Showing papers by "Istanbul University published in 2010"
TL;DR: Treatment with cabazitaxel plus prednisone has important clinical antitumour activity, improving overall survival in patients with metastatic castration-resistant prostate cancer whose disease has progressed during or after docetaxel-based therapy.
2,910 citations
Hacettepe University1, Istituto Giannina Gaslini2, Aarhus University3, Rambam Health Care Campus4, Istanbul University5, Catholic University of the Sacred Heart6, University of São Paulo7, Sheba Medical Center8, Seconda Università degli Studi di Napoli9, University of Latvia10, Rio de Janeiro State University11, University of Zagreb12, University of Chieti-Pescara13, Alfaisal University14, Saint Petersburg State Pediatric Medical University15, Charité16, Children's Memorial Hospital17, Autonomous University of Madrid18, University of Tartu19, Innsbruck Medical University20, Tbilisi State Medical University21, University of Genoa22
TL;DR: The previously proposed classification criteria for Henoch–Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (C-WG) and c-Takayasu arteritis ( c-TA) are validated.
Abstract: Objectives To validate the previously proposed classification criteria for Henoch–Schonlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA). Methods Step 1: retrospective/prospective web-data collection for children with HSP, c-PAN, c-WG and c-TA with age at diagnosis ≤18 years. Step 2: blinded classification by consensus panel of a representative sample of 280 cases. Step 3: statistical (sensitivity, specificity, area under the curve and κ-agreement) and nominal group technique consensus evaluations. Results 827 patients with HSP, 150 with c-PAN, 60 with c-WG, 87 with c-TA and 52 with c-other were compared with each other. A patient was classified as HSP in the presence of purpura or petechiae (mandatory) with lower limb predominance plus one of four criteria: (1) abdominal pain; (2) histopathology (IgA); (3) arthritis or arthralgia; (4) renal involvement. Classification of c-PAN required a systemic inflammatory disease with evidence of necrotising vasculitis OR angiographic abnormalities of medium-/small-sized arteries (mandatory criterion) plus one of five criteria: (1) skin involvement; (2) myalgia/muscle tenderness; (3) hypertension; (4) peripheral neuropathy; (5) renal involvement. Classification of c-WG required three of six criteria: (1) histopathological evidence of granulomatous inflammation; (2) upper airway involvement; (3) laryngo-tracheo-bronchial involvement; (4) pulmonary involvement (x-ray/CT); (5) antineutrophilic cytoplasmic antibody positivity; (6) renal involvement. Classification of c-TA required typical angiographic abnormalities of the aorta or its main branches and pulmonary arteries (mandatory criterion) plus one of five criteria: (1) pulse deficit or claudication; (2) blood pressure discrepancy in any limb; (3) bruits; (4) hypertension; (5) elevated acute phase reactant. Conclusion European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society propose validated classification criteria for HSP, c-PAN, c-WG and c-TA with high sensitivity/specificity.
1,063 citations
University of Glasgow1, University of Oxford2, University of Texas Health Science Center at San Antonio3, Novartis4, Moscow State University5, University of North Carolina at Chapel Hill6, University College Cork7, Federal University of São Paulo8, National Taiwan University9, Centre Hospitalier Universitaire de Nantes10, The Chinese University of Hong Kong11, University of Leicester12, University of California, Berkeley13, University of Bern14, Tulane University15, Royal North Shore Hospital16, Medical University of Warsaw17, Harvard University18, Istanbul University19, University of Tromsø20, University of Washington21, Alfred Hospital22, University of Toronto23, University of Cape Town24, Cordoba University25, University of Illinois at Chicago26, Lahey Hospital & Medical Center27, University Medical Center Utrecht28, Umeå University29, Dresden University of Technology30, University of Liège31, Aarhus University32, Cardiovascular Institute of the South33, University of Copenhagen34, Semmelweis University35, University of Helsinki36, Duke University37
TL;DR: Among patients with impaired glucose tolerance and cardiovascular disease or risk factors, the use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events.
Abstract: BACKGROUND: It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance. METHODS: In this double-blind, randomized clinical trial with a 2-by-2 factorial design, we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan (up to 160 mg daily) or placebo (and nateglinide or placebo) in addition to lifestyle modification. We then followed the patients for a median of 5.0 years for the development of diabetes (6.5 years for vital status). We studied the effects of valsartan on the occurrence of three coprimary outcomes: the development of diabetes; an extended composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable angina; and a core composite outcome that excluded unstable angina and revascularization. RESULTS: The cumulative incidence of diabetes was 33.1% in the valsartan group, as compared with 36.8% in the placebo group (hazard ratio in the valsartan group, 0.86; 95% confidence interval [CI], 0.80 to 0.92; P<0.001). Valsartan, as compared with placebo, did not significantly reduce the incidence of either the extended cardiovascular outcome (14.5% vs. 14.8%; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.43) or the core cardiovascular outcome (8.1% vs. 8.1%; hazard ratio, 0.99; 95% CI, 0.86 to 1.14; P=0.85). CONCLUSIONS: Among patients with impaired glucose tolerance and cardiovascular disease or risk factors, the use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events. (ClinicalTrials.gov number, NCT00097786.)
620 citations
National Institutes of Health1, Istanbul University2, University of Texas MD Anderson Cancer Center3, University of Birmingham4, Northwestern University5, Athens Regional Medical Center6, King's College London7, Queen Mary University of London8, University of Manchester9, KAIST10, Yonsei University11
TL;DR: The known association of Behçet's disease with HLA-B*51 was confirmed and a second, independent association within the MHC Class I region was identified and the disease-associated IL10 variant was associated with diminished mRNA expression and low protein production.
Abstract: Behcet's disease is a genetically complex disease of unknown etiology characterized by recurrent inflammatory attacks affecting the orogenital mucosa, eyes and skin. We performed a genome-wide association study with 311,459 SNPs in 1,215 individuals with Behcet's disease (cases) and 1,278 healthy controls from Turkey. We confirmed the known association of Behcet's disease with HLA-B*51 and identified a second, independent association within the MHC Class I region. We also identified an association at IL10 (rs1518111, P = 1.88 x 10(-8)). Using a meta-analysis with an additional five cohorts from Turkey, the Middle East, Europe and Asia, comprising a total of 2,430 cases and 2,660 controls, we identified associations at IL10 (rs1518111, P = 3.54 x 10(-18), odds ratio = 1.45, 95% CI 1.34-1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 x 10(-9), OR = 1.28, 95% CI 1.18-1.39). The disease-associated IL10 variant (the rs1518111 A allele) was associated with diminished mRNA expression and low protein production.
576 citations
TL;DR: The use of whole-exome sequencing is demonstrated to overcome obstacles by identifying recessive mutations in WD repeat domain 62 (WDR62) as the cause of a wide spectrum of severe cerebral cortical malformations including microcephaly, pachygyria with cortical thickening as well as hypoplasia of the corpus callosum.
Abstract: The development of the human cerebral cortex is an orchestrated process involving the generation of neural progenitors in the periventricular germinal zones, cell proliferation characterized by symmetric and asymmetric mitoses, followed by migration of post-mitotic neurons to their final destinations in six highly ordered, functionally specialized layers. An understanding of the molecular mechanisms guiding these intricate processes is in its infancy, substantially driven by the discovery of rare mutations that cause malformations of cortical development. Mapping of disease loci in putative Mendelian forms of malformations of cortical development has been hindered by marked locus heterogeneity, small kindred sizes and diagnostic classifications that may not reflect molecular pathogenesis. Here we demonstrate the use of whole-exome sequencing to overcome these obstacles by identifying recessive mutations in WD repeat domain 62 (WDR62) as the cause of a wide spectrum of severe cerebral cortical malformations including microcephaly, pachygyria with cortical thickening as well as hypoplasia of the corpus callosum. Some patients with mutations in WDR62 had evidence of additional abnormalities including lissencephaly, schizencephaly, polymicrogyria and, in one instance, cerebellar hypoplasia, all traits traditionally regarded as distinct entities. In mice and humans, WDR62 transcripts and protein are enriched in neural progenitors within the ventricular and subventricular zones. Expression of WDR62 in the neocortex is transient, spanning the period of embryonic neurogenesis. Unlike other known microcephaly genes, WDR62 does not apparently associate with centrosomes and is predominantly nuclear in localization. These findings unify previously disparate aspects of cerebral cortical development and highlight the use of whole-exome sequencing to identify disease loci in settings in which traditional methods have proved challenging.
489 citations
TL;DR: A detailed literature review of the recent applications of the analytic hierarchy process (AHP) and analytic network process (ANP) group decision‐making methodologies shows that during the years 2005‐2009, use of the AHP technique has continued to increase exponentially.
Abstract: Purpose – The purpose of this paper is to present a detailed literature review of the recent applications of the analytic hierarchy process (AHP) and analytic network process (ANP) group decision‐making methodologies.Design/methodology/approach – Among more than 600 related papers published in the period 2005‐2009, a total of 232 application articles published in highly reputed international academic journals were selected and referenced in this paper. Papers were categorized according to application areas, subject titles, publication date, country of origin, academic journals, and integrated methodologies, and are summarized herein by various tables and charts.Findings – The findings show that during the years 2005‐2009, use of the AHP technique has continued to increase exponentially. Moreover, it is expected that ANP will gain more popularity in the future, as the benefits of ANP become better understood. Applications of AHP have been dominant in manufacturing, followed by the environmental management ...
463 citations
University of Oxford1, University of Texas Health Science Center at San Antonio2, University of Leicester3, Duke University4, Novartis5, Moscow State University6, University of North Carolina at Chapel Hill7, University College Cork8, Federal University of São Paulo9, National Taiwan University10, The Chinese University of Hong Kong11, University of California, San Francisco12, Veterans Health Administration13, University of Bern14, University of California, San Diego15, Tulane University16, University of Sydney17, Medical University of Warsaw18, Harvard University19, Istanbul University20, University of Oslo21, University of Washington22, Monash University23, University of Eastern Finland24, University of Toronto25, University of Cape Town26, National University of Cordoba27, University of Illinois at Chicago28, Lahey Hospital & Medical Center29, Massachusetts Institute of Technology30, National and Kapodistrian University of Athens31, Utrecht University32, Umeå University33, Dresden University of Technology34, University of Liège35, Aarhus University36, University of Buenos Aires37, Masaryk University38, University of Copenhagen39, Semmelweis University40, Mario Negri Institute for Pharmacological Research41, University of Helsinki42
TL;DR: Among persons with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors, assignment to nateglinide for 5 years did not reduce the incidence of diabetes or the coprimary composite cardiovascular outcomes.
Abstract: After adjustment for multiple testing, nateglinide, as compared with placebo, did not significantly reduce the cumulative incidence of diabetes (36% and 34%, respectively; hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15; P = 0.05), the core composite cardiovascular outcome (7.9% and 8.3%, respectively; hazard ratio, 0.94, 95% CI, 0.82 to 1.09; P = 0.43), or the extended composite cardiovascular outcome (14.2% and 15.2%, respectively; hazard ratio, 0.93, 95% CI, 0.83 to 1.03; P = 0.16). Nateglinide did, however, increase the risk of hypoglycemia. Conclusions Among persons with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors, assignment to nateglinide for 5 years did not reduce the incidence of diabetes or the coprimary composite cardiovascular outcomes. (ClinicalTrials.gov number, NCT00097786.)
436 citations
TL;DR: A highly consistent pattern of Glx-level reductions in major depressive disorder and elevations in bipolar disorder is found and these patterns suggest that the glutamate-related metabolite pool is constricted in major depressed disorder and expanded inipolar disorder.
411 citations
Paris Descartes University1, University of Paris2, Charité3, King Saud University4, Harvard University5, University of Manchester6, Kyushu University7, Vanderbilt University8, University of Freiburg9, University of Debrecen10, Alfaisal University11, University of South Florida12, National Institutes of Health13, University of Oxford14, University of British Columbia15, University of Toronto16, Boston Children's Hospital17, National Defense Medical College18, State University of New York Upstate Medical University19, Dalhousie University20, Royal Children's Hospital21, François Rabelais University22, Cambridge University Hospitals NHS Foundation Trust23, University College London24, Istanbul University25, Autonomous University of Barcelona26, University of Barcelona27, University of Zurich28, Medical College of Wisconsin29, Katholieke Universiteit Leuven30
TL;DR: IRAK-4 and MyD88 deficiencies predispose patients to recurrent life-threatening bacterial diseases, such as invasive pneumococcal disease in particular, in infancy and early childhood, with weak signs of inflammation.
377 citations
TL;DR: In this paper, the efficacy and safety of memantine were investigated in patients with mild to moderate Parkinson's disease dementia (PDD) or dementia with Lewy bodies (DLB).
Abstract: Summary Background Previous studies have suggested that patients with Lewy-body-related dementias might benefit from treatment with the N-methyl D-aspartate receptor antagonist memantine, but further data are needed. Therefore, the efficacy and safety of memantine were investigated in patients with mild to moderate Parkinson's disease dementia (PDD) or dementia with Lewy bodies (DLB). Methods Patients (≥50 years of age) with mild to moderate PDD or DLB were recruited from 30 specialist centres in Austria, France, Germany, the UK, Greece, Italy, Spain, and Turkey. They were randomly assigned to placebo or memantine (20 mg per day) according to a computer-generated list. Patients and all physicians who had contact with them were masked to treatment assignment. No primary endpoint was defined. Safety analyses were done for all patients who took at least one dose of memantine or placebo, and efficacy analyses were done for all patients who had at least one valid postbaseline assessment. This trial is registered with ClinicalTrials.gov, number NCT00855686. Findings Of the 199 patients randomly assigned to treatment, 34 with DLB and 62 with PDD were given memantine, and 41 with DLB and 58 with PDD were given placebo. 159 (80%) patients completed the study: 80 in the memantine group and 79 in the placebo group. 93 patients treated with memantine and 97 patients treated with placebo were included in the efficacy analysis. At week 24, patients with DLB who received memantine showed greater improvement according to Alzheimer's disease cooperative study (ADCS)-clinical global impression of change scores than did those who received placebo (mean change from baseline 3·3 vs 3·9, respectively, difference −0·6 [95% CI −1·2 to −0·1]; p=0·023). No significant differences were noted between the two treatments in patients with PDD (3·6 with memantine vs 3·8 with placebo, −0·1 [−0·6 to 0·3]; p=0·576) or in the total population (3·5 with memantine vs 3·8 with placebo, −0·3 [−0·7 to 0·1]; p=0·120). Neuropsychiatric-inventory scores showed significantly greater improvement in the memantine group than in the placebo group (−4·3 vs 1·7, respectively, −5·9 [−11·6 to −0·2]; p=0·041) in patients with DLB, but not in those with PDD (−1·6 vs −0·1, respectively, −1·4 [−5·9 to 3·0]; p=0·522) or in the total patient population (−2·6 vs 0·4, respectively, −2·9 [−6·3 to 0·5]; p=0·092). In most of the cognitive test scores, ADCS-activities of daily living, and Zarit caregiver burden scores, there were no significant differences between the two treatment groups in any of the study populations. The incidence of adverse events and number of discontinuations due to adverse events were similar in the two groups. The most common serious adverse events were stroke (n=3 in memantine group), falls (n=2 in memantine group; n=1 in placebo group), and worsening of dementia (n=2 in memantine group). Interpretation Memantine seems to improve global clinical status and behavioural symptoms of patients with mild to moderate DLB, and might be an option for treatment of these patients. Funding Lundbeck.
375 citations
TL;DR: The circadian timing system is composed of molecular clocks, which drive 24-h changes in xenobiotic metabolism and detoxification, cell cycle events, DNA repair, apoptosis, and angiogenesis, so that they tick in synchrony in the host tissues that can be damaged by anticancer agents.
Abstract: The circadian timing system is composed of molecular clocks, which drive 24-h changes in xenobiotic metabolism and detoxification, cell cycle events, DNA repair, apoptosis, and angiogenesis. The cellular circadian clocks are coordinated by endogenous physiological rhythms, so that they tick in synchrony in the host tissues that can be damaged by anticancer agents. As a result, circadian timing can modify 2- to 10-fold the tolerability of anticancer medications in experimental models and in cancer patients. Improved efficacy is also seen when drugs are given near their respective times of best tolerability, due to (a) inherently poor circadian entrainment of tumors and (b) persistent circadian entrainment of healthy tissues. Conversely, host clocks are disrupted whenever anticancer drugs are administered at their most toxic time. On the other hand, circadian disruption accelerates experimental and clinical cancer processes. Gender, circadian physiology, clock genes, and cell cycle critically affect outcome on cancer chronotherapeutics. Mathematical and systems biology approaches currently develop and integrate theoretical, experimental, and technological tools in order to further optimize and personalize the circadian administration of cancer treatments.
TL;DR: Depression, dementia, functional dependence and multiple co-morbidities were associated with poor nutritional status andMalnutrition risk showed positive correlation with the number of existing geriatric syndromes.
TL;DR: The study indicates that deletions of NRXN1 predispose to a wide spectrum of developmental disorders, including autism spectrum disorders, mental retardation, language delays and hypotonia.
Abstract: Research has implicated mutations in the gene for neurexin-1 (NRXN1) in a variety of conditions including autism, schizophrenia, and nicotine dependence. To our knowledge, there have been no published reports describing the breadth of the phenotype associated with mutations in NRXN1. We present a medical record review of subjects with deletions involving exonic sequences of NRXN1. We ascertained cases from 3,540 individuals referred clinically for comparative genomic hybridization testing from March 2007 to January 2009. Twelve subjects were identified with exonic deletions. The phenotype of individuals with NRXN1 deletion is variable and includes autism spectrum disorders, mental retardation, language delays, and hypotonia. There was a statistically significant increase in NRXN1 deletion in our clinical sample compared to control populations described in the literature (P = 8.9 x 10(-7)). Three additional subjects with NRXN1 deletions and autism were identified through the Homozygosity Mapping Collaborative for Autism, and this deletion segregated with the phenotype. Our study indicates that deletions of NRXN1 predispose to a wide spectrum of developmental disorders.
TL;DR: Broderick et al. as mentioned in this paper provided a comprehensive review of the evidence-based guidelines written over the past decade and reviewed the priapism literature from 2003 to 2009, concluding that prompt diagnosis and appropriate management are necessary to spare patients ineffective interventions and maximize erectile function outcomes.
TL;DR: Results show that distance between the transmitter and receiver has a minor effect on the achievable data rate whereas the energy budget’s effect is significant and it is shown that selecting appropriate threshold and symbol duration parameters are crucial to the performance of the system.
TL;DR: Whole-exome sequencing reveals a homozygous splice-site mutation in the gene encoding STIM1 in a child with classic Kaposi sarcoma.
Abstract: Classic Kaposi sarcoma (KS) is exceedingly rare in children from the Mediterranean Basin, despite the high prevalence of human herpesvirus-8 (HHV-8) infection in this region. We hypothesized that rare single-gene inborn errors of immunity to HHV-8 may underlie classic KS in childhood. We investigated a child with no other unusually severe infectious or tumoral phenotype who died from disseminated KS at two years of age. Whole-exome sequencing in the patient revealed a homozygous splice-site mutation in STIM1, the gene encoding stromal interaction molecule 1, which regulates store-operated Ca(2+) entry. STIM1 mRNA splicing, protein production, and Ca(2+) influx were completely abolished in EBV-transformed B cell lines from the patient, but were rescued by the expression of wild-type STIM1. Based on the previous discovery of STIM1 deficiency in a single family with a severe T cell immunodeficiency and the much higher risk of KS in individuals with acquired T cell deficiencies, we conclude that STIM1 T cell deficiency precipitated the development of lethal KS in this child upon infection with HHV-8. Our report provides the first evidence that isolated classic KS in childhood may result from single-gene defects and provides proof-of-principle that whole-exome sequencing in single patients can decipher the genetic basis of rare inborn errors.
TL;DR: This work highlights the current plasmid-mediated dissemination of the OXA-48 carbapenemase worldwide and identifies similar 70-kb plasmids carrying the blaOXA- 48 gene.
Abstract: Eighteen carbapenem-resistant, OXA-48-positive enterobacterial isolates recovered from Turkey, Lebanon, Egypt, France, and Belgium were analyzed. In most isolates, similar 70-kb plasmids carrying the carbapenemase gene bla(OXA-48) were identified. That gene was located within either transposon Tn1999 or transposon Tn1999.2, which was always inserted within the same gene. This work highlights the current plasmid-mediated dissemination of the OXA-48 carbapenemase worldwide.
TL;DR: High AIP, a surrogate of small LDL particle size, reflects obesity and hyperinsulinemia in men and high CRP status in women, and predicted diabetes and high blood pressure in both sexes after adjustment for age and CRP.
Ludwig Maximilian University of Munich1, Istanbul University2, VU University Amsterdam3, Autonomous University of Madrid4, Great Ormond Street Hospital5, Centra6, University of Tübingen7, Ankara University8, Boston Children's Hospital9, Coventry Health Care10, Cliniques Universitaires Saint-Luc11, Karolinska Institutet12
TL;DR: The updated European consensus 2009 summarises the current understanding regarding an integrated, multidisciplinary treatment approach using Botulinum toxin for the treatment of children with cerebral palsy.
TL;DR: In this article, the authors present the Swift observations of GRB 090515 and compare it to other gamma-ray bursts (GRBs) in the Swift sample, and suggest it might be energy injection from an unstable millisecond pulsar contributing to their emission.
Abstract: The majority of short gamma-ray bursts (SGRBs) are thought to originate from the merger of compact binary systems collapsing directly to form a black hole. However, it has been proposed that both SGRBs and long gamma-ray bursts (LGRBs) may, on rare occasions, form an unstable millisecond pulsar (magnetar) prior to final collapse. GRB 090515, detected by the Swift satellite was extremely short, with a T90 of 0.036 ± 0.016 s, and had a very low fluence of 2 × 10−8 erg cm−2 and faint optical afterglow. Despite this, the 0.3–10 keV flux in the first 200 s was the highest observed for an SGRB by the Swift X-ray Telescope (XRT). The X-ray light curve showed an unusual plateau and steep decay, becoming undetectable after ∼500 s. This behaviour is similar to that observed in some long bursts proposed to have magnetars contributing to their emission.
In this paper, we present the Swift observations of GRB 090515 and compare it to other gamma-ray bursts (GRBs) in the Swift sample. Additionally, we present optical observations from Gemini, which detected an afterglow of magnitude 26.4 ± 0.1 at T+ 1.7 h after the burst. We discuss potential causes of the unusual 0.3–10 keV emission and suggest it might be energy injection from an unstable millisecond pulsar. Using the duration and flux of the plateau of GRB 090515, we place constraints on the millisecond pulsar spin period and magnetic field.
TL;DR: Genetic defects in the ATP13A2, PLA2G6, FBXO7, and SPG11 genes are identified, suggesting that these four genes account for many cases of Levodopa responsive parkinsonism with pyramidal signs cases formerly categorized clinically as pallido‐pyramidal syndrome.
Abstract: Seven autosomal recessive genes associated with juvenile and young-onset Levodopa-responsive parkinsonism have been identified. Mutations in PRKN, DJ-1, and PINK1 are associated with a rather pure parkinsonian phenotype, and have a more benign course with sustained treatment response and absence of dementia. On the other hand, Kufor-Rakeb syndrome has additional signs, which distinguish it clearly from Parkinson's disease including supranuclear vertical gaze palsy, myoclonic jerks, pyramidal signs, and cognitive impairment. Neurodegeneration with brain iron accumulation type I (Hallervorden-Spatz syndrome) due to mutations in PANK2 gene may share similar features with Kufor-Rakeb syndrome. Mutations in three other genes, PLA2G6 (PARK14), FBXO7 (PARK15), and Spatacsin (SPG11) also produce clinical similar phenotypes in that they presented with rapidly progressive parkinsonism, initially responsive to Levodopa treatment but later, developed additional features including cognitive decline and loss of Levodopa responsiveness. Here, using homozygosity mapping and sequence analysis in families with complex parkinsonisms, we identified genetic defects in the ATP13A2 (1 family), PLA2G6 (1 family) FBXO7 (2 families), and SPG11 (1 family). The genetic heterogeneity was surprising given their initially common clinical features. On careful review, we found the FBXO7 cases to have a phenotype more similar to PRKN gene associated parkinsonism. The ATP13A2 and PLA2G6 cases were more seriously disabled with additional swallowing problems, dystonic features, severe in some, and usually pyramidal involvement including pyramidal weakness. These data suggest that these four genes account for many cases of Levodopa responsive parkinsonism with pyramidal signs cases formerly categorized clinically as pallido-pyramidal syndrome.
TL;DR: It is indicated that mutations in the spatascin gene could cause a much wider spectrum of clinical features than previously recognized, including autosomal recessive juvenile amyotrophic lateral sclerosis.
Abstract: The mutation of the spatacsin gene is the single most common cause of autosomal recessive hereditary spastic paraplegia with thin corpus callosum. Common clinical, pathological and genetic features between amyotrophic lateral sclerosis and hereditary spastic paraplegia motivated us to investigate 25 families with autosomal recessive juvenile amyotrophic lateral sclerosis and long-term survival for mutations in the spatascin gene. The inclusion criterion was a diagnosis of clinically definite amyotrophic lateral sclerosis according to the revised El Escorial criteria. The exclusion criterion was a diagnosis of hereditary spastic paraplegia with thin corpus callosum in line with an established protocol. Additional pathological and genetic evaluations were also performed. Surprisingly, 12 sequence alterations in the spatacsin gene (one of which is novel, IVS30 + 1 G > A) were identified in 10 unrelated pedigrees with autosomal recessive juvenile amyotrophic lateral sclerosis and long-term survival. The countries of origin of these families were Italy, Brazil, Canada, Japan and Turkey. The variants seemed to be pathogenic since they co-segregated with the disease in all pedigrees, were absent in controls and were associated with amyotrophic lateral sclerosis neuropathology in one member of one of these families for whom central nervous system tissue was available. Our study indicates that mutations in the spatascin gene could cause a much wider spectrum of clinical features than previously recognized, including autosomal recessive juvenile amyotrophic lateral sclerosis.
TL;DR: At week 12 of peginterferon alfa‐2a treatment for HBeAg‐negative CHB, a solid stopping rule was established with a combination of declines in serum HBV DNA and HBsAg levels from the baseline.
TL;DR: This paper constitutes the first attempt at deciphering the mitochondrial and nuclear relationships of Mediterranean leuciscins but also a test of biogeographical hypotheses that could have determined the current distribution of Circum-Mediterranean leucISCins.
Abstract: Background
Leuciscinae is a subfamily belonging to the Cyprinidae fish family that is widely distributed in Circum-Mediterranean region. Many efforts have been carried out to deciphering the evolutionary history of this group. Thus, different biogeographical scenarios have tried to explain the colonization of Europe and Mediterranean area by cyprinids, such as the "north dispersal" or the "Lago Mare dispersal" models. Most recently, Pleistocene glaciations influenced the distribution of leuciscins, especially in North and Central Europe. Weighing up these biogeographical scenarios, this paper constitutes not only the first attempt at deciphering the mitochondrial and nuclear relationships of Mediterranean leuciscins but also a test of biogeographical hypotheses that could have determined the current distribution of Circum-Mediterranean leuciscins.
TL;DR: In this article, the authors focus on the brand personalities of places and examine the applicability of this concept for city brands by employing a factor analysis method based on data collected from 898 college students.
Abstract: Purpose – In recent years, brand personality as a branding construct has received considerable interest, which has led to a significant effort to develop tools to measure the personality of brands. Although the majority of these studies have focused on the brand personality of conventional product brands, the new boundaries of marketing obviously necessitate the application of branding constructs to non‐traditional products such as places. This study aims to focus on brand personalities of places, and to examine the applicability of this concept for city brands.Design/methodology/approach – The research employs a factor analysis method based on data collected from 898 college students.Findings – The findings of the study reveal that differentiating places with regard to their brand personalities is achievable. The paper introduces two new dimensions of brand personality for cities.Originality/value – The extraction of two new factors that contribute to place brand personalities is considered a major contr...
TL;DR: It is speculated that alterations in the relative levels of ERbeta and ERalpha in endometrial tissue dictate E2-regulated PR expression, such that a decreased ERalpha-tauomicron-ERbeta ratio may result in suppression of PR.
Abstract: Loss of progesterone signaling in the endometrium may be a causal factor in the development of endometriosis, and progesterone resistance is commonly observed in women with this disease. In endometriotic stromal cells, the levels of progesterone receptor (PR), particularly the PR-B isoform, are significantly decreased, leading to a loss of paracrine signaling. PR deficiency likely underlies the development of progesterone resistance in women with endometriosis who no longer respond to progestin therapy. Here we review the complex epigenetic and transcriptional mechanisms leading to PR deficiency. The initial event may involve deficient methylation of the estrogen receptor (ER)beta promoter resulting in pathologic overexpression of ERbeta in endometriotic stromal cells. We speculate that alterations in the relative levels of ERbeta and ERalpha in endometrial tissue dictate E2-regulated PR expression, such that a decreased ERalpha-tauomicron-ERbeta ratio may result in suppression of PR. In this review, we propose a molecular model that may be responsible for changes in ERbeta and ERalpha leading to PR loss and progesterone resistance in endometriosis.
TL;DR: An evaluation of using various methods for face recognition using wavelet decomposition and Eigenfaces method which is based on Principal Component Analysis (PCA) and Wavelet-SVM approach for classification step.
Abstract: In this study, we present an evaluation of using various methods for face recognition. As feature extracting techniques we benefit from wavelet decomposition and Eigenfaces method which is based on Principal Component Analysis (PCA). After generating feature vectors, distance classifier and Support Vector Machines (SVMs) are used for classification step. We examined the classification accuracy according to increasing dimension of training set, chosen feature extractor-classifier pairs and chosen kernel function for SVM classifier. As test set we used ORL face database which is known as a standard face database for face recognition applications including 400 images of 40 people. At the end of the overall separation task, we obtained the classification accuracy 98.1% with Wavelet-SVM approach for 240 image training set.
TL;DR: Proline supplements seem to improve olive salt tolerance by amelioration of some antioxidative enzyme activities, photosynthetic activity, and, so, plant growth and the preservation of a suitable plant water status under salinity conditions.
Abstract: The ability of exogenous compatible solutes, such as proline, to counteract salt inhibitory effects in olive plants ( Olea europaea L. cv. Chemlali) was investigated. Two-year-old olive trees were subjected to different saline water irrigation levels supplied or not with exogenous proline. Leaf water relations (relative water content, water potential), photosynthetic activity, and leaf chlorophyll content decreased under either saline water level. The proline supplement mitigated the reduction of growth and photosynthetic activity under salt stress, and the mitigating effect of proline was different among treatments. The increment rate of leaf relative water content (RWC) in the presence of 25 and 50 mM proline was 4.45 and 6.67%, respectively, in comparison to values recorded in SS1-treated plants (plants irrigated with water containing 100 mM NaCl). In SS2 (200 mM NaCl) plus proline-treated plants, this increase was 1.14 times for 25 mM proline and 1.19 times for 50 mM proline higher than those recorded in severe salt stress treatment (SS2). In response to salt stress, Chemlali olive plants seem to activate a complex antioxidative defense system that was displayed via the increase of activities of superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX) and the decrease of polyphenol oxidase (PPO) under either salt stress treatment. The exogenous application of proline improved the antioxidative enzyme activities of salt-stressed olive plants. Indeed, in young or old leaf tissues, the highest levels of these antioxidant enzymes activities were recorded in (SS2 + P2)-treated plants (plants irrigated with water containing 200 mM NaCl plus 50 mM proline). In young leaves, this increase was 2.11, 2.96, and 2.76 times, respectively, for SOD, APX, and CAT enzyme activities in comparison to their respective activities in control plants (nonstressed plants irrigated with fresh water). In old leaves, this increase was 2, 2.41, and 2.48 times, respectively, for the various enzymes. If compared to high water salinity-treated plants (SS2), this increase was 1.1, 1.3, and 1.4 times in young leaves, respectively, for SOD, APX, and CAT activities. From these results, the proline supplements seem to improve olive salt tolerance by amelioration of some antioxidative enzyme activities, photosynthetic activity, and, so, plant growth and the preservation of a suitable plant water status under salinity conditions. More to the point, the decrease of soluble sugars contents in proline treated-plants revealed the important osmoprotectant effect played by the added proline in such a way that limited the need of salt-stressed plants for soluble sugars synthesis.
TL;DR: Preliminary results revealed that some of the compounds exhibited promising antimicrobial activities against Mycobacterium tuberculosis H37Rv.
University of Erlangen-Nuremberg1, Boston Children's Hospital2, University of Michigan3, United Arab Emirates University4, Oslo University Hospital5, Istanbul University6, Leicester Royal Infirmary7, Charles University in Prague8, Great Ormond Street Hospital9, Seoul National University10, Medical University of Silesia11, Claude Bernard University Lyon 112, University of Cape Town13, Université libre de Bruxelles14, Cincinnati Children's Hospital Medical Center15, Utrecht University16, Inova Fairfax Hospital17, University of Rostock18, Necker-Enfants Malades Hospital19, St George's, University of London20, University of Hawaii at Manoa21, Nottingham University Hospitals NHS Trust22, Heidelberg University23, Otto-von-Guericke University Magdeburg24
TL;DR: The majority of disease‐causing LAMB2 mutations are truncating, consistent with the hypothesis that loss of laminin β2 function is the molecular basis of Pierson syndrome.
Abstract: Mutations of LAMB2 typically cause autosomal recessive Pierson syndrome, a disorder characterized by congenital nephrotic syndrome, ocular and neurologic abnormalities, but may occasionally be associated with milder or oligosymptomatic disease variants. LAMB2 encodes the basement membrane protein laminin β2 which is incorporated in specific heterotrimeric laminin isoforms and has an expression pattern corresponding to the pattern of organ manifestations in Pierson syndrome. Herein we review all previously reported and several novel LAMB2 mutations in relation to the associated phenotype in patients from 39 unrelated families. The majority of disease-causing LAMB2 mutations are truncating, consistent with the hypothesis that loss of laminin β2 function is the molecular basis of Pierson syndrome. While truncating mutations are distributed across the entire gene, missense mutations are clearly clustered in the N-terminal LN domain, which is important for intermolecular interactions. There is an association of missense mutations and small in frame deletions with a higher mean age at onset of renal disease and with absence of neurologic abnormalities, thus suggesting that at least some of these may represent hypomorphic alleles. Nevertheless, genotype alone does not appear to explain the full range of clinical variability, and therefore hitherto unidentified modifiers are likely to exist.