Efficacy and Safety of Inhaled Carbon Monoxide during Pulmonary Inflammation in Mice

Background: Pulmonary inflammation is a major contributor to morbidity in a variety of respiratory disorders, but treatment options are limited. Here we investigate the efficacy, safety and mechanism of action of low dose inhaled carbon monoxide (CO) using a mouse model of lipopolysaccharide (LPS)-induced pulmonary inflammation. Methodology: Mice were exposed to 0–500 ppm inhaled CO for periods of up to 24 hours prior to and following intratracheal instillation of 10 ng LPS. Animals were sacrificed and assessed for intraalveolar neutrophil influx and cytokine levels, flow cytometric determination of neutrophil number and activation in blood, lung and lavage fluid samples, or neutrophil mobilisation from bone marrow. Principal Findings: When administered for 24 hours both before and after LPS, inhaled CO of 100 ppm or more reduced intraalveolar neutrophil infiltration by 40–50%, although doses above 100 ppm were associated with either high carboxyhemoglobin, weight loss or reduced physical activity. This anti-inflammatory effect of CO did not require pre-exposure before induction of injury. 100 ppm CO exposure attenuated neutrophil sequestration within the pulmonary vasculature as well as LPS-induced neutrophilia at 6 hours after LPS, likely due to abrogation of neutrophil mobilisation from bone marrow. In contrast to such apparently beneficial effects, 100 ppm inhaled CO induced an increase in pulmonary barrier permeability as determined by lavage fluid protein content and translocation of labelled albumin from blood to the alveolar space

Intergenerational educational mobility is associated with cardiovascular disease risk behaviours in a cohort of young Australian adults: The Childhood Determinants of Adult Health (CDAH) Study

<p>Abstract</p> <p>Background</p> <p>Although educational disparity has been linked to single risk behaviours, it has not previously been studied as a predictor of overall lifestyle. We examined if current education, parental education or educational mobility between generations was associated with healthy lifestyles in young Australian adults.</p> <p>Methods</p> <p>In 2004-06, participant and parental education (high [bachelor degree or higher], intermediate [vocational training], low [secondary school only]) were assessed. Educational mobility was defined as: stable high (participant and parent in high group), stable intermediate (participant and parent in intermediate group), stable low (participant and parent in low group), downwardly (lower group than parent) and upwardly (higher group than parent) mobile. We derived a lifestyle score from 10 healthy behaviours (BMI, non-smoking, alcohol consumption, leisure time physical activity and six components of diet). Scores >4 indicated a high healthy lifestyle score. We estimated the likelihood of having a high healthy lifestyle score by education (participant and parent) and educational mobility.</p> <p>Results</p> <p>Complete data were available for 1973 participants (53% female, age range 26 to 36 years). Those with lower education were less likely to have healthy lifestyles. Parental education was not associated with having a high healthy lifestyle score after adjustment for participant's education. Those who moved upward or downward were as likely to have a high healthy lifestyle score as those in the group they attained.</p> <p>Conclusions</p> <p>We found clear disparities in health behaviour by participant education and intergenerational educational mobility. People attaining a higher level of education than their parents appeared protected from developing an unhealthy lifestyle suggesting that population-wide improvements in education may be important for health.</p

Gravitational Waves and Gamma-Rays from a Binary Neutron Star Merger: GW170817 and GRB 170817A

On 2017 August 17, the gravitational-wave event GW170817 was observed by the Advanced LIGO and Virgo detectors, and the gamma-ray burst (GRB) GRB 170817A was observed independently by the Fermi Gamma-ray Burst Monitor, and the Anti-Coincidence Shield for the Spectrometer for the International Gamma-Ray Astrophysics Laboratory. The probability of the near-simultaneous temporal and spatial observation of GRB 170817A and GW170817 occurring by chance is $5.0\times {10}^{-8}$. We therefore confirm binary neutron star mergers as a progenitor of short GRBs. The association of GW170817 and GRB 170817A provides new insight into fundamental physics and the origin of short GRBs. We use the observed time delay of $(+1.74\pm 0.05)\,{\rm{s}}$ between GRB 170817A and GW170817 to: (i) constrain the difference between the speed of gravity and the speed of light to be between $-3\times {10}^{-15}$ and $+7\times {10}^{-16}$ times the speed of light, (ii) place new bounds on the violation of Lorentz invariance, (iii) present a new test of the equivalence principle by constraining the Shapiro delay between gravitational and electromagnetic radiation. We also use the time delay to constrain the size and bulk Lorentz factor of the region emitting the gamma-rays. GRB 170817A is the closest short GRB with a known distance, but is between 2 and 6 orders of magnitude less energetic than other bursts with measured redshift. A new generation of gamma-ray detectors, and subthreshold searches in existing detectors, will be essential to detect similar short bursts at greater distances. Finally, we predict a joint detection rate for the Fermi Gamma-ray Burst Monitor and the Advanced LIGO and Virgo detectors of 0.1-1.4 per year during the 2018-2019 observing run and 0.3-1.7 per year at design sensitivity

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

First Measurement of the Hubble Constant from a Dark Standard Siren using the Dark Energy Survey Galaxies and the LIGO/Virgo Binary-Black-hole Merger GW170814

We present a multi-messenger measurement of the Hubble constant H 0 using the binary–black-hole merger GW170814 as a standard siren, combined with a photometric redshift catalog from the Dark Energy Survey (DES). The luminosity distance is obtained from the gravitational wave signal detected by the Laser Interferometer Gravitational-Wave Observatory (LIGO)/Virgo Collaboration (LVC) on 2017 August 14, and the redshift information is provided by the DES Year 3 data. Black hole mergers such as GW170814 are expected to lack bright electromagnetic emission to uniquely identify their host galaxies and build an object-by-object Hubble diagram. However, they are suitable for a statistical measurement, provided that a galaxy catalog of adequate depth and redshift completion is available. Here we present the first Hubble parameter measurement using a black hole merger. Our analysis results in ${H}_{0}={75}_{-32}^{+40}\,\mathrm{km}\,{{\rm{s}}}^{-1}\,{\mathrm{Mpc}}^{-1}$, which is consistent with both SN Ia and cosmic microwave background measurements of the Hubble constant. The quoted 68% credible region comprises 60% of the uniform prior range [20, 140] km s−1 Mpc−1, and it depends on the assumed prior range. If we take a broader prior of [10, 220] km s−1 Mpc−1, we find {H}_{0 {78}_{-24}^{+96}\,\mathrm{km}\,{{\rm{s}}}^{-1}\,{\mathrm{Mpc}}^{-1} (57% of the prior range). Although a weak constraint on the Hubble constant from a single event is expected using the dark siren method, a multifold increase in the LVC event rate is anticipated in the coming years and combinations of many sirens will lead to improved constraints on H 0

Percepção da imagem corporal de crianças e adolescentes com diferentes níveis socio-econômicos na cidade de Florianópolis, Santa Catarina, Brasil Body image perception in children and adolescents with different socio-economic status in the city of Florianópolis, in the State of Santa Catarina, Brazil

OBJETIVOS: identificar a percepção da imagem corporal em diferentes níveis socioeconômicos de crianças e adolescentes. MÉTODOS: estudo transversal realizado no município de Florianópolis, Santa Catarina, no ano de 2006. Quatrocentos e dois escolares, com média de idade de 11,35 ± 1,98 anos, matriculados nas séries finais do ensino fundamental, foram investigados. A percepção da imagem corporal foi identificada por meio do protocolo de silhuetas de Stunkard e o nível socioeconômico pelos critérios propostos pela Associação Nacional de Empresas e Pesquisa (ANEP). Foram calculadas razões de prevalências para insatisfação pelo excesso de peso e pela magreza. RESULTADOS: no sexo masculino, a silhueta 3 foi a mais citada nas classes alta e média e a 4 na baixa; no feminino a silhueta 2 foi a mais citada nas classes alta e baixa e a 3 na média considerando a percepção real de sua silhueta. A silhueta 3 para o sexo masculino e a 2 para o feminino foram consideradas ideais pelo maior percentual de escolares. Os jovens da classe baixa apresentaram maiores prevalências de insatisfação pelo excesso de peso em relação os da classe alta. CONCLUSÕES: houve uma tendência dos escolares das classes mais altas apresentarem insatisfação pela magreza e das mais baixas pelo excesso de peso.<br>OBJECTIVES: to identify the body image perception in children and adolescents from different socio-economic backgrounds. METHODS: a cross-cutting study was carried out in the city of Florianópolis, in the State of Santa Catarina, Brazil, in the year 2006. Four hundred and two schoolchildren, with an average age of 11.35 ± 1.98 years, enrolled in the final years of primary school were investigated. Body image perception was identified using the Stunkard silhouettes protocol and socio-economic status was evaluated using the criteria proposed by the National Pres and Research Association (ANEP). Prevalence ratios were calculated for dissatisfaction arising from perceived excessive weight or excessive thinness. RESULTS: among males, silhouette 3 was the one most often chosen among those from the upper and middle classes, whereas those of lower socio-economic status opted for silhouette 4; middle and upper class girls, however, opted for silhouette 2 was chosen and girls from less privileged backgrounds tended to select silhouette 3 as best representing their own silhouette. Silhouette 3 for males and 2 for females are considered to be the ideal for most school-age children. Less privileged young people had a higher prevalence of dissatisfaction arising from excess weight than more privileged ones. CONCLUSIONS: there was a tendency to children of a higher social status to be dissatisfied because they regarded themselves as being too thin and for children of lower social status to be dissatisfied because they perceived themselves to be overweight

A single NFκB system for both canonical and non-canonical signaling

Two distinct nuclear factor κB (NFκB) signaling pathways have been described; the canonical pathway that mediates inflammatory responses, and the non-canonical pathway that is involved in immune cell differentiation and maturation and secondary lymphoid organogenesis. The former is dependent on the IκB kinase adaptor molecule NEMO, the latter is independent of it. Here, we review the molecular mechanisms of regulation in each signaling axis and attempt to relate the apparent regulatory logic to the physiological function. Further, we review the recent evidence for extensive cross-regulation between these two signaling axes and summarize them in a wiring diagram. These observations suggest that NEMO-dependent and -independent signaling should be viewed within the context of a single NFκB signaling system, which mediates signaling from both inflammatory and organogenic stimuli in an integrated manner. As in other regulatory biological systems, a systems approach including mathematical models that include quantitative and kinetic information will be necessary to characterize the network properties that mediate physiological function, and that may break down to cause or contribute to pathology