Gross Haas (beefqueen97)

Environmental health research is at a promising stage for more precisely identifying gene-environment components of disease. Simplistic models and reductionist approaches that have been the norm both in toxicology and in clinical medicine are beginning to be replaced with a more holistic or systems biology approach. We are slowly moving to an understanding that the time between an exposure and its consequence as a diagnosed disease is a time during which many different biochemical changes are occurring and a time during which many biomarkers of disease progression could be identified and used. With such information in hand, clinicians would be able to intervene early in disease progression. With such information, environmental health researchers and policy makers could more reliably identify which elements in our environment need to be controlled or reduced and which populations need the most protection. With such information, the incidence of many human diseases could be dramatically reduced.Glioma are common malignant brain tumors, among which glioblastoma multiforme (GBM) has the worst prognosis. Different studies of GBM revealed that targeting nuclear-factor-κB (NF-κB) induced an attenuation tumor proliferation and prolonged cell survival. TBK1 (TANK TRAF (TNF (tumor-necrosis-factor) receptor-associated factor)-associated NF-κB activator-binding kinase 1) is a serine/threonine-protein kinase and it is a member of the IκB kinase (IKK) family, involved in NF-κB pathway activation. The aim of this study was to investigate the potential effect of BX795, an inhibitor of TBK1, in an in vitro and ex vivo model of GBM. GBM cell lines (U87 and U138) and primary GBM cells were treated with different concentrations of BX795 at different time-points (24, 48 and 72h) to evaluate cell viability, autophagy, inflammation and apoptosis. Our results demonstrated that BX795 10 μM was able to reduce cell viability, showing antiproliferative effect both in U87, U138 and primary GBM cells. Moreover, treatment with BX795 10 μM increased the pro-apoptotic proteins Bax, p53, caspase-3 and caspase-9 whereas the anti-apoptotic Bcl-2 expression was reduced. Additionally our results showed a marked decrease of autophagy following BX795 treatment, reducing Atg7, Atg 5/12 and AKT expression. The anti-inflammatory effect of BX795 was demonstrated by a significantly reduction of NIK, IKKα and TNF-α expression, accompanied by a down-regulation of angiogenesis. Furthermore, in primary GBMs cell, BX795 10 μM was able to reduce TBK1 pathway activation and SOX3 expression. Nazartinib clinical trial In conclusion, these findings showed that TBK1 is involved in GBM proliferation demonstrating that the inhibitor BX795, thanks its abilities, could improve therapeutic strategies for GBM treatment. The Odon Device™ is a new device for assisted vaginal birth that employs an air cuff around the fetal head for traction. Assisted vaginal birth (AVB) is a vital health intervention that can result in better outcomes for mothers and their babies when complications arise in the second stage of labour. Unfortunately, instruments for AVB (forceps and ventouse) are often not used in settings where there is most clinical need often due to lack of training and resources, resulting in maternal and neonatal morbidity and mortality which could have been prevented. This is often due to a lack of trained operators as well as difficulties in the sterilisation and maintenance of AVB devices. This novel, single use device has the potential to mitigate these difficulties as it is single use and is potentially simpler to use than forceps and ventouse. All the studies of the Odon Device to date (pre-clinical, preliminary developmental and clinical) suggest that the Odon Device does not present a higher risk to mothers or babaternal, neonatal and device outcomes. Safety data will be reviewed following every birth exploring maternal, neonatal and device risks. Using A'Hern approach