COLORECTAL CANCER IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: PRELIMINARY RESULTS FROM AN ONGOING CASE-CONTROL STUDY

Background and Aim:Understanding the risk factors for colorectal cancer (CRC) is crucial to the development of effective strategies for its prevention. meta-analysis and epidemiological studies have already shown that type 2 diabetes mellitus (DM) is associated with an increased risk of CRC and have provided data to support a positive relationship between these diseases. Material and Methods: We retrospectively evaluated 741 consecutive caucasian patients with type 2 DM who underewnt colonoscopic screening cof CRC and followed in our tertiary referrral center in 200-208 for incidence of CRC. Patients were stratified based on gender, age, body mass index (MBI), alchool and NSAIDS assumption, family history for cancer blood glycated hemoglobin levels, hypertension, hypertrigliceridemia, age at diabetes onset and duration, treatment with insulin or other hypoglicemic drugs. A total of 257 consecutive control patients were selected from a cohort of patients followed as outpatients for thyroid diseases. Results: At a median follow-up of 132,5 months (range 33,3-175,7) 56 cases of cancer (prevalence 7,56%) occurred; among these, 14 cases of CRC were reported (prevalence 18,8%) among the diabetic patients, while only one case (prevalence 0,004%) occurred in the control group, although this difference is not statistically significant (chi-square 2,9, P=0,08). Median duration of DM to CRC diagnosis was 156 months (range 1-768). At the univariate analysis older age (p=0,001), and diabetes duration (p=0,001) were related to higher risk of cancer, while metformin seems to be protective towards cancer (p=0,058). in the subset of patients with CRC, older age (p=0,001) and diabetes duration (p=0,001) were related to higher risk of CRC, such as treatment with sulphonylureas (p=0,01). Conclusions: Our preliminbar data show that the prevalence of CRC in the cohort of patients with type 2 DM was higher compared to that from our control group, and to that from the National Tumor Register up 2010 (0,5%). Furthermore we could interestingly hypotize that sulphonylureas may play a role in CRC carcinogenesis altering the physiological insulin secretion

Inhibition of PbGP43 expression may suggest that gp43 is a virulence factor in Paracoccidioides brasiliensis

ABSTARCT: Glycoprotein gp43 is an immunodominant diagnostic antigen for paracoccidioidomycosis caused by Paracoccidioides brasiliensis. It is abundantly secreted in isolates such as Pb339. It is structurally related to beta-1,3-exoglucanases, however inactive. Its function in fungal biology is unknown, but it elicits humoral, innate and protective cellular immune responses; it binds to extracellular matrix-associated proteins. In this study we applied an antisense RNA (aRNA) technology and Agrobacterium tumefaciens-mediated transformation to generate mitotically stable PbGP43 mutants (PbGP43 aRNA) derived from wild type Pb339 to study its role in P. brasiliensis biology and during infection. Control PbEV was transformed with empty vector. Growth curve, cell vitality and morphology of PbGP43 aRNA mutants were indistinguishable from those of controls. PbGP43 expression was reduced 80-85% in mutants 1 and 2, as determined by real time PCR, correlating with a massive decrease in gp43 expression. This was shown by immunoblotting of culture supernatants revealed with anti-gp43 mouse monoclonal and rabbit polyclonal antibodies, and also by affinity-ligand assays of extracellular molecules with laminin and fibronectin. In vitro, there was significantly increased TNF-α production and reduced yeast recovery when PbGP43 aRNA1 was exposed to IFN-γ-stimulated macrophages, suggesting reduced binding/uptake and/or increased killing. In vivo, fungal burden in lungs of BALB/c mice infected with silenced mutant was negligible and associated with decreased lung ΙΛ-10 and IL-6. Therefore, our results correlated low gp43 expression with lower pathogenicity in mice, but that will be definitely proven when PbGP43 knockouts become available.

Identification and characterization of Tc1/mariner-like DNA transposons in genomes of the pathogenic fungi of the Paracoccidioides species complex

<p>Abstract</p> <p>Background</p> <p><it>Paracoccidioides brasiliensis </it>(Eukaryota, Fungi, Ascomycota) is a thermodimorphic fungus, the etiological agent of paracoccidioidomycosis, the most important systemic mycoses in Latin America. Three isolates corresponding to distinct phylogenetic lineages of the <it>Paracoccidioides </it>species complex had their genomes sequenced. In this study the identification and characterization of class II transposable elements in the genomes of these fungi was carried out.</p> <p>Results</p> <p>A genomic survey for DNA transposons in the sequence assemblies of <it>Paracoccidioides</it>, a genus recently proposed to encompass species <it>P. brasiliensis </it>(harboring phylogenetic lineages S1, PS2, PS3) and <it>P. lutzii </it>(<it>Pb01-like </it>isolates), has been completed. Eight new <it>Tc1/mariner </it>families, referred to as Trem (<b>Tr</b>ansposable <b>e</b>lement <b>m</b>ariner), labeled A through H were identified. Elements from each family have 65-80% sequence similarity with other <it>Tc1/mariner </it>elements. They are flanked by 2-bp TA target site duplications and different termini. Encoded DDD-transposases, some of which have complete ORFs, indicated that they could be functionally active. The distribution of Trem elements varied between the genomic sequences characterized as belonging to <it>P. brasiliensis </it>(S1 and PS2) and <it>P. lutzii</it>. TremC and H elements would have been present in a hypothetical ancestor common to <it>P. brasiliensis </it>and <it>P. lutzii</it>, while TremA, B and F elements were either acquired by <it>P. brasiliensis </it>or lost by <it>P. lutzii </it>after speciation. Although TremD and TremE share about 70% similarity, they are specific to <it>P. brasiliensis </it>and <it>P. lutzii</it>, respectively. This suggests that these elements could either have been present in a hypothetical common ancestor and have evolved divergently after the split between <it>P. brasiliensis </it>and <it>P. Lutzii</it>, or have been independently acquired by horizontal transfer.</p> <p>Conclusions</p> <p>New families of <it>Tc1/mariner </it>DNA transposons in the genomic assemblies of the <it>Paracoccidioides </it>species complex are described. Families were distinguished based on significant BLAST identities between transposases and/or TIRs. The expansion of Trem in a putative ancestor common to the species <it>P. brasiliensis </it>and <it>P. lutzii </it>would have given origin to TremC and TremH, while other elements could have been acquired or lost after speciation had occurred. The results may contribute to our understanding of the organization and architecture of genomes in the genus <it>Paracoccidioides</it>.</p

Empreendedorismo em turismo rural: o caso do Norte de Portugal

A presente dissertação tem como objectivo principal estudar o empreendedorismo em turismo rural: o caso do Norte de Portugal, recorrendo para isso, a uma análise quantitativa. A análise efectuada é baseada numa amostra formada por empresas pertencentes ao sector do turismo em Portugal do Norte de Portugal que fossem empresas activas e que tivessem registado na base de dados um contacto de e-mail. Foram apuradas 267 empresas a quem se enviou um questionário tendo-se obtido 41 respostas válidas, sendo esse o número de empresas da nossa amostra final. Além dos dados obtidos via questionário foram recolhidos dados económico-financeiros através da base de dados empresarial SABI (Sistema de Análise de Balanços Ibéricos). Os resultados obtidos indicam que um maior nível de internacionalização, bem como mais elevadas habilitações académicas dos gestores das empresas se associam a melhores níveis de desempenho organizacional.This dissertation´s main objective is to study entrepreneurship in rural tourism: the case of Northern Portugal, using a quantitative analysis. The analysis is based on a sample of companies belonging to the tourism sector in northern Portugal who were active companies and had registered an e-mail contact in the database. To a total of 267 companies a questionnaire was sent and 41 valid answers were obtained, which is the number of companies in our final sample. In addition to the data obtained through the questionnaire, economic and financial data was collected through the SABI (Iberian Balance Sheet Analysis System) business database. The results obtained indicate that a higher level of internationalization and higher academic qualifications of company managers are associated with a better level of organizational performance

Gene Copy-Number Variation in Haploid and Diploid Strains of the Yeast Saccharomyces cerevisiae

The increasing ability to sequence and compare multiple individual genomes within a species has highlighted the fact that copy-number variation (CNV) is a substantial and underappreciated source of genetic diversity. Chromosome-scale mutations occur at rates orders of magnitude higher than base substitutions, yet our understanding of the mechanisms leading to CNVs has been lagging. We examined CNV in a region of chromosome 5 (chr5) in haploid and diploid strains of Saccharomyces cerevisiae. We optimized a CNV detection assay based on a reporter cassette containing the SFA1 and CUP1 genes that confer gene dosage-dependent tolerance to formaldehyde and copper, respectively. This optimized reporter allowed the selection of low-order gene amplification events, going from one copy to two copies in haploids and from two to three copies in diploids. In haploid strains, most events involved tandem segmental duplications mediated by nonallelic homologous recombination between flanking direct repeats, primarily Ty1 elements. In diploids, most events involved the formation of a recurrent nonreciprocal translocation between a chr5 Ty1 element and another Ty1 repeat on chr13. In addition to amplification events, a subset of clones displaying elevated resistance to formaldehyde had point mutations within the SFA1 coding sequence. These mutations were all dominant and are proposed to result in hyperactive forms of the formaldehyde dehydrogenase enzyme

GERD in the elderly: an endoscopic experience.

Analyzing medical issues related to the elderly patients, particularly in the gastroenterological sphere, Gastro-Esophageal Reflux Disease (GERD) seems to be a disease that reaches an important role in terms of diagnosis and therapy, as well as adversely affect the quality of life of these “frail” patients. Comorbidities that affect these patients often lead to reduce the importance of this disease, which in fact, not infrequently, it is difficult to identify because of mild symptom picture compared to younger patients. Is important to remember that GERD, although in most cases provokes only vague dyspeptic symptoms, can also lead to serious complications, such as bleeding especially in patients with impaired hemostasis, aspiration pneumonia, or even to cancerization of Barrett’s esophagus. In addition, there are several factors favoring GERD, for example polypharmacy carried out for other conditions, which can modify the physiology of the anti-reflux mechanisms. This review addresses the problem of GERD, analyzing it in all its aspects

Therapeutic DNA Vaccine Encoding Peptide P10 against Experimental Paracoccidioidomycosis

Paracoccidioidomycosis (PCM), caused by Paracoccidioides brasiliensis, is the most prevalent invasive fungal disease in South America. Systemic mycoses are the 10th most common cause of death among infectious diseases in Brazil and PCM is responsible for more than 50% of deaths due to fungal infections. PCM is typically treated with sulfonamides, amphotericin B or azoles, although complete eradication of the fungus may not occur and relapsing disease is frequently reported. A 15-mer peptide from the major diagnostic antigen gp43, named P10, can induce a strong T-CD4+ helper-1 immune response in mice. The TEPITOPE algorithm and experimental data have confirmed that most HLA-DR molecules can present P10, which suggests that P10 is a candidate antigen for a PCM vaccine. In the current work, the therapeutic efficacy of plasmid immunization with P10 and/or IL-12 inserts was tested in murine models of PCM. When given prior to or after infection with P. brasiliensis virulent Pb 18 isolate, plasmid-vaccination with P10 and/or IL-12 inserts successfully reduced the fungal burden in lungs of infected mice. In fact, intramuscular administration of a combination of plasmids expressing P10 and IL-12 given weekly for one month, followed by single injections every month for 3 months restored normal lung architecture and eradicated the fungus in mice that were infected one month prior to treatment. The data indicate that immunization with these plasmids is a powerful procedure for prevention and treatment of experimental PCM, with the perspective of being also effective in human patients

Long-term proactive management of psoriasis with calcipotriol and betamethasone dipropionate foam: an Italian consensus through a combined nominal group technique and Delphi approach

Background: Although long-term management of psoriasis is paramount, this approach is challenging in clinical practice. In the recent PSO-LONG trial, a fixed-dose combination of betamethasone dipropionate (BD) and calcipotriol (Cal) foam applied twice a week on non-consecutive days for 52 weeks (proactive treatment) reduced the risk of relapse. However, the role of Cal/BD foam in the long-term management of psoriasis needs further clarifications. The ProActive Management (PAM) program, a nationwide Italian project, aims at reaching a consensus on the role of proactive management of psoriasis. Methods: A steering committee generated some statements through the nominal group technique (NGT). The statements were voted by an expert panel in an adapted Delphi voting process. Results: Eighteen statements were proposed, and the majority of them (14/18) reached a consensus during the Delphi voting. The need to provide long-term proactive topical treatment to reduce the risk of relapse for the treatment of challenging diseases sites or in patients where phototherapy or systemic therapies are contraindicated/ineffective was widely recognized. A consensus was reached about the possibility to associate the proactive treatment with systemic and biological therapies, without the need for dose intensification, thus favoring a prolonged remission. Moreover, the proactive treatment was recognized as more effective than weekend therapy in increasing time free from relapses. Approaches to improve adherence, on the other hand, need further investigation. Conclusions: The inclusion in guidelines of a proactive strategy among the effective treatment options will be a fundamental step in the evolution of a mild-moderate psoriasis therapeutic approach