A prospective study on contrast-enhanced magnetic resonance imaging of testicular lesions: distinctive features of Leydig cell tumours

OBJECTIVES: Up to 20 % of incidentally found testicular lesions are benign Leydig cell tumours (LCTs). This study evaluates the role of contrast-enhanced magnetic resonance imaging (MRI) in the identification of LCTs in a large prospective cohort study. MATERIALS AND METHODS: We enrolled 44 consecutive patients with at least one solid non-palpable testicular lesion who underwent scrotal MRI. Margins of the lesions, signal intensity and pattern of wash-in and wash-out were analysed by two radiologists. The frequency distribution of malignant and benign MRI features in the different groups was compared by using the chi-squared or Fisher's exact test. Sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy were calculated. RESULTS: The sensitivity of scrotal MRI to diagnose LCTs was 89.47 % with 95.65 % specificity; sensitivity for malignant lesions was 95.65 % with 80.95 % specificity. A markedly hypointense signal on T2-WI, rapid and marked wash-in followed by a prolonged washout were distinctive features significantly associated with LCTs. Malignant lesions were significantly associated with blurred margins, weak hypointense signal on T2-WI ,and weak and progressive wash-in. The overall diagnostic accuracy was 93 %. CONCLUSIONS: LCTs have distinctive contrast-enhanced MRI features that allow the differential diagnosis of incidental testicular lesions. KEY POINTS: • MRI is able to characterize testicular lesions suggesting a specific diagnosis. • Rapid and marked wash-in is a common feature of Leydig cell tumours. • Markedly hypointense T2-WI signal is significantly correlated with benign lesions. • Blurred margins and weak hypointense T2-WI signal are correlated with malignant tumours. • Weak and progressive wash-in features are present in 85 % of seminomatous lesions

Phosphine‐Catalyzed [3+2] Cycloaddition of Aza‐Aurones and Allenoates: Enantioselective Synthesis of 2‐Spirocyclopentyl‐Indolin‐3‐Ones

An enantioselective phosphine-catalyzed [3+2] cycloaddition between aza-aurones and allenoates is here described. The reaction proceeded under mild reaction conditions to afford 2-spirocyclopentyl indolin-3-one derivatives as single gamma-isomer and with high levels of stereocontrol

Caracterização dos usuários hipertensos e diabéticos acompanhados em uma unidade de saúde da família

The objective of this study is to characterize hypertensive and diabetic users accompanied at a family health unit, of a municipality in the southern region of Brazil. Quantitative, descriptive and illustrative study, involving hypertensive and/or diabetics users registered in a family health unit. The data were collected through of a semistructured script to capture the profile. For analysis of data, the information was confronted with the literature of the area, as well as reflections. It was observed a greater prevalence of females and age equal to or above 60 years. The level of schooling prevailed in Incomplete Elementary Education, in addition of the Illiteracy, and the most of the people were retired. The hypertension was also highlighted. The data refer to an important public health issue related to the difficulty of users’ access and the social, economic and political consequences related to management decision making.O objetivo deste estudo é caracterizar os usuários hipertensos e diabéticos acompanhados em uma unidade de saúde da família, de um município da região Sul do Brasil. Estudo quantitativo, descritivo e ilustrativo, envolvendo usuários hipertensos e/ou diabéticos cadastrados em uma Unidade de Saúde da Família. Os dados foram coletados por meio de um roteiro semiestruturado para a captação do perfil. Para análise dos dados, as informações foram confrontadas com a literatura da área, bem como reflexões. Observou-se maior prevalência do sexo feminino e idade igual ou acima de 60 anos. O nível de escolaridade prevaleceu o Ensino Fundamental Incompleto, além do Analfabetismo, e a maioria das pessoas era aposentada. Também se destacou a hipertensão. Os dados reportam a uma importante questão de Saúde Pública referente à dificuldade de acesso dos usuários e as consequências sociais, econômicas e políticas relacionadas à tomada de decisão da gestão

Tethering Carbohydrates to the Vinyliminium Ligand of Antiproliferative Organometallic Diiron Complexes

Four propargyl O-glycosides derivatized with mannose, glucose, and fructose moieties were synthesized and then incorporated within a diiron structure as part of a vinyliminium ligand. Hence, six glycoconjugated diiron complexes, [2−5]CF3SO3 (see Scheme 1) and the nonglycosylated analogues [6a−b]CF3SO3, were obtained in high yields and unambiguously characterized by elemental analysis, mass spectrometry, and IR and multinuclear NMR spectroscopies. All compounds exhibited a significant stability in DMSO-d6/D2O solution, with 63−89% of the complexes unaltered after 72 h at 37 °C and also in the cell culture medium. The cytotoxicity of [2−6]CF3SO3, as well as that of previously reported 7 and 8, was assessed on CT26 (mouse colon carcinoma), U87 (humanglioblastoma), MCF-7 human breast adenocarcinoma), and RPE-1 (human normal retina pigmented epithelium) cell lines. In general, the IC50 values correlate with the hydrophobicity of the compounds (measured as octanol−water partition coefficients) and do not show an appreciable level of selectivity against cancer cells with respect to the nontumor ones

Mismatch repair gene defects in sporadic colorectal cancer enhance immune surveillance

Background: There is evidence that colorectal cancers (CRC) with DNA mismatch repair deficiency (MMR-D) are associated with a better prognosis than the generality of large bowel malignancies. Since an active immune surveillance process has been demonstrated to influence CRC outcome, we investigated whether MMR-D can enhance the immune response in CRC. Patients and Methods: A group of 113 consecutive patients operated for CRC (42 stage I or II and 71 with stage III or IV) was retrospectively analyzed. The expression of MMR genes (MSH2, MLH1, MSH6 and PSM2) and co-stimulatory molecule CD80 was assessed by tissue microarray immunohistochemistry. In addition, tumor infiltrating mononuclear cells (TIMC) and T cell subpopulations (CD4, CD8, T-bet and FoxP-3) were quantified. The effect of specific siRNA (siMSH2, siMLH1, siMSH6 and siPSM2) transfection in HT29 on CD80 expression was quantified by flow cytometry. Non parametric statistics and survival analysis were used. Results: Patients with MMR-D showed a higher T-bet/CD4 ratio (p = 0.02), a higher rate of CD80 expression and CD8 lymphocyte infiltration compared to those with no MMR-D. Moreover, in the MMR-D group, the Treg marker FoxP-3 was not expressed (p = 0.05). MMR-D patients with stage I or II and T-bet expression had a significant better survival (p = 0.009). Silencing of MSH2, MLH1 and MSH6, but not PSM2, significantly increased the rate of CD80+ HT29 cells (p = 0.007, p = 0.023 and p = 0.015, respectively). Conclusions: CRC with MMR-D showed a higher CD80 expression, and CD8+ and Th1 T-cell infiltration. In vitro silencing of MSH2, MLH1 and MSH6 significantly increased CD80+ cell rate. These results suggest an enhanced immune surveillance mechanism in presence of MMR-D

Mutant p53 proteins counteract autophagic mechanism sensitizing cancer cells to mTOR inhibition

Mutations in TP53 gene play a pivotal role in tumorigenesis and cancer development. Here, we report that gain-of-function mutant p53 proteins inhibit the autophagic pathway favoring antiapoptotic effects as well as proliferation of pancreas and breast cancer cells. We found that mutant p53 significantly counteracts the formation of autophagic vesicles and their fusion with lysosomes throughout the repression of some key autophagy-related proteins and enzymes as BECN1 (and P-BECN1), DRAM1, ATG12, SESN1/2 and P-AMPK with the concomitant stimulation of mTOR signaling. As a paradigm of this mechanism, we show that atg12 gene repression was mediated by the recruitment of the p50 NF-\u3baB/mutant p53 protein complex onto the atg12 promoter. Either mutant p53 or p50 NF-\u3baB depletion downregulates atg12 gene expression. We further correlated the low expression levels of autophagic genes (atg12, becn1, sesn1, and dram1) with a reduced relapse free survival (RFS) and distant metastasis free survival (DMFS) of breast cancer patients carrying TP53 gene mutations conferring a prognostic value to this mutant p53-and autophagy-related signature. Interestingly, the mutant p53-driven mTOR stimulation sensitized cancer cells to the treatment with the mTOR inhibitor everolimus. All these results reveal a novel mechanism through which mutant p53 proteins promote cancer cell proliferation with the concomitant inhibition of autophagy

First report in italy of the exotic mosquito species Aedes (Finlaya) koreicus, a potential vector of arboviruses and filariae

BACKGROUND: In the Veneto region (north-eastern Italy) an entomological surveillance system has been implemented since the introduction of the Asian tiger mosquito (Aedes albopictus) in 1991. During the routine monitoring activity in a tiger mosquito-free area, an unexpected mosquito was noticed, which clearly did not belong to the recorded Italian fauna. FINDINGS: At the end of May 2011, twelve larvae and pupae were collected in a small village in Belluno province (Veneto region) from a single manhole. Ten adults reared in the laboratory were morphologically and genetically identified as Aedes (Finlaya) koreicus (Edwards, 1917), a species native to Southeast Asia. The subsequent investigations carried out in the following months in the same village provided evidence that this species had become established locally. Entomological and epidemiological investigations are currently ongoing in the surrounding area, to verify the eventual extension of the species outside the village and to trace back the route of entry into Italy. CONCLUSIONS: This is the first report in Italy of the introduction of the exotic mosquito Ae. koreicus. This species has been shown experimentally to be competent in the transmission of the Japanese encephalitis virus and of the dog heartworm Dirofilaria immitis and is considered a potential vector of other arboviruses. Thus, the establishment of this species may increase the current risk or pose new potential threats, for human and animal health. This finding considerably complicates the entomological monitoring of the Asian tiger mosquito Ae. albopictus in Italy and stresses the importance of implementing the entomological surveillance for the early detection of and the rapid response against invasive mosquito species

Extracellular matrix composition modulates the responsiveness of differentiated and stem pancreatic cancer cells to lipophilic derivate of gemcitabine

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease. Gemcitabine (GEM) is used as the gold standard drug in PDAC treatment. However, due to its poor efficacy, it remains urgent to identify novel strategies to overcome resistance issues. In this context, an intense stroma reaction and the presence of cancer stem cells (CSCs) have been shown to influence PDAC aggressiveness, metastatic potential, and chemoresistance. Methods: We used three-dimensional (3D) organotypic cultures grown on an extracellular matrix composed of Matrigel or collagen I to test the effect of the new potential therapeutic prodrug 4-(N)-stearoyl-GEM, called C18GEM. We analyzed C18GEM cytotoxic activity, intracellular uptake, apoptosis, necrosis, and autophagy induction in both Panc1 cell line (P) and their derived CSCs. Results: PDAC CSCs show higher sensitivity to C18GEM treatment when cultured in both two-dimensional (2D) and 3D conditions, especially on collagen I, in comparison to GEM. The intracellular uptake mechanisms of C18GEM are mainly due to membrane nucleoside transporters' expression and fatty acid translocase CD36 in Panc1 P cells and to clathrin-mediated endocytosis and CD36 in Panc1 CSCs. Furthermore, C18GEM induces an increase in cell death compared to GEM in both cell lines grown on 2D and 3D cultures. Finally, C18GEM stimulated protective autophagy in Panc1 P and CSCs cultured on 3D conditions. Conclusion: We propose C18GEM together with autophagy inhibitors as a valid alternative therapeutic approach in PDAC treatment

Survey of intestinal parasites among primary school children inhabitants of different rural communities in Rio Grande do Sul State

Um trabalho de extensão comunitária foi realizado em três assentamentos de colonos sem terra, Fazenda de São Pedro, Charqueadas e Capela de Santana, nas proximidades de Porto Alegre, RS. O objetivo desta pesquisa foi determinar o índice de infecção de parasitas intestinais nas crianças residentes nessas comunidades rurais. Este estudo, executado em 140 crianças, de zero a 14 anos revelou que 45% (63) estavam infectadas por uma ou mais espécies de enteroparasitas. O maior percentual obtido para protozoários foi de 15,7% (22) para Giardia lamblia e entre os helmintos, ancilostomídeos com 15,7% (22) e Strongyloides stercoralis e Hymenolepis nana com 7,9% (11) respectivamente.An integrated programma and a survey of intestinal parasites were carried out in three rural communities inhabitants of Fazenda de São Pedro, Charqueadas and Capela de Santana near Porto Alegre, RS. In order to determine the infection rate of intestinal parasites in primary school children from these communities a total of 140 stools specimens were collected and screened for the presence of intestinal protozoa and helminths. One or more parasites were demonstrated in 45% (63) of the students population. The most common intestinal parasites in this study were Giardia lamblia and hookworms, 15.7% (22). Other intestinal helminths found less frequently were Strongyloides stercoralis and Hymenolepis nana both with 7.85% (11)