Deficits in cognitive flexibility are prominent in stress-related psychiatric disorders, including depression. Ketamine has rapid antidepressant efficacy, but it is unknown if ketamine improves cognitive symptoms. In rats, 2 weeks chronic intermittent cold (CIC) stress impairs reversal learning, a form of cognitive flexibility mediated by the orbitofrontal cortex (OFC) that we have used previously to model cognitive dysfunction in depression. We have shown that activating JAK2/STAT3 signaling in the OFC rescued the CIC stress-induced reversal learning deficit. Thus, in the present study we determined whether ketamine also corrects the stress-induced reversal learning deficit, and if JAK2/STAT3 signaling is involved in this effect. A single injection of ketamine (10 mg/kg, i.p.) 24 h prior to testing rescued the CIC stress-induced reversal learning deficit. CIC stress decreased JAK2 phosphorylation in the OFC, and ketamine restored pJAK2 levels within 2 h post injection. The JAK2 inhibitor AG490 given systemically or into the OFC at the time of ketamine injection prevented its beneficial effect on reversal learning. We then tested the role of JAK2/STAT3 in ketamine-induced plasticity in the OFC. Ketamine depressed local field potentials evoked in the OFC by excitatory thalamic afferent stimulation, and this was prevented by JAK2 inhibition in the OFC. Further, in both the OFC and primary cortical neurons in culture, ketamine increased expression of the neural plasticity-related protein Arc, and this was prevented by JAK2 inhibition. These results suggest that the JAK2/STAT3 signaling pathway is a novel mechanism by which ketamine exerts its therapeutic effects on stress-induced cognitive dysfunction in the OFC.
Background It is being increasingly recognized that orthopedic implants are associated with adverse tissue responses, mediated by degradation products. Recent interest has been focused on the production of metal ions from hip arthroplasty. Few studies have reviewed fracture fixation devices and their metal ion production.Methods 61 subjects were enlisted into the study, with 3 subgroups. 21 subjects had Russell-Taylor intramedullary tibial nails in situ for 26 (21-32) months (316LVm stainless steel), 20 subjects had TriGen intramedullary tibial nails in situ for 43 (35-51) months (Ti-6Al-4V titanium alloy), and the remaining 20 subjects did not have any implant in situ and served as controls. Blood samples were taken and serum chromium, molybdenum, titanium, aluminium, and vanadium concentrations were measured using inductively coupled plasma (ICP) techniques.Results The 3 groups were matched for age, sex, and BMI. The subjects with Russell-Taylor nails had elevated levels of chromium (0.10 µg/L) with median concentrations 2.5 times higher than those of the control group. The subjects with TriGen nails had less significantly elevated levels of titanium (6.5 µg/L).Interpretation Stainless steel implants show significant differences from titanium implants in the dissemination of metal ions. Although the levels of chromium were elevated, the overall levels were modest when compared to published data regarding metal ion release and hip arthroplasty. Intramedullary nails are, however, often used in younger patients. If not removed, they may result in prolonged exposure to metal ions.
This article demonstrates the progress that medicine, psychiatry, religion, and anthropology have made toward a variant perspective, of masturbation. Researchers documented the suffering and damage caused by classically ingrained religious and medical distortions.The "secret sin" of Judeo-Christianity and the "social disease" of nineteenth-century medicine has paradoxially become the therapy for various forms of psychosexual dysfunction. Catholic, Protestant, and Jewish denominations polarize opinions from rigorous orthodoxy to unconditional acceptance of this psychosexual behavior as a source of emotional homeostasis.
This article demonstrates how masturbation, based on a misconception of Genesis 38:7-10, was judged harshly in both Judaism and Christianity, laying the foundation historically for social and religious hostility toward sex. Masturbation, known as the "secret sin," a threat to the human race, and an ontic evil, was condemned officially in 1054 by Pope Leo IX.From the medieval era to Victorianism there evolved new distortions of religion and science, so that masturbation was regarded as unnatural sex, murder, a diabolical practice, and the cause of two-thirds of all diseases and disorders including insanity, neurosis, and neurasthenia. Masturbation has historically served as the catalyst for social change in sexual attitudes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.