Domain and Geometry Agnostic CNNs for Left Atrium Segmentation in 3D Ultrasound

Segmentation of the left atrium and deriving its size can help to predict and detect various cardiovascular conditions. Automation of this process in 3D Ultrasound image data is desirable, since manual delineations are time-consuming, challenging and observer-dependent. Convolutional neural networks have made improvements in computer vision and in medical image analysis. They have successfully been applied to segmentation tasks and were extended to work on volumetric data. In this paper we introduce a combined deep-learning based approach on volumetric segmentation in Ultrasound acquisitions with incorporation of prior knowledge about left atrial shape and imaging device. The results show, that including a shape prior helps the domain adaptation and the accuracy of segmentation is further increased with adversarial learning

Focal Malignant Liver Lesions: Diagnosis by Dynamic Incremental CT, Early Phase

The purpose of our study was to evaluate the accuracy of dynamic incremental bolus-enhanced conventional CT (DICT) with intravenous contrast administration, early phase, in the diagnosis of malignancy of focal liver lesions. A total of 122 lesions were selected in 74 patients considering the following criteria: lesion diameter 10 mm or more, number of lesions less than six per study, except in multiple angiomatosis and the existence of a valid criteria of definitive diagnosis. Lesions were categorized into seven levels of diagnostic confidence of malignancy compared with the definitive diagnosis for acquisition of a receiver-operator-characteristic (ROC) curve analysis and to determine the sensitivity and specificity of the technique. Forty-six and 70 lesions were correctly diagnosed as malignant and benign, respectively; there were 2 false-positive and 4 false-negative diagnoses of malignancy and the sensitivity and specificity obtained were 92 and 97%. The DICT early phase was confirmed as a highly accurate method in the characterization and diagnosis of malignancy of focal liver lesions, requiring an optimal technical performance and judicious analysis of existing semiological data

Genetically engineered-MSC therapies for non-unions, delayed unions and critical-size bone defects

The normal bone regeneration process is a complex and coordinated series of events involving different cell types and molecules. However, this process is impaired in critical-size/large bone defects, with non-unions or delayed unions remaining a major clinical problem. Novel strategies are needed to aid the current therapeutic approaches. Mesenchymal stem/stromal cells (MSCs) are able to promote bone regeneration. Their beneficial effects can be improved by modulating the expression levels of specific genes with the purpose of stimulating MSC proliferation, osteogenic differentiation or their immunomodulatory capacity. In this context, the genetic engineering of MSCs is expected to further enhance their pro-regenerative properties and accelerate bone healing. Herein, we review the most promising molecular candidates (protein-coding and non-coding transcripts) and discuss the different methodologies to engineer and deliver MSCs, mainly focusing on in vivo animal studies. Considering the potential of the MSC secretome for bone repair, this topic has also been addressed. Furthermore, the promising results of clinical studies using MSC for bone regeneration are discussed. Finally, we debate the advantages and limitations of using MSCs, or genetically-engineered MSCs, and their potential as promoters of bone fracture regeneration/repair.This project is supported by Fundação para a Ciência e a Tecnologia (FCT)—in the framework of the project POCI-01-0145-FEDER-031402-R2Bone, under the PORTUGAL 2020 Partnership Agreement, through ERDF, co-funded by FEDER/FNR, and national funding (through FCT – Fundação para a Ciência e a Tecnologia, I.P., provided by the contract-program and according to numbers 4, 5 and 6 of art. 23 of Law No. 57/2016 of 29 August 2016, as amended by Law No. 57/2017 of 19 July 2017). RG, JHT, and MIA are supported by FCT, through the FCT Investigator Program (IF/00638/2014), SFRH/BD/112832/2015, and DL 57/2016/CP1360/CT0008, respectively

Pichia stipitis xylose reductase helps detoxifying lignocellulosic hydrolysate by reducing 5-hydroxymethyl-furfural (HMF)

<p>Abstract</p> <p>Background</p> <p><it>Pichia stipitis </it>xylose reductase (Ps-XR) has been used to design <it>Saccharomyces cerevisiae </it>strains that are able to ferment xylose. One example is the industrial <it>S. cerevisiae </it>xylose-consuming strain TMB3400, which was constructed by expression of <it>P. stipitis </it>xylose reductase and xylitol dehydrogenase and overexpression of endogenous xylulose kinase in the industrial <it>S. cerevisiae </it>strain USM21.</p> <p>Results</p> <p>In this study, we demonstrate that strain TMB3400 not only converts xylose, but also displays higher tolerance to lignocellulosic hydrolysate during anaerobic batch fermentation as well as 3 times higher <it>in vitro </it>HMF and furfural reduction activity than the control strain USM21. Using laboratory strains producing various levels of Ps-XR, we confirm that Ps-XR is able to reduce HMF both <it>in vitro </it>and <it>in vivo</it>. Ps-XR overexpression increases the <it>in vivo </it>HMF conversion rate by approximately 20%, thereby improving yeast tolerance towards HMF. Further purification of Ps-XR shows that HMF is a substrate inhibitor of the enzyme.</p> <p>Conclusion</p> <p>We demonstrate for the first time that xylose reductase is also able to reduce the furaldehyde compounds that are present in undetoxified lignocellulosic hydrolysates. Possible implications of this newly characterized activity of Ps-XR on lignocellulosic hydrolysate fermentation are discussed.</p

Mesenchymal Stromal Cell Secretome: Influencing Therapeutic Potential by Cellular Pre-conditioning

Mesenchymal stromal cells (MSCs) are self-renewing, culture-expandable adult stem cells that have been isolated from a variety of tissues, and possess multipotent differentiation capacity, immunomodulatory properties, and are relatively non-immunogenic. Due to this unique set of characteristics, these cells have attracted great interest in the field of regenerative medicine and have been shown to possess pronounced therapeutic potential in many different pathologies. MSCs' mode of action involves a strong paracrine component resulting from the high levels of bioactive molecules they secrete in response to the local microenvironment. For this reason, MSCs' secretome is currently being explored in several clinical contexts, either using MSC-conditioned media (CM) or purified MSC-derived extracellular vesicles (EVs) to modulate tissue response to a wide array of injuries. Rather than being a constant mixture of molecular factors, MSCs' secretome is known to be dependent on the diverse stimuli present in the microenvironment that MSCs encounter. As such, the composition of the MSCs' secretome can be modulated by preconditioning the MSCs during in vitro culture. This manuscript reviews the existent literature on how preconditioning of MSCs affects the therapeutic potential of their secretome, focusing on MSCs' immunomodulatory and regenerative features, thereby providing new insights for the therapeutic use of MSCs' secretome.We would like to acknowledge Norte Portugal Regional Operational Programme (NORTE 2020) in the framework of the project “Bioengineered Therapies for Infectious Diseases and Tissue Regeneration” (NORTE-01-0145-FEDER-000012). We also acknowledge Fundação para a Ciência e a Tecnologia (FCT) and Fundo Europeu de Desenvolvimento Regional (FEDER) funds through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020-in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). We also acknowledge EUROSPINE TRF for the funded project “Disc Regeneration, Immuno, and Neuro Modulation” , ref. 2017_05 . In addition, JF and RG also acknowledge FCT for funding the BiotechHealth Ph.D. fellowship (PD/BD/135486/2018) and the FCT Investigator Grant (IF/00638/2014), respectively

In vivo Skin Irritation Potential of a Castanea sativa (Chestnut) Leaf Extract, a Putative Natural Antioxidant for Topical Application

Topical application of natural antioxidants has proven to be effective in protecting the skin against ultraviolet-mediated oxidative damage and provides a straightforward way to strengthen the endogenous protection system. However, natural products can provoke skin adverse effects, such as allergic and irritant contact dermatitis. Skin irritation potential of Castanea sativa leaf ethanol:water (7:3) extract was investigated by performing an in vivo patch test in 20 volunteers. Before performing the irritation test, the selection of the solvent and extraction method was guided by the 1,1-diphenyl-2-picryl hydrazyl (DPPH) free radical scavenging test and polyphenols extraction (measured by the Folin Ciocalteu assay). Iron-chelating activity and the phenolic composition (high performance liquid chromatography/diode array detection) were evaluated for the extract obtained under optimized conditions. The extraction method adopted consisted in 5 short extractions (10 min.) with ethanol:water (7:3), performed at 40 degrees. The IC(50) found for the iron chelation and DPPH scavenging assays were 132.94 +/- 9.72 and 12.58 +/- 0.54 microg/ml (mean +/- S.E.M.), respectively. The total phenolic content was found to be 283.8 +/- 8.74 mg GAE/g extract (mean +/- S.E.M.). Five phenolic compounds were identified in the extract, namely, chlorogenic acid, ellagic acid, rutin, isoquercitrin and hyperoside. The patch test carried out showed that, with respect to irritant effects, this extract can be regarded as safe for topical application

Interaction between atypical microorganisms and E. coli in catheter-associated urinary tract biofilms

Most biofilms involved in catheter-associated urinary tract infections (CAUTIs) are polymicrobial, with disease causing (eg Escherichia coli) and atypical microorganisms (eg Delftia tsuruhatensis) frequently inhabiting the same catheter. Nevertheless, there is a lack of knowledge about the role of atypical microorganisms. Here, single and dual-species biofilms consisting of E. coli and atypical bacteria (D. tsuruhatensis and Achromobacter xylosoxidans), were evaluated. All species were good biofilm producers (Log 5.84–7.25 CFU cm−2 at 192 h) in artificial urine. The ability of atypical species to form a biofilm appeared to be hampered by the presence of E. coli. Additionally, when E. coli was added to a pre-formed biofilm of the atypical species, it seemed to take advantage of the first colonizers to accelerate adhesion, even when added at lower concentrations. The results suggest a greater ability of E. coli to form biofilms in conditions mimicking the CAUTIs, whatever the pre-existing microbiota and the inoculum concentration.This work was supported by the Portuguese Science Foundation (FCT), DNA mimics Research Project [Ref. PIC/IC/82815/2007] from the FCT and MCTES; PhD Fellowship [SFRH/BD/82663/2011]; and Postdoctoral Fellowship [SFRH/BPD/74480/2010]. The authors would like to thank to M. Fenice M and A. Steinbuchel for kindly providing the Delftia tsuruhatensis BM90 and Achromobacter xylosoxidans B3 species, respectively