Non-invasive monitoring of Streptococcus pyogenes vaccine efficacy using biophotonic imaging.

Streptococcus pyogenes infection of the nasopharynx represents a key step in the pathogenic cycle of this organism and a major focus for vaccine development, requiring robust models to facilitate the screening of potentially protective antigens. One antigen that may be an important target for vaccination is the chemokine protease, SpyCEP, which is cell surface-associated and plays a role in pathogenesis. Biophotonic imaging (BPI) can non-invasively characterize the spatial location and abundance of bioluminescent bacteria in vivo. We have developed a bioluminescent derivative of a pharyngeal S. pyogenes strain by transformation of an emm75 clinical isolate with the luxABCDE operon. Evaluation of isogenic recombinant strains in vitro and in vivo confirmed that bioluminescence conferred a growth deficit that manifests as a fitness cost during infection. Notwithstanding this, bioluminescence expression permitted non-invasive longitudinal quantitation of S. pyogenes within the murine nasopharynx albeit with a detection limit corresponding to approximately 10(5) bacterial colony forming units (CFU) in this region. Vaccination of mice with heat killed streptococci, or with SpyCEP led to a specific IgG response in the serum. BPI demonstrated that both vaccine candidates reduced S. pyogenes bioluminescence emission over the course of nasopharyngeal infection. The work suggests the potential for BPI to be used in the non-invasive longitudinal evaluation of potential S. pyogenes vaccines

Efficacy of live B1 or Ulster 2C Newcastle disease vaccines simultaneously vaccinated with inactivated oil adjuvant vaccine for protection of Newcastle disease virus in broiler chickens

Two hundred, one-day-old broiler chicks were divided into groups 1, 2 and 3 containing 60, 70 and 70 chicks, respectively. The groups were divided into subgroups of 10 chicks that were vaccinated according to the following scheme: group 1 unvaccinated control, group 2 vaccinated subcutaneously at 1 day old with inactivated oil adjuvant vaccine (IOAV) in combination with live B1 vaccine. Group 3 was vaccinated in the same mode as group 2 with IOAV and live Ulster 2C vaccine. All birds were challenged when they were 28 days old. Mortality rate, body weight gain and feed conversion ratio (FCR) were monitored before and after challenge. All the chickens in group 1 died, indicating that there was no disease resistance of this unvaccinated control group of chickens. Conversely, the monitored disease resistance of chickens in groups 2 and 3 was 68.57% ± 18.64 and 88.57% ± 9.00, respectively (P < 0.05). The morbidity of chickens in groups 2 and 3 was 37.89% ± 14.36 and 14.76% ± 12.40, respectively (P < 0.05). The body weight gain, feed intake and FCR of group 3 were significantly better than those of group 2 (P < 0.05) during 1–42 days old. The simultaneous vaccination with B1 or Ulster 2C and IOAV of 1-day-old chicks gave some protection of 28-day-old broilers without a booster vaccination

Genome Sizes and the Benford Distribution

BACKGROUND: Data on the number of Open Reading Frames (ORFs) coded by genomes from the 3 domains of Life show the presence of some notable general features. These include essential differences between the Prokaryotes and Eukaryotes, with the number of ORFs growing linearly with total genome size for the former, but only logarithmically for the latter. RESULTS: Simply by assuming that the (protein) coding and non-coding fractions of the genome must have different dynamics and that the non-coding fraction must be particularly versatile and therefore be controlled by a variety of (unspecified) probability distribution functions (pdf's), we are able to predict that the number of ORFs for Eukaryotes follows a Benford distribution and must therefore have a specific logarithmic form. Using the data for the 1000+ genomes available to us in early 2010, we find that the Benford distribution provides excellent fits to the data over several orders of magnitude. CONCLUSIONS: In its linear regime the Benford distribution produces excellent fits to the Prokaryote data, while the full non-linear form of the distribution similarly provides an excellent fit to the Eukaryote data. Furthermore, in their region of overlap the salient features are statistically congruent. This allows us to interpret the difference between Prokaryotes and Eukaryotes as the manifestation of the increased demand in the biological functions required for the larger Eukaryotes, to estimate some minimal genome sizes, and to predict a maximal Prokaryote genome size on the order of 8-12 megabasepairs. These results naturally allow a mathematical interpretation in terms of maximal entropy and, therefore, most efficient information transmission

A Model of Brain Circulation and Metabolism: NIRS Signal Changes during Physiological Challenges

We construct a model of brain circulation and energy metabolism. The model is designed to explain experimental data and predict the response of the circulation and metabolism to a variety of stimuli, in particular, changes in arterial blood pressure, CO2 levels, O2 levels, and functional activation. Significant model outputs are predictions about blood flow, metabolic rate, and quantities measurable noninvasively using near-infrared spectroscopy (NIRS), including cerebral blood volume and oxygenation and the redox state of the CuA centre in cytochrome c oxidase. These quantities are now frequently measured in clinical settings; however the relationship between the measurements and the underlying physiological events is in general complex. We anticipate that the model will play an important role in helping to understand the NIRS signals, in particular, the cytochrome signal, which has been hard to interpret. A range of model simulations are presented, and model outputs are compared to published data obtained from both in vivo and in vitro settings. The comparisons are encouraging, showing that the model is able to reproduce observed behaviour in response to various stimuli

Optimal functional outcome measures for assessing treatment for Dupuytren's disease: A systematic review and recommendations for future practice

This article is available through the Brunel Open Access Publishing Fund. Copyright © 2013 Ball et al.; licensee BioMed Central Ltd.Background: Dupuytren's disease of the hand is a common condition affecting the palmar fascia, resulting in progressive flexion deformities of the digits and hence limitation of hand function. The optimal treatment remains unclear as outcomes studies have used a variety of measures for assessment. Methods: A literature search was performed for all publications describing surgical treatment, percutaneous needle aponeurotomy or collagenase injection for primary or recurrent Dupuytren’s disease where outcomes had been monitored using functional measures. Results: Ninety-one studies met the inclusion criteria. Twenty-two studies reported outcomes using patient reported outcome measures (PROMs) ranging from validated questionnaires to self-reported measures for return to work and self-rated disability. The Disability of Arm, Shoulder and Hand (DASH) score was the most utilised patient-reported function measure (n=11). Patient satisfaction was reported by eighteen studies but no single method was used consistently. Range of movement was the most frequent physical measure and was reported in all 91 studies. However, the methods of measurement and reporting varied, with seventeen different techniques being used. Other physical measures included grip and pinch strength and sensibility, again with variations in measurement protocols. The mean follow-up time ranged from 2 weeks to 17 years. Conclusions: There is little consistency in the reporting of outcomes for interventions in patients with Dupuytren’s disease, making it impossible to compare the efficacy of different treatment modalities. Although there are limitations to the existing generic patient reported outcomes measures, a combination of these together with a disease-specific questionnaire, and physical measures of active and passive individual joint Range of movement (ROM), grip and sensibility using standardised protocols should be used for future outcomes studies. As Dupuytren’s disease tends to recur following treatment as well as extend to involve other areas of the hand, follow-up times should be standardised and designed to capture both short and long term outcomes

Impact of flavonoid-rich black tea and beetroot juice on postprandial peripheral vascular resistance and glucose homeostasis in obese, insulin-resistant men: a randomized controlled trial.

BACKGROUND: Insulin-stimulated muscle blood flow facilitates plasma glucose disposal after a meal, a mechanism that is impaired in obese, insulin-resistant volunteers. Nitrate- or flavonoid-rich products, through their proposed effects on nitric oxide, may improve postprandial blood flow and, subsequently, glucose disposal. To investigate whether a single dose of nitrate-rich beetroot juice or flavonoid-rich black tea lowers postprandial muscle vascular resistance in obese volunteers and alters postprandial glucose or insulin concentrations. METHOD: In a randomised, controlled, cross-over study, 16 obese, insulin-resistant males consumed 75 g glucose, which was combined with 100 ml black tea, beetroot juice or control (water). Peripheral vascular resistance (VR), calculated as mean arterial pressure divided by blood flow, was assessed in the arm and leg conduit arteries, resistance arteries and muscle microcirculation across 3 h (every 30-min) after the oral glucose load. RESULTS: During control, we found no postprandial response in VR in conduit, resistance and microvessels (all P > 0.05). Black tea decreased VR compared to control in conduit, resistance and microvessels (all P < 0.05). Beetroot juice decreased postprandial VR in resistance vessels, but not in conduit artery and microvessels. Although postprandial glucose response was similar after all interventions, postprandial insulin response was attenuated by ~29 % after tea (P < 0.0005), but not beetroot juice. CONCLUSIONS: A single dose of black tea decreased peripheral VR across upper and lower limbs after a glucose load which was accompanied by a lower insulin response. Future studies in insulin-resistant subjects are warranted to confirm the observed effects and to explore whether long-term regular tea consumption affects glucose homeostasis. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov on 30(th) November 2012 (NCT01746329)

Observation of an Exotic S=+1S=+1 Baryon in Exclusive Photoproduction from the Deuteron

In an exclusive measurement of the reaction $\gamma d \to K^+ K^- p n$, a narrow peak that can be attributed to an exotic baryon with strangeness $S=+1$ is seen in the $K^+n$ invariant mass spectrum. The peak is at $1.542\pm 0.005$ GeV/c$^2$ with a measured width of 0.021 GeV/c$^2$ FWHM, which is largely determined by experimental mass resolution. The statistical significance of the peak is $5.2 \pm 0.6 \sigma$. The mass and width of the observed peak are consistent with recent reports of a narrow $S=+1$ baryon by other experimental groups.Comment: 5 pages, 5 figure

Measurement of Beam-Spin Asymmetries for Deep Inelastic π+\pi^+ Electroproduction

We report the first evidence for a non-zero beam-spin azimuthal asymmetry in the electroproduction of positive pions in the deep-inelastic region. Data have been obtained using a polarized electron beam of 4.3 GeV with the CLAS detector at the Thomas Jefferson National Accelerator Facility (JLab). The amplitude of the $\sin\phi$ modulation increases with the momentum of the pion relative to the virtual photon, $z$, with an average amplitude of $0.038 \pm 0.005 \pm 0.003$ for $0.5 < z < 0.8$ range.Comment: 5 pages, RevTEX4, 3 figures, 2 table

Measurement of the Polarized Structure Function σLT′\sigma_{LT^\prime} for p(e⃗,e′p)πop(\vec{e},e'p)\pi^o in the Δ(1232)\Delta(1232) Resonance Region

The polarized longitudinal-transverse structure function $\sigma_{LT^\prime}$ has been measured in the $\Delta(1232)$ resonance region at $Q^2=0.40$ and 0.65 GeV$^2$. Data for the $p(\vec e,e'p)\pi^o$ reaction were taken at Jefferson Lab with the CEBAF Large Acceptance Spectrometer (CLAS) using longitudinally polarized electrons at an energy of 1.515 GeV. For the first time a complete angular distribution was measured, permitting the separation of different non-resonant amplitudes using a partial wave analysis. Comparison with previous beam asymmetry measurements at MAMI indicate a deviation from the predicted $Q^2$ dependence of $\sigma_{LT^{\prime}}$ using recent phenomenological models.Comment: 5 pages, LaTex, 4 eps figures: to be published in PRC/Rapid Communications. Version 2 has revised Q^2 analysi

Two-Nucleon Momentum Distributions Measured in 3He(e,e'pp)n

We have measured the 3He(e,e'pp)n reaction at 2.2 GeV over a wide kinematic range. The kinetic energy distribution for `fast' nucleons (p > 250 MeV/c) peaks where two nucleons each have 20% or less, and the third nucleon has most of the transferred energy. These fast pp and pn pairs are back-to-back with little momentum along the three-momentum transfer, indicating that they are spectators. Experimental and theoretical evidence indicates that we have measured distorted two-nucleon momentum distributions by striking the third nucleon and detecting the spectator correlated pair.Comment: 6 pages, 5 figures, submitted to PR