Mechanical measurements of heterogeneity and length scale effects in PEG-based hydrogels.

Colloidal-probe spherical indentation load-relaxation experiments with a probe radius of 3 μm are conducted on poly(ethylene glycol) (PEG) hydrogel materials to quantify their steady-state mechanical properties and time-dependent transport properties via a single experiment. PEG-based hydrogels are shown to be heterogeneous in both morphology and mechanical stiffness at this scale; a linear-harmonic interpolation of hyperelastic Mooney-Rivlin and Boussinesq flat-punch indentation models was used to describe the steady-state response of the hydrogels and determine upper and lower bounds for indentation moduli. Analysis of the transient load-relaxation response during displacement-controlled hold periods provides a means of extracting two time constants τ1 and τ2, where τ1 and τ2 are assigned to the viscoelastic and poroelastic properties, respectively. Large τ2 values at small indentation depths provide evidence of a non-equilibrium state characterized by a phenomenon that restricts poroelastic fluid flow through the material; for larger indentations, the variability in τ2 values decreases and pore sizes estimated from τ2via indentation approach those measured via macroscopic swelling experiments. The contact probe methodology developed here provides a means of assessing hydrogel heterogeneity, including time-dependent mechanical and transport properties, and has potential implications in hydrogel biomedical and engineering applications.The authors would like to acknowledge funding from the National Institutes of Health.This is the author accepted manuscript. The final version is available from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C5SM01210

Coordinated grid and place cell replay during rest

Hippocampal replay has been hypothesized to underlie memory consolidation and navigational planning, yet the involvement of grid cells in replay is unknown. During replay we found grid cells to be spatially coherent with place cells, encoding locations 11 ms delayed relative to the hippocampus, with directionally modulated grid cells and forward replay exhibiting the greatest coherence with the CA1 area of the hippocampus. This suggests grid cells are engaged during the consolidation of spatial memories to the neocortex

Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop

<p>Abstract</p> <p>Background</p> <p>Envenomation by crotaline snakes (rattlesnake, cottonmouth, copperhead) is a complex, potentially lethal condition affecting thousands of people in the United States each year. Treatment of crotaline envenomation is not standardized, and significant variation in practice exists.</p> <p>Methods</p> <p>A geographically diverse panel of experts was convened for the purpose of deriving an evidence-informed unified treatment algorithm. Research staff analyzed the extant medical literature and performed targeted analyses of existing databases to inform specific clinical decisions. A trained external facilitator used modified Delphi and structured consensus methodology to achieve consensus on the final treatment algorithm.</p> <p>Results</p> <p>A unified treatment algorithm was produced and endorsed by all nine expert panel members. This algorithm provides guidance about clinical and laboratory observations, indications for and dosing of antivenom, adjunctive therapies, post-stabilization care, and management of complications from envenomation and therapy.</p> <p>Conclusions</p> <p>Clinical manifestations and ideal treatment of crotaline snakebite differ greatly, and can result in severe complications. Using a modified Delphi method, we provide evidence-informed treatment guidelines in an attempt to reduce variation in care and possibly improve clinical outcomes.</p

Does the Effectiveness of Control Measures Depend on the Influenza Pandemic Profile?

BACKGROUND: Although strategies to contain influenza pandemics are well studied, the characterization and the implications of different geographical and temporal diffusion patterns of the pandemic have been given less attention. METHODOLOGY/MAIN FINDINGS: Using a well-documented metapopulation model incorporating air travel between 52 major world cities, we identified potential influenza pandemic diffusion profiles and examined how the impact of interventions might be affected by this heterogeneity. Clustering methods applied to a set of pandemic simulations, characterized by seven parameters related to the conditions of emergence that were varied following Latin hypercube sampling, were used to identify six pandemic profiles exhibiting different characteristics notably in terms of global burden (from 415 to >160 million of cases) and duration (from 26 to 360 days). A multivariate sensitivity analysis showed that the transmission rate and proportion of susceptibles have a strong impact on the pandemic diffusion. The correlation between interventions and pandemic outcomes were analyzed for two specific profiles: a fast, massive pandemic and a slow building, long-lasting one. In both cases, the date of introduction for five control measures (masks, isolation, prophylactic or therapeutic use of antivirals, vaccination) correlated strongly with pandemic outcomes. Conversely, the coverage and efficacy of these interventions only moderately correlated with pandemic outcomes in the case of a massive pandemic. Pre-pandemic vaccination influenced pandemic outcomes in both profiles, while travel restriction was the only measure without any measurable effect in either. CONCLUSIONS: our study highlights: (i) the great heterogeneity in possible profiles of a future influenza pandemic; (ii) the value of being well prepared in every country since a pandemic may have heavy consequences wherever and whenever it starts; (iii) the need to quickly implement control measures and even to anticipate pandemic emergence through pre-pandemic vaccination; and (iv) the value of combining all available control measures except perhaps travel restrictions

GDR γ-ray decay in 156Dy∗ from regions selected on temperature and angular momentum

The strength distribution of the GDR built on highly excited states in a restricted temperature domain in Dy-156 and Dy-155 nuclei has been deduced by subtraction of gamma-ray spectra obtained for the decay of Dy-154* and Dy-156* from regions selected on angular momentum. The resulting difference spectra have been analyzed within the statistical model. The results show a large deformation (\beta\ similar to 0.51 +/- 0.29 and 0.35 +/- 0.14) for the angular-momentum regions with [J] similar to 32 ($) over bar h at T approximate to 1.8 +/- 0.2 MeV and [J] similar to 46 ($) over bar h at T approximate to 1.7 +/- 0.2 MeV respectively, in satisfactory agreement with calculations performed in the framework of Landau theory of shape transitions and statistical fluctuations. The deduced centroid energies are in agreement with the systematics of the GDR built on the ground state. The width of the GDR shows a systematic increase with increasing temperature

The human FK506-binding proteins: characterization of human FKBP19

Analysis of the human repertoire of the FK506-binding protein (FKBP) family of peptidyl-prolyl cis/trans isomerases has identified an expansion of genes that code for human FKBPs in the secretory pathway. There are distinct differences in tissue distribution and expression levels of each variant. In this article we describe the characterization of human FKBP19 (Entrez Gene ID: FKBP11), an FK506-binding protein predominantly expressed in vertebrate secretory tissues. The FKBP19 sequence comprises a cleavable N-terminal signal sequence followed by a putative peptidyl-prolyl cis/trans isomerase domain with homology to FKBP12. This domain binds FK506 weakly in vitro. FKBP19 mRNA is abundant in human pancreas and other secretory tissues and high levels of FKBP19 protein are detected in the acinar cells of mouse pancreas

The incidence of smoking and risk factors for smoking initiation in medical faculty students: cohort study

BACKGROUND: Medical education requires detailed investigation because it is a period during which the attitudes and behaviors of physicians develop. The purpose of this study was to calculate the yearly smoking prevalence and incidence rates of medical faculty students and to identify the risk factors for adopting smoking behaviour. METHODS: This is a cohort study in which every student was asked about their smoking habits at the time of first registration to the medical faculty, and was monitored every year. Smoking prevalence, yearly incidence of initiation of smoking and average years of smoking were calculated in analysis. RESULTS: At the time of registration, 21.8% of the students smoked. At the end of six years, males had smoked for an average of 2.6 ± 3.0 years and females for 1.0 ± 1.8 years (p < 0.05). Of the 93 medical students who were not smokers at the time of registration, 30 (32.3%) were smokers at the end of the 6 years of the course. CONCLUSION: The first 3 years of medical education are the most risky period for initiation of smoking. We found that factors such as being male, having a smoking friend in the same environment and having a high trait anxiety score were related to the initiation of smoking. Targeted smoking training should be mandatory for students in the Medical Faculty

Candida soluble cell wall β-glucan facilitates ovalbumin-induced allergic airway inflammation in mice: Possible role of antigen-presenting cells

<p>Abstract</p> <p>Background</p> <p>Although fungi have been implicated as initiating/deteriorating factors for allergic asthma, their contributing components have not been fully elucidated. We previously isolated soluble β-glucan from <it>Candida albicans </it>(CSBG) (Ohno et al., 2007). In the present study, the effects of CSBG exposure on airway immunopathology in the presence or absence of other immunogenic allergen was investigated <it>in vivo</it>, and their cellular mechanisms were analyzed both <it>in vivo </it>and <it>in vitro</it>.</p> <p>Methods</p> <p><it>In vivo</it>, ICR mice were divided into 4 experimental groups: vehicle, CSBG (25 μg/animal), ovalbumin (OVA: 2 μg/animal), and CSBG + OVA were repeatedly administered intratracheally. The bronchoalveolar lavage cellular profile, lung histology, levels of cytokines and chemokines in the lung homogenates, the expression pattern of antigen-presenting cell (APC)-related molecules in the lung digests, and serum immunoglobulin values were studied. <it>In vitro</it>, the impacts of CSBG (0–12.5 μg/ml) on the phenotype and function of immune cells such as splenocytes and bone marrow-derived dendritic cells (BMDCs) were evaluated in terms of cell proliferation, the surface expression of APC-related molecules, and OVA-mediated T-cell proliferating activity.</p> <p>Results</p> <p><it>In vivo</it>, repeated pulmonary exposure to CSBG induced neutrophilic airway inflammation in the absence of OVA, and markedly exacerbated OVA-related eosinophilic airway inflammation with mucus metaplasia in mice, which was concomitant with the amplified lung expression of Th2 cytokines and IL-17A and chemokines related to allergic response. Exposure to CSBG plus OVA increased the number of cells bearing MHC class II with or without CD80 in the lung compared to that of others. <it>In vitro</it>, CSBG significantly augmented splenocyte proliferation in the presence or absence of OVA. Further, CSBG increased the expression of APC-related molecules such as CD80, CD86, and DEC205 on BMDCs and amplified OVA-mediated T-cell proliferation through BMDCs.</p> <p>Conclusion</p> <p>CSBG potentiates allergic airway inflammation with maladaptive Th immunity, and this potentiation was associated with the enhanced activation of APCs including DC.</p