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.     

Ring‐opening polymerization of lactones initiated by diphenylzinc–coinitiator systems

Diphenylzinc, alone or in combination with water and butanone as coinitiators, was used as a polymerization initiator system for a variety of lactones at varying temperatures. The resulting data indicate that the course of the polymerization is greatly influenced by the lactone structure, as well as by the molar ratio of coinitiator to diphenylzinc. When used alone, diphenylzinc exhibited high activity as an initiator in δ‐valerolactone polymerizations, although it was less efficient when used in the β‐butyrolactone and the β‐propiolactone polymerizations. Activity in the polymerization of β‐lactones was increased by adding small amounts of butanone or water. It was also observed that the diphenylzinc–butanone combination was more effective than the diphenylzinc–water mixture in the polymerizations of β‐butyrolactone and β‐propiolactone. Copyright © 2003 Society of Chemical Industry     

Manual dexterity of older Mexican American adults: a cross-sectional pilot experimental investigation

This paper reports results from an experimental pilot study performed to quantify the manual dexterity of older Mexican American adults. The Purdue pegboard test, a two-arm coordination test, and a hand-tool dexterity test were used in this study. To enable cross-sectional comparisons of manual dexterity measures of older Mexican American adults with young Mexican American adults, these tests were administered to 18 older Mexican American adults aged 63–85 (mean age: 71.3 years, SD: 7.0 years), recruited from senior recreation centers in El Paso, and eighteen young adults aged 21–32 (mean age: 25.6 years, SD: 3.8 years) recruited from the student body at the University of Texas at El Paso. For the Purdue pegboard test, the number of pegs placed in 30 s using the preferred hand, the non-preferred hand, and both hands were first individually monitored. Then, scores on an assembly task using the Purdue pegboard were obtained. For the two-arm coordination test, participants were required to trace a star pattern with a stylus using both hands. The time for task completion and the number of errors made during task performance were monitored. For the hand-tool dexterity test, participants were required to use common hand tools and remove nuts and bolts from one side of a wooden upright, and to assemble nuts and bolts in the corresponding holes on the other side of the upright. The time taken for task completion was recorded. Since modified Levene's test showed equality of variances, two sample t-tests, comparing the mean responses of older adults with the mean responses of young adults for each individual test, were conducted. Results indicate that responses for the older adults were statistically significant different (p<0.001) from young adults for all Purdue pegboard tasks. On the average, older adults performed significantly slower (p<0.001) than young adults on the two-arm coordination test, and committed more errors before task completion (p<0.05). Older adults also took longer to complete the hand-tool dexterity task compared to their younger counterparts (p<0.05). In addition to the t-tests, manual dexterity performance measures from older adults were regressed with age to determine the cross-sectional age effects on manual dexterity measures. Results indicate that all Purdue pegboard performance measures were significantly affected by age (p<0.05). The time to complete the two-arm coordination test was significantly linearly related to age (p<0.05). However, the number of errors committed by older adults in the performance of the two-arm coordination test was not significantly linearly related to age. Time to complete the hand-tool dexterity was also significantly linearly related to age (p<0.05). Accommodating age-related changes in manual dexterity is important for job design in industry, especially in industries employing older adults requiring significant assembly and hand-tool use.

Relevance to industry

Given the aging of the industrial workforce, it is important to understand how manual dexterity is affected by age, so that jobs requiring significant manual dexterity for task initiation, task performance and task completion are designed to fit older adult dexterity levels.     

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)     

Interface formed between visceral peritoneum and experimental polypropylene or polytetrafluoroethylene abdominal wall implants

The objective of this work was to study the healing process at the interface between biomaterial and visceral peritoneum. Implants of polytetrafluoroethylene (ePTFE) and polypropylene prostheses were introduced into the abdominal wall of New Zealand rabbits. The behaviour of the biomaterials was analysed using light and scanning electron microscopy and immunohistochemistry in which a specific anti-rabbit macrophage monoclonal antibody (RAM 11) was employed. According to macroscopic observation, there was significantly fewer adhesions prosthesis-viscera to ePTFE than to polypropylene implants. After ePTFE implantation, restoration of the peritoneum took place in an orderly fashion. When polypropylene was used, the peritoneum formed was a disorderly tissue in which small areas of haemorrhage and necrosis could be seen to coincide with the appearance of adhesions. The number of labelled macrophages peaked 14 days after ePTFE or polypropylene implantation, after which it decreased gradually. It is concluded that, given the low rate of adhesion provoked by PTFE, this material is ideal for implants contiguous to the peritoneal cavity viscera. The macrophage response does not determine the use of one material or the other. The structure of the newly formed peritoneum and development of adhesions depends on the porosity of the biomaterial.