Graves’ orbitopathy (GO) is an autoimmune disorder and the main extrathyroidal expression of Graves’ disease. There is a spectrum of ocular involvement in Graves’ disease, from complete absence of ...symptoms and signs to sight-threatening conditions. The prevalence of GO varies in different published series of Graves’ patients, due to confounding factors (new diagnosis
vs
long-lasting disease, way of defining and assessing ocular involvement, treatment of hyperthyroidism with potentially GO-modifying treatments, such as radioiodine). Recent studies, however, suggest that most Graves’ patients have mild or no GO at presentation, while moderate-to-severe GO is rare, and sight-threatening GO (mostly due to dysthyroid optic neuropathy) is exceptional in non-tertiary referral centers. The natural course of GO is incompletely defined, particularly in patients with moderate-to-severe GO, because these patients require prompt and disease-modifying therapies for orbital disease. In patients with mild GO at presentation, progression to severe forms is rare, while partial or complete remission is frequent. Progression of pre-existing GO or
de novo
occurrence of GO is more likely in smokers. There seems to be a trend towards a decline in progression of GO, possibly due to a better control of risk factors (cigarette smoking, thyroid dysfunction,
etc
.) and a closer interaction between endocrinologists and ophthalmologists allowing an improved integrated management of thyroid and orbital disease.
Both IDH1 mutation and MGMT promoter methylation are associated with longer survival. We investigated the ability of imaging correlates to serve as noninvasive biomarkers for these molecularly ...defined GBM subtypes.
MR imaging from 202 patients with GBM was retrospectively assessed for nonenhancing tumor and edema among other imaging features. IDH1 mutational and MGMT promoter methylation status were determined by DNA sequencing and methylation-specific PCR, respectively. Overall survival was determined by using a multivariate Cox model and the Kaplan-Meier method with a log rank test. A logistic regression model followed by ROC analysis was used to classify the IDH1 mutation and methylation status by using imaging features.
MGMT promoter methylation and IDH1 mutation were associated with longer median survival. Edema levels stratified survival for methylated but not unmethylated tumors. Median survival for methylated tumors with little/no edema was 2476 days (95% CI, 795), compared with 586 days (95% CI, 507-654) for unmethylated tumors or tumors with edema. All IDH1 mutant tumors were nCET positive, and most (11/14, 79%) were located in the frontal lobe. Imaging features including larger tumor size and nCET could be used to determine IDH1 mutational status with 97.5% accuracy, but poorly predicted MGMT promoter methylation.
Imaging features are potentially predictive of IDH1 mutational status but were poorly correlated with MGMT promoter methylation. Edema stratifies survival in MGMT promoter methylated but not in unmethylated tumors; patients with methylated tumors with little or no edema have particularly long survival.
Serial focussed ion beam scanning electron microscopy (FIB/SEM) enables imaging and assessment of subcellular structures on the mesoscale (10 nm to 10 µm). When applied to vitrified samples, serial ...FIB/SEM is also a means to target specific structures in cells and tissues while maintaining constituents' hydration shells for in situ structural biology downstream. However, the application of serial FIB/SEM imaging of non-stained cryogenic biological samples is limited due to low contrast, curtaining, and charging artefacts. We address these challenges using a cryogenic plasma FIB/SEM. We evaluated the choice of plasma ion source and imaging regimes to produce high-quality SEM images of a range of different biological samples. Using an automated workflow we produced three-dimensional volumes of bacteria, human cells, and tissue, and calculated estimates for their resolution, typically achieving 20-50 nm. Additionally, a tag-free localisation tool for regions of interest is needed to drive the application of in situ structural biology towards tissue. The combination of serial FIB/SEM with plasma-based ion sources promises a framework for targeting specific features in bulk-frozen samples (>100 µm) to produce lamellae for cryogenic electron tomography.
Residential kitchen cooking generates significant amount of gases and particulate pollutants and is regarded as a major pollutant source in residential microenvironments. Existing risk assessments ...always assume well-mixed condition. We used a portable nephelometer to measure PM3.5 oil particle concentration in a kitchen under low air exchange rate condition. Two sampling locations were chosen: one near (0.3
m) and another far (2.8
m) from the cooking stove. Numerical simulation was also used to model the particle transport in a model kitchen. Particles passing through the pre-defined sampling areas were tracked and counted. The simulated results agree reasonably well with the measured concentration. It shows that concentration at the near-field is almost three times as high as that at the far-field. Exposure assessment results based on well-mixed assumption should be applied with caution.
The differentiation of intracranial atherosclerosis (ICAS) and embolism is important.
In cases of ICAS, we observe a phenomenon that we call the “post-stent-deployment effect”; that is, all major ...branches are clearly visible beyond the occlusion segment when the stent is deployed at the site of occlusion. Our objective is to evaluates whether this post-stent-deployment effect can be used to differentiate ICAS from embolism in the distal M1 segment occlusion.
We conduct a retrospective study which reviewed consecutive patients with acute distal M1 segment and in whom recanalization was achieved by endovascular treatment. The post-stent-deployment effect was assessed in these patients. The sensitivity, specificity, positive predictive values (PPV), and accuracy of the post-stent-deployment effect for prediction of ICAS were assessed.
From January 2015 to July 2018, a total of 80 patients were evaluated. The post-stent-deployment effect was more frequently observed in patients with ICAS than in those with embolism (100% vs 15.0%, P < .001). For identifying ICAS in distal M1 segment, the sensitivity, specificity, PPV, and accuracy of the post-stent-deployment effect were 100%, 85.0%, 69.0%, and 88.7%, respectively.
Our study finds that the sensitivity and accuracy of the post-stent-deployment effect in predicting distal M1 segment ICAS occlusion in patients with acute symptoms was high, and it may be useful in identifying ICAS lesion.
•All branches are visible when stent is deployed and was called as post-stent- deployment effect.•This effect was more frequently observed in ICAS lesion than in embolism.•Identifying ICAS lesion, the sensitivity and accuracy of this effect were high.
Salmonella enterica serovar Typhimurium is a flagellated bacterium and one of the leading causes of gastroenteritis in humans. Bacterial flagellin is required for motility and also a prime target of ...the innate immune system. Innate immune recognition of flagellin is mediated by at least two independent pathways, TLR5 and Naip5-Naip6/NlrC4/Caspase-1. The functional significance of each of the two independent flagellin recognition systems for host defense against wild type Salmonella infection is complex, and innate immune detection of flagellin contributes to both protection and susceptibility. We hypothesized that efficient modulation of flagellin expression in vivo permits Salmonella to evade innate immune detection and limit the functional role of flagellin-specific host innate defenses. To test this hypothesis, we used Salmonella deficient in the anti-sigma factor flgM, which overproduce flagella and are attenuated in vivo. In this study we demonstrate that flagellin recognition by the innate immune system is responsible for the attenuation of flgM(-) S. Typhimurium, and dissect the contribution of each flagellin recognition pathway to bacterial clearance and inflammation. We demonstrate that caspase-1 controls mucosal and systemic infection of flgM(-) S. Typhimurium, and also limits intestinal inflammation and injury. In contrast, TLR5 paradoxically promotes bacterial colonization in the cecum and systemic infection, but attenuates intestinal inflammation. Our results indicate that Salmonella evasion of caspase-1 dependent flagellin recognition is critical for establishing infection and that evasion of TLR5 and caspase-1 dependent flagellin recognition helps Salmonella induce intestinal inflammation and establish a niche in the inflamed gut.
Background Cutaneous leishmaniasis is an endemic disease in Surinam. The disease was treated until the early 1970s with pentavalent antimony. Pentamidine mesylate was introduced by Niemel in 1973 for ...the treatment of cutaneous leishmaniasis in Surinam.
Materials and methods In this retrospective study, we evaluate the results of treatment with pentamidine mesylate in 235 patients and with pentamidine isethionate in 80 patients.
Results In the pentamidine mesylate‐ and pentamidine isethionate‐treated groups, a cure rate (healing without relapse) of nearly 90% was found. Relapses were seen in approximately 10% of patients in both groups. Minor side‐effects, such as pain at the injection site, bitter taste, and nausea, were seen with both drugs in about 65% of patients. Complaints of the respiratory tract were seen in less than 10% of patients in the pentamidine isethionate‐treated group, but were uncommon in the pentamidine mesylate‐treated group.
Conclusions Pentamidine mesylate and isethionate have similar safety, efficacy, and side‐effect profiles in the treatment of cutaneous leishmaniasis in Surinam.
Sympathetic nerve activity is known to be important in ventricular arrhythmogenesis, but there is little information on the relation between the distribution of cardiac sympathetic nerves and the ...occurrence of spontaneous ventricular arrhythmias in humans.
We studied 53 native hearts of transplant recipients, 5 hearts obtained at autopsy of patients who died of noncardiac causes, and 7 ventricular tissues that had been surgically resected from the origin of ventricular tachycardia. The history was reviewed to determine the presence (group 1A) or absence (group 1B) of spontaneous ventricular arrhythmias. Immunocytochemical staining for S100 protein, neurofilament protein, tyrosine hydroxylase, and protein gene product 9.5 was performed to study the distribution and the density of sympathetic nerves. The average left ventricular ejection fraction was 0.22+/-0.07. A total of 30 patients had documented ventricular arrhythmias, including ventricular tachycardia and sudden cardiac death. A regional increase in sympathetic nerves was observed around the diseased myocardium and blood vessels in all 30 hearts. The density of nerve fibers as determined morphometrically was significantly higher in group 1A patients (total nerve number 19.6+/-11.2/mm(2), total nerve length 3.3+/-3.0 mm/mm(2)) than in group 1B patients (total nerve number 13.5+/-6.1/mm(2), total nerve length 2.0+/-1.1 mm/mm(2), P<0. 05 and P<0.01, respectively).
There is an association between a history of spontaneous ventricular arrhythmia and an increased density of sympathetic nerves in patients with severe heart failure. These findings suggest that abnormally increased postinjury sympathetic nerve density may be in part responsible for the occurrence of ventricular arrhythmia and sudden cardiac death in these patients.
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