Scaling to produce size-independent indices of echocardiographic derived aortic root dimensions in elite Rugby Football League players

The assessment of aortic root dimensions is important in cardiac pre-participation screening. Scaling of cardiac dimensions removes the impact of body size allowing meaningful inter/intra group comparisons. Developing appropriate scaling approaches, scaling variables and extending the application to major vessels is warranted so underlying pathology can be detected and managed appropriately. The study aims to define relationships between aortic root dimensions and body surface area/height. Two hundred and twenty elite Rugby Football League athletes were recruited. All participants completed anthropometric assessments, a 12-lead ECG and echocardiogram. Aortic root was measured at the aortic annulus, sinus of valsalva, sinotubular junction and the proximal ascending aorta. Linear and allometric scaling were performed on the relationship between aortic measurements and body surface area/height. Absolute aortic root measurements fell within normal population data (mean ± standard deviation (range): aortic annulus: 22 ± 2 (17–28) mm, sinus of valsalva: 28 ± 3 (20–38) mm, sinotubular junction: 22 ± 3 (14–33) mm, proximal ascending aorta: 22 ± 3 (15–31) mm). Linear scaling to height produced size-independent indices at all aortic measurement sites (P 0.05). Allometric scaling, using both body surface area and height, produced size-independent indices at all sites (P < 0.05). We recommend linearly scaling aortic root dimensions to height in elite Rugby Football League athletes and discourage the use of body surface area as a linear scaling quantity. Allometric scaling is also effective when using both body surface area and height. © The British Medical Ultrasound Society 2019

Artificial immune systems

The biological immune system is a robust, complex, adaptive system that defends the body from foreign pathogens. It is able to categorize all cells (or molecules) within the body as self or nonself substances. It does this with the help of a distributed task force that has the intelligence to take action from a local and also a global perspective using its network of chemical messengers for communication. There are two major branches of the immune system. The innate immune system is an unchanging mechanism that detects and destroys certain invading organisms, whilst the adaptive immune system responds to previously unknown foreign cells and builds a response to them that can remain in the body over a long period of time. This remarkable information processing biological system has caught the attention of computer science in recent years

Ontology-based, Tissue MicroArray oriented, image centered tissue bank

<p>Abstract</p> <p>Background</p> <p>Tissue MicroArray technique is becoming increasingly important in pathology for the validation of experimental data from transcriptomic analysis. This approach produces many images which need to be properly managed, if possible with an infrastructure able to support tissue sharing between institutes. Moreover, the available frameworks oriented to Tissue MicroArray provide good storage for clinical patient, sample treatment and block construction information, but their utility is limited by the lack of data integration with biomolecular information.</p> <p>Results</p> <p>In this work we propose a Tissue MicroArray web oriented system to support researchers in managing bio-samples and, through the use of ontologies, enables tissue sharing aimed at the design of Tissue MicroArray experiments and results evaluation. Indeed, our system provides ontological description both for pre-analysis tissue images and for post-process analysis image results, which is crucial for information exchange. Moreover, working on well-defined terms it is then possible to query web resources for literature articles to integrate both pathology and bioinformatics data.</p> <p>Conclusions</p> <p>Using this system, users associate an ontology-based description to each image uploaded into the database and also integrate results with the ontological description of biosequences identified in every tissue. Moreover, it is possible to integrate the ontological description provided by the user with a full compliant gene ontology definition, enabling statistical studies about correlation between the analyzed pathology and the most commonly related biological processes.</p

Genetic, environmental and stochastic factors in monozygotic twin discordance with a focus on epigenetic differences

PMCID: PMC3566971This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

An increased fraction of circulating miR-363 and miR-16 is particle bound in patients with chronic lymphocytic leukaemia as compared to normal subjects.

In vitro culture studies have shown that miR-363 is enriched in extracellular vesicles from chronic lymphocytic leukaemia cells. We wondered whether miR-363 was detectable in plasma, which is an essential precondition for further studies to assess its usefulness as a biomarker. Using samples from two clinical trials: one enrolling patients with advanced disease and the other asymptomatic patients with early stage disease, we determined plasma miR-363 levels and secondly investigated the distribution of this miRNA between plasma and particle bound fractions in patients and normal subjects.Advanced disease (n = 95) was associated with higher levels of miR-363 than early stage disease (n = 45) or normal subjects (n = 11) but there was no association with markers of prognosis. The distribution of specific miRNA between particle bound and plasma protein fractions was investigated using size exclusion chromatography on plasma from patients (n = 4) and normal subjects (n = 3). ~ 20% of total miR-16 and miR-363 is particle bound in patients while there was no detectable particle bound material in normal subjects. Our work demonstrates that miR-363 levels are raised in chronic lymphocytic leukaemia patients and raises the possibility that distribution of circulating miRNA between plasma fractions differs in health and disease

Capecitabine and mitomycin C as third-line therapy for patients with metastatic colorectal cancer resistant to fluorouracil and irinotecan

Protracted venous infusion 5-fluorouracil (5FU) combined with mitomycin C (MMC) has demonstrated significant activity against metastatic colorectal cancer. Owing to potential synergy based upon upregulation of thymidine phosphorylase by MMC, the combination of capecitabine and MMC may improve outcomes in irinotecan-refractory disease. Eligible patients with progressive disease during or within 6 months of second-line chemotherapy were treated with capecitabine (1250 mg m−2 twice daily) days 1–14 every 3 weeks and MMC (7 mg m−2 IV bolus) once every 6 weeks. A total of 36 patients were recruited, with a median age of 64 years (range 40–77), and 23 patients (78%) were performance status 0–1. The objective response rate was 15.2%. In all, 48.5% of patients had stable disease. Median failure-free survival was 5.4 months (95% CI 4.6–6.2). Median overall survival was 9.3 months (95% CI: 6.9–11.7). Grade 3 toxicities were palmar-plantar erythema 16.7%, vomiting 8.3%, diarrhoea 2.8%, anaemia 8.3%, and neutropenia 2.8%. No patients developed haemolytic uraemic syndrome. Symptomatic improvement occurred for pain, bowel symptoms, and dyspnoea. Capecitabine in combination with MMC is an effective regimen for metastatic colorectal cancer resistant to 5FU and irinotecan with an acceptable toxicity profile and a convenient administration schedule

Assessing Conservation Values: Biodiversity and Endemicity in Tropical Land Use Systems

Despite an increasing amount of data on the effects of tropical land use on continental forest fauna and flora, it is debatable whether the choice of the indicator variables allows for a proper evaluation of the role of modified habitats in mitigating the global biodiversity crisis. While many single-taxon studies have highlighted that species with narrow geographic ranges especially suffer from habitat modification, there is no multi-taxa study available which consistently focuses on geographic range composition of the studied indicator groups. We compiled geographic range data for 180 bird, 119 butterfly, 204 tree and 219 understorey plant species sampled along a gradient of habitat modification ranging from near-primary forest through young secondary forest and agroforestry systems to annual crops in the southwestern lowlands of Cameroon. We found very similar patterns of declining species richness with increasing habitat modification between taxon-specific groups of similar geographic range categories. At the 8 km2 spatial level, estimated richness of endemic species declined in all groups by 21% (birds) to 91% (trees) from forests to annual crops, while estimated richness of widespread species increased by +101% (trees) to +275% (understorey plants), or remained stable (- 2%, butterflies). Even traditional agroforestry systems lost estimated endemic species richness by - 18% (birds) to - 90% (understorey plants). Endemic species richness of one taxon explained between 37% and 57% of others (positive correlations) and taxon-specific richness in widespread species explained up to 76% of variation in richness of endemic species (negative correlations). The key implication of this study is that the range size aspect is fundamental in assessments of conservation value via species inventory data from modified habitats. The study also suggests that even ecologically friendly agricultural matrices may be of much lower value for tropical conservation than indicated by mere biodiversity value

Decreased expression of the mannose 6- phosphate/insulin-like growth factor-II receptor promotes growth of human breast cancer cells

BACKGROUND: Loss or mutation of the mannose 6-phosphate/insulin-like growth factor-II receptor (M6P/IGF2R) has been found in breast cancer. However, whether or not decreased levels of functional M6P/IGF2R directly contribute to the process of carcinogenesis needs to be further verified by functional studies. METHODS: In this study, using viral and ribozyme strategies we reduced the expression of M6P/IGF2R in human breast cancer cells and then examined the effect on growth and apoptosis of these cells. RESULTS: Our results showed that infection of MCF-7 cells with the adenovirus carrying a ribozyme targeted against the M6P/IGF2R mRNA dramatically reduced the level of transcripts and the functional activity of M6P/IGF2R in these cells. Accordingly, cells treated with the ribozyme exhibited a higher growth rate and a lower apoptotic index than control cells (infected with a control vector). Furthermore, decreased expression of M6P/IGF2R enhanced IGF-II-induced proliferation and reduced cell susceptibility to TNF-induced apoptosis. CONCLUSIONS: These results suggest that M6P/IGF2R functions as a growth suppressor and its loss or mutation may contribute to development and progression of cancer. This study also demonstrates that adenoviral delivery of the ribozyme provides a useful tool for investigating the role of M6P/IGF2R in regulation of cell growth

Identification of Dmrt2a downstream genes during zebrafish early development using a timely controlled approach

This research was supported by FCT (Portugal) grant (PTDC/SAU-BID/119627/2010) given to L.S. L.S. was supported by an IF contract from FCT (Portugal). R.A.P. was supported by a PhD fellowship (SFRH/BD/87607/2012) from FCT (Portugal). Publication was sponsored by LISBOA-01-0145-FEDER-007391, project co-funded by FEDER through POR Lisboa 2020 - Programa Operacional Regional de Lisboa, PORTUGAL 2020 and by Fundacao para a Ciencia e a Tecnologia.BACKGROUND: Dmrt2a is a zinc finger like transcription factor with several roles during zebrafish early development: left-right asymmetry, synchronisation of the somite clock genes and fast muscle differentiation. Despite the described functions, Dmrt2a mechanism of action is unknown. Therefore, with this work, we propose to identify Dmrt2a downstream genes during zebrafish early development. RESULTS: We generated and validated a heat-shock inducible transgenic line, to timely control dmrt2a overexpression, and dmrt2a mutant lines. We characterised dmrt2a overexpression phenotype and verified that it was very similar to the one described after knockdown of this gene, with left-right asymmetry defects and desynchronisation of somite clock genes. Additionally, we identified a new phenotype of somite border malformation. We generated several dmrt2a mutant lines, but we only detected a weak to negligible phenotype. As dmrt2a has a paralog gene, dmrt2b, with similar functions and expression pattern, we evaluated the possibility of redundancy. We found that dmrt2b does not seem to compensate the lack of dmrt2a. Furthermore, we took advantage of one of our mutant lines to confirm dmrt2a morpholino specificity, which was previously shown to be a robust knockdown tool in two independent studies. Using the described genetic tools to perform and validate a microarray, we were able to identify six genes downstream of Dmrt2a: foxj1b, pxdc1b, cxcl12b, etv2, foxc1b and cyp1a. CONCLUSIONS: In this work, we generated and validated several genetic tools for dmrt2a and identified six genes downstream of this transcription factor. The identified genes will be crucial to the future understanding of Dmrt2a mechanism of action in zebrafish.publishersversionpublishe

Fusion between Leishmania amazonensis and Leishmania major Parasitophorous Vacuoles: Live Imaging of Coinfected Macrophages

Protozoan parasites of the genus Leishmania alternate between flagellated, elongated extracellular promastigotes found in insect vectors, and round-shaped amastigotes enclosed in phagolysosome-like Parasitophorous Vacuoles (PVs) of infected mammalian host cells. Leishmania amazonensis amastigotes occupy large PVs which may contain many parasites; in contrast, single amastigotes of Leishmania major lodge in small, tight PVs, which undergo fission as parasites divide. To determine if PVs of these Leishmania species can fuse with each other, mouse macrophages in culture were infected with non-fluorescent L. amazonensis amastigotes and, 48 h later, superinfected with fluorescent L. major amastigotes or promastigotes. Fusion was investigated by time-lapse image acquisition of living cells and inferred from the colocalization of parasites of the two species in the same PVs. Survival, multiplication and differentiation of parasites that did or did not share the same vacuoles were also investigated. Fusion of PVs containing L. amazonensis and L. major amastigotes was not found. However, PVs containing L. major promastigotes did fuse with pre-established L. amazonensis PVs. In these chimeric vacuoles, L. major promastigotes remained motile and multiplied, but did not differentiate into amastigotes. In contrast, in doubly infected cells, within their own, unfused PVs metacyclic-enriched L. major promastigotes, but not log phase promastigotes - which were destroyed - differentiated into proliferating amastigotes. The results indicate that PVs, presumably customized by L. major amastigotes or promastigotes, differ in their ability to fuse with L. amazonensis PVs. Additionally, a species-specific PV was required for L. major destruction or differentiation – a requirement for which mechanisms remain unknown. The observations reported in this paper should be useful in further studies of the interactions between PVs to different species of Leishmania parasites, and of the mechanisms involved in the recognition and fusion of PVs