In this 24-week trial, glucosamine and chondroitin sulfate were not more effective, alone or in combination, than placebo in controlling pain in patients with osteoarthritis of the knee. In secondary ...analyses, however, in the subgroup of patients with moderate-to-severe osteoarthritis, those given both glucosamine and chondroitin sulfate were more likely than those given placebo to have a decrease in pain (79 percent vs. 54 percent).
In this trial, glucosamine and chondroitin sulfate were not more effective, alone or in combination, than placebo in controlling pain in patients with osteoarthritis of the knee.
Osteoarthritis is the most common of the arthritides, affecting at least 20 million Americans, a number that is expected to double over the next two decades.
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Currently available medical therapies primarily address the treatment of joint pain in patients with osteoarthritis.
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Analgesics as well as traditional and cyclooxygenase-2–selective nonsteroidal antiinflammatory drugs (NSAIDs) have suboptimal effectiveness,
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and there is some question about their safety, especially in the light of recent reports of increased cardiovascular risk.
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The dietary supplements glucosamine and chondroitin sulfate have been advocated, especially in the lay media, as safe and effective options for the management . . .
Using a large dataset of hand-collected information on activist interventions from 2008 to 2014, we examine why certain hedge funds succeed in the face of competition. We document that the top hedge ...funds succeed, not merely because of how they select targets, but because they acquire a reputation for what we label “clout and expertise.” These hedge funds do not intervene more frequently; to the contrary, activists with more interventions are associated with lower returns. Instead, top activists have a demonstrated ability to succeed in difficult interventions by targeting large firms, launching successful proxy fights, filing and winning lawsuits, pressuring target boards through the media, overcoming anti-takeover defenses, and replacing board members. These activists' successes appear to result more from board representation, improved performance, and monitoring management than from capital structure or dividend policy changes.
•Top activists have a reputation for what we label “clout and expertise.”•Top activists have an ability to succeed in difficult interventions by targeting large firms.•Top activists launch successful proxy fights, and file and win lawsuits.•Top activists overcome anti-takeover defenses, and replace board members.•Top activists successes appear to result from board representation and monitoring management.
A fundamental process in the development and progression of heart failure is fibrotic remodeling, characterized by excessive deposition of extracellular matrix proteins in response to injury. ...Currently, therapies that effectively target and reverse cardiac fibrosis are lacking, warranting novel therapeutic strategies and reliable methods to study their effect. Using a gelatin methacryloyl hydrogel, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and human fetal cardiac fibroblasts (hfCF), we developed a multi-cellular mechanically tunable 3D
model of human cardiac fibrosis. This model was used to evaluate the effects of a promising anti-fibrotic drug-pirfenidone-and yields proof-of-concept of the drug testing potential of this platform. Our study demonstrates that pirfenidone has anti-fibrotic effects but does not reverse all TGF-β1 induced pro-fibrotic changes, which provides new insights into its mechanism of action.
Platelet transfusion is a very common lifesaving medical procedure. Not widely known is the fact that platelets, unlike other blood cells, rapidly leave the circulation if refrigerated prior to ...transfusion. This peculiarity requires blood services to store platelets at room temperature, limiting platelet supplies for clinical needs. Here, we describe the mechanism of this clearance system, a longstanding mystery. Chilling platelets clusters their von Willebrand (vWf) receptors, eliciting recognition of mouse and human platelets by hepatic macrophage complement type 3 (CR3) receptors. CR3-expressing but not CR3-deficient mice exposed to cold rapidly decrease platelet counts. Cooling primes platelets for activation. We propose that platelets are thermosensors, primed at peripheral sites where most injuries occurred throughout evolution. Clearance prevents pathologic thrombosis by primed platelets. Chilled platelets bind vWf and function normally in vitro and ex vivo after transfusion into CR3-deficient mice. Therefore, GPIb modification might permit cold platelet storage.
Background: Adverse drug reactions (ADRs) are recognised causes of increased mortality, morbidity, and high healthcare costs. The contribution of healthcare students to ADR databases is essential and ...has enabled continued drug detection to such an extent that it has led to identifying unsuspected and rare ADR signals.
Objectives: The study aims to evaluate healthcare students’ knowledge, attitude, and practice (KAP) toward ADR reporting.
Methods: This descriptive, cross-sectional study was conducted among 265 healthcare students of Namakkal district, Tamil Nadu, from various departments. A three-section questionnaire was developed in English and distributed online from July to October 2020. Each participant received a score for each KAP section.
Results: Of the 265 healthcare students included in the study, 56.98% were female. The majority were pharmacy students 132 (49.81%), followed by medical 74 (27.92%) and nursing 59 (22.26%) students. There was a significant difference in ADR reporting among healthcare students. KAP of ADR reporting was higher among pharmacy students (88.68%) compared to the medical (19.25%) and nursing students (29.63%), with a p-value of 0.05.
Conclusion: This study showed that pharmacy students had more awareness of ADR reporting than other healthcare students due to pharmacovigilance courses in their curriculum and adequate training during clerkships and internships. Hence, it is necessary to include pharmacovigilance and ADR reporting in other healthcare curriculum to reduce ADR underreporting in the future. Periodic educational interventions can improve these parameters of pharmacovigilance.
Cellular senescence, the irreversible proliferative arrest seen in somatic cells after a limited number of divisions, is considered a crucial barrier to cancer, but direct evidence for this in vivo ...was lacking until recently. The best-known form of human cell senescence is attributed to telomere shortening and a DNA-damage response through p53 and p21. There is also a more rapid form of senescence, dependent on the p16-retinoblastoma pathway. p16 (CDKN2A) is a known melanoma susceptibility gene. Here, we use retrovirally mediated gene transfer to confirm that the normal form of senescence in cultured human melanocytes involves p16, since disruption of the p16/retinoblastoma pathway is required as well as telomerase activation for immortalisation. Expression (immunostaining) patterns of senescence mediators and markers in melanocytic lesions provide strong evidence that cell senescence occurs in benign melanocytic naevi (moles) in vivo and does not involve p53 or p21 upregulation, although p16 is widely expressed. In comparison, dysplastic naevi and early (radial growth-phase, RGP) melanomas show less p16 and some p53 and p21 immunostaining. All RGP melanomas expressed p21, suggesting areas of p53-mediated senescence, while most areas of advanced (vertical growth-phase) melanomas lacked both p16 and p21, implying escape from both forms of senescence (immortalisation). Moreover, nuclear p16 but not p21 expression can be induced in human melanocytes by oncogenic BRAF, as found in around 80% of naevi. We conclude that cell senescence can form a barrier to melanoma development. This also provides a potential explanation of why p16 is a melanoma suppressor gene.
The synthesis of a new benzocyclobutene based polymer, PSBBB, designed as a dielectric material for use in organic thin film transistors was reported. Compared to conventional benzocyclobutene-based ...materials, the introduction of a butoxide substituent at the 7-position of the benzocyclobutene pendant unit on the polymer allowed PSBBB to be cross-linked at temperatures of 120 °C, thus rendering it compatible with the processing requirements of flexible plastic substrates. The cross-linking behavior of PSBBB was investigated by Fourier transform infrared spectroscopy and differential scanning calorimetry, demonstrating cross-linking of the polymer after curing at 120 °C. Bottom-gate bottom-contact organic thin film transistors were fabricated using PSBBB as dielectric, affording a performance comparable to that of other dielectric polymeric materials.
High-fidelity intracranial electrode arrays for recording and stimulating brain activity have facilitated major advances in the treatment of neurological conditions over the past decade. Traditional ...arrays require direct implantation into the brain via open craniotomy, which can lead to inflammatory tissue responses, necessitating development of minimally invasive approaches that avoid brain trauma. Here we demonstrate the feasibility of chronically recording brain activity from within a vein using a passive stent-electrode recording array (stentrode). We achieved implantation into a superficial cortical vein overlying the motor cortex via catheter angiography and demonstrate neural recordings in freely moving sheep for up to 190 d. Spectral content and bandwidth of vascular electrocorticography were comparable to those of recordings from epidural surface arrays. Venous internal lumen patency was maintained for the duration of implantation. Stentrodes may have wide ranging applications as a neural interface for treatment of a range of neurological conditions.
•Compact and optimized reaction mechanism for UVO biodiesel and1-Hexanol blend.•Model consists of 588 reactions and 139 species.•Faster engine simulation, using CFD softwares.•Validated for Ignition ...delay, flame speed, species mole fraction and combustion.
In this study, a compact kinetic model consisting of 588 reactions and 139 species is proposed for 1-Hexanol and used vegetable oil (UVO) biodiesel blend for simulating internal combustion (IC) engines. Suitable modifications were made to the pre-exponential factor to ascertain predictive performance comparable to the investigational results. This reduced reaction model was validated with experimental data from the published work for laminar flames speed, ignition delay and species mole fractions. The reduced mechanism and the experimental results are comparable within a factor of 1.3–2.5. A zero-dimensional single zone model was employed for simulating internal combustion engine conditions with the reduced mechanism using Cantera software and the results are analogous and as expected from the simulation study. The reduced reaction mechanism could be utilized by the researchers working on alternative fuels to simulate and study the combustion of used vegetable oil/1-Hexanol blend in an engine using computational fluid dynamics (CFD) modeling software.
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