Integrative analysis of ex vivo studies and microarray reveals the novel inhibitor effects of trehalose on the pathogenesis of pterygium.

Pterygium is a frequent eye surface condition that is characterized by a high rate of proliferation, fibrovascular development, cellular migration, corneal infiltration, and angiogenesis. We investigated that ex vivo primary pterygium and conjunctival cell cultures were generated to analyze the effect of trehalose on cellular proliferation. After trehalose treatment, we performed microarray analysis to evaluate changes in the mRNA profile. We analyzed gene ontology (GO) and KEGG pathways to identify hub genes that changed expression levels after treatment and were associated with pterygium development. We selected three genes to verify their expression levels using qRT-PCR. The study also evaluated the impact of trehalose treatment on cell migration through a wound-healing assay. Our results suggested that pterygium cell proliferation was inhibited in a dose-dependent manner by trehalose. 2354 DEG were identified in pterygium and conjunctiva cells treated with trehalose compared to untreated groups. Functional enrichment analysis showed that differentially expressed mRNAs are involved in proliferation, vasculature development, and cell migration. We identified ten hub genes including upregulated (RANBP3L, SLC5A3, RERG, ANKRD1, DHCR7, RAB27B, GPRC5B, MSMO1, ASPN, DRAM1) and downregulated (TNC, PTGS2, GREM2, NPTX1, NR4A1, HMOX1, CXCL12, IL6, MYH2, TXNIP). Microarray analysis and functional investigations suggest that trehalose affects the pathogenesis of pterygium by modifying the expression of genes involved in crucial pathways related to cell function.

Coenzyme Q10 and Vitamin E Regulate the Bioactivity of Human Corneal Fibroblast Cells.

Purpose: Corneal fibroblasts are involved in the wound healing of the cornea with proliferation, migration, and differentiation processes. Coenzyme Q10 (CoQ10) and vitamin E can enhance corneal wound healing when applied after a corneal lesion as an eye drop. Thus, this study was performed to determine the potential efficiency of a CoQ10 ophthalmical solution containing a CoQ10 and vitamin E D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-derived formulation in human corneal fibroblasts (HCFs) in vitro. Methods: Primary HCFs were obtained from cadaveric corneal tissue, and cell viability was determined using MTT assay at 24 and 72 h. Cell migration was evaluated using an in vitro wound healing assay, and mRNA expressions of collagen type I (COL-I), collagen type III (COL-III), lumican, hyaluronan, matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, tissue inhibitors of MMP (TIMP)-1, TIMP-2, interleukin (IL)-1ß, IL-6, IL-8, and IL-10 were assessed using reverse transcription polymerase chain reaction at 24 and 72 h. Results: At various concentrations of CoQ10 ophthalmical solution (CoQ10-os), cell viability and wound healing rates of HCFs increased compared with the control group. The expressions of COL-I, COL-III, lumican, and hyaluronan were increased by CoQ10-os, whereas those of MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2, and TIMP-3 were not affected by CoQ10-os at 24 and 72 h. In treating HCFs with a CoQ10-os medium, IL-1ß, IL-6, and IL-8 decreased, whereas IL-10 was significantly increased in a time- and dose-dependent manner. Conclusions: The findings indicate that CoQ10 and vitamin E-TPGS are potent regulators of the bioactivity of HCFs, thus supporting their potential application as ophthalmical solutions in therapies aimed at the fast regeneration of damaged cornea tissues.

Investigation of the recurrent vitreous hemorrhage risk factors after early 25G vitrectomy in diabetic vitreous hemorrhage.

Vitreous hemorrhage (VH) is one of the main causes of vision loss in diabetic retinopathy (DRP). Early surgery increases the visibility of the retina, allowing early recognition of DRP complications and additional treatments. One of the most important reasons affecting success after surgery is recurrent vitreous hemorrhage (RVH). We aimed to investigate the risk factors for RVH after early 25G vitrectomy in diabetic VH. Eighty eyes of eighty patients who underwent early 25G PPV surgery with a diagnosis of VH due to proliferative diabetic retinopathy (PDR) were included in this retrospective study. Vision acuity changes and intraocular pressure (IOP) changes were compared. The effect of arterial hypertension (HT), coronary artery disease (CAD), preoperative antiglaucomatous usage, and anticoagulant usage on RVH was investigated. A value of P < .05 was accepted as statistically significant. Postoperative RVH was observed in 18 (22.5%) patients. There was no correlation between the age of the patients and the development of postoperative RVH (r = -0.197, P = .08). The rate of HT and the mean HbA1C levels were found to be higher in the patients who developed RVH than in those who did not (P = .04 and < 0.001, respectively). The presence of CAD, preoperative glaucoma disease, and the use of anticoagulants did not have any effect on RVH (P = .229, 0.843, 0.932, respectively). HT and increased HbA1c were found to be risk factors for RVH in VH patients who underwent 25G vitrectomy in the early period in our study.

[Fungal Keratitis Associated with Curvularia lunata: First Case Report from Türkiye]. / Curvularia lunata'ya Bagli Gelisen Fungal Keratit: Türkiye'den Ilk Olgu Raporu.

Fungal keratitis is a medical emergency that is among the most common causes of blindness in developing countries. The type of the agent may vary depending on the geographical conditions under which the patient lives, trauma exposure, the use of contact lenses and profession. Curvularia spp. is a saprophytic genus that rarely causes systemic disease in humans and has 250 species identified to date. They proliferate in soil and plants and spread to the environment with their spores and the formation of blackish and fluffy colonies is its most well-known morphological feature. There may be difficulties in cultivating brown (dematiaceous) fungi. Due to the similarity between the genera, conventional methods remain inadequate for diagnosis. In this report, a case of fungal keratitis associated with C.lunata was presented. Seventy-five years-old female patient admitted to the hospital with the symptoms of stinging pain, blurred vision, and swelling in the right eye. Her symptoms had begun four days ago after her eye was hit by a plant. The patient who had a history of peripheral neuropathy due to diabetes mellitus (DM) was hospitalized with a preliminary diagnosis of keratitis, and in the cultures of the patient's corneal scraping samples, the filamentous, black pigment-forming colonies of the pathogen growing on 5% sheep blood agar and potato dextrose agar showing an aerial hyphal structure, were stained with lactophenol cotton blue and examined under the microscope. The microscopic examination revealed geniculate conidiophores with brown pigmentation. On top of these structures were tetralocular macroconidia, one of which appeared to be larger than the main axis. The fungus was subjected to molecular identification with the prediagnosis of Curvularia/Bipolaris. DNA extraction of the ITS region polymerase chain reaction amplification and Sanger sequencing were performed for molecular identification. Sanger sequencing identified the agent to be Curvularia lunata with a similarity rate of 99.79% (NCBI-GenBank Nucleotide ID: OR365075). In vitro antifungal susceptibility of C.lunata was evaluated by microdilution method. Itraconazole and amphotericin B showed higher activity against C.lunata compared to other antifungals while fluconazole was the least active antifungal. Intrastromal and subconjunctival voriconazole injection was applied to the patient who was unresponsive to empirically initiated oral moxifloxacin and different topical treatments (vancomycin, ceftazidime, flucanozole, ganciclovir, cyclopentolate hydrochloride, hyaluronic acid and trehalose). After injection, right penetrating keratoplasty was applied due to increased thinning of the ulcerated area. No pathogen was detected in cultures taken after keratoplasty. Rare fungi should be considered in cases of keratitis that are difficult to treat. Fungal keratitis caused by brown fungi are clinically similar to each other and effective treatment protocols cannot be implemented without a species identification. Identification of the pathogen will enable genus-specific treatment. This will also help prevent complications that may occur. This article aims to present a case of fungal keratitis associated with C.lunata.

A cross-sectional study investigating the effects of argon laser retinal photocoagulation on lens clarity and corneal endothelial cells.

Background: The mechanism of argon laser retinal photocoagulation (ALRP) treatment is to apply thermal-induced retinal pigment epithelium damage. Light passes through the anterior optical segments of the eye to reach the retina. Lens densitometry is a noninvasive and quantitative measurement providing information about corneal and lens clarity. Objectives: This study aimed to investigate whether laser light affects lens clarity and corneal endothelial cells. Design: This was a prospective, cross-sectional study. Methods: Lens densitometric (LD) analysis and specular microscopy were performed before, after, and 1 month after ALRP treatment, by an expert ophthalmologist, blinded to the medical status of the patients. LD analysis was performed using a Pentacam HR (Oculus, Wetzlar, Germany) and a Specular Microscope CEM-530 (Nidek, Japan) was used for endothelial cell analysis. Results: The evaluation was made on 81 eyes of 41 patients, with a mean age of 54.46 ± 6.7 years. LD, after ALRP, was significantly more than before ALRP (p < 0.001). There was no statistically significant difference in LD, before ALRP, and 1 month after ALRP (p = 0.262). There was a statistically significant increase in LD after ALRP compared to before ALRP, but it decreased after 1 month. There was an increase in the coefficient of variance (CV) after ALRP compared to before ALRP but it was not statistically significant (p = 0.188). There was no statistically significant difference in CV between before ALRP and 1 month after ALRP (p = 1.000). There was no statistically significant difference in the cell density, the hexagonality percentage between before ALRP, after ALRP, and 1 month after ALRP (p = 0.993, and 0.863, respectively). Conclusion: ALRP may affect the lens densitometry temporarily during the procedure. Thermal damage may be the reason for increased lens densitometry.

Imaging features of radiation-induced lung disease and its relationship with clinical and dosimetric factors in breast cancer patients.

Aim: The aim is to extensively evaluate imaging features of radiation induced lung disease in breast cancer patients and to determine the relationship of imaging alterations with dosimetric parameters and patient related characteristics. Materials and Methods: A total of 76 breast cancer patients undergoing radiotherapy (RT) were studied retrospectively by case notes, treatment plans, dosimetric parameters, and chest computed tomography (CT) scans. Time intervals, that chest CT scans were acquired, were grouped as 1-6 months, 7-12 months, 13-18 months and more than 18 months after RT. Chest CTs (one or more for each patient) were assessed for the presence of ground glass opacity, septal thickening, consolidation/patchy pulmonary opacity/alveolar infiltrates, subpleural air cyst, air bronchogram, parenchymal bands, traction bronchiectasis, pleural/subpleural thickening and pulmonary volume loss. These alterations were scored by applying a system devised by Nishioka et al. Nishioka scores were analyzed for the relationship with clinical and dosimetric factors. Statistical Analysis Used: IBM SPSS Statistics for Windows, version 22.0 (IBM Corp., Armonk, N.Y., USA) was used to analyze data. Results: Median follow-up time was 49 months. Advanced age and aromatase inhibitor intake were correlated with higher Nishioka scores for 1-6 months' period. However, both were found nonsignificant in multivariate analysis. Nishioka scores of CT scans acquired more than 12 months after RT were positively correlated with mean lung dose, V5, V20, V30, and V40. Receiver operating characteristic analysis revealed that V5 for ipsilateral lung was the most robust dosimetric parameter predicting chronic lung injury. V5 >41% indicates the development of radiological lung changes. Conclusions: Keeping V5 ≤41% for ipsilateral lung could provide avoiding chronic lung sequelae.

The effect of the ATM inhibitor AZD0156 on the radiosensitivity of human breast cancer and lung fibroblast cells.

Aims: To evaluate the effect of the combination of irradiation and AZD0156 on apoptosis, cell cycle progression, and clonogenic survival in human breast cancer and fibroblast cells. Methods and Material: Estrogen receptor-positive breast cancer cell line MCF-7 and healthy lung fibroblast cell line WI-38 were obtained. Following employing proliferation analysis, cytotoxicity analysis was done to calculate the IC50 values of AZD0156 in MCF-7 and WI-38 cell lines. Following the application of AZD0156 and irradiation, flow cytometry analysis was performed for evaluating cell cycle distribution and the extent of apoptosis. Plating efficiency and surviving fraction were calculated for the clonogenic assay. Statistical Analysis Used: SPSS Statistics for Windows, Version 17.0. (SPSS Inc. Chicago) and GraphPad Prism Version 6.0 for Windows (GraphPad Software, San Diego, California USA) softwares were used to analyze data. Results: AZD0156 and irradiation dose of 2-10 Gy had no effect on apoptosis on MCF-7 cells. The combination treatment of AZD0156 and 2 Gy, 4 Gy, 6 Gy, 8 Gy, and 10 Gy irradiation induced G0/G1 phase arrest by 1.79, 1.79, 1.50, 1.25, and 1.52-fold compared to the control group, respectively on MCF-7 cell lines. Combination treatment of AZD0156 and each different irradiation dose affected clonogenic survival owing to increased radiosensitivity (p: 0.02). AZD0156 and irradiation dose of 2 Gy, 4 Gy, 6 Gy, 8 Gy, and 10 Gy decreased the cell viability rate of WI-38 cells by 1.05, 1.18, 1.22, 1.04, and 1.05-fold compared to the control group, respectively. No efficacy was detected on cell cycle analysis, and clonogenic survival was not significantly decreased in WI-38 cells. Conclusion: The combination use of irradiation and AZD0156 has improved efficacy of tumor cell-specific cell cycle arrest and decreasing clonogenic survival.

Preoperative radiotherapy with concomitant chemotherapy in extremity soft tissue sarcomas: long-term results of a single center.

PURPOSE: To assess oncological outcomes of patients receiving neoadjuvant radiochemotherapy (RCT) for soft tissue sarcoma (STS) of the extremities. METHODS: Patients who were treated with preoperative radiotherapy and concomitant chemotherapy-3 cycles of mitomycin/doxorubicin/cisplatin (MAP) or 2-4 cycles of doxorubicin/cisplatin (AP)-followed by surgery were analyzed retrospectively. Survival rates were estimated, and prognostic factors were identified. RESULTS: Between 1994 and 2017, a total of 108 patients were included. Median ages were 43 years and 51 years for patients receiving MAP and AP, respectively. The 5­year local relapse-free survival (LRFS), disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) were 94.1, 63.6, 75.3, and 71.9%, respectively. In the multivariate analysis, significant predictors were identified as follows: de novo or R1/R2 resected tumor on admission before RCT (p = 0.017; hazard ratio [HR] 0.112, 95% confidence interval [CI] 0.019-0.675) and R0 resection after RCT (p = 0.010; HR 0.121, 95% CI 0.024-0.598) for LRFS; female gender (p = 0.042; HR 0.569, 95% CI 0.330-0.979) and liposarcoma histology (p = 0.014; HR 0.436, 95% CI 0.224-0.845) for DFS; liposarcoma histology (p = 0.003; HR 0.114, 95% CI 0.027-0.478) and AP regimen (p = 0.017; HR 0.371, 95% CI 0.165-0.836) for DSS; age ≤ 45 years (p = 0.043; HR 0.537, 95% CI 0.294-0.980) and liposarcoma histology (p = 0.006; HR 0.318, 95% CI 0.141-0.716) for OS, respectively. CONCLUSION: An increased risk for local failure seems to exist for patients with relapsed tumor on admission and having positive surgical margins after neoadjuvant RCT. Intensity of chemotherapy influenced DSS but not OS, which could be due to younger patients receiving MAP.

Molecular genetic etiology by whole exome sequence analysis in cases with familial type 1 diabetes mellitus without HLA haplotype predisposition or incomplete predisposition.

OBJECTIVES: Familial transmission is observed in approximately 10% of cases with type 1 diabetes mellitus (T1DM). The most important gene determining susceptibility is the human leukocyte antigen complex (HLA) located on chromosome 6. More than 50 susceptible loci are associated with T1DM susceptibility have been identified in genes other than HLA. In this study, it was aimed to investigate the molecular genetic etiology by whole-exome sequence (WES) analysis in cases with familial T1DM with no or weakly detected HLA tissue type susceptibility. We aimed to identify new genes responsible for the development of type 1 diabetes and to reveal new genes that have not been shown in the literature before. METHODS: Cases with at least one T1DM diagnosis in first-degree relatives were included in the study. In the first step, HLA DQ2 and DQ8 loci, which are known to be associated with T1DM susceptibility, were investigated by. In the second step, the presence of variants that could explain the situation was investigated by WES analysis in patients who were negative for both HLA DQ2 and HLA DQ8 haplotypes, HLA DQ2 negative, HLA DQ8 positive, and HLA DQ2 positive and HLA DQ8 negative patients. RESULTS: The mean age and duration of diabetes of the 30 cases (Girl/Male: 17/13) were 14.9 ± 6 and 7.56 ± 3.84 years, respectively. There was consanguineous marriage in 5 (16%) of the families. As a result of filtering all exome sequence analysis data of two cases with DQ2 (DQB1*02) (-) and DQ8 (DQB1*03:02) (-), seven cases with DQ2 (DQB1*02) (+) and DQ8 (DQB1*03:02) (-), and one case with DQ2 (DQB1*02) (-) and DQ8 (DQB1*03:02) (+), seven different variants in seven different genes were detected in five cases. The pathogenicity of the detected variants were determined according to the "American College of Medical Genetics and Genomics (ACMG)" criteria. These seven variants detected were evaluated as high-score VUS (Variants of unknown/uncertain significance). In the segregation study conducted for the mutation in the POLG gene detected in case 5, this variant was detected in the mother of the case and his brother with T1DM. Segregation studies are ongoing for variants detected in other affected individuals in the family. CONCLUSIONS: In conclusion, in this study, seven different variants in seven different genes were detected in five patients by WES analysis in familial T1DM patients with no or weak HLA tissue type susceptibility. These seven variants detected were evaluated as high-score VUS. POLG might be a novel candidate gene responsible for susceptibility to T1DM. Non-HLA genes directly responsible for the development of T1DM were not detected in any of the cases.

Investigating the Blink Reflex Abnormality in Dry Eye Patients.

Introduction Dry eye is an ocular surface disorder caused by increased evaporation, decreased tear production, or mixed form. Tears are secreted by the lacrimal gland after lacrimal nerve stimulation connected to the facial nerve. In nerve damage, tear secretion decreases, and dry eye develops. Our aim is to investigate the presence of pathology in the facial trigeminal nerve and neuronal pathways that provide reflex connections between these nerves by measuring the blink reflex in patients with dry eyes. Methods Schirmer test and tear breakup time were performed. Tear breakup time measurement was repeated three times, and the average of three was accepted. Tear breakup time <10 seconds and Schirmer test <10 mm without local anesthesia were accepted as dry eye. Patients having traumatic corneal pathology, ectatic corneal disease, inflammatory and microbial keratitis, previous ocular surgery, glaucoma, diabetic retinopathy, and chronic neurological diseases were excluded. The control group was randomly formed from 42 eyes of 21 healthy volunteers. Blink reflex was measured in both groups, and the R1 and R2 responses of the two groups were compared. Written consent was obtained from the patient (or legal guardian) so that her medical data could be published. Results There was no significant difference between the two groups in R1 and R2 responses in both eyes. There was no significant difference in terms of gender between the two groups (p=0.100). The mean age in the patient group was significantly higher than in the control group (p<0.000). The mean Schirmer test in the patient group was 8.6±1.1 mm in the right eye and 8.97±1.0 mm in the left eye. Conclusion There was no central pathology observed in terms of reflex blinking in dry eye disease. However, in future studies, brainstem fiesta sequence magnetic resonance imaging (MRI) can be planned to evaluate central pathologies in more detail.

Sheared two-dimensional radiofrequency excitation for off-resonance robustness and fat suppression in reduced field-of-view imaging.

PURPOSE: Two-dimensional (2D) echo-planar radiofrequency (RF) pulses are widely used for reduced field-of-view (FOV) imaging in applications such as diffusion-weighted imaging. However, long pulse durations render the 2D RF pulses sensitive to off-resonance effects, causing local signal losses in reduced-FOV images. This work aims to achieve off-resonance robustness for 2D RF pulses via a sheared trajectory design. THEORY AND METHODS: A sheared 2D RF pulse design is proposed to reduce pulse durations while covering identical excitation k-space extent as a standard 2D RF pulse. For a given shear angle, the number of sheared trajectory lines is minimized to obtain the shortest pulse duration, such that the excitation replicas are repositioned outside the slice stack to guarantee unlimited slice coverage. A target fat/water signal ratio of 5% is chosen to achieve robust fat suppression. RESULTS: Simulations, imaging experiments on a custom head and neck phantom, and in vivo imaging experiments in the spinal cord at 3 T demonstrate that the sheared 2D RF design provides significant improvement in image quality while preserving profile sharpnesses. In regions with high off-resonance effects, the sheared 2D RF pulse improves the signal by more than 50% when compared to the standard 2D RF pulse. CONCLUSION: The proposed sheared 2D RF design successfully reduces pulse durations, exhibiting significantly improved through-plane off-resonance robustness, while providing unlimited slice coverage and high fidelity fat suppression. This method will be especially beneficial in regions suffering from a variety of off-resonance effects, such as spinal cord and breast.

Effect of individualized cognitive and postural task difficulty levels on postural control during dual task condition.

BACKGROUND: Previous dual task studies suggested that the difficulty of the concurrent cognitive and motor tasks may not be challenging to the same degree for each person. This study approaches this problem by setting individualized difficulty levels for tasks to examine the dual task interference. RESEARCH QUESTION: Do the features of postural sway depend on increased individualized difficulty levels of concurrent cognitive and postural activities? METHODS: 20 young healthy participants (10 male, 10 female) took part in the study. Before the experiments, cognitive task difficulty (No-, Medium-, High) has been set individually. Subjects performed postural tasks (quiet stance, voluntary sway) concurrently with or without a cognitive task which based on simple arithmetic calculations. Postural sway features were examined. RESULTS: Postural sway features were affected by individualized difficulty level of concurrent cognitive and postural activities. In voluntary sway, as a more challenging postural task, higher reductions were observed for such sway features as COP velocity and range in AP direction. SIGNIFICANCE: This study signaled task-specific changes in postural sway features. When the difficulty levels were set individually, the effect of motor and cognitive dual task was more apparent when the balance requirement of the primary motor task increased.

Propolis Extract Regulates microRNA Expression in Glioblastoma and Brain Cancer Stem Cells.

BACKGROUND: Grade IV gliomas are classified as glioblastoma (GBM), which is the most malignant brain cancer type. Various genetic and epigenetic mechanisms play a role in the initiation and progression of GBM. MicroRNAs (miRNAs) are small, non-coding RNA molecules that belong to the main epigenetic regulatory RNA class that plays different roles in either physiological or pathological conditions, including GBM pathogenesis regulating expression levels of the target genes. Brain Cancer Stem Cells (BCSCs) are responsible for poor prognosis, including therapy resistance and relapse. Epigenetic regulation mediated by miRNAs is also a critical component of BCSC selfrenewal and differentiation properties. Propolis is a resinous substance collected by honey bees from various plant sources. The flavonoid content of propolis varies depending on the collection region and the extraction method. Although there are studies that include the effects of different originated-propolis on the miRNA expression levels of the glioblastoma cells, the impact on the BCSCs has not been studied yet. OBJECTIVE: This study aims to evaluate the effects of propolis obtained from Aydin, a city in western Turkey, on miRNA expression levels of BCSCs and GBM cells. METHODS: Aydin propolis was dissolved in 60% ethanol, and after evaporation, distilled water was added to prepare the propolis stock solution. The flavonoids content of the Aydin propolis was determined by MS Q-TOF analysis. Commercially obtained U87MG and BCSCs were used as in-vitro brain cancer models. Cytotoxic and apoptotic effects of Aydin propolis were determined via WST-1 assay and Annexin V test, respectively. The miRNA expression profile was investigated using the real-time qRT-PCR method. The fold changes were calculated by the2-ΔΔCt method. The miRNA-mRNA-pathway interactions, including significantly altered miRNAs, were determined using different bioinformatics tools and databases. RESULTS: Quercetin 3-methyl ether was the main component of the Aydin propolis. Aydin propolis did not show significant cytotoxic and apoptotic effects on both GBM and BCSCs up to 2mg/ml concentration. Aydin propolis treatment decreased the expression of nine miRNAs in the U87MG and five miRNAs in the BCSCs. Moreover, ten miRNAs have upregulated from 2.22 to 10.56 folds in propolis treated GBM cells compared to the control group significantly (p<0.05). In the study, the potential roles of two new miRNAs, whose regulations in glioma were not previously defined, were identified. One of them was miR-30d-5p, a novel potential oncomiR in GBM, which was 2.46 folds downregulated in Aydin propolis treated GBM cells. The other one is miR-335-5p, which is a potential tumor suppressor miR in GBM, that was 5.66 folds upregulated in Aydin propolis treated GBM cells. FOXO pathway, its upstream and downstream regulators, and critically neuronal developmental regulators, NOTCH and WNT pathways, were determined as the most deregulated pathways in Aydin propolis treated cells. CONCLUSION: The determination of the anti-cancer effect of Aydin propolis on the miRNA expression of GBM, especially on cancer stem cells, may contribute to the elucidation of brain cancer genetics by supporting further analyses.

Constrained Ellipse Fitting for Efficient Parameter Mapping With Phase-Cycled bSSFP MRI.

Balanced steady-state free precession (bSSFP) imaging enables high scan efficiency in MRI, but differs from conventional sequences in terms of elevated sensitivity to main field inhomogeneity and nonstandard [Formula: see text]-weighted tissue contrast. To address these limitations, multiple bSSFP images of the same anatomy are commonly acquired with a set of different RF phase-cycling increments. Joint processing of phase-cycled acquisitions serves to mitigate sensitivity to field inhomogeneity. Recently phase-cycled bSSFP acquisitions were also leveraged to estimate relaxation parameters based on explicit signal models. While effective, these model-based methods often involve a large number of acquisitions (N ≈ 10-16), degrading scan efficiency. Here, we propose a new constrained ellipse fitting method (CELF) for parameter estimation with improved efficiency and accuracy in phase-cycled bSSFP MRI. CELF is based on the elliptical signal model framework for complex bSSFP signals; and it introduces geometrical constraints on ellipse properties to improve estimation efficiency, and dictionary-based identification to improve estimation accuracy. CELF generates maps of [Formula: see text], [Formula: see text], off-resonance and on-resonant bSSFP signal by employing a separate [Formula: see text] map to mitigate sensitivity to flip angle variations. Our results indicate that CELF can produce accurate off-resonance and banding-free bSSFP maps with as few as N = 4 acquisitions, while estimation accuracy for relaxation parameters is notably limited by biases from microstructural sensitivity of bSSFP imaging.

Analysis and mitigation of noise in simultaneous transmission and reception in MRI.

PURPOSE: In simultaneous transmission and reception (STAR) MRI, along with the coupling of the excitation pulse to the received signal, noise, and undesired distortions (spurs) coming from the transmit chain also leak into the acquired signal and degrade image quality. Here, properties of this coupled noise and its relationship with the transmit amplifier gain, transmit chain noise density, isolation performance, and imaging bandwidth are analyzed. It is demonstrated that by utilizing a recently proposed STAR technique, the transmit noise can be reduced. The importance of achieving high isolation and careful selection of the corresponding parameters are demonstrated. THEORY AND METHODS: A cancellation algorithm, together with a vector modulator, is used for transmit-receive isolation. The scanner is modeled as a pipeline of blocks to demonstrate the noise contribution from each block. With higher isolation, coupled transmit noise can be reduced to the point that the dominant noise source becomes acquisition noise, as in the case for pulsed MRI. Amplifiers with different gain and noise properties are used in the experiments to verify the derived noise-transmit parameter relation. RESULTS: With the proposed technique, more than 80 dB isolation in the analog domain is achieved. The leakage noise and the spurs coupled from the transmit chain, are reduced. It is shown that the transmit gain plays the most critical role in determining sufficient isolation, whereas the amplifier noise figure does not contribute as much. CONCLUSION: The transmit noise and the spurs in STAR imaging are analyzed and mitigated by using a vector modulator.

The Evaluation of the Relation Between Iris and Choroidal Thickness.

Purpose: The study aimed to investigate the relationship between iris thickness (IT) and choroidal thickness (CT) in healthy subjects.Materials and Methods: Forty-five healthy participants (24 women, 21 men) aged 18-62 years were included in the study. The iris thickness was measured by anterior segment optical coherence tomography (AS-OCT). The iris thickness was measured at 750 µm (IT750T) and 2000 µm (IT2000T) from the temporal scleral spur. The iris thickness was measured at 750 µm (IT750N) and 2000 µm (IT2000N) from the nasal scleral spur. Choroidal thickness was measured by optical coherence tomography. Choroid thickness was measured at 750 µm (CT750N, CT750T) and 2000 µm (CT2000N, CT2000T) from the center of the fovea on both the nasal and temporal sides.Results: There were significant correlations between CT750T and IT750T, IT750N, IT2000N (r = 0.409, p=0.005; r = 0.396, p=0.007; r = 0.329, p=0.02, respectively). There were significant correlations between CT2000T and IT750T, IT750N, IT2000N (r = 0.383, p=0.009; r = 0.478, p=0.001; r = 0.331, p0=0.02, respectively).Conclusions: There was a significant correlation between CT and IT thicknesses at different points.

Risk and protective factors for mental disorders with onset in childhood/adolescence: An umbrella review of published meta-analyses of observational longitudinal studies.

The patho-etiology of mental disorders with onset in childhood or adolescence remains largely unknown. We conducted an umbrella review of meta-analyses (MAs) on environmental factors associated with mental disorders with onset in childhood/adolescence. We searched Pubmed-MEDLINE/EMBASE/PsycInfo databases, last search April 29th, 2020. Quality of MAs was measured with AMSTAR-2. Out of 6851 initial references, ten articles met inclusion criteria, providing 23 associations between 12 potential environmental factors and nine disorders (cases: 8884; N = 3,660,670). While almost half of the associations were nominally significant, none of them met criteria from either convincing or highly suggestive evidence. A single association was supported by suggestive evidence (maternal exposure to lithium or antipsychotics with neuromotor deficits), but it was affected by confounding by indication. Ten more associations had weak evidence, and 12 associations were not statistically significant. Quality of meta-analyses was rated as high in two, moderate in one, low in four, critically low in two, and not pertinent in one (individual participant data). Methodologically-sound research is needed in this field.

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences.

BACKGROUND: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies in patients with locally advanced or metastatic platinum-resistant urothelial carcinoma. OBJECTIVE: To compare the real-life experience and data of clinical trials on ATZ treatment in metastatic urothelial carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy from an expanded access program were retrospectively studied. Data of patients were obtained from their files and hospital records. Safety was evaluated for patients treated with at least one cycle of ATZ. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was objective response rate (ORR). The secondary endpoints are overall survival (OS), progression-free survival (PFS), duration of response, and safety profile of patients. Kaplan-Meier methods were used to calculate median follow-up and estimate PFS and OS. RESULTS AND LIMITATIONS: Data of 115 enrolled patients were analyzed. Most of the patients (92.3%, n = 106) had received chemotherapy regimen only once prior to ATZ. The median follow-up duration was 23.5 mo. The complete response rate, partial response rate, and ORR were 8.7% (n = 10), 20.0% (n = 23), and 28.7% (n = 33), respectively. The median duration of response was 20.4 mo (95% confidence interval [CI], 6.47-28.8). Of the 33 patients who responded to treatment, 60% (n = 20) had an ongoing response at the time of the analysis. PFS and OS with ATZ were 3.8 mo (95% CI, 2.25-5.49) and 9.8 mo (95% CI, 6.7-12.9), respectively. All-cause and any-grade adverse events were observed in 113 (98%) patients. Of the patients, 64% experienced a treatment-related adverse event of any grade and 24 (21.2%) had a grade 3-4 treatment-related adverse event. Limitations of the study included its retrospective design, and determination of treatment response based on clinical notes and local radiographic studies. CONCLUSIONS: In these real-life data, ATZ was effective and well tolerated in patients with metastatic urothelial carcinoma who have progressed with platinum-based first-line chemotherapy. ATZ is an effective and tolerable treatment for patients with locally advanced or metastatic platinum-resistant urothelial carcinoma in our study, similar to previously reported trials. PATIENT SUMMARY: Atezolizumab is effective and well-tolerated in patients with metastatic urothelial cancer who progressed with first-line chemotherapy, consistent with the outcomes of the previous clinical trials in this setting.

Tear Film Functions and Dry Eye Symptoms in Young Patients with Pterygium.

OBJECTIVES: This study was performed to evaluate the Schirmer II test (ST2) results, tear breakup time (TBUT) findings, and Ocular Surface Disease Index (OSDI) scores of pterygium patients under 30 years of age, and to compare the results with pterygium patients aged 30 years and older and healthy controls. METHODS: Eighty-four eyes of 60 patients who had primary pterygium and were younger than 30 years of age (Group 1), 79 eyes of 53 patients who had primary pterygium and were 30 years of age and older (Group 2), and 64 eyes of 64 healthy controls (Group 3) were included in the study. The results of ST2 and TBUT tests and the OSDI questionnaire scores were recorded and compared. RESULTS: Group 1 had lower TBUT values compared to Group 2 and the control group (p= 0.03 and p<0.001, respectively). Group 1 had lower ST2 values than the control group (p<0.001). There was no significant difference in the ST2 results between Group 1 and Group 2 (p=0.08). Group 1 had higher OSDI scores than the control group (p=0.003). There was no significant difference in the OSDI scores between Group 1 and Group 2 (p=0.7). CONCLUSION: The results indicated that young patients with pterygium had lower ST2 results, lower TBUT values, and higher OSDI scores compared to the control group, and lower TBUT values compared to older patients with pterygium. Tear film abnormality may be a factor in the pterygium pathogenesis, especially in young patients, and may increase the vulnerability of the ocular surface of young people to environmental factors, leading to pterygium formation.