The role of Muller cell glucocorticoid signaling in diabetic retinopathy.

Diabetic retinopathy (DR) is a sight-threatening complication associated with the highly prevalent diabetes disorder. Both the microvascular damage and neurodegeneration detected in the retina caused by chronic hyperglycemia have brought special attention to Muller cells, the major macroglia of the retina that are responsible for retinal homeostasis. Given the role of glucocorticoid signaling in anti-inflammatory responses and the almost exclusive expression of glucocorticoid receptors (GRs) in retinal Muller cells, administration of corticosteroid agonists as a potential treatment option has been widely studied. Although these approaches have been moderately efficacious in treating or de-escalating DR pathomechanisms, there are various side effects and gaps of knowledge with regard to introducing exogenous glucocorticoids to the diseased retina. In this paper, we provide a review of the literature concerning the available evidence for the role of Muller cell glucocorticoid signaling in DR and we discuss previously investigated approaches in modulating this system as possible treatment options. Furthermore, we propose a novel alternative to the available choices of treatment by using gene therapy as a tool to regulate the expression of GR in retinal Muller cells. Upregulating GR expression allows for induced glucocorticoid signaling with more enduring effects compared to injection of agonists. Hence, repetitive injections would no longer be required. Lastly, side effects of glucocorticoid therapy such as glucocorticoid resistance of GR following chronic exposure to excess ligands or agonists can be avoided

Effect of tranexamic acid on early postvitrectomy diabetic haemorrhage; a randomised clinical trial

Aims: To evaluate the effect of tranexamic acid on early postvitrectomy haemorrhage in diabetic patients. Methods: In a clinical trial, 62 diabetic patients scheduled for vitrectomy were randomly assigned to two groups. The treatment group (32 eyes) received two doses of tranexamic acid (10 mg/kg) shortly before and after the operation intravenously, continued orally for 4 days (20 mg/kg/8 hours). The control group (30 eyes) received no medication. Both media clarity and visual acuity were compared during 4 weeks. Results: Four weeks after surgery visual acuity was low (⩽1 metre counting fingers) in 21.4%, moderate (>1 metre counting fingers but<20/200) in 14.3%, and good (⩾20/200) in 64.3% of the treated group. Corresponding figures in the control group were 26.1%, 26.1%, and 47.8%, respectively. These differences were of no statistical significance. The ratio of mild to severe vitreous haemorrhage during the first 4 days and after 4 weeks was 79% to 21% and 82% to 18% in the treatment group and 76.7% to 23.3% and 78.3% to 21.7% in the control group respectively, which showed no statistically significant difference. Conclusion: Tranexamic acid, with the method of administration in this study, had no effect on reducing early postvitrectomy haemorrhage in diabetic patients

Correlation of serum ceruloplasmin with preeclampsia

&quot;nBackground: Preeclampsia is a disorder of pregnancy with increased maternal and perinatal morbidity and mortality. An imbalance between free radical induced lipid peroxidation and antioxidant system has been suggested as possible pathogenesis of preeclapsia. It has been shown correlation of some serum antioxidant agents (for example ceruloplasmin) with preeclampsia and its severity. The purpose of this study was to evaluate of this correlation. &quot;nMethods: In a analytic case-control study, in clinic and delivery unit of Mirza Koochak Khan university hospital, Tehran, we evaluated 90 pregnant women of 19-38 years old with gestational age higher than 20 weeks in two groups, case (preeclampsia) and control (healty mother). Case group was devided into two groups; mild preeclampsia (n=30) and severe preeclampsia (n=30). Patients with preeclampsia (n=60) had either early (n=41) or late preeclampsia (n=19). Control group included 30 normotensive pregnant women. Serum Ceruroplasmin level was measured. Then relationship between this factor and preeclampsia was studied. &quot;nResults: The mean level of serum ceruloplasmin in women with severe preeclampsia (390.83mg/dl) and mild preeclampsia (319.43mg/dl) was higher than control group (212.7mg/dl). Likewise it was significantly higher in severe preeclampsia than mild (P&amp;lt;0.001) and higher in early (373.28mg/dl) than late preeclampsi (298.34mg/dl) (P&amp;lt;0.01). &quot;nConclusions: Our data suggest that serum ceruroplasmin level may predict preeclampsia occurrance and its severity. Likewise antioxidant theryapy before the onset of preeclampsia in an attempt to decrease its frequency should be considered

Enhanced expression of Cyclin D1 and C-myc, a prognostic factor and possible mechanism for recurrence of papillary thyroid carcinoma

A direct association has been shown between Cyclin D1 and C-myc gene expressions and the proliferation of human thyroid tumor cells. Our previous study showed that increased β catenin led to a reduction in disease-free probability in patients with papillary thyroid cancer. This study was designed to investigate Cyclin D1 and C-myc genes as targets for β catenin function in PTC and to determine the association between genes expression and staging, recurrence, metastasis, and disease-free survival of PTC. This study was conducted via a thorough investigation of available data from medical records as well as paraffin blocks of 77 out of 400 patients over a 10-year period. Cyclin D1 and C-myc gene expression levels were measured using real-time polymerase chain reaction (RT-PCR) and the Kaplan-Meier method was used to evaluate disease-free survival. Higher levels of Cyclin D1 and C-myc gene expressions were observed in patients with recurrence by 8.5 (P = 0.004) and 19.5 (p = 0.0001) folds, respectively. A significant positive correlation was found between Cyclin D1 expression and the cumulative dose of radioactive iodine received by patients (r = �0.2, p value = 0.03). The ten-year survival rate in the patients included in this study was 98.25 while disease-free survival was 48.1. Higher Cyclin D1 and C-myc gene expression levels were observed in patients with recurrence/distant metastasis. Inversely, lower expression of Cyclin D1 and C-myc genes were associated with better survival of patients (SD, 0.142-0.052) (Mantel-Cox test, P = 0.002). The enhancement of Cyclin D1 and C-myc gene expression may be a potential mechanism for recurrence and aggressiveness of PTC. © 2020, The Author(s)

Predicting response to repetitive transcranial magnetic stimulation in patients with schizophrenia using structural magnetic resonance imaging: a multisite machine learning analysis

Background: The variability of responses to plasticity-inducing repetitive transcranial magnetic stimulation (rTMS) challenges its successful application in psychiatric care. No objective means currently exists to individually predict the patients' response to rTMS. Methods: We used machine learning to develop and validate such tools using the pre-treatment structural Magnetic Resonance Images (sMRI) of 92 patients with schizophrenia enrolled in the multisite RESIS trial (http://clinicaltrials.gov, NCT00783120): patients were randomized to either active (N = 45) or sham (N = 47) 10-Hz rTMS applied to the left dorsolateral prefrontal cortex 5 days per week for 21 days. The prediction target was nonresponse vs response defined by a ≥20% pre-post Positive and Negative Syndrome Scale (PANSS) negative score reduction. Results: Our models predicted this endpoint with a cross-validated balanced accuracy (BAC) of 85% (nonresponse/response: 79%/90%) in patients receiving active rTMS, but only with 51% (48%/55%) in the sham-treated sample. Leave-site-out cross-validation demonstrated cross-site generalizability of the active rTMS predictor despite smaller training samples (BAC: 71%). The predictive pre-treatment pattern involved gray matter density reductions in prefrontal, insular, medio-temporal, and cerebellar cortices, and increments in parietal and thalamic structures. The low BAC of 58% produced by the active rTMS predictor in sham-treated patients, as well as its poor performance in predicting positive symptom courses supported the therapeutic specificity of this brain pattern. Conclusions: Individual responses to active rTMS in patients with predominant negative schizophrenia may be accurately predicted using structural neuromarkers. Further multisite studies are needed to externally validate the proposed treatment stratifier and develop more personalized and biologically informed rTMS interventions