Kinase Activity Profiling of Pneumococcal Pneumonia

Background: Pneumonia represents a major health burden. Previous work demonstrated that although the induction of inflammation is important for adequate host defense against pneumonia, an inability to regulate the host's inflammatory response within the lung later during infection can be detrimental. Intracellular signaling pathways commonly rely on activation of kinases, and kinases play an essential role in the regulation of the inflammatory response of immune cells. Methodology/Principal Findings: Pneumonia was induced in mice via intranasal instillation of Streptococcus (S.) pneumoniae. Kinomics peptide arrays, exhibiting 1024 specific consensus sequences for protein kinases, were used to produce a systems biology analysis of cellular kinase activity during the course of pneumonia. Several differences in kinase activity revealed by the arrays were validated in lung homogenates of individual mice using western blot. We identified cascades of activated kinases showing that chemotoxic stress and a T helper 1 response were induced during the course of pneumococcal pneumonia. In addition, our data point to a reduction in WNT activity in lungs of S. pneumoniae infected mice. Moreover, this study demonstrated a reduction in overall CDK activity implying alterations in cell cycle biology. Conclusions/Significance: This s

Complications of skin treatments using Energy Based Devices

Bij het gebruik van lasers en soortgelijke apparatuur voor huidbehandelingen wordt energie van of naar de huid overgedragen, bijvoorbeeld door licht om te zetten in warmte. Hiermee worden delen van de huid, zoals haren, verwijderd of 'beschadigd' en bloedvaatjes 'dichtgeschroeid' om ze te laten verdwijnen. Uit onderzoek van het RIVM blijkt dat alle onderzochte huidbehandelingen complicaties tot gevolg kunnen hebben. Deze kunnen licht en tijdelijk van aard zijn, zoals roodheid en zwelling, maar ook ernstig en blijvend, zoals verbranding en littekens. Complicaties als gevolg van behandelingen met laser- en zogeheten Intense Pulsed Light apparatuur blijken relatief lang aan te houden en vaak voor te komen. Complicaties als gevolg van ultrasound behandelingen en behandelingen van acne met LED-licht houden juist relatief kort aan en komen minder vaak voor. Uit dit onderzoek blijkt ook dat het niet mogelijk is af te bakenen welke laserapparatuur veilig is. De brancheorganisatie van schoonheidsspecialisten gaf aan behoefte te hebben aan een dergelijke afbakening. Hiermee worden eerdere conclusies van het RIVM uit 2015 hierover bevestigd. Verder is in dit vervolgonderzoek de definitie gespecificeerd voor behandelingen van de huid met alle apparatuur die energie overdraagt (Energy Based Devices). In de praktijk bleek het niet duidelijk te zijn welke behandelingen hieronder vielen. De definitie is gebruikt om te bepalen welke behandelingen die in schoonheidssalons worden uitgevoerd Energy Based Device-behandelingen van de huid zijn. De aanleiding van het vervolgonderzoek is het voornemen van de minister van VWS in 2016 om het uitvoeren van behandelingen met lasers en aanverwante apparatuur in de toekomst alleen toe te staan voor artsen en huidtherapeuten. Het voornemen van de minister leidde tot diverse reacties bij beroepsbeoefenaren, in het bijzonder bij schoonheidsspecialisten.Using lasers and similar devices in skin treatments involves the transfer of energy to the skin, for example by converting light to heat. Through this method, parts of the skin, like hairs, can be removed or 'damaged' and small blood vessels can be cauterised so that they disappear. According to research carried out by the Dutch National Institute for Public Health and the Environment (RIVM), all of the treatments investigated are subject to potential complications. These may be mild and temporary in nature, such as redness and swelling, but they may also be more severe and permanent, such as burns or scars. Complications resulting from treatment with laser and so-called Intense Pulsed Light devices appear to continue for a relatively long period and to occur relatively frequently. In contrast, complications resulting from ultrasound treatment and from the treatment of acne with LED light continue for a relatively short period and occur less frequently. This research shows that it is not possible to distinguish between lasers that are safe to use and those that are not. The need for such a distinction has been expressed by the professional body representing beauty therapists. This outcome confirms the earlier conclusion of an RIVM investigation on this topic published in 2015. This follow-up study also specifies the definition of skin treatments with all kinds of energy-transferring devices (Energy Based Devices). In practice, it remained unclear which of these treatments could be classified as such. The definition has been used to determine which treatments performed by beauty therapists can be classified as treatments of the skin with Energy Based Devices. This follow-up study is a consequence of the policy proposition of the Dutch Minister of Health, Welfare and Sport in 2016 to restrict the performance of skin treatments using lasers and similar devices to physicians and skin therapists.This proposition has led to diverse reactions from professionals in the field, and in particular beauty therapists.Ministerie van VW

Complicaties van behandelingen van de huid met Energy Based Devices

Bij het gebruik van lasers en soortgelijke apparatuur voor huidbehandelingen wordt energie van of naar de huid overgedragen, bijvoorbeeld door licht om te zetten in warmte. Hiermee worden delen van de huid, zoals haren, verwijderd of 'beschadigd' en bloedvaatjes 'dichtgeschroeid' om ze te laten verdwijnen. Uit onderzoek van het RIVM blijkt dat alle onderzochte huidbehandelingen complicaties tot gevolg kunnen hebben. Deze kunnen licht en tijdelijk van aard zijn, zoals roodheid en zwelling, maar ook ernstig en blijvend, zoals verbranding en littekens. Complicaties als gevolg van behandelingen met laser- en zogeheten Intense Pulsed Light apparatuur blijken relatief lang aan te houden en vaak voor te komen. Complicaties als gevolg van ultrasound behandelingen en behandelingen van acne met LED-licht houden juist relatief kort aan en komen minder vaak voor. Uit dit onderzoek blijkt ook dat het niet mogelijk is af te bakenen welke laserapparatuur veilig is. De brancheorganisatie van schoonheidsspecialisten gaf aan behoefte te hebben aan een dergelijke afbakening. Hiermee worden eerdere conclusies van het RIVM uit 2015 hierover bevestigd. Verder is in dit vervolgonderzoek de definitie gespecificeerd voor behandelingen van de huid met alle apparatuur die energie overdraagt (Energy Based Devices). In de praktijk bleek het niet duidelijk te zijn welke behandelingen hieronder vielen. De definitie is gebruikt om te bepalen welke behandelingen die in schoonheidssalons worden uitgevoerd Energy Based Device-behandelingen van de huid zijn. De aanleiding van het vervolgonderzoek is het voornemen van de minister van VWS in 2016 om het uitvoeren van behandelingen met lasers en aanverwante apparatuur in de toekomst alleen toe te staan voor artsen en huidtherapeuten. Het voornemen van de minister leidde tot diverse reacties bij beroepsbeoefenaren, in het bijzonder bij schoonheidsspecialisten

Surveillance and Follow-Up Strategies in Patients With High-Grade Dysplasia in Barrett's Esophagus: A Dutch Population-Based Study

OBJECTIVES : In patients with high-grade dysplasia ( HGD) in Barrett's esophagus (BE), it is incompletely known which factors are associated with developing esophageal adenocarcinoma (EAC). We analyzed prior biopsy and follow-up strategies in a large nationwide population-based cohort of patients with HGD in BE, and identified predictors of EAC progression. METHODS : Prior biopsy records and follow-up evaluations were studied in patients with HGD in BE diagnosed between 1999 and 2008, using PALGA, a nationwide network and registry of histopathology and cytopathology in the Netherlands. Multivariate Cox proportional hazards regression analysis was performed to identify predictors for prevalent ( 6 months) EAC. RESULTS : In total, 827 patients with HGD in BE were included. Follow-up data after HGD diagnosis were available in 699 (85%) patients. In 249 (36%) of these patients, an EAC was detected (14.1 EACs per 100 person-years). The risk of prevalent EAC (n = 177) was lower with previous surveillance (hazards ratio 0.7; 95% confidence interval 0.5-0.9), unifocal HGD (0.3;0.2-0.6), diagnosis in a university hospital (0.5;0.3-0.9), endoscopic resection (0.5;0.3-0.7), or ablation (0.0;0.0-0.3); and higher CONCLUSIONS : In this cohort of patients with HGD in BE, the EAC detection rate was 14.1 per 100 person-years and 4.2 per 100 person-years after excluding prevalent cases. The risk of both prevalent and incident EAC was reduced with previous surveillance and endoscopic treatment, while it was increased with older age

A comparative analysis by SAGE of gene expression profiles of Barrett's esophagus, normal squamous esophagus, and gastric cardia

Background & Aims: The metaplastic process In which the normal squamous epithelium of the distal esophagus is replaced by columnar-lined epithelium, known as Barrett's esophagus (BE), is poorly understood. The aim of this study was to define, analyze, and compare transcription profiles of BE, normal cardia epithelium, and squamous epithelium to gain more Insight into the process of metaplasia and to identify uniquely expressed genes in these epithelia. Methods: Serial analysis of gene expression was applied for obtaining transcription libraries of biopsy specimens taken from a BE-affected patient with intestinal type of metaplasia and from normal squamous and gastric cardia epithelia. Validation of results by reverse-transcription polymerase chain reaction and immunoblotting was performed using tissues of 20 patients with BE. Results: More than :120,000 tags were sequenced. Between BE and squamous 776, and between BE and gastric cardia 534 tags were significantly differentially expressed (

Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (P-combined = 4.09 x 10(-9); odds ratio (OR) = 1.21, 95% confidence interval (CI) = 1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (P-combined = 2.74 x 10(-10); OR = 1.14, 95% CI = 1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus