7-nitroindazole attenuates 6-hydroxydopamine-induced spatial learning deficits and dopamine neuron loss in a presymptomatic animal model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder in which loss of dopaminergic (DA) neurons (>50%) in the substantia nigra (SN) precedes most of the overt motor symptoms, making early diagnosis and treatment interventions difficult. Because PD has been associated with free radicals generated by nitric oxide, this study tested whether treatments of 7-nitroindazole (7NI), a nitric-oxide-synthase inhibitor, could reduce cognitive deficits that often emerge before overt motor symptoms in a presymptomatic rat model of PD. Rats were given intraperitoneal injections of 50 mg/kg 7NI (or vehicle) just before receiving bilateral, intrastriatal injections of the DA-toxin, 6-hydroxydopamine (6-OHDA). The rats were then given a battery of motor tasks, and their learning ability was assessed using a spatial reversal task in a water-T maze. Results indicate that 7NI treatments attenuate 6-OHDA-induced spatial learning deficits and protect against DA cell loss in the SN, suggesting that 7NI may have potential as an early, presymptomatic pharmacotherapy for PD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of antimicrobial use in agricultural animals on drug-resistant foodborne salmonellosis in humans: A systematic literature review

Controversy continues concerning antimicrobial use in food animals and its relationship to drug-resistant infections in humans. We systematically reviewed published literature for evidence of a relationship between antimicrobial use in agricultural animals and drug-resistant meat or dairy-borne non-typhoidal salmonellosis in humans. Based on publications from the United States (U.S.), Canada, and Denmark from January 2010 to July 2014, 858 articles received title and abstract review, 104 met study criteria for full article review with 68 retained for which data are presented. Antibiotic exposure in both cattle and humans found an increased likelihood of Salmonella colonization, whereas in chickens, animals not exposed to antibiotics (organic) were more likely to be Salmonella positive and those that had antibiotic exposure were more likely to harbor antimicrobial resistant Salmonella organisms. In swine literature, only tylosin exposure was examined and no correlation was found among exposure, Salmonella colonization, or antimicrobial resistance. No studies that identified farm antimicrobial use also traced antimicrobial-resistant Salmonella from farm to fork.     

Impact of 100% Fruit Juice Consumption on Diet and Weight Status of Children: An Evidence-based Review

Consumption of 100% fruit juice remains controversial for its potential adverse impact on weight and displacement of essential foods in the diets of children. A systematic review of the literature published from 1995–2013 was conducted using the PubMed database to evaluate associations between intake of 100% fruit juice and weight/adiposity and nutrient intake/adequacy among children of 1 to 18 years of age. Weight status outcome measures included body mass index (BMI), BMI z-score, ponderal index, obesity, weight gain, adiposity measures, and body composition. Nutrient outcome measures included intake and adequacy of shortfall nutrients. Data extraction and analysis was conducted according to the Academy of Nutrition and Dietetics Evidence Analysis Process. Twenty-two studies on weight status provided evidence that did not support an association between 100% fruit juice consumption and weight/adiposity in children after controlling for energy intake. Limited evidence from eight studies suggests that children consuming 100% fruit juice have higher intake and adequacy of dietary fiber, vitamin C, magnesium, and potassium. Differences in methodology and study designs preclude causal determination of 100% fruit juice as sole influencer of weight status or nutrient intake/adequacy of shortfall nutrients. In context of a healthy dietary pattern, evidence suggests that consumption of 100% fruit juice may provide beneficial nutrients without contributing to pediatric obesity.     

Anaerobic biotransformation of tetrabromobisphenol A, tetrachlorobisphenol A, and bisphenol A in estuarine sediments

Biotransformation of the flame retardants tetrabromobisphenol A and tetrachlorobisphenol A, and their ultimate biodehalogenation product, bisphenol A, was examined in anoxic estuarine sediments. Dehalogenation of tetrabromobisphenol A and tetrachlorobisphenol A was examined under conditions promoting either methanogenesis or sulfate reduction as the primary terminal electron-accepting process. Complete dehalogenation of tetrabromobisphenol A to bisphenol A with no further degradation of bisphenol A, was observed under both methanogenic and sulfate-reducing conditions. Dehalogenation of tetrachlorobisphenol A under both methanogenic and sulfate-reducing conditions resulted in the accumulation of a persistent dichlorinated bisphenol A isomer, while no bisphenol A was formed. Co-amendment of sediment enrichments with either 2,6-dibromo- or 2,6-dichlorophenol did not affect the extent of dehalogenation as compared to sediments that were amended only with the flame retardants. Sediment cultures pre-acclimated on 2-bromophenol dehalogenated the flame retardants in a manner similar to that of fresh sediments. No loss of bisphenol A was observed in separate incubations within 162 days under conditions promoting either methanogenesis, sulfate-reduction, iron(III)-reduction, or nitrate-reduction. Furthermore, identical enrichments that readily degraded 4-hydroxybenzoate, a structural analogue of bisphenol A, did not exhibit bisphenol A degradation. The dehalogenation of tetrabromo- and tetrachlorobisphenol A and the potential for accumulation of bisphenol A in anoxic sediments is significant given the widespread use of these chemicals.     

Designing Microgels for Cell Culture and Controlled Assembly of Tissue Microenvironments

Micrometer‐sized hydrogels, termed microgels, are emerging as multifunctional platforms that can recapitulate tissue heterogeneity in engineered cell microenvironments. The microgels can function as either individual cell culture units or can be assembled into larger scaffolds. In this manner, individual microgels can be customized for single or multicell coculture applications, or heterogeneous populations can be used as building blocks to create microporous assembled scaffolds that more closely mimic tissue heterogeneities. The inherent versatility of these materials allows user‐defined control of the microenvironments, from the order of singly encapsulated cells to entire 3D cell scaffolds. These hydrogel scaffolds are promising for moving towards personalized medicine approaches and recapitulating the multifaceted microenvironments that exist in vivo.     

A patient-specific computational model of hypoxia-modulated radiation resistance in glioblastoma using 18F-FMISO-PET

Glioblastoma multiforme (GBM) is a highly invasive primary brain tumour that has poor prognosis despite aggressive treatment. A hallmark of these tumours is diffuse invasion into the surrounding brain, necessitating a multi-modal treatment approach, including surgery, radiation and chemotherapy. We have previously demonstrated the ability of our model to predict radiographic response immediately following radiation therapy in individual GBM patients using a simplified geometry of the brain and theoretical radiation dose. Using only two pre-treatment magnetic resonance imaging scans, we calculate net rates of proliferation and invasion as well as radiation sensitivity for a patient''s disease. Here, we present the application of our clinically targeted modelling approach to a single glioblastoma patient as a demonstration of our method. We apply our model in the full three-dimensional architecture of the brain to quantify the effects of regional resistance to radiation owing to hypoxia in vivo determined by [¹⁸F]-fluoromisonidazole positron emission tomography (FMISO-PET) and the patient-specific three-dimensional radiation treatment plan. Incorporation of hypoxia into our model with FMISO-PET increases the model–data agreement by an order of magnitude. This improvement was robust to our definition of hypoxia or the degree of radiation resistance quantified with the FMISO-PET image and our computational model, respectively. This work demonstrates a useful application of patient-specific modelling in personalized medicine and how mathematical modelling has the potential to unify multi-modality imaging and radiation treatment planning.     

In Situ Control of Cell Substrate Microtopographies Using Photolabile Hydrogels

Substratum topography can play a significant role in regulating cellular function and fate. To study cellular responses to biophysical cues, researchers have developed dynamic methods for controlling cell morphology; however, many of these platforms are limited to one transition between two predefined substratum topographies. To afford the user additional control over the presentation of microtopographic cues to cell populations, a photolabile, PEG‐based hydrogel system is presented in which precisely engineered topographic cues can be formed in situ by controlled erosion. Here, the ability to produce precisely engineered static microtopographies in the hydrogel surface is first established. Human mesenchymal stem cell (hMSC) response to topographies with features of subcellular dimensions (～5 to 40 μm) and with various aspect ratios increasing from 1:1 to infinity (e.g., channels) are quantified, and the dynamic nature of the culture system is demonstrated by sequentially presenting a series of topographies through in situ modifications and quantifying reversible changes in cell morphology in response to substratum topographies altered in real time.     

Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells

Cell-matrix interactions have critical roles in regeneration, development and disease. The work presented here demonstrates that encapsulated human mesenchymal stem cells (hMSCs) can be induced to differentiate down osteogenic and adipogenic pathways by controlling their three-dimensional environment using tethered small-molecule chemical functional groups. Hydrogels were formed using sufficiently low concentrations of tether molecules to maintain constant physical characteristics, encapsulation of hMSCs in three dimensions prevented changes in cell morphology, and hMSCs were shown to differentiate in normal growth media, indicating that the small-molecule functional groups induced differentiation. To our knowledge, this is the first example where synthetic matrices are shown to control induction of multiple hMSC lineages purely through interactions with small-molecule chemical functional groups tethered to the hydrogel material. Strategies using simple chemistry to control complex biological processes would be particularly powerful as they could make production of therapeutic materials simpler, cheaper and more easily controlled.