Clinical and molecular characterization of diffuse large B-cell lymphomas with 13q14.3 deletion.

Background: Deletions at 13q14.3 are common in chronic lymphocytic leukemia and are also present in diffuse large B-cell lymphomas (DLBCL) but never in immunodeficiency-related DLBCL. To characterize DLBCL with 13q14.3 deletions, we combined genome-wide DNA profiling, gene expression and clinical data in a large DLBCL series treated with rituximab, cyclophosphamide, doxorubicine, vincristine and prednisone repeated every 21 days (R-CHOP21). Patients and methods: Affymetrix GeneChip Human Mapping 250K NspI and U133 plus 2.0 gene were used. MicroRNA (miRNA) expression was studied were by real-time PCR. Median follow-up of patients was 4.9 years. Results: Deletions at 13q14.3, comprising DLEU2/MIR15A/MIR16, occurred in 22/166 (13%) cases. The deletion was wider, including also RB1, in 19/22 cases. Samples with del(13q14.3) had concomitant specific aberrations. No reduced MIR15A/MIR16 expression was observed, but 172 transcripts were significantly differential expressed. Among the deregulated genes, there were RB1 and FAS, both commonly deleted at genomic level. No differences in outcome were observed in patients treated with R-CHOP21. Conclusions: Cases with 13q14.3 deletions appear as group of DLBCL characterized by common genetic and biologic features. Deletions at 13q14.3 might contribute to DLBCL pathogenesis by two mechanisms: deregulating the cell cycle control mainly due RB1 loss and contributing to immune escape, due to FAS down-regulation

Genomic deletion and promoter methylation status of Hypermethylated in Cancer 1 (HIC1) in mantle cell lymphoma

Mantle cell lymphomas (MCL), characterized by the t(11;14)(q13;q32), frequently carry secondary genetic alterations such as deletions in chromosome 17p involving the TP53 locus. Given that the association between TP53-deletions and concurrent mutations of the remaining allele is weak and based on our recent report that the Hypermethylated in Cancer 1 (HIC1) gene, that is located telomeric to the TP53 gene, may be targeted by deletions in 17p in diffuse large B-cell lymphoma (DLBCL), we investigated whether HIC1 inactivations might also occur in MCL. Monoallelic deletions of the TP53 locus were detected in 18 out of 59 MCL (31%), while overexpression of p53 protein occurred in only 8 out of 18 of these MCL (44%). In TP53-deleted MCL, the HIC1 gene locus was co-deleted in 11 out of 18 cases (61%). However, neither TP53 nor HIC1 deletions did affect survival of MCL patients. In most analyzed cases, no hypermethylation of the HIC1 exon 1A promoter was observed (17 out of 20, 85%). However, in MCL cell lines without HIC1-hypermethylation, the mRNA expression levels of HIC1 were nevertheless significantly reduced, when compared to reactive lymph node specimens, pointing to the occurrence of mechanisms other than epigenetic or genetic events for the inactivation of HIC1 in this entity

Community projects: an experimental analysis of a fair implementation process

We define and experimentally test a public provision mechanism that meets three basic ethical requirements and allows community members to influence, via monetary bids, which of several projects is implemented. For each project, participants are assigned personal values, which can be positive or negative. We provide either public or private information about personal values. This produces two distinct public provision games, which are experimentally implemented and analyzed for various projects. In spite of the complex experimental task, participants do not rely on bidding their own personal values as an obvious simple heuristic whose general acceptance would result in fair and efficient outcomes. Rather, they rely on strategic underbidding. Although underbidding is affected by projects’ characteristics, the provision mechanism mostly leads to the implementation of the most efficient project

The spectrum of ATM missense variants and their contribution to contralateral breast cancer

Heterozygous carriers of ATM mutations are at increased risk of breast cancer. In this case-control study, we evaluated the significance of germline ATM missense variants to the risk of contralateral breast cancer (CBC). We have determined the spectrum and frequency of ATM missense variants in 443 breast cancer patients diagnosed before age 50, including 247 patients who subsequently developed CBC. Twenty-one per cent of the women with unilateral breast cancer and 17% of the women with CBC had at least one ATM germline missense variant, indicating no significant difference in variant frequency between these two groups. We have found that carriers of an ATM missense mutation, who were treated with radiotherapy for the first breast tumour, developed their second tumour on average in a 92-month interval compared to a 136-month mean interval for those CBC patients who neither received RT nor carried a germline variant, (p = 0.029). Our results indicate that the presence of ATM variants does not have a major impact on the overall risk of CBC. However, the combination of RT and (certain) ATM missense variants seems to accelerate tumour development

Synthesis and White-Light Emission of ZnO/HfO2: Eu Nanocables

ZnO/HfO2:Eu nanocables were prepared by radio frequency sputtering with electrospun ZnO nanofibers as cores. The well-crystallized ZnO/HfO2:Eu nanocables showed a uniform intact core–shell structure, which consisted of a hexagonal ZnO core and a monoclinic HfO2 shell. The photoluminescence properties of the samples were characterized. A white-light band emission consisted of blue, green, and red emissions was observed in the nanocables. The blue and green emissions can be attributed to the zinc vacancy and oxygen vacancy defects in ZnO/HfO2:Eu nanocables, and the yellow–red emissions are derived from the inner 4f-shell transitions of corresponding Eu3+ ions in HfO2:Eu shells. Enhanced white-light emission was observed in the nanocables. The enhancement of the emission is ascribed to the structural changes after coaxial synthesis

Engaging diverse underserved communities to bridge the mammography divide

<p>Abstract</p> <p>Background</p> <p>Breast cancer screening continues to be underutilized by the population in general, but is particularly underutilized by traditionally underserved minority populations. Two of the most at risk female minority groups are American Indians/Alaska Natives (AI/AN) and Latinas. American Indian women have the poorest recorded 5-year cancer survival rates of any ethnic group while breast cancer is the number one cause of cancer mortality among Latina women. Breast cancer screening rates for both minority groups are near or at the lowest among all racial/ethnic groups. As with other health screening behaviors, women may intend to get a mammogram but their intentions may not result in initiation or follow through of the examination process. An accumulating body of research, however, demonstrates the efficacy of developing 'implementation intentions' that define when, where, and how a specific behavior will be performed. The formulation of intended steps in addition to addressing potential barriers to test completion can increase a person's self-efficacy, operationalize and strengthen their intention to act, and close gaps between behavioral intention and completion. To date, an evaluation of the formulation of implementation intentions for breast cancer screening has not been conducted with minority populations.</p> <p>Methods/Design</p> <p>In the proposed program, community health workers will meet with rural-dwelling Latina and American Indian women one-on-one to educate them about breast cancer and screening and guide them through a computerized and culturally tailored "implementation intentions" program, called <it>Healthy Living Kansas - Breast Health</it>, to promote breast cancer screening utilization. We will target Latina and AI/AN women from two distinct rural Kansas communities. Women attending community events will be invited by CHWs to participate and be randomized to either a mammography "implementation intentions" (<b>MI</b>^<b>2</b>) intervention or a comparison general breast cancer prevention informational intervention (<b>C</b>). CHWs will be armed with notebook computers loaded with our Healthy Living Kansas - Breast Health program and guide their peers through the program. Women in the <b>MI</b>^{<b>2 </b>}condition will receive assistance with operationalizing their screening intentions and identifying and addressing their stated screening barriers with the goal of guiding them toward accessing screening services near their community. Outcomes will be evaluated at 120-days post randomization via self-report and will include mammography utilization status, barriers, and movement along a behavioral stages of readiness to screen model.</p> <p>Discussion</p> <p>This highly innovative project will be guided and initiated by AI/AN and Latina community members and will test the practical application of emerging behavioral theory among minority persons living in rural communities.</p> <p>Trial Registration</p> <p>ClinicalTrials (NCT): <a href="http://www.clinicaltrials.gov/ct2/show/NCT01267110">NCT01267110</a></p

High-Throughput Analysis of Synthetic Peptides for the Immunodiagnosis of Canine Visceral Leishmaniasis

Globally, the number of new human cases of visceral leishmaniasis (VL) is estimated to be approximately 500,000 per year. This is the most severe of all forms of leishmaniasis, and the zoonotic form of VL, caused by Leishmania infantum (also known as Leishmania chagasi), represents 20% of human visceral leishmaniasis worldwide; additionally, its prevalence is increasing in urban and peri-urban areas of the tropics. In Brazil, the identification and elimination of infected dogs, which act as a reservoir for Leishmania parasites, is a control measure employed in addition to the use of insecticides against the vectors and the identification and treatment of infected humans. Currently, the diagnostic methods employed to identify infected animals are not able to detect all of these dogs, which compromises the effectiveness of control measures. Moreover, one of the most important issues in controlling VL is the difficulty of diagnosing asymptomatic dogs, which act as parasite reservoirs. Therefore, to contribute to the improvement of the diagnostic methods for CVL, we aimed to identify and characterize new antigens that were more sensitive and specific and could be applied in epidemiologic surveys