Quantification of sprouting angiogenesis under the effect of different growth factors involved in the tumor microenvironmen

One of the most important problems in tumor control is the management of metastatic process. Angiogenesis or the formation of new blood vessels from preexisting ones plays a crucial role in the expansion of the tumor by providing oxygen, nutrition and conduits for cancer cells to invade and metastasize new tissues¹. Abnormalities of growth factors (GFs) released such as PDGFs (Platelet Derived Growth Factor) could be involved in malignant human diseases2,3. Inflammation and cancer present similar mechanisms of development including angiogenesis or cell proliferation4. In order to know the effect on sprouting promotion of GFs existent in the tumor environment such as VEGF (Vascular Endothelial Growth Factor), PDGF, BMP2 (Bone Morphogenetic Protein 2) or TGF-ß (Transforming Growth Factor-ß), we have developed a microfluidic-based test based on devices designed by Farahat et al. (2012)5, which allows to the user the quantification of sprouting formation under the effect of these GFs. TGF-ß pathway involved in tumor progression in multiple human cancers, instigates phenotypical changes affecting to the cell growth, differentiation and migration6. Knowing the overexpression of GFs such as VEGF or BMP2 in tumors7,8, we aimed to compare its effect on endothelial cells in angiogenesis. Analyzing the promotion of sprout in normal conditions under GFs addition would be possible to determine which of these molecules could decrease or promote the advance of the endothelial cells. The results obtained in this work indicated that VEGF is the most important factor to enhance the angiogenic process while non-specific factors such as BMP2 or TGF-ß show a low effectiveness. In the case of PDGF, the negative effect of this molecule observed in our assays could be explained by the non-optimal balance of concentration. Furthermore, we are currently working to quantify the effect of fluid flow on the sprouting promotion

Migration of mineral oil aromatic hydrocarbons (MOAH) from cardboard containers to dry food and prediction tool

This research aimed to study the migration of mineral oil aromatic hydrocarbons (MOAH) from primary carton packages to dry foods, using 16 aromatic hydrocarbons as model substances, covering a wide range of molecular masses and chemical structures. Migration experiments were performed using modified polyphenylene oxide as a food simulant and couscous and polenta as dry foods. The migration tests were carried out to simulate storage at room temperature for long periods and in hot food containers as the worst scenario. Multivariate analysis algorithms were applied to correlate and group the migration of model substances, and a partial least squares regression (PLSR) model was built to predict the worst-case migration. The results showed strong correlations in the migration patterns of the model substances, based on their volatility, food matrix, migration time and temperature. Different behaviour between the migration of the most volatile and the heaviest model substances was observed

Mechano-sensing and cell migration: A 3D model approach

Cell migration is essential for tissue development in different physiological and pathological conditions. It is a complex process orchestrated by chemistry, biological factors, microstructure and surrounding mechanical properties. Focusing on the mechanical interactions, cells do not only exert forces on the matrix that surrounds them, but they also sense and react to mechanical cues in a process called mechano-sensing. Here, we hypothesize the involvement of mechano-sensing in the regulation of directional cell migration through a three-dimensional (3D) matrix. For this purpose, we develop a 3D numerical model of individual cell migration, which incorporates the mechano-sensing process of the cell as the main mechanism regulating its movement. Consistent with this hypothesis, we found that factors, such as substrate stiffness, boundary conditions and external forces, regulate specific and distinct cell movements

Evaluation and optimization of the Sysmex UF1000i system for the screening of urinary tract infection in primary health care elderly patients

Objective Urinary tract infections (UTIs) are a common problem in the elderly population. Urine culture is still considered the "gold standard" to diagnose infection in this population. However, urine cultures are laborious and costly, and most samples will yield no growth. Methods An evaluation was made of the Sysmex UF-1000i flow cytometer as a screening tool for UTI in an elderly population older than 65 years who lived in the community, using 346 urine samples submitted for culture. Results The Receiver Operating Characteristic (ROC) analysis showed a significant difference (P < 0.01) between 0.98 bacteria area under the curve value and 0.82 of white blood cells (WBC). The combination of both counts for screening did not show any improvement in specificity or sensitivity. According to our data, the use of a single cut-off point of 200 bacteria/μL is suggested, in which the sensitivity and specificity were 99.11% and 91.59%, respectively, with a NPV of 99.49%. Moreover, this cut-off value could avoid 60.24% of the samples to be cultured, with a minimal false negative results rate of 0.87%. Conclusions The stratification of age groups stratification helps in selecting a more adjusted Sysmex UF1000i cut-off limit, leading to an improvement in the screening parameters that would imply a better management of these infections, as well as a high reduction in the workload and cost savings

Matrix architecture plays a pivotal role in 3D osteoblast migration: The effect of interstitial fluid flow

Osteoblast migration is a crucial process in bone regeneration, which is strongly regulated by interstitial fluid flow. However, the exact role that such flow exerts on osteoblast migration is still unclear. To deepen the understanding of this phenomenon, we cultured human osteoblasts on 3D microfluidic devices under different fluid flow regimes. Our results show that a slow fluid flow rate by itself is not able to alter the 3D migratory patterns of osteoblasts in collagen-based gels but that at higher fluid flow rates (increased flow velocity) may indirectly influence cell movement by altering the collagen microstructure. In fact, we observed that high fluid flow rates (1 µl/min) are able to alter the collagen matrix architecture and to indirectly modulate the migration pattern. However, when these collagen scaffolds were crosslinked with a chemical crosslinker, specifically, transglutaminase II, we did not find significant alterations in the scaffold architecture or in osteoblast movement. Therefore, our data suggest that high interstitial fluid flow rates can regulate osteoblast migration by means of modifying the orientation of collagen fibers. Together, these results highlight the crucial role of the matrix architecture in 3D osteoblast migration. In addition, we show that interstitial fluid flow in conjunction with the matrix architecture regulates the osteoblast morphology in 3D

Gaseous time projection chambers for rare event detection: Results from the T-REX project. II. Dark matter

As part of the T-REX project, a number of R&D and prototyping activities have been carried out during the last years to explore the applicability of Micromegas-read gaseous TPCs in rare event searches like double beta decay (DBD), axion research and low-mass WIMP searches. While in the companion paper we focus on DBD, in this paper we focus on the results regarding the search for dark matter candidates, both axions and WIMPs. Small ultra-low background Micromegas detectors are used to image the x-ray signal expected in axion helioscopes like CAST at CERN. Background levels as low as $0.8\times 10^{-6}$ c keV$^{-1}$cm$^{-2}$s$^{-1}$ have already been achieved in CAST while values down to $\sim10^{-7}$ c keV$^{-1}$cm$^{-2}$s$^{-1}$ have been obtained in a test bench placed underground in the Laboratorio Subterr\'aneo de Canfranc. Prospects to consolidate and further reduce these values down to $\sim10^{-8}$ c keV$^{-1}$cm$^{-2}$s$^{-1}$will be described. Such detectors, placed at the focal point of x-ray telescopes in the future IAXO experiment, would allow for 10$^5$ better signal-to-noise ratio than CAST, and search for solar axions with $g_{a\gamma}$ down to few 10$^{12}$ GeV$^{-1}$, well into unexplored axion parameter space. In addition, a scaled-up version of these TPCs, properly shielded and placed underground, can be competitive in the search for low-mass WIMPs. The TREX-DM prototype, with $\sim$0.300 kg of Ar at 10 bar, or alternatively $\sim$0.160 kg of Ne at 10 bar, and energy threshold well below 1 keV, has been built to test this concept. We will describe the main technical solutions developed, as well as the results from the commissioning phase on surface. The anticipated sensitivity of this technique might reach $\sim10^{-44}$ cm$^2$ for low mass ($<10$ GeV) WIMPs, well beyond current experimental limits in this mass range.Comment: Published in JCAP. New version with erratum incorporated (new figure 14

Pyrethroid bioaccumulation in Mediterranen dolphins

Pyrethroids are organic pollutants with high hydrophobicity used as insecticides. Concern exists about aquatic organisms¿ exposure to their toxicity. They were believed to be converted to non-toxic metabolites in mammals, but our group has detected them in human breast milk and has proved their bioaccumulation in marine mammals and river fish. The present study investigates the occurrence of pyrethroid compounds in liver samples from striped dolphins (Stenella coeruleoalba)and common dolphins (Delphinus delphis) from southern Spain, as the first attempt to determine the occurrence and bioaccumulation and distribution of pyrethroids in marine mammal tissues from the Mediterranean Sea. Samples of dolphin tissue were collected from the Abloran Sea (south of Spain) between 2003 and 2010, including 37 liver samples from striped dolphin and different tissues¿blubber, muscle, liver, brain and kidneys¿from 11 common dolphins. The analytical method monitored 10 pyrethroids, including cypermethrin and detamethrin. For the sample preparation?lyophilized sample was spiked with internal standards, extracted by sonication and underwent a clean-up with alumina and C18 SPE cartridges. Extracts were analysed by GC-NCI-MS/MS. Method recoveries for the pyrethroids ranged 53-116?% and method LODs and LOQs were 0.02-0.46?ng/g and 0.08-1.54?ng/g, respectively. Pyrethroids were detected in 87?% of the striped dolphins and 100?% of the common dolphins, with total concentrations of nd-5,210?ng/g?lw and 69-2,036?ng/g?lw, respectively. These levels were higher than those reported found in dolphins from Brazil (7.0-68?ng/g?lw). Permethrin and tetramethrin were the main contributors to the pyrethroid profiles for all tissues. The samples of striped dolphins where used to observe that bioaccumulation of pyrethroids was unlike that of persistent organic pollutants (POPs), as pyrethroid levels were not correlated to the age of the specimens. Levels slightly increase from calves to juveniles, whereas juveniles present similar levels to adults. Metabolization of pyrethroids after achieving sexual maturity might account for this pattern. Because of the pyrethroids lipophilic behaviour, blubber was the most contaminated tissue and brain showed the lowest levels. Normalizing the data to the lipid content, the highest value was for muscle by far, suggesting a preference for that tissue. SETA

A Micromegas-based low-background x-ray detector coupled to a slumped-glass telescope for axion research

We report on the design, construction and operation of a low background x-ray detection line composed of a shielded Micromegas (micromesh gaseous structure) detector of the microbulk technique. The detector is made from radiopure materials and is placed at the focal point of a $\sim$~5 cm diameter, 1.3 m focal-length, cone-approximation Wolter I x-ray telescope (XRT) comprised of thermally-formed (or "slumped") glass substrates deposited with multilayer coatings. The system has been conceived as a technological pathfinder for the future International Axion Observatory (IAXO), as it combines two of the techniques (optic and detector) proposed in the conceptual design of the project. It is innovative for two reasons: it is the first time an x-ray optic has been designed and fabricated specifically for axion research, and the first time a Micromegas detector has been operated with an x-ray optic. The line has been installed at one end of the CERN Axion Solar Telescope (CAST) magnet and is currently looking for solar axions. The combination of the XRT and Micromegas detector provides the best signal-to-noise ratio obtained so far by any detection system of the CAST experiment with a background rate of 5.4$\times$10$^{-3}\;$counts per hour in the energy region-of-interest and signal spot area.Comment: 21 pages, 16 figure

Surgical treatment of congenital pseudoarthrosis of the clavicle: Our 22-year, single-center experience

Objectives: This study reports the surgical outcomes in a patient cohort with congenital pseudarthrosis of the clavicle (CPC). Patients and methods: A total of nine pediatric patients (5 males, 4 females; mean age: 4.43 years; range, 2 to 12 years) who were diagnosed with CPC and treated surgically with a minimum one-year follow-up between January 1996 and December 2018 were retrospectively analyzed. The patients were divided into two groups according to the fixation method as the Kirschner wire (K-wire; Group A, n=2) or stabilization with a plate (Group B, n=7). The physical function and symptoms were evaluated using the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) scale. Results: The mean age at the time of diagnosis was 2.95 (range, 0 to 12) years. Six cases were atrophic pseudarthrosis and three cases were hypertrophic. Radiographic consolidation occurred in all cases with a mean duration of 103.8±39.1 days, indicating no significant difference between the groups (p>0.05). Complications registered were a K-wire breakage in a patient in Group A and an internal fixation plate loosening in a patient in Group B. The mean postoperative follow-up was 2.98±1.82 years. The QuickDASH score was 0 points in all patients. Conclusion: The early surgical indication based on refreshment of the pseudarthrosis focus, with bone autograft interposition when a failure exists to restore adequate clavicular length, and fixation are reliable alternatives with favorable clinical and radiological results in the mid- and long-term with fewer complications