Superswelling Microneedle Arrays for Dermal Interstitial Fluid (Prote)Omics

The noninvasive sampling of dermal interstitial fluid (ISF) for the monitoring of clinical biomarkers is a greatly appealing area of research. The identification of molecular biomarkers in biological fluids has been accelerated with -omics analyses but remains limited in ISF because of its time-consuming and complex extraction process. Here, the generation of microneedle (MN) patches made of superabsorbent acrylate-based hydrogels for the rapid sampling of dermal ISF is described to explore its proteome. In depth, iterative optimization allows the identification of novel acrylate-based compositions with the required chemical, mechanical, and biocompatibility properties allowing proteomic analysis of the extracted ISF for the first time after sampling with swelling MNs. The generated MN arrays show no cytotoxic effect, successfully cross the stratum corneum, and can collect up to 6 µL of dermal ISF in 10 min in vivo. Proteomics lead to the detection of 176 clinically relevant biomarkers in the collected samples validating the use of ISF as a relevant bodily fluid for disease monitoring and diagnostic. Importantly, it is discovered that extraction fingerprint is strongly dependent on the MNs chemistry, and thus specific biomarkers could be selectively extracted by tuning the composition of the patch, making the system versatile and specific.     

Quantitative Proteomic Approach Reveals Altered Metabolic Pathways in Response to the Inhibition of Lysine Deacetylases in A549 Cells under Normoxia and Hypoxia

Growing evidence is showing that acetylation plays an essential role in cancer, but studies on the impact of KDAC inhibition (KDACi) on the metabolic profile are still in their infancy. Here, we analyzed, by using an iTRAQ-based quantitative proteomics approach, the changes in the proteome of KRAS-mutated non-small cell lung cancer (NSCLC) A549 cells in response to trichostatin-A (TSA) and nicotinamide (NAM) under normoxia and hypoxia. Part of this response was further validated by molecular and biochemical analyses and correlated with the proliferation rates, apoptotic cell death, and activation of ROS scavenging mechanisms in opposition to the ROS production. Despite the differences among the KDAC inhibitors, up-regulation of glycolysis, TCA cycle, oxidative phosphorylation and fatty acid synthesis emerged as a common metabolic response underlying KDACi. We also observed that some of the KDACi effects at metabolic levels are enhanced under hypoxia. Furthermore, we used a drug repositioning machine learning approach to list candidate metabolic therapeutic agents for KRAS mutated NSCLC. Together, these results allow us to better understand the metabolic regulations underlying KDACi in NSCLC, taking into account the microenvironment of tumors related to hypoxia, and bring new insights for the future rational design of new therapies.     

Organizational determinants of IT adoption in the pharmaceutical distribution sector

The aim of this paper is to propose new organizational factors that might explain the differences in the extent and the speed of IT adoption. With this in mind, we carried out an analysis of 16 cases in the pharmaceutical distribution sector in Spain. The results indicate that there are certain intangible assets that favour the introduction and development of IT. Among these are a frank and fluid communication between departments and members of the organization, low levels of conflict, the explicit support of top management towards IT adoption and learning and creative skills of IT-staff. In addition to these factors, we found others that we propose as catalysts of IT adoption. Among these we might mention the special relationship between the member-clients and the company in the case of cooperative firms.     

Adsorption and decomposition of H2S on Pd(1 1 1) surface: a first-principles study

Gradient-corrected density functional theory was used to investigate the adsorption of H₂S on Pd(1 1 1) surface. Molecular adsorption was found to be stable with H₂S binding preferentially at top sites. In addition, the adsorption of other S moieties (SH and S) was investigated. SH and S were found to be preferentially bind at the bridge and fcc sites, respectively. The reaction pathways and energy profiles for H₂S decomposition giving rise to adsorbed S and H were determined. Both H₂S_(ad) → SH_(ad) + H_(ad) and SH_(ad) → S_(ad) + H_(ad) reactions were found to have low barriers and high exothermicities. This reveals that the decomposition of H₂S on Pd(1 1 1) surface is a facile process.     

The Gender Congruency Effect and the Selection of Freestanding and Bound Morphemes: Evidence From Croatian.

The authors report 3 picture-word interference experiments in which they explore some properties of the agreement process in speech production. In Experiment 1, Croatian speakers were asked to produce utterances in which the noun's gender value had an impact on the selection of gender-marked freestanding morphemes (pronouns) while ignoring the presentation of same- or different-gender distractor words. In Experiments 2 and 3, Croatian speakers were asked to name the same pictures using noun phrases in which the noun's gender value surfaced as an inflectional suffix. Different-gender distractors interfered more than same-gender distractors (the gender congruency effect) in Experiment 1, but not in Experiments 2 and 3. These contrasting results show that the cause of the gender congruency effect is not at the level where lexical-grammatical information is selected but at the level of selection of freestanding morphemes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

When more is less: A counterintuitive effect of distractor frequency in the picture-word interference paradigm.

Pictures were shown with superimposed word distractors of high and low frequency. Low-frequency distractors produced greater interference on picture naming than did high-frequency distractors. This distractor frequency effect was not affected by manipulations that facilitated or hindered distractor recognition. Interference was reduced for distractors that were read aloud several times prior to being shown in the picture-naming task. Together these findings suggest that the distractor frequency effect has its locus at some stage of lexical access for production. Other findings further constrain hypotheses about which level of speech production is involved in the effect. The distractor frequency effect has implications for models of lexical processing in speaking as well as for accounts of picture-word interference and the frequency effect. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Urodynamic picture in high spinal cord ischemia, induced by addictive use of cocaine. Report of a case

Since in vitro experiments had excluded interactions between Fe-gluconate (Fe-gluc) and magnesium-L-aspartate hydrochloride (MAH) in aqueous solutions the present in vivo studies seemed to be justified. Animal studies: Rats were kept on magnesium-(Mg)- and iron-(Fe)- sufficient and deficient diets. The intragastral administration of Fe-gluc significantly increased plasma Fe after 3 h, either given alone, or in combination with MAH (inducing hypermagnesemia). Same results were obtained when fortified diets were offered to Fe/Mg-deficient animals. Human studies: The combination of Fe-gluc (2 x 50 mg Fe per day, per os) plus MAH (2 x 7.5 mmol Mg per day, p.o.) was well tolerated by healthy volunteers. Single dose experiments revealed that Fe-gluc alone and in combination with MAH increased plasma Fe levels during 3 h to the same extent. Two groups of pregnant women with moderately reduced hemoglobin levels either received Fe-gluc (out-patients) or its combination with MAH (at least temporarily hospitalised because of preterm labor). Treatments were well tolerated. Hemoglobin levels did not further decrease, as expected without Fe supplements, during the course of pregnancy, thus indicating the therapeutic availability of the electrolytes in both study groups. Progesterone-induced constipation is frequently observed during pregnancy; hence stool softening reported by 50% of the women receiving Fe-gluc plus MAH (versus 33% in the Fe-gluc group) can be regarded as desirable effect. It is concluded that MAH does not interfere with the enteral absorption of Fe-gluc when both electrolytes are orally administered together. Taking both electrolytes together instead of 2 to 3 h apart from each other, as actually recommended, means a less complicated dosage regimen and probably improves compliance.     

New species of Aeromonas isolated in Cuba

One hundred and fifty-five strains of Aeromonas isolated in the stools of children under 5 years presenting with acute diarrheal disease were studied. Using the Aerokey II system for the identification of species, 47 strains were identified as Aeromonas caviae, 58 as Aeromonas hydrophila, 23 as Aeromonas veronii biovar sobria, 14 as Aeromonas trota, 9 as Aeromonas veronii biovar veronii, 2 as Aeromonas jandaei and 2 as Aeromonas shubertii, Emphasis is placed on the advantages of this method which allowed for the classification of new species not identified previously in our country.     

Development of an RVE using a DEM–FEM scheme under modified approximate periodic boundary condition to estimate the elastic mechanical properties of open foams

Engineering with Computers - In this article, a methodology based on Discrete Element Method (DEM) and Finite Elements Method (FEM) combined with modified Approximate Periodic Boundary Condition...