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1 and 30.0 months after R0 resection (p&nbsp;=&nbsp;0.184), and 23.6 and 20.5 months after R1 resection (p&nbsp;=&nbsp;0.005). CONCLUSION This analysis demonstrated that AT did not yield OS benefit for patients who had neoadjuvant therapy and R0 resection and a statistically significant, although relatively short, improvement in OS for patients who underwent R1 resection. Ni-containing CO-dehydrogenases (CODHs) allow some microorganisms to couple ATP synthesis to CO oxidation, or to use either CO or CO2 as a source of carbon. The recent detailed characterizations of some of them has evidenced a great diversity in terms of catalytic properties and resistance to O2. In an effort to increase the number of available CODHs, we have heterologously produced in Desulfovibrio fructosovorans, purified and characterized the two CooS-type CODHs (CooS1 and CooS2) from the hyperthermophilic archaeon Thermococcus sp. AM4 (Tc). We have also crystallized CooS2, which is coupled in vivo to a hydrogenase. CooS1 and CooS2 are homodimers, and harbour five metalloclusters two NiFe4S4 C clusters, two [4Fe4S] B clusters and one interfacial [4Fe4S] D cluster. We show that both are dependent on a maturase, CooC1 or CooC2, which is interchangeable. The homologous protein CooC3 does not allow Ni insertion in either CooS. The two CODHs from Tc have similar properties they can both oxidize and produce CO. The Michaelis constants (Km) are in the microM range for CO and in the mM range (CODH 1) or above (CODH 2) for CO2. Product inhibition is observed only for CO2 reduction, consistent with CO2 binding being much weaker than CO binding. The two enzymes are rather O2 sensitive (similarly to CODH II from Carboxydothermus hydrogenoformans), and react more slowly with O2 than any other CODH for which these data are available. V.Cadmium (Cd), a toxic environment contaminant, induces reactive oxygen species (ROS)-mediated neuronal apoptosis and consequential neurodegenerative disorders. Metformin, an anti-diabetic drug, has recently received a great attention owing to its protection against neurodegenerative diseases. However, little is known regarding the effect of metformin on Cd-induced neurotoxicity. Here we show that metformin effectively prevented Cd-evoked apoptotic cell death in neuronal cells, by suppressing Cd activation of c-Jun N-terminal kinases (JNK), which was attributed to blocking Cd inactivation of protein phosphatase 5 (PP5) and AMP-activated protein kinase (AMPK). Inhibition of JNK with SP600125, knockdown of c-Jun, or overexpression of PP5 potentiated metformin's inhibitory effect on Cd-induced phosphorylation of JNK/c-Jun and apoptosis. Activation of AMPK with AICAR or ectopic expression of constitutively active AMPKα strengthened the inhibitory effects of metformin on Cd-induced phosphorylation of JNK/c-Jun and apoptosis, whereas expression of dominant negative AMPKα weakened these effects of metformin. Metformin repressed Cd-induced ROS, thereby diminishing cell death. N-acetyl-l-cysteine enhanced the inhibitory effects of metformin on Cd-induced ROS and apoptosis. Moreover, using Mito-TEMPO, we further demonstrated that metformin attenuated Cd-induced cell death by suppressing induction of mitochondrial ROS. Taken together, these results indicate that metformin prevents mitochondrial ROS inactivation of PP5 and AMPK, thus attenuating Cd-induced JNK activation and apoptosis in neuronal cells. Our data highlight that metformin may be a promising drug for prevention of Cd-induced oxidative stress and neurodegenerative diseases. This study aimed to assess the cytotoxic effect of low molecular weight components (LMWC) and conventional silicone oils (SOs) 1000&nbsp;cSt with different degree of purification (raw, intermediate, and purified) using in vitro cytotoxicity tests. Direct contact cytotoxicity tests were performed in BALB 3T3 and human retinal pigment epithelial cells (ARPE-19) using quantitative and qualitative evaluation according to the ISO 10993-5 (2009) standards. Conventional SOs 1000&nbsp;cSt in form of raw, intermediate (intermediate product obtained during distillation process), and purified SO (final product after distillation) and a concentrate of LMWC (including siloxane chains with molecular weight up to 1557&nbsp;g/mol) were directly applied to 100% of cell layer area for 24&nbsp;h. Cell viability was quantified using 3-(4,5-dimethylthiazole-2-yl)-2,5-28 diphenyltetrazolium bromide (MTT) and neutral red uptake assays in ARPE-19 and BALB3T3, respectively. All tested samples, including the concentrate of LMWC, resulted to be not cytotoxic according to ISO 10993-5 in both qualitative and quantitative evaluations. However, the cellular viability was significantly higher in the intermediate and purified SO compared with the raw SO in ARPE-19&nbsp;cells. No reduction in cell viability was detected by LMWC. The absence of cytotoxicity was observed for all tested samples in both BALB3T3 and ARPE-19 after 24&nbsp;h of application. A direct cytotoxic effect is not likely to be involved in the potential complications related to SO and LMWC. Long-term potential adverse effects of SO could be related to the raw material and to different concentrations of LMWC. The intraepithelial corneal nerves (ICNs) that innervate the corneal epithelium are maintained through interactions with corneal epithelial cells and the extracellular matrix they produce. One to several axons bundle together within the basal cell layer and extend parallel to the ocular surface or branch and extend apically. Here we use 3-dimentional (3D) ultrastructural reconstructions of control and trephine injured mouse corneal epithelium and stroma produced using Focused Ion Beam Scanning Electron Microscope (FIB-SEM) to determine whether corneal epithelial or immune cells resident in the epithelium remove axonal debris and degrade it in their lysosomes after trephine injury to the cornea. We demonstrate that axonal fragments are internalized in the corneal epithelium and accumulate within electron dense structures consistent with lysosomes 3 h after trephine injury in both epithelial and immune cells located among the basal cells of the trephine injured cornea. Confocal imaging showed fewer CD45+ immune cells within the corneal epithelium after trephine injury compared to controls. The resolution obtained using FIB-SEM also allowed us to show that the presence of sensory axons at the basal aspect of the epithelial basal cells close to the anterior aspect of the epithelial basement membrane (EBM) is associated with a focal reduction in EBM thickness. In addition, we show using FIB-SEM and confocal imaging that superficial trephine injuries that do not penetrate the stroma, damage the integrity of anterior stromal nerves. [https://www.selleckchem.com/products/ms-275.html Entinostat mouse] These studies are the first to look at the mouse cornea following nerve injury using FIB-SEM. INTRODUCTION There is a need to find alternative treatments for MEe. Bromfenac has shown promise in inhibiting the COX-2 enzymatic pathway that partially causes the inflammatory cascade which contributes to the precipitation of ME. However, like other NSAID's, its intraocular half-life is limited. We hypothesize that a delayed-release liposome formulation containing bromfenac might provide a similar anti-inflammatory effect as long-lasting steroid release systems without the well-known steroidal side-effects. We introduced a novel formulation with these characteristics into the vitreous cavity of rabbit eyes in order to evaluate its safety profile. MATERIAL AND METHODS 10 left eyes of rabbits were injected with the liposome-encapsulated bromfenac suspension (100&nbsp;μg/0.1&nbsp;ml). Basal ERG's were recorded. Total follow-up time was 3 months, at which point ERG's were repeated and eyes were enucleated for histopathological study. Total amplitude and implicit times were recorded. A difference of 25% in either recording was considered significant. Significance was assessed using the paired-t test and Wilcoxon matched-pairs signed-rank test. A p-value of less then 0.05 was considered significant. RESULTS No significant changes were recorded in ERG measurements after 3 months when compared to basal measurements. Histopathological analysis of retinal specimens found no traces of liposome-induced toxicity. CONCLUSION The liposome-encapsulated bromfenac suspension (100&nbsp;μg/0.1&nbsp;ml) is not toxic and has been proven safe to use in an animal model. Therefore, this formulation shows promise as a possible future alternative treatment for ME and should be further studied to show its biological effect and efficacy. PURPOSE Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening disease, of which genetic abnormalities are considered as important risk factors. The present research aims at identifying causal variants in Chinese patients with sporadic non-syndromic type A TAAD (ATAAD). MATERIALS AND METHODS Whole exome sequencing (WES) was performed on 73 sporadic Chinese patients with ATAAD, 30 TAAD associated genes were curated for bioinformatic analyses. Clinical differences were compared between patients with and without causal variants. RESULTS 15 pathogenic/likely pathogenic variants were identified (8 novel and 7 previously described) in 4 known TAAD-causal genes (FBN1, TGFBR2, SMAD3 and ACTA2) in 15 individuals, including 11 variants in FBN1 (7 missense, 3 truncating, and 1 splicing variants), 2 missense variants in TGFBR2, 1 ACTA2 frameshift variant and 1 SMAD3 frameshift variant. Significant clinical differences were found between patients with and without causal variants. Patients with TAAD-causal variants proved to have an earlier onset age, a more dilated aorta, and relatively intractable subtypes. Even without risk factor like hypertension, they might still suffer from TAAD with TAAD-causal variants. CONCLUSIONS The variants identified in our research might not only result in the occurrence of ATAAD, but also add complexities and difficulties to the clinical practice. Our data demonstrated that WES was an effective tool for determining genetic etiologies of non-syndromic ATAAD and could be helpful in genetic counseling for ATAAD patients and their at-risk family members. The prevalence of bipolar disorders in patients requesting bariatric surgery is estimated to be 1.5% to 3.4%. There are currently no specific recommendations regarding the way bariatric surgery should be managed in the context of bipolar disorder. The aim was to document the benefit-risk of bariatric surgery in patients with bipolar disorders. A systematic literature review was carried out. In addition, results were reported from a survey of current clinical practice in French referent centers for obesity care. Finally, 3 clinical cases from the "Severe Obesity Outcome Network" cohort are described. This systematic review shows there are few studies in the literature regarding the outcomes of bariatric surgery in patients with bipolar disorders and no randomized, controlled trials. Weight loss appeared similar in all patients, but psychiatric complications were sometimes reported in those with bipolar disorders. Almost all 11 referent centers for obesity care that responded had carried out bariatric surgery in patients with stable bipolar disorders. Postsurgical psychiatric destabilization occurred and included, at least, a need to reinforce treatment and follow-up. In the 3 case studies, postsurgical manic or hypomanic decompensation occurred. Thus, although effective in terms of weight loss, bariatric surgery could be a destabilizing factor for those with bipolar disorders. Current practice is to contraindicate surgery in patients with unstable disorders. There are insufficient data to conclude on the benefits and safety of bariatric surgery in patients with stable bipolar disease. Further studies are required to fully determine the benefits and risks.