Role of cellular senescence and NOX4-mediated oxidative stress in systemic sclerosis pathogenesis.

Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and numerous internal organs and a severe fibroproliferative vasculopathy resulting frequently in severe disability and high mortality. Although the etiology of SSc is unknown and the detailed mechanisms responsible for the fibrotic process have not been fully elucidated, one important observation from a large US population study was the demonstration of a late onset of SSc with a peak incidence between 45 and 54 years of age in African-American females and between 65 and 74 years of age in white females. Although it is not appropriate to consider SSc as a disease of aging, the possibility that senescence changes in the cellular elements involved in its pathogenesis may play a role has not been thoroughly examined. The process of cellular senescence is extremely complex, and the mechanisms, molecular events, and signaling pathways involved have not been fully elucidated; however, there is strong evidence to support the concept that oxidative stress caused by the excessive generation of reactive oxygen species may be one important mechanism involved. On the other hand, numerous studies have implicated oxidative stress in SSc pathogenesis, thus, suggesting a plausible mechanism in which excessive oxidative stress induces cellular senescence and that the molecular events associated with this complex process play an important role in the fibrotic and fibroproliferative vasculopathy characteristic of SSc. Here, recent studies examining the role of cellular senescence and of oxidative stress in SSc pathogenesis will be reviewed

Factors associated with problem drinking among women employed in food and recreational facilities in northern Tanzania.

BACKGROUND: There is growing evidence that alcohol consumption is associated with increased risk of HIV infection. To determine factors associated with problem drinking, we analyzed data collected in two prospective cohorts of at-risk female food and recreational facility workers in northern Tanzania. METHODS: We enrolled HIV seronegative women aged 18-44 years and employed in the towns of Geita, Kahama, Moshi, and Shinyanga. At enrolment, women were interviewed to obtain information about alcohol use, using CAGE and AUDIT screening scales, and risk factors for HIV infection. Blood and genital samples were collected for detection of HIV and sexually transmitted infections (STIs). We characterized alcohol use, concordance, and agreement of the scales, and examined the associations between characteristics of participants and problem drinking as defined by both scales using logistic regression. Lastly, we assessed problem drinking as a risk factor for recent sexual behavior and prevalent STIs. RESULTS: Among enrollees, 68% women reported ever drinking alcohol; of these 76% reported drinking alcohol in the past 12 months. The prevalence of problem drinking was 20% using CAGE and 13% using AUDIT. Overall concordance between the scales was 75.0% with a Kappa statistic of 0.58. After adjusting for age, independent factors associated with problem drinking, on both scales, were marital status, occupation, facility type, increasing number of lifetime sexual partners, and transactional sex in the past 12 months. In addition, women who were problem drinkers on either scale were more likely to report having ≥ 1 sexual partner (CAGE: aOR = 1.56, 95% confidence interval, CI: 1.10-2.23; AUDIT: aOR = 2.00, 95% CI: 1.34-3.00) and transactional sex (CAGE: aOR = 1.79, 95% CI: 1.26-2.56; AUDIT: aOR = 1.51, 95% CI: 1.04-2.18), in the past 3 months. CONCLUSION: These findings suggest that interventions to reduce problem drinking in this population may reduce high-risk sexual behaviors and contribute in lowering the risk of HIV infection

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Assessing the Nature of the Distribution of Localised States in Bulk GaAsBi.

A comprehensive assessment of the nature of the distribution of sub band-gap energy states in bulk GaAsBi is presented using power and temperature dependent photoluminescence spectroscopy. The observation of a characteristic red-blue-red shift in the peak luminescence energy indicates the presence of short-range alloy disorder in the material. A decrease in the carrier localisation energy demonstrates the strong excitation power dependence of localised state behaviour and is attributed to the filling of energy states furthest from the valence band edge. Analysis of the photoluminescence lineshape at low temperature presents strong evidence for a Gaussian distribution of localised states that extends from the valence band edge. Furthermore, a rate model is employed to understand the non-uniform thermal quenching of the photoluminescence and indicates the presence of two Gaussian-like distributions making up the density of localised states. These components are attributed to the presence of microscopic fluctuations in Bi content, due to short-range alloy disorder across the GaAsBi layer, and the formation of Bi related point defects, resulting from low temperature growth

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

The ongoing pursuit of neuroprotective therapies in Parkinson disease

Many agents developed for neuroprotective treatment of Parkinson disease (PD) have shown great promise in the laboratory, but none have translated to positive results in patients with PD. Potential neuroprotective drugs, such as ubiquinone, creatine and PYM50028, have failed to show any clinical benefits in recent high-profile clinical trials. This 'failure to translate' is likely to be related primarily to our incomplete understanding of the pathogenic mechanisms underlying PD, and excessive reliance on data from toxin-based animal models to judge which agents should be selected for clinical trials. Restricted resources inevitably mean that difficult compromises must be made in terms of trial design, and reliable estimation of efficacy is further hampered by the absence of validated biomarkers of disease progression. Drug development in PD dementia has been mostly unsuccessful; however, emerging biochemical, genetic and pathological evidence suggests a link between tau and amyloid-β deposition and cognitive decline in PD, potentially opening up new possibilities for therapeutic intervention. This Review discusses the most important 'druggable' disease mechanisms in PD, as well as the most-promising drugs that are being evaluated for their potential efficiency in treatment of motor and cognitive impairments in PD

AMPK in Pathogens

During host–pathogen interactions, a complex web of events is crucial for the outcome of infection. Pathogen recognition triggers powerful cellular signaling events that is translated into the induction and maintenance of innate and adaptive host immunity against infection. In opposition, pathogens employ active mechanisms to manipulate host cell regulatory pathways toward their proliferation and survival. Among these, subversion of host cell energy metabolism by pathogens is currently recognized to play an important role in microbial growth and persistence. Extensive studies have documented the role of AMP-activated protein kinase (AMPK) signaling, a central cellular hub involved in the regulation of energy homeostasis, in host–pathogen interactions. Here, we highlight the most recent advances detailing how pathogens hijack cellular metabolism by suppressing or increasing the activity of the host energy sensor AMPK. We also address the role of lower eukaryote AMPK orthologues in the adaptive process to the host microenvironment and their contribution for pathogen survival, differentiation, and growth. Finally, we review the effects of pharmacological or genetic AMPK modulation on pathogen growth and persistence.CIHR -Canadian Institutes of Health Researc

Uso de iodóforo tópico em feridas crônicas: revisão da literatura

La investigación trata de una revisión de la literatura a cerca de la utilización del yodo tópico y/o compuestos en el tratamiento de las heridas crónicas. Se buscaran los ensayos clínicos en el Cochrane. Catorce (n=24) publicaciones estaban de acuerdo con los criterios de inclusión, y fueran analizadas según las características de las revistas y ensayos y clasificadas como: yodo versus otros agentes tópicos (7/ 50%); yodo versus curativos (6/ 42,9%) y yodo versus sin yodo (1/ 7,1%). Fueran obtenidos resultados favorables a la utilización del yodo y/o compuestos en 50% de los artículos analizados. Cuanto a las tendencias de los resultados, 6 de 8 publicaciones, a cerca de la de cicatrización de las heridas y prevención de infección, fueran favorables; 4 de 5 fueran no favorables solamente para la cicatrización, y el resultado del único trabajo con indicación del uso para tratamiento de infección de herida fue no favorable.Trata-se de revisão de literatura relacionada ao uso de iodóforos tópicos no tratamento de feridas crônicas. Os ensaios clínicos foram localizados por meio da Base de Dados Cochrane de Revisões Sistemáticas e Registro Cochrane Central de Ensayos Controlados. Quatorze (58,3%), dentre 24 artigos, atenderam os critérios de inclusão, analisados quanto às características dos periódicos e dos estudos e classificados em três grupos: iodóforo versus outros agentes tópicos (7 ou 50%); iodóforo versus coberturas (6 ou 42,9%) e iodóforo versus sem iodóforo (1 ou 7,1%). Resultados favoráveis à utilização dos iodóforos ocorreram em 50% dos artigos analisados. Quanto às tendências dos resultados, seis, dentre oito artigos, que tratavam de cicatrização de feridas e prevenção de infecção, foram favoráveis; quatro, dentre cinco, foram desfavoráveis somente para a cicatrização e no único ensaio em que houve indicação do seu uso para tratamento de infecção de ferida o resultado foi desfavorável.This study aimed to do a review of the literature regarding the use of topic iodine and/or compounds in the treatment of chronic wounds. The clinical trials were searched in the Cochrane database. Fourteen (58.3%) among 24 studies fulfilled the inclusion criteria. The articles were analyzed regarding journal and study characteristics and classified into three groups: Iodine versus other topic agents (7/ 50%); Iodine versus different dressings (6/ 42.9%); Iodine versus without Iodine (1/ 7.1%). Favorable results for the use of Iodine or similar product occurred in 50% of the analyzed studies. Six out of 8 trials showed favorable results for healing and infection prevention/ treatment; 4 out of 5 were not favorable when the healing objective was investigated and 1 study for infection treatment showed no favorable result