Validation of a predictive method for sunscreen formula evaluation using gene expression analysis in a Chinese reconstructed full-thickness skin model.

OBJECTIVE: This study aimed to establish a predictive in vitro method for assessing the photoprotective properties of sunscreens using a reconstructed full-thickness skin model. MATERIALS AND METHODS: A full-thickness skin model reconstructed with human fibroblasts and keratinocytes isolated from Chinese skin was exposed to daily UV radiation (DUVR). We examined the transcriptomic response, identifying genes for which expression was modulated by DUVR in a dose-dependent manner. We then validated the methodology for efficacy evaluation of different sunscreens formulas. RESULTS: The reconstructed skin model was histologically consistent with human skin, and upon DUVR exposure, the constituent fibroblasts and keratinocytes exhibited transcriptomic alterations in pathways associated with oxidative stress, inflammation and extracellular matrix remodelling. When used to evaluate sunscreen protection on the model, the observed level of protection from UV-induced gene expression was consistent with the corresponding protection factors determined clinically and allowed for statistical ranking of sunscreen efficacy. CONCLUSIONS: Within this study we show that quantification of gene modulation within the reconstructed skin model is a biologically relevant approach with sensitivity and predictability to evaluate photoprotection products.

OBJECTIF: Cette étude visait à établir une méthode prédictive in vitro permettant d'évaluer les propriétés photoprotectrices des écrans solaires à l'aide d'un modèle de peau reconstruite sur toute son épaisseur. MATÉRIELS ET MÉTHODES: Un modèle de peau reconstruite sur toute son épaisseur avec des fibroblastes et des kératinocytes humains isolés à partir de peaux chinoises a été exposé au rayonnement UV quotidien (DUVR). Nous avons examiné la réponse transcriptomique en identifiant les gènes dont l'expression était modulée par le DUVR de façon dépendante à la dose. Nous avons ensuite validé la méthodologie d'évaluation de l'efficacité des formules des différents écrans solaires. RÉSULTATS: Le modèle de peau reconstruite correspondait histologiquement à de la peau humaine, et lors de l'exposition à des DUVR, les fibroblastes et les kératinocytes qui la composaient présentaient des altérations transcriptomiques des voies associées au stress oxydatif, à l'inflammation et au remodelage de la matrice extracellulaire. Lorsque ce modèle a été utilisé pour évaluer la protection solaire, le niveau de protection observé de l'expression génique induite par les UV correspondait aux facteurs de protection cliniques déterminés correspondants et permettait un classement statistique de l'efficacité de la protection solaire. CONCLUSIONS: Dans cette étude, nous montrons que la quantification de la modulation génique dans le modèle de peau reconstruite est une approche biologiquement pertinente offrant une sensibilité et une prédictibilité pour évaluer les produits de photoprotection.

Polygonum multiflorum Radix extract protects human foreskin melanocytes from oxidative stress in vitro and potentiates hair follicle pigmentation ex vivo.

OBJECTIVE: To examine the ability of an extract from traditional Chinese medicine, Polygonum multiflorum Radix, to protect melanocyte viability from oxidative stress, a key mechanism in the initiation and progression of hair greying. METHODS: To assess the antioxidant capacity of Polygonum multiflorum Radix extract, primary human foreskin melanocytes were treated with a commercially available Polygonum multiflorum Radix extract added to culture medium and exposed to hydrogen peroxide (H2 O2 ), using intracellular reactive oxygen species concentrations and glutathione/protein ratios as endpoints. To improve solubility for cosmetic uses, a new Polygonum multiflorum Radix extract was derived. As hair greying is the consequence of melanocyte disappearance in an oxidative stress environment, we checked whether the antioxidant capacity of the new Polygonum multiflorum Radix extract could preserve melanocyte viability in response to H2 O2 -induced oxidative stress, and preserve pigmentation within ex vivo human hair follicles. RESULTS: In vitro treatment of primary human foreskin melanocytes with traditional available Polygonum multiflorum Radix extract resulted in decreased intracellular ROS accumulation in response to H2 O2 exposure with a concomitant preservation of glutathione-to-protein ratio, consistent with a protective response against H2 O2 exposure and demonstrating the promise of this extract for protecting melanocytes against oxidative stress. Melanocytes treated with the improved Polygonum multiflorum Radix extract exhibited attenuated H2 O2 -induced cell death, demonstrating a clear cytoprotective effect. Treatment of ex vivo human hair follicles with the improved Polygonum multiflorum Radix extract resulted in a higher level of melanin compared to vehicle-treated controls, demonstrating an ex vivo protective effect on hair pigmentation. CONCLUSION: Polygonum multiflorum Radix extract protects in vitro primary human foreskin melanocytes from the deleterious effects of H2 O2 exposure and improves pigmentation within ex vivo human hair follicles, demonstrating the utility of Polygonum multiflorum Radix extract as a potential active ingredient for the protection of melanocytes against premature death. This data provides in vitro mechanistic evidence consistent with existing in vivo studies for the use of Polygonum multiflorum Radix extract as a strategy for the prevention of oxidative stress-induced hair greying, in line with traditional Polygonum multiflorum Radix uses.

Observation of an energy-dependent difference in elliptic flow between particles and antiparticles in relativistic heavy ion collisions.

Elliptic flow (v(2)) values for identified particles at midrapidity in Au + Au collisions, measured by the STAR experiment in the beam energy scan at RHIC at sqrt[s(NN)] = 7.7-62.4 GeV, are presented. A beam-energy-dependent difference of the values of v(2) between particles and corresponding antiparticles was observed. The difference increases with decreasing beam energy and is larger for baryons compared to mesons. This implies that, at lower energies, particles and antiparticles are not consistent with the universal number-of-constituent-quark scaling of v(2) that was observed at sqrt[s(NN)] = 200 GeV.

Measurement of J/ψ azimuthal anisotropy in Au+Au collisions at sqrt[s(NN)]=200 GeV.

The measurement of J/ψ azimuthal anisotropy is presented as a function of transverse momentum for different centralities in Au+Au collisions at sqrt[s(NN)]=200 GeV. The measured J/ψ elliptic flow is consistent with zero within errors for transverse momentum between 2 and 10 GeV/c. Our measurement suggests that J/ψ particles with relatively large transverse momenta are not dominantly produced by coalescence from thermalized charm quarks, when comparing to model calculations.

Tetrazolium reduction allows assessment of biofilm formation by Campylobacter jejuni in a food matrix model.

AIMS: To develop a staining method for specific detection of metabolically active (viable) cells in biofilms of the foodborne pathogen Campylobacter jejuni. METHODS AND RESULTS: Conversion of 2,3,5 triphenyltetrazolium chloride (TTC) to insoluble, red 1,3,5-triphenylformazan (TPF) was dependent on metabolic activity of Camp. jejuni. When used with chicken juice, TTC staining allowed quantification of Camp. jejuni biofilm levels, whereas the commonly used dye, crystal violet, gave high levels of nonspecific staining of food matrix components (chicken juice). The assay was optimized to allow for monitoring of biofilm levels and adapted to monitor levels of Camp. jejuni in broth media. CONCLUSIONS: Staining with TTC allows for the quantification of metabolically active Camp. jejuni and thus allows for quantification of viable cells in biofilms and food matrices. The TTC staining method can be adapted to quantify bacterial cell concentration in a food matrix model, where the accepted method of A600 measurement is not suitable due to interference by components of the food matrix. SIGNIFICANCE AND IMPACT OF THE STUDY: 2,3,5 Triphenyltetrazolium chloride (TTC) staining is a low-cost technique suitable for use in biofilm analysis, allowing rapid and simple imaging of metabolically active cells and increasing the methods available for biofilm assessment and quantification.

Persistence of the efficacy of zoster vaccine in the shingles prevention study and the short-term persistence substudy.

BACKGROUND: The Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Study 403) demonstrated that zoster vaccine was efficacious through 4 years after vaccination. The Short-Term Persistence Substudy (STPS) was initiated after the SPS to further assess the persistence of vaccine efficacy. METHODS: The STPS re-enrolled 7320 vaccine and 6950 placebo recipients from the 38 546-subject SPS population. Methods of surveillance, case determination, and follow-up were analogous to those in the SPS. Vaccine efficacy for herpes zoster (HZ) burden of illness, incidence of postherpetic neuralgia (PHN), and incidence of HZ were assessed for the STPS population, for the combined SPS and STPS populations, and for each year through year 7 after vaccination. RESULTS: In the STPS as compared to the SPS, vaccine efficacy for HZ burden of illness decreased from 61.1% to 50.1%, vaccine efficacy for the incidence of PHN decreased from 66.5% to 60.1%, and vaccine efficacy for the incidence of HZ decreased from 51.3% to 39.6%, although the differences were not statistically significant. Analysis of vaccine efficacy in each year after vaccination for all 3 outcomes showed a decrease in vaccine efficacy after year 1, with a further decline thereafter. Vaccine efficacy was statistically significant for the incidence of HZ and the HZ burden of illness through year 5. CONCLUSIONS: Vaccine efficacy for each study outcome was lower in the STPS than in the SPS. There is evidence of the persistence of vaccine efficacy through year 5 after vaccination but, vaccine efficacy is uncertain beyond that point.

Strangeness enhancement in Cu-Cu and Au-Au collisions at √S(NN)=200 GeV.

We report new STAR measurements of midrapidity yields for the Λ, Λ[over ¯], K(S)(0), Ξ(-), Ξ[over ¯](+), Ω(-), Ω[over ¯](+) particles in Cu+Cu collisions at √S(NN)==200 GeV, and midrapidity yields for the Λ, Λ[over ¯], K(S)(0) particles in Au+Au at √S(NN)==200 GeV. We show that, at a given number of participating nucleons, the production of strange hadrons is higher in Cu+Cu collisions than in Au+Au collisions at the same center-of-mass energy. We find that aspects of the enhancement factors for all particles can be described by a parametrization based on the fraction of participants that undergo multiple collisions.

Identified hadron compositions in p+p and Au+Au collisions at high transverse momenta at √S(NN)=200 GeV.

We report transverse momentum (p(T)≤15 GeV/c) spectra of π(±), K(±), p, p[over ¯], K(S)(0), and ρ(0) at midrapidity in p+p and Au+Au collisions at √S(NN)=200 GeV. Perturbative QCD calculations are consistent with π(±) spectra in p+p collisions but do not reproduce K and p(p[over ¯]) spectra. The observed decreasing antiparticle-to-particle ratios with increasing p(T) provide experimental evidence for varying quark and gluon jet contributions to high-p(T) hadron yields. The relative hadron abundances in Au+Au at p(T)≳8 GeV/c are measured to be similar to the p+p results, despite the expected Casimir effect for parton energy loss.

Directed flow of identified particles in Au+Au collisions at √[SNN]=200 GeV at RHIC.

STAR's measurements of directed flow (v1) around midrapidity for π±, K±, KS0, p, and p[over ¯] in Au+Au collisions at √[sNN]=200 GeV are presented. A negative v1(y) slope is observed for most of produced particles (π±, K±, KS0, and p[over ¯]). In 5%-30% central collisions, a sizable difference is present between the v1(y) slope of protons and antiprotons, with the former being consistent with zero within errors. The v1 excitation function is presented. Comparisons to model calculations (RQMD, UrQMD, AMPT, QGSM with parton recombination, and a hydrodynamics model with a tilted source) are made. For those models which have calculations of v1 for both pions and protons, none of them can describe v1(y) for pions and protons simultaneously. The hydrodynamics model with a tilted source as currently implemented cannot explain the centrality dependence of the difference between the v1(y) slopes of protons and antiprotons.

Detection of a direct carbon dioxide effect in continental river runoff records.

Continental runoff has increased through the twentieth century despite more intensive human water consumption. Possible reasons for the increase include: climate change and variability, deforestation, solar dimming, and direct atmospheric carbon dioxide (CO2) effects on plant transpiration. All of these mechanisms have the potential to affect precipitation and/or evaporation and thereby modify runoff. Here we use a mechanistic land-surface model and optimal fingerprinting statistical techniques to attribute observational runoff changes into contributions due to these factors. The model successfully captures the climate-driven inter-annual runoff variability, but twentieth-century climate alone is insufficient to explain the runoff trends. Instead we find that the trends are consistent with a suppression of plant transpiration due to CO2-induced stomatal closure. This result will affect projections of freshwater availability, and also represents the detection of a direct CO2 effect on the functioning of the terrestrial biosphere.

Measurement of the parity-violating longitudinal single-spin asymmetry for W± boson production in polarized proton-proton collisions at sqrt[s] = 500 GeV.

We report the first measurement of the parity-violating single-spin asymmetries for midrapidity decay positrons and electrons from W+ and W- boson production in longitudinally polarized proton-proton collisions at sqrt[s] = 500 GeV by the STAR experiment at RHIC. The measured asymmetries, A(L)(W+) = -0.27 ± 0.10(stat.) ± 0.02(syst.) ± 0.03(norm.) and A(L)(W-) = 0.14 ± 0.19(stat.) ± 0.02(syst.) ± 0.01(norm.), are consistent with theory predictions, which are large and of opposite sign. These predictions are based on polarized quark and antiquark distribution functions constrained by polarized deep-inelastic scattering measurements.

Rock glaciers represent hidden water stores in the Himalaya.

In the high mountains of Asia, ongoing glacier retreat threatens human and ecological systems through reduced water availability. Rock glaciers are climatically more resistant than glaciers and contain valuable water volume equivalents (WVEQ). Across High Mountain Asia (HMA) the WVEQ of rock glaciers is poorly quantified, and thus their hydrological significance versus glaciers is unknown. Here we present the first systematic assessment of Himalayan rock glaciers, totalling ~25,000 landforms with an areal coverage of ~3747 km2. We calculate the WVEQ of Himalayan rock glaciers to be 51.80 ± 10.36 km3. Their comparative importance versus glaciers (rock glacier: glacier WVEQ ratio) is 1:25, which means that they constitute hydrologically valuable long-term water stores. In the context of climate-driven glacier recession, their relative hydrological value will likely increase. These cryospheric stores should be included in future scenario modelling to understand their role in sustainable water management for HMA.

High transverse momentum triggered correlations over a large pseudorapidity acceptance in Au + Au collisions at square root(s(NN)) = 200 GeV.

A measurement of two-particle correlations with a high transverse momentum trigger particle (p(T)(trig) > 2.5 GeV/c) is presented for Au+Au collisions at square root(s(NN)) = 200 GeV over the uniquely broad longitudinal acceptance of the PHOBOS detector (-4 < Delta eta < 2). A broadening of the away-side azimuthal correlation compared to elementary collisions is observed at all Delta eta. As in p+p collisions, the near side is characterized by a peak of correlated partners at small angle relative to the trigger particle. However, in central Au+Au collisions an additional correlation extended in Delta eta and known as the "ridge" is found to reach at least |Delta eta| approximately = 4. The ridge yield is largely independent of Delta eta over the measured range, and it decreases towards more peripheral collisions. For the chosen (p(T)(trig) cut, the ridge yield is consistent with zero for events with less than roughly 100 participating nucleons.

Three-particle coincidence of the long range pseudorapidity correlation in high energy nucleus-nucleus collisions.

We report the first three-particle coincidence measurement in pseudorapidity (Δη) between a high transverse momentum (p⊥) trigger particle and two lower p⊥ associated particles within azimuth |Δϕ|<0.7 in square root of s(NN)=200 GeV d+Au and Au+Au collisions. Charge ordering properties are exploited to separate the jetlike component and the ridge (long range Δη correlation). The results indicate that the correlation of ridge particles are uniform not only with respect to the trigger particle but also between themselves event by event in our measured Δη. In addition, the production of the ridge appears to be uncorrelated to the presence of the narrow jetlike component.

Higher moments of net proton multiplicity distributions at RHIC.

We report the first measurements of the kurtosis (κ), skewness (S), and variance (σ2) of net-proton multiplicity (Np-Np) distributions at midrapidity for Au+Au collisions at square root of s(NN)=19.6, 62.4, and 200 GeV corresponding to baryon chemical potentials (µB) between 200 and 20 MeV. Our measurements of the products κσ2 and Sσ, which can be related to theoretical calculations sensitive to baryon number susceptibilities and long-range correlations, are constant as functions of collision centrality. We compare these products with results from lattice QCD and various models without a critical point and study the square root of s(NN) dependence of κσ2. From the measurements at the three beam energies, we find no evidence for a critical point in the QCD phase diagram for µB below 200 MeV.

Measurement of the bottom quark contribution to nonphotonic electron production in p + p collisions at √s=200 GeV.

The contribution of B meson decays to nonphotonic electrons, which are mainly produced by the semileptonic decays of heavy-flavor mesons, in p + p collisions at √s=200 GeV has been measured using azimuthal correlations between nonphotonic electrons and hadrons. The extracted B decay contribution is approximately 50% at a transverse momentum of pT≥5 GeV/c. These measurements constrain the nuclear modification factor for electrons from B and D meson decays. The result indicates that B meson production in heavy ion collisions is also suppressed at high pT.

Event-by-event fluctuations of azimuthal particle anisotropy in Au+Au collisions at square root(sNN) = 200 GeV.

This Letter presents the first measurement of event-by-event fluctuations of the elliptic flow parameter v(2) in Au+Au collisions at square root(s(NN))=200 GeV as a function of collision centrality. The relative nonstatistical fluctuations of the v(2) parameter are found to be approximately 40%. The results, including contributions from event-by-event elliptic flow fluctuations and from azimuthal correlations that are unrelated to the reaction plane (nonflow correlations), establish an upper limit on the magnitude of underlying elliptic flow fluctuations. This limit is consistent with predictions based on spatial fluctuations of the participating nucleons in the initial nuclear overlap region. These results provide important constraints on models of the initial state and hydrodynamic evolution of relativistic heavy ion collisions.

Growth of long range forward-backward multiplicity correlations with centrality in Au + Au collisions at square root of sNN = 200 GeV.

Forward-backward multiplicity correlation strengths have been measured with the STAR detector for Au + Au and p + p collisions at square root of s(NN) = 200 GeV. Strong short- and long-range correlations (LRC) are seen in central Au + Au collisions. The magnitude of these correlations decrease with decreasing centrality until only short-range correlations are observed in peripheral Au + Au collisions. Both the dual parton model (DPM) and the color glass condensate (CGC) predict the existence of the long-range correlations. In the DPM, the fluctuation in the number of elementary (parton) inelastic collisions produces the LRC. In the CGC, longitudinal color flux tubes generate the LRC. The data are in qualitative agreement with the predictions of the DPM and indicate the presence of multiple parton interactions.

Azimuthal charged-particle correlations and possible local strong parity violation.

Parity-odd domains, corresponding to nontrivial topological solutions of the QCD vacuum, might be created during relativistic heavy-ion collisions. These domains are predicted to lead to charge separation of quarks along the system's orbital momentum axis. We investigate a three-particle azimuthal correlator which is a P even observable, but directly sensitive to the charge separation effect. We report measurements of charged hadrons near center-of-mass rapidity with this observable in Au + Au and Cu + Cu collisions at square root of s(NN) = 200 GeV using the STAR detector. A signal consistent with several expectations from the theory is detected. We discuss possible contributions from other effects that are not related to parity violation.

A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.