DNA Topoisomerase I Gene Copy Number and mRNA Expression Assessed as Predictive Biomarkers for Adjuvant Irinotecan in Stage II/III Colon Cancer.

PURPOSE: Prospective-retrospective assessment of theTOP1gene copy number andTOP1mRNA expression as predictive biomarkers for adjuvant irinotecan in stage II/III colon cancer. EXPERIMENTAL DESIGN: Formalin-fixed, paraffin-embedded tissue microarrays were obtained from an adjuvant colon cancer trial (PETACC3) where patients were randomized to 5-fluorouracil/folinic acid with or without additional irinotecan.TOP1copy number status was analyzed by fluorescencein situhybridization (FISH) using aTOP1/CEN20 dual-probe combination.TOP1mRNA data were available from previous analyses. RESULTS: TOP1FISH and follow-up data were obtained from 534 patients.TOP1gain was identified in 27% using a single-probe enumeration strategy (≥4TOP1signals per cell) and in 31% when defined by aTOP1/CEN20 ratio ≥ 1.5. The effect of additional irinotecan was not dependent onTOP1FISH status.TOP1mRNA data were available from 580 patients with stage III disease. Benefit of irinotecan was restricted to patients characterized byTOP1mRNA expression ≥ third quartile (RFS: HRadjusted, 0.59;P= 0.09; OS: HRadjusted, 0.44;P= 0.03). The treatment byTOP1mRNA interaction was not statistically significant, but in exploratory multivariable fractional polynomial interaction analysis, increasingTOP1mRNA values appeared to be associated with increasing benefit of irinotecan. CONCLUSIONS: In contrast to theTOP1copy number, a trend was demonstrated for a predictive property ofTOP1mRNA expression. On the basis ofTOP1mRNA, it might be possible to identify a subgroup of patients where an irinotecan doublet is a clinically relevant option in the adjuvant setting of colon cancer.Clin Cancer Res; 22(7); 1621-31. ©2015 AACR.

Danos ao DNA promovidos por ácido 5-aminolevulínico: possível associação com o desenvolvimento de carcinoma hepatocelular em portadores de porfiria aguda intermitente

5-Aminolevulinic acid (ALA) is a heme precursor accumulated in acute intermittent porphyria (AIP), which might be associated with hepatocellular carcinoma (HCC) in symptomatic patients. Under metal catalyzed oxidation, ALA and its cyclic dimerization product, 3,6-dihydropyrazine-2,5-dipropanoic acid, produce reactive oxygen species that damage plasmid and calf thymus DNA bases, increase the steady state level of 8-oxo-7,8-dihydro-2´-deoxyguanosine in liver DNA and promote mitochondrial DNA damage. The final product of ALA, 4,5-dioxovaleric acid (DOVA), is able to alkylate guanine moieties, producing adducts. ALA and DOVA are mutagenic in bacteria. This review shows an up-to-date literature data that reinforce the hypothesis that the DNA damage induced by ALA may be associated with the development of HCC in AIP patients.

Concentrar els à pats en 12 hores evita el sobrepès

L'obesitat és un dels principals factors de risc per a moltes patologies, com la diabetis de tipus II, la cirrosi no alcohòlica, les malalties cardiovasculars i diversos tipus de càncer. La major part de tractaments contra l'obesitat i de recomanacions per evitar el sobrepès se centren en la dieta, principalment en la quantitat i el contingut nutricional del menjar, i en el nombre d'àpats diaris. Però l'investigador Satchidananda Panda i els seus col·laboradors, del departament de gastroenterologia de la Universitat de Califòrnia a San Diego (EUA), han identificat un altre factor que és també molt important: el temps que passa entre el primer i l'últim àpat del dia. Segons han publicat a Cell Metabolism, aquest interval no hauria de superar les dotze hores.

Effect of hydrodynamics on modelling, monitoring and control of crystallization

Crystallization is a purification method used to obtain crystalline product of a certain crystal size. It is one of the oldest industrial unit processes and commonly used in modern industry due to its good purification capability from rather impure solutions with reasonably low energy consumption. However, the process is extremely challenging to model and control because it involves inhomogeneous mixing and many simultaneous phenomena such as nucleation, crystal growth and agglomeration. All these phenomena are dependent on supersaturation, i.e. the difference between actual liquid phase concentration and solubility. Homogeneous mass and heat transfer in the crystallizer would greatly simplify modelling and control of crystallization processes, such conditions are, however, not the reality, especially in industrial scale processes. Consequently, the hydrodynamics of crystallizers, i.e. the combination of mixing, feed and product removal flows, and recycling of the suspension, needs to be thoroughly investigated. Understanding of hydrodynamics is important in crystallization, especially inlargerscale equipment where uniform flow conditions are difficult to attain. It is also important to understand different size scales of mixing; micro-, meso- and macromixing. Fast processes, like nucleation and chemical reactions, are typically highly dependent on micro- and mesomixing but macromixing, which equalizes the concentrations of all the species within the entire crystallizer, cannot be disregarded. This study investigates the influence of hydrodynamics on crystallization processes. Modelling of crystallizers with the mixed suspension mixed product removal (MSMPR) theory (ideal mixing), computational fluid dynamics (CFD), and a compartmental multiblock model is compared. The importance of proper verification of CFD and multiblock models is demonstrated. In addition, the influence of different hydrodynamic conditions on reactive crystallization process control is studied. Finally, the effect of extreme local supersaturation is studied using power ultrasound to initiate nucleation. The present work shows that mixing and chemical feeding conditions clearly affect induction time and cluster formation, nucleation, growth kinetics, and agglomeration. Consequently, the properties of crystalline end products, e.g. crystal size and crystal habit, can be influenced by management of mixing and feeding conditions. Impurities may have varying impacts on crystallization processes. As an example, manganese ions were shown to replace magnesium ions in the crystal lattice of magnesium sulphate heptahydrate, increasing the crystal growth rate significantly, whereas sodium ions showed no interaction at all. Modelling of continuous crystallization based on MSMPR theory showed that the model is feasible in a small laboratoryscale crystallizer, whereas in larger pilot- and industrial-scale crystallizers hydrodynamic effects should be taken into account. For that reason, CFD and multiblock modelling are shown to be effective tools for modelling crystallization with inhomogeneous mixing. The present work shows also that selection of the measurement point, or points in the case of multiprobe systems, is crucial when process analytical technology (PAT) is used to control larger scale crystallization. The thesis concludes by describing how control of local supersaturation by highly localized ultrasound was successfully applied to induce nucleation and to control polymorphism in reactive crystallization of L-glutamic acid.

Relação entre resistência de linhagens tropicais de milho à podridão de espiga e ao acúmulo de fumonisinas provocados por Fusarium verticillioides

A infecção de grãos de milho por Fusarium verticillioides, agente causal da podridão da espiga, pode resultar na produção de micotoxinas do grupo das fumonisinas. A resistência genética é a forma de controle mais eficiente dessa enfermidade. Assim, o objetivo do trabalho foi buscar fontes de resistência em linhagens de milho tropical à F. verticillioides e à produção de fumonisinas. Seis linhagens tropicais de milho, três, pré-classificadas como resistentes e três, pré-classificadas como suscetíveis à F. verticillioides, foram submetidas à inoculação do patógeno e posteriormente, avaliadas quanto à severidade da podridão de espiga, incidência de grãos sintomáticos e concentração de fumonisinas. Os resultados mostraram que as linhagens R1 e R3 apresentaram alta resistência à infecção do patógeno. No entanto, apenas a R3 foi resistente ao acúmulo de fumonisinas. Dessa forma, sugere-se que a ausência de relação entre intensidade da doença e níveis de fumonisinas seja fator inerente desse patossistema. Assim, não é possível assegurar que grãos assintomáticos quanto à infecção por F. verticillioides, estejam livres de contaminação por fumonisinas.

Reação de cultivares de tangerineira à antracnose sob diferentes sistemas de irrigação

A tangerineira é uma das espécies de Citrus mais importantes, comercialmente. No entanto, é elevada a quantidade de patógenos que afetam a cultura, destacando-se o fungo Colletotrichum gloeosporioides, causador da antracnose. A antracnose pode resultar em grandes prejuízos econômicos, ocasionando perdas de produção e qualidade dos frutos. O objetivo deste trabalho foi avaliar a resistência de cultivares de tangerineira à antracnose em diferentes sistemas de irrigação. Foi estudada a incidência da antracnose em três cultivares de tangerineira, sob três sistemas de cultivo. Utilizaram-se as cultivares 'Murcote', 'Ponkan' e 'Cravo', enxertadas sobre porta-enxerto de limão Cravo e os sistemas de irrigação por microaspersão e por gotejamento. Uma testemunha de sequeiro foi incluída. Os resultados mostraram que as plantas cultivadas sob irrigação são mais resistentes à antracnose que aquelas sob regime de sequeiro, sendo que a cultivar Ponkan apresentou maior resistência genética á antracnose. Verificou-se também que existe correlação positiva entre a incidência baseada no percentual de plantas afetadas e a incidência com base no número de ramos afetados por planta.

Yhteiskunnan käyttövoima - kotona kirjova nainen

Kirjallisuusarvostelu

Hoitotyötä eri kulttuureissa

Kirjallisuusarvostelu

Opinto-opas 2012 : sotatieteiden maisterin tutkinto : SM3-kurssi : SMSIV : SMOHJ12-kurssi

Maanpuolustuskorkeakoulun vuoden 2012 opinto-opas on jaettu neljään osaan: yleiseen osaan sekä kolmeen eriytyvään osaan, sotatieteiden kandidaatin, sotatieteiden maisterin ja yleisesikuntaupseerin tutkinnon oppaaseen. Yleisessä osassa kerrotaan opiskelusta Maanpuolustuskorkeakoulussa, esitellään sotatieteelliset tutkinnot ja tutkintovaatimukset sekä sotatieteellisten oppiaineiden tavoitteet kaikilla tutkintotasoilla. Eriytyvät osat keskittyvät tutkintotasojen opetussuunnitelmiin, opintokokonaisuuksiin ja opintojaksoihin sekä mahdollistavat opintopolkujen suunnittelun. Tämä opinto-opas on suunnattu Maanpuolustuskorkeakoulun kaikille sotatieteiden maisteriopiskelijoille. Pääosa heistä opiskelee upseerin virkaan johtavaa tutkintoa. Lisäksi oman ryhmänsä muodostavat maisteriohjaajaopiskelijat sekä opiskelijat, joiden tutkinto ei johda upseerin virkaan. Sotatieteiden maisteritutkinnon opinto-opas alkaa sotatieteiden maisteritutkinnon esittelyllä ja opintojen vaiheiden kuvauksella. Kappaleen lopussa kuvataan tutkinnon opintopolut. Toinen kappale keskittyy kuvaamaan sotatieteiden maisterin tutkintoa, joka ei johda upseerin virkaan. Kolmas kappale on opiskelijoille tärkein kappale. Siinä esitetään sotatieteiden maisterin tutkintojen opintokokonaisuudet ja opintojaksokuvaukset. Suositeltavaa on, että opiskelija käyttää opintojen suunnitteluun sekä yleistä että eriytyvää osaa. Nämä kaksi opasta muodostavat yhdessä tiiviin tietopaketin. Jos opinnoista ja niiden suunnittelusta herää kysymyksiä, käänny kurssinjohtajan, Opintoasiainosaston henkilökunnan tai PAT-koulujen henkilökunnan puoleen.

Caracterização histológica e imuno-histoquímica das lesões de tuberculose em bovinos e de linfadenite granulomatosa em suínos

Mycobacterium sp. induz inflama&#231;&#227;o granuloma-tosa em diferentes esp&#233;cies animais. Mycobacterium bovis e o complexo Mycobacterium avium s&#227;o importantes pat&#243;genos de bovinos e su&#237;nos e podem causar infec&#231;&#227;o em humanos, principalmente imunossuprimidos. Perdas na produ&#231;&#227;o, barreiras comerciais e preju&#237;zos por condena&#231;&#227;o de carca&#231;as em abatedouro/frigor&#237;fico est&#227;o atrelados &#224; ocorr&#234;ncia dessas infec&#231;&#245;es, com preju&#237;zos econ&#244;micos significativos. Foi realizado um estudo de casos diagnosticados como tuberculose em bovinos e linfadenite granulomatosa em su&#237;nos no Setor de Patologia Veterin&#225;ria da Universidade Federal do Rio Grande do Sul (SPV-UFRGS) no per&#237;odo de janeiro de 2007 a dezembro de 2011. Dados referentes &#224; ra&#231;a, ao sexo, &#224; idade e ao hist&#243;rico cl&#237;nico foram compilados dos livros de registro e analisados. As caracter&#237;sticas histol&#243;gicas das les&#245;es em linfonodos e pulm&#245;es foram avaliadas em Hematoxilina-Eosina, com predom&#237;nio de c&#233;lulas gigantes nas les&#245;es de tuberculose bovina e de macr&#243;fagos epitelioides em su&#237;nos. As t&#233;cnicas histoqu&#237;micas de Ziehl-Neelsen e Tricr&#244;mico de Masson foram utilizadas para evidenciar, respectivamente, bacilos &#225;lcool-&#225;cido resistentes e tecido conjuntivo fibroso nas les&#245;es. A t&#233;cnica de imuno-histoqu&#237;mica foi utilizada em aproximadamente 30% dos casos estudados de cada esp&#233;cie, selecionados aleatoriamente, para a caracteriza&#231;&#227;o do infiltrado linfoc&#237;tico. Foram utilizados os anticorpos anti-CD3 para a marca&#231;&#227;o de linf&#243;citos T e anti-CD79&#945;cy para a marca&#231;&#227;o de linf&#243;citos B. Linf&#243;citos T predominaram nas les&#245;es em ambas as esp&#233;cies, com diferen&#231;a estatisticamente significativa entre as m&#233;dias dos linf&#243;citos T e linf&#243;citos B. Foi usado o teste t pareado, com t=5,501 (p<0,001) nas les&#245;es dos bovinos e t=5,826 (p<0,001) para as les&#245;es de linfadenite dos su&#237;nos. Adicionalmente foram marcados macr&#243;fagos com o uso do anticorpo anti-CD68 para bovinos e anti-Lisozima para su&#237;nos. Al&#233;m desses, o anticorpo policlonal anti-Mycobacterium tuberculosis foi utilizado para a detec&#231;&#227;o de bact&#233;rias do g&#234;nero Mycobacterium, com imunomarca&#231;&#227;o positiva em todos os casos e, nos casos dos su&#237;nos, houve marca&#231;&#227;o anti-Mycobacterium avium.

Competição de azevém (Lolium multiflorum L. ) com duas cultivares de trigo

Com os objetivos de avaliar a habilidade de duas cultivares de trigo em competir com azevém (Lolium multiflorum, L.) e de estimar os efeitos da concorrência de várias densidades desta espécie sobre a cultura, foi conduzido experimento a campo durante a estação de crescimento de 1978, na Estação Experimental Agronõmica da UFRGS, em Guaíba, RS. Foram comparadas as cultivares de trigo 'E-7414' e 'PAT-7219', na população de 300 plantas por m', com azevém semeado nas densidades de 0, 2,5, 5,0, 10,0 e 20,0 kg/ha, as quais originaram populações médias de 0, 130, 210, 470 e 750 plantas por m² , respectivamente. A competição entre as espécies foi mantida durante o ciclo da cultura. Para o rendimento de grãos da cultivar 'E-7414', a competição exercida pelo azevém ocasionou decréscimos variáveis entre 18% e 56%, dependendo da infestação; enquanto para a cultivar 'PAT-7219', as reduções no rendimento de grãos se situaram entre 4c é 22%, conforme a densidade do azevém. Enquanto para 'PAT-7219' não foram significativas as reduções no rendimento de grãos, para `E-7414' os decréscimos verificados alcançaram significância estatística. A análise do peso da matéria seca do azevém demonstrou que este aumentou proporcionalmente ao aumento de sua população, mas que aquela variável foi significativamente menor quando o azevém esteve competindo com 'PAT-7219' do que com `E-7414'. Em média, diminuiu em 31% a matéria seca do azevém produzida sob 'PAT-7219' em relação à `E-7414'.

Opinto-opas 2014 : sotatieteiden maisterin tutkinto : SM5-kurssi, SMOHJ14-kurssi, SMSIV14

Opinto-oppaan yleisessä osassa kerrotaan opiskelusta Maanpuolustuskorkeakoulussa sekä sen alaisissa puolustushaara-, aselaji- ja toimialakouluissa (PAT-koulut). Tämä kädessäsi oleva eriytyvä opas keskittyy sotatieteiden maisteriopintoihin (SM). Sotatieteiden maisteriopiskelijoita ovat upseerin virkaan johtavia opintoja opiskelevat upseerit (SM), ohjaajaksi (lentäjät) opiskelevat upseerit (SMOHJ) sekä opiskelijat, jotka opiskelevat kansallisen ja kansainvälisen turvallisuuden asiantuntijoiksi (SMSIV). Sotatieteiden maisteritutkinnon opinto-oppaassa kuvataan SM-tutkinnon kokonaisuus, opintojen sisältö, opintopolut ja opintojaksokuvaukset. Suunniteltaessa tulevia opintoja ja niiden toteutusta opiskelija saa tietoja opinto-oppaiden yleisestä ja yksityiskohtaisesta osasta. Ohjausta ja neuvontaa opintojen suunnitteluun annetaan Opintoasiainosastolla, Maisteriosastolla sekä PAT-kouluilla.

Poliporóides (Basidiomycota) em fragmentos de mata no perímetro urbano de São José do Rio Preto, São Paulo, Brasil

Foi realizado levantamento das espécies de fungos poliporóides que ocorrem no perímetro urbano do município de São José do Rio Preto (20º49'12" S, 49º22'44" W), Estado de São Paulo, Brasil. Foram identificadas 18 espécies pertencentes a 11 gêneros de Agaricales (Schizophyllaceae), Hymenochaetales (Hymenochaetaceae) e Polyporales (Ganodermataceae, Gloeophyllaceae, Meruliaceae e Polyporaceae): Coriolopsis floccosa (Jungh.) Ryvarden, C. polyzona (Pers.) Ryvarden, Datronia caperata (Berk.) Ryvarden, D. mollis (Somf.:Fr.) Donk., Ganoderma australe (Fr.) Pat., Gloeophyllum striatum (Sw.) Murrill, Gloeoporus thelephoroides (Hook.) G. Cunn., Hexagonia hirta (P. Beauv.) Fr., H. hydnoides (Sw.) M. Fidalgo, H. papyracea Berk., Polyporus tenuiculus (P. Beauv.) Fr., Phellinus callimorphus (Lév.) Ryvarden, P. gilvus (Schwein.) Pat., P. umbrinellus (Bres.) Herrera &amp; Bondartseva, Pycnoporus sanguineus (L.) Murrill, Schizophyllum commune Fr., S. umbrinum Berk. e Trametes modesta (Kunze:Fr.) Ryvarden. Datronia mollis é nova citação para o Estado de São Paulo. São apresentados chave de identificação, descrições e comentários para cada táxon estudado.

Low occurrence of occult hepatitis B virus infection and high frequency of hepatitis C virus genotype 3 in hepatocellular carcinoma in Brazil

Occult hepatitis B virus (HBV) infection has been reported among patients with hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC). Our aim was to evaluate the presence of occult HBV infection in patients with HCV-related liver cirrhosis (LC) with or without HCC in São Paulo, Brazil. Serum and liver tissue samples from 50 hepatitis B surface antigen-negative patients with HCV-related LC who underwent liver transplantation at the University of São Paulo School of Medicine Hospital from 1993 to 2004 were divided into groups with LC only (N = 33) and with LC plus HCC (N = 17). HBV DNA was assayed for serum and paraffin-embedded liver tissue (tumoral and non-tumoral) using real time PCR and only 1 case with HCC had HBV DNA-positive serum. All liver samples were negative. HCV genotype 3 was detected in 17/39 (43.7%) cases. In conclusion, using a sensitive real time PCR directed to detect HBV variants circulating in Brazil, occult hepatitis B infection was not found among HCV-positive cirrhotic patients and was rarely found among HCV-positive HCC patients. These results are probably related to the low prevalence of HBV infection in our population. Furthermore, we have also shown that HCV genotype 3 is frequently found in Brazilian cirrhotic patients, particularly when they also have HCC. More studies involving a large number of cases should be carried out to confirm these data and to further characterize Brazilian HCV genotype isolates to elucidate genetic features that might be related to its carcinogenic potential.

Does hepatocellular carcinoma in non-alcoholic steatohepatitis exist in cirrhotic and non-cirrhotic patients?

Non-alcoholic steatohepatitis (NASH) has been associated with hepatocellular carcinoma (HCC) often arising in histologically advanced disease when steatohepatitis is not active (cryptogenic cirrhosis). Our objective was to characterize patients with HCC and active, histologically defined steatohepatitis. Among 394 patients with HCC detected by ultrasound imaging over 8 years and staged by the Barcelona Clinic Liver Cancer (BCLC) criteria, we identified 7 cases (1.7%) with HCC occurring in the setting of active biopsy-proven NASH. All were negative for other liver diseases such as hepatitis C, hepatitis B, autoimmune hepatitis, Wilson disease, and hemochromatosis. The patients (4 males and 3 females, age 63 ± 13 years) were either overweight (4) or obese (3); 57% were diabetic and 28.5% had dyslipidemia. Cirrhosis was present in 6 of 7 patients, but 1 patient had well-differentiated HCC in the setting of NASH without cirrhosis (fibrosis stage 1) based on repeated liver biopsies, the absence of portal hypertension by clinical and radiographic evaluations and by direct surgical inspection. Among the cirrhotic patients, 71.4% were clinically staged as Child A and 14.2% as Child B. Tumor size ranged from 1.0 to 5.2 cm and 5 of 7 patients were classified as early stage; 46% of all nodules were hyper-echoic and 57% were <3 cm. HCC was well differentiated in 1/6 and moderately differentiated in 5/6. Alpha-fetoprotein was <100 ng/mL in all patients. HCC in patients with active steatohepatitis is often multifocal, may precede clinically advanced disease and occurs without diagnostic levels of alpha-fetoprotein. Importantly, HCC may occur in NASH in the absence of cirrhosis. More aggressive screening of NASH patients may be warranted.