Retinal ischemia, one of the most common cause of visual loss, is associated with blood flow inadequacy and subsequent tissue injury. In this setting, some treatments that can counteract glutamate increase, arouse interest in ischemic pathogenesis. Ketamine, a potent N-methyl-d-aspartate (NMDA) receptor antagonist, provides a neuroprotective pathway via decreasing the excitotoxicity triggered by excess glutamatergic. Thus, the goal of this study was to evaluate the safety of intravitreal use of ketamine and their potential protective effects on retinal cells in retinal ischemia/reperfusion model. Initially, ketamine toxicity was evaluated by cytotoxicity assay and Hen's egg chorioallantoic membrane (HET-CAM) method. Afterward, some ketamine concentrations were tested in rat's eyes to verify the safety of the intravitreal use. To investigate the neuroprotective effect on retinal, a single intravitreal injection of ketamine in concentrations of 0.059 mmol.L-1 and 0.118 mmol.L-1 was performed one day before the ntravitreal ketamine showed a number of retinal cells significantly higher than the vehicle group. In TUNEL assay a reduction on TUNEL-positive cells was observed in all the layers for both concentrations which allow to affirm that ketamine contributes to reducing cell death in the retina. Transmission electron microscopy (TEM) reaffirms this finding. Ketamine intravitreal pretreatment showed reduced ultrastructural changes. Our findings demonstrate that ketamine is safe for intravitreal use in doses up to 0.118 mmol.L-1. They seem to be particularly efficient to protect the retina from ischemic injury.Tramadol, a weak agonist of mu-opioid receptors, causes seizure via several mechanisms. Preconditioning has been purposed to reduce the epileptic seizures in animal models of epilepsy. The preconditioning effect of tramadol on seizure is not studied yet. This study was designed to evaluate the preconditioning effect of ultra-low dose of tramadol on the seizures induced by tramadol at high dose. Furthermore, regarding the critical role of glutamate signaling in the pathogenesis of epilepsy, the effect of preconditioning on some glutamate signaling elements was also examined. Male Wistar rats received tramadol (2 mg/kg, i.p) or normal saline (1 mL/kg, i.p) in preconditioning and control groups, respectively. After 4 days, the challenging tramadol dose (150 mg/kg) was injected to all rats. Epileptic behaviors were recorded during 50 min. The expression of Norbin (as a regulator of metabotropic glutamate receptor 5), Calponin3 (as a regulator of excitatory synaptic markers), NR1 (NMDA receptor subunit 1) and GluR1 (AMPA receptor subunit 1) was measured in hippocampus, prefrontal cortex (PFC) and amygdala. Preconditioning decreased the number and duration of tremors and tonic-clonic seizures. Norbin, Calponin3, NR1 and GluR1 expression were decreased in hippocampus, and preconditioning had no effect on them. In contrast, it increased Norbin expression in PFC and amygdala, and attenuated NR1 and GluR1 upregulation following tramadol at high dose. These findings indicated that preconditioning by ultra-low dose of tramadol protected the animals against seizures following high dose of tramadol mediated, at least in part, by Norbin up regulation, and NR1 and GluR1 down regulation. The railway industry in Indonesia has grown substantially in the past five years, with greater network and tracks length that will double in 2030. There has been a growing concern, however, that fatigue among front-line personnel have not been addressed satisfactorily. This study aimed at evaluating the degree of fatigue among passenger train drivers and suggested practical recommendations to the Indonesian Railway Company. A total of 32 train drivers (driving for about 4h during the morning or afternoon shifts) agreed to participate in the study. Subjective and objective measures of fatigue (and sleepiness) were obtained prior to, during, and immediately following the end of a duty. Fatigue and driving performance were also determined based on (off-line) analysis of continuous video recordings of the drivers performing the duty. Fatigue generally increased as a function of time and, for some, 2h of driving was sufficient in inducing substantial level of fatigue increase. GYY4137 order Unlike the morning shift, the ain this study that the company pay a much closer attention to the work-sleep schedules, and to improve sleep quality by redesigning better sleeping arrangements.Chronotype refers to individual differences in the timing of circadian sleep-wake cycles and subjective alertness throughout the day. It is a potential factor influencing people's driving behaviour, but no research has explored the mechanisms underlying this topic. The current study aimed to explore the relationship between morningness-eveningness preferences and driving behaviour and the mediating effect of visual search between them. Thirty-eight drivers were selected to participate in this study based on their chronotype. They were divided into morning-type and evening-type groups by their score on the reduced Morningness-Eveningness Questionnaire (rMEQ). Both groups completed a visual search task and a simulated driving task in a morning session and an evening session. The results showed that morningness-eveningness preferences had synchronous effects on basic driving performance; specifically, morning-type drivers showed better driving behaviour in the morning than in the evening, and evening-type drivers showed the opposite trend. Furthermore, visual search abilities showed a mediating effect between morningness-eveningness preference and driving performance. The mechanisms underlying these results are discussed. Related results and data could aid with schedule arrangements for professional drivers.TK1646 is a highly thermostable single strand specific 3'-5' exonuclease. Exonucleases play important role in maintaining the genome integrity at elevated temperatures. Therefore, it is important to examine the factors contributing to thermostability of these exonucleases. In this study we report on production, purification and characterization of S187G and Y50H mutants of TK1646, focusing on the factors leading to thermostability of TK1646. Characterization of the recombinant proteins indicated that these substitutions did not drastically affect the catalysis of single stranded DNA. However, both of these substitutions reduced the thermostability of the recombinant proteins. Half-lives of Y50H and S187G mutants were 95 and 155 min, respectively, at 100 °C in comparison to 180 min of the wild type. Bioinformatics analysis indicated an increase in solvent accessibility of the mutated residues and disruption of hydrogens bonds. Molecular modelling and superimposition of the 3D structures of the mutants and the wild type demonstrated that one of the active site residues, Glu145, was shifted away from the metal ion in both the mutants which may be responsible for the decrease in catalytic activity.