P2X7 regulates ependymo-radial glial cell proliferation in adult Danio rerio following spinal cord injury.

In contrast to mammals, zebrafish undergo successful neural regeneration following spinal cord injury. Spinal cord ependymo-radial glia (ERG) undergo injury-induced proliferation and neuronal differentiation to replace damaged cells and restore motor function. However, the molecular cues driving these processes remain elusive. Here, we demonstrate that the evolutionarily conserved P2X7 receptors are widely distributed on neurons and ERG within the zebrafish spinal cord. At the protein level, the P2X7 receptor expressed in zebrafish is a truncated splice variant of the full-length variant found in mammals. The protein expression of this 50 kDa isoform was significantly downregulated at 7 days post-injury (dpi) but returned to basal levels at 14 dpi when compared to naïve controls. Pharmacological activation of P2X7 following SCI resulted in a greater number of proliferating cells around the central canal by 7 dpi but did not affect neuronal differentiation at 14 dpi. Our findings suggest that unlike in mammals, P2X7 signaling may not play a maladaptive role following SCI in adult zebrafish and may also work to curb the proliferative response of ERG following injury.

Design and rationale of re-energize fontan: Randomized exercise intervention designed to maximize fitness in fontan patients.

In this manuscript, we describe the design and rationale of a randomized controlled trial in pediatric Fontan patients to test the hypothesis that a live-video-supervised exercise (aerobic+resistance) intervention will improve cardiac and physical capacity; muscle mass, strength, and function; and endothelial function. Survival of children with single ventricles beyond the neonatal period has increased dramatically with the staged Fontan palliation. Yet, long-term morbidity remains high. By age 40, 50% of Fontan patients will have died or undergone heart transplantation. Factors that contribute to onset and progression of heart failure in Fontan patients remain incompletely understood. However, it is established that Fontan patients have poor exercise capacity which is associated with a greater risk of morbidity and mortality. Furthermore, decreased muscle mass, abnormal muscle function, and endothelial dysfunction in this patient population is known to contribute to disease progression. In adult patients with 2 ventricles and heart failure, reduced exercise capacity, muscle mass, and muscle strength are powerful predictors of poor outcomes, and exercise interventions can not only improve exercise capacity and muscle mass, but also reverse endothelial dysfunction. Despite these known benefits of exercise, pediatric Fontan patients do not exercise routinely due to their chronic condition, perceived restrictions to exercise, and parental overprotection. Limited exercise interventions in children with congenital heart disease have demonstrated that exercise is safe and effective; however, these studies have been conducted in small, heterogeneous groups, and most had few Fontan patients. Critically, adherence is a major limitation in pediatric exercise interventions delivered on-site, with adherence rates as low as 10%, due to distance from site, transportation difficulties, and missed school or workdays. To overcome these challenges, we utilize live-video conferencing to deliver the supervised exercise sessions. Our multidisciplinary team of experts will assess the effectiveness of a live-video-supervised exercise intervention, rigorously designed to maximize adherence, and improve key and novel measures of health in pediatric Fontan patients associated with poor long-term outcomes. Our ultimate goal is the translation of this model to clinical application as an "exercise prescription" to intervene early in pediatric Fontan patients and decrease long-term morbidity and mortality.

Digital games for type 1 and type 2 diabetes: underpinning theory with three illustrative examples.

Digital games are an important class of eHealth interventions in diabetes, made possible by the Internet and a good range of affordable mobile devices (eg, mobile phones and tablets) available to consumers these days. Gamifying disease management can help children, adolescents, and adults with diabetes to better cope with their lifelong condition. Gamification and social in-game components are used to motivate players/patients and positively change their behavior and lifestyle. In this paper, we start by presenting the main challenges facing people with diabetes-children/adolescents and adults-from a clinical perspective, followed by three short illustrative examples of mobile and desktop game apps and platforms designed by Ayogo Health, Inc. (Vancouver, BC, Canada) for type 1 diabetes (one example) and type 2 diabetes (two examples). The games target different age groups with different needs-children with type 1 diabetes versus adults with type 2 diabetes. The paper is not meant to be an exhaustive review of all digital game offerings available for people with type 1 and type 2 diabetes, but rather to serve as a taster of a few of the game genres on offer today for both types of diabetes, with a brief discussion of (1) some of the underpinning psychological mechanisms of gamified digital interventions and platforms as self-management adherence tools, and more, in diabetes, and (2) some of the hypothesized potential benefits that might be gained from their routine use by people with diabetes. More research evidence from full-scale evaluation studies is needed and expected in the near future that will quantify, qualify, and establish the evidence base concerning this gamification potential, such as what works in each age group/patient type, what does not, and under which settings and criteria.

Scalable antifouling reverse osmosis membranes utilizing perfluorophenyl azide photochemistry.

We present a method to produce anti-fouling reverse osmosis (RO) membranes that maintains the process and scalability of current RO membrane manufacturing. Utilizing perfluorophenyl azide (PFPA) photochemistry, commercial reverse osmosis membranes were dipped into an aqueous solution containing PFPA-terminated poly(ethyleneglycol) species and then exposed to ultraviolet light under ambient conditions, a process that can easily be adapted to a roll-to-roll process. Successful covalent modification of commercial reverse osmosis membranes was confirmed with attenuated total reflectance infrared spectroscopy and contact angle measurements. By employing X-ray photoelectron spectroscopy, it was determined that PFPAs undergo UV-generated nitrene addition and bind to the membrane through an aziridine linkage. After modification with the PFPA-PEG derivatives, the reverse osmosis membranes exhibit high fouling-resistance.

Bacteria-polymeric membrane interactions: atomic force microscopy and XDLVO predictions.

Atomic force microscopy (AFM) in conjunction with a bioprobe developed using a polydopamine wet adhesive was used to directly measure the adhesive force between bacteria and different polymeric membrane surfaces. Bacterial cells of Pseudomonas putida and Bacillus subtilis were immobilized onto the tip of a standard AFM cantilever, and force measurements made using the modified cantilever on various membranes. Interaction forces measured with the bacterial probe were compared, qualitatively, to predictions by the extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory with steric interactions included. The XDLVO theory predicted attractive interactions between low energy hydrophobic membranes with high energy hydrophilic bacterium (P. putida). It also predicted a shallow primary maximum with the most hydrophilic bacterium, B. subtilis . Discrepancies between predictions using the XDLVO theory and theory require involvement of factors such as bridging effects. Differences in interaction between P. putida and B. subtilis are attributed to acid-base interactions and steric interactions. P. putida is Gram negative with lipopolysaccharides present in the outer cell membrane. A variation in forces of adhesion for bacteria on polymeric membranes studied was interpreted in terms of hydrophilicity and interfacial surface potential calculated from physicochemical properties.

MCL1 is deregulated in subgroups of diffuse large B-cell lymphoma.

Myeloid cell leukemia-1 (MCL1) is an anti-apoptotic member of the BCL2 family that is deregulated in various solid and hematological malignancies. However, its role in the molecular pathogenesis of diffuse large B-cell lymphoma (DLBCL) is unclear. We analyzed gene expression profiling data from 350 DLBCL patient samples and detected that activated B-cell-like (ABC) DLBCLs express MCL1 at significantly higher levels compared with germinal center B-cell-like DLBCL patient samples (P=2.7 × 10(-10)). Immunohistochemistry confirmed high MCL1 protein expression predominantly in ABC DLBCL in an independent patient cohort (n=249; P=0.001). To elucidate molecular mechanisms leading to aberrant MCL1 expression, we analyzed array comparative genomic hybridization data of 203 DLBCL samples and identified recurrent chromosomal gains/amplifications of the MCL1 locus that occurred in 26% of ABC DLBCLs. In addition, aberrant STAT3 signaling contributed to high MCL1 expression in this subtype. Knockdown of MCL1 as well as treatment with the BH3-mimetic obatoclax induced apoptotic cell death in MCL1-positive DLBCL cell lines. In summary, MCL1 is deregulated in a significant fraction of ABC DLBCLs and contributes to therapy resistance. These data suggest that specific inhibition of MCL1 might be utilized therapeutically in a subset of DLBCLs.

Improved antifouling properties of polymer membranes using a 'layer-by-layer' mediated method.

Polymeric reverse osmosis membranes were modified with antifouling polymer brushes through a 'layer by layer' (LBL) mediated method. Based on pure physical electrostatic interaction, the attachment of LBL films did not alter separation performance of the membranes. In addition, the incorporation of an LBL film also helped to amplify the number of potential reaction sites on the membrane surfaces for attachment of antifouling polymer brushes, which were then attached to the surface. Attachment of the brushes included two different approaches, grafting to and grafting from. Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS) and water contact angle measurements showed successful growth of the LBL films and subsequently the polymer brushes. Using this method to modify reverse osmosis membranes, preliminary performance testing showed the antifouling properties of the as-modified membranes were much better than the virgin membrane with no significant loss in water flux and salt rejection.

Impacts of Operating Conditions and Solution Chemistry on Osmotic Membrane Structure and Performance.

Herein, we report on changes in the performance of a commercial cellulose triacetate (CTA) membrane, imparted by varied operating conditions and solution chemistries. Changes to feed and draw solution flow rate did not significantly alter the CTA membrane's water permeability, salt permeability, or membrane structural parameter when operated with the membrane skin layer facing the draw solution (PRO-mode). However, water and salt permeability increased with increasing feed or draw solution temperature, while the membrane structural parameter decreased with increasing draw solution, possibly due to changes in polymer intermolecular interactions. High ionic strength draw solutions may de-swell the CTA membrane via charge neutralization, which resulted in lower water permeability, higher salt permeability, and lower structural parameter. This observed trend was further exacerbated by the presence of divalent cations which tends to swell the polymer to a greater extent. Finally, the calculated CTA membrane's structural parameter was lower and less sensitive to external factors when operated in PRO-mode, but highly sensitive to the same factors when the skin layer faced the feed solution (FO-mode), presumably due to swelling/de-swelling of the saturated porous substructure by the draw solution. This is a first attempt aimed at systematically evaluating the changes in performance of the CTA membrane due to operating conditions and solution chemistry, shedding new insight into the possible advantages and disadvantages of this material in certain applications.