bluuebunny/crossref_metadata_2025 huggingface dataset:
Discriminative ability of the generic and condition-specific Child-Oral Impacts on Daily Performances (Child-OIDP) by the Limpopo-Arusha School Health (LASH) Project: A cross-sectional study
Authors: Mbawalla Hawa S , Mtaya Matilda , Masalu Joyce R , Brudvik Pongsri , Astrom Anne N
Published: May 2011

Background

Generic and condition-specific (CS) oral-health-related quality-of-life (OHRQoL) instruments assess the impacts of general oral conditions and specific oral diseases. Focusing schoolchildren from Arusha and Dar es Salaam, in Tanzania, this study compared the discriminative ability of the generic Child OIDP with respect to dental caries and periodontal problems across the study sites. Secondly, the discriminative ability of the generic-and the CS Child OIDP attributed to dental caries, periodontal problems and malocclusion was compared with respect to various oral conditions as part of a construct validation.

Methods

In Arusha, 1077 school children (mean age 14.9 years, range 12-17 years) and 1601 school children in Dar es Salaam (mean age 13.0 years, range 12-14 years) underwent oral clinical examinations and completed the Kiswahili version of the generic and CS Child-OIDP inventories. The discriminative ability was assessed as differences in overall mean and prevalence scores between groups, corresponding effect sizes and odd ratios, OR.

Results

The differences in the prevalence scores and the overall mean generic Child-OIDP scores were significant between the groups with (DMFT > 0) and without (DMFT = 0) caries experience and with (simplified oral hygiene index [OHI-S] > 1) and without periodontal problems (OHI-S ≤ 1) in Arusha and Dar es Salaam. In Dar es Salaam, differences in the generic and CS Child-OIDP scores were observed between the groups with and without dental caries, differences in the generic Child-OIDP scores were observed between the groups with and without periodontal problems, and differences in the CS Child-OIDP scores were observed between malocclusion groups. The adjusted OR for the association between dental caries and the CS Child-OIDP score attributed to dental caries was 5.4. The adjusted OR for the association between malocclusion and CS Child-OIDP attributed to malocclusion varied from 8.8 to 2.5.

Conclusion

The generic Child-OIDP discriminated equally well between children with and without dental caries and periodontal problems across socio-culturally different study sites. Compared with its generic form, the CS Child-OIDP discriminated most strongly between children with and without dental caries and malocclusion. The CS Child OIDP attributed to dental caries and malocclusion seems to be better suited to support clinical indicators when estimating oral health needs among school children in Tanzania.
Methylation levels of the "long interspersed nucleotide element-1" repetitive sequences predict survival of melanoma patients
Authors: Sigalotti Luca , Fratta Elisabetta , Bidoli Ettore , Covre Alessia , Parisi Giulia , Colizzi Francesca , Coral Sandra , Massarut Samuele , Kirkwood John M , Maio Michele
Published: May 2011

Background

The prognosis of cutaneous melanoma (CM) differs for patients with identical clinico-pathological stage, and no molecular markers discriminating the prognosis of stage III individuals have been established. Genome-wide alterations in DNA methylation are a common event in cancer. This study aimed to define the prognostic value of genomic DNA methylation levels in stage III CM patients.

Methods

Overall level of genomic DNA methylation was measured using bisulfite pyrosequencing at three CpG sites (CpG1, CpG2, CpG3) of theLong Interspersed Nucleotide Element-1(LINE-1) sequences in short-term CM cultures from 42 stage IIIC patients. The impact ofLINE-1methylation on overall survival (OS) was assessed using Cox regression and Kaplan-Meier analysis.

Results

Hypomethylation (i.e., methylation below median) at CpG2 and CpG3 sites significantly associated with improved prognosis of CM, CpG3 showing the strongest association. Patients with hypomethylated CpG3 had increased OS (P = 0.01, log-rank = 6.39) by Kaplan-Meyer analysis. Median OS of patients with hypomethylated or hypermethylated CpG3 were 31.9 and 11.5 months, respectively. The 5 year OS for patients with hypomethylated CpG3 was 48% compared to 7% for patients with hypermethylated sequences. Among the variables examined by Cox regression analysis,LINE-1methylation at CpG2 and CpG3 was the only predictor of OS (Hazard Ratio = 2.63, for hypermethylated CpG3; 95% Confidence Interval: 1.21-5.69;P= 0.01).

Conclusion

LINE-1methylation is identified as a molecular marker of prognosis for CM patients in stage IIIC. Evaluation ofLINE-1promises to represent a key tool for driving the most appropriate clinical management of stage III CM patients.
Allergen-specific T cell quantity in blood is higher in allergic compared to nonallergic individuals
Authors: Ueno-Yamanouchi Aito , Khan Faisal M , Serushago Bazir , Bowen Tom , Lu Cathy , Luider Joanne , Storek Jan
Published: May 2011

Background

Allergen-specific IgE production is a hallmark of allergic asthma/rhinitis/eczema. Theoretically this could be due to a high number of allergen-specific B cells or allergen-specific T cells helping allergen-specific B cells differentiate into IgE-producing plasma cells. Here, we determined whether the number of allergen-specific B cells or T helper (Th) cells is higher in allergic individuals compared to nonallergic individuals.

Methods

A total of 52 allergic individuals and 32 nonallergic individuals were studied. The allergen-specific B and Th cells were enumerated by culturing CFSE-loaded blood mononuclear cells for 7-days with allergen (cat, Timothy or birch), and determining the number of proliferating B or Th cells (diluting CFSE) by flow cytometry. Allergen-specific IgE concentration was determined by fluorescent enzymoimmunoassay (FEIA).

Results

The quantities of proliferating Th cells but not proliferating B cells specific for cat, Timothy and birch were significantly higher in cat-, Timothy- and birch-allergic individuals compared to nonallergic individuals. The titer of allergen-specific IgE showed significant correlation with allergen-specific Th cells and not with allergen-specific B cells for all 3 allergens.

Conclusions

A high number of allergen-specific proliferating Th cells, but not proliferating B cells, may play a role in the pathogenesis of allergic asthma/rhinitis/eczema.
Classically and alternatively activated bone marrow derived macrophages differ in cytoskeletal functions and migration towards specific CNS cell types
Authors: Vereyken Elly JF , Heijnen Priscilla DAM , Baron Wia , de Vries Elga HE , Dijkstra Christine D , Teunissen Charlotte E
Published: May 2011

Background

Macrophages play an important role in neuroinflammatory diseases such as multiple sclerosis (MS) and spinal cord injury (SCI), being involved in both damage and repair. The divergent effects of macrophages might be explained by their different activation status: classically activated (CA/M1), pro-inflammatory, macrophages and alternatively activated (AA/M2), growth promoting, macrophages. Little is known about the effect of macrophages with these phenotypes in the central nervous system (CNS) and how they influence pathogenesis. The aim of this study was therefore to determine the characteristics of these phenotypically different macrophages in the context of the CNS in anin vitrosetting.

Results

Here we show that bone marrow derived CA and AA macrophages have a distinct migratory capacity towards medium conditioned by various cell types of the CNS. AA macrophages were preferentially attracted by the low weight (< 10 kD) fraction of neuronal conditioned medium, while CA macrophages were attracted in higher numbers by astrocyte- and oligodendrocyte conditioned medium. Intrinsic motility was twice as high in AA macrophages compared to CA macrophages. The adhesion to extracellular matrix molecules (ECM) was significantly enhanced in CA macrophages compared to control and AA macrophages. The actin cytoskeleton was differentially organized between CA and AA macrophages, possibly due to greater activity of the GTPases RhoA and Rac in CA macrophages. Phagocytosis of myelin and neuronal fragments was increased in CA macrophages compared to AA macrophages. The increase in myelin phagocytosis was associated with higher expression of CR3/MAC-1 in CA macrophages.

Conclusion

In conclusion, since AA macrophages are more motile and are attracted by NCM, they are prone to migrate towards neurons in the CNS. CA macrophages have a lower motility and a stronger adhesion to ECM. In neuroinflammatory diseases the restricted migration and motility of CA macrophages might limit lesion size due to bystander damage.
The presence of tomato leaf curl Kerala virus AC3 protein enhances viral DNA replication and modulates virus induced gene-silencing mechanism in tomato plants
Authors: Pasumarthy Kalyan K , Mukherjee Sunil K , Choudhury Nirupam R
Published: May 2011

Background

Geminiviruses encode few viral proteins. Most of the geminiviral proteins are multifunctional and influence various host cellular processes for the successful viral infection. Though few viral proteins like AC1 and AC2 are well characterized for their multiple functions, role of AC3 in the successful viral infection has not been investigated in detail.

Results

We performed phage display analysis with the purified recombinant AC3 protein with Maltose Binding Protein as fusion tag (MBP-AC3). Putative AC3 interacting peptides identified through phage display were observed to be homologous to peptides of proteins from various metabolisms. We grouped these putative AC3 interacting peptides according to the known metabolic function of the homologous peptide containing proteins. In order to check if AC3 influences any of these particular metabolic pathways, we designed vectors for assaying DNA replication and virus induced gene-silencing of host gene PCNA. Investigation with these vectors indicated that AC3 enhances viral replication in the host plant tomato. In the PCNA gene-silencing experiment, we observed that the presence of functional AC3 ORF strongly manifested the stunted phenotype associated with the virus induced gene-silencing of PCNA in tomato plants.

Conclusions

Through the phage display analysis proteins from various metabolic pathways were identified as putative AC3 interacting proteins. By utilizing the vectors developed, we could analyze the role of AC3 in viral DNA replication and host gene-silencing. Our studies indicate that AC3 is also a multifunctional protein.
Interplay of recombination and selection in the genomes of Chlamydia trachomatis
Authors: Joseph Sandeep J , Didelot Xavier , Gandhi Khanjan , Dean Deborah , Read Timothy D
Published: May 2011

Background

Chlamydia trachomatis is an obligate intracellular bacterial parasite, which causes several severe and debilitating diseases in humans. This study uses comparative genomic analyses of 12 complete published C. trachomatis genomes to assess the contribution of recombination and selection in this pathogen and to understand the major evolutionary forces acting on the genome of this bacterium.

Results

The conserved core genes of C. trachomatis are a large proportion of the pan-genome: we identified 836 core genes in C. trachomatis out of a range of 874-927 total genes in each genome. The ratio of recombination events compared to mutation (ρ/θ) was 0.07 based on ancestral reconstructions using the ClonalFrame tool, but recombination had a significant effect on genetic diversification (r/m = 0.71). The distance-dependent decay of linkage disequilibrium also indicated that C. trachomatis populations behaved intermediately between sexual and clonal extremes. Fifty-five genes were identified as having a history of recombination and 92 were under positive selection based on statistical tests. Twenty-three genes showed evidence of being under both positive selection and recombination, which included genes with a known role in virulence and pathogencity (e.g., ompA, pmps, tarp). Analysis of inter-clade recombination flux indicated non-uniform currents of recombination between clades, which suggests the possibility of spatial population structure in C. trachomatis infections.

Conclusions

C. trachomatis is the archetype of a bacterial species where recombination is relatively frequent yet gene gains by horizontal gene transfer (HGT) and losses (by deletion) are rare. Gene conversion occurs at sites across the whole C. trachomatis genome but may be more often fixed in genes that are under diversifying selection. Furthermore, genome sequencing will reveal patterns of serotype specific gene exchange and selection that will generate important research questions for understanding C. trachomatis pathogenesis.

Reviewers

This article was reviewed by Dr. Jeremy Selengut, Dr. Lee S. Katz (nominated by Dr. I. King Jordan) and Dr. Arcady Mushegian.
Alk3 controls nephron number and androgen production via lineage-specific effects in intermediate mesoderm
Authors: Di Giovanni Valeria , Alday Adrian , Chi Lijun , Mishina Yuji , Rosenblum Norman D.
Published: May 2011

The mammalian kidney and male reproductive system are both derived from the intermediate mesoderm. The spatial and temporal expression of bone morphogenetic protein (BMP) 2 and BMP4 and their cognate receptor, activin like kinase 3 (ALK3), suggests a functional role for BMP-ALK3 signaling during formation of intermediate mesoderm-derivative organs. Here, we define cell autonomous functions for Alk3 in the kidney and male gonad in mice with CRE-mediated Alk3 inactivation targeted to intermediate mesoderm progenitors (Alk3IMP null). Alk3-deficient mice exhibit simple renal hypoplasia characterized by decreases in both kidney size and nephron number but normal tissue architecture. These defects are preceded by a decreased contribution of Alk3-deleted cells to the metanephric blastema and reduced expression of Osr1 and SIX2, which mark nephron progenitor cells. Mutant mice are also characterized by defects in intermediate mesoderm-derived genital tissues with fewer mesonephric tubules and testicular Leydig cells, epithelial vacuolization in the postnatal corpus epididymis, and decreased serum testosterone levels and reduced fertility. Analysis of ALK3-dependent signaling effectors revealed lineage-specific reduction of phospho-p38 MAPK in metanephric mesenchyme and phospho-SMAD1/5/8 in the testis. Together, these results demonstrate a requirement for Alk3 in distinct progenitor cell populations derived from the intermediate mesoderm.
Gpr126 is essential for peripheral nerve development and myelination in mammals
Authors: Monk Kelly R. , Oshima Kazuo , Jörs Simone , Heller Stefan , Talbot William S.
Published: May 2011

In peripheral nerves, Schwann cells form the myelin sheath that insulates axons and allows rapid propagation of action potentials. Although a number of regulators of Schwann cell development are known, the signaling pathways that control myelination are incompletely understood. In this study, we show that Gpr126 is essential for myelination and other aspects of peripheral nerve development in mammals. A mutation in Gpr126 causes a severe congenital hypomyelinating peripheral neuropathy in mice, and expression of differentiated Schwann cell markers, including Pou3f1, Egr2, myelin protein zero and myelin basic protein, is reduced. Ultrastructural studies of Gpr126−/− mice showed that axonal sorting by Schwann cells is delayed, Remak bundles (non-myelinating Schwann cells associated with small caliber axons) are not observed, and Schwann cells are ultimately arrested at the promyelinating stage. Additionally, ectopic perineurial fibroblasts form aberrant fascicles throughout the endoneurium of the mutant sciatic nerve. This analysis shows that Gpr126 is required for Schwann cell myelination in mammals, and defines new roles for Gpr126 in axonal sorting, formation of mature non-myelinating Schwann cells and organization of the perineurium.
The Tpr protein regulates export of mRNAs with retained introns that traffic through the Nxf1 pathway
Authors: Coyle John H. , Bor Yeou-Cherng , Rekosh David , Hammarskjold Marie-Louise
Published: May 2011

Post-transcriptional regulation of mRNA includes restriction mechanisms to prevent export and expression of mRNAs that are incompletely spliced. Here we present evidence that the mammalian protein Tpr is involved in this restriction. To study the role of Tpr in export of mRNA with retained introns, we used reporters in which the mRNA was exported either via the Nxf1/Nxt1 pathway using a CTE or via the Crm1 pathway using Rev/RRE. Our data show that even modest knockdown of Tpr using RNAi leads to a significant increase in export and translation from the mRNA containing the CTE. In contrast, Tpr perturbation has no effect on export of mRNA containing the RRE, either in the absence or presence of Rev. Also, no effects were observed on export of a completely spliced mRNA. Taken together, our results indicate that Tpr plays an important role in quality control of mRNA trafficked on the Nxf1 pathway.
Gut Liking for the Ordinary: Incorporating Design Fluency Improves Automobile Sales Forecasts
Authors: Landwehr Jan R. , Labroo Aparna A. , Herrmann Andreas
Published: May 2011

Automotive sales forecasts traditionally focus on predictors such as advertising, brand preference, life cycle position, retail price, and technological sophistication. The quality of the cars' design is, however, an often-neglected variable in such models. We show that incorporating objective measures of design prototypicality and design complexity in sales forecasting models improves their prediction by up to 19%. To this end, we professionally photographed the frontal designs of 28 popular models, morphed the images, and created objective prototypicality (car-to-morph Euclidian proximity) and complexity (size of a compressed image file) scores for each car. Results show that prototypical but complex car designs feel surprisingly fluent to process, and that this form of surprising fluency evokes positive gut reactions that become associated with the design and positively impact car sales. It is important to note that the effect holds for both economy (functionality oriented) and premium (identity oriented) cars, as well as when the above-mentioned traditional forecasting variables are considered. These findings are counter to a common intuition that consumers like unusual–complex designs that reflect their individuality or prototypical–simple designs that are functional.
Translating pharmacogenetics into clinical practice: interleukin (IL)28B and inosine triphosphatase (ITPA) polymophisms in hepatitis C virus (HCV) infection
Authors: Cariani Elisabetta , Villa Erica , Rota Cristina , Critelli Rosina , Trenti Tommaso
Published: May 2011

Hepatitis C virus (HCV) infection is frequently characterized by evolution to chronicity and by a variable clinical course of the disease. The clinical heterogeneities of HCV infection and the imperfect predictability of the response to interferon (IFN) have suggested the need to search for a genetic basis of clinical features. This led to the discovery of genetic polymorphisms playing a major role in the evolution of infection, as well as on treatment response and adverse effects. This review will cover recent reports on the subject, focusing on the potential use of the new genetic markers in the diagnostic algorithm for the stratification of patients for personalized antiviral regimens.
Ultra Low Tin Quaternary Alloys PWR Performance—Impact of Tin Content on Corrosion Resistance, Irradiation Growth, and Mechanical Properties
Authors: Chabretou V. , Hoffmann P. B. , Trapp-Pritsching S. , Garner G. , Barberis P. , Rebeyrolle V. , Vermoyal J. J.
Published: May 2011

The performance of Zr1NbSnFe alloys within the range of Sn 0–0.65 % and Fe 0.03–0.35 % were studied through irradiation of fuel rods in two pressurized water reactors (PWRs) operating with significantly different fuel management strategies. Material test rod irradiations have also been launched in order to determine irradiation growth and corrosion behaviour on tubes irradiated under conditions representative of guide tubes. Results show that the increase in tin content up to 0.3 % does not significantly change the corrosion resistance nor the hydrogen pick-up compared to Zr1Nb alloy, while ensuring a higher creep resistance and an improved dimensional stability. On the contrary, at 0.5 % Sn, the corrosion resistance can be significantly degraded under demanding conditions. The iron addition to the alloy can be considered as a second order parameter for both corrosion and creep properties.
Production and properties of transuranium elements
Authors: Nagame Y. , Hirata M.
Published: May 2011

We summarize historical perspective of the transuranium elements, neptunium (Np) through lawrencium (Lr), and recent progress on production, and nuclear and chemical properties of these elements. Exotic decay properties of heavy nuclei are also introduced. Chemical properties of transuranium elements in aqueous and solid states are summarized based on the actinide concept.
Spectroscopy of actinide and transactinide nuclei
Authors: Herzberg R.-D. , Cox D. M.
Published: May 2011

The role of isomers for nuclei with Z ≥ 100 is discussed. Recent advances in experimental instrumentation leading to combined in-beam gamma ray and conversion electron spectroscopy are discussed. The rotational spectra of nuclei with Z ≥ 94 and their moments of inertia are discussed. Examples for in-beam spectroscopy leading to the discovery and identification of isomers are given in 248,250Fm. Here some attention is given to the assignment of nuclear configurations from g-factors measured via the branching ratios of coupled bands built on the isomers. A full list of the longest lived isomers in nuclei with Z ≥ 82 is given.
Small Molecule Tunnelling Systems: Variation of Isotope Effects
Authors: Jakobušić Brala Cvijeta , Karković Ana , Klepac Katarina , Vučinović Ana Marija , Pilepić Viktor , Uršić Stanko
Published: May 2011

Variations of the kinetic isotope effects and tunnelling regime in two small molecule tunnelling systems, the reaction of ascorbate monoanion with hexacyanoferrate(III) ions in water-acetonitrile (1:1 v/v), water-dioxane (1:1 v/v) and the oxidation of ascorbate with ferricinium ions in water were investigated. The kinetic isotope effects and tunnelling regime undergo to changes due to presence of cations in the reactions. The evidence comprise: 1.) the spectroscopic and kinetic evidences for the interaction of ascorbate monoanion with hexacyanoferrate(III) ions in water-acetonitrile (1:1 v/v), water-dioxane (1:1 v/v) and for the oxidation of ascorbate with ferricinium ions in water; 2.) for the interaction of ascorbate monoanion with hexacyanoferrate(III) ions: a) the observation of change of KIE from k
H/k
D=8.25(0.09) in water-acetonitrile (1:1 v/v) to 5.86(0.17) in presence of 0.1 M K+ in the same solvent; b) the observation of change of KIE from k
H/k
D=8.37(0.16) in water-dioxane (1:1 v/v) to 5.75(0.1) in presence of 0.3 M Na+ in the same solvent; c) the observation of change of isotope effect on the Arrhenius pre-factors, from A
H/A
D=0.49(0.09) in the reaction in water-acetonitrile (1:1 v/v) to A
H/A
D=0.14(0.02) in presence of 0.1 M K+ in the same solvent; d) the observation of change of isotope effect on the Arrhenius pre-factors, from A
H/A
D=0.046(0.008) in the reaction in water-dioxane (1:1 v/v) to A
H/A
D=0.07(0.01) in presence of 0.3 M Na+ in the same solvent; 3.) for the oxidation of ascorbate with ferricinium ions: a) the observation of change of KIE from k
H/k
D=1.91(0.02) in water to k
H/k
D=2.01(0.03) in presence of 0.5 M Na+; b) the observation of change of isotope effect on the Arrhenius pre-factors, from A
H/A
D=0.80(0.09) in the reaction in water to A
H/A
D=0.52(0.10) in presence of 0.5 M Na+; c) the observation of change of KIE from k
H/k
D=1.91(0.02) in water to k
H/k
D=1.72(0.02) in presence of 0.1 M of acetate ion; d) the observation of catalysis by acetate ions in the reaction. These results were discussed tentatively following a framework of Marcus-like tunnelling model, taking into account differences between the transition structures in the reactions and dynamical features of the systems.
Dihydrotestosterone upregulates the expression of epidermal growth factor receptor and ERBB2 in androgen receptor-positive bladder cancer cells
Authors: Zheng Yichun , Izumi Koji , Yao Jorge L , Miyamoto Hiroshi
Published: May 2011

Androgen receptor (AR) signals play important roles in bladder carcinogenesis and tumor progression. Activation of the epidermal growth factor receptor (EGFR) family, including EGFR and ERBB2, leads to bladder cancer cell growth and correlates with poor patients' prognosis. However, cross talk between AR and EGFR/ERBB2 pathways in bladder cancer remains poorly understood. In AR-positive bladder cancer UMUC3 and TCC-SUP cells, dihydrotestosterone (DHT) increased the expression of EGFR and ERBB2 both in mRNA and in protein levels, and an anti-androgen hydroxyflutamide antagonized the effect of DHT. The necessity of AR was confirmed by silencing the receptor, using short hairpin RNA (shRNA), in UMUC3 cells, as well as by expressing the receptor in AR-negative 5637 cells. Of note were much higher basal levels of EGFR and ERBB2 in UMUC3-control-shRNA than in UMUC3-AR-shRNA and those of EGFR in 5637-AR than in 5637-V. DHT additionally upregulated the levels of phosphorylation of EGFR (pEGFR) and its downstream proteins AKT (pAKT) and ERK1/2 (pERK), induced by EGF treatment, in AR-positive cells. Immunohistochemistry on cystectomy specimens showed strong associations between expressions of AR and EGFR (P=0.0136), pEGFR (P=0.0041), ERBB2 (P=0.0331), or pERK (P=0.0274), but not of pAKT (P=0.5555). The Kaplan–Meier and log-rank tests further revealed that positivity of AR (P=0.0005), EGFR (P=0.2425), pEGFR (P=0.1579), ERBB2 (P=0.2997), or pERK (P=0.1270) and negativity of pAKT (P=0.0483) were associated with tumor progression. Our results indicate that AR activation upregulates the expression of EGFR and ERBB2 in bladder cancer cells. AR signals may thus contribute to the progression of bladder cancer via regulation of the EGFR/ERBB2 pathways.
Killing the second messenger: targeting loss of cell cycle control in endocrine-resistant breast cancer
Authors: Lange Carol A , Yee Douglas
Published: May 2011

The majority (∼70%) of breast cancers are steroid hormone receptor (SR) positive at the time of diagnosis. Endocrine therapies that target estrogen receptor α (ERα) action (tamoxifen, toremifene, fulvestrant) or estrogen synthesis (aromatase inhibitors: letrozole, anastrozole, exemestane; or ovarian suppression) are a clinical mainstay. However, up to 50% of SR+ breast cancers exhibit de novo or acquired resistance to these clinical interventions. Mechanisms of resistance to endocrine therapies often include upregulation and/or activation of signal transduction pathways that input to cell cycle regulation. Cyclin D1, the regulatory subunit of cyclin-dependent protein kinases four and six (CDK4/6) serves as a convergence point for multiple signaling pathways. In a recent paper entitled ‘Therapeutically Activating Retinoblastoma (RB): Reestablishing Cell Cycle Control in Endocrine Therapy-Resistant Breast Cancer’, Thangavel et al. reported maintenance of cyclin D1 expression and RB phosphorylation in the face of ER ablation in multiple breast cancer cell line models of endocrine resistance. RB-dysfunction defined a unique gene signature that was associated with luminal B-type breast cancer and predictive of poor response to endocrine therapies. Notably, a new CDK4/6 inhibitor (PD-0332991) was capable of inducing growth arrest by a mechanism that was most consistent with cellular senescence. In this review, these findings are discussed in the context of SRs as important mediators of cell cycle progression, and the frequent loss of cell cycle checkpoint control that typifies breast cancer progression. These studies provide renewed hope of effectively stabilizing endocrine-resistant breast cancers using available complementary (to endocrine-based therapies) cytostatic agents in the form of CDK4/6 inhibitors.
Production, purification and characterization of a thermostable β-1,3-glucanase (laminarinase) produced by Moniliophthora perniciosa
Authors: Sena Amanda R. , Júnior Gildomar L.V. , Góes Neto Aristóteles , Taranto Alex G. , Pirovani Carlos P. , Cascardo Júlio C.M. , Zingali Russolina B. , Bezerra Marcos A. , Assis Sandra A.
Published: May 2011

The enzyme glucanase from Moniliophthora perniciosa was produced in liquid medium and purified from the culture supernatant. A multivariate statistical approach (Response Surface Methodology - RSM) was employed to evaluate the effect of variables, including inducer (yeast extract) and fermentation time, on secreted glucanase activities M. perniciosa detected in the culture medium. The crude enzyme present in the supernatant was purified in two steps: precipitation with ammonium sulfate (70%) and gel filtration chromatography on Sephacryl S-200. The best inducer and fermentation time for glucanase activities were 5.9 g L-1 and 13 days, respectively. The results revealed three different isoforms (GLUI, GLUII and GLUIII) with purification factors of 4.33, 1.86 and 3.03, respectively. The partially purified enzymatic extract showed an optimum pH of 5.0 and an optimum temperature of 40°C. The enzymatic activity increased in the presence of KCl at all concentrations studied. The glucanase activity was highest in the presence of 0.2 M NaCl. The enzyme showed high thermal stability, losing only 10.20% of its specific activity after 40 minutes of incubation at 90°C. A purified enzyme with relatively good thermostability that is stable at low pH might be used in future industrial applications.
Computed tomography in neurocysticercosis a 10-year long evolution analysis of 100 patients with an appraisal of a new classification
Authors: Machado L. R. , Nobrega J. P. S. , Barros N. G. , Livramento J. A. , Bacheschi L. A. , Spina -França A.
Published: May 2011

Three hundred land fifty seven computed tomography (CT) from 100 different patients with neurocysticercosis (NC) were studied between 1979 and 1988. All patients were treated with praziquantel (PZQ). A new classification attempting to recognize the CT evolution profile in NC as well as assigning a possible link between CT findings and biological conditions of cysts is evaluated. It was possible to conclude that: intact cysts remain unchanged in consecutive CTs by 11 months and exhibit signs of degeneration in about 18 months after PZQ drug therapy; degenerating cysts can be detected by 10.5 months, disappear in 11 months and become nodular calcifications in about 25 months. Therefore, a time period of at least 36 months can be estimated for the complete evolution profile of cysts in the brain parenchyma.
Tratamento da neurocisticercose com praziquantel
Authors: Vianna L. G. , Macedo V. , Mello P. , Souza H. A. O. , Costa J. M.
Published: May 2011

27 pacientes com neurocisticercose foram tratados com praziquantel, utilizado em doses progressivamente crescentes até alcançar 50 mg/kg/dia, por período de 21 dias, associado a dexametasona. Os doentes foram avaliados clínica e laboratorialmente durante o tratamento e, aqueles que completaram um ano de evolução, repetiram os testes imunofluorescência e ELISA neste período. Cefaléia foi o sintoma encontrado mais freqüentemente durante o tratamento, ocorrendo em 37% dos pacientes; 18,5% dos doentes apresentaram hipertensão intracraniana, um deles evoluindo para o óbito; 25,9% dos enfermos tiveram que suspender o praziquantel antes de completar o tratamento, devido ao surgimento de complicações importantes. Nos exames laboratoriais realizados no sétimo dia de tratamento, 33,3% dos pacientes apresentaram anormalidades, sendo leucocitose a mais freqüente. No período de um ano, 72,2% dos enfermos tiveram melhora do quadro clínico, enquanto os testes imunológicos tornaram-se não-reagentes no soro em 45,4% dos doentes e no LCR em 42,8%. Entretanto, nem sempre houve coincidência da melhora clínica com a apresentação dos testes imunológicos não-reagentes. No presente trabalho, não é possível afirmar que os testes imunológicos não-reagentes, assim como a melhora clínica dos pacientes, sejam conseqüentes à eficácia do tratamento com o praziquantel. Devido à grande freqüência e gravidade das complicações deste tratamento, os pacientes devem ser avaliados individualmente quanto aos riscos versus os benefícios dele.
HTLV-1 antibodies in serum and cerebrospinal fluid in tropical spastic paraparesis in Brazil
Authors: Spina-França A. , Livramento J. A. , Machado L. R. , Gomes H. R. , Vianna L. S. , Castro L. H. M. , Nobrega J. P. S. , Baciheschi L. A.
Published: May 2011

HTLV-l antibodies were investigated in serum and in CSF of 150 patients with neurologic disorders mainly myelopathies. The patients were considered into three groups according to the possible relationship of their disease to the presence of HTLV-l antibodies: no relationship risk (control group), occasional risk group, and possible risk group. In this latter are 56 patients with crural spastic paraparesis or paraplegia of unknown etiology (SP). HTLV-l antibodies were tested by the passive particle-agglutination method for anti-ATLA antibody detection. The search was negative in all patients of the control group, and positive (serum and/or CSF) in 16.5% of the patients from the second group and in 55.4% of the SP patients group. Clinical patterns in SP cases with HTLV-l antibodies were those of tropical spastic paraparesis (TSP). CSF patterns considered (cytology, protein content and gamma-globulins rate) were different between TSP group with HTLV-l antibodies in CSF and SP group with no HTLV-l antibodies detection either in serum or in CSF. The difference was significant. Results of this investigation confirm the high incidence of TSP in Brazil, and bring additional indication for searching HTLV-l antibodies in the CSF.
Observações sobre o deslocamento da dura-máter nas punções cisternais laterais
Authors: Rossitti Sandro L. , Araújo João Flávio M. , Sperlescu Alexander , Balbo Roque J.
Published: May 2011

Estudo da anatomia dinâmica da punção cisternal lateral (suboccipital e C1-2) em cadáveres frescos, sob visão direta da dura-máter da junção crânio-vertebral. O deslocamento («tenda») da dura foi observado em todas as punções (n = 42), em média 3,46 mm (2 a 6 mm).
Associação de doença de wilson e síndrome extrapiramidal não Wilsoniana na mesma família
Authors: Barbosa Egberto R. , Kostow Ursula P. , Cançado Roberto Hirsch Eduardo R. , Scaff M. , Canelas Horacio M.
Published: May 2011

Distúrbios do movimento, geralmente de tipo distónico, têm sido relatados em heterozigotos para doença de Wilson (DW). O presente relato assinala a presença em uma mesma família de heterozigoto para DW com quadro distónico e sua sobrinha com quadro clássico de DW. Discutem-se as peculiaridades dessa família, comparando-se aos dados da literatura, bem como os possíveis mecanismos etiopatrogênicos envolvidos.
Associação rara: polimiosite, miastenia grave e timoma
Authors: Boekel V. Van , Godoy J. M. , Menezes J. M. T.
Published: May 2011

Fundamentados no fato de que, tanto na literatura nacional quanto na estrangeira, inexiste referência da associação de polimiosite, miastenia grave e timoma em adulto jovem do sexo masculino, os autores se propõem a descrever um caso da citada síndrome. O paciente aqui apresentado teve sua doença iniciada aos 22 anos de idade, atingindo sua expressão clínica máxima 4 anos miais tarde. No estudo em apreço, são enfatizadas as dificuldades no diagnóstico diferencial entre polimiosite e miastenia grave, doenças que, a principio, têm suas manifestações clinicas características, de modo geral bem individualizadas. Na presente observação chamamos a atenção para a possível existência de aspectos clínicos sugestivos de miastenia em enfermos com polimiosite e, por outro lado, alterações histopatológicas típicas de polimiosite em músculos de miastênicos, inviabilizando muitas vezes o diagnóstico clínico de certeza.
Síndrome de lennox-gastaut com início na vida adulta? a respeito de um caso
Authors: Trevisol-Bittencourt P. C. , Sander J. W. A. S.
Published: May 2011

Apesar de ter sido relatada anteriormente, a sindrome de Lennox-Gastaut (SLG) só foi definitivamente aceita como entidade distinta em 1966. Desde então, o epônimo tem sido utilizado para designar encefalopatia severa da infância, caracterizada fundamentalmente por crises epilépticas refratárias de diversos tipos associadas com alterações eletrográficas típicas. Entretanto, vários autores consideram que o rótulo de SLG está abrigando quadros nosológicos distintos, que deveriam ser separados e individualizados. Ilustrando esta situação, o caso de um paciente que iniciou quadro de «SLG-like» aos 20 anos de idade é relatado. Adicionando mais confusão, alguns casos semelhantes têm sido descritos nos últimos anos sob variada nomenclatura. Desde que um dos principais critérios para o diagnóstico da SLG é a idade dependência, como deverão então ser chamados tais quadros? Revisão dos critérios empregados para o diagnóstico da SLG se faz necessária.
Global aphasia as a predictor of mortality in the acute phase of a first stroke
Authors: Oliveira F F , Damasceno B P
Published: May 2011

OBJECTIVE: To establish whether vascular aphasic syndromes can predict stroke outcomes. METHOD: Thirty-seven adults were evaluated for speech and language within 72 hours after a single first-ever ischemic brain lesion, in blind association to CT and/or MR. RESULTS: Speech or language disabilities were found in seven (87.5%) of the eight deceased patients and twenty-six (89.7%) of the twenty-nine survivors. Global aphasia was identified in eleven patients, all with left hemisphere lesions (nine mute; five deceased), consisting on a risk factor for death in the acute stroke phase (ρ=0.022). Age (z=1.65; ρ>0.09), thrombolysis (ρ=0.591), infarct size (ρ=0.076) and side (ρ=0.649) did not significantly influence survival. Absence of aphasia did not predict a better evolution, regardless of the affected hemisphere. Prevalence of cardiovascular risk factors was similar for all patient groups. CONCLUSION: Global aphasia in acute stroke can adversely affect prognosis, translated into impairment of dominant perisylvian vascular territories, with mutism as an important semiological element.
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS): typical clinical and neuroimaging features in a Brazilian family
Authors: Pedroso J L , Braga-Neto P , Abrahão A , Rivero R L M , Abdalla C , Abdala N , Barsottini O G P
Published: May 2011

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurodegenerative disorder characterized by late-infantile onset spastic ataxia and other neurological features. ARSACS has a high prevalence in northeastern Quebec, Canada. Several ARSACS cases have been reported outside Canada in recent decades. This is the first report of typical clinical and neuroimaging features in a Brazilian family with probable diagnosis of ARSACS.
Brain stem and cerebellum volumetric analysis of Machado Joseph disease patients
Authors: Camargos S T , Marques-Jr W , Santos A C
Published: May 2011

Machado-Joseph disease, or spinocerebellar ataxia type 3(MJD/SCA3), is the most frequent late onset spinocerebellar ataxia and results from a CAG repeat expansion in the ataxin-3 gene. Previous studies have found correlation between atrophy of cerebellum and brainstem with age and CAG repeats, although no such correlation has been found with disease duration and clinical manifestations. In this study we test the hypothesis that atrophy of cerebellum and brainstem in MJD/SCA3 is related to clinical severity, disease duration and CAG repeat length as well as to other variables such as age and ICARS (International Cooperative Ataxia Rating Scale). Whole brain high resolution MRI and volumetric measurement with cranial volume normalization were obtained from 15 MJD/SCA3 patients and 15 normal, age and sex-matchedcontrols. We applied ICARS and compared the score with volumes and CAG number, disease duration and age. We found significant correlation of both brain stem and cerebellar atrophy with CAG repeat length, age, disease duration and degree of disability. The Spearman rank correlation was stronger with volumetric reduction of the cerebellum than with brain stem. Our data allow us to conclude that volumetric analysis might reveal progressive degeneration after disease onset, which in turn is linked to both age and number of CAG repeat expansions in SCA 3.
Cross-cultural translation of the INSPIRIT-R for Brazil and its applicability among epilepsy patients
Authors: Veronez I S , Bicalho M A H , Claudino L S , Walz R , Lin K
Published: May 2011

OBJECTIVE: To describe the cross-cultural adaptation of the INSPIRIT-R instrument for evaluation of religious and spiritual experiences into a Brazilian Portuguese version and its applicability among epileptic patients. METHOD: After the translation and back-translation phases, a multidisciplinary committee compared the back-translation with the original text in order to evaluate its content, comprehensibility, conceptual equivalence, cultural and contextual adjustment for Brazilian population. Lastly, the final version was tested on 50 long-term followed-up outpatients with a confirmed diagnosis of epilepsy in Florianópolis, SC, Brazil. RESULTS: The patients' mean age was 33.7 years (18-55) and 26 (52%) were women. They had attended school for a mean of 8.0 years (3-17) years. Most of them (80%) were Catholics and 82% had a confirmed diagnosis of temporal lobe epilepsy. In the final Portuguese version, questions 3, 7C and 7E required slight modifications, along with the layout of question 7. CONCLUSION: The Brazilian Portuguese version of the INSPIRIT-R instrument was easily understood by most of the patients, after minimal modifications.
Validation of the EuroQol quality of life questionnaire on stroke victims
Authors: Pinto E B , Maso I , Vilela R N R , Santos L C , Oliveira-Filho J
Published: May 2011

OBJECTIVE: To validate a quality of life scale, EuroQoL, on stroke patients. METHOD: 67 patients were scored simultaneously for EuroQoL-5 Dimensions (EQ-5D), NIH Stroke Scale (NIHSS) and modified Barthel Index (mBI). Pearson test was used to correlate each scale. Additionally, 31 patients were examined by two independent evaluators on the same day through application of EQ-5D. Kappa statistics were used to evaluate interobserver agreement. RESULTS: EQ-5D showed good correlation with both stroke severity (NIHSS, r= -0.404, P<0.001) and degree of impairment on activities of daily living (mBI, r=0.512, P<0.001). We noticed a good interobserver agreement (k>0.60) in all dimensions evaluated (P<0.01). CONCLUSION: We demonstrated that EQ-5D is reproducible and valid on evaluation of quality of life in patients post stroke in Brazil.
Odors as triggering and worsening factors for migraine in men
Authors: Lima A M , Sapienza G B , Giraud V O , Fragoso Y D
Published: May 2011

OBJECTIVE: To assess the role of odors in triggering or worsening migraine in men. METHOD: Ninety-eight male migraineurs from the general population were assessed individually through questionnaires. Environmental factors relating to their migraine were reported, with special focus on the role of odors. RESULTS: Odors were the second most frequent triggering factor for migraine attacks (48%), behind stressful situations (59%). Likewise, odors were the second most frequent worsening factor (73%), just behind excessive light (74%). Thirty-three individuals (33.4%) stated that odors were both triggering and worsening factors for their migraine attacks. Perfume, cigarette smoke and cleaning products were the most frequent migraine-related odors reported by these male migraineurs. CONCLUSION: This was the first study to assess the role of odors in migraine exclusively in men. There was a high degree of odor-related migraine among these men, thus suggesting that patient education could alert such individuals to gender-related factors, since different triggering and worsening factors have been reported by males and females.
Lipoic acid effects on glutamate and taurine concentrations in rat hippocampus after pilocarpine-induced seizures
Authors: Santos P S , Campêlo L M L , Freitas R L M , Feitosa C M , Saldanha G B , Freitas R M
Published: May 2011

Pilocarpine-induced seizures can be mediated by increases in oxidative stress and by cerebral amino acid changes. The present research suggests that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the lipoic acid (LA) effects in glutamate and taurine contents in rat hippocampus after pilocarpine-induced seizures. Wistar rats were treated intraperitoneally (i.p.) with 0.9% saline (Control), pilocarpine (400 mg/kg, Pilocarpine), LA (10 mg/kg, LA), and the association of LA (10 mg/kg) plus pilocarpine (400 mg/kg), that was injected 30 min before of administration of LA (LA plus pilocarpine). Animals were observed during 24 h. The amino acid concentrations were measured using high-performance liquid chromatograph (HPLC). In pilocarpine group, it was observed a significant increase in glutamate content (37%) and a decrease in taurine level (18%) in rat hippocampus, when compared to control group. Antioxidant pretreatment significantly reduced the glutamate level (28%) and augmented taurine content (32%) in rat hippocampus, when compared to pilocarpine group. Our findings strongly support amino acid changes in hippocampus during seizures induced by pilocarpine, and suggest that glutamate-induced brain damage plays a crucial role in pathogenic consequences of seizures, and imply that strong protective effect could be achieved using lipoic acid through the release or decrease in metabolization rate of taurine amino acid during seizures.
Factors associated with health-related quality of life for adults with stroke sequelae
Authors: Fróes K S S O , Valdés M T M , Lopes D P L O , Silva C E P
Published: May 2011

OBJECTIVE: To assess health-related quality of life (HRQoL) among adults with stroke sequelae and to identify the factors that influenced the domains of HRQoL. METHOD: The subjects were adults with stroke who were admitted to a rehabilitation program between March and August 2008. They were investigated using the following instruments: Medical Outcomes 36-Item Short-Form Health Survey (SF-36), Functional Independence Measure (FIM) and Beck Depression Inventory (BDI). Sixty-four adults of mean age 58.8 years were evaluated. RESULTS: The individuals who had had their injuries for longer times and who were more independent and younger had better HRQoL regarding physical functioning. Social participation was associated with better HRQoL, and there was a difference between groups with and without depressive symptoms. CONCLUSION: HRQoL was compromised primarily with regard to functional characteristics. Moreover, the presence of depressive symptoms contributed towards a decline in HRQoL. Rehabilitation needs to focus on improving functionality and social participation, which may stimulate reductions in depressive symptoms and improvement of HRQoL.