The Diagnostic Accuracy of Double-Layer Sign in Detection of Macular Neovascularization Secondary to Central Serous Chorioretinopathy

PURPOSE: To investigate the diagnostic value of elevated retinal pigment epithelium (RPE) and double-layer sign (DLS) in identifying macular neovascularization (MNV) secondary to central serous chorioretinopathy (CSCR). DESIGN: Retrospective, cross-sectional study. METHODS: Patients with CSCR underwent optical coherence tomography (OCT) and OCT angiography (OCT-A) scanning at Moorfields Eye Hospital. OCT scans were reviewed to identify the presence/absence of an RPE elevation. The maximum length and maximum height of the elevated RPE were measured. A minimum length of 1000 µm and a maximum height of 150 µm were used to define the "double-layer sign". Other qualitative anatomical features were also graded from OCT scans. OCT-A was examined to confirm the presence/absence of MNV. Binary logistic regression analyses were used to assess the association between OCT features and the detection of MNV on OCT-A. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated to assess the diagnostic accuracy. RESULTS: One hundred and sixty-three eyes from 132 patients were included. Elevated RPE was detected in 148 eyes (91%). OCT-A-confirmed MNV was detected in 54 eyes (33%). The sensitivity and specificity of RPE elevation were 100% and 13.8%, respectively. DLS was identified in 95 eyes (58%). The sensitivity and specificity of DLS for detecting MNV were 87% and 56%, respectively. Hyper-reflectivity and non-homogeneity of the sub-RPE space were independently associated with MNV within the DLS (odds ratio, 17.7 and 14.8, p<0.001 and p=0.02, respectively). None of the other demographic or anatomical features associated with MNV. The presence of non-homogeneous hyper-reflective RPE elevation had a sensitivity and specificity of 98% and 67%, with PPV and NPV of 60% and 99%, respectively. CONCLUSIONS: Non-homogeneous and hyper-reflective space under an elevated RPE of any length or height indicates an eye with higher risk of MNV than DLS. OCT-A should at least be performed for these eyes to confirm the presence of MNV and treat accordingly

Innate Immune Training of Granulopoiesis Promotes Anti-tumor Activity

Trained innate immunity, induced via modulation of mature myeloid cells or their bone marrow progenitors, mediates sustained increased responsiveness to secondary challenges. Here, we investigated whether anti-tumor immunity can be enhanced through induction of trained immunity. Pre-treatment of mice with beta-glucan, a fungal-derived prototypical agonist of trained immunity, resulted in diminished tumor growth. The anti-tumor effect of beta-glucan-induced trained immunity was associated with transcriptomic and epigenetic rewiring of granulopoiesis and neutrophil reprogramming toward an anti-tumor phenotype; this process required type I interferon signaling irrespective of adaptive immunity in the host. Adoptive transfer of neutrophils from beta-glucan-trained mice to naive recipients suppressed tumor growth in the latter in a ROS-dependent manner. Moreover, the anti-tumor effect of beta-glucan-induced trained granulopoiesis was transmissible by bone marrow transplantation to recipient naive mice. Our findings identify a novel and therapeutically relevant anti-tumor facet of trained immunity involving appropriate rewiring of granulopoiesis

Discordant effect of body mass index on bone mineral density and speed of sound

BACKGROUND: Increased BMI may affect the determination of bone mineral density (BMD) by dual X-ray absorptiometry (DXA) and speed of sound (SOS) measured across bones. Preliminary data suggest that axial SOS is less affected by soft tissue. The purpose of this study is to evaluate the effect of body mass index (BMI) on BMD and SOS measured along bones. METHODS: We compared axial BMD determined by DXA with SOS along the phalanx, radius and tibia in 22 overweight (BMI > 27 kg/m(2)), and 11 lean (BMI = 21 kg/m(2)) postmenopausal women. Serum bone specific alkaline phosphatase and urinary deoxypyridinoline excretion determined bone turnover. RESULTS: Mean femoral neck – but not lumbar spine BMD was higher in the overweight – as compared with the lean group (0.70 ± 0.82, -0.99 ± 0.52, P < 0.00001). Femoral neck BMD in the overweight – but not in the lean group highly correlated with BMI (R = 0.68. P < 0.0001). Mean SOS at all measurement sites was similar in both groups and did not correlate with BMI. Bone turnover was similar in the two study groups. CONCLUSIONS: The high BMI of postmenopausal women may result in spuriously high BMD. SOS measured along bones may be a more appropriate means for evaluating bones of overweight women

Transcriptional and Proteomic Analysis of the Aspergillus fumigatus ΔprtT Protease-Deficient Mutant

Aspergillus fumigatus is the most common opportunistic mold pathogen of humans, infecting immunocompromised patients. The fungus invades the lungs and other organs, causing severe damage. Penetration of the pulmonary epithelium is a key step in the infectious process. A. fumigatus produces extracellular proteases to degrade the host structural barriers. The A. fumigatus transcription factor PrtT controls the expression of multiple secreted proteases. PrtT shows similarity to the fungal Gal4-type Zn(2)-Cys(6) DNA-binding domain of several transcription factors. In this work, we further investigate the function of this transcription factor by performing a transcriptional and a proteomic analysis of the ΔprtT mutant. Unexpectedly, microarray analysis revealed that in addition to the expected decrease in protease expression, expression of genes involved in iron uptake and ergosterol synthesis was dramatically decreased in the ΔprtT mutant. A second finding of interest is that deletion of prtT resulted in the upregulation of four secondary metabolite clusters, including genes for the biosynthesis of toxic pseurotin A. Proteomic analysis identified reduced levels of three secreted proteases (ALP1 protease, TppA, AFUA_2G01250) and increased levels of three secreted polysaccharide-degrading enzymes in the ΔprtT mutant possibly in response to its inability to derive sufficient nourishment from protein breakdown. This report highlights the complexity of gene regulation by PrtT, and suggests a potential novel link between the regulation of protease secretion and the control of iron uptake, ergosterol biosynthesis and secondary metabolite production in A. fumigatus

Tumor necrosis factor-α gene promoter −308 and −238 polymorphisms and its serum level in psoriasis

Background: Psoriasis is a chronic, immune-mediated, inflammatory skin disease affecting genetically predisposed individuals and requiring long-term treatment. The etiology of psoriasis is not fully understood. This article aimed to determine association between genetic polymorphisms in tumor necrosis factor-α (TNF -α) promoter −308 (rs1800629) and −238 (rs 361,525) and its serum level in psoriasis patients. Methods: The study was conducted on 70 patients with psoriasis and 70 age and sex-matched, healthy individuals. All patients were subjected to history taking and complete medical examination. The polymorphisms of TNF -α promoter gene −308 (rs1800629) and −238 (rs 361,525) were detected by real time PCR and Serum levels of TNF -α were measured by ELISA technique. Results: AG polymorphism and A allele of TNF-α −238 G/A (rs 361,525) were significantly more in patients than controls, whereas AG polymorphism and A allele of TNF-α −308 G/A (rs1800629) were significantly more in controls than patients. There were significant high levels of TNF-α in serum of patients in comparison to controls. Conclusions: The AG polymorphism and A allele of TNF-α −238G/A (rs 361,525) may act as a risk factor for occurrence of psoriasis, whereas AG polymorphism and A allele of TNF-α −308G/A (rs1800629) may have protective role. There is pivotal role of TNF-α as a pro-inflammatory mediator in pathogenesis of psoriasis

Spectrum subtraction as a complementary method for six resolution techniques resolving overlapping spectra; application to multicomponent veterinary formulation with greenness and whiteness assessment

Abstract Mathematical filtration is an efficient tool to resolve the overlapping spectra of binary mixtures in zero or first order form. Herein, a comparative study was conducted between six economic, accurate and precise spectrophotometric methods for determination of Triclabendazole (TCB) and Levamisole HCl (LVM). Each component was resolved with minimum mathematical steps in its zero-order absorption spectrum by ratio subtraction, constant multiplication, and the recent factorized response method; coupled with spectrum subtraction. In addition, the mixture was resolved in its first derivative form by derivative subtraction, D1 constant multiplication, and the recent D1 factorized response method; coupled with spectrum subtraction. Results obtained were also compared to those obtained from constant value, concentration value, and derivative ratio methods. The linearity range was found to be either 1.0–10.0 µg/mL or 2.0–20.0 µg/mL for TCB, and 2.0–14.0 µg/mL for LVM with LOD of 0.08 µg/mL and 0.19 µg/mL, respectively. Validation of the proposed methods was performed according to VICH guidelines. Results obtained from the statistical data showed no significant difference regarding accuracy and precision compared to the reported methods. The developed spectrophotometric methods followed the principles of green analytical chemistry, in which the green assessment was done through four tools, called, National Environmental Methods Index (NEMI), Analytical Eco-Scale (AES), Green Analytical Procedure Index (GAPI) and Analytical greenness metric (AGREE). Also, a white assessment was performed using RGB model. The proposed methods could offer an economic alternative for the routine analysis of bulk materials and combined veterinary dosage form. Graphical Abstrac