698 research outputs found
Dopamine restores reward prediction errors in old age
No full textSenescence affects the ability to utilize information about the likelihood of rewards for optimal decision-making. Using functional magnetic resonance imaging in humans, we found that healthy older adults had an abnormal signature of expected value, resulting in an incomplete reward prediction error (RPE) signal in the nucleus accumbens, a brain region that receives rich input projections from substantia nigra/ventral tegmental area (SN/VTA) dopaminergic neurons. Structural connectivity between SN/VTA and striatum, measured by diffusion tensor imaging, was tightly coupled to inter-individual differences in the expression of this expected reward value signal. The dopamine precursor levodopa (L-DOPA) increased the task-based learning rate and task performance in some older adults to the level of young adults. This drug effect was linked to restoration of a canonical neural RPE. Our results identify a neurochemical signature underlying abnormal reward processing in older adults and indicate that this can be modulated by L-DOPA
Dynamical mean-field theory of realistic spin glasses beyond independent-mode approximation. II. Effect of reaction field
No full textThe author extends the previous calculation on a dynamical mean-field theory of realistic spin glasses (Chowdhury and Mookerjee) so as to incorporate the effect of the reaction field. The 'ordering temperature' of a mode is shown to depend not only on the corresponding eigenvalue of the random matrix J but also on the structure of the whole spectrum
Biomechanical signals and the C-type natriuretic peptide counteract catabolic activities induced by IL-1? in chondrocyte/agarose constructs
No full textIntroduction: The present study examined the effect of C-type natriuretic peptide (CNP) on the anabolic and catabolic activities in chondrocyte/agarose constructs subjected to dynamic compression. Methods: Constructs were cultured under free-swelling conditions or subjected to dynamic compression with low (0.1 to 100 pM) or high concentrations (1 to 1,000 nM) of CNP, interleukin-1? (IL-1?), and/or KT-5823 (inhibits cyclic GMP-dependent protein kinase II (PKGII)). Anabolic and catabolic activities were assessed as follows: nitric oxide (NO) and prostaglandin E2 (PGE2) release, and [3H]-thymidine and 35SO4 incorporation were quantified by using biochemical assays. Gene expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), aggrecan, and collagen type II were assessed with real-time quantitative PCR (qPCR). Two-way ANOVA and the post hoc Bonferroni-corrected t tests were used to examine data. Results: CNP reduced NO and PGE2 release and partially restored [3H]-thymidine and 35SO4 incorporation in constructs cultured with IL-1?. The response was dependent on the concentration of CNP, such that 100 pM increased [3H]-thymidine incorporation (P < 0.001). This is in contrast to 35SO4 incorporation, which was enhanced with 100 or 1000 nM CNP in the presence and absence of IL-1? (P < 0.001). Stimulation by both dynamic compression and CNP and/or the PKGII inhibitor further reduced NO and PGE2 release and restored [3H]-thymidine and 35SO4 incorporation. In the presence and absence of IL-1?, the magnitude of stimulation for [3H]-thymidine and 35SO4 incorporation by dynamic compression was dependent on the concentration of CNP and the response was inhibited with the PKGII inhibitor. In addition, stimulation by CNP and/or dynamic compression reduced IL-1?-induced iNOS and COX-2 expression and restored aggrecan and collagen type II expression. The catabolic response was not further influenced with the PKGII inhibitor in IL-1?-treated constructs. Conclusions: Treatment with CNP and dynamic compression increased anabolic activities and blocked catabolic effects induced by IL-1?. The anabolic response was PKGII mediated and raises important questions about the molecular mechanisms of CNP with mechanical signals in cartilage. Therapeutic agents like CNP could be administered in conjunction with controlled exercise therapy to slow the OA disease progression and to repair damaged cartilage. The findings from this research provide the potential for developing novel agents to slow the pathophysiologic mechanisms and to treat OA in the young and old. <br/
The Effects of the COVID-19 pandemic in the UK- at a Local, National and International level perspective from the Emergency Department
No full textContext: There is a significant burden on all emergency services in the management and prevention of the novel COVID-19 transmission. The effects are felt right across the World with certain geographical areas being most affected, it has affected all countries irrespective of their healthcare infrastructure. It has been suggested that certain parts of World that are prone to natural disasters are better prepared for pandemics. However, this is completely unfound as major economies are overwhelmed with the effects of the COVID-19 and it becomes completely irrelevant of any past experiences as these have been in never seen before scale. Evidence acquisition: The national fight against COVID-19 has been dubbed as the greatest fight for the National Health Service (NHS) with the entire United Kingdom under lockdown and the unfamiliar situation not seen before in peacetime. The general understanding of the disease process is that it has profound effects on the elderly and those with significant underlying health conditions such as cardiovascular, respiratory amongst others. However, it has surfaced from time to time that the very young are being affected and at times unfortunately been fatal. Results/Measures: The United Kingdom has been in a lockdown just like several nations across the globe in a desperate measure to limit the spread of the virus. There have been weeks of planning at every level for all possible eventualities with regards to the ongoing COVID-19 pandemic. All routine operations and procedures have been cancelled only procedures that emergency life and limb saving and cancer surgery continue to take place in hospitals all across the hospitals in the NHS. Widespread measures such as social distancing, calling a dedicated helpline for information and advice rather than attending the nearest Emergency Department have led to a significant number of presentations to the Emergency Department. Conclusions: The main concerns that remains for the NHS and other countries that have been affected is that once the lockdown restrictions are slowly eased will lead to a significant resurgence of cases that will overwhelm their respective healthcare infrastructures. From a clinician perspective, the main concern is the potential late presentations of the acutely unwell patients. This is the sentiment that is likely to be felt by many of my critical care colleagues working across NHS hospitals
Quality Improvement Project in the introduction of Major Trauma and Major Haemorrhage Protocol
No full textIntroduction: We recognised there was a need for a set criterion for the activation of MHP andMTTA at our Trust. The main aim is to streamline the trauma care that our patients would receivearound the clock. Ours is a large Major Trauma Unit regularly receiving a large volume of traumapatients of varying severity of injury
Objective: The use of a checklist for the initial management of MTTA and MHP to ensure the process is streamlined and led by the trauma team leader. This wouldhelp reduce the cognitive load that is often presented to the team leader. This would also help directjunior team members with limited experience in the initial management of major trauma.
Method/Intervention: An initial survey about MTTA and MHP from senior clinicians was carriedout. Several teaching sessions were undertaken. In addition to this, an algorithm for the initialmanagement in terms of transfer protocol was also introduced.
Results: From the clinicians’perspective, 89% of the respondents felt that the use of MHP and MTTA protocol would reduce thecognitive load whilst managing major trauma. There was an improvement in the level of confidenceof clinicians in the initial management of major trauma from 52.9 % to 89%.
Conclusion: Throughthis project, we hope that there is a better understanding of the need to have pre-defined criteria foractivation for MTTA and MTP for several reasons as highlighted in the article. The eventual aim of theproject is to streamline the initial management of the majorly injured patient and undertake thenecessary practical steps
The role of lactate to guide resuscitation: A clinician\u27s perspective
No full text’Doctor, this patient’s lactate is raised at 4mmol/l, do you want to prescribe some fluid?’’. There have been many a time where we as clinicians have had similar encounters in our clinical journey. The reaction would be to prescribe intravenous crystalloids, however with time and recent emphasis on the importance of damage control/source control resuscitation this has been realised to be fraught with errors. The approach differs if the resuscitation is a medical or trauma based. The aim of this article is to explore some of the concerns that the emergency and critical care clinicians have from a raised lactate
An interesting case of an atraumatic painful swollen limb in a pregnant woman
No full textPhlegmasia cerulea dolens is an uncommon complication of deep venous thrombosis. This is associated with high rates of morbidity if not treated effectively. We present a young lady 13 weeks pregnant with one-day history of left lower limb swelling with pain and discolouration. Bedside ultrasonography revealed thrombosis occluding the common femoral vein and collateral femoral vein. She had history of neonatal alloimmune thrombocytopaenia (NAIT), and had immunotherapy previously. The safest option was to give low molecular weight heparin (LMWH) on an inpatient basis. Anticoagulation with LMWH has been well established as thromboprophylaxis during pregnancy, however, the safety profile of systemic anticoagulation is matter of debate. As highlighted in this scenario the management needs to be tailored on an individual basis. The cause for the extensive deep vein thrombosis could be possibly due to the recent immunoglobulin therapy, undiagnosed prothrombotic state (outwith pregnancy) or the procoagulant state associated with pregnancy
Peer review report 1 on “Attitudes of surgeons to the use of postoperative markers of the systemic inflammatory response following elective surgery”
No full textAuthor Co-Citation Analysis (ACA): a powerful tool for representing implicit knowledge of scholar knowledge workers
No full textIn the last decade, knowledge has emerged as one of the most important and valuable organizational assets. Gradually this importance caused to emergence of new discipline entitled ―knowledge management‖. However one of the major challenges of knowledge management is conversion implicit or tacit knowledge to explicit knowledge. Thus Making knowledge visible so that it can be better accessed, discussed, valued or generally managed is a long-standing objective in knowledge management. Accordingly in this paper author co- citation analysis (ACA) will be proposed as an efficient technique of knowledge visualization in academia (Scholar knowledge workers)
Next Generation Business Handbook: New Strategies from Tomorrow’s Thought Leaders
No full textDonald Gibson is a contributing author, Returning Human to HR Management.”, pp. 887-902.
Book description: Next Generation Business Handbook offers strategies for the next generation of business success from the best business schools around the world. Presents fresh ideas from the young, up-and-coming business thinkers and experts from the world\u27s best business schools. Coverage of topics like career imprinting and operating in a virtual workspace that are receiving increased attention in organizations. Organized around Chowdhury\u27s next generation business model. - Publisher description.https://digitalcommons.fairfield.edu/business-books/1018/thumbnail.jp
- …
