bluuebunny/crossref_metadata_2025 huggingface dataset:
An Analysis of Potentially Prolactin-Related Adverse Events and Abnormal Prolactin Values in Randomized Clinical Trials with Paliperidone Palmitate
Authors: Einarson Thomas R , Hemels Michiel EH , Nuamah Isaac , Gopal Srihari , Coppola Danielle , Hough David
Published: September 2012

Background:

Paliperidone palmitate has been associated with serum prolactin elevations in some patients. However, few individuals with elevated prolactin levels (hyperprolactinomia) have symptomatic potentially prolactin-related adverse events (PPR-AEs).

Objective:

To quantify rates of hyperprolactinemia in subjects treated with the newly marketed paliperidone palmitate long-acting injection (PP-LAI) in randomized clinical trials, summarize rates of PPR-AEs in those trials by sex and dose, and determine how many PPR-AEs required treatment.

Methods:

Numbers and rates of investigator-reported hyperprolactinemia and PPR-AEs wore obtained from the sponsor's clinical trial database and have been included in regulatory filings. Results were tabulated for males, females, and overall, and by dose administered, using descriptive statistics. Those requiring treatment were described as well.

Results:

There were 3173 subjects (61.4% males) exposed to PP-LAI in 10 clinical trials; 2831 (89.2%) patients had recorded prolactin levels, including 1759 males (90, 3% of exposed males) and 1072 females (87.5% of exposed females). Overall, at any time, prolactin levels were elevated for 38.8% of the subjects (39.5% for males and 37.7% for females; p = 0.354 between sexes). However, them was no significant correlation between monthly dose and proportion of subjects with elevated prolactin levels (p = 0.109). There were 115 PPR-AEs in 107 patients (3.4%); 51 (44.3% of PPR-AEs) cases represented asymptomatic hyperprolactinemia. The remaining 64 symptomatic PPR-AEs affected 2.0% of the total number of subjects. Fifteen events in 13 participants (0.41% of patients or 4.7 events/1000 patients) required treatment.

Conclusions:

Clinicians should periodically assess patients on paliperidone palmitate for any PPR-AEs and carefully assess the benefits and risks when managing these effects.
Perceived benefits of active engagement with making music in community settings
Authors: Hallam Susan , Creech Andrea , Varvarigou Maria , McQueen Hilary
Published: September 2012

This article focuses on the reported benefits of participation in music activities, identified by participants of the Music for Life Project. The participants engaged in weekly music activities offered in three locations: two centres in London and one in the North of England. Their
responses were collected through questionnaires and focus group interviews. Music participants attributed improvements in quality of life to active engagement with music, and a wide range of cognitive, social, emotional and physical benefits were reported. This article offers an insight into
what participants said about improved health, social interactions, emotional support and learning that occurred as a result of active involvement in music.
Development of core technologies on EUV mask and resist for sub-20-nm half pitch generation
Authors: Inoue Soichi , Amano Tsuyoshi , Itani Toshiro , Watanabe Hidehiro , Mori Ichiro , Watanabe Takeo , Kinoshita Hiroo , Miyai Hiroki , Hatakeyama Masahiro
Published: September 2012

This paper reports on the current status for the key infrastructures of the extreme ultraviolet lithography (EUVL) for sub-20-nm half pitch (hp) generation. More specifically, the inspection technologies for EUV mask and resist-related technologies will be dedicatedly discussed. First, the actinic blank inspector is strongly required especially for sub-20-nm hp generation. The basic configuration of the prototyping tool will be presented. Second, the basic configuration of the newly developing patterned mask inspector (PMI) consisting of the projection-type optics for the electron beam (EB) will be presented. The primary challenge for the EUV resist is the concurrent improvements of resolution, line width roughness, sensitivity, and outgas. The basic performance of the EUV resist and preliminary validation of the outgas qualification for sub-20-nm hp will be presented.
Beginning With ‘One More Thing’: Pragmatics and editorial intervention in the work of Raymond Carver
Authors: Clark, Billy
Published: September 2012

This paper considers Raymond Carver's writing and Gordon Lish's editorial interventions in that writing from the perspective of an approach to pragmatic stylistics which focuses in particular on inferential processes. Building on some fairly informal classroom work, it considers a small number of specific differences between two versions of the story ‘One More Thing’. It considers the contrasting nature of inferences which each version is likely to give rise to and argues that this approach helps us to understand the nature of the changes. In particular, it helps to understand the nature of Lish's interventions and to develop a more sophisticated understanding of the extent to which this might be described in terms of a contrast between a more ‘minimalist’ and a more ‘expansive’ style.
Myelin Gene Regulatory Factor Is Required for Maintenance of Myelin and Mature Oligodendrocyte Identity in the Adult CNS
Authors: Koenning Matthias , Jackson Stacey , Hay Curtis M. , Faux Clare , Kilpatrick Trevor J. , Willingham Melanie , Emery Ben
Published: September 2012

Although the transcription factors required for the generation of oligodendrocytes and CNS myelination during development have been relatively well established, it is not known whether continued expression of the same factors is required for the maintenance of myelin in the adult. Here, we use an inducible conditional knock-out strategy to investigate whether continued oligodendrocyte expression of the recently identified transcription factor myelin gene regulatory factor (MRF) is required to maintain the integrity of myelin in the adult CNS. Genetic ablation of MRF in mature oligodendrocytes within the adult CNS resulted in a delayed but severe CNS demyelination, with clinical symptoms beginning at 5 weeks and peaking at 8 weeks after ablation of MRF. This demyelination was accompanied by microglial/macrophage infiltration and axonal damage. Transcripts for myelin genes, such as proteolipid protein, MAG, MBP, and myelin oligodendrocyte glycoprotein, were rapidly downregulated after ablation of MRF, indicating an ongoing requirement for MRF in the expression of these genes. Subsequently, a proportion of the recombined oligodendrocytes undergo apoptosis over a period of weeks. Surviving oligodendrocytes gradually lose the expression of mature markers such as CC1 antigen and their association with myelin, without reexpressing oligodendrocyte progenitor markers or reentering the cell cycle. These results demonstrate that ongoing expression of MRF within the adult CNS is critical to maintain mature oligodendrocyte identity and the integrity of CNS myelin.
Dynamics of Local Input Normalization Result from Balanced Short- and Long-Range Intracortical Interactions in Area V1
Authors: Reynaud Alexandre , Masson Guillaume S. , Chavane Frédéric
Published: September 2012

To efficiently drive many behaviors, sensory systems have to integrate the activity of large neuronal populations within a limited time window. These populations need to rapidly achieve a robust representation of the input image, probably through canonical computations such as divisive normalization. However, little is known about the dynamics of the corticocortical interactions implementing these rapid and robust computations. Here, we measured the real-time activity of a large neuronal population in V1 using voltage-sensitive dye imaging in behaving monkeys. We found that contrast gain of the population increases over time with a time constant of ∼30 ms and propagates laterally over the cortical surface. This dynamic is well accounted for by a divisive normalization achieved through a recurrent network that transiently increases in size after response onset with a slow swelling speed of 0.007–0.014 m/s, suggesting a polysynaptic intracortical origin. In the presence of a surround, this normalization pool is gradually balanced by lateral inputs propagating from distant cortical locations. This results in a centripetal propagation of surround suppression at a speed of 0.1–0.3 m/s, congruent with horizontal intracortical axons speed. We propose that a simple generalized normalization scheme can account for both the dynamical contrast response function through recurrent polysynaptic intracortical loops and for the surround suppression through long-range monosynaptic horizontal spread. Our results demonstrate that V1 achieves a rapid and robust context-dependent input normalization through a timely push–pull between local and lateral networks. We suggest that divisive normalization, a fundamental canonical computation, should be considered as a dynamic process.
Repeated Stress Dysregulates κ-Opioid Receptor Signaling in the Dorsal Raphe through a p38α MAPK-Dependent Mechanism
Authors: Lemos Julia C. , Roth Clarisse A. , Messinger Daniel I. , Gill Harminder K. , Phillips Paul E. M. , Chavkin Charles
Published: September 2012

Repeated stress releases dynorphins and causes subsequent activation of κ-opioid receptors (KORs) in limbic brain regions. The serotonergic dorsal raphe nucleus (DRN) has previously been found to be an important site of action for the dysphoric effects of dynorphin-κ-opioid receptor system activation during stress-evoked behaviors, and KOR-induced activation of p38α mitogen-activated protein kinase (MAPK) in serotonergic neurons was found to be a critical mediator of the aversive properties of stress. Yet, how dynorphins and KORs functionally regulate the excitability of serotonergic DRN neurons both in adaptive and pathological stress states is poorly understood. Here we report that acute KOR activation by the selective agonist U69,593 [(+)-(5α,7α,8β)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]benzeneacetamide] inhibits serotonergic neuronal excitability within the DRN through both presynaptic inhibition of excitatory synaptic transmission and postsynaptic activation of G-protein-gated inwardly rectifying potassium channels (GIRKs) electrophysiologically recorded in brain slices. C57BL/6 mice subjected to repeated swim, stress sessions had significantly reduced KOR-mediated GIRK currents recorded in serotonergic neurons in DRN postsynaptically, without significantly affecting presynaptic KOR-mediated regulation of excitatory transmission. This effect was blocked by genetic excision of p38α MAPK selectively from serotonergic neurons. An increase in phospho-immunoreactivity suggests that this functional dysregulation may be a consequence of tyrosine phosphorylation of GIRK (KIR3.1) channels. These data elucidate a mechanism for stress-induced dysregulation of the excitability of neurons in the DRN and identify a functional target of stress-induced p38α MAPK activation that may underlie some of the negative effects of pathological stress exposure.
Occipital Transcranial Magnetic Stimulation Has an Activity-Dependent Suppressive Effect
Authors: Perini Francesca , Cattaneo Luigi , Carrasco Marisa , Schwarzbach Jens V.
Published: September 2012

The effects of transcranial magnetic stimulation (TMS) vary depending on the brain state at the stimulation moment. Four mechanisms have been proposed to underlie these effects: (1) virtual lesion—TMS suppresses neural signals; (2) preferential activation of less active neurons—TMS drives up activity in the stimulated area, but active neurons are saturating; (3) noise generation—TMS adds random neuronal activity, and its effect interacts with stimulus intensity; and (4) noise generation—TMS adds random neuronal activity, and its effect depends on TMS intensity. Here we explore these hypotheses by investigating the effects of TMS on early visual cortex by assessing the contrast response function while varying the adaptation state of the observers. We tested human participants in an orientation discrimination task, in which performance is contingent upon contrast sensitivity. Before each trial, neuronal activation of visual cortex was altered through contrast adaptation to two flickering gratings. In a factorial design, with or without adaptation, a single TMS pulse was delivered simultaneously with targets of varying contrast. Adaptation decreased contrast sensitivity. The effect of TMS on performance was state dependent: TMS decreased contrast sensitivity in the absence of adaptation but increased it after adaptation. None of the proposed mechanisms can account for the results in their entirety, in particular, for the facilitatory effect at intermediate to high contrasts after adaptation. We propose an alternative hypothesis: TMS effects are activity dependent, so that TMS suppresses the most active neurons and thereby changes the balance between excitation and inhibition.
Traumatic Noise Activates Rho-Family GTPases through Transient Cellular Energy Depletion
Authors: Chen Fu-Quan , Zheng Hong-Wei , Hill Kayla , Sha Su-Hua
Published: September 2012

Small GTPases mediate transmembrane signaling and regulate the actin cytoskeleton in eukaryotic cells. Here, we characterize the auditory pathology of adult male CBA/J mice exposed to traumatic noise (2–20 kHz; 106 dB; 2 h). Loss of outer hair cells was evident 1 h after noise exposure in the basal region of the cochlea and spread apically with time, leading to permanent threshold shifts of 35, 60, and 65 dB at 8, 16, and 32 kHz. Several biochemical and molecular changes correlated temporally with the loss of cells. Immediately after exposure, the concentration of ATP decreased in cochlear tissue and reached a minimum after 1 h while the immunofluorescent signal for p-AMPKα significantly increased in sensory hair cells at that time. Levels of active Rac1 increased, whereas those of active RhoA decreased significantly 1 h after noise attaining a plateau at 1–3 h; the formation of a RhoA-p140mDia complex was consistent with an activation of Rho GTPase pathways. Also at 1–3 h after exposure, the caspase-independent cell death marker, Endo G, translocated to the nuclei of outer hair cells. Finally, experiments with the inner ear HEI-OC1 cell line demonstrated that the energy-depleting agent oligomycin enhanced both Rac1 activity and cell death. The sum of the results suggests that traumatic noise induces transient cellular ATP depletion and activates Rho GTPase pathways, leading to death of outer hair cells in the cochlea.
Charging and Aggregation of Positively Charged Colloidal Latex Particles in Presence of Multivalent Polycarboxylate Anions
Authors: Sadeghpour Amin , Szilágyi István , Borkovec Michal
Published: September 2012

Colloidal stability and charging behavior of amidine latex particles in the presence of multivalent oligomers of acrylic acid was investigated by electrophoresis and light scattering. The data were interpreted quantitatively with the theory of Derjaguin, Landau, Verwey and Overbeek (DLVO) whereby the surface potentials were estimated from electrophoresis. Monomer leads to slow aggregation at low concentrations and to rapid aggregation at high concentrations, as characteristic for simple salts. The oligomers induce a charge reversal of the particles. Close to the isoelectric point (IEP) aggregation is rapid while the suspension becomes stable away from this point. At high oligomer concentrations, the aggregation becomes rapid again. The agreement between DLVO theory and experiment is good close to the IEP. At higher oligomer concentrations, the theory predicts larger stabilities than observed experimentally. While inter-particle forces seem to be well described by DLVO theory near the IEP, additional attractive non-DLVO forces are becoming relevant at higher concentrations.
Non NIPAM Based Smart Microgels: Systematic Variation of the Volume Phase Transition Temperature by Copolymerization
Authors: Wedel Bastian , Zeiser Michael , Hellweg Thomas
Published: September 2012

Thermoresponsive copolymer microgels based on N-n-propylacrylamide (NNPAM) and N-isopropylmethacrylamide (NIPMAM) with varying compositions were synthesized via precipitation polymerization. Photon correlation spectroscopy (PCS) and turbidity measurements were used to investigate their volume phase transition. A linear correlation between the nominal composition and the volume phase transition temperature (VPTT) was observed. Furthermore, the hydrodynamic radii of the particles exhibit a linear dependency on the nominal composition. The presented system is suitable for the synthesis of thermoresponsive microgels with a well defined VPTT or size and gives access to tune these two crucial parameters in a systematic and controlled way by simply choosing the right composition of the monomer feed. Additionally, the first derivatives of the swelling curves obtained from turbidity measurements were analyzed in detail, allowing a quantitative comparison of the phase transition of different microgels.
Impaired quality of life in patients in long-term remission of Cushing's syndrome of both adrenal and pituitary origin: a remaining effect of long-standing hypercortisolism?
Authors: Wagenmakers M A E M , Netea-Maier R T , Prins J B , Dekkers T , den Heijer M , Hermus A R M M
Published: August 2012

Objective

The determinants that cause impaired quality of life (QOL) in patients in long-term remission of Cushing's syndrome (CS) are unknown. The aim of this study was to get more insight into the patient and disease characteristics related to impaired QOL in these patients.

Design

Cross-sectional study.

Methods

The QOL of 123 patients in remission of CS (age 52.2±12.0 years, 106 women, duration of remission 13.3±10.4 years, 80% pituitary CS), assessed with seven validated questionnaires, was compared with the QOL of an age- and sex-matched control group (n=105). To investigate the influence of the aetiology of CS on QOL, patients in remission of pituitary and adrenal CS were compared. Furthermore, the influence of hormonal deficiencies, treatment strategy, duration of remission, gender and age on QOL was investigated.

Results

QOL in the total patient group and each patient subgroup was significantly worse on practically all dimensions of questionnaires compared with the control group (P<0.05), except for patients in remission of pituitary CS without hormonal deficiencies who had an impaired QOL on 50% of the QOL dimensions. Subgroup analysis revealed no difference in QOL between different patient groups, especially no difference between patients in remission of adrenal and pituitary CS. Female gender and a shorter duration of remission had a negative influence on QOL in the patient group.

Conclusions

QOL remains impaired in patients in long-term remission of CS regardless of aetiology, presence of hormonal deficiencies and treatment strategies. More research is needed to establish the causes.
Krüppel-like factor 5 in human breast carcinoma: a potent prognostic factor induced by androgens
Authors: Takagi Kiyoshi , Miki Yasuhiro , Onodera Yoshiaki , Nakamura Yasuhiro , Ishida Takanori , Watanabe Mika , Inoue Satoshi , Sasano Hironobu , Suzuki Takashi
Published: August 2012

Krüppel-like factor 5 (intestinal) or Krüppel-like factor 5 (KLF5) is a zinc finger-containing transcription factor and involved in important biological processes including cell proliferation and differentiation. However, clinical significance of KLF5 protein has remained largely unknown in breast cancer. Therefore, in this study, we immunolocalized KLF5 in 113 human breast carcinoma cases. KLF5 immunoreactivity was frequently detected in the nuclei of breast carcinoma cells, and median value of the ratio of KLF5-positive carcinoma cells was 30% and was positively associated with the status of androgen receptor. KLF5 immunoreactivity was also significantly associated with increased risk of recurrence and worse clinical outcome in breast cancer patients by univariate analyses, and subsequent multivariate analyses demonstrated that KLF5 immunoreactivity was an independent prognostic factor for both disease-free and breast cancer-specific survival of the patients. We then examined possible regulation of KLF5 by androgen using MCF-7 breast carcinoma cells. KLF5 mRNA was induced by biologically active androgen 5α-dihydrotestosterone in a dose- and time-dependent manner in MCF-7 cells. In addition, results of transfection experiments demonstrated that proliferation activity of MCF-7 cells was significantly associated with the KLF5 expression level. These findings suggest that KLF5 is an androgen-responsive gene in human breast carcinomas and play important roles in the progression of breast carcinomas. KLF5 immunoreactivity is therefore considered a potent prognostic factor in human breast cancers.
The cellular and molecular mechanisms by which insulin influences breast cancer risk and progression
Authors: Rose David P , Vona-Davis Linda
Published: August 2012

Epidemiological studies have related hyperinsulinemia and type 2 diabetes to an increased breast cancer risk, an aggressive and metastatic phenotype, and a poor prognosis. Furthermore, diabetic retinopathy arises from pathological angiogenesis, which is also essential for breast cancer growth and metastasis. Insulin stimulates the proliferation of some human breast cancer cell linesin vitroby mechanisms that use both the phosphatidylinositol-3 kinase and the mitogen-activated protein kinase/Akt signaling pathways; it is also a cell survival (anti-apoptotic) agent and enhances tumor cell migration and invasive capacity. Hyperinsulinemia affects breast cancer cells via the endocrine system, but experimental studies suggest the importance of paracrine mechanisms operating by the effects of insulin on the secretion of adipokines from tumor-associated adipose tissue. In such a system, one adipokine, leptin, has stimulatory paracrine effects on breast cancer cell proliferation and survival, while a second, adiponectin, is inhibitory. Leptin, vascular endothelial growth factor, another insulin-regulated adipokine, and insulin itself also stimulate angiogenesis. Insulin has complex interactions with estrogens: it induces adipose stromal cell aromatase and tumor cell sex steroid hormone receptor expression and suppresses sex hormone-binding globulin, which may enhance estrogen synthesis and bioactivity with consequent promotion of estrogen-dependent breast cancer. All these actions influence the later steps in breast cancer development but genetic studies are also revealing connections between gene abnormalities related to type 2 diabetes and the initiation stage of breast carcinogenesis. Understanding the various mechanisms by which insulin participates in breast cancer cell biology provides opportunities for novel approaches to treatment.
QUALICOPC – Primary care study on quality, costs and equity in European countries: The Hungarian branch
Authors: Rurik Imre , Boerma W. G. Wienke , Kolozsvári László Róbert , Lánczi Levente István , Mester Lajos , Móczár Csaba , Schäfer L. A. Willemijn , Schmidt Péter , Torzsa Péter , Végh Mária , Gronewegen P. Peter
Published: August 2012

The importance of primary care has already been recognized in the developed countries, where the structure and function of primary care is very heterogeneous. In the QUALICOPC study, the costs, quality and equity of primary care systems will be compared in the 34 participating countries. Representative samples of primary care practices were recruited in Hungary. An evaluation with questionnaire was performed in 222 practices on the work circumstances, conditions, competency and financial initiatives. Ten patients in each practice were also questioned by independent fieldworkers. In this work, the methodology and Hungarian experience are described. The final results of the international evaluation will be analyzed and published later. It is expected that data obtained from the QUALICOPC study may prove to be useful in health service planning and may be shared with policy makers. Orv. Hetil., 2012, 153, 1396–1400.
Toxicity and residual control of Plutella xylostella L. (Lepidoptera: Plutellidae) with Bacillus thuringiensis Berliner and insecticides
Authors: Moraes Carla Pedroso de , Foerster Luis Amilton
Published: September 2012

Plutella xylostella L. is the most important worldwide pest of cruciferous plants and indiscriminate use of insecticides has led to the resistance of the species to different groups. This research was conducted to compare the toxicity and persistence of two strains of Bacillus thuringiensis to P. xylostella larvae. Concentrations between 125 and 500g 100L-1 of water of the commercial products were evaluated and compared to the insect growth inhibitor diflubenzuron and to the neurotoxic pyrethroid deltamethrin. The efficacy of the insecticides was compared between treated plants kept indoor greenhouse and outdoor. Third instar larvae were more susceptible to B. thuringiensis than first instar ones. Agree and Dipel showed similar control rates of third instars until 10 days after treatment, but on the 15th day, Agree was significantly more efficient than Dipel. Both B. thuringiensis formulations showed a reduction in mortality after 10 days when the treated plants were exposed to natural weather conditions in comparison to the same treatments kept inside greenhouse. Dimilin (100g 100L-1 of water) and deltamethrin (30ml of commercial product 100L-1 of water) were not efficient to control third instar larvae of P. xylostella. This inefficiency cannot be attributed to a resistant population of P. xylostella since the larval population used in the experiments was not subjected to insecticide pressure, once the crop was organically cultivated all year round. The results showed that both formulations of B. thuringiensis are sound alternatives for the control of the diamondback moth in organically conducted cruciferous crops, considering the high residual control provided under subtropical weather conditions.
Densitometria da vértebra dorsal, osso pleural e osso neural em tartarugas verdes hígidas por tomografia computadorizada quantitativa
Authors: Oliveira Jannine Forattini de , Rossi Júnior João Luiz , Leite Flaviana Lima Guião , Oliveira Daniel Capucho de , Costa Lorena Adão Vescovi Séllos , Silva Ieverton Cleiton Correia da , Teixeira Marcelo Weinstein , Costa Fabiano Séllos
Published: September 2012

A tomografia computadorizada quantitativa (TCQ) é uma técnica com alta sensibilidade, aplicabilidade e precisão no diagnóstico de perda de massa óssea, entretanto a falta de valores de normalidade para animais silvestres limita a sua aplicação clínica. O presente estudo objetiva estabelecer valores médios de radiodensidade do osso trabecular das vértebras dorsais, osso pleural e osso neural de tartarugas marinhas juvenis hígidas utilizando a TCQ. Para isso, utilizou-se um grupo experimental de cinco animais que foram submetidos a exames de tomografia computadorizada helicoidal, sendo as mensurações da radiodensidade óssea realizadas ao nível da terceira, quarta e quinta vértebras dorsais. Os valores médios de radiodensidade do osso trabecular das vértebras dorsais, osso pleural e osso neural foram, respectivamente, de 287,4±39,1, 1093,74±100,4 e 1089,6±86,5 unidades Hounsfield (HU). Estudos complementares devem ser realizados em diferentes espécies e faixas etárias de quelônios para favorecer a aplicação clínica desta técnica.
Carotenoides bixina e norbixina extraídos do urucum (Bixa orellana L.) como antioxidantes em produtos cárneos
Authors: Garcia Carlos Eduardo Rocha , Bolognesi Vinícius José , Dias Josiane de Fátima Gaspari , Miguel Obdúlio Gomes , Costa Camila Klocker
Published: September 2012

A oxidação lipídica é uma das principais alterações que acometem os derivados cárneos em razão da composição química rica em lipídios e íons ferro, utilização de processos térmicos e de moagem, além do frequente uso do cloreto de sódio, um reconhecido catalisador desta reação. Os antioxidantes são substâncias utilizadas para inibir ou retardar a rancidez oxidativa, porém, seu uso desperta a atenção de consumidores e agências reguladoras, quanto à segurança que acompanha o consumo de aditivos sintéticos. Este trabalho teve por objetivo avaliar o uso dos carotenoides bixina e norbixina como antioxidantes em produtos cárneos por meio da revisão de suas características químicas, métodos de obtenção, toxicidade e aplicações tecnológicas. Esses pigmentos são extraídos das sementes do urucum (Bixa orellana L.) por métodos que envolvem o uso de solventes orgânicos, extração supercrítica ou ainda a utilização da tecnologia de micro-ondas. No Brasil, o uso dessas substâncias é previsto na legislação como corante alimentício, porém, estes carotenoides apresentam extensas cadeias carbônicas insaturadas que permitem a adição de radicais livres e lhes conferem a capacidade de atuar como antioxidantes. As diferenças estruturais entre bixina e norbixina resultam em particularidades quanto à polaridade, solubilidade, coloração e, por consequência, determinam singulares aplicações tecnológicas. Nas concentrações previstas pelas agências reguladoras, o consumo desses carotenoides é seguro e além das aplicações como corante, podem ser utilizados pela indústria como antioxidantes naturais, oportunizando uma alternativa capaz de substituir ou minimizar o uso de aditivos sintéticos em produtos cárneos.
Association between human leukocyte antigens and graft-versus-host disease occurrence after allogenic hematopoietic stem cell transplantation
Authors: Cardozo Daniela Máira , Lieber Sofia Rocha , Marques Silvia Barbosa Dutra , Aranha Francisco José , Vigorito Afonso Celso , Souza Cármino Antonio de , Visentainer Jeane Eliete Laguila
Published: September 2012

CONTEXT AND OBJECTIVE: Graft-versus-host disease (GVHD) is one of the complications following allogenic stem cell transplantation. This study investigated an association between human leukocyte antigen (HLA) and the occurrence of acute and chronic GVHD in patients who had received stem cell transplantations from HLA-identical siblings. DESIGN AND SETTING: Retrospective study at Hematology and Hemotherapy Center, Universidade Estadual de Campinas (Unicamp). METHODS: The participants were 176 patients whose first transplant was between 1997 and 2009. HLA genotyping was performed serologically and using the polymerase chain reaction with specific primer sequence. RESULTS: Acute GVHD was positively associated with HLA-A10 (P = 0.0007), HLA-A26 (P = 0.002), B55 (P = 0.001), DRB1*15 (P = 0.0211) and DQB1*05 (P = 0.038), while HLA-B16 (P = 0.0333) was more frequent in patients without acute GVHD. Chronic GVHD was positively associated with HLA-A9 (P = 0.01) and A23 (P = 0.0292) and negatively with HLA-A2 (P = 0.0031) and B53 (P = 0.0116). HLA-B35 (P = 0.0373), B49 (P = 0.0155) and B55 (P = 0.0024) were higher in patients with acute GVHD grade 3 or above, than in other patients. In patients with extensive chronic GVHD, HLA-A9 (P = 0.0004), A24 (P = 0.0059) and A26 (P = 0.0411) were higher than in other patients, while HLA-A2 was lower (P = 0.0097). CONCLUSION: This study suggests that HLA can influence the incidence and severity of acute and chronic GVHD. However, a study with a better design and more patients will be needed to confirm these results.
Cephalometric evaluation of the airway space and hyoid bone in children with normal and atypical deglutition: correlation study
Authors: Machado Júnior Almiro José , Crespo Agrício Nubiato
Published: September 2012

CONTEXT AND OBJECTIVE: Although there is a close relationship between swallowing and breathing, there are no studies evaluating the radiographic anatomy of the airway and its possible correlation with the radiographic position of the hyoid bone. The aim of this study was to evaluate the possible correlation of the radiographic position of the hyoid bone and airway space (PAS) in lateral radiographs on children with atypical deglutition, in comparison with those with normal swallowing. DESIGN AND SETTING: Cross-sectional analytical study with control group in a public university. METHODS: Using cephalometric analysis on lateral teleradiographs, the distance from the hyoid bone to the mandibular plane (MP-H) and the distance from the hyoid bone to the tuber (T-H) were correlated with the PAS measurement (airway) in two groups: 55 teleradiographs in the experimental group (with atypical deglutition) and 55 teleradiographs in the control group (normal deglutition). Both groups included subjects at the mixed dentition stage. RESULTS: The variable T-H presented a statistically significant correlation with PAS (0.0286) and the variable MP-H had a significant correlation with the variable PAS (0.0053). This positive correlation was significant only in the control group and not in the group with atypical swallowing. CONCLUSIONS: There was a positive correlation between the MP-H and PAS measurements and between the T-H and PAS measurements only in the group with normal swallowing. These correlations were not observed in the group with atypical swallowing.
Modelo experimental de perfusão pulmonar ex vivo em ratos: avaliação histopatológica e de apoptose celular em pulmões preservados com solução de baixo potássio dextrana vs. solução histidina-triptofano-cetoglutarato
Authors: Simões Edson Azevedo , Cardoso Paulo Francisco Guerreiro , Pêgo-Fernandes Paulo Manuel , Canzian Mauro , Pazetti Rogério , Braga Karina Andriguetti de Oliveira , Nepomuceno Natalia Aparecida , Jatene Fabio Biscegli
Published: September 2012

OBJETIVO: Comparar os achados histopatológicos e de apoptose em pulmões de ratos preservados em soluções low-potassium dextran (LPD, baixo potássio dextrana), histidine-tryptophan-ketoglutarate (HTK, histidina-triptofano-cetoglutarato) ou salina normal (SN) em 6 h e 12 h de isquemia pela utilização de um modelo experimental de perfusão pulmonar ex vivo. MÉTODOS: Sessenta ratos Wistar foram anestesiados, randomizados e submetidos à perfusão anterógrada pela artéria pulmonar com uma das soluções preservadoras. Após a extração, os blocos cardiopulmonares foram preservados por 6 ou 12 h a 4ºC, sendo então reperfundidos com sangue homólogo em um sistema de perfusão ex vivo durante 60 min. Ao final da reperfusão, fragmentos do lobo médio foram extraídos e processados para histopatologia, sendo avaliados os seguintes parâmetros: congestão, edema alveolar, hemorragia alveolar, hemorragia, infiltrado inflamatório e infiltrado intersticial. O grau de apoptose foi avaliado pelo método TdT-mediated dUTP nick end labeling. RESULTADOS: A histopatologia demonstrou que todos os pulmões preservados com SN apresentaram edema alveolar após 12 h de isquemia. Não houve diferenças em relação ao grau de apoptose nos grupos estudados. CONCLUSÕES: No presente estudo, os achados histopatológicos e de apoptose foram semelhantes com o uso das soluções LPD e HTK, enquanto a presença de edema foi significativamente maior com o uso de SN.
Hiperinsuflação manual combinada com compressão torácica expiratória para redução do período de internação em UTI em pacientes críticos sob ventilação mecânica
Authors: Berti Juliana Savini Wey , Tonon Elisiane , Ronchi Carlos Fernando , Berti Heloisa Wey , Stefano Laércio Martins de , Gut Ana Lúcia , Padovani Carlos Roberto , Ferreira Ana Lucia Anjos
Published: September 2012

OBJETIVO: Embora a hiperinsuflação manual (HM) seja largamente usada para a remoção de secreções pulmonares, não há evidências para sua recomendação como rotina na prática clínica. O objetivo do estudo foi avaliar o efeito da HM combinada com compressão torácica expiratória (CTE) na duração de internação em UTI e no tempo de ventilação mecânica (VM) em pacientes sob VM. MÉTODOS: Ensaio clínico prospectivo, randomizado e controlado com pacientes de UTI sob VM em um hospital acadêmico terciário entre janeiro de 2004 e janeiro de 2005. Dentre os 49 pacientes que preencheram os critérios do estudo, 24 e 25 foram randomicamente alocados nos grupos fisioterapia respiratória (FR) e controle, respectivamente, sendo que 6 e 8 foram retirados do estudo. Durante o período de observação de 5 dias, os pacientes do grupo FR receberam HM combinada com CTE, enquanto os controles receberam o tratamento padrão de enfermagem. RESULTADOS: Os dois grupos apresentaram características basais semelhantes. A intervenção teve efeito positivo na duração de VM, alta da UTI e escore de Murray. Houve diferenças significativas entre os grupos controle e FR em relação à taxa de sucesso no desmame nos dias 2 (0,0% vs. 37,5%), 3 (0,0% vs. 37,5%), 4 (5,3 vs. 37,5%) e 5 (15,9% vs. 37,5%), assim como à taxa de alta da UTI nos dias 3 (0% vs. 25%), 4 (0% vs. 31%) e 5 (0% vs. 31%). No grupo FR, houve uma melhora significante no escore de Murray no dia 5. CONCLUSÕES: Nossos resultados mostraram que o uso combinado de HM e CTE por 5 dias acelerou o processo de desmame e de alta da UTI.
Obtenção de extratos de guaraná ricos em cafeína por processo enzimático e adsorção de taninos
Authors: Ribeiro Bernardo Dias , Coelho Maria Alice Zarur , Barreto Daniel Weingart
Published: September 2012

As bebidas sabor guaraná são muito populares no Brasil e têm apresentado um excelente potencial de vendas no mercado externo. De acordo com as leis brasileiras, bebidas sabor guaraná devem conter entre 0,02 g a 0,2 g de semente de guaraná ou equivalente, para cada 100 mL de produto. Tais teores são usualmente obtidos pela adição de um extrato concentrado hidroalcoólico ou xarope de açúcar contendo extrato de guaraná diretamente à bebida. A utilização desses extratos em concentrações mais elevadas, entretanto, é limitada pela presença dos taninos, que conferem adstringência e coloração escura ao produto final. Neste trabalho, foi estudado o desenvolvimento de um processo enzimático para obtenção de extratos não alcoólicos de guaraná, de forma a produzir um extrato contendo baixas concentrações de taninos e teores elevados de cafeína, utilizando-se planejamento experimental e processos de adsorção. Por meio de um planejamento fatorial fracionário, foram determinadas as quantidades de 0,25% (v/v) de pectinase e 0,1% (v/v) de glucoamilase, sendo mantidas no planejamento composto central, que obteve como condições ótimas: 0,23% (v/v) de celulase, 0,86% (v/v) de hemicelulase e 1% (v/v) de alfa-amilase durante 5,5 h de extração a 200 rpm e 50 °C, obtendo-se uma relação cafeína/tanino de 1,65. Com o processo de adsorção com óxido de magnésio a 10% (p/v), foi alcançada uma relação de cafeína-tanino de 7,3.
Inter-annual chemical stratification in Brazilian natural lakes: meromixis and hypolimnetic memory
Authors: Barbosa Luciana Gomes , Barbosa Francisco Antonio Rodrigues , Bicudo Carlos Eduardo de Mattos
Published: September 2012

AIM: chemical stratification and the patterns of light limitation and nutrients of two natural lakes, one shallow and the other one deep, were comparatively evaluated, both lakes located in the southeast Brazil. METHODS: pH, electrical conductivity, dissolved oxygen, total dissolved solids and nutrients were monthly collected during 5 consecutive years at the vertical profile of the two lakes. RESULTS: multivariate analysis indicated that the long thermal stratification period favored the occurrence of chemical stratification in the two lakes. However, in the deeper lake the stratified thermal profile with high hypolimnetic nutrient concentration, electrical conductivity, total dissolved solids and redox potential indicated that the mixing was not complete even during the annual circulation period, suggesting a slight meromixis and a high chemical stability at the hypolimnion. In the shallower lake, high light attenuation and high availability of nitrogen forms (mainly N-NH4) and phosphorus was observed along the water column, even during stratification. In the deeper lake, N and P co-limitation and low light attenuation coefficients were detected. CONCLUSION: thermal and chemical stratification patterns indicated that the Carioca lake is a shallow, turbid, nutrient rich, whereas the Dom Helvecio lake is a deep, clear, oligotrophic system with a tendency towards meromixis and the isolation of solutes in the hypolimnion. Consequently, meromixis was compared to a "hypolimnetic memory", which was defined, in the case of the deeper lake, as the maintenance of the chemical stratification along the years, during the lake thermal circulation period.
Scale microfossils from the mid-Neoproterozoic Fifteenmile Group, Yukon Territory
Authors: Cohen Phoebe A. , Knoll Andrew H.
Published: September 2012

Microscopic phosphatic scales are found in limestones and cherts from the 812–717 million year old Fifteenmile Group of the Yukon Territory. These enigmatic microfossils, which to date have not been identified in any other locality, display a diversity of intricate morphologies. Here we describe six new genera containing 17 new species of scale microfossils obtained from macerated limestone. We also revise existing taxa described originally from chert thin sections and now additionally freed from limestone by acid dissolution. New taxa described here are:Archaeoxybaphon serratacapacisn. sp.,Archeoxybaphon serratapusillan. sp.,Paleoscutula inornatan. gen. n. sp.,Paleoscutula serratan. gen. n. sp.,Paleoscutula convocationisn. gen n. sp.,Hexacatillus allmoniin. gen. n. sp.,Hexacatillus retetantillusn. sp.,Quadrireticulum allisoniaen. gen. n. sp.,Quadrireticulum palmaspinosumn. gen. n. sp.,Circidentatus pistricisn. gen. n. sp.,Circidentatus variodentatusn. gen. n. sp.,Ospercapatera awramikiin. gen. n. sp.,Circitorquis soccusn. gen. n. sp.,Paleohexadictyon alexandraen. sp.,Paleomegasquama arctoan. sp.,Petasisquama petasusn. sp., andThorakidictyon circireticulumn. gen. n. sp. Taxa described or amended here areCharacodictyon skolopiumAllison and Hilgert, 1986,Paleohexadictyon myriotrematumAllison and Hilgert, 1986,Archeoxybaphon polykeramoides(Allison and Hilgert, 1986) emend.,Paleohexadictyon litosum(Allison and Hilgert, 1986) emend., andThorakidictyon myriocanthum(Allison and Hilgert, 1986) n. comb. Many eukaryotic clades include species with surficial scales but none provides a close morphological analog to the Fifteenmile scales. Nonetheless, comparative and functional morphology suggest that the diversification of heavily armored and morphologically complex cell-coverings records a changing ecological landscape in Neoproterozoic seas.
Performance management framework for managing agent contractors
Authors: Costello Seosamh B. , Nuttall Simon R. , Powell James E. , Arrowsmith Richard
Published: August 2012

This paper describes a performance management framework for managing agent contractors working on the UK Highways Agency trunk road network. At the core of the framework is a performance hierarchy which links the operational activities carried out by the managing agent contractors with the key business outcomes of the Highways Agency. The hierarchy is weighted to allow the relative importance of hierarchy elements to be accurately represented, and to avoid the default position whereby everything is considered equally important. The framework utilises performance flags to visually represent performance at higher levels in the hierarchy, based on red, amber and green scores assigned at the lowest level in the hierarchy. The performance flags have the ability to show the detail behind a performance score, whereby a proportion of the flag will be green, a proportion amber and the remainder red depending on the frequency and weightings assigned to the lower contributing levels in the hierarchy. In an effort to reduce subjectivity in performance scoring, a scoring guidance document has been prepared in support of the framework. The performance management and continual improvement process is carried out on a monthly cycle akin to the standard improvement cycle of ‘plan, do, check, act'. The main benefits of implementing this process include reduced subjectivity, thereby allowing comparability between managing agent contractors, increased visibility, increased dialogue, targeted evidence-based decision making and auditability. All of the above will help to drive improved effectiveness and efficiency in the delivery of managing agent contracts.
Geographic information system-based railway maintenance and renewal system
Authors: Guler Hakan
Published: August 2012

Increasing demand for railway transportation requires large amounts of money to be spent on maintenance and renewal. In both industrialised and developing countries, one of the main problems of railway companies is regarding track maintenance and renewal. Cost reduction and better control of maintenance processes therefore increase the efficiency of the railway system. The modern railway infrastructure maintenance management system requires a condition-based diagnostic concept covering all railway infrastructure components. This paper describes a decision support system approach, using a tool called MR.GIS (maintenance and renewal based on geographic information system), to analyse the track components and suggests methods for helping the track managers and engineers decide when maintenance is necessary and when is the best time for renewal. The tool enables the users to visualise and analyse the railway track data which is no longer possible using the manual methods. The tool analyses the track with its rich database including decision rules. These decision rules were developed by the specialist professionals and the working procedure of the tool was built on these rules. On the other hand the four major components of GIS, namely encoding, management, analysis and reporting, were integrated with the tool to enable a good advance on planning of maintenance and renewal activities. The developed system was successfully implemented to the railway tracks provided by Turkish State Railways and the expectations of Turkish State Railways were mostly fulfilled.
Complications After Implant Site Ridge Preservation and Delayed Implant Placement: A Case Report
Authors: Deporter Douglas A.
Published: September 2012

Introduction: The patient required removal of teeth #2 and #3 as a result of advanced bone loss and an endodontic–periodontic lesion at tooth #3.

Case Presentation: The patient began taking metronidazole, 250 mg every 8 hours, 24 hours before surgery. Both teeth were extracted, and, after thorough debridement using curets and saline irrigation, their sockets were packed with bovine porous bone mineral covered by a dense polytetrafluoroethylene (PTFE) barrier secured with sutures. The barrier was removed at 1 month. After 6 months healing, two dental implants were placed using submerged technique. Four months later, the implants were uncovered and restored with cement‐retained crowns. The patient was contacted 1 year after restoration for reevaluation, at which time both implants showed bone loss. At site #2, a large subgingival cement deposit was seen in radiographs. At tooth #3, bone loss mirrored the original endodontic–periodontic lesion, suggesting that it had not been eradicated. Amoxicillin, 500 mg every 8 hours, was prescribed beginning 24 hours before surgery. The cement on implant #2 was removed, and the associated defect was debrided. Implant #3 was explanted, and its socket was debrided and regrafted using bovine porous bone mineral covered with calcium sulfate paste and then a dense PTFE barrier. The barrier was removed at 1 month, and the sites were allowed to heal for 7 months before replacing implant #3. The replacement crown for implant #3 was screw retained, and both implants appeared healthy 1 year later.

Conclusion: Extraction site preservation grafting with xenograft and a barrier is an accepted treatment option but may on occasion result in complications, including failure of dental implants.