AAV-mediated and pharmacological induction of Hsp70 expression stimulates survival of retinal ganglion cells following axonal injury.

We evaluated the effect of AAV2- and 17-AAG (17-N-allylamino-17-demethoxygeldanamycin)-mediated upregulation of Hsp70 expression on the survival of retinal ganglion cells (RGCs) injured by optic nerve crush (ONC). AAV2-Hsp70 expression in the retina was primarily observed in the ganglion cell layer. Approximately 75% of all transfected cells were RGCs. RGC survival in AAV2-Hsp70-injected animals was increased by an average of 110% 2 weeks after the axonal injury compared with the control. The increase in cell numbers was not even across the retinas with a maximum effect of approximately 306% observed in the inferior quadrant. 17-AAG-mediated induction of Hsp70 expression has been associated with cell protection in various models of neurodegenerative diseases. We show here that a single intravitreal injection of 17-AAG (0.2 ug ul(-1)) results in an increased survival of ONC-injured RGCs by approximately 49% compared with the vehicle-treated animals. Expression of Hsp70 in retinas of 17-AAG-treated animals was upregulated approximately by twofold compared with control animals. Our data support the idea that the upregulation of Hsp70 has a beneficial effect on the survival of injured RGCs, and the induction of this protein could be viewed as a potential neuroprotective strategy for optic neuropathies

Asymmetric phenotype of Axenfeld-Rieger anomaly and aniridia associated with a novel PITX2 mutation

PurposeTo evaluate the asymmetry of the anterior segment phenotype between the two eyes of a patient with Axenfeld-Rieger syndrome (ARS).MethodsThe entire database of a tertiary glaucoma practice was screened for patients with ARS. The medical records of patients with ARS were reviewed. The clinical characteristics of ocular examination of the two eyes of each patient were recorded and compared. Dental and medical information were also reviewed where available. The anterior segment phenotype was tabulated to assess asymmetry. Asymmetric anterior segment characteristics of patients with ARS were compared with reported cases in the literature.ResultsEight patients with ARS were identified from screening of more than 5,000 patients of a tertiary glaucoma practice. All patients had Axenfeld-Rieger anomaly in both eyes except one patient presented with an asymmetric phenotype of the anterior segment with features of Axenfeld-Rieger anomaly in one eye, but aniridia in the other eye. This patient had non-ocular findings including flat midface, hypodontia with lack of an upper incisor, and redundant periumbilical skin, typical for ARS. A heterozygous C>T nucleotide substitution was identified in exon 4 of the pituitary homeobox 2 (PITX2) gene, resulting in the replacement of a glutamine codon (CAG) with a stop codon (TAG) at amino acid position 67. This mutation is denoted c.199C>T at the cDNA level or p.Gln67Stop (or Q67X) at the protein level. Only three cases with asymmetric anterior segment phenotype between the two eyes of a patient with AGS have been reported in the literature.ConclusionsVariability in phenotype may occur between the two eyes of an individual affected by ARS. The current case undermines the advantage of genetic testing to correctly diagnose a rare disease

A Comparison of the effectiveness of cooperative and individual teaching methods on educational achievement of English in grade one of high school

The purpose of this study was to compare cooperative teaching and individual teaching on educational achievement in English in grade one of high school (female students). This study is a quasi-experimental study with pre-test- and post- test with two experimental groups. The Statistical population was high school's first grade female students of Mahabad. For sampling, multi-stage cluster sampling was used. The sample size was 52 consist of 25 and 27 members in the experimental group (1) and (2) in which cooperation and individual teaching methods were used respectively. In order to equalize the members of groups the student's GPA were controlled and pre-test and IQ test were done. The results showed no significant difference between groups.The pre-test was a researcher-made. Reliability of the pre-test was obtained 0.83. The cooperative and individual methods were done for 2 months and then post- test was carried out. The results showed no significant differences between them. T-test analyzes shows significant differences between the two groups so that the first experimental group (cooperative) showed better performance in educational achievement

Methylation and protein expression of DNA repair genes: association with chemotherapy exposure and survival in sporadic ovarian and peritoneal carcinomas

<p>Abstract</p> <p>Background</p> <p>DNA repair genes critically regulate the cellular response to chemotherapy and epigenetic regulation of these genes may be influenced by chemotherapy exposure. Restoration of BRCA1 and BRCA2 mediates resistance to platinum chemotherapy in recurrent BRCA1 and BRCA2 mutated hereditary ovarian carcinomas. We evaluated BRCA1, BRCA2, and MLH1 protein expression in 115 sporadic primary ovarian carcinomas, of which 31 had paired recurrent neoplasms collected after chemotherapy. Additionally, we assessed whether promoter methylation of BRCA1, MLH1 or FANCF influenced response to chemotherapy or explained alterations in protein expression after chemotherapy exposure.</p> <p>Results</p> <p>Of 115 primary sporadic ovarian carcinomas, 39 (34%) had low BRCA1 protein and 49 (42%) had low BRCA2 expression. BRCA1 and BRCA2 protein expression were highly concordant (p < 0.0001). MLH1 protein loss occurred in 28/115 (24%) primary neoplasms. BRCA1 protein loss in primary neoplasms was associated with better survival (p = 0.02 Log Rank test) and remained significant after accounting for either stage or age in a multivariate model (p = 0.04, Cox proportional hazards). In paired specimens, BRCA1 protein expression increased in 13/21 (62%) and BRCA2 protein expression increased in 15/21 (71%) of recurrent carcinomas with low or intermediate protein in the paired primary. In contrast MLH1 expression was rarely decreased in recurrent carcinomas (1/33, 3%). Similar frequencies of MLH1, BRCA1, and FANCF promoter methylation occurred in primary carcinomas without previous chemotherapy, after neoadjuvant chemotherapy, or in recurrent neoplasms.</p> <p>Conclusion</p> <p>Low BRCA1 expression in primary sporadic ovarian carcinoma is associated with prolonged survival. Recurrent ovarian carcinomas commonly have increased BRCA1 and/or BRCA2 protein expression post chemotherapy exposure which could mediate resistance to platinum based therapies. However, alterations in expression of these proteins after chemotherapy are not commonly mediated by promoter methylation, and other regulatory mechanisms are likely to contribute to these alterations.</p

Common carotid segmentation in 18F-sodium fluoride PET/CT scans: Head-to-head comparison of artificial intelligence-based and manual method

Background: Carotid atherosclerosis is a major cause of stroke, traditionally diagnosed late. Positron emission tomography/computed tomography (PET/CT) with 18F-sodium fluoride (NaF) detects arterial wall micro-calcification long before macro-calcification becomes detectable by ultrasound, CT or magnetic resonance imaging. However, manual PET/CT processing is time-consuming and requires experience. We compared a convolutional neural network (CNN) approach with manual segmentation of the common carotids. Methods: Segmentation in NaF-PET/CT scans of 29 healthy volunteers and 20 angina pectoris patients were compared for segmented volume (Vol) and mean, maximal, and total standardized uptake values (SUVmean, SUVmax, and\ua0SUVtotal). SUVmean was the average of SUVmeans within the VOI, SUVmax the highest SUV in all voxels in the VOI, and SUVtotal the SUVmean multiplied by the Vol of the VOI. Intra\ua0and Interobserver variability with manual segmentation was examined in 25 randomly selected scans. Results: Bias for Vol, SUVmean, SUVmax, and SUVtotal were 1.33 \ub1 2.06, −0.01 \ub1 0.05, 0.09 \ub1 0.48, and 1.18 \ub1 1.99 in the left and 1.89 \ub1 1.5, −0.07 \ub1 0.12, 0.05 \ub1 0.47, and 1.61 \ub1 1.47, respectively, in the right common carotid artery. Manual segmentation lasted typically 20 min versus 1 min with the CNN-based approach. Mean Vol deviation at repeat manual segmentation was 14% and 27% in left and right common carotids. Conclusions: CNN-based segmentation was much faster and provided SUVmean values virtually identical to manually obtained ones, suggesting CNN-based analysis as a promising substitute of slow and cumbersome manual processing

Nanoparticle-stabilized microemulsions for enhanced oil recovery from heterogeneous rocks

Surfactant-stabilized microemulsions (MEs) are often used to reduce the capillary forces responsible for trapping residual oil inside rocks. Recent studies showed that the presence of nanoparticles (NPs) in ME could enhance oil recovery, however their interfacial interactions and the impact of rock characteristics is still unclear. The objective of this study was to understand the effect of microemulsions stabilized by nanoparticles (MENP) on pore-scale fluid displacement mechanisms in a heterogeneous rock such as Arkose. A novel method was developed to synthesize silicon oxide in-situ in a ME. These nanoparticles had less tendency to agglomerate compared to nanopowders and promoted the formation of Pickering emulsions. The impact of ME and MENP on oil displacement in Arkose was examined using microtomography integrated with miniature core flooding. Aged cores were subjected to flooding with different aqueous solutions to investigate the effectiveness of ME and MENP in enhancing oil recovery. We found that ME promoted oil mobilization by reducing IFT and enhancing emulsification. The ability of ME to solubilize adsorbed oil layers contributed to a wettability alteration from oil-wet to weakly water-wet. Therefore, ME could remove 20.0% of additional oil after waterflooding. The incremental oil removal with MENP compared to waterflooding (34.3%) was higher than that of ME due to the emulsification of oil into even smaller droplets where NPs and surfactants synergistically interacted at the interface. The small oil droplets could penetrate small capillary elements of the rock that were inaccessible to ME, leading to stronger wettability alteration especially in carbonate cement

Pore-scale dynamics of nanofluid-enhanced NAPL displacement in carbonate rock

This study presents a pore-scale investigation of two-phase flow dynamics during nanofluid flooding in subsurface formations containing non-aqueous phase liquids (NAPLs) such as crude oils. The goal was to gain fundamental understanding of the dominant displacement mechanisms of NAPL at different stages of nanofluid injection in a carbonate rock using x-ray microtomography integrated with a miniature core-flooding system. The nanofluid consisted of surfactant-based microemulsions with in-situ synthesized silica nanoparticles. After establishing its initial wettability state, the carbonate core sample was subjected to various pore volumes (PV) of nanofluid flooding (from 0.5 to 10) to examine the impact on NAPL flow dynamics. We found that most NAPL mobilization occurred within the first PV of injection, removing nearly 50% of NAPL from the rock. The nanofluid invaded into larger pores first due to a sharp decrease in NAPL/brine interfacial tension (from 14 to 0.5 mN/m) and contact angle (from 140 to 88°). With higher amount of nanofluid delivered into the pores through advection, over 90% of NAPL droplets were emulsified and their size decreased from 9 to 3 μm. Subsequent nanofluid injection could further remove NAPL from the smaller pores by altering the thickness of NAPL layers adsorbed on the rock. This dynamic solubilization process reached equilibrium after 5 PV of injection, leading to a reduced layer thickness (from 12 to 0.2 μm), a narrower in-situ contact angle distribution around 81°, and an additional 16% of NAPL removal

Complications and carcinogenic effects of mustard gas - A systematic review and meta-analysis in Iran

Background: Catastrophic effects of mustard gas as a chemical warfare agent have always been a major problem for those exposed to this agent. In this meta-analysis it was tried to evaluate carcinogenesis, ocular, cutaneous and respiratory complications of mustard gas exposure among Iranians who had been exposed to this agent during the Iran-Iraq war. Materials and Methods: In this meta-analysis, the required data were collected using keywords "mustard gas", "sulfur mustard", "cancer", "neoplasm", "respiratory complications", "ocular complications", "lung disease", "chronic complication", "eye", "skin", "cutaneous complication", "carcinogenesis" and their combination with keywords "Iran", "Iranian", "prevalence", "mortality" and their Farsi equivalent terms from the databases of SID, Iranmedex, Magiran, Pubmed, Science Direct, Google Search engine, Gray Literature and Reference of References. To determine the prevalence of each complication and perform meta-analysis, CMA: 2 (Comprehensive Meta-Analysis) software with a randomized model was used. Results: Of the 542 articles found, 7 national articles, consistent with the aims of this study were selected. Metaanalysis of seven papers revealed that cancer risk, especially cancer of the respiratory system was elevated, so that the relative risk (RR) of cancer role of mustard gas was inconsistent from 2/1 to 4 in this survey. Also prevalence of delayed skin disorders due to sulfur mustard was 94.6, pulmonary complications 94.5 and ocular complications 89.9. The incidence of various cancers in victims exposed to mustard gas was 1.7 worldwide where the rate was 2.2 in Iranian victims of the Iraq-Iran war. Conclusions: Based on present study the prevalence of delayed mustard gas related cutaneous, pulmonary and ocular complications is above 90 and risk of carcinogenesis is higher in comparison to worldwide statistics. This may suggest need for long-term and persistent follow-up and rehabilitation procedures es for populations exposed to this agent

PET/CT imaging of spinal inflammation and microcalcification in patients with low back pain: A pilot study on the quantification by artificial intelligence-based segmentation

Background: Current imaging modalities are often incapable of identifying nociceptive sources of low back pain (LBP). We aimed to characterize these by means of positron emission tomography/computed tomography (PET/CT) of the lumbar spine region applying tracers 18F-fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF) targeting inflammation and active microcalcification, respectively. Methods: Using artificial intelligence (AI)-based quantification, we compared PET findings in two sex- and age-matched groups, a case group of seven males and five females, mean age 45 \ub1 14 years, with ongoing LBP and a similar control group of 12 pain-free individuals. PET/CT scans were segmented into three distinct volumes of interest (VOIs): lumbar vertebral bodies, facet joints and intervertebral discs. Maximum, mean and total standardized uptake values (SUVmax, SUVmean and SUVtotal) for FDG and NaF uptake in the 3 VOIs were measured and compared between groups. Holm–Bonferroni correction was applied to adjust for multiple testing. Results: FDG uptake was slightly higher in most locations of the LBP group including higher SUVmean in the intervertebral discs (0.96 \ub1 0.34 vs. 0.69 \ub1 0.15). All NaF uptake values were higher in cases, including higher SUVmax in the intervertebral discs (11.63 \ub1 3.29 vs. 9.45 \ub1 1.32) and facet joints (14.98 \ub1 6.55 vs. 10.60 \ub1 2.97). Conclusion: Observed intergroup differences suggest acute inflammation and microcalcification as possible nociceptive causes of LBP. AI-based quantification of relevant lumbar VOIs in PET/CT scans of LBP patients and controls appears to be feasible. These promising, early findings warrant further investigation and confirmation

Pore-scale Modeling of Viscous Flow and Induced Forces in Dense Sphere Packings

We propose a method for effectively upscaling incompressible viscous flow in large random polydispersed sphere packings: the emphasis of this method is on the determination of the forces applied on the solid particles by the fluid. Pore bodies and their connections are defined locally through a regular Delaunay triangulation of the packings. Viscous flow equations are upscaled at the pore level, and approximated with a finite volume numerical scheme. We compare numerical simulations of the proposed method to detailed finite element (FEM) simulations of the Stokes equations for assemblies of 8 to 200 spheres. A good agreement is found both in terms of forces exerted on the solid particles and effective permeability coefficients