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??Objective??To study the influence of the inlay on the stress of the remained tooth tissue??three-dimensional finite element is used to analyse stress distributions of the tooth endured different MOD inlay restore at different remaining buccal wall thickness. Methods??Using ANSYS Workbench 15.0 software to established 3d finite element model of mandibular first molar restored by all-ceramic inlay restoration with designed MOD cavities. Analyzing the influences of different remaining buccal wall thickness to the stress distribution and tendency of the teeth. Results??Different remaining buccal wall thickness of the tooth tissue on the stress level had a certain influence??the lowest stress level was the remaining buccal wall thickness of 2 mm. The stress level of occlusal coverage restoration was higher than inlay restoration. Conclusion??The study found that different remaining buccal wall thickness of the tooth tissue on the stress level have a certain influence??try to keep healthy dentine??avoid enamel without foundation is effective means of inlay restoration reducing the risk of tooth fracture. Remaining more tooth tissue is not suggested to restore occlusal coverage.     

Effects of ketamine administration on mTOR and reticulum stress signaling pathways in the brain after the infusion of rapamycin into prefrontal cortex

Recent studies show that activation of the mTOR signaling pathway is required for the rapid antidepressant actions of glutamate N-methyl-D-aspartate (NMDA) receptor antagonists. A relationship between mTOR kinase and the endoplasmic reticulum (ER) stress pathway, also known as the unfolded protein response (UPR) has been shown. We evaluate the effects of ketamine administration on the mTOR signaling pathway and proteins of UPR in the prefrontal cortex (PFC), hippocampus, amygdala and nucleus accumbens, after the inhibiton of mTOR signaling in the PFC. Male adult Wistar rats received pharmacological mTOR inhibitor, rapamycin (0.2 nmol), or vehicle into the PFC and then a single dose of ketamine (15 mg/kg, i.p.). The immunocontent of mTOR, eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), eukaryotic elongation factor 2 kinase (eEF2K) homologous protein (CHOP), PKR-like ER kinase (PERK) and inositol-requiring enzyme 1 (IRE1) – alpha were determined in the brain. The mTOR levels were reduced in the rapamycin group treated with saline and ketamine in the PFC; p4EBP1 levels were reduced in the rapamycin group treated with ketamine in the PFC and nucleus accumbens; the levels of peEF2K were increased in the PFC in the vehicle group treated with ketamine and reduced in the rapamycin group treated with ketamine. The PERK and IRE1-alpha levels were decreased in the PFC in the rapamycin group treated with ketamine. Our results suggest that mTOR signaling inhibition by rapamycin could be involved, at least in part, with the mechanism of action of ketamine; and the ketamine antidepressant on ER stress pathway could be also mediated by mTOR signaling pathway in certain brain structures.     

Melatonin receptor‐mediated protection against myocardial ischemia/reperfusion injury: role of SIRT1

Melatonin confers cardioprotective effect against myocardial ischemia/reperfusion (MI/R) injury by reducing oxidative stress. Activation of silent information regulator 1 (SIRT1) signaling also reduces MI/R injury. We hypothesize that melatonin may protect against MI/R injury by activating SIRT1 signaling. This study investigated the protective effect of melatonin treatment on MI/R heart and elucidated its potential mechanisms. Rats were exposed to melatonin treatment in the presence or the absence of the melatonin receptor antagonist luzindole or SIRT1 inhibitor EX527 and then subjected to MI/R operation. Melatonin conferred a cardioprotective effect by improving postischemic cardiac function, decreasing infarct size, reducing apoptotic index, diminishing serum creatine kinase and lactate dehydrogenase release, upregulating SIRT1, Bcl‐2 expression and downregulating Bax, caspase‐3 and cleaved caspase‐3 expression. Melatonin treatment also resulted in reduced myocardium superoxide generation, gp91^phox expression, malondialdehyde level, and increased myocardium superoxide dismutase (SOD) level, which indicate that the MI/R‐induced oxidative stress was significantly attenuated. However, these protective effects were blocked by EX527 or luzindole, indicating that SIRT1 signaling and melatonin receptor may be specifically involved in these effects. In summary, our results demonstrate that melatonin treatment attenuates MI/R injury by reducing oxidative stress damage via activation of SIRT1 signaling in a receptor‐dependent manner.     

A review study on medicinal plants used in the treatment of learning and memory impairments

Alzheimer's disease (AD) is a progressive brain disorder that gradually impairs the person's memory and ability to learn, reasoning, judgment, communication and daily activities. AD is characterized clinically by cognitive impairment and pathologically by the deposition of β amyloid plaques and neurofibrillary tangles, and the degeneration of the cholinergic basal forebrain. During the progression of AD patients may produce changes in personality and behavior, such as anxiety, paranoia, confusion, hallucinations and also to experience delusions and fantasies. The first neurotransmitter defect discovered in AD involved acetylcholine as cholinergic function is required for short-term memory. Oxidative stress may underlie the progressive neurodegeneration characteristic of AD. Brain structures supporting memory are uniquely sensitive to oxidative stress due to their elevated demand for oxygen. The neurodegenerative process in AD may involve β amyloid toxicity. Neurotoxicity of β amyloid appears to involve oxidative stress. Currently, there is no cure for this disease but in new treatments, reveals a new horizon on the biology of this disease. This paper reviews the effects of a number of commonly used types of herbal medicines for the treatment of AD. The objective of this article was to review evidences from controlled studies in order to determine whether herbs can be useful in the treatment of cognitive disorders in the elderly.     

Evaluation of in silico,in vitro α-amylase inhibition potential and antidiabetic activity of Pterospermum acerifolium bark

Context: Pterospermum acerifolium (L.) Willd (Sterculiaceae) has been traditionally used in the treatment of diabetes mellitus but no scientific data has been published supporting the claimed ethnomedical use.

Objective: The present study was designed to estimate the in silico, in vitro α-amylase inhibition potential and anti-diabetic activity of Pterospermum acerifolium bark.

Materials and methods: In silico studies were performed between human pancreatic α-amylase (HPA) and β-sitosterol by using autodock 4.2 software. In vitro α-amylase inhibition study was carried out with 50% ethanol extract of the bark (PABEE) and its various fractions. The active ethyl acetate fraction (PABEF) was sub-fractionated into three fractions (PABE1, PABE2 and PABE3). Two doses (15 and 30?mg/kg) based on acute toxicity studies, of the above fractions were subjected to antidiabetic screening in vivo by STZ-nicotinamide induced type II diabetic rats.

Results: In silico studies showed the potent inhibition of β-sitosterol on human pancreatic amylase (HPA) with an estimated inhibition constant (K_i) of 269.35?nmol and two hydrogen bond interactions. PABEF showed marked α-amylase inhibition (69.94%) compared to other fractions. Diabetic rats treated with PABE3 (30?mg/kg) reduced the levels of fasting blood glucose, HbA1c, ALT, AST, ALP, triglycerides, total cholesterol, TBARS significantly (p?p?Conclusion: The present study confirmed the antihyperglycemic activity along with its status on hepatic biomarkers, antihyperlipidemic and antioxidant properties of Pterospermum acerifolium bark.     

The Impact of Alexithymia on Desire for Alcohol during a Social Stress Test

Background: Alexithymia is a personality construct comprising difficulty in identifying and describing emotions and externally oriented thinking. Its role in heavy and problematic alcohol consumption is well documented, together with its relationship with social stress. However, little research has examined whether social stress has any effect on desire for alcohol among alexithymic individuals. Objectives: In this experimental study, we explored the relationship between alexithymia and desire for alcohol in response to an experimental social stressor. Methods: One hundred and thirty eight social drinkers completed the Toronto Alexithymia Scale, self-report measures of alcohol consumption and a stress-inducing task. Desire for alcohol was measured at three time points: baseline, stressor and recovery. Results: Correlation analysis demonstrated that alexithymia was associated with significantly higher rates of alcohol consumption and higher levels of desire for alcohol. Mixed measures ANOVA demonstrated a significant main effect of alexithymia and a significant group by time effect of alexithymia on desire for alcohol. Conclusions/Importance: The findings demonstrate increased desire for alcohol before, during and after a social stressor among alexithymic participants. These findings offer an insight into the relationship between alexithymia, social stress and alcohol consumption.     

Novel stress increases hypothalamic-pituitary-adrenal activity in mice with a raised bite

Background and objectiveIn humans, occlusal disharmony may cause various physical complaints, including head and neck ache, stiffness in the shoulder and neck, and arthrosis of the temporomandibular joints. Occlusal disharmony induced by raising the bite in rodents, increases plasma corticosterone levels, which leads to morphologic changes in the hippocampus and altered hippocampus-related behavior. The paraventricular nucleus (PVN) of the hypothalamus regulates the hypothalamic-pituitary-adrenal system. Chronically stressed animals exposed to a novel stress exhibit higher adrenocorticotropic hormone levels than naive control animals. We hypothesized that there would be different response of the corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP) to a novel acute stress with occlusal disharmony.DesignIn order to investigate how exposure of mice with occlusal disharmony to a novel acute stress (restraint stress) affects the PVN, we induced occlusal disharmony by raising the vertical dimension of the bite (bite-raised condition) and examined the expression of corticotrophin releasing hormone (CRH) mRNA and arginine vasopressin (AVP) mRNA in mouse PVN.ResultsCRH mRNA expression was increased in the PVN of the bite-raised group 90 min after the bite-raising procedure, but the expression was recovered to the control level at 14 days. AVP mRNA expression in the PVN was normal at 90 min, and increased significantly 14 days after the bite-raising procedure. Exposure to restraint stress in the bite-raised mice induced a significant increase in CRH mRNA expression in the PVN.ConclusionsThe bite-raising procedure induced a rapid CRH mRNA response and a slower AVP mRNA response in the parvocellular PVN of the hypothalamus. Exposure to a novel stress following the bite-raising procedure further reinforced the CRH stress response. Thus, occlusal disharmony, such as that induced by raising the bite, may be a risk factor for hypersensitivity to a novel stress.     

The Seventh Door

An oncologist reflects on the personal toll physicians experience while taking care of the very sick and the journey they must take, facing real and perceived failures when patients suffer poor outcomes, to find the renewed energy to go on with their chosen mission.