60 research outputs found

    Gonadal function in male patients after treatment for malignant lymphomas, with emphasis on chemotherapy

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    Gonadal function was assessed in male lymphoma survivors based on serum hormone levels (LH, FSH, testosterone, SHBG), and was related to treatment, age and observation time. Male patients ⩽50 years at diagnosis treated for Hodgkin's (HL) and/or non-Hodgkin's lymphoma (NHL) at the Norwegian Radium Hospital from 1 January 1980 to 31 December 2002 were included. Five treatment groups were defined: 1: radiotherapy only and/or low gonadotoxic chemotherapy (both HL and NHL)(‘No/low'), 2: medium gonadotoxicity chemotherapy for NHL (‘med-NHL'), 3: medium gonadotoxicity chemotherapy for HL (‘med-HL'), 4: highly gonadotoxic chemotherapy for NHL (‘high-NHL'), 5: highly gonadotoxic chemotherapy for HL (‘high-HL'). Gonadal hormone levels were categorised into three groups: 1: All gonadal hormones within normal range (normal), 2: Isolated elevated FSH, with LH, SHBG and testosterone within normal range (exocrine hypogonadism), 3: Testosterone below and/or LH above normal range (endocrine hypogonadism). One hundred and forty-four (49%) of the patients had normal gonadal hormones, 60 (20%) displayed exocrine hypogonadism and almost one-third (n=90, 30%) had endocrine hypogonadism. Compared to those treated with no/low gonadotoxic chemotherapy patients from all other treatment groups had significantly elevated risk for exocrine hypogonadism. Patients from the other treatment groups, except those in the med-NHL group, also had significantly elevated risk for endocrine hypogonadism compared with the group treated with no/low gonadotoxic chemotherapy. Men aged above 50 years at survey were about five times more likely to have endocrine hypogonadism compared with those less than 40 years. Because of the adverse health effects following long-lasting endocrine hypogonadism, gonadal hormones should be assessed regularly in male lymphoma survivors, especially after treatment with alkylating agents and high-dose chemotherapy with autologous stem cell support and in male patients who are 50 years and older

    Dental Occlusion in a Split Amazon Indigenous Population: Genetics Prevails over Environment

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    Background: Studies examining human and nonhuman primates have supported the hypothesis that the recent increase in the occurrence of misalignment of teeth and/or incorrect relation of dental arches, named dental malocclusion, is mainly attributed to the availability of a more processed diet and the reduced need for powerful masticatory action. For the first time on live human populations, genetic and tooth wear influences on occlusal variation were examined in a split indigenous population. The Arara-Iriri people are descendants of a single couple expelled from a larger village. In the resultant village, expansion occurred through the mating of close relatives, resulting in marked genetic cohesion with substantial genetic differences. Methodology/Principal Findings: Dental malocclusion, tooth wear and inbreeding coefficient were evaluated. The sample examined was composed of 176 individuals from both villages. Prevalence Ratio and descriptive differences in the outcomes frequency for each developmental stage of the dentition were considered. Statistical differences between the villages were examined using the chi-square test or Fisher’s exact statistic. Tooth wear and the inbreeding coefficient (F) between the villages was tested with Mann-Whitney statistics. All the statistics were performed using two-tailed distribution at p#0.05. The coefficient inbreeding (F) confirmed the frequent incestuous unions among the Arara-Iriri indigenous group. Despite the tooth wear similarities, we found a striking difference in occlusal patterns between the two Arara villages. In the original village, dental malocclusion was present in about one third of the population; whilst in the resultant village, the occurrence was almost doubled. Furthermore, the morphological characteristics of malocclusion were strongly different between the groups. Conclusions/Significance: Our findings downplay the widespread influence of tooth wear, a direct evidence of what an individual ate in the past, on occlusal variation of living human populations. They also suggest that genetics plays the most important role on dental malocclusion etiology

    Investigating porcine parvoviruses genogroup 2 infection using in situ polymerase chain reaction

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    Abstract Background Porcine parvovirus 2 (PPV2) was detected in swine serum without showing any relationship with disease. The emergence of the virus seemed to be a unique event until other genetically highly similar parvoviruses were identified in China and, later in 2012, the presence of the virus was also described in Europe. PPV2 is widely distributed in pig populations where it is suspected to be involved in respiratory conditions, based on its frequent detection in lung samples. In order to investigate the potential pathogenic involvement of PPV2, 60 dead pigs were examined from two farms. They were necropsied and tested for PPV2 and PCV2 (Porcine circovirus type 2) by PCR; by Brown and Brenn (B&B) staining for bacteria; by immunohistochemistry (IHC) to detect CD3, Swine leukocyte antigen class II DQ (SLAIIDQ), lysozyme, porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza (SIV), Mycoplasma hyopneumoniae (Mhyo); and by in situ hybridization (ISH) to detect ssDNA and dsDNA of PCV2. PPV2 positive samples were subjected to in situ polymerase chain reaction (IS-PCR) including double staining method to detect PPV2 and host cell markers. To calculate statistical difference we used GENMOD or LOGISTIC procedures in Statistical Analysis System (SAS®). Results We found that the PPV2 was localized mostly in lymphocytes in lungs, lymph nodes and liver. Neither CD3 antigen nor lysozyme was expressed by these infected cells. In contrast, low levels of SLAIIDQ were expressed by infected cells, suggesting that PPV2 may have a specific tropism for immature B lymphocytes and/or NK lymphocytes though possibly not T lymphocytes. Conclusion The overall conclusion of this study indicates that PPV2 may contribute to the pathogenesis of pneumonia

    Mural Cell Associated VEGF Is Required for Organotypic Vessel Formation

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    Background: Blood vessels comprise endothelial cells, mural cells (pericytes/vascular smooth muscle cells) and basement membrane. During angiogenesis, mural cells are recruited to sprouting endothelial cells and define a stabilizing context, comprising cell-cell contacts, secreted growth factors and extracellular matrix components, that drives vessel maturation and resistance to anti-angiogenic therapeutics. Methods and Findings: To better understand the basis for mural cell regulation of angiogenesis, we conducted high content imaging analysis on a microtiter plate format in vitro organotypic blood vessel system comprising primary human endothelial cells co-cultured with primary human mural cells. We show that endothelial cells co-cultured with mural cells undergo an extensive series of phenotypic changes reflective of several facets of blood vessel formation and maturation: Loss of cell proliferation, pathfinding-like cell migration, branching morphogenesis, basement membrane extracellular matrix protein deposition, lumen formation, anastamosis and development of a stabilized capillary-like network. This phenotypic sequence required endothelial-mural cell-cell contact, mural cell-derived VEGF and endothelial VEGFR2 signaling. Inhibiting formation of adherens junctions or basement membrane structures abrogated network formation. Notably, inhibition of mural cell VEGF expression could not be rescued by exogenous VEGF. Conclusions: These results suggest a unique role for mural cell-associated VEGF in driving vessel formation and maturation

    Anti-cancer drug validation: the contribution of tissue engineered models

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    Abstract Drug toxicity frequently goes concealed until clinical trials stage, which is the most challenging, dangerous and expensive stage of drug development. Both the cultures of cancer cells in traditional 2D assays and animal studies have limitations that cannot ever be unraveled by improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. Considering the NCI60, a panel of 60 cancer cell lines representative of 9 different cancer types: leukemia, lung, colorectal, central nervous system (CNS), melanoma, ovarian, renal, prostate and breast, we propose to review current Bstate of art^ on the 9 cancer types specifically addressing the 3D tissue models that have been developed and used in drug discovery processes as an alternative to complement their studyThis article is a result of the project FROnTHERA (NORTE-01-0145-FEDER-000023), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This article was also supported by the EU Framework Programme for Research and Innovation HORIZON 2020 (H2020) under grant agreement n° 668983 — FoReCaST. FCT distinction attributed to Joaquim M. Oliveira (IF/00423/2012) and Vitor M. Correlo (IF/01214/2014) under the Investigator FCT program is also greatly acknowledged.info:eu-repo/semantics/publishedVersio

    Public perceptions of shale gas in the UK : framing effects and decision heuristics

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    Using two equivalent descriptions of the shale gas development process, we asked individuals to indicate their levels of support as well as their perceptions of the risks and costs involved. In version 1, shale gas development was framed as ‘fracking’, whereas under version 2 it was framed as ‘using hydraulic pressure to extract natural gas from the ground’. We find that individuals’ support for shale gas development is much lower when using the term ‘fracking’ as opposed to the synonymous descriptive term, and moreover, these differences were substantive. Our analysis suggests that these differences appear to be largely the result of different assessments of the risks associated with ‘fracking’ as opposed to ‘using hydraulic pressure to extract natural gas from the ground’. Our proposed explanation for these differences rests on the idea that shale gas development is a technical and complex process and many individuals will be bounded by the rationality of scientific knowledge when it comes to understanding this process. In turn, individuals may be relying on simple decision heuristics shaped by the way this issue is framed by the media and other interested parties which may constrain meaningful discourse on this topic with the public. Our findings also highlight some of the potential pitfalls when it comes to relying on survey research for assessing the public’s views towards complex environmental issues

    Automatic extraction of dislocated horizons from 3D seismic data using nonlocal trace matching

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    Extracting key horizons from seismic images is an important element of the seismic interpretation workflow. Although numerous computer-assisted horizon extraction methods exist, they are typically sensitive to structural and stratigraphic discontinuities. As a result, these computer-assisted methods have difficulties in extracting noncoherent dislocated horizons. We have developed a new data-driven method to correlate, track, and extract horizons from seismic volumes with complex geologic structures. Our method correlates seismic horizons across discontinuities and does not require user input in the form of seed points or prior identification of faults. Furthermore, the method is robust toward amplitude changes along a seismic horizon and does not jump from peak to trough or vice versa. We use a large sliding window and match full-length seismic traces using nonlocal dynamic time warping to extract grids of correlated points for our target horizons. Through computed accuracy measurements, we discard nonaccurate correlations before interpolating complete seismic horizons. Because our method does not require manually picked seed points or prior structural restoration, it does not rely on interpretive experience or geologic knowledge. The proposed method is applied on different real and complex seismic images, with two case examples from the southwestern Barents Sea, and one on the open source Netherlands F3 seismic data

    The influence of birth weight and length on bone mineral density and content in adolescence: The Tromsø Study, Fit Futures

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    This is the author accepted manuscript. The final version is available from Springer via the DOI in this record The influence of birth weight and length on bone mineral parameters in adolescence is unclear. We found a positive association between birth size and bone mineral content, attenuated by lifestyle factors. This highlights the impact of environmental stimuli and lifestyle during growth. PURPOSE: The influence of birth weight and length on bone mineral density and content later in life is unclear, especially in adolescence. This study evaluated the impact of birth weight and length on bone mineral density and content among adolescents. METHODS: We included 961 participants from the population-based Fit Futures study (2010-2011). Dual-energy X-ray absorptiometry (DXA) was used to measure bone mineral density (BMD) and bone mineral content (BMC) at femoral neck (FN), total hip (TH) and total body (TB). BMD and BMC measures were linked with birth weight and length ascertained from the Medical Birth Registry of Norway. Linear regression models were used to investigate the influence of birth parameters on BMD and BMC. RESULTS: Birth weight was positively associated with BMD-TB and BMC at all sites among girls; standardized β coefficients [95% CI] were 0.11 [0.01, 0.20] for BMD-TB and 0.15 [0.06, 0.24], 0.18 [0.09, 0.28] and 0.29 [0.20, 0.38] for BMC-FN, TH and TB, respectively. In boys, birth weight was positively associated with BMC at all sites with estimates of 0.10 [0.01, 0.19], 0.12 [0.03, 0.21] and 0.15 [0.07, 0.24] for FN, TH and TB, respectively. Corresponding analyses using birth length as exposure gave significantly positive associations with BMC at all sites in both sexes. The significant positive association between birth weight and BMC-TB in girls, and birth length and BMC-TB in boys remained after multivariable adjustment. CONCLUSIONS: We found a positive association between birth size and BMC in adolescence. However, this association was attenuated after adjustment for weight, height and physical activity during adolescence.Northern Norway Regional Health Authoritie
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