bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced Calreticulin Levels Link Endoplasmic Reticulum Stress and Fas-Triggered Cell Death in Motoneurons Vulnerable to ALS
Authors: Bernard-Marissal Nathalie , Moumen Anice , Sunyach Claire , Pellegrino Christophe , Dudley Keith , Henderson Christopher E. , Raoul Cédric , Pettmann Brigitte
Published: April 2012

Cellular responses to protein misfolding are thought to play key roles in triggering neurodegeneration. In the mutant superoxide dismutase (mSOD1) model of amyotrophic lateral sclerosis (ALS), subsets of motoneurons are selectively vulnerable to degeneration. Fast fatigable motoneurons selectively activate an endoplasmic reticulum (ER) stress response that drives their early degeneration while a subset of mSOD1 motoneurons show exacerbated sensitivity to activation of the motoneuron-specific Fas/NO pathway. However, the links between the two mechanisms and the molecular basis of their cellular specificity remained unclear. We show that Fas activation leads, specifically in mSOD1 motoneurons, to reductions in levels of calreticulin (CRT), a calcium-binding ER chaperone. Decreased expression of CRT is both necessary and sufficient to trigger SOD1G93Amotoneuron death through the Fas/NO pathway. In SOD1G93Amicein vivo, reductions in CRT precede muscle denervation and are restricted to vulnerable motor pools.In vitro, both reduced CRT and Fas activation trigger an ER stress response that is restricted to, and required for death of, vulnerable SOD1G93Amotoneurons. Our data reveal CRT as a critical link between a motoneuron-specific death pathway and the ER stress response and point to a role of CRT levels in modulating motoneuron vulnerability to ALS.
Pinceau Organization in the Cerebellum Requires Distinct Functions of Neurofascin in Purkinje and Basket Neurons during Postnatal Development
Authors: Buttermore Elizabeth D. , Piochon Claire , Wallace Michael L. , Philpot Benjamin D. , Hansel Christian , Bhat Manzoor A.
Published: April 2012

Basket axon collaterals synapse onto the Purkinje soma/axon initial segment (AIS) area to form specialized structures, the pinceau, which are critical for normal cerebellar function. Mechanistic details of how the pinceau become organized during cerebellar development are poorly understood. Loss of cytoskeletal adaptor protein Ankyrin G (AnkG) results in mislocalization of the cell adhesion molecule Neurofascin (Nfasc) at the Purkinje AIS and abnormal organization of the pinceau. Loss of Nfasc in adult Purkinje neurons leads to slow disorganization of the Purkinje AIS and pinceau morphology. Here, we used mouse conditional knock-out techniques to show that selective loss of Nfasc, specifically in Purkinje neurons during early development, prevented maturation of the AIS and resulted in loss of Purkinje neuron spontaneous activity and pinceau disorganization. Loss of Nfasc in both Purkinje and basket neurons caused abnormal basket axon collateral branching and targeting to Purkinje soma/AIS, leading to extensive pinceau disorganization, Purkinje neuron degeneration, and severe ataxia. Our studies reveal that the Purkinje Nfasc is required for AIS maturation and for maintaining stable contacts between basket axon terminals and the Purkinje AIS during pinceau organization, while the basket neuron Nfasc in combination with Purkinje Nfasc is required for proper basket axon collateral outgrowth and targeting to Purkinje soma/AIS. Thus, cerebellar pinceau organization requires coordinated mechanisms involving specific Nfasc functions in both Purkinje and basket neurons.
G-Protein-Coupled Receptor 30 Mediates Rapid Neuroprotective Effects of Estrogen via Depression of NR2B-Containing NMDA Receptors
Authors: Liu Shui-bing , Zhang Nan , Guo Yan-yan , Zhao Rong , Shi Tian-yao , Feng Shu-fang , Wang Shi-quan , Yang Qi , Li Xiao-qiang , Wu Yu-mei , Ma Lan , Hou Ying , Xiong Li-ze , Zhang Weiqi , Zhao Ming-gao
Published: April 2012

17-β-Estradiol (E2) is a steroid hormone involved in neuroprotection against excitotoxicity and other forms of brain injury. Through genomic and nongenomic mechanisms, E2 modulates neuronal excitability and signal transmission by regulating NMDA and non-NMDA receptors. However, the mechanisms and identity of the receptors involved remain unclear, even though studies have suggested that estrogen G-protein-coupled receptor 30 (GPR30) is linked to protection against ischemic injury. In the culture cortical neurons, treatment with E2 and the GPR30 agonist G1 for 45 min attenuated the excitotoxicity induced by NMDA exposure. The acute neuroprotection mediated by GPR30 is dependent on G-protein-coupled signals and ERK1/2 activation, but independent on transcription or translation. Knockdown of GPR30 using short hairpin RNAs (shRNAs) significantly reduced the E2-induced rapid neuroprotection. Patch-clamp recordings revealed that GPR30 activation depressed exogenous NMDA-elicited currents. Short-term GPR30 activation did not affect the expression of either NR2A- or NR2B-containing NMDARs; however, it depressed NR2B subunit phosphorylation at Ser-1303 by inhibiting the dephosphorylation of death-associated protein kinase 1 (DAPK1). DAPK1 knockdown using shRNAs significantly blocked NR2B subunit phosphorylation at Ser-1303 and abolished the GPR30-mediated depression of exogenous NMDA-elicited currents. Lateral ventricle injection of the GPR30 agonist G1 (0.2 μg) provided significant neuroprotection in the ovariectomized female mice subjected to middle cerebral artery occlusion. These findings provide direct evidence that fast neuroprotection by estradiol is partially mediated by GPR30 and the subsequent downregulation of NR2B-containing NMDARs. The modulation of DAPK1 activity by GPR30 may be an important mediator of estradiol-dependent neuroprotection.
Central Cardiovascular Circuits Contribute to the Neurovascular Dysfunction in Angiotensin II Hypertension
Authors: Capone Carmen , Faraco Giuseppe , Peterson Jeffrey R. , Coleman Christal , Anrather Josef , Milner Teresa A. , Pickel Virginia M. , Davisson Robin L. , Iadecola Costantino
Published: April 2012

Hypertension, a powerful risk factor for stroke and dementia, has damaging effects on the brain and its vessels. In particular, hypertension alters vital cerebrovascular control mechanisms linking neural activity to cerebral perfusion. In experimental models of slow-developing hypertension, free radical signaling in the subfornical organ (SFO), one of the forebrain circumventricular organs, is critical for the hormonal release and sympathetic activation driving the elevation in arterial pressure. However, the contribution of this central mechanism to the cerebrovascular alterations induced by hypertension remains uncertain. We tested the hypothesis that free radical production in the SFO is involved in the alterations in cerebrovascular regulation produced by hypertension. In a mouse model of gradual hypertension induced by chronic administration of subpressor doses of angiotensin II (AngII), suppression of free radicals in the SFO by overexpression of CuZn-superoxide dismutase (CuZnSOD) prevented the alteration in neurovascular coupling and endothelium-dependent responses in somatosensory cortex induced by hypertension. The SFO mediates the dysfunction via two signaling pathways. One involves SFO-dependent activation of the paraventricular hypothalamic nucleus, elevations in plasma vasopressin, upregulation of endothelin-1 in cerebral resistance arterioles and activation of endothelin type A receptors. The other pathway depends on activation of cerebrovascular AngII type 1 (AT1) receptors by AngII. Both pathways mediate vasomotor dysfunction by inducing vascular oxidative stress. The findings implicate for the first time the SFO and its efferent hypothalamic pathways in the cerebrovascular alterations induced by AngII, and identify vasopressin and endothelin-1 as potential therapeutic targets to counteract the devastating effects of hypertension on the brain.
Synergistic effect of p53 on TSA-induced stanniocalcin 1 expression in human nasopharyngeal carcinoma cells, CNE2
Authors: Ching L Y , Yeung Bonnie H Y , Wong Chris K C
Published: April 2012

Human stanniocalcin 1 (STC1) has recently been identified as a putative protein factor involved in cellular apoptosis. The use of histone deacetylase inhibitor (i.e. trichostatin A (TSA)) and doxorubicin (Dox) is one of the common treatment methods to induce apoptosis in human cancer cells. A study on TSA and Dox-mediated apoptosis may shed light on the regulation and function of STC1 in cancer treatment. In this study, TSA and Dox cotreatment in human nasopharyngeal carcinoma cells (CNE2) elicited synergistic effects on STC1 gene expression and cellular apoptosis. An activation of p53 (TP53) transcriptional activity in Dox- or Dox+TSA-treated cells was revealed by the increased expression levels of p53 mRNA/protein as well as p53-driven luciferase activities. To elucidate the possible involvement of p53 in STC1 gene transcription, a vector expressing wild-type or dominant negative (DN) p53 was transiently transfected into the cells. Both STC1 promoter luciferase constructs and chromatin immunoprecipitation assays did not support the direct role of p53 in STC1 gene transactivation. However, the synergistic effects of p53 on the induction of NF-κB phosphorylation and the recruitment of acetylated histone H3 in STC1 promoter were observed in TSA-cotreated cells. The overexpression of exogenous STC1 sensitized apoptosis in Dox-treated cells. Taken together, this study provides data to show the cross talk of NF-κB, p53, and histone protein in the regulation of STC1 expression and function.
Secrets, Gossip and Betrayal
Authors: Knibbe Kim
Published: April 2012

This article discusses the process of doing fieldwork on the role of religion in moral orientation and then writing about it as a series of small betrayals. During the research it became clear that to gain insight into the ways in which moral worlds are constructed and the place of religious institutions and their representatives in these moral worlds, it was very important to understand how individual "shameful" secrets were produced. Furthermore, it was through gossip that I became familiar with the ways people related to the church as an institution with a moral discourse, and with its representatives, the local parish priests. Both in sociology and in anthropology, gossip is seen as a way of creating a shared moral universe. This article examines the ways in which the researcher becomes part of social processes through the sharing of secrets and gossip, and the ethical difficulties that arise from this: on the one hand, it seems imperative not to betray secrets, not to repeat gossip, not to betray the atmosphere of complicity surrounding this. On the other hand, not analyzing how individual secrets are produced through social and cultural processes and ignoring the role of gossip meant leaving out some of the most significant data. Furthermore, it shows that by paying attention to the ways in which gossip and secrets circulate, one can go beyond the “case study” approach that limits much qualitative research on religion.
Esophageal manometry findings and degree of acid exposure in short and long Barrett's esophagus
Authors: Helman Laura , Biccas Beatriz Nunes , Lemme Eponina M. O. , Novais Paula , Fittipaldi Viviane
Published: April 2012

CONTEXT: Barrett's esophagus (BE) is characterized by intestinal metaplasia in the distal esophagus and is classified as short-segment (<3 cm - SSBE) or long-segment (>3 cm - LSSBE). It is suggested that LSSBE is associated with more severe esophageal motor abnormalities and increased acid exposure time than SSBE. OBJECTIVE: To evaluate the prevalence of esophageal manometriy abnormalities and acid exposure times in patients with SSBE and LSSBE. METHODS: Barrett's esophagus patients identified by upper endoscopy and confirmed by histopathology were, retrospectively, reviewed and divided into two groups: SSBE and LSBE. Demographic data, symptom duration, prevalence of hiatal hernia, lower esophagus sphincter basal pressure, prevalence of esophageal body abnormalities and acid exposure times were evaluated. RESULTS: Forty-six patients with SSBE (24 males - 52.2%, mean age of 55.2 years) and 28 patients with LSBE (18 males - 64.3%, mean age of 50.5 years). Mean symptom duration was 9.9 years for SSBE and 12.9 years for LSSBE. Hiatal hernia was present in 84.2% of SSBE, 96.3% of LSBE; average lower esophagus sphincter pressure in SSBE 9.15 mm Hg, in LSBE 6.99 mm Hg; lower esophagus sphincter hypotension in SSBE was 65.9%, in LSSBE 82.1%; aperistalsis in SSBE 6.5%, LSSBE 3.6%; mild/moderate ineffective esophageal motility in SSBE 34.8%, LSBE 46.4%; severe moderate ineffective esophageal motility in SSBE 10.9%, LSBE 7,1%; nutcracker esophagus/segmental nutcracker esophagus in SSBE 8.6%, LSBE 0%; normal body in SSBE 39.1%, in LSBE 42.9%, no statistical difference for any of these values (P<0.05). Average % total time pH<4 in SSBE 9.12, LSBE 17.27 (P<0.000); % time pH<4 upright in SSBE 11.91; LSBE 24.29 (P=0.003); % time pH<4 supine in SSBE 10.86, LSBE 33.26 (P = 0.000). CONCLUSION: There was no difference between the prevalence of motor disorders in patients with SSBE and LSSBE. Acid reflux in upright and supine positions was more intense in LSBE.
Intercorrência entre leucose enzoótica e brucelose em búfalos (Bubalus bubalis) em sistema de produção extensivo
Authors: Chaves Nancyleni P , Bezerra Danilo C. , Santos Larissa S. dos , Sá Janaira S. , Santos Hamilton P , Pereira Hélder de M.
Published: April 2012

Objetivou-se com este estudo avaliar a intercorrência entre leucose enzoótica e brucelose em búfalos (Bubalus bubalis) em sistema de produção extensivo, pelo estabelecimento da prevalência de bubalinos reagentes às provas diagnósticas específicas. Foram analisados sorologicamente 232 animais, pela técnica de imunodifusão dupla em gel de agarose para diagnóstico de leucose enzoótica e o teste do antígeno acidificado tamponado, seguida pelos testes confirmatórios 2-mercaptoetanol e soroaglutinação lenta em tubos para diagnóstico de brucelose. As prevalências de búfalos que apresentaram positividade para leucose e brucelose foram 4,21% (10/232) e 5,18% (12/232), respectivamente. Os resultados obtidos nesta pesquisa permitiram concluir que as infecções estudadas encontram-se presentes na população avaliada, entretanto, com baixa prevalência e sem dependência de ocorrência entre ambas.
Forma e função dos músculos perineais da viscacha (Lagostomus maximus)
Authors: Pieri Naira C.G , Flamini Alicia M. , Barbeito Claudio G , Casals Juliana B , Roque Beatriz K , Favaron Phelipe O , Miglino Maria Angelica , Martins Daniele S.
Published: April 2012

Entre as espécies de roedores já estudadas podemos destacar a grande variação na morfologia do aparelho reprodutor masculino. Assim, considerando a importância ecológica dos roedores, e a grande representatividade numérica quanto geográfica destes animais, bem como a escassez que aborda a anatomia reprodutiva, desenvolvemos este trabalho com um roedor histricomorfo da América do Sul, a viscacha. Este animal apresenta algumas características reprodutivas bem peculiares, desta forma descreveremos a anatomia macroscópica da musculatura perineal, e o papel dos músculos no comportamento copulatório desta espécie. A região perineal da viscacha é composta por cinco músculos, sendo que três músculos encontram-se dispostos no diafragama urogenital superficial, Musculus ischiocavernosus, M. bulbocavernosus e M. bulbospongiosus, e pelos músculos que se encontram no diafragma pélvico, M. levator ani e M. retractor penis. Sendo assim, destacamos que o estudo do assoalho pélvico em animais silvestres é de grande valia, uma vez que contribuem com o melhor entendimento dos mecanismos relacionados â ereção e ejaculação; ou seja colaboram com os estudos sobre a reprodução dos animais.
Obstrução intestinal no idoso
Authors: Henry Maria Aparecida Coelho de Arruda , Lerco Mauro Masson , Oliveira Walmar Kerche de , Crippa Leandro Teodoro , Monteiro Paulo Augusto Zeratti , Lombardi Ismael Augusto Silva , Rodrigues Gabriel Doreto
Published: April 2012

RACIONAL: O envelhecimento da população é realidade sentida na vivência diária, levando à necessidade associada de prover cuidados médicos eletivos e de emergência a um número cada vez maior de idosos. OBJETIVO: Avaliar os aspectos clínicos, terapêuticos e evolutivos de pacientes idosos com obstrução intestinal atendidos no Hospital das Clínicas da Faculdade de Medicina de Botucatu - UNESP. MÉTODOS: Análise retrospectiva de pacientes internados no período de janeiro de 2002 a dezembro de 2006. Foram estudados 50 pacientes, 24 homens e 26 mulheres, com idade média de 74,7 ± 7,4 anos, analisando-se a diferenciação entre obstrução funcional e orgânica; a freqüência das causas obstrutivas; a mortalidade; a incidência dos sinais e sintomas; e correlação laboratorial. RESULTADOS: O quadro obstrutivo intestinal teve as seguintes causas: brida (38%), câncer de colon (24%), hérnias (12%), impactacão fecal (12%), carcinomatose (10%) e volvo da sigmóide (4%). A mortalidade foi de 18% associada à complicações infecciosas em todos os pacientes. CONCLUSÕES: a) A distinção entre a obstrução intestinal funcional e orgânica oferece dificuldade no idoso; b) o câncer do colon constitui-se em importante causa de obstrução intestinal com quadro obstrutivo já na primeira manifestação clínica desse tumor; c) bridas e hérnias são igualmente importantes na etiologia da obstrução intestinal; d) os sinais clínicos obstrutivos são poucos evidentes no idoso e a leucometria é mais fidedigna para este diagnóstico.
Risco nutricional e complicações em obesos hospitalizados submetidos à cirurgia
Authors: Raslan Mariana , Horie Lilian Mika , Barbosa-Silva Maria Cristina Gonzáles , Camargo Patrícia , Castro Melina , Goastico Sabrina S. V. , Nascimento Mariana , Dias Maria Carolina Gonçalves , Cecconello Ivan , Waitzberg Dan L.
Published: April 2012

RACIONAL: Risco nutricional mede o potencial de morbimortalidade associado ao estado nutricional. A obesidade é um distúrbio nutricional cada vez mais presente em hospitais gerais e pode estar acompanhada de alteração nutricional com conseqüências prejudiciais à evolução clínica do doente, além de ser fator associado a complicações pós-operatórias e morte. OBJETIVO: Identificar o risco nutricional através da ferramenta de triagem nutricional Malnutrition Universal Screening Tool e verificar o desfecho de complicações pós-operatórias, buscando associação entre risco nutricional e obesidade. MÉTODOS: Avaliaram-se 433 pacientes adultos hospitalizados em enfermarias cirúrgicas variadas, Na admissão hospitalar mediu-se peso e altura corpóreos. Aplicou-se a triagem nutricional após definição da obesidade pelo Índice de Massa Corpórea (Kg/m2) e classificação em grau I (30-34,99 Kg/m2); grau II (35-39,99 Kg/m2); grau III (±40,00 Kg/m²). Os pacientes foram seguidos até a alta hospitalar ou óbito para acompanhar sua evolução clínica. RESULTADOS: Dentre os pacientes avaliados, 17,1% foram obesos. O risco nutricional nos pacientes obesos foi 23%. Ocorreram complicações em pacientes das enfermarias cirúrgicas de esôfago, vias biliares, vascular, cabeça e pescoço. As complicações apresentadas incluíram infecções pulmonares, de parede abdominal e urinária, fístulas gastrintestinal, biliar e pancreática, insuficiência respiratória, atelectasia lobar, e sangramento pós-operatório. CONCLUSÕES: Obesos hospitalizados podem apresentam risco nutricional sendo a obesidade grau I a mais freqüente entre eles em hospital geral. Houve associação positiva entre risco nutricional e freqüência de complicações justificando triagem nutricional na admissão hospitalar como rotina, incluindo pacientes com sobrepeso e obesidade.
Cross-cultural adaptation of the Work Disability Diagnosis Interview (WoDDI) for the Brazilian context
Authors: Mininel Vivian Aline , Felli Vanda Elisa Andres , Loisel Patrick , Marziale Maria Helena Palucci
Published: April 2012

The Work Disability Diagnosis Interview (WoDDI) is a structured interview guide developed by the University of Sherbrooke, Canada to help clinicians detect the most important work-related disability predictors and to identify one or more causes of prolonged absenteeism. This methodological study aims for the cross-cultural adaptation of the WoDDI for the Brazilian context. The method followed international guidelines for studies of this kind, including the following steps: initial translation, synthesis of translations, back translation, evaluation by an expert committee and testing of the penultimate version. These steps allowed obtaining conceptual, semantic, idiomatic, experiential and operational equivalences, in addition to content validity. The results showed that the translated WoDDI is adapted to the Brazilian context and can be used after training.
Associations among socio-demographic and clinical factors and the quality of life of ostomized patients
Authors: Pereira Adriana Pelegrini dos Santos , Cesarino Claudia Bernardi , Martins Marielza Regina Ismael , Pinto Maria Helena , Netinho João Gomes
Published: April 2012

This study identifies the socio-demographic and clinical factors of patients with irreversible colostomy secondary to colorectal cancer and correlates them with quality of life (QOL). It is a cross-sectional study. Socio-demographic and clinical data were collected through interviews and the WHOQOL-bref to assess QOL. The sample comprised 60 patients. Most of the patients were male, elderly individuals, half were married and half did not have a sexual partner, with complete primary education, receiving up to two times the minimum wage, carried a stoma for three months on average, were instructed they would carry a stoma, but did not have their stoma marked prior to surgery. The average QOL score was 75.500, while the psychological, social and physical domains were the most affected. No statistically significant differences were found in QOL in relation to the following socio-demographic and clinical factors: female gender, low income, no sexual partners, and lack of instruction. The patients with an intestinal stoma presented a satisfactory QOL.
Hospitalization of children under five years of age due to avoidable causes
Authors: Oliveira Rosana Rosseto de , Costa Josane Rosenilda da , Mathias Thais Aidar de Freitas
Published: April 2012

This study characterizes the profile of hospital morbidity according to the main diagnosis upon admission, in individuals younger than five years old, residents of three cities (Maringá, Sarandi and Paiçandu) in the Paraná state, Brazil. Information contained in hospital admission forms from 1998 to 2009 was used. The hospitalizations of 41,220 individuals younger than five years old were analyzed. The results indicate a decline of 16.1% in hospital admissions of patients younger than five years old in relation to the total number of admissions in all age groups. As for the main diagnoses, there were diseases of the respiratory system (55.6%), infectious and parasitic diseases (14.8%) and diseases originating in the perinatal period (12.9%). Such conditions can be avoided by implementing primary health care measures, which shows the need to intensify the actions recommended by the programs directed to child health.
Borderline tuberculoid leprosy associated with primary cutaneous histoplasmosis
Authors: Nascimento Carolina Ribas do , Soares Ronita Rocelina Carvalhal Silva , Martelli Antônio Carlos Ceribelli , Andrade Maria Izilda , Cury Filho Milton
Published: April 2012

We describe a case of borderline tuberculoid leprosy associated with primary cutaneous histoplasmosis in a patient who presented at our hospital with skin lesions and joint complaints.
As ideias dos alunos nas pesquisas de formação inicial de professores de ciências
Authors: Harres João Batista Siqueira , Pizzato Michelle Camara , Sebastiany Ana Paula , Cenci Danielle , Eidelwein Giane , Diehl Ivan Francisco , Mörs Marlete
Published: April 2012

Considerando as ideias dos alunos componente importante na formação de futuros professo-res, apresenta-se uma revisão de pesquisas que implementaram estratégias curriculares inovadoras para promoção da evolução do conhecimento profissional. A análise centrou-se na consideração da existência e do uso didático das ideias dos alunos em 18 artigos publicados, entre 1995 e 2005, nas principais revistas internacionais (em língua inglesa) da área. São apresentadas as características destas pesquisas em termos da metodologia, contexto e perspectiva teórico-prática das abordagens curriculares formativas implementadas. O desenvolvimento profissional alcançado pelos futuros docentes envolvidos foi comparado para identificação de obstáculos e avanços nesse processo. Questões de ordem epistemológica e de coerência entre a intervenção formativa e o modelo didático tomado como referência, pelos pesquisadores/formadores, para avaliar o desenvolvimento profissional inicial destes docentes são elencadas na tentativa de se entender por que, de modo geral, a mudança alcançada é pequena.
Da psicanálise ao ensino de ciências: o "desejo do docente" e o "professor como um lugar"
Authors: Arruda Sergio de Mello , Passos Marinez Meneghello
Published: April 2012

Apresentamos, neste trabalho, reflexões produzidas no contexto de um grupo de pesquisa, deflagradas a partir da seguinte questão: seria possível fundamentar a Formação de Professores como uma metáfora a Lacan? Como resposta positiva a esta questão, discutimos aqui dois exemplos: (i) inicialmente, apresentaremos a ideia de "desejo do docente", um conceito que poderia operar no campo da Formação de Professores de maneira semelhante ao desejo do analista no campo da Psicanálise; (ii) em seguida, a metáfora do "professor como um lugar". A apresentação de cada um dos pontos é seguida de extratos de diálogos entre pesquisadores, que ocorreram durante um encontro de pesquisa. Como foi possível mostrar, por meio da apresentação dos diálogos, a proposta de metaforizar frases da psicanálise de orientação lacaniana produziu discussões ricas em ideias e questões originais, dentro do enfoque geral de evidenciar suas implicações para o ensino de ciências e para a educação.
The European Medicines Agency Review of Cabazitaxel (Jevtana®) for the Treatment of Hormone-Refractory Metastatic Prostate Cancer: Summary of the Scientific Assessment of the Committee for Medicinal Products for Human Use
Authors: Pean Elias , Demolis Pierre , Moreau Alexandre , Hemmings Robert James , O'Connor Daniel , Brown David , Shepard Terry , Abadie Eric , Pignatti Francesco
Published: April 2012

Learning Objectives:

After completing this course, the reader will be able to: Summarize the efficacy outcomes of cabazitaxel pivotal trials in the treatment of hormone-refractory metastatic prostate cancer.Describe the safety profile and most common adverse effects of cabazitaxel in patients with hormone-refractory metastatic prostate cancer.

CME This article is available for continuing medical education credit at CME.TheOncologist.com

On March 17, 2011 the European Commission issued a marketing authorization valid throughout the European Union for Jevtana® (Sanofi-Aventis, Paris, France) for the treatment of patients with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen.

The active substance of Jevtana® is cabazitaxel acetone solvate, an antineoplastic agent that acts by disrupting the microtubular network in cells. The recommended dose of cabazitaxel is 25 mg/m2 administered as a 1-hour i.v. infusion every 3 weeks in combination with oral prednisone or prednisolone, 10 mg, administered daily throughout treatment.

In the main study submitted for this application, a 2.4-month longer median overall survival time and a 30% lower risk for death were observed for cabazitaxel, compared with mitoxantrone. The most common side effects with cabazitaxel were anemia, leukopenia, neutropenia, thrombocytopenia, and diarrhea.

This paper summarizes the scientific review of the application leading to approval in the European Union. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the European Medicines Agency Web site (http://www.ema.europa.eu).
Lapatinib for Advanced or Metastatic Breast Cancer
Authors: Opdam Frans L. , Guchelaar Henk-Jan , Beijnen Jos H. , Schellens Jan H.M.
Published: April 2012

Lapatinib is a potent reversible and selective inhibitor of the tyrosine kinase domains of epidermal growth factor receptor and human epidermal growth factor receptor (HER)-2 that exerts its action by competitive binding to the intracellular ATP-binding site of the receptor. It is registered for the treatment of advanced or metastatic HER-2+ breast cancer in combination with capecitabine and for hormone receptor–positive breast cancer in combination with an aromatase inhibitor. Lapatinib administered orally once daily is moderately to well tolerated, with rash and gastrointestinal adverse events as the main toxicities. In studies on the efficacy of lapatinib, direct comparisons between lapatinib and trastuzumab are lacking. Results of ongoing randomized phase III studies with lapatinib or trastuzumab in combination with taxanes as first-line agents for metastatic breast cancer as well as in the neoadjuvant and adjuvant settings are awaited.
Bevacizumab-Based Therapies in the First-Line Treatment of Metastatic Colorectal Cancer
Authors: Strickler John H. , Hurwitz Herbert I.
Published: April 2012

Since its approval for the first-line treatment of metastatic colorectal cancer (mCRC), bevacizumab has become a standard treatment option in combination with chemotherapy for patients with mCRC. Bevacizumab has demonstrated efficacy in combination with a number of different backbone chemotherapy regimens, and its widespread use has introduced several important questions regarding the selection and optimization of bevacizumab-based treatment regimens, its use in various patient populations, and the identification of associated adverse events. This review discusses the results of several phase II and phase III clinical trials, as well as large observational studies, to address the use of bevacizumab in the treatment of patients with mCRC in the first-line setting.
Identifying the Root Cause of Drilling Vibration and Stick-Slip Enables Fit-for-Purpose Solutions
Authors: Wu Xianping , Karuppiah Venki , Nagaraj Mahavir , Partin Uyen , Machado Marcia , Franco Mariana , Duvvuru Hari
Published: April 2012

Severe vibration and stick-slip are devastating dysfunctions that significantly limit drilling performance. They cause equipment failure and increase non-productive time driving up field development costs. The evolution of real-time downhole measurement technologies can monitor the onset and severity of vibrations and stick-slip. However, the low-frequency of the measurement data and increasing BHA complexity, the information does not necessarily pinpoint the root cause of drilling dysfunction. Drillers are often forced to live with the trial-and-error process to mitigate vibrations/stick-slip, which is an expensive and inefficient approach.

Combining the engineering expertise with an advanced drilling dynamics model, the service provider has successfully identified the root cause of vibration and stick-slip in a number of challenging drilling applications worldwide. This enables engineers to concentrate on fit-for-purpose solutions rather than the traditional trial-and-error approach.Two case studies are discussed to outline and document the analysis process and the underlying solution technologies.

Case study-1: drilling a 16” section in a Middle East gas field through heavily interbedded formations with hard stringers was damaging project economics. The root cause of damage was identified as bit whirl and axial vibration. The PDC was redesigned to improve durability and achieved the longest 16” run in this field with ROP 18% faster than the best offset.

Case study-2: hole enlargement while drilling a 17½” x 20” section offshore Brazil was challenging due to hard and abrasive formations. Premature reamer cutter wear was identified as the root cause for stick-slip. A new-generation of abrasion resistant cutters was implemented on the reamer and the BHA was optimized to reduce the weight at the reamer. The new assembly drilled and enlarged shoe-to-shoe in one run with minimum stick-slip and vibration.
A Survey of Mučnik and Medvedev Degrees
Authors: Hinman Peter G.
Published: April 2012

We survey the theory of Mučnik (weak) and Medvedev (strong) degrees of subsets of ωω with particular attention to the degrees of subsets of ω2. Sections 1–6 present the major definitions and results in a uniform notation. Sections 7–16 present proofs, some more complete than others, of the major results of the subject together with much of the required background material.
Some results about (+) proved by iterated forcing
Authors: Ishiu Tetsuya , Larson Paul B.
Published: April 2012

We shall show the consistency of CH+⌝(+) and CH+(+)+there are no club guessing sequences on ω1. We shall also prove that ◊+ does not imply the existence of a strong club guessing sequence on ω1.
On rational limits of Shelah–Spencer graphs
Authors: Brody Justin , Laskowski M. C.
Published: April 2012

Given a sequence {αn} in (0,1) converging to a rational, we examine the model theoretic properties of structures obtained as limits of Shelah-Spencer graphsG(). We show that in most cases the model theory is either extremely well-behaved or extremely wild, and characterize when each occurs.
Truth definitions without exponentiation and the Σ1 collection scheme
Authors: Adamowicz Zofia , Kołodziejczyk Leszek Aleksander , Paris J.
Published: April 2012

We prove that:

• if there is a model of IΔ0 + ¬exp with cofinal Σ1-definable elements and a Σ1 truth definition for Σ1 sentences, then IΔ0 + ¬exp + ¬BΣ1 is consistent,

• there is a model of IΔ0 + Ω1 + ¬exp with cofinal Σ1-definable elements, both a Σ2 and a Π2 truth definition for Σ1 sentences, and for each n ≥ 2, a Σn truth definition for Σn sentences.

The latter result is obtained by constructing a model with a recursive truth-preserving translation of Σ1 sentences into boolean combinations of sentences.

We also present an old but previously unpublished proof of the consistency of IΔ0 + ¬exp + ¬BΣ1 under the assumption that the size parameter in Lessan's Δ0 universal formula is optimal. We then discuss a possible reason why proving the consistency of IΔ0 + ¬exp + ¬BΣ1 unconditionally has turned out to be so difficult.
Sharpened lower bounds for cut elimination
Authors: Buss Samuel R.
Published: April 2012

We present sharpened lower bounds on the size of cut free proofs for first-order logic. Prior lower bounds for eliminating cuts from a proof established superexponential lower bounds as a stack of exponentials, with the height of the stack proportional to the maximum depthdof the formulas in the original proof. Our results remove the constant of proportionality, giving an exponential stack of height equal tod−O(1). The proof method is based on more efficiently expressing the Gentzen–Solovay cut formulas as low depth formulas.
On the complexity of proof deskolemization
Authors: Baaz Matthias , Hetzl Stefan , Weller Daniel
Published: April 2012

We consider the following problem: Given a proof of the Skolemization of a formulaF, what is the length of the shortest proof ofF? For the restriction of this question to cut-free proofs we prove corresponding exponential upper and lower bounds.
Association of High Pulse Pressure With Proteinuria in Subjects With Diabetes, Prediabetes, or Normal Glucose Tolerance in a Large Japanese General Population Sample
Authors: Yano Yuichiro , Sato Yuji , Fujimoto Shouichi , Konta Tsuneo , Iseki Kunitoshi , Moriyama Toshiki , Yamagata Kunihiro , Tsuruya Kazuhiko , Yoshida Hideaki , Asahi Koichi , Kurahashi Issei , Ohashi Yasuo , Watanabe Tsuyoshi
Published: April 2012

OBJECTIVE

To examine whether there is a difference in the association between high pulse pressure and proteinuria, independent of other blood pressure (BP) indices, such as systolic or diastolic BP, among subjects with diabetes, prediabetes, or normal glucose tolerance.

RESEARCH DESIGN AND METHODS

Using a nationwide health checkup database of 228,778 Japanese aged ≥20 years (mean 63.2 years; 39.3% men; none had pre-existing cardiovascular disease), we examined the association between high pulse pressure, defined as the highest quintile of pulse pressure (≥63 mmHg, n = 40,511), and proteinuria (≥1+ on dipstick, n = 12,090) separately in subjects with diabetes (n = 27,913), prediabetes (n = 100,214), and normal glucose tolerance (n = 100,651).

RESULTS

The prevalence of proteinuria was different among subjects with diabetes, prediabetes, and normal glucose tolerance (11.3 vs. 5.0 vs. 3.9%, respectively; P < 0.001). In subjects with diabetes, but not those with prediabetes or normal glucose tolerance, high pulse pressure was associated with proteinuria independently of significant covariates, including systolic BP (odds ratio 1.15 [95% CI 1.04–1.28]) or diastolic or mean BP (all P < 0.01). In patients with diabetes, a +1 SD increase of pulse pressure (+13 mmHg) was associated with proteinuria, even after adjustment for systolic BP (1.07 [1.00–1.13]) or diastolic or mean BP (all P < 0.05).

CONCLUSIONS

Among the Japanese general population, there was a significant difference in the association between high pulse pressure and proteinuria among subjects with diabetes, prediabetes, and normal glucose tolerance. Only in diabetes was high pulse pressure associated with proteinuria independent of systolic, diastolic, or mean BP levels.
Spectroscopy of thin polyaniline films deposited during chemical oxidation of aniline
Authors: Trchová Miroslava , Morávková Zuzana , Šeděnková Ivana , Stejskal Jaroslav
Published: April 2012

Any surface immersed in the aqueous reaction mixture used for the preparation of polyaniline becomes coated with a polyaniline film of submicrometre thickness. In this way, various materials can be modified by an overlayer of conducting polymer. The present review illustrates the role of infrared, Raman, and UV-VIS spectroscopies in the studies of polyaniline film growth. Spectroscopic methods are crucial in the evaluation of the performance of polyaniline films alone or in combination with nanoparticles of noble metals. The assessment of film ageing and stability can be followed conveniently by these methods. Carbonization of polyaniline films to nitrogen-containing carbon analogues is also discussed.
Design and evaluation of moxifloxacin hydrochloride ocular inserts
Authors: Pawar Pravin , Katara Rajesh , Majumdar Dipak
Published: April 2012

Design and evaluation of moxifloxacin hydrochloride ocular inserts

The objective of the present investigation was to prepare and evaluate ocular inserts of moxifloxacin. An ocular insert was made from an aqueous dispersion of moxifloxacin, sodium alginate, polyvinyl alcohol, and dibutyl phthalate by the film casting method. The ocular insert (5.5 mm diameter) was cross-linked by CaCl2and was coated with Eudragit S-100, RL-100, RS-100, E-100 or L-100. Thein vitrodrug drainage/permeation studies were carried out using an all-glass modified Franz diffusion cell. The drug concentration and mucoadhesion time of the ocular insert were found satisfactory. Cross-linking and coating with polymers extended the drainage from inserts. The cross-linked ocular insert coated with Eudragit RL-100 showed maximum drug permeation compared to other formulations.
The Effects of Erythropoietin on Bacterial Translocation and Inflammatory Response in an Experimental Intestinal Obstruction Model in Rats / Uticaj Eritropoetina Na Bakterijsku Translokaciju I Inflamatorni Odgovor U Eksperimentalnom Modelu Intestinalne Opstrukcije Kod Pacova
Authors: Kapan Murat , Onder Akın , Yuksel Hatice , Evliyaoglu Osman , Firat Ugur , Tekin Recep , Gul Mesut , Aliosmanoglu Ibrahim
Published: April 2012

Background:Intestinal obstruction results in distortion of balance of antiinflammatory cytokines and release of oxidants, and also leads to bacterial translocation, sepsis and multiple organ failure. Asymmetric dimethylarginine is related to multiple organ failure as a new prognostic marker. Erythropoietin reduces the inflammatory response by decreasing the levels of proinflammatory cytokines and cytokine-induced apoptosis. In this study, we aimed to investigate the effectiveness of erythropoietin in reducing the severity of bacterial translocation and inflammatory response after intestinal obstruction and the relation between asymmetric dimethylarginine and inflammatory markers.

Methods:Forty Wistar albino rats (200-250 g) were divided into 4 groups as follows: Group 1 (Sham), only ileocaecal junction dissection; Group 2 (Erythropoietin), ileocaecal junction dissection and 3000 lU/kg erythropoietin subcutaneously; Group 3 (Intestinal Obstruction), complete ileal ligation; Group 4 (Intestinal Obstruction + Erythropoietin), complete ileal ligation and 3000 IU/kg erythropoietin subcutaneously. After 24 hours, the rats were sacrificed by taking blood from the heart for biochemical analyses. Peritoneal swab culture, liver, mesenteric lymph nodes, spleen and ileum were collected for microbiological and histopathological examinations.

Results:Erythropoietin reduced the secretion of inflammatory cytokines, oxidative damage and bacterial translocation, prevented the formation of inflammatory changes in the intestine, liver, spleen and mesenteric lymph nodes,and also significantly prevented the formation of intestinal damage after intestinal obstruction (p<0.05). Conclusions: Asymmetric dimethylarginine levels did not differ between the groups. Erythropoietin may be useful to preserve from intestinal injury and related sepsis in patients with intestinal obstruction. Asymmetric dimethylarginine is not a suitable prognostic marker.
Hyperphosphatemia - The Risk Factor for Adverse Outcome in Maintenance Hemodialysis Patients
Authors: Petrović Dejan , Obrenović Radmila , Trbojević-Stanković Jasna , Majkić-Singh Nada , Stojimirović Biljana
Published: April 2012

Hyperphosphatemia - The Risk Factor for Adverse Outcome in Maintenance Hemodialysis Patients

Hyperphosphatemia is a potent stimulator of vascular and valvular calcifications in hemodialysis patients. To determine the prevalence of hyperphosphatemia and assess its effect on the outcome of hemodialysis patients, a total of 115 chronic hemodialysis patients were studied. Laboratory parameters were determined at baseline, and after 12 and 24 months of follow-up. Valvular calcification was assessed with echocardiography. Laboratory parameters were statistically analyzed with ANOVA. Survival analysis was performed with the Kaplan-Meier test and Log-Rank test. Hyperphosphatemia was present in 31.30% of the patients, high calcium-phosphate (Ca × P) product in 36.52% and valvular calcifications in 48.70%. Patients with serum phosphate >2.10 mmol/L and Ca × P product >5.65 mmol2/L2at baseline were at high risk for all-cause and cardiovascular mortality. Hyperphosphatemia is a risk factor for adverse outcome in patients on regular hemodialysis.
Association Between Telomere Shortening and Ageing During Occupational Exposure
Authors: Eshkoor Sima , Jahanshiri Fatemeh , Ismail Patimah , Rahman Sabariah , Moin Saidi , Adon Mohd
Published: April 2012

Association Between Telomere Shortening and Ageing During Occupational Exposure

Telomere length is considered as a biomarker of ageing, resulting in shortening during the process. The present investigation was an attempt to determine the relative telomere length in mechanical workshop workers. Telomere length shortening in cells during occupational exposure causes accelerated ageing. Genomic DNA was isolated from buccal epithelial cells collected from 240 individuals, comprising two groups of 120 exposed workers and 120 unexposed controls. Telomere length was measured by using real time PCR. Both telomere (T) and single copy gene (S) specific primers were used to compute the relative T/S ratio and expressed as the relative telomere length. Telomere length differed significantly between the workers and controls (p<0.05). The results showed an indirect and significant association (r=-0.356, p=0.001) between age and telomere length in the workers. This study showed that the difference in telomere length shortening was statistically significant (p<0.05) between the workers and controls. It was concluded that occupational exposure acts as a risk factor to enhance telomere length shortening and accelerate ageing.
Analysis of Codon 972 (Gly → Arg) Polymorphism in IRS-1 Gene in Type 2 Diabetic Population
Authors: Kumar Robby , Sharan Nishant
Published: April 2012

Analysis of Codon 972 (Gly → Arg) Polymorphism in IRS-1 Gene in Type 2 Diabetic Population

Polymorphism of Insulin Receptor Substrate-1, especially the GGG→AGG (Gly-Arg) substitution at codon 972, is one of the major factors leading to the development of type 2 diabetes mellitus. This defect in IRS-1 causes insulin resistance along with many other consequences. It generally impairs insulin signalling via the phosphadylinositol-3 (PI3)-Kinase pathway. In this study, the heterozygous Gly→Arg substitution at codon 972 of the IRS-1 gene was found in 2 of the 43 control Indian subjects, which is higher than normal when compared with the other population. The prevalence of the codon 972 GGG→AGG substitutions was found to be around 4.6%, which may be due to a predisposition factor. In diabetic subjects, on the other hand, 5 out of 43 showed substitution at codon 972, with a percent prevalence of 14%, establishing the role of the polymorphism of IRS-1 codon in the prevalence of diabetes mellitus.
Empirical investigation of two designs of incline solar water desalination system
Authors: Agboola Phillips , Egelioglu Fuat
Published: April 2012

Empirical investigation of two designs of incline solar water desalination system

This paper presents an experimental investigation of two incline solar water desalination (ISWD) systems. One design uses spray jets for spraying water onto the absorber plate, while the other uses a longitudinal slot for getting the inlet water on the absorber plate. The first ever ISWD system constructed and tested by Aybar et al (2005) used the longitudinal slot with a maximum daily production of 2.995 kg/m2 day. The Aybar et al design produced 3.4 kg/m2-day while the new design produced 6.41 kg/m2-day for wick on absorber plate system day during the hottest months in Famagusta (July-August 2010). Also tested was the influence of porous media (wire mesh), wick on the absorber plate. The effect of number of spray jets used in the system on the daily productivity and efficiency of the systems were also investigated.
Performance of silica aerogels modified with amino functional groups in PB(II) and CD(II) removal from aqueous solutions
Authors: Faghihian Hossein , Nourmoradi Heshmatollah , Shokouhi Maryam
Published: April 2012

Performance of silica aerogels modified with amino functional groups in PB(II) and CD(II) removal from aqueous solutions

The adsorption behavior of Pb(II) and Cd(II) ions in aqueous solutions on silica aerogels modified with amino propyl triethoxysilane was investigated as a function of pH, contact time, adsorbate concentration and adsorbent dose. It was found that maximum adsorption of Pb(II) and Cd(II) ions occurs at pH 6.0 and pH 8.0, respectively. The optimum contact time to obtain equilibrium adsorption with the modified silica aerogel was experimentally found to be around 48h. Adsorption isotherms clearly indicated that the adsorption behavior of metals ions on the modified silica aerogels is fitted well with both the Langmuir and Freundlich isotherms. The maximum adsorption capacities of Pb(II) and Cd(II) on modified silica aerogel were found to be 45.45mg/g and 35.71mg/g, respectively. The results indicated that silica aerogels modified with amino functional groups can be used as an efficient adsorbent in the removal of metal ions such as Pb(II) and Cd(II) from aqueous solutions.