individual strengths and weaknesses based on the nature and degree of ID.MethodThis is a narrative review for which a comprehensive search was conducted to identify evidence for prescribing commonly used AEDs to people with ID including genetic syndromes specifically associated with epilepsy.ResultsA detailed analysis of the results has highlighted the urgent requirement for suitable and reliable evidence in AED prescribing amongst adults with epilepsy and ID as no studies taking account of the response to AEDs of the ID populations based on the WHO Diagnostic and Statistical Manual of Mental Disorders criteria of clinical severity of ID were identified.ConclusionThere is a significant shortfall in suitably powered studies to provide sufficient evidence for safe prescribing of AEDs to people with ID.
Anti–tumor necrosis factor alpha therapy (adalimumab) in Rasmussen's encephalitis: An open pilot study
Authors: Lagarde Stanislas , Villeneuve Nathalie , Trébuchon Agnès , Kaphan Elsa , Lepine Anne , McGonigal Aileen , Roubertie Agathe , Barthez Marie‐Anne J. , Trommsdorff Valérie , Lefranc Jérémie , Wehbi Samer , des Portes Vincent , Laguitton Virginie , Quartier Pierre , Scavarda Didier , Giusiano Bernard , Milh Mathieu , Bulteau Christine , Bartolomei Fabrice 
Published: April 2016

SummaryObjectiveRasmussen's encephalitis (RE) is a severe chronic inflammatory brain disease affecting one cerebral hemisphere and leading to drug‐resistant epilepsy, progressive neurologic deficit, and unilateral brain atrophy. Hemispherotomy remains the gold standard treatment but causes permanent functional impairment. No standardized medical treatment protocol currently exists for patients prior to indication of hemispherotomy, although some immunotherapies have shown partial efficacy with functional preservation but poor antiseizure effect. Some studies suggest a role for tumor necrosis factor alpha (TNF‐α) in RE pathophysiology.MethodsWe report an open‐label study evaluating the efficacy and the safety of anti‐TNF‐α therapy (adalimumab) in 11 patients with RE. The primary outcome criterion was the decrease of seizure frequency. The secondary outcome criteria were neurologic and cognitive outcomes and existence of side effects.ResultsAdalimumab was introduced with a median delay of 31 months after seizure onset (range 1 month to 16 years), and follow‐up was for a median period of 18 months (range 9–54 months). There was a significant seizure frequency decrease after adalimumab administration (from a median of 360 to a median of 32 seizures per quarter, p ≤ 0.01). Statistical analysis showed that adalimumab had a significant intrinsic effect (p < 0.005) independent from disease fluctuations. Five patients (45%) were found to have sustained improvement over consecutive quarters in seizure frequency (decrease of 50%) on adalimumab. Three of these five patients also had no further neurocognitive deterioration. Adalimumab was well tolerated.SignificanceOur study reports efficacy of adalimumab in terms of seizure frequency control. In addition, stabilization of functional decline occurred in three patients. This efficacy might be particularly relevant for atypical slowly progressive forms of RE, in which hemispherotomy is not clearly indicated. Due to our study limitations, further studies are mandatory to confirm these preliminary results.
Susceptible and protective associations ofHLA DRB1*/DQB1* alleles and haplotypes with ischaemic stroke
Authors: Murali V. , Rathika C. , Ramgopal S. , Padma Malini R. , Arun Kumar M. J. , Neethi Arasu V. , Jeyaram Illiayaraja K. , Balakrishnan K. 
Published: April 2016

SummaryStroke has emerged as the second commonest cause of mortality worldwide and is a major public health problem. For the first time, we present here the association of human leucocyte antigen (HLA)‐DRB1*/DQB1* alleles and haplotypes with ischaemic stroke in South Indian patients. Ischaemic stroke (IS) cases and controls were genotyped forHLA‐DRB1*/DQB1* alleles by polymerase chain reaction sequence‐specific primers (PCR‐SSP) method. The frequencies ofHLAclassIIalleles such asDRB1*04,DRB1*07,DRB1*11,DRB1*12,DRB1*13,DQB1*02 andDQB1*07 were high inISpatients than in the age‐ and gender‐matched controls, suggesting that the individuals with these alleles are susceptible to ischaemic stroke in South India. The frequencies of alleles such asDRB1*03,DRB1*10,DRB1*14,DQB1*04 andDQB1*05 were less inIScases than in the controls, suggesting a protective association. HaplotypesDRB1*04‐DQB1*0301,DRB1*07‐DQB1*02,DRB1*07‐DQB1*0301,DRB1*11‐DQB1*0301 andDRB1*13‐DQB1*06 were found to be high inISpatients conferring susceptibility. The frequency of haplotypeDRB1*10‐DQB1*05 was high in controls conferring protection.IS‐LVDand gender‐stratified analysis too confirmed these susceptible and protective associations.Thus, HLA‐DRB1*/DQB1* alleles and haplotypes strongly predispose South Indian population to ischaemic stroke. Further studies in different populations with large sample size or the meta‐analysis are needed to explain the exact mechanism of associations ofHLAgene(s) withIS.
Tumour‐associated macrophages correlate with microvascular bed extension in colorectal cancer patients
Authors: Marech Ilaria , Ammendola Michele , Sacco Rosario , Sammarco Giuseppe , Zuccalà Valeria , Zizzo Nicola , Leporini Christian , Luposella Maria , Patruno Rosa , Filippelli Gianfranco , Russo Emilio , Porcelli Mariangela , Gadaleta Cosmo Damiano , De Sarro Giovambattista , Ranieri Girolamo 
Published: April 2016

AbstractTumour‐associated macrophages (TAMs) represent pivotal components of tumour microenvironment promoting angiogenesis, tumour progression and invasion. In colorectal cancer (CRC), there are no conclusive data about the role of TAMs in angiogenesis‐mediated tumour progression. In this study, we aimed to evaluate a correlation between TAMs, TAM immunostained area (TAMIA) microvascular density (MVD), endothelial area (EA) and cancer cells positive to VEGF‐A (CCP‐VEGF‐A) in primary tumour tissue of locally advanced CRC patients undergone to radical surgery. A series of 76 patients with CRC were selected and evaluated by immunohistochemistry and image analysis. An anti‐CD68 antibody was employed to assess TAMs and TAMIA expression, an anti‐CD34 antibody was utilized to detect MVD and EA expression, whereas an anti‐VEGF‐A antibody was used to detect CCP‐VEGF‐A; then, tumour sections were evaluated by image analysis methods. The mean ± S.D. of TAMs, MVD and CCP‐VEGF‐A was 65.58 ± 21.14, 28.53 ± 7.75 and 63% ± 37%, respectively; the mean ± S.D. of TAMIA and EA was 438.37 ± 124.14μ2 and 186.73 ± 67.22μ2, respectively. A significant correlation was found between TAMs, TAMIA, MVD and EA each other (r ranging from 0.69 to 0.84; P ranging from 0.000 to 0.004). The high level of expression of TAMs and TAMIA in tumour tissue and the significant correlation with both MVD and EA illustrate that TAMs could represent a marker that plays an important role in promoting angiogenesis‐mediated CRC. In this context, novel agents killing TAMs might be evaluated in clinical trials as a new anti‐angiogenic approach.
Manual versus sonic powered toothbrushing in patients with intellectual disability: a cluster‐randomized clinical trial
Authors: García‐Carrillo Ana , Jover Antonio , Plá Rafael , Martorell Almudena , Sota Cristina , Gómez‐Moreno Gerardo , Figuero Elena , Sanz Mariano , Herrera David 
Published: April 2016

AbstractObjectivesTo compare the use of sonic powered or manual toothbrush in patients with intellectual disability (ID) in terms of plaque (PlI) and gingival (GI) indices and adverse effects.Material and MethodsSubjects with ID were recruited for this cluster‐randomized, single blinded (examiner), 6‐month clinical trial, comparing powered versus manual toothbrushing. Outcome variables included PlI and GI, evaluated at baseline and 3 months after supervised toothbrushing and after 3 additional months of unsupervised used. Clinical outcome variables were analysed by repeated measures ANCOVA considering time and group as factors and respective baseline values as covariates (generalized linear model).ResultsSixty‐four patients (34 male, mean age 34.5) in six clusters were included in the study. No statistically significant effect of toothbrushing group was observed for PlI or GI. A significant effect of time was identified (p < 0.001) with mean reductions ranging 0.44–0.45 for PlI and 0.30–0.36 for GI from baseline to 3–6 months. No relevant adverse effect or technical problems were observed.ConclusionThe tested sonic powered toothbrush was as effective and safe as the manual toothbrush. The use of powered or manual toothbrushes, together with fluoride toothpaste, may improve plaque and gingivitis levels, in patients with mild to limit ID.
A pilot study of active enzyme levels in gingival crevicular fluid of patients with chronic periodontal disease
Authors: Gul Sarhang S. , Douglas Charles W. I. , Griffiths Gareth S. , Rawlinson Andrew 
Published: April 2016

AbstractAimTo determine whether combinations of enzymes in gingival crevicular fluid (GCF) can act as improved biomarkers compared with single enzymes for predicting the outcome of treatment and also for diagnosing the clinical status of sites.MethodsThirty subjects with chronic periodontitis were recruited to a 12‐month longitudinal pilot study. GCF samples from three representative sites: healthy (≤3 mm), deep non‐bleeding (NB) (≥6 mm) and deep bleeding (DB) (≥6 mm) sites and clinical data were collected at baseline, 3 months, 6 months and 12 months following periodontal treatment. Active enzyme levels (MMP‐8, cathepsin G, elastase, trypsin‐like activity and sialidase) in GCF samples were assessed. The enzyme profiles and clinical data of each site were analysed for correlation and logistic regression was performed to find the predictive value of the active enzyme levels regarding the outcome of treatment.ResultsTwenty‐two individuals completed the study. All active enzyme levels were significantly higher in diseased sites than healthy sites. Logistic regression showed that the combination of MMP8, elastase and sialidase provided accurate predictions of treatment outcome (88% for NB and 86% for DB), which was significantly better than each enzyme alone (61%).ConclusionThis pilot has suggested that combined active enzyme profiling could provide significant prediction of outcome of treatment.
‘Who Knows What?’ in New Venture Teams: Transactive Memory Systems as a Micro‐Foundation of Entrepreneurial Orientation
Authors: Dai Ye , Roundy Philip T. , Chok Jay I. , Ding Fangsheng , Byun Gukdo 
Published: April 2016

AbstractThe increasing importance of entrepreneurial behaviour has led scholars to embrace the idea that an entrepreneurial orientation (EO) is an important predictor of firm performance. While EO occupies a central position in strategic entrepreneurship research, scholars have yet to explore its origins in new ventures. Drawing on the knowledge‐based and cognitive views, we theorize that a new venture team's transactive memory system is a cognitive mechanism that spurs the development of an EO. In a field study of high‐tech new ventures in China, we examined the relationship between venture teams’ transactive memory systems (representing the distribution, integration, and utilization of the teams’ knowledge) and EO and the moderating influence of team‐, firm‐, and environment‐level factors. We found that the transactive memory system of a new venture team enhanced their EO and that this relationship was positively influenced by intra‐team trust, the structural organicity of a venture, and environmental dynamism. Our findings provide novel insights into the micro‐foundations of TMS in developing an EO in new ventures.
Admixture mapping identifies introgressed genomic regions in North American canids
Authors: vonHoldt Bridgett M. , Kays Roland , Pollinger John P. , Wayne Robert K. 
Published: April 2016

AbstractHybrid zones typically contain novel gene combinations that can be tested by natural selection in a unique genetic context. Parental haplotypes that increase fitness can introgress beyond the hybrid zone, into the range of parental species. We used the Affymetrix canine SNP genotyping array to identify genomic regions tagged by multiple ancestry informative markers that are more frequent in an admixed population than expected. We surveyed a hybrid zone formed in the last 100 years as coyotes expanded their range into eastern North America. Concomitant with expansion, coyotes hybridized with wolves and some populations became more wolflike, such that coyotes in the northeast have the largest body size of any coyote population. Using a set of 3102 ancestry informative markers, we identified 60 differentially introgressed regions in 44 canines across this admixture zone. These regions are characterized by an excess of exogenous ancestry and, in northeastern coyotes, are enriched for genes affecting body size and skeletal proportions. Further, introgressed wolf‐derived alleles have penetrated into Southern US coyote populations. Because no wolves currently exist in this area, these alleles are unlikely to have originated from recent hybridization. Instead, they probably originated from intraspecific gene flow or ancient admixture. We show that grey wolf and coyote admixture has far‐reaching effects and, in addition to phenotypically transforming admixed populations, allows for the differential movement of alleles from different parental species to be tested in new genomic backgrounds.
Dutch Pain Specialists’ Adherence to the Multidisciplinary Guideline on Treating Pain in Patients with Cancer: A Case Vignette Study
Authors: Besse Kees , Steegers Monique , Vernooij‐Dassen Myrra , Vissers Kris , Engels Yvonne 
Published: April 2016

AbstractBackgroundMany patients with cancer suffer from pain, which is often not optimally treated. In 2008, the evidence‐based, multidisciplinary Dutch guideline on the diagnosis and treatment of pain in this patient group was published. We assessed knowledge about and adherence to the guideline by pain specialists.MethodsA cross‐sectional case vignette survey describing a palliative patient with intractable pancreatic cancer and pain was sent to all 350 Dutch anesthesiologists registered as pain specialists at the Netherlands Association of Anesthesiology. Descriptive statistics were conducted.ResultsNinety‐three pain specialists completed the questionnaire (27%). The majority appeared to follow the guideline recommendations on pharmacological (99%) and invasive treatment (95%) in the diverse stages of the disease. However, the recommendation to use a one‐dimensional pain scale to evaluate the effect of pain treatment and the recommendation to perform a multidimensional pain assessment if the patient in pain is in a deteriorating stage were only followed by a minority of the respondents (23% and 15%, respectively).ConclusionsRegarding most recommendations, Dutch pain specialists know and intend to follow the national multidisciplinary cancer pain guideline. Yet, only a minority of them perform structural pain assessment of the patient with cancer pain. However, as the response rate was low (27%), the results should be interpreted with caution and cannot be generalized to the entire population of pain specialists in the Netherlands. We recommend that, in the guideline update and implementation programs, more attention be given to thorough assessment of the patient with pain and cancer.