bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detecting acute neurotoxicity during platinum chemotherapy by neurophysiological assessment of motor nerve hyperexcitability
Authors: Hill Andrew , Bergin Peter , Hanning Fritha , Thompson Paul , Findlay Michael , Damianovich Dragan , McKeage Mark J 
Published: August 2010

Abstract

Background
Platinum-based drugs, such as cisplatin and oxaliplatin, are well-known for inducing chronic sensory neuropathies but their acute and motor neurotoxicities are less well characterised. Use was made of nerve conduction studies and needle electromyography (EMG) to assess motor nerve excitability in cancer patients during their first treatment cycle with platinum-based chemotherapy in this study.

Methods
Twenty-nine adult cancer patients had a neurophysiological assessment either before oxaliplatin plus capecitabine, on days 2 to 4 or 14 to 20 after oxaliplatin plus capecitabine, or on days 2 to 4 after carboplatin plus paclitaxel or cisplatin, undertaken by a neurophysiologist who was blinded to patient and treatment details. Patients completed a symptom questionnaire at the end of the treatment cycle.

Results
Abnormal spontaneous high frequency motor fibre action potentials were detected in 100% of patients (n = 6) and 72% of muscles (n = 22) on days 2 to 4 post-oxaliplatin, and in 25% of patients (n = 8) and 13% of muscles (n = 32) on days 14 to 20 post-oxaliplatin, but in none of the patients (n = 14) or muscles (n = 56) tested prior to oxaliplatin or on days 2 to 4 after carboplatin plus paclitaxel or cisplatin. Repetitive compound motor action potentials were less sensitive and less specific than spontaneous high frequency motor fibre action potentials for detection of acute oxaliplatin-induced motor nerve hyperexcitability but were present in 71% of patients (n = 7) and 32% of muscles (n = 32) on days 2 to 4 after oxaliplatin treatment. Acute neurotoxicity symptoms, most commonly cold-induced paraesthesiae and jaw or throat tightness, were reported by all patients treated with oxaliplatin (n = 22) and none of those treated with carboplatin plus paclitaxel or cisplatin (n = 6).

Conclusions
Abnormal spontaneous high frequency motor fibre activity is a sensitive and specific endpoint of acute oxaliplatin-induced motor nerve hyperexcitability, detectable on EMG on days 2 to 4 post-treatment. Objective EMG assessment of motor nerve excitability could compliment patient-reported symptomatic endpoints of acute oxaliplatin-induced neurotoxicity in future studies.
Molecular analysis of ex-vivo CD133+ GBM cells revealed a common invasive and angiogenic profile but different proliferative signatures among high grade gliomas
Authors: Garcia Juan L , Perez-Caro Maria , Gomez-Moreta Juan A , Gonzalez Francisco , Ortiz Javier , Blanco Oscar , Sancho Magdalena , Hernandez-Rivas Jesus M , Gonzalez-Sarmiento Rogelio , Sanchez-Martin Manuel 
Published: August 2010

Abstract

Background
Gliomas are the most common type of primary brain tumours, and in this group glioblastomas (GBMs) are the higher-grade gliomas with fast progression and unfortunate prognosis. Two major aspects of glioma biology that contributes to its awful prognosis are the formation of new blood vessels through the process of angiogenesis and the invasion of glioma cells. Despite of advances, two-year survival for GBM patients with optimal therapy is less than 30%. Even in those patients with low-grade gliomas, that imply a moderately good prognosis, treatment is almost never curative. Recent studies have demonstrated the existence of a small fraction of glioma cells with characteristics of neural stem cells which are able to grow in vitro forming neurospheres and that can be isolated in vivo using surface markers such as CD133. The aim of this study was to define the molecular signature of GBM cells expressing CD133 in comparison with non expressing CD133 cells. This molecular classification could lead to the finding of new potential therapeutic targets for the rationale treatment of high grade GBM.

Methods
Eight fresh, primary and non cultured GBMs were used in order to study the gene expression signatures from its CD133 positive and negative populations isolated by FACS-sorting. Dataset was generated with Affymetrix U133 Plus 2 arrays and analysed using the software of the Affymetrix Expression Console. In addition, genomic analysis of these tumours was carried out by CGH arrays, FISH studies and MLPA;

Results
Gene expression analysis of CD133+ vs. CD133- cell population from each tumour showed that CD133+ cells presented common characteristics in all glioblastoma samples (up-regulation of genes involved in angiogenesis, permeability and down-regulation of genes implicated in cell assembly, neural cell organization and neurological disorders). Furthermore, unsupervised clustering of gene expression led us to distinguish between two groups of samples: those discriminated by tumour location and, the most importantly, the group discriminated by their proliferative potential;

Conclusions
Primary glioblastomas could be sub-classified according to the properties of their CD133+ cells. The molecular characterization of these potential stem cell populations could be critical to find new therapeutic targets and to develop an effective therapy for these tumours with very dismal prognosis.
Cross-species comparison of aCGH data from mouse and human BRCA1- and BRCA2-mutated breast cancers
Authors: Holstege Henne , van Beers Erik , Velds Arno , Liu Xiaoling , Joosse Simon A , Klarenbeek Sjoerd , Schut Eva , Kerkhoven Ron , Klijn Christiaan N , Wessels Lodewyk FA , Nederlof Petra M , Jonkers Jos 
Published: August 2010

AbstractBackgroundGenomic gains and losses are a result of genomic instability in many types of cancers.BRCA1- andBRCA2-mutated breast cancers are associated with increased amounts of chromosomal aberrations, presumably due their functions in genome repair. Some of these genomic aberrations may harbor genes whose absence or overexpression may give rise to cellular growth advantage. So far, it has not been easy to identify the driver genes underlying gains and losses. A powerful approach to identify these driver genes could be a cross-species comparison of array comparative genomic hybridization (aCGH) data from cognate mouse and human tumors. Orthologous regions of mouse and human tumors that are commonly gained or lost might represent essential genomic regions selected for gain or loss during tumor development.MethodsTo identify genomic regions that are associated withBRCA1- andBRCA2-mutated breast cancers we compared aCGH data from 130 mouseBrca1Δ/Δ;p53Δ/Δ,Brca2Δ/Δ;p53Δ/Δandp53Δ/Δmammary tumor groups with 103 humanBRCA1-mutated,BRCA2-mutated and non-hereditary breast cancers.ResultsOur genome-wide cross-species analysis yielded a complete collection of loci and genes that are commonly gained or lost in mouse and human breast cancer. Principal common CNAs were the well knownMYC-associated gain andRB1/INTS6-associated loss that occurred in all mouse and human tumor groups, and theAURKA-associated gain occurred in BRCA2-related tumors from both species. However, there were also important differences between tumor profiles of both species, such as the prominent gain on chromosome 10 in mouseBrca2Δ/Δ;p53Δ/Δtumors and the PIK3CA associated 3q gain in humanBRCA1-mutated tumors, which occurred in tumors from one species but not in tumors from the other species. This disparity in recurrent aberrations in mouse and human tumors might be due to differences in tumor cell type or genomic organization between both species.ConclusionsThe selection of the oncogenome during mouse and human breast tumor development is markedly different, apart from the MYC gain and RB1-associated loss. These differences should be kept in mind when using mouse models for preclinical studies.
Early exposure to secondhand tobacco smoke and the development of allergic diseases in 4 year old children in Malmö, Sweden
Authors: Hansen Kristina , Mangrio Elisabeth , Lindström Martin , Rosvall Maria 
Published: August 2010

Abstract

Background
Earlier studies have shown an association between secondhand tobacco smoke and allergy development in children. Furthermore, there is an increased risk of developing an allergy if the parents have an allergy. However, there are only few studies investigating the potential synergistic effect of secondhand tobacco smoke and allergic heredity on the development of an allergy.

Methods
The study was population-based cross-sectional with retrospective information on presence of secondhand tobacco smoke during early life. The study population consisted of children who visited the Child Health Care (CHC) centres in Malmö for their 4-year health checkup during 2006-2008 and whose parents answered a self-administered questionnaire (n = 4,278 children). The questionnaire was distributed to parents of children registered with the CHC and invited for the 4-year checkup during the study period.

Results
There was a two to four times increased odds of the child having an allergy or having sought medical care due to allergic symptoms if at least one parent had an allergy, while there were rather small increased odds related to presence of secondhand smoke during the child's first month in life or at the age of 8 months. However, children with heredity for allergies and with presence of secondhand tobacco smoke during their first year in life had highly increased odds of developing an allergy and having sought medical care due to allergic symptoms at 4 years of age. Thus, there was a synergistic effect enhancing the independent effects of heredity and exposure to secondhand tobacco smoke on allergy development.

Conclusions
Children with a family history of allergies and early exposure to secondhand tobacco smoke is a risk group that prevention and intervention should pay extra attention to. The tobacco smoke effect on children is an essential and urgent question considering it not being self chosen, possibly giving life lasting negative health effects and being possible to reduce.
The prevalence of dental erosion and associated risk factors in 12-13-year-old school children in Southern China
Authors: Wang Ping , Lin Huan Cai , Chen Jian Hong , Liang Huan You 
Published: August 2010

AbstractBackgroundDental erosion has been investigated in developed and developing countries and the prevalence varies considerably in different countries, geographic locations, and age groups. With the lifestyle of the Chinese people changing significantly over the decades, dental erosion has begun to receive more attention. However, the information about dental erosion in China is scarce. The purpose of this study was to explore the prevalence of dental erosion and associated risk factors in 12-13-year-old school children in Guangzhou, Southern China.MethodsThis cross-sectional survey was performed by two trained, calibrated examiners. A stratified random sample of 12-13-year-old children (774 boys and 725 girls) from 10 schools was examined for dental erosion using the diagnostic criteria of Eccles and the index of O'Sullivan was applied to record the distribution, severity, and amount of the lesions. Data on the socio-economic status, health behaviours, and general health involved in the etiology of dental erosion were obtained from a self-completed questionnaire. The analyses were performed using SPSS software.ResultsAt least one tooth surface with signs of erosion was found in 416 children (27.3%). The most frequently affected teeth were the central incisors (upper central incisors, 16.3% and 15.9%; lower central incisors, 17.4% and 14.8%). The most frequently affected surface was the incisal or occlusal edge (43.2%). The loss of enamel contour was present in 54.6% of the tooth surfaces with erosion. Of the affected tooth surfaces, 69.3% had greater than one-half of the tooth surface was affected. The results from logistic regression analysis demonstrated that the children who were female, consumed carbonated drinks once a week or more, and those whose mothers were educated to the primary level tended to have more dental erosion.ConclusionsDental erosion in 12-13-year-old Chinese school children is becoming a significant problem. A strategy of offering preventive care, including more campaigns promoting a healthier lifestyle for those at risk of dental erosion should be conducted in Chinese children and their parents.
The CONSTANCES cohort: an open epidemiological laboratory
Authors: Zins Marie , Bonenfant Sébastien , Carton Matthieu , Coeuret-Pellicer Mireille , Guéguen Alice , Gourmelen Julie , Nachtigal Mélissa , Ozguler Anna , Quesnot Ariane , Ribet Céline , Rodrigues Grégory , Serrano Angel , Sitta Rémi , Brigand Alain , Henny Joseph , Goldberg Marcel 
Published: August 2010

Abstract

Background
Prospective cohorts represent an essential design for epidemiological studies and allow for the study of the combined effects of lifestyle, environment, genetic predisposition, and other risk factors on a large variety of disease endpoints. The CONSTANCES cohort is intended to provide public health information and to serve as an "open epidemiologic laboratory" accessible to the epidemiologic research community. Although designed as a "general-purpose" cohort with very broad coverage, it will particularly focus on occupational and social determinants of health, and on aging.

Methods/Design
The CONSTANCES cohort is designed as a randomly selected representative sample of French adults aged 18-69 years at inception; 200,000 subjects will be included over a five-year period. At inclusion, the selected subjects will be invited to fill a questionnaire and to attend a Health Screening Center (HSC) for a comprehensive health examination: weight, height, blood pressure, electrocardiogram, vision, auditory, spirometry, and biological parameters; for those aged 45 years and older, a specific work-up of functional, physical, and cognitive capacities will be performed. A biobank will be set up. The follow-up includes a yearly self-administered questionnaire, and a periodic visit to an HSC. Social and work-related events and health data will be collected from the French national retirement, health and death databases. The data that will be collected include social and demographic characteristics, socioeconomic status, life events, behaviors, and occupational factors. The health data will cover a wide spectrum: self-reported health scales, reported prevalent and incident diseases, long-term chronic diseases and hospitalizations, sick-leaves, handicaps, limitations, disabilities and injuries, healthcare utilization and services provided, and causes of death.
To take into account non-participation at inclusion and attrition throughout the longitudinal follow-up, a cohort of non-participants will be set up and followed through the same national databases as participants.
A field-pilot was performed in 2010 in seven HSCs, which included about 3,500 subjects; it showed a satisfactory structure of the sample and a good validity of the collected data.

Discussion
The constitution of the full eligible sample is planned during the last trimester of 2010, and the cohort will be launched at the beginning of 2011.
Fluoroscopically guided transforaminal epidural dry needling for lumbar spinal stenosis using a specially designed needle
Authors: Ahn Kang , Jhun Hyung-Joon , Lim Tae-Kyun , Lee Yong-Seung 
Published: August 2010

Abstract

Background
This report describes the methodological approach and clinical application of a minimally invasive intervention to treat lumbar spinal stenosis (LSS).

Methods
Thirty-four patients with LSS underwent fluoroscopically guided transforaminal epidural dry needling using a specially designed flexed Round Needle. The needle was inserted 8-12 cm lateral to the midline at the level of the stenosis and advanced to a position between the anterior side of the facet joint and pedicle up to the outer-third of the pedicle. The needle was advanced medially and backed laterally within a few millimetres along the canal side of the inferior articular process between the facet joint and pedicle. The procedure was completed when a marked reduction in resistance was felt at the tip of the needle. The procedure was performed bilaterally at the level of the stenosis.

Results
The average follow-up period was 12.9 ± 1.1 months. The visual analogue scale (VAS) pain score was reduced from 7.3 ± 2.0 to 4.6 ± 2.5 points, the Oswestry Disability Index (ODI) score decreased from 41.4 ± 17.2 to 25.5 ± 12.6% and the average self-rated improvement was 52.6 ± 33.1%. The VAS scores indicated that 14 (41.2%) patients reported a "good" to "excellent" treatment response, while 11 (32.4%) had a "good" to "excellent" treatment response on the ODI and 22 (64.7%) had a "good" to "excellent" treatment response on the self-rated improvement scale.

Conclusions
These results suggest that fluoroscopically guided transforaminal epidural dry needling is effective for managing LSS.
The relationship between the presence of anti-cyclic citrullinated peptide antibodies and clinical phenotype in very early rheumatoid arthritis
Authors: Cader Mohammed Z , Filer Andrew D , Buckley Christopher D , Raza Karim 
Published: August 2010

Abstract

Background
Anti-cyclic citrullinated peptide (anti-CCP) antibodies are highly specific for RA, but are not detectable in all RA patients. The aim of this study was to establish whether the clinical phenotypes of anti-CCP positive and negative disease are distinct at the earliest clinically apparent phase of disease.

Methods
Patients were recruited from the Birmingham early inflammatory arthritis clinic. Participants were included in the current study if they presented within 3 months of symptom onset and fulfilled 1987 ACR criteria for RA at some point during an 18 month follow-up. Data were collected on demographic variables, joint symptoms and tender (n = 68) and swollen (n = 66) joint counts. CRP, ESR, rheumatoid factor and anti-CCP2 status were measured.

Results
92 patients were included (48 anti-CCP positive). The anti-CCP positive and negative groups were comparable in terms of demographic variables, inflammatory markers, joint counts and 1987 ACR classification criteria, except that more anti-CCP positive patients were rheumatoid factor positive (83.3% vs. 11.4%, p < 0.01). There was no significant difference in the pattern of joint involvement, except for an increased prevalence of knee joint swelling in anti-CCP positive patients (42.9% vs. 22.2%, p = 0.03).

Conclusions
Patients with and without anti-CCP antibodies present in a similar way, even within three months of clinically apparent disease that eventually develops into RA.
Polyphenols of Camellia sinenesis decrease mortality, hepatic injury and generation of cytokines and reactive oxygen and nitrogen species after hemorrhage/resuscitation in rats
Authors: Lehnert Mark , Lind Henrik , Zhong Zhi , Schoonhoven Robert , Marzi Ingo , Lemasters John J 
Published: August 2010

AbstractBackgroundReactive oxygen species (ROS) and reactive nitrogen species (RNS) are produced during hemorrhagic shock and resuscitation (H/R), which may contribute to multiple organ failure. TheAimof this study was to test the hypothesis that green tea (Camellia sinenesis) extract containing 85% polyphenols decreases injury after H/R in rats by scavenging ROS and RNS.MethodsFemale Sprague Dawley rats were given 100 mg polyphenol extract/kg body weight or vehicle 2 h prior to hemorrhagic shock. H/R was induced by two protocols: 1) withdrawal of blood to a mean arterial pressure of 40 mm Hg followed by further withdrawals to decrease blood pressure progressively to 28 mm Hg over 1 h (severe), and 2) withdrawal of blood to a sustained hypotension of 40 mm Hg for 1 h (moderate). Rats were then resuscitated over 1 h with 60% of the shed blood volume plus twice the shed blood volume of lactated Ringer's solution. Serum samples were collected at 10 min and 2 h after resuscitation. At 2 or 18 h, livers were harvested for cytokine and 3-nitrotyrosine quantification, immunohistochemical detection of 4-hydroxynonenol (4-HNE) and inducible nitric oxide synthase (iNOS) protein expression.ResultsAfter severe H/R, 18-h survival increased from 20% after vehicle to 70% after polyphenols (p < 0.05). After moderate H/R, survival was greater (80%) and not different between vehicle and polyphenols. In moderate H/R, serum alanine aminotransferase (ALT) increased at 10 min and 2 h postresuscitation to 345 and 545 IU/L, respectively. Polyphenol treatment blunted this increase to 153 and 252 IU/L at 10 min and 2 h (p < 0.01). Polyphenols also blunted increases in liver homogenates of TNFα (7.0 pg/mg with vehicle vs. 4.9 pg/mg with polyphenols, p < 0.05), IL-1β (0.80 vs. 0.37 pg/mg, p < 0.05), IL-6 (6.9 vs. 5.1 pg/mg, p < 0.05) and nitrotyrosine (1.9 pg/mg vs. 0.6 pg/mg, p < 0.05) measured 18 h after H/R. Hepatic 4-HNE immunostaining indicative of lipid peroxidation also decreased from 4.8% after vehicle to 1.5% after polyphenols (p < 0.05). By contrast, polyphenols did not block increased iNOS expression at 2 h after H/R.ConclusionPolyphenols decrease ROS/RNS formation and are beneficial after hemorrhagic shock and resuscitation.
Production of glycoprotein vaccines in Escherichia coli
Authors: Ihssen Julian , Kowarik Michael , Dilettoso Sandro , Tanner Cyril , Wacker Michael , Thöny-Meyer Linda 
Published: August 2010

Abstract

Background
Conjugate vaccines in which polysaccharide antigens are covalently linked to carrier proteins belong to the most effective and safest vaccines against bacterial pathogens. State-of-the art production of conjugate vaccines using chemical methods is a laborious, multi-step process. In vivo enzymatic coupling using the general glycosylation pathway of Campylobacter jejuni in recombinant Escherichia coli has been suggested as a simpler method for producing conjugate vaccines. In this study we describe the in vivo biosynthesis of two novel conjugate vaccine candidates against Shigella dysenteriae type 1, an important bacterial pathogen causing severe gastro-intestinal disease states mainly in developing countries.

Results
Two different periplasmic carrier proteins, AcrA from C. jejuni and a toxoid form of Pseudomonas aeruginosa exotoxin were glycosylated with Shigella O antigens in E. coli. Starting from shake flask cultivation in standard complex medium a lab-scale fed-batch process was developed for glycoconjugate production. It was found that efficiency of glycosylation but not carrier protein expression was highly susceptible to the physiological state at induction. After induction glycoconjugates generally appeared later than unglycosylated carrier protein, suggesting that glycosylation was the rate-limiting step for synthesis of conjugate vaccines in E. coli. Glycoconjugate synthesis, in particular expression of oligosaccharyltransferase PglB, strongly inhibited growth of E. coli cells after induction, making it necessary to separate biomass growth and recombinant protein expression phases. With a simple pulse and linear feed strategy and the use of semi-defined glycerol medium, volumetric glycoconjugate yield was increased 30 to 50-fold.

Conclusions
The presented data demonstrate that glycosylated proteins can be produced in recombinant E. coli at a larger scale. The described methodologies constitute an important step towards cost-effective in vivo production of conjugate vaccines, which in future may be used for combating severe infectious diseases, particularly in developing countries.