Alveolar fluid in acute respiratory distress syndrome promotes fibroblast migration: role of platelet-derived growth factor pathway

OBJECTIVES: Fibroblast migration is an initiating step in fibroproliferation; its involvement during acute lung injury and acute respiratory distress syndrome remains poorly understood. The aims of this study were: 1) to determine whether bronchoalveolar lavage fluids from patients with acute lung injury/acute respiratory distress syndrome modulate lung fibroblast migration; 2) to assess lung fibroblast migration\u27s clinical relevance; and 3) to evaluate the role of the platelet-derived growth factor pathway in this effect. DESIGN: Prospective cohort study. SETTING: Three intensive care units of a large tertiary referral center. PATIENTS: Ninety-three ventilated patients requiring bronchoalveolar lavage fluids were enrolled (48 with acute respiratory distress syndrome, 33 with acute lung injury, and 12 ventilated patients without acute lung injury/acute respiratory distress syndrome). INTERVENTIONS: After bronchoalveolar lavage fluids collection during standard care, the patients were followed up for 28 days and clinical outcomes were recorded. Migration assays were performed by using a Transwell model; bronchoalveolar lavage fluids platelet-derived growth factor and soluble platelet-derived growth factor receptor-alpha were characterized by Western blot and measured by ELISA. MEASUREMENTS AND MAIN RESULTS: Most of the bronchoalveolar lavage fluids inhibited basal fibroblast migration. Bronchoalveolar lavage fluids chemotactic index increased with severity of lung injury (28% in patients without acute lung injury/acute respiratory distress syndrome and with acute lung injury vs. 91% in acute respiratory distress syndrome patients; p = .016). In acute lung injury/acute respiratory distress syndrome patients, inhibition of basal fibroblast migration by bronchoalveolar lavage fluids below 52% was independently associated with a lower 28-day mortality (odds ratio [95% confidence interval] 0.313 [0.10-0.98], p = .046). Platelet-derived growth factor-related peptides and soluble platelet-derived growth factor-Ralpha were detected in all bronchoalveolar lavage fluids from acute lung injury/acute respiratory distress syndrome patients. The effect of bronchoalveolar lavage fluids stimulating migration was inhibited by a specific platelet-derived growth factor receptor inhibitor (AG1296). Bronchoalveolar lavage fluids inhibiting migration reversed the effect of rh-platelet-derived growth factor-BB and reduced by 40% the binding of 125I-platelet-derived growth factor-BB to fibroblast cell surface in favor of a role for platelet-derived growth factor-sRalpha. CONCLUSIONS: : Together, our results suggest that during acute lung injury, fibroblast migration is modulated by bronchoalveolar lavage fluids through a platelet-derived growth factor/platelet-derived growth factor-sRalpha balance. Migration is associated with clinical severity and patient 28-day mortality

Imaging tests in determination of brain death

In this issue, an excellent review is published on the imaging findings in non-neonatal hypoxic-ischemic encephalopathy [1]. The authors also go into detail on imaging “brain death”, an entity that is currently causing debate as far as the imaging approach is concerned. Brain death refers to the irreversible end of all brain activity due to necrosis of neurons. The diagnosis of brain death allows organ donation for transplantation or withdrawal of life support. Legal standard and/or practice guidelines are currently present in most countries. There is uniform agreement on the clinical neurological examination to evaluate absence of brain function. This examination includes the assessment of coma, the absence of brain reflexes, and the assessment of apnea. Some guidelines require a confirmatory test for the diagnosis o

Ovarian Activity and Oestrous Signs among Group-Housed, Lactating Sows: Influence of Behaviour, Environment and Production

Animal welfare concerns require the development of housing systems that allow the animals to express their natural behaviour. One example of this is the group-housing system for lactating sows. The present study aimed at exploring ovarian activity in such a system. Thirty-eight sows farrowing individually outdoors during spring and summer, and indoors during autumn and winter, and group-housed in groups of four during weeks 3–7 of the lactation period, were monitored regarding reproductive functions, behaviour and production during their first to fourth lactation period. Average ovulation frequency during lactation was 47%. Only 50% of these ovulating cases were accompanied by a standing oestrus. Lactational ovulation frequency was higher in later parities (p < 0.001). Ovulation frequency was higher (p < 0.05) during winter (74%) and spring (69%), than during summer (10%) and autumn (23%). Occurrence of lactational ovulation was associated with some aspects of suckling behaviour and also with litter weight gain (p < 0.05). Forty-nine per cent of the lactational ovulations occurred during the seventh week of lactation. Timing of ovulation seemed positively (p = 0.08) associated with weight loss during lactation. Compared with the sows that were anoestrus during lactation, oestradiol-17β values were higher (p < 0.05) only in the week before occurrence of lactational ovulation. Weaning-to-oestrous interval was prolonged (p < 0.05) among the sows that ovulated during lactation. The present study identifies several factors influencing ovarian activity among group-housed sows, thereby providing tools for the control of lactational ovulation in group-housing systems

A Highly Conserved Program of Neuronal Microexons Is Misregulated in Autistic Brains

SummaryAlternative splicing (AS) generates vast transcriptomic and proteomic complexity. However, which of the myriad of detected AS events provide important biological functions is not well understood. Here, we define the largest program of functionally coordinated, neural-regulated AS described to date in mammals. Relative to all other types of AS within this program, 3-15 nucleotide “microexons” display the most striking evolutionary conservation and switch-like regulation. These microexons modulate the function of interaction domains of proteins involved in neurogenesis. Most neural microexons are regulated by the neuronal-specific splicing factor nSR100/SRRM4, through its binding to adjacent intronic enhancer motifs. Neural microexons are frequently misregulated in the brains of individuals with autism spectrum disorder, and this misregulation is associated with reduced levels of nSR100. The results thus reveal a highly conserved program of dynamic microexon regulation associated with the remodeling of protein-interaction networks during neurogenesis, the misregulation of which is linked to autism

Rochechouart 2017-Drilling Campaign: First Results

No abstract available

The Socio-economic Gradient of Alcohol Use: An Analysis of Nationally Representative Survey Data from 55 Low and Middle income Countries:Socio-economic Gradient of Alcohol Use in 55 Low- and Middle-Income Countries.

BACKGROUND: Alcohol is a leading risk factor for over 200 conditions and an important contributor to socioeconomic health inequalities. However, little is known about the associations between individuals’ socioeconomic circumstances and alcohol consumption, especially heavy episodic drinking (HED; ≥5 drinks on one occasion) in low-income or middle-income countries. We investigated the association between individual and household level socioeconomic status, and alcohol drinking habits in these settings. METHODS: In this pooled analysis of individual-level data, we used available nationally representative surveys—mainly WHO Stepwise Approach to Surveillance surveys—conducted in 55 low-income and middle-income countries between 2005 and 2017 reporting on alcohol use. Surveys from participants aged 15 years or older were included. Logistic regression models controlling for age, country, and survey year stratified by sex and country income groups were used to investigate associations between two indicators of socioeconomic status (individual educational attainment and household wealth) and alcohol use (current drinking and HED amongst current drinkers). FINDINGS: Surveys from 336 287 participants were included in the analysis. Among males, the highest prevalence of both current drinking and HED was found in lower-middle-income countries (L-MICs; current drinking 49·9% [95% CI 48·7–51·2] and HED 63·3% [61·0–65·7]). Among females, the prevalence of current drinking was highest in upper-middle-income countries (U-MIC; 29·5% [26·1–33·2]), and the prevalence of HED was highest in low-income countries (LICs; 36·8% [33·6–40·2]). Clear gradients in the prevalence of current drinking were observed across all country income groups, with a higher prevalence among participants with high socioeconomic status. However, in U-MICs, current drinkers with low socioeconomic status were more likely to engage in HED than participants with high socioeconomic status; the opposite was observed in LICs, and no association between socioeconomic status and HED was found in L-MICs. INTERPRETATION: The findings call for urgent alcohol control policies and interventions in LICs and L-MICs to reduce harmful HED. Moreover, alcohol control policies need to be targeted at socially disadvantaged groups in U-MICs. FUNDING: Deutsche Forschungsgemeinschaft and the National Center for Advancing Translational Sciences of the US National Institutes of Health

How are time-dependent childbearing intentions realized? Realization, postponement, abandonment, bringing forward

Our study aims to identify factors that facilitate or inhibit the realization of fertility intentions. The analysis uses data collected in the first two waves of a Hungarian longitudinal survey. Fertility intentions recorded at the first wave pertain to the subsequent 3-year period, just similar to the behavior variable measuring the realization of intentions, i.e., a birth within the 3-year period in question. For this analysis, we used the respondents’ demographic, socio-structural, and orientational traits recorded at the first interview. Our findings show that age, parity, and partnership play a determining role in the realization of fertility intentions, but employment status, religious affiliation, and overall life satisfaction all exhibit significant effects. A marked gender difference was detected not only with regard to employment status but in the area of values and orientations as well.L’objectif de notre étude est d’identifier les facteurs qui facilitent ou inhibent la réalisation des intentions de fécondité. L’analyse s’appuie sur les deux premières vagues d’une enquête longitudinale menée en Hongrie. Les intentions de fécondité recueillies dans le cadre de la première vague concernent la période des trois années à venir, de la même façon que la variable de comportement mesurant la réalisation des intentions, à savoir, une naissance survenue au cours de cette même période. Les caractéristiques démographiques et socio-structurelles, de même que certaines dispositions personnelles recueillies lors du premier entretien ont été utilisées dans l’analyse. Nos résultats indiquent qu’à la fois l’âge, la parité, et la situation de couple jouent un rôle capital dans la réalisation des intentions et aussi que la situation d’emploi, l’appartenance religieuse et le niveau de satisfaction par rapport à la vie exercent une influence significative. Une différence prononcée entre hommes et femmes est mise en évidence en matière de situation d’emploi et également dans le domaine des valeurs et des dispositions personnelles

The LHC test string: first operational experience

CERN operates the first version of the LHC Test String which consists of one quadrupole and three 10-m twin aperture dipole magnets. An experimental programme aiming at the validation of the LHC systems started in February 1995. During this programme the string has been powered 100 times 35 of which at 12.4 kA or above. The experiments have yielded a number of results some of which, like quench recovery for cryogenics, have modified the design of subsystems of LHC. Others, like controlled helium leaks in the cold bore and quench propagation bewteen magnets, have given a better understanding on the evolution of the phenomena inside a string of superconducting magnets cooled at superfluid helium temperatures. Following the experimental programme, the string will be powered up and powered down in one hour cycles as a fatigue test of the structure thus simulating 20 years of operation of LHC