Effect of milk on fibronectin and collagen type I binding to Staphylococcus aureus and coagulase-negative staphylococci isolated from bovine mastitis.
Tryptic soy broth (TSB)-grown cells of Staphylococcus aureus isolated from acute and chronic bovine mastitis bound mainly 125I-fibronectin (Fn) [corrected], whereas strains of nine species of coagulase-negative staphylococci showed a predominant interaction with 125I-collagen (Cn) [corrected] type I. A particle agglutination assay (PAA) was used to examine the interaction of coagulase-negative staphylococci with 125I-Fn and 125I-Cn immobilized on latex. All 368 coagulase-negative staphylococci demonstrated high 125I-Cn and moderate to low 125I-Fn interactions in the PAA. Cn-PAA reactivity was high among strains of Staphylococcus xylosus (84.2%), Staphylococcus simulans (77.8%), Staphylococcus epidermidis (76.7%), and Staphylococcus hyicus (74.3%), whereas all six Staphylococcus capitis strains clumped Cn-PAA reagent. Incubating TSB-grown cells in 10% skim milk for 1 h decreased the 125I-Fn- and 125I-Cn-binding affinity in most of the S. aureus and coagulase-negative staphylococci, while growth in 10% skim milk for 18 h resulted in more than 90% decrease or complete loss of interaction with these proteins. Decreased 125I-Fn binding in the presence of milk was correlated with protease production but not with 125I-Cn binding.


Analysis of spectral characteristics of photonic bandgap waveguides.
A numerical model based on a scalar beam propagation method is applied to study light transmission in photonic bandgap (PBG) waveguides. The similarity between a cylindrical waveguide with concentric layers of different indices and an analogous planar waveguide is demonstrated by comparing their transmission spectra that are numerically shown to have coinciding wavelengths for their respective transmission maxima and minima. Furthermore, the numerical model indicates the existence of two regimes of light propagation depending on the wavelength. Bragg scattering off the multiple high-index/low-index layers of the cladding determines the transmission spectrum for long wavelengths. As the wavelength decreases, the spectral features are found to be almost independent of the pitch of the multi-layer Bragg mirror stack. An analytical model based on an antiresonant reflecting guidance mechanism is developed to accurately predict the location of the transmission minima and maxima observed in the simulations when the wavelength of the launched light is short. Mode computations also show that the optical field is concentrated mostly in the core and the surrounding first high-index layers in the short-wavelength regime while the field extends well into the outermost layers of the Bragg structure for longer wavelengths. A simple physical model of the reflectivity at the core/high-index layer interface is used to intuitively understand some aspects of the numerical results as the transmission spectrum transitions from the short- to the long-wavelength regime.


High thermal stability of correlated color temperature using current compensation in hybrid warm white high-voltage LEDs.
This study experimentally and numerically examines the correlated color temperature (CCT) stability issue for hybrid warm white high-voltage light-emitting diodes (HV-LEDs) by using a current compensation method. This method could efficiently maintain the CCT stability factor at approximately 1.0 and yield greater color uniformity with Δu'v' values ranging from 0.017 to 0.003 in CIE 1976 chromaticity coordinates. The simulation results show that the red chip intensity drop is the primary cause of CCT instability in the hybrid warm white system when the temperature increases. Therefore, Furthermore, results indicate that the relative lumen drop improves from 21% to 15% by using a current compensation method.


Marital behavior, oxytocin, vasopressin, and wound healing.
Animal studies have implicated oxytocin and vasopressin in social bonding, physiological stress responses, and wound healing. In humans, endogenous oxytocin and vasopressin levels covary with perceptions of relationship quality, marital behaviors, and physiological stress responses. To investigate relationships among marital behavior, oxytocin, vasopressin, and wound healing, and to determine the characteristics of individuals with the highest neuropeptide levels, 37 couples were admitted for a 24-h visit in a hospital research unit. After small blister wounds were created on their forearm, couples participated in a structured social support interaction task. Blister sites were monitored daily following discharge to assess wound repair speed. Blood samples were collected for oxytocin, vasopressin, and cytokine analyses. Higher oxytocin levels were associated with more positive communication behaviors during the structured interaction task. Furthermore, individuals in the upper oxytocin quartile healed blister wounds faster than participants in lower oxytocin quartiles. Higher vasopressin levels were related to fewer negative communication behaviors and greater tumor necrosis factor-alpha production. Moreover, women in the upper vasopressin quartile healed the experimental wounds faster than the remainder of the sample. These data confirm and extend prior evidence implicating oxytocin and vasopressin in couples' positive and negative communication behaviors, and also provide further evidence of their role in an important health outcome, wound healing.


Substance P-induced pulmonary vasoreactivity in isolated perfused guinea pig lung.
We examined the effects of the neuropeptide substance P on pulmonary hemodynamic and transvascular fluid filtration in isolated Ringer's-perfused and blood-enriched Ringer's-perfused guinea pig lung and on albumin flux across bovine pulmonary artery endothelial monolayer. Mean pulmonary artery, left atrial, and capillary pressures were determined and used to calculate arterial and venous resistances, and lung weight was continuously monitored. Substance P (0.01-1.0 microM) caused marked increases in pulmonary arterial pressure, capillary pressure, venous resistance, and lung weight within 3-5 minutes after administration. These responses remained elevated above baseline at the end of the 30-minute experimental period in the Ringer's-perfused lungs but not in the blood-enriched Ringer's-perfused lungs. Substance P did not alter the capillary filtration coefficient in isolated lungs and transendothelial albumin permeability in the endothelial monolayer. Substance P resulted in an increase in venous effluent thromboxane B2 concentrations in perfused lungs but had no effect on 6-keto-prostaglandin F1 alpha concentrations. Papaverine (0.27 mM) (a smooth-muscle relaxant) abolished the pulmonary microvascular response to substance P in Ringer's-perfused lungs, and meclofenamate (0.15 mM) (a cyclooxygenase inhibitor) attenuated the pulmonary vasoconstriction and lung weight increase. Pyrilamine (1.0 microM) (a histamine1-receptor antagonist) did not alter the responses to substance P. In conclusion, substance P does not affect pulmonary vascular permeability to water and protein. Substance P induces an intense pulmonary vasoconstriction (due to greater constriction of postcapillary vessels) and an elevation in pulmonary capillary pressure that increases net transvascular fluid filtration.(ABSTRACT TRUNCATED AT 250 WORDS)


Randomized controlled trial of a home-visiting intervention on infant cognitive development in peri-urban South Africa.
To determine whether, in an impoverished South African community, an intervention that benefitted infant attachment also benefitted cognitive development. Pregnant females were randomized to intervention (n=220) and no-treatment control groups (n=229). The intervention was home-based parenting support for attachment, delivered until 6 months postpartum. At 18 months, infants were assessed on attachment and cognitive development (Bayley Scales Mental Development Index [MDI]) (n=127 intervention, n=136 control participants). Infant MDI was examined in relation to intervention, socio-economic risk, antenatal depression, and infant sex and attachment. Overall, there was little effect of the intervention on MDI (p=0.094, d=0.20), but there was an interaction between intervention and risk (p=0.03, ηp2=0.02). MDI scores of infants of lower risk intervention group mothers were, on average, 4.84 points higher than those of other infants (p=0.002, d=0.41). Antenatal depression was not significant once intervention and risk were controlled (p=0.08); there was no association between infant MDI and either sex (p=0.41) or attachment (p=0.56). Parenting interventions for infant cognitive development may benefit from inclusion of specific components to support infant cognition beyond those that support attachment, and may be most effective for infants over 6 months. They may need augmentation with other input where adversity is extreme.


Hyperpolarized MRS: New tool to study real-time brain function and metabolism.
The advent of dissolution dynamic nuclear polarization (DNP) led to the emergence of a new kind of magnetic resonance (MR) measurements providing the opportunity to probe metabolism in vivo in real time. It has been shown that, following the injection of hyperpolarized substrates prepared using dissolution DNP, specific metabolic bioprobes that can be used to differentiate between healthy and pathological tissue in preclinical and clinical studies can be readily detected by MR thanks to the tremendous signal enhancement. The present article aims at reviewing the studies of cerebral function and metabolism based on the use of hyperpolarized MR. The constraints and future opportunities that this technology could offer are discussed.


Scabies in healthcare settings.
In industrialized countries, epidemics of scabies are mainly described within families or in institutions such as healthcare settings. Control of institutional scabies is associated with a considerable working and economic burden, but guidelines for the management are scarce. The prevalence of institutional scabies is probably underestimated. Identified risk factors for institutional scabies outbreaks include the institution type, extensive physical contact with patients and movement of patients, the existence of crusted scabies, a long diagnostic delay and failures in implementation of infection control or treatment plans.Atypical clinical features (hyperinfestation, scabies in the elderly or in children) may be misdiagnosed. Control of institutional scabies outbreaks relies on prompt recognition of the index case, constitution of an outbreak management team, determination of the extent of the outbreak and risk factors for spread, immediate implementation of infection control practices, adequate education of all involved persons, simultaneous treatment of cases and of all exposed individuals and concomitant environmental disinfection. Prolonged surveillance is imperative to eradicate scabies. The inclusion of institutionalized patients in randomized controlled trials would be beneficial as present data concerning scabicide effectiveness are obtained from trials that recruited individual participants and do not take into account a global strategy.


SOCRAT Platform Design: A Web Architecture for Interactive Visual Analytics Applications.
The modern web is a successful platform for large scale interactive web applications, including visualizations. However, there are no established design principles for building complex visual analytics (VA) web applications that could efficiently integrate visualizations with data management, computational transformation, hypothesis testing, and knowledge discovery. This imposes a time-consuming design and development process on many researchers and developers. To address these challenges, we consider the design requirements for the development of a module-based VA system architecture, adopting existing practices of large scale web application development. We present the preliminary design and implementation of an open-source platform for Statistics Online Computational Resource Analytical Toolbox (SOCRAT). This platform defines: (1) a specification for an architecture for building VA applications with multi-level modularity, and (2) methods for optimizing module interaction, re-usage, and extension. To demonstrate how this platform can be used to integrate a number of data management, interactive visualization, and analysis tools, we implement an example application for simple VA tasks including raw data input and representation, interactive visualization and analysis.


The omega-3 fatty acid eicosapentaenoic acid is required for normal alcohol response behaviors in C. elegans.
Alcohol addiction is a widespread societal problem, for which there are few treatments. There are significant genetic and environmental influences on abuse liability, and understanding these factors will be important for the identification of susceptible individuals and the development of effective pharmacotherapies. In humans, the level of response to alcohol is strongly predictive of subsequent alcohol abuse. Level of response is a combination of counteracting responses to alcohol, the level of sensitivity to the drug and the degree to which tolerance develops during the drug exposure, called acute functional tolerance. We use the simple and well-characterized nervous system of Caenorhabditis elegans to model the acute behavioral effects of ethanol to identify genetic and environmental factors that influence level of response to ethanol. Given the strong molecular conservation between the neurobiological machinery of worms and humans, cellular-level effects of ethanol are likely to be conserved. Increasingly, variation in long-chain polyunsaturated fatty acid levels has been implicated in complex neurobiological phenotypes in humans, and we recently found that fatty acid levels modify ethanol responses in worms. Here, we report that 1) eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, is required for the development of acute functional tolerance, 2) dietary supplementation of eicosapentaenoic acid is sufficient for acute tolerance, and 3) dietary eicosapentaenoic acid can alter the wild-type response to ethanol. These results suggest that genetic variation influencing long-chain polyunsaturated fatty acid levels may be important abuse liability loci, and that dietary polyunsaturated fatty acids may be an important environmental modulator of the behavioral response to ethanol.


Fabrication of One-Dimensional Zigzag [6,6]-Phenyl-C61-Butyric Acid Methyl Ester Nanoribbons from Two-Dimensional Nanosheets.
One-dimensional (1D) zigzag [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) nanoribbons are produced by folding two-dimensional ultrathin PCBM nanosheets in a simple solvent process. The unique 1D PCBM nanostructures exhibit uniform width of 3.8 ± 0.3 nm, equivalent to four PCBM molecules, and lengths of 20-400 nm. These nanoribbons show well-defined crystalline structure, comprising PCBM molecules in a hexagonal arrangement without trapped solvent molecules. First-principle calculations and detailed experimental characterization provide an insight into the structure and formation mechanism of the 1D PCBM nanoribbons. Given their dimensions and physical properties, we foresee that these nanostructures should be ideal as acceptor material in organic solar cells.


Development of Trypanosoma cruzi in vitro assays to identify compounds suitable for progression in Chagas' disease drug discovery.
Chagas' disease is responsible for significant mortality and morbidity in Latin America. Current treatments display variable efficacy and have adverse side effects, hence more effective, better tolerated drugs are needed. However, recent efforts have proved unsuccessful with failure of the ergosterol biosynthesis inhibitor posaconazole in phase II clinical trials despite promising in vitro and in vivo studies. The lack of translation between laboratory experiments and clinical outcome is a major issue for further drug discovery efforts. Our goal was to identify cell-based assays that could differentiate current nitro-aromatic drugs nifurtimox and benznidazole from posaconazole. Using a panel of T. cruzi strains including the six major lineages (TcI-VI), we found that strain PAH179 (TcV) was markedly less susceptible to posaconazole in vitro. Determination of parasite doubling and cycling times as well as EdU labelling experiments all indicate that this lack of sensitivity is due to the slow doubling and cycling time of strain PAH179. This is in accordance with ergosterol biosynthesis inhibition by posaconazole leading to critically low ergosterol levels only after multiple rounds of division, and is further supported by the lack of effect of posaconazole on the non-replicative trypomastigote form. A washout experiment with prolonged posaconazole treatment showed that, even for more rapidly replicating strains, this compound cannot clear all parasites, indicative of a heterogeneous parasite population in vitro and potentially the presence of quiescent parasites. Benznidazole in contrast was able to kill all parasites. The work presented here shows clear differentiation between the nitro-aromatic drugs and posaconazole in several assays, and suggests that in vitro there may be clinically relevant heterogeneity in the parasite population that can be revealed in long-term washout experiments. Based on these findings we have adjusted our in vitro screening cascade so that only the most promising compounds are progressed to in vivo experiments.


Opioid sensitivity in mice selectively bred to consume or not consume methamphetamine.
There has been little investigation of genetic factors and associated mechanisms that influence risk for development of methamphetamine (MA) dependence. Selectively bred mouse lines that exhibit high (MAHDR) or low (MALDR) levels of MA intake in a two-bottle choice MA drinking (MADR) procedure provide a genetic tool for this purpose. These lines were used to determine whether opioid sensitivity and MA intake are genetically associated, because opioid-mediated pathways influence some effects of MA. Sensitivity to the analgesic effects of the μ-opioid receptor (MOP-r) agonist fentanyl (0.05, 0.1, 0.2, 0.4 mg/kg) was examined using two acute thermal tests (hot plate and tail flick) and one chronic pain test (magnesium sulfate abdominal constriction). Locomotor stimulant responses to fentanyl (0.05, 0.1, 0.2, 0.4 mg/kg) and morphine (10, 20, 30 mg/kg) were also examined. In addition, MADR was measured in the progenitor strains [(C57BL/6J (B6), DBA/2J (D2)] of the F2 population from which the selected lines were generated. The MADR lines did not differ in sensitivity to the analgesic effects of fentanyl; however, MALDR mice exhibited greater locomotor activation than MAHDR mice to both fentanyl and morphine. D2 mice consumed more MA than B6 mice. The line differences for MA consumption and morphine activation recapitulated B6 and D2 strain differences for these two traits, but not strain differences previously found for opioid analgesic responses. These results support a negative genetic correlation between MA consumption and sensitivity to the stimulant effects of opioids and suggest the involvement of MOP-r regulated systems in MA intake.


Tyrosinase inhibitors from natural and synthetic sources: structure, inhibition mechanism and perspective for the future.
Tyrosinase is known to be a key enzyme in melanin biosynthesis, involved in determining the color of mammalian skin and hair. Various dermatological disorders, such as melasma, age spots and sites of actinic damage, arise from the accumulation of an excessive level of epidermal pigmentation. In addition, unfavorable enzymatic browning of plant-derived foods by tyrosinase causes a decrease in nutritional quality and economic loss of food products. The inadequacy of current conventional techniques to prevent tyrosinase action encourages us to seek new potent tyrosinase inhibitors. This article overviews the various inhibitors obtained from natural and synthetic sources with their industrial importance.


[Financial and economic sustainability of public spending on health care by local governments: an analysis of data from municipalities in Mato Grosso State, Brazil].
Brazil's Unified National Health System is financed according to a model known as fiscal federalism, the fund-sharing rules of the Social Security Budget, Ministry of Health norms, and Constitutional Amendment 29 (EC-29), which links Federal, State, and municipal resources to health. This article discusses the sustainability of public spending on health at the municipal level. Twenty-one municipalities were studied, using municipal budget data. From 1996 to 2006, total current per capita revenues increased by 280% above the accumulated inflation and Gross Domestic Product, varying by size of municipality, which also defined the composition of the municipal budgets. Meanwhile, the budget comprising the basis for EC-29 increased less (178%), thus placing limits on the municipal share of health spending. The results observed in these municipalities are believed to reflect the reality in thousands of other Brazilian municipalities, thus jeopardizing the capacity for municipal investment in health, especially beginning in 2008. The situation may become even worse, considering the repeal of the so-called Bank Transaction Tax (CPMF), Bills of Law 306/08 and 233/08 (currently under review in the National Congress), and the world recession stemming from the U.S. financial crisis.


On the Identification of Noise Covariances and Adaptive Kalman Filtering: A New Look at a 50 Year-Old Problem.
The Kalman filter requires knowledge of the noise statistics; however, the noise covariances are generally unknown. Although this problem has a long history, reliable algorithms for their estimation are scant, and necessary and sufficient conditions for identifiability of the covariances are in dispute. We address both of these issues in this paper. We first present the necessary and sufficient condition for unknown noise covariance estimation; these conditions are related to the rank of a matrix involving the auto and cross-covariances of a weighted sum of innovations, where the weights are the coefficients of the minimal polynomial of the closed-loop system transition matrix of a stable, but not necessarily optimal, Kalman filter. We present an optimization criterion and a novel six-step approach based on a successive approximation, coupled with a gradient algorithm with adaptive step sizes, to estimate the steady-state Kalman filter gain, the unknown noise covariance matrices, as well as the state prediction (and updated) error covariance matrix. Our approach enforces the structural assumptions on unknown noise covariances and ensures symmetry and positive definiteness of the estimated covariance matrices. We provide several approaches to estimate the unknown measurement noise covariance R via post-fit residuals, an approach not yet exploited in the literature. The validation of the proposed method on five different test cases from the literature demonstrates that the proposed method significantly outperforms previous state-of-the-art methods. It also offers a number of novel machine learning motivated approaches, such as sequential (one sample at a time) and mini-batch-based methods, to speed up the computations.


In situ microparticle analysis of marine phytoplankton cells with infrared laser-based optical tweezers.
We describe the application of infrared optical tweezers to the in situ microparticle analysis of marine phytoplankton cells. A Nd:YAG laser (λ= 1064 nm) trap is used to confine and manipulate single Nannochloris and Synechococcus cells in an enriched seawater medium while spectral fluorescence and Lorenz-Mie backscatter signals are simultaneously acquired under a variety of excitation and trapping conditions. Variations in the measured fluorescence intensities of chlorophyll a (Chl a) and phycoerythrin pigments in phytoplankton cells are observed. These variations are related, in part, to basic intrasample variability, but they also indicate that increasing ultraviolet-exposure time and infrared trapping power may have short-term effects on cellular physiology that are related to Chl a photobleaching and laser-induced heating, respectively. The use of optical tweezers to study the factors that affect marine cell physiology and the processes of absorption, scattering, and attenuation by individual cells, organisms, and particulate matter that contribute to optical closure on a microscopic scale are also described.


Marine microbes see a sea of gradients.
Marine bacteria influence Earth's environmental dynamics in fundamental ways by controlling the biogeochemistry and productivity of the oceans. These large-scale consequences result from the combined effect of countless interactions occurring at the level of the individual cells. At these small scales, the ocean is surprisingly heterogeneous, and microbes experience an environment of pervasive and dynamic chemical and physical gradients. Many species actively exploit this heterogeneity, while others rely on gradient-independent adaptations. This is an exciting time to explore this frontier of oceanography, but understanding microbial behavior and competition in the context of the water column's microarchitecture calls for new ecological frameworks, such as a microbial optimal foraging theory, to determine the relevant trade-offs and global consequences of microbial life in a sea of gradients.


A likelihood-based method for testing for nonstochastic variation of diversification rates in phylogenies.
Observed variations in rates of taxonomic diversification have been attributed to a range of factors including biological innovations, ecosystem restructuring, and environmental changes. Before inferring causality of any particular factor, however, it is critical to demonstrate that the observed variation in diversity is significantly greater than that expected from natural stochastic processes. Relative tests that assess whether observed asymmetry in species richness between sister taxa in monophyletic pairs is greater than would be expected under a symmetric model have been used widely in studies of rate heterogeneity and are particularly useful for groups in which paleontological data are problematic. Although one such test introduced by Slowinski and Guyer a decade ago has been applied to a wide range of clades and evolutionary questions, the statistical behavior of the test has not been examined extensively, particularly when used with Fisher's procedure for combining probabilities to analyze data from multiple independent taxon pairs. Here, certain pragmatic difficulties with the Slowinski-Guyer test are described, further details of the development of a recently introduced likelihood-based relative rates test are presented, and standard simulation procedures are used to assess the behavior of the two tests in a range of situations to determine: (1) the accuracy of the tests' nominal Type I error rate; (2) the statistical power of the tests; (3) the sensitivity of the tests to inclusion of taxon pairs with few species; (4) the behavior of the tests with datasets comprised of few taxon pairs; and (5) the sensitivity of the tests to certain violations of the null model assumptions. Our results indicate that in most biologically plausible scenarios, the likelihood-based test has superior statistical properties in terms of both Type I error rate and power, and we found no scenario in which the Slowinski-Guyer test was distinctly superior, although the degree of the discrepancy varies among the different scenarios. The Slowinski-Guyer test tends to be much more conservative (i.e., very disinclined to reject the null hypothesis) in datasets with many small pairs. In most situations, the performance of both the likelihood-based test and particularly the Slowinski-Guyer test improve when pairs with few species are excluded from the computation, although this is balanced against a decline in the tests' power and accuracy as fewer pairs are included in the dataset. The performance of both tests is quite poor when they are applied to datasets in which the taxon sizes do not conform to the distribution implied by the usual null model. Thus, results of analyses of taxonomic rate heterogeneity using the Slowinski-Guyer test can be misleading because the test's ability to reject the null hypothesis (equal rates) when true is often inaccurate and its ability to reject the null hypothesis when the alternative (unequal rates) is true is poor, particularly when small taxon pairs are included. Although not always perfect, the likelihood-based test provides a more accurate and powerful alternative as a relative rates test.


Multimorbidity, service organization and clinical decision making in primary care: a qualitative study.
Primary care professionals often manage patients with multiple long-term health conditions, but managing multimorbidity is challenging given time and resource constraints and interactions between conditions. To explore GP and nurse perceptions of multimorbidity and the influence on service organization and clinical decision making. A qualitative interview study with primary care professionals in practices in Greater Manchester, U.K. Interviews were conducted with 15 GPs and 10 practice nurses. Primary care professionals identified tensions between delivering care to meet quality targets and fulfilling the patient's agenda, tensions which are exacerbated in multimorbidity. They were aware of the inconvenience suffered by patients through attendance at multiple clinic appointments when care was structured around individual conditions. They reported difficulties managing patients with multimorbidity in limited consultation time, which led to adoption of an 'additive-sequential' decision-making model which dealt with problems in priority order until consultation resources were exhausted, when further management was deferred. Other challenges included the need for patients to co-ordinate their care, the difficulties of self-management support in multimorbidity and problems of making sense of the relationships between physical and mental health. Doctor and nurse accounts included limited consideration of multimorbidity in terms of the interactions between conditions or synergies between management of different conditions. Primary care professionals identify a number of challenges in care for multimorbidity and adopt a particular model of decision making to deliver care for multiple individual conditions. However, they did not describe specific decision making around managing multimorbidity per se.


Antimicrobial compounds in tears.
The tear film coats the cornea and conjunctiva and serves several important functions. It provides lubrication, prevents drying of the ocular surface epithelia, helps provide a smooth surface for refracting light, supplies oxygen and is an important component of the innate defense system of the eye providing protection against a range of potential pathogens. This review describes both classic antimicrobial compounds found in tears such as lysozyme and some more recently identified such as members of the cationic antimicrobial peptide family and surfactant protein-D as well as potential new candidate molecules that may contribute to antimicrobial protection. As is readily evident from the literature review herein, tears, like all mucosal fluids, contain a plethora of molecules with known antimicrobial effects. That all of these are active in vivo is debatable as many are present in low concentrations, may be influenced by other tear components such as the ionic environment, and antimicrobial action may be only one of several activities ascribed to the molecule. However, there are many studies showing synergistic/additive interactions between several of the tear antimicrobials and it is highly likely that cooperativity between molecules is the primary way tears are able to afford significant antimicrobial protection to the ocular surface in vivo. In addition to effects on pathogen growth and survival some tear components prevent epithelial cell invasion and promote the epithelial expression of innate defense molecules. Given the protective role of tears a number of scenarios can be envisaged that may affect the amount and/or activity of tear antimicrobials and hence compromise tear immunity. Two such situations, dry eye disease and contact lens wear, are discussed here.


Biochemical and Molecular Investigation of In Vitro Antioxidant and Anticancer Activity Spectrum of Crude Extracts of Willow Leaves Salix safsaf.
Organic fractions and extracts of willow (Salix safsaf) leaves, produced by sequential solvent extraction as well as infusion and decoction, exhibited anticancer potencies in four cancerous cell lines, including breast (MCF-7), colorectal (HCT-116), cervical (HeLa) and liver (HepG2). Results of the MTT assay revealed that chloroform (CHCl3) and ethyl acetate (EtOAc)-soluble fractions exhibited specific anticancer activities as marginal toxicities were observed against two non-cancerous control cell lines (BJ-1 and MCF-12). Ultra-high-resolution mass spectrometry Q-Exactive™ HF Hybrid Quadrupole-Orbitrap™ coupled with liquid chromatography (UHPLC) indicated that both extracts are enriched in features belonging to major phenolic and purine derivatives. Fluorescence-activated cell sorter analysis (FACS), employing annexin V-FITC/PI double staining indicated that the observed cytotoxic potency was mediated via apoptosis. FACS analysis, monitoring the increase in fluorescence signal, associated with oxidation of DCFH to DCF, indicated that the mechanism of apoptosis is independent of reactive oxygen species (ROS). Results of immunoblotting and RT-qPCR assays showed that treatment with organic fractions under investigation resulted in significant up-regulation of pro-apoptotic protein and mRNA markers for Caspase-3, p53 and Bax, whereas it resulted in a significant reduction in amounts of both protein and mRNA of the anti-apoptotic marker Bcl-2. FACS analysis also indicated that pre-treatment and co-treatment of human amniotic epithelial (WISH) cells exposed to the ROS H2O2 with EtOAc fraction provide a cytoprotective and antioxidant capacity against generated oxidative stress. In conclusion, our findings highlight the importance of natural phenolic and flavonoid compounds with unparalleled and unique antioxidant and anticancer properties.


Alveolar bone resorption induced by CD4+CD45RB high-density T-cell transfer in immunocompromised mice.
The aims of this study are to determine whether the antigen-inexperienced (naive, CD45RB high-density) T-cell (CD4(+)CD45RB(High) T-cell) transfer model is associated with alveolar bone resorption, to elucidate the local osteogenic/adipogenic potential of alveolar bone marrow stromal cells (ABCs) from T-cell-transferred animals, and to investigate the systemic osteogenic potential by transplanting human periodontal ligament stem cells (hPDLSCs) into these animals. CD4(+)CD45RB(High) and CD4(+)CD45RB(Low) (antigen-experienced [memory, CD45RB low-density]) T cells were sorted and transferred into severe combined immunodeficiency (SCID) mice to induce inflammatory bowel disease-like syndrome (n = 8). hPDLSCs were transplanted into T-cell-transferred SCID mice to examine ectopic cementum formation 8 weeks after T-cell transfer. The mandibles and tibias of these mice were retrieved for microcomputed tomography (micro-CT), histomorphometric analysis, and isolation of ABCs 16 weeks after T-cell transfer. The in vitro osteogenic and adipogenic potentials of the ABCs were evaluated. Histologic and micro-CT analysis revealed that the transfer of CD4(+)CD45RB(High) T-cell subset was sufficient for alveolar bone resorption and affected the osteogenic/adipogenic potential of ABCs. Furthermore, it was found that CD4(+)CD45RB(High) T-cell-transferred animals have decreased systemic osteogenic potential, as evidenced using the in vivo ectopic hPDLSC transplantation model. CD4(+)CD45RB(High) T-cell transfer induced both alveolar bone resorption and reduced systemic osteogenic potential, with a concomitant downregulation of the osteogenic potential of ABCs.


Antioxidant activity, color, carotenoids composition, minerals, vitamin C and sensory quality of organic and conventional mandarin juice, cv. Orogrande.
The effects of organic farming on antioxidant activity, CIE L*a*b* color, carotenoids composition, minerals contents, vitamin C and sensory quality of Orogrande mandarin juices were studied. Independent of the farming type, mandarin juices can be considered as good source of some important nutrients, such as potassium and antioxidant chemicals, for example, β-cryptoxanthin. Organic farming of mandarin resulted in juices with higher antioxidant activity, total carotenoids concentrations, minerals (Ca, K and Fe) contents, vitamin C content, more appealing and intense orange color and better sensory quality. For instance, organic Orogrande juice contained significantly (p < 0.001) higher total carotenoids content (22.7 ± 0.3 mg/L) than conventional juice (15.7 ± 0.4 mg/L); a similar pattern was observed for the antioxidant activity, with values being 0.076±0.004 and 0.053 ± 0.003 mM Trolox m/L in organic and conventional juices, respectively. A trained panel stated that organic Orogrande juices had higher intensities of orange color, fresh mandarin and floral aromas than conventional juices.


Inhibition of human cancer cell growth by 1,25-dihydroxyvitamin D3 metabolites.
Specific high-affinity 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] receptors, which can undergo hormone-dependent activation and nuclear localization, have been demonstrated in a wide variety of established human cancer cell lines and surgically obtained human cancer tissues. 1,25-(OH)2D3 has been reported by some workers to stimulate cancer cell replication at low "physiological" concentrations and by ourselves and others to inhibit at higher concentrations. We report here that 1,25-(OH)2D3 had a biphasic effect on the replication of two distinct human cancer cell lines, i.e., the breast cancer T-47D and the malignant melanoma MM96, an effect analogous to that of estrogens on the breast cancer cell line MCF-7. These inhibitory effects were accompanied by marked morphological changes. Furthermore, two known metabolites of 1,25-(OH)2D3, i.e., 1,24,25-trihydroxyvitamin D3 and 1,25,26-trihydroxyvitamin D3, which compete for binding to the 1,25-(OH)2D3 receptor, did not stimulate but were almost equipotent with 1,25-(OH)2D3 in inhibiting the replication of both cell lines. The stimulatory but not the inhibitory effect of 1,25-(OH)2D3 was abolished by cortisone. These 1,25-dihydroxyvitamin D3 metabolites show promise for the inhibition of cancer growth, analogous to the effect of estrogens and antiestrogens in breast cancer but with potential application in a much wider range of human cancers.


Gene conversion and transfer of genetic information within the inverted region of inversion heterozygotes.
Prior studies of recombination which monitor exchange events in exceedingly short intervals (i.e., separable sites within a cistron) reveal that the basic event in recombination involves a non-reciprocal transfer of information, termed conversion. As a logical consequence of the model suggested by the work in Drosophila, the present investigation examined recombination between rosy mutant alleles (ry:3-52.0) in Drosophila melanogaster in a paracentric inversion (In(3R)P(18)) heterozygote, which placed the rosy region approximately at the center of the inverted region. Comparison of the results of this study with experiments carried out in standard chromosome homozygotes reveals a dramatic suppression of classical crossovers between the rosy mutant alleles in the inversion heterozygote. However, conversions continue to occur for all rosy mutant alleles in all heterozygous combinations in the inversion heterozygote. Moreover, the order of magnitude of conversion frequencies seen in the inversion heterozygote does not change from that seen in the standard chromosome homozygote study. The significance of these observations with reference to the role of rearrangements as barriers of information transfer is discussed. Particular attention is directed to the elaborate inversion polymorphisms seen in natural populations, and to notions concerning their role in the evolution of adaptive gene complexes.


Adjuvant effect of liposome in chicken result from induction of nitric oxide.
Intranasal delivery of liposome-encapsulated inactivated Newcastle Disease virus (NDV) is known to be an effective vaccine for inducing immunity in the respiratory tract from our previous reports. Four-week-old specific pathogen-free chickens were intranasally immunized with NDV entrapped in phosphatidylcholine-liposomes (PC-Lip). The mucosal levels of anti-NDV s-immunoglobulin A (IgA), serum IgG, a high hemagglutination inhibition titer (1:640), and the high survival rate with the PC-Lip vaccine were comparable to those of our previous report. The immune mechanisms of the PC-Lip adjuvant were determined by in vitro cellular experiments using the NO production of chicken spleen macrophages. The most important finding of this study was proving that macrophages were stimulated by PC-Lip via the extracellular regulated kinase (ERK) 1/2 and nuclear factor (NF)-κB activation pathways. This finding may be useful for developing potent mucosal vaccine delivery systems in the future.


Modifiable lifestyle behaviours impact the health-related quality of life of bladder cancer survivors.
To examine health behaviours in bladder cancer survivors including physical activity (PA), body mass index, diet quality, smoking and alcohol consumption, and to explore their relationship with health-related quality of life (HRQoL). Cross-sectional questionnaire packages were distributed to bladder cancer survivors (muscle-invasive bladder cancer [MIBC] and non-muscle-invasive bladder cancer [NMIBC]) aged >18 years, and proficient in English. Lifestyle behaviours were measured using established measures/questions, and reported using descriptive statistics. HRQoL was assessed using the validated Bladder Utility Symptom Scale, and its association with lifestyle behaviours was evaluated using analysis of covariance (ancova) and multivariate regression analyses. A total of 586 participants completed the questionnaire (52% response rate). The mean (SD) age was 67.3 (10.2) years, and 68% were male. PA guidelines were met by 20% (n = 117) and 22.7% (n = 133) met dietary guidelines. In all, 60.9% (n = 357) were overweight/obese, and the vast majority met alcohol recommendations (n = 521, 92.5%) and were current non-smokers (n = 535, 91.0%). Health behaviours did not differ between MIBC and NMIBC, and cancer treatment stages. Sufficient PA, healthy diet, and non-smoking were significantly associated with HRQoL, and the number of health behaviours participants engaged in was positively associated with HRQoL (P < 0.001). Bladder cancer survivors are not meeting guidelines for important lifestyle behaviours that may improve their overall HRQoL. Future research should investigate the impact of behavioural and educational interventions for health behaviours on HRQoL in this population.


Lifelong personal health data and application software via virtual machines in the cloud.
Personal Health Records (PHRs) should remain the lifelong property of patients, who should be able to show them conveniently and securely to selected caregivers and institutions. In this paper, we present MyPHRMachines, a cloud-based PHR system taking a radically new architectural solution to health record portability. In MyPHRMachines, health-related data and the application software to view and/or analyze it are separately deployed in the PHR system. After uploading their medical data to MyPHRMachines, patients can access them again from remote virtual machines that contain the right software to visualize and analyze them without any need for conversion. Patients can share their remote virtual machine session with selected caregivers, who will need only a Web browser to access the pre-loaded fragments of their lifelong PHR. We discuss a prototype of MyPHRMachines applied to two use cases, i.e., radiology image sharing and personalized medicine.


Assessment of amide I spectroscopic maps for a gas-phase peptide using IR-UV double-resonance spectroscopy and density functional theory calculations.
The spectroscopy of amide I vibrations has become a powerful tool for exploring protein structure and dynamics. To help with spectral interpretation, it is often useful to perform molecular dynamics (MD) simulations. To connect spectroscopic experiments to simulations in an efficient manner, several researchers have proposed "maps," which relate observables in classical MD simulations to quantum spectroscopic variables. It can be difficult to discern whether errors in the theoretical results (compared to experiment) arise from inaccuracies in the MD trajectories or in the maps themselves. In this work, we evaluate spectroscopic maps independently from MD simulations by comparing experimental and theoretical spectra for a single conformation of the α-helical model peptide Ac-Phe-(Ala)5-Lys-H(+) in the gas phase. Conformation-specific experimental spectra are obtained for the unlabeled peptide and for several singly and doubly (13)C-labeled variants using infrared-ultraviolet double-resonance spectroscopy, and these spectra are found to be well-modeled by density functional theory (DFT) calculations at the B3LYP/6-31G** level. We then compare DFT results for the deuterated and (13)C(18)O-labeled peptide with those from spectroscopic maps developed and used previously by the Skinner group. We find that the maps are typically accurate to within a few cm(-1) for both frequencies and couplings, having larger errors only for the frequencies of terminal amides.


The small RNA repertoire of Dictyostelium discoideum and its regulation by components of the RNAi pathway.
Small RNAs play crucial roles in regulation of gene expression in many eukaryotes. Here, we report the cloning and characterization of 18-26 nt RNAs in the social amoeba Dictyostelium discoideum. This survey uncovered developmentally regulated microRNA candidates whose biogenesis, at least in one case, is dependent on a Dicer homolog, DrnB. Furthermore, we identified a large number of 21 nt RNAs originating from the DIRS-1 retrotransposon, clusters of which have been suggested to constitute centromeres. Small RNAs from another retrotransposon, Skipper, were significantly up-regulated in strains depleted of the second Dicer-like protein, DrnA, and a putative RNA-dependent RNA polymerase, RrpC. In contrast, the expression of DIRS-1 small RNAs was not altered in any of the analyzed strains. This suggests the presence of multiple RNAi pathways in D. discoideum. In addition, we isolated several small RNAs with antisense complementarity to mRNAs. Three of these mRNAs are developmentally regulated. Interestingly, all three corresponding genes express longer antisense RNAs from which the small RNAs may originate. In at least one case, the longer antisense RNA is complementary to the spliced but not the unspliced pre-mRNA, indicating synthesis by an RNA-dependent RNA polymerase.


Cell-penetrating peptides selectively targeting SMAD3 inhibit profibrotic TGF-β signaling.
TGF-β is considered a master switch in the pathogenesis of organ fibrosis. The primary mediators of this activity are the SMAD proteins, particularly SMAD3. In the current study, we have developed a cell-penetrating peptide (CPP) conjugate of the HIV TAT protein that is fused to an aminoterminal sequence of sorting nexin 9 (SNX9), which was previously shown to bind phosphorylated SMAD3 (pSMAD3). We determined that specifically preventing the nuclear import of pSMAD3 using the TAT-SNX9 peptide inhibited profibrotic TGF-β activity in murine cells and human lung fibroblasts as well as in vivo with no demonstrable toxicity. TGF-β signaling mediated by pSMAD2, bone morphogenetic protein 4 (BMP4), EGF, or PDGF was unaffected by the TAT-SNX9 peptide. Furthermore, while the TAT-SNX9 peptide prevented TGF-β's profibrotic activity in vitro as well as in 2 murine treatment models of pulmonary fibrosis, a 3-amino acid point mutant that was unable to bind pSMAD3 proved ineffective. These findings indicate that specifically targeting pSMAD3 can ameliorate both the direct and indirect fibroproliferative actions of TGF-β.


Chronic conditions and sleep problems among adults aged 50 years or over in nine countries: a multi-country study.
Data on the association between chronic conditions or the number of chronic conditions and sleep problems in low- or middle-income countries is scarce, and global comparisons of these associations with high-income countries have not been conducted. Data on 42116 individuals 50 years and older from nationally-representative samples of the Collaborative Research on Ageing in Europe (Finland, Poland, Spain) and the World Health Organization's Study on Global Ageing and Adult Health (China, Ghana, India, Mexico, Russia, South Africa) conducted between 2011-2012 and 2007-2010 respectively were analyzed. The association between nine chronic conditions (angina, arthritis, asthma, chronic lung disease, depression, diabetes, hypertension, obesity, and stroke) and self-reported severe/extreme sleep problems in the past 30 days was estimated by logistic regression with multiple variables. The age-adjusted prevalence of sleep problems ranged from 2.8% (China) to 17.0% (Poland). After adjustment for confounders, angina (OR 1.75-2.78), arthritis (OR 1.39-2.46), and depression (OR 1.75-5.12) were significantly associated with sleep problems in the majority or all of the countries. Sleep problems were also significantly associated with: asthma in Finland, Spain, and India; chronic lung disease in Poland, Spain, Ghana, and South Africa; diabetes in India; and stroke in China, Ghana, and India. A linear dose-dependent relationship between the number of chronic conditions and sleep problems was observed in all countries. Compared to no chronic conditions, the OR (95%CI) for 1,2,3, and ≥ 4 chronic conditions was 1.41 (1.09-1.82), 2.55 (1.99-3.27), 3.22 (2.52-4.11), and 7.62 (5.88-9.87) respectively in the overall sample. Identifying co-existing sleep problems among patients with chronic conditions and treating them simultaneously may lead to better treatment outcome. Clinicians should be aware of the high risk for sleep problems among patients with multimorbidity. Future studies are needed to elucidate the best treatment options for comorbid sleep problems especially in developing country settings.


Co-occurring mental illness and health care utilization and expenditures in adults with obesity and chronic physical illness.
The objectives of the study were to compare health care expenditures between adults with and without mental illness among individuals with obesity and chronic physical illness. We performed a cross-sectional analysis of 2440 adults (older than age 21) with obesity using a nationally representative survey of households, the Medical Expenditure Panel Survey. Chronic physical illness consisted of self-reported asthma, diabetes, heart disease, hypertension, or osteoarthritis. Mental illness included affective disorders; anxiety, somatoform, dissociative, personality disorders; and schizophrenia. Utilization and expenditures by type of service (total, inpatient, outpatient, emergency room, pharmacy, and other) were the dependent variables. Chi-square tests, logistic regression on likelihood of use, and ordinary least squares regression on logged expenditures among users were performed. All regressions controlled for gender, race/ethnicity, age, martial status, region, education, employment, poverty status, health insurance, smoking, and exercise. All analyses accounted for the complex design of the survey. We found that 25% of adults with obesity and physical illness had a mental illness. The average total expenditures for obese adults with physical illness and mental illness were $9897; average expenditures were $6584 for those with physical illness only. Mean pharmacy expenditures for obese adults with physical illness and mental illness and for those with physical illness only were $3343 and $1756, respectively. After controlling for all independent variables, among adults with obesity and physical illness, those with mental illness were more likely to use emergency services and had higher total, outpatient, and pharmaceutical expenditures than those without mental illness. Among individuals with obesity and chronic physical illness, expenditures increased when mental illness is added. Our study findings suggest cost-savings efforts should examine the reasons for high utilization and expenditures for those with obesity, chronic physical illness, and mental illness.


Mortality in Puerto Rico after Hurricane Maria.
Quantifying the effect of natural disasters on society is critical for recovery of public health services and infrastructure. The death toll can be difficult to assess in the aftermath of a major disaster. In September 2017, Hurricane Maria caused massive infrastructural damage to Puerto Rico, but its effect on mortality remains contentious. The official death count is 64. Using a representative, stratified sample, we surveyed 3299 randomly chosen households across Puerto Rico to produce an independent estimate of all-cause mortality after the hurricane. Respondents were asked about displacement, infrastructure loss, and causes of death. We calculated excess deaths by comparing our estimated post-hurricane mortality rate with official rates for the same period in 2016. From the survey data, we estimated a mortality rate of 14.3 deaths (95% confidence interval [CI], 9.8 to 18.9) per 1000 persons from September 20 through December 31, 2017. This rate yielded a total of 4645 excess deaths during this period (95% CI, 793 to 8498), equivalent to a 62% increase in the mortality rate as compared with the same period in 2016. However, this number is likely to be an underestimate because of survivor bias. The mortality rate remained high through the end of December 2017, and one third of the deaths were attributed to delayed or interrupted health care. Hurricane-related migration was substantial. This household-based survey suggests that the number of excess deaths related to Hurricane Maria in Puerto Rico is more than 70 times the official estimate. (Funded by the Harvard T.H. Chan School of Public Health and others.).


Mating-induced differential coding of plant odour and sex pheromone in a male moth.
Innate behaviours in animals can be influenced by several factors, such as the environment, experience, or physiological status. This behavioural plasticity originates from changes in the underlying neuronal substrate. A well-described form of plasticity is induced by mating. In both vertebrates and invertebrates, males experience a post-ejaculatory refractory period, during which they avoid new females. In the male moth Agrotis ipsilon, mating induces a transient inhibition of responses to the female-produced sex pheromone. To understand the neural bases of this inhibition and its possible odour specificity, we carried out a detailed analysis of the response characteristics of the different neuron types from the periphery to the central level. We examined the response patterns of pheromone-sensitive and plant volatile-sensitive neurons in virgin and mated male moths. By using intracellular recordings, we showed that mating changes the response characteristics of pheromone-sensitive antennal lobe (AL) neurons, and thus decreases their sensitivity to sex pheromone. Individual olfactory receptor neuron (ORN) recordings and calcium imaging experiments indicated that pheromone sensory input remains constant. On the other hand, calcium responses to non-pheromonal odours (plant volatiles) increased after mating, as reflected by increased firing frequencies of plant-sensitive AL neurons, although ORN responses to heptanal remained unchanged. We suggest that differential processing of pheromone and plant odours allows mated males to transiently block their central pheromone detection system, and increase non-pheromonal odour detection in order to efficiently locate food sources.


CO2 chemosensing in rat oesophagus.
Acid in the oesophageal lumen is often sensed as heartburn. It was hypothesised that luminal CO(2), a permeant gas, rather than H(+), permeates through the epithelium, and is converted to H(+), producing an afferent neural signal by activating chemosensors. The rat lower oesophageal mucosa was superfused with pH 7.0 buffer, and pH 1.0 or pH 6.4 high CO(2) (P(CO2) = 260 Torr) solutions with or without the cell-permeant carbonic anhydrase (CA) inhibitor methazolamide (MTZ, 1 mM), the cell-impermeant CA inhibitor benzolamide (BNZ, 0.1 mM), the transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine (CPZ, 0.5 mM) or the acid-sensing ion channel (ASIC) inhibitor amiloride (0.1 mM). Interstitial pH (pH(int)) was measured with 5',6'-carboxyfluorescein (5 mg/kg intravenously) loaded into the interstitial space, and blood flow was measured with laser-Doppler. Perfusion of a high CO(2) solution induced hyperaemia without changing pH(int), mimicking the effect of pH 1.0 perfusion. Perfused MTZ, BNZ, CPZ and amiloride all inhibited CO(2)-induced hyperaemia. CA XIV was expressed in the prickle cells, with CA XII in the basal cells. TRPV1 was expressed in the stratum granulosum and in the muscularis mucosa, whereas all ASICs were expressed in the prickle cells, with ASIC3 additionally in the muscularis mucosa. The response to CO(2) perfusion suggests that CO(2) diffuses through the stratum epithelium, interacting with TRPV1 and ASICs in the epithelium or in the submucosa. Inhibition of the hyperaemic response to luminal CO(2) by CA, TRPV1 and ASIC inhibitors implicates CA and these chemosensors in transduction of the luminal acid signal. Transepithelial CO(2) permeation may explain how luminal H(+) equivalents can rapidly be transduced into hyperaemia, and the sensation of heartburn.


Influences on the use of observational methods by practitioners when identifying risk factors in physical work.
Most observational methods for musculoskeletal disorder risk assessment have been developed by researchers to be applied in specific situations, and practitioners could find difficulties in their use in real-work conditions. The main objective of this study was to identify the factors which have an influence on how useful the observational techniques are perceived to be by practitioners and to what extent these factors influence their perception. A survey was conducted on practitioners regarding the problems normally encountered when implementing these methods, as well as the perceived overall utility of these techniques. The results show that practitioners place particular importance on the support the methods provide in making decisions regarding changes in work systems and how applicable they are to different types of jobs. The results of this study can serve as guide to researchers for the development of new assessment techniques that are more useful and applicable in real-work situations.


Assessment of healthiness among long term inhabiting army soldiers in dry zone of Sri Lanka.
Military personnel, because of the unique nature of their duties, are reluctant to face stressors. Living in hot and humid conditions they frequently suffer dehydration. Army soldiers living in dry zone of Sri Lanka, were screened for chronic kidney disease (CKD), common non-communicable diseases and methicillin resistant Staphylococcus aureus (MRSA) colonization. Albumin creatinine ratio > 30 mg/g urine taken as cut-off for detection of CKD. Screened 417 soldiers, all were men and body mass index were 21.4 ± 2.2 kg/m2. They smoke 0.5 ± 0.1 pack years while consume alcohol 32 ± 3 units/week and were having 100/min average daily moderate physical activity. Eight of them (0.2%) were having essential hypertension, 4 (0.1%) of them were having diabetes mellitus. Blood cholesterol was within normal range. CKD unknown etiology (CKDu) prevalence among screened army soldiers was 0.009. All were from native army recruits. Further, 71.2% had MRSA colonization. In a group of middle aged army recruits, despite tobacco smoking and moderate level of alcohol consumption while continuously having healthy dietary practices with physical activities would leads to low prevalence of communicable diseases. Further, compared to native group of solders, visitors but living long time recruits CKDu incidence is zero.


The role of Candida albicans homologous recombination factors Rad54 and Rdh54 in DNA damage sensitivity.
The fungal pathogen Candida albicans is frequently seen in immune suppressed patients, and resistance to one of the most widely used antifungals, fluconazole (FLC), can evolve rapidly. In recent years it has become clear that plasticity of the Candida albicans genome contributes to drug resistance through loss of heterozygosity (LOH) at resistance genes and gross chromosomal rearrangements that amplify gene copy number of resistance associated genes. This study addresses the role of the homologous recombination factors Rad54 and Rdh54 in cell growth, DNA damage and FLC resistance in Candida albicans. The data presented here support a role for homologous recombination in cell growth and DNA damage sensitivity, as Candida albicans rad54Δ/rad54Δ mutants were hypersensitive to MMS and menadione, and had an aberrant cell and nuclear morphology. The Candida albicans rad54Δ/rad54Δ mutant was defective in invasion of Spider agar, presumably due to the altered cellular morphology. In contrast, mutation of the related gene RDH54 did not contribute significantly to DNA damage resistance and cell growth, and deletion of either Candida albicans RAD54 or Candida albicans RDH54 did not alter FLC susceptibility. Together, these results support a role for homologous recombination in genome stability under nondamaging conditions. The nuclear morphology defects in the rad54Δ/rad54Δ mutants show that Rad54 performs an essential role during mitotic growth and that in its absence, cells arrest in G2. The viability of the single mutant rad54Δ/rad54Δ and the inability to construct the double mutant rad54Δ/rad54Δ rdh54Δ/rdh54Δ suggests that Rdh54 can partially compensate for Rad54 during mitotic growth.


[Pharmacotherapeutics for the New Coronavirus Pneumonia].
The New Coronavirus Pneumonia (NCP, also named as COVID-19 by WHO on Feb 11 2020, is now causing a severe public health emergency in China since. The number of diagnosed cases is more than 40,000 until the submission of this manuscript. Coronavirus has caused several epidemic situations world widely, but the present contagious disease caused by 2019 new Coronavirus is unprecedentedly fulminating. The published cohorts of 2019 new Coronavirus (n-Cov) are single-center studies, or retrospective studies. We here share the therapeutic experiences of NCP treatment with literature review. Combination of Ribavirin and Interferon-α is recommended by the 5(th) edition National Health Commission's Regimen (Revised Edition) because of the effect on MERS (Middle East Respiratory Syndrome), and the effectiveness of Lopinavir/Ritonavir and Remdisivir needs to be confirmed by randomized controlled trial (RCT), given the situation of no specific antivirus drug on NCP is unavailable. Systemic glucocorticosteroid is recommended as a short term use (1~2 mg.kg(-1).d(-1), 3~5d ) by the 5(th) edition National Health Commission's Regimen (Revised Edition) yet RCTs are expected to confirm the effectiveness. Inappropriate application of antibiotics should be avoided, especially the combination of broad-spectrum antibiotics, for the NCP is not often complicated with bacterial infection.


Comparing potential COI and SSU rDNA barcodes for assessing the diversity and phylogenetic relationships of cyphoderiid testate amoebae (Rhizaria: Euglyphida).
The mitochondrial Cytochrome Oxidase Subunit 1 gene (COI) has been promoted as an ideal "DNA barcode" for animal species and other groups of eukaryotes. However, the utility of the COI marker for species level discrimination and for phylogenetic analyses has yet to be tested within the Rhizaria. Accordingly, we analysed mitochondrial COI gene sequences and nuclear small subunit rDNA (SSU) sequences from several morphospecies of euglyphid testate amoebae (Cercozoa, Rhizaria) in order to evaluate the utility of these DNA markers for species discrimination and phylogenetic reconstructions. Sequences were obtained from eleven populations belonging to sixCyphoderiamorphospecies that were isolated from field samples in North America and Europe. Mean inter-population COI sequence dissimilarities were on average 2.9 times greater than in the SSU, while the intra-population sequence dissimilarities were higher in the SSU (0-0.95%) than in the COI (0%); this suggests that the COI fragment is valuable for discriminating Cyphoderiidae isolates. Our study also demonstrated that COI sequences are useful for inferring phylogenetic relationships among Cyphoderiidae isolates. COI and SSU tree topologies were very similar even though the COI fragment used in these analyses (500bp) was much shorter than the SSU sequences (1600bp). Altogether, these results demonstrate the utility of the COI as a potential taxonomic DNA barcode for assessing cyphoderiid species diversity and for inferring phylogenetic relationships within the group.


A Study into the Evolutionary Divergence of the Core Promoter Elements of PRPF31 and TFPT.
Mutations in PRPF31 have been implicated in retinitis pigmentosa, a blinding disease caused by degeneration of rod photoreceptors. The disease mechanism in the majority of cases is haploinsufficiency. Crucially, attempts at generation of animal models of disease have proved unsuccessful, yielding animals with a visual phenotype that does not mirror human disease. This suggests that, in these animals, the transcriptional regulation of PRPF31 is different to humans and compared to other species. Study of the evolution of the PRPF31 core promoter has important implications for our understanding of human disease, as disease phenotype is modified by differentially expressed alleles in the population. PRPF31 lies in a head-to-head arrangement with TFPT, a gene involved in cellular apoptosis. The two genes were shown to share common regulatory elements in the human genome. In this study, the core promoters of PRPF31 and TFPT were characterised by dual-luciferase reporter assay using genomic DNA from the green monkey, domestic dog and house mouse. It was found that the core promoters were conserved between human and monkey. In dog, the TFPT core promoter was conserved, but different PRPF31 gene architecture meant the gene was controlled by a long-range promoter lying some 2000bp from the transcription start site. There was very low level of conservation (<20%) of the PRPF31 5' region between mouse and human. It was shown that mouse populations did not show variable Prpf31 expression levels, revealing a potential explanation for the lack of phenotype observed in the Prpf31 knock-out mouse model.


Time spent in hospital by children: trends in the Oxford Record Linkage Study area.
Routine statistics of hospital care are conventionally based on episodes of care. Thus, whilst statistics on lengths of stay per episode of hospital care are readily available, information is not routinely collected on the total time spent in hospital by individuals who experience several episodes of care. This paper presents data from the Oxford Record Linkage Study which was used to calculate the total length of time spent in hospital by children in each year from 1975-84. The findings of this study provide reassurance that, despite the increase in admission rates in childhood during this period, the total length of time children spend in hospital has generally declined.


The speed of blood pressure fluctuations in patients with chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD) has been associated with increased risk for cardiovascular disease but mechanisms underlying this association are incompletely understood. The speed of beat-to-beat changes in systolic blood pressure (vSBP) was found to be pronounced in patients with elevated cardiovascular risk. Although increased vSBP may thus be a contributing mechanism to cardiovascular morbidity, no data exist on vSBP in patients with COPD. Therefore, the purpose of this study was to evaluate whether there is an association between severity of COPD and vSBP. Resting beat-to-beat blood pressure was recorded during 5 min. vSBP was assessed by calculating the slopes of oscillatory fluctuations in SBP for different inter-beat intervals (IBI). Univariate and multivariate analyses were performed to evaluate the association between forced expiratory volume in 1 s (FEV1) and vSBP. This study comprised 60 patients with COPD (24 females) with a mean [SD] FEV1 of 45.4 [22.7] %predicted and 34 healthy controls. Short-term fluctuations in SBP were more pronounced in patients with COPD compared to healthy controls. There was a significant inverse correlation between FEV1 and vSBP (r=-0.41, p=0.001). Even after adjustment for covariates in multivariate analysis, FEV1 was found to be independently associated with vSBP. Patients with COPD are characterised by steeper blood pressure changes than healthy controls. The speed of fluctuations in SBP is associated with the severity of airflow limitation. Increased vSBP may be a mechanism underpinning the association between COPD and cardiovascular disease.


Diagnosis and treatment of melanoma. European consensus-based interdisciplinary guideline - Update 2016.
Cutaneous melanoma (CM) is potentially the most dangerous form of skin tumour and causes 90% of skin cancer mortality. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum, the European Association of Dermato-Oncology and the European Organisation of Research and Treatment of Cancer was formed to make recommendations on CM diagnosis and treatment, based on systematic literature reviews and the experts' experience. Diagnosis is made clinically using dermoscopy and staging is based upon the AJCC system. CMs are excised with 1-2 cm safety margins. Sentinel lymph node dissection is routinely offered as a staging procedure in patients with tumours >1 mm in thickness, although there is as yet no clear survival benefit for this approach. Interferon-α treatment may be offered to patients with stage II and III melanoma as an adjuvant therapy, as this treatment increases at least the disease-free survival and less clear the overall survival (OS) time. The treatment is however associated with significant toxicity. In distant metastasis, all options of surgical therapy have to be considered thoroughly. In the absence of surgical options, systemic treatment is indicated. For first-line treatment particularly in BRAF wild-type patients, immunotherapy with PD-1 antibodies alone or in combination with CTLA-4 antibodies should be considered. BRAF inhibitors like dabrafenib and vemurafenib in combination with the MEK inhibitors trametinib and cobimetinib for BRAF mutated patients should be offered as first or second line treatment. Therapeutic decisions in stage IV patients should be primarily made by an interdisciplinary oncology team ('Tumour Board').


Liver Metastasis Is Facilitated by the Adherence of Circulating Tumor Cells to Vascular Fibronectin Deposits.
The interaction between circulating tumor cells (CTC) and endothelial cells during extravasation is a critical process during metastatic colonization, but its mechanisms remain poorly characterized. Here we report that the luminal side of liver blood vessels contains fibronectin deposits that are enriched in mice bearing primary tumors and are also present in vessels from human livers affected with metastases. Cancer cells attached to endothelial fibronectin deposits via talin1, a major component of focal adhesions. Talin1 depletion impaired cancer cell adhesion to the endothelium and transendothelial migration, resulting in reduced liver metastasis formation in vivo Talin1 expression levels in patient CTC's correlated with prognosis and therapy response. Together, our findings uncover a new mechanism for liver metastasis formation involving an active contribution of hepatic vascular fibronectin and talin1 in cancer cells. Cancer Res; 77(13); 3431-41. ©2017 AACR.


Perturbation of the O-U-O Angle in Uranyl by Coordination to a 12-Membered Macrocycle.
Reaction of [UO2Cl2(THF)2]2 (THF = tetrahydrofuran) with 2 equiv of (H)N4 ((H)N4 = 2,11-diaza[3,3](2,6) pyridinophane) or (Me)N4 ((Me)N4 = N,N'-dimethyl-2,11-diaza[3,3](2,6) pyridinophane), in MeCN, results in the formation of UO2Cl2((R)N4) (R = H; 1; Me, 2), which were isolated as yellow-orange solids in good yields. Similarly, reaction of UO2(OTf)2(THF)3 with (H)N4 in MeCN results in the formation of UO2(OTf)2((H)N4) (3), as an orange powder in 76% yield. Finally, reaction of UO2(OTf)2(THF)3 with (Me)N4 in THF results in the formation of [UO2(OTf)(THF)((H)N4)][OTf] (4), as an orange powder in 73% yield. Complexes 1-4 were fully characterized, including characterization by X-ray crystallography. These complexes exhibit the smallest O-U-O bond angles measured to date, ranging from 168.2(3)° (for 2) to 161.7(5)° (for 4), a consequence of an unfavorable steric interaction between the oxo ligands and the macrocycle backbone. A Raman spectroscopic study of 1-4 reveals no correlation between O-U-O angle and the U═O νsym mode. However, complexes 1 and 2 do feature lower U═O νsym modes than complexes 3 and 4, which can be rationalized by the stronger donor strength of Cl(-) versus OTf(-). This observation suggests that the identity of the equatorial ligands has a greater effect on the U═O νsym frequency than does a change in O-U-O angle, at least when the changes in the O-U-O angles are small.


Outcomes and Management Considerations in Patients on Dialysis Undergoing Laparoscopic Radical Nephrectomy for Renal-Cell Carcinoma.
To analyze the perioperative outcomes and management considerations in patients with dialysis-dependent end-stage renal disease (ESRD) undergoing laparoscopic radical nephrectomy for renal-cell carcinoma (RCC). There were 224 consecutive laparoscopic radical nephrectomies reviewed. Of those, 37 patients with ESRD were identified and compared with 187 patients with sporadic RCC. Evaluable parameters included age, sex, race, side of surgery, medical comorbidities, body mass index, American Society of Anesthesiologist (ASA) scoring, and age adjusted Charlson Comorbidity Index. All complications occurring intraoperatively and within the first 30 days were classified as per the Clavien classification system. Presurgical workup and transplant considerations were evaluated. Demographic and clinical characteristics were compared using Student t tests and chi-square tests for categoric variables. Compared with non-ESRD patients, those with ESRD were younger and had smaller tumors. ASA was significantly higher in the ESRD group (P<0.001). Mean blood loss was similar between ESRD patients and non-ESRD patients. Overall complication rates were higher in patients with ESRD. Pathologic characteristics of ESRD renal masses included a higher proportion of papillary RCC. Patients with RCC associated with ESRD tend to have a higher ASA class and lower grade tumors. In addition, this population is at increased risk of surgical complications and more likely to need transfusions. Careful preoperative preparation and intraoperative anesthetic management are crucial to minimize patient morbidity and improve outcomes.


Susceptibility of Ochlerotatus taeniorhynchus and Culex nigripalpus for Eeverglades virus.
Everglades virus (EVEV), an alphavirus in the Venezuelan equine encephalitis (VEE) complex, is a mosquito-borne human pathogen endemic to South Florida. Field isolations of EVEV from Culex (Melanoconion) cedecei and laboratory susceptibility experiments established this species as its primary vector. However, isolates of EVEV from Ochlerotatus taeniorhynchus and Culex nigripalpus, more abundant and widespread species in South Florida, suggested that they also transmit EVEV and could infect many people. We performed susceptibility experiments with F(1) generation Oc. taeniorhynchus and Cx. nigripalpus to evaluate their permissiveness to EVEV infection. In contrast to the high degree of susceptibility of Cx. (Mel.) cedecei, Oc. taeniorhynchus and Cx. nigripalpus were relatively refractory to oral EVEV infection, indicating that they are probably not important vectors. Identification of vectors involved in enzootic EVEV transmission will assist in understanding potential changes in vector use that could accompany the emergence of epizootic or epidemic EVEV.


Testing logistic regression coefficients with clustered data and few positive outcomes.
Applications frequently involve logistic regression analysis with clustered data where there are few positive outcomes in some of the independent variable categories. For example, an application is given here that analyzes the association of asthma with various demographic variables and risk factors using data from the third National Health and Nutrition Examination Survey, a weighted multi stage cluster sample. Although there are 742 asthma cases in all (out of 18,395 individuals), for one of the categories of one of the independent variables there are only 25 asthma cases (out of 695 individuals). Generalized Wald and score hypothesis tests, which use appropriate cluster-level variance estimators, and a bootstrap hypothesis test have been proposed for testing logistic regression coefficients with cluster samples. When there are few positive outcomes, simulations presented in this paper show that these tests can sometimes have either inflated or very conservative levels. A simulation-based method is proposed for testing logistic regression coefficients with cluster samples when there are few positive outcomes. This testing methodology is shown to compare favorably with the generalized Wald and score tests and the bootstrap hypothesis test in terms of maintaining nominal levels. The proposed method is also useful when testing goodness-of-fit of logistic regression models using deciles-of-risk tables.


Normative data on development of neural and behavioral mechanisms underlying attention orienting toward social-emotional stimuli: an exploratory study.
The ability of positive and negative facial signals to influence attention orienting is crucial to social functioning. Given the dramatic developmental change in neural architecture supporting social function, positive and negative facial cues may influence attention orienting differently in relatively young or old individuals. However, virtually no research examines such age-related differences in the neural circuitry supporting attention orienting to emotional faces. We examined age-related correlations in attention-orienting biases to positive and negative face emotions in a healthy sample (N=37; 9-40 years old) using functional magnetic resonance imaging and a dot-probe task. The dot-probe task in an fMRI setting yields both behavioral and neural indices of attention biases towards or away from an emotional cue (happy or angry face). In the full sample, angry-face attention bias scores did not correlate with age, and age did not correlate with brain activation to angry faces. However, age did positively correlate with attention bias towards happy faces; age also negatively correlated with left cuneus and left caudate activation to a happy bias fMRI contrast. Secondary analyses suggested age-related changes in attention bias to happy faces. The tendency in younger children to direct attention away from happy faces (relative to neutral faces) was diminished in the older age groups, in tandem with increasing neural deactivation. Implications for future work on developmental changes in attention-emotion processing are discussed.


Short-term diesel exhaust inhalation in a controlled human crossover study is associated with changes in DNA methylation of circulating mononuclear cells in asthmatics.
Changes in DNA methylation have been associated with traffic-related air pollution in observational studies, but the specific mechanisms and temporal dynamics therein have not been explored in a controlled study of asthmatics. In this study, we investigate short-term effects of diesel exhaust inhalation on DNA methylation levels at CpG sites across the genome in circulating blood in asthmatics. A double-blind crossover study of filtered air and diesel exhaust exposures was performed on sixteen non-smoking asthmatic subjects. Blood samples were collected pre-exposure, and then 6 and 30 hours post-exposure. Peripheral blood mononuclear cell DNA methylation was interrogated using the Illumina Infinium HumanMethylation450 Array. Exposure-related changes in DNA methylation were identified. In addition, CpG sites overlapping with Alu or LINE1 repetitive elements and candidate microRNA loci were also analyzed. DNA methylation at 2827 CpG sites were affected by exposure to diesel exhaust but not filtered air; these sites enriched for genes involved in protein kinase and NFkB pathways. CpG sites with significant changes in response to diesel exhaust exposure primarily became less methylated, with a site residing within GSTP1 being among the significant hits. Diesel exhaust-associated change was also found for CpG sites overlapping with Alu and LINE1 elements as well as for a site within miR-21. Short-term exposure to diesel exhaust resulted in DNA methylation changes at CpG sites residing in genes involved in inflammation and oxidative stress response, repetitive elements, and microRNA. This provides plausibility for the role of DNA methylation in pathways by which airborne particulate matter impacts gene expression and offers support for including DNA methylation analysis in future efforts to understand the interactions between environmental exposures and biological systems.


Extended Fenton's process: toward improving biodegradability of drilling wastewater.
In this study, an extended Fenton process was used to improve biodegradability of the waste drilling mud containing bio-refractory polymers. Variation of biodegradability and organics with different molecular weights with the oxidation time were investigated during the Fenton oxidation process. Although the residual total organic carbon (TOC) arrived at a stable level soon after oxidation reaction, organics with the lower molecular weight increased and its biodegradability was improved significantly in the extended oxidation process, which originated from decomposition of residual H2O2 catalyzed by transformation of the Fe3+/Fe2+ and organoradicals. Under the conditions that follow: pH 3.0, H2O2 500 mg L-1, Fe2+ 250 mg L-1, oxidation time 120 min, further TOC removal of 35.9% and biochemical oxygen demand and total organic carbon (BOD/TOC) ratio of 0.83 was achieved. At the biological test, a substantial increase in TOC degradation by biological treatment with extension of Fenton oxidation time was observed. Finally, more than 90% biological removal of the TOC was achieved for the 120 min oxidation treatment. The experimental results highlight that an extended process can be adopted to improve the biodegradability of wastewater by utilization of the slow reaction of hydrogen peroxide with Fe3+ and organoradicals.


Definitions of sedentary in physical-activity-intervention trials: a summary of the literature.
This review describes the definitions of sedentary used to screen community-dwelling adults in physical-activity-intervention trials published from 2000 to 2005. Results of 42 trials showed that definitions of sedentary varied from <20 to <150 min/week of physical activity, and few reported the type (work, household, or leisure) or intensity of activity that was used to screen participants. The range of "sedentary" samples makes it difficult to compare trial results or generalize findings. Published reports of exercise trials would be more useful to practitioners and researchers if they included an explicit description of the cut point used to define sedentary adults in the sample, in terms of maximum minutes or days per week of activity and the wording of the screening measure in terms of type and intensity of activity.


Corticospinal excitability underlying digit force planning for grasping in humans.
Control of digit forces for grasping relies on sensorimotor memory gained from prior experience with the same or similar objects and on online sensory feedback. However, little is known about neural mechanisms underlying digit force planning. We addressed this question by quantifying the temporal evolution of corticospinal excitability (CSE) using single-pulse transcranial magnetic stimulation (TMS) during two reach-to-grasp tasks. These tasks differed in terms of the magnitude of force exerted on the same points on the object to isolate digit force planning from reach and grasp planning. We also addressed the role of intracortical circuitry within primary motor cortex (M1) by quantifying the balance between short intracortical inhibition and facilitation using paired-pulse TMS on the same tasks. Eighteen right-handed subjects were visually cued to plan digit placement at predetermined locations on the object and subsequently to exert either negligible force ("low-force" task, LF) or 10% of their maximum pinch force ("high-force" task, HF) on the object. We found that the HF task elicited significantly smaller CSE than the LF task, but only when the TMS pulse coincided with the signal to initiate the reach. This force planning-related CSE modulation was specific to the muscles involved in the performance of both tasks. Interestingly, digit force planning did not result in modulation of M1 intracortical inhibitory and facilitatory circuitry. Our findings suggest that planning of digit forces reflected by CSE modulation starts well before object contact and appears to be driven by inputs from frontoparietal areas other than M1.


Work resumption or not after rehabilitation? A descriptive study from six social insurance offices.
The objective of this study was to describe measures and outcomes of vocational rehabilitation at six local national insurance offices in the same county in Sweden. Data were collected from mainframe registers and other records at each office. There were great differences in sickness allowance, incapacity rate, selected rehabilitation measures and resuming work. The percentage of sick-listed people who received any rehabilitation measure differed from 1.2 to 8.7%. The gender distribution for the study population was 36% men and 64% women and the predominant diagnosis was musculoskeletal pain conditions, which was followed by psychiatric disorders. Outcomes varied from office B, which reported 58% fully fit after completed planned rehabilitation, to office C, which reported only 24% fully fit. The clear differences in outcome between the offices indicate that various rehabilitation measures differ in effectiveness. The rehabilitation measure 'investigation of working ability' was not linked to any great proportion of people resuming work, but showed a greater correspondence to full disability pension. There were also large differences in social and demographic factors in the different municipalities. The effect of these on the rehabilitation process requires further investigation.


Sense of coherence and the motivational process of the job-demands-resources model.
This longitudinal study systematically examines the various roles played by the personal resource "sense of coherence" (SoC) in the motivational process described by the job-demands-resources model. SoC captures the extent to which people perceive their life as comprehensible, manageable and meaningful, and there is evidence of its influence in many health-related outcomes. The first aim here was to establish whether a resourceful working environment builds up SoC and whether SoC leads to work engagement. A second aim was to test reverse relationships: how work engagement leads to SoC and how SoC in turn relates to job resources. A third aim was to assess whether SoC boosts the relationship between job resources and work engagement. The study utilized a 3-wave, 3-month panel design, involving 940 employees working in a broad range of occupations and economic sectors. The results of longitudinal structural equation modeling show that job resources predict SoC and SoC predicts work engagement, suggesting a mediating role of SoC. In addition, SoC predicts job resources, suggesting reciprocal relationships between job resources and SoC. No boosting effect of SoC was found. Overall, the present findings support the view that providing employees with a resourceful working environment will help to build their SoC. The effects of SoC on perceptual, appraisal, and behavioral processes may in turn lead to enhanced job resources and positive outcomes such as greater work engagement.


Evaluation of standardized sample collection, packaging, and decontamination procedures to assess cross-contamination potential during Bacillus anthracis incident response operations.
Sample collection procedures and primary receptacle (sample container and bag) decontamination methods should prevent contaminant transfer between contaminated and non-contaminated surfaces and areas during bio-incident operations. Cross-contamination of personnel, equipment, or sample containers may result in the exfiltration of biological agent from the exclusion (hot) zone and have unintended negative consequences on response resources, activities and outcomes. The current study was designed to: (1) evaluate currently recommended sample collection and packaging procedures to identify procedural steps that may increase the likelihood of spore exfiltration or contaminant transfer; (2) evaluate the efficacy of currently recommended primary receptacle decontamination procedures; and (3) evaluate the efficacy of outer packaging decontamination methods. Wet- and dry-deposited fluorescent tracer powder was used in contaminant transfer tests to qualitatively evaluate the currently-recommended sample collection procedures. Bacillus atrophaeus spores, a surrogate for Bacillus anthracis, were used to evaluate the efficacy of spray- and wipe-based decontamination procedures. Both decontamination procedures were quantitatively evaluated on three types of sample packaging materials (corrugated fiberboard, polystyrene foam, and polyethylene plastic), and two contamination mechanisms (wet or dry inoculums). Contaminant transfer results suggested that size-appropriate gloves should be worn by personnel, templates should not be taped to or removed from surfaces, and primary receptacles should be selected carefully. The decontamination tests indicated that wipe-based decontamination procedures may be more effective than spray-based procedures; efficacy was not influenced by material type but was affected by the inoculation method. Incomplete surface decontamination was observed in all tests with dry inoculums. This study provides a foundation for optimizing current B. anthracis response procedures to minimize contaminant exfiltration.


Exposure to Solar UV During Outdoor Construction Work in Britain.
Excessive exposure to ultraviolet (UV) radiation from the sun in summer can cause skin cancer and in Britain there are around 1500 new cases of non-melanoma skin cancer (NMSC) each year, caused by exposure to solar UV at work. Little is known about the magnitude of UV exposure amongst outdoor construction workers in Britain, although this is one of the main groups at risk. The aim of this paper is to summarise measurements of erythema-weighted UVB radiation amongst construction workers in Scotland and the Southeast of England and interpret the data in terms of the risk of NMSC. The measurements were made as part of an intervention study using short mobile phone text messages to alter worker behaviour to either reduce UV exposure in summer or increase serum vitamin D in winter; the intervention is only briefly reported here. Data were collected from 67 workers from 9 worksites, of whom 41 provided measures of UV exposure for 758 working days. Daily exposure ranged from 0 to 13.47 standard erythema dose (SED), with the mean exposure for outdoor workers being 2.0 SED and the corresponding value for indoor workers being 0.7 SED. These data were obtained from a sensor located on the back of the workers hard hat; others have measured exposure on the wrist or upper arm and these locations probably, on average, have higher levels of UV exposure. It is likely that an outdoor construction worker in Britain could accumulate sufficient solar UV exposure over 30-40 years of work to more than double their risk of NMSC. We argue that employers in Britain should take a more proactive approach to manage sun safety and they should take responsibility for skin health surveillance for their workers.


Hemorrhagic vasculopathy after treatment of central nervous system neoplasia in childhood: diagnosis and follow-up.
To review the clinical data, imaging findings, and intermediate outcomes of a series of children with hemorrhagic vasculopathy after treatment for intracranial neoplasia. We retrospectively analyzed the medical records and imaging examinations of 20 pediatric patients (ages 1 to 15 years) with intracranial neoplasia in whom delayed intracranial hemorrhage developed after cranial irradiation or radiation combined with systemic or intrathecal chemotherapy. Patients with intracranial hemorrhage from other identifiable causes were excluded. Histopathologic analysis was available in four patients. Twenty patients with delayed intracranial hemorrhage received cranial irradiation alone (n = 9) or combined radiation and chemotherapy (n = 11) for primary brain tumors (n = 13), leukemia (n = 6), or lymphoma (n = 1). Imaging findings were consistent with hemorrhages of varying ages. The hemorrhages were not associated with tumor recurrence nor second tumors. Except for location of the hemorrhage, no significant relationship was established between outcome and original diagnosis, radiation dose (range, 1800 to 6000 centigray), chemotherapeutic agent or dosage, age at treatment, or interval between therapy and hemorrhage (mean, 8.1 years). Only brain stem hemorrhage was associated with a poor outcome. In children with central nervous system neoplasia who have undergone cranial irradiation, or radiation combined with chemotherapy, delayed intracranial hemorrhage may develop.


Quantitative fluorescence and elastic scattering tissue polarimetry using an Eigenvalue calibrated spectroscopic Mueller matrix system.
A novel spectroscopic Mueller matrix system has been developed and explored for both fluorescence and elastic scattering polarimetric measurements from biological tissues. The 4 × 4 Mueller matrix measurement strategy is based on sixteen spectrally resolved (λ = 400 - 800 nm) measurements performed by sequentially generating and analyzing four elliptical polarization states. Eigenvalue calibration of the system ensured high accuracy of Mueller matrix measurement over a broad wavelength range, either for forward or backscattering geometry. The system was explored for quantitative fluorescence and elastic scattering spectroscopic polarimetric studies on normal and precancerous tissue sections from human uterine cervix. The fluorescence spectroscopic Mueller matrices yielded an interesting diattenuation parameter, exhibiting differences between normal and precancerous tissues.


Homozygosity in the ApoE 4 polymorphism is associated with dysphagic symptoms in older adults.
Apolipoprotein E (ApoE) is the most well-described genetic risk factor for Alzheimer's disease and nonpathological cognitive decline. While possession of the E2 allele may have protective properties, substantial research evidence suggests the E4 allele increases the risk of cognitive degeneration. As neurodegenerative processes are implicated in swallowing dysfunction, we hypothesized that the presence of ApoE 4 would be predictive of dysphagia symptoms in older adults. Eight hundred members of a genetically well characterized community dwelling elderly cohort received the Sydney oropharyngeal dysphagia questionnaire via mail. Cognitive function was also measured using the modified Telephone Interview of Cognitive Status (TiCS-m) and depression with the Geriatric Depression Score (GDS). ApoE allele was genotyped on blood samples from all subjects and data analyzed using standard statistical software (SPSS version 16). Completed questionnaire response rate was 79% (23.5% men, 76.5% women; mean age 81 ± 5 years; range 69-98 years). Possession of one or more of the ApoE 4 and 2 alleles was found in 23.5% and 16%, respectively. Swallowing score was significantly related to GDS (rho 0.133, P < 0.001**) and age (rho 0.107, P < 0.007**) but not general cognitive function as measured by TICS-m. Self-reported swallowing function was not significantly associated with heterozygosity of any allele or homozygosity for E2 or E3 alleles. Although infrequent (1.1% of all subjects) ApoE E4 homozygosity was significantly associated with higher swallowing scores compared to all other allele combinations (P = 0.033) and while attenuated, was still predicted in multivariate regression modeling (B = 0.812; SE = 0.323; P = 0.012). We report the association between ApoE 4 homozygous genotype and self-reported oropharyngeal dysphagia symptoms in community-dwelling older adults. As this association is weakened by the multivariate analysis and the population frequency of ApoE 4 allele homozygosity is low, this finding while intriguing requires replication in larger independent cohorts.