True-scale biomimetic multi-generation airway platforms of the human bronchial epithelium for in vitro cytotoxicity screening

Lung exposure to inhaled particulate matter may injure the epithelial tissue and lead to a loss of function in affected regions via inflammation for example. Screening for the critical contaminate concentrations may provide essential information towards damage assessment and epithelial healing. To date, most approaches have typically relied on traditional in vitro well plate assays or alternatively in vivo animal experiments. Yet, such methods manifest some outstanding disadvantages such as the inability to capture physiological flow and aerosol deposition characteristics as well as significant differences in anatomy, immune system and inflammatory responses compared to humans. The advent of organ-on-chip platforms has shown promising results to reconcile many such drawbacks. In an attempt to provide an attractive in vitro gateway to monitor airway health, we discuss here a novel biomimetic platform which emulates the bronchial epithelium of a human upper airway, allowing to study organ-level characteristics in a homeostatic cellular microenvironment. This device reconstitutes a multi-generation pulmonary epithelial airway environment, capturing realistic respiratory transport phenomena and critical cellular barrier functions at an air-liquid interface (ALI), in analogy to the bronchial lumen. As a proof of concept, we demonstrate its feasibility for in vitro based assays by exposing the device to cytotoxic aerosolized particles under respiratory flow conditions. Subsequently, we investigate the cytotoxic effects of these particles including cellular viability, cytokine and mucus secretion as a function of local particle deposition patterns. Ultimately, our bronchial airway models are intended to provide off-the-shelf in vitro kits geared for the end-user interested in a wide range of broader biological assays that may be attractive for cytotoxicity and drug screening. Please click Additional Files below to see the full abstract

Electroconductive Hydrogel Based on Functional Poly(Ethylenedioxy Thiophene).

Poly(ethylene dioxythiophene) with functional pendant groups bearing double bonds is synthesized and employed for the fabrication of electroactive hydrogels with advantageous characteristics: covalently cross-linked porous 3D scaffolds with notable swelling ratio, appropriate mechanical properties, electroactivity in physiological conditions, and suitability for proliferation and differentiation of C2C12 cells. This is a new approach for the fabrication of conductive engineered constructs

An exploratory study of the relationship between four candidate genes and neurocognitive performance in adult ADHD

Since neurocognitive performance is a possible endophenotype for Attention Deficit Hyperactivity Disorder (ADHD) we explored the relationship between four genetic polymorphisms and neurocognitive performance in adults with ADHD. We genotyped a sample of 45 adults with ADHD at four candidate polymorphisms for the disorder (DRD4 48 base pair (bp) repeat, DRD4 120 bp duplicated repeat, SLC6A3 (DAT1) 40 bp variable number of tandem repeats (VNTR), and COMT Val158Met). We then sub-grouped the sample for each polymorphism by genotype or by the presence of the (putative) ADHD risk allele and compared the performance of the subgroups on a large battery of neurocognitive tests. The COMT Val158Met polymorphism was related to differences in IQ and reaction time, both of the DRD4 polymorphisms (48 bp repeat and 120 bp duplication) showed an association with verbal memory skills, and the SLC6A3 40 bp VNTR polymorphism could be linked to differences in inhibition. Interestingly, the presence of the risk alleles in DRD4 and SLC6A3 was related to better cognitive performance. Our findings contribute to an improved understanding of the functional implications of risk genes for ADHD

Impaired executive function in male MDMA ("ecsatsy") users.

Rationale: Long-term users of ecstasy have shown impaired performance on a multitude of cognitive abilities (most notably memory, attention, executive function). Research into the pattern of MDMA effects on executive functions remains fragmented, however. Objectives: To determine more systematically what aspects of executive function are affected by a history of MDMA use, by using a model that divides executive functions into cognitive flexibility, information updating and monitoring, and inhibition of pre-potent responses. Methods: MDMA users and controls who abstained from ecstasy and other substances for at least 2 weeks were tested with a computerized cognitive test battery to assess their abilities on tasks that measure the three submodalities of executive function, and their combined contribution on two more complex executive tasks. Because of sex-differential effects of MDMA reported in the literature, data from males and females were analyzed separately. Results: Male MDMA users performed significantly worse on the tasks that tap on cognitive flexibility and on the combined executive function tasks; no differences were found on the other cognitive tasks. Female users showed no impairments on any of the tasks. Conclusions: The present data suggest that a history of MDMA use selectively impairs executive function. In male users, cognitive flexibility was impaired and increased perseverative behavior was observed. The inability to adjust behavior rapidly and flexibly may have repercussions for daily life activities

On exact solutions for quantum particles with spin S= 0, 1/2, 1 and de Sitter event horizon

Exact wave solutions for particles with spin 0, 1/2 and 1 in the static coordinates of the de Sitter space-time model are examined in detail. Firstly, for a scalar particle, two pairs of linearly independent solutions are specified explicitly: running and standing waves. A known algorithm for calculation of the reflection coefficient $R_{\epsilon j}$ on the background of the de Sitter space-time model is analyzed. It is shown that the determination of R_{\epsilon j} requires an additional constrain on quantum numbers \epsilon \rho / \hbar c >> j, where \rho is a curvature radius. When taken into account of this condition, the R_{\epsilon j} vanishes identically. It is claimed that the calculation of the reflection coefficient R_{\epsilon j} is not required at all because there is no barrier in an effective potential curve on the background of the de Sitter space-time. The same conclusion holds for arbitrary particles with higher spins, it is demonstrated explicitly with the help of exact solutions for electromagnetic and Dirac fields.Comment: 30 pages. This paper is an updated and more comprehensive version of the old paper V.M. Red'kov. On Particle penetrating through de Sitter horizon. Minsk (1991) 22 pages Deposited in VINITI 30.09.91, 3842 - B9

Predicting hippocampal atrophy in a sample of non-demented older adults at increased risk for Alzheimer\u27s disease with two novel memory transfer tests

Hippocampal atrophy (HA) in non-demented older adults presents as an increased risk for the development of Alzheimer\u27s disease (AD), thus early detection of HA will facilitate clinical and research endeavors. This study examined whether HA in non-demented older adults would affect performance on two experimental memory transfer tests. Forty non-demented, healthy, older adults (mean age 69.58 years, SD = 8.28) were administered a transitive inference test, an acquired equivalence test, and a paragraph recall test. Qualitative ratings of hippocampal atrophy were based on magnetic resonance images, and participants were grouped as HA− or HA+. As hypothesized, the HA− and HA+ groups performed equally well on the initial learning phases of the two experimental memory tests. However, on the transfer phases of the experimental tests, the hypothesized between-group effects were not seen. There were also no significant effects of HA group on the paragraph recall test. Unplanned analyses of females\u27 performance on the transitive inference tests revealed a significant effect of HA on transitive probe errors but not on non-transitive probe errors. A differential vulnerability to hippocampal atrophy in females is hypothesized, though the current study lacks statistical power to fully understand this issue

A case of legionella pneumonia caused by home use of continuous positive airway pressure

A 67-year-old woman with morbid obesity and severe obstructive sleep apnea presented to the emergency department with 2 days of productive cough, fever, shortness of breath and loose stools. A chest x-ray showed extensive bilateral infiltrates, and she was quickly intubated for acute hypoxic respiratory failure. A urine legionella antigen test was positive, and she was admitted to the intensive care unit with a diagnosis of severe legionella pneumonia. She improved over the next week with a course of levofloxacin. Once improved, the state health department visited her home and interviewed her husband and determined that she had not been cleaning her continuous positive pressure mask, tubing and humidifier appropriately. They concluded that the legionella likely came from her continuous positive airway pressure equipment. Cases of legionella pneumonia have frequently been reported through infected water supplies and even respiratory equipment. It is crucial that the mask and tubing used with these devices are cleaned appropriately to minimize the risk of infection