Zobrazení zdroje stránky Lauridsensmall1720

5 mg/kg/day, i.p.) in tumor-bearing mice not only alleviated muscle wasting, but also prolonged survival. Therefore, nilotinib appears to be a promising treatment for human cancer cachexia due to its selective inhibition of p38β MAPK. SIGNIFICANCE These findings demonstrate that prevention of p38β MAPK-mediated activation of p300 by the FDA-approved kinase inhibitor, nilotinib, ameliorates cancer cachexia, representing a potential therapeutic strategy against this syndrome.<br /><br /> To summarise the evidence for non-pharmacological management of low back pain (LBP) in athletes, a common problem in sport that can negatively impact performance and contribute to early retirement.<br /><br /> Five databases (EMBASE, Medline, CINAHL, Web of Science, Scopus) were searched from inception to September 2020. The main outcomes of interest were pain, disability and return to sport (RTS).<br /><br /> Among 1629 references, 14 randomised controlled trials (RCTs) involving 541 athletes were included. The trials had biases across multiple domains including performance, attrition and reporting. Treatments included exercise, biomechanical modifications and manual therapy. There were no trials evaluating the efficacy of surgery or injections. Exercise was the most frequently investigated treatment; no RTS data were reported for any exercise intervention. There was a reduction in pain and disability reported after all treatments.<br /><br /> While several treatments for LBP in athletes improved pain and function, it was unclear what the most effective treatments were, and for whom. Exercise approaches generally reduced pain and improved function in athletes with LBP, but the effect on RTS is unknown. No conclusions regarding the value of manual therapy (massage, spinal manipulation) or biomechanical modifications alone could be drawn because of insufficient evidence. High-quality RCTs are urgently needed to determine the effect of commonly used interventions in treating LBP in athletes.<br /><br />While several treatments for LBP in athletes improved pain and function, it was unclear what the most effective treatments were, and for whom. Exercise approaches generally reduced pain and improved function in athletes with LBP, but the effect on RTS is unknown. No conclusions regarding the value of manual therapy (massage, spinal manipulation) or biomechanical modifications alone could be drawn because of insufficient evidence. High-quality RCTs are urgently needed to determine the effect of commonly used interventions in treating LBP in athletes.For millions of years, endogenous retroelements have remained transcriptionally silent within mammalian genomes by epigenetic mechanisms. Modern anticancer therapies targeting the epigenetic machinery awaken retroelement expression, inducing antiviral responses that eliminate tumors through mechanisms not completely understood. Here, we find that massive binding of epigenetically activated retroelements by RIG-I and MDA5 viral sensors promotes ATP hydrolysis and depletes intracellular energy, driving tumor killing independently of immune signaling. Energy depletion boosts compensatory ATP production by switching glycolysis to mitochondrial oxidative phosphorylation, thereby reversing the Warburg effect. However, hyperfunctional succinate dehydrogenase in mitochondrial electron transport chain generates excessive oxidative stress that unleashes RIP1-mediated necroptosis. To maintain ATP generation, hyperactive mitochondrial membrane blocks intrinsic apoptosis by increasing BCL2 dependency. Accordingly, drugs targeting BCL2 family proteins and epigenetic inhibitors yield synergistic responses in multiple cancer types. Thus, epigenetic therapy kills cancer cells by rewiring mitochondrial metabolism upon retroelement activation, which primes mitochondria to apoptosis by BH3-mimetics. SIGNIFICANCE The state of viral mimicry induced by epigenetic therapies in cancer cells remodels mitochondrial metabolism and drives caspase-independent tumor cell death, which sensitizes to BCL2 inhibitor drugs. This novel mechanism underlies clinical efficacy of hypomethylating agents and venetoclax in acute myeloid leukemia, suggesting similar combination therapies for other incurable cancers.This article is highlighted in the In This Issue feature, p. 995.Published series on COVID-19 support the notion that patients with cancer are a particularly vulnerable population. There is a confluence of risk factors between cancer and COVID-19, and cancer care and treatments increase exposure to the virus and may dampen natural immune responses. The available evidence supports the conclusion that patients with cancer, in particular with hematologic malignancies, should be considered among the very high-risk groups for priority COVID-19 vaccination.<br /><br /> Individuals who accompany a loved one through medical assistance in dying (MAiD) have to live with the experience and the psychological, moral and social consequences of their involvement in the process long after the death occurs.<br /><br /> To explore the legacy of a MAiD death for individuals who accompanied a loved one through the process.<br /><br /> Using a qualitative descriptive approach we conducted semi-structured interviews to collect data from family members who had accompanied a loved one through MAiD. [https://www.selleckchem.com/products/ca-170.html AUPM-170 order] Data were analysed using conventional content analysis.<br /><br /> 16 family members of 14 patients who received MAiD at a Canadian hospital with an interdisciplinary MAiD programme.<br /><br /> The main theme in the analysis is the opposing tensions experienced by individuals who accompany a loved one through a MAiD death, which we conceptualise as a double-edge experience. This double-edge experience is illustrated through four thematic opposing tensions (1) support for patient autonomy and ambivalence about the MAiD choice, (2) gratitude for suffering relieved for loved one and grief for lost time with loved one, (3) time as a gift and time as a burden and (4) positive legacy and challenging bereavement experience.<br /><br /> The nature of the MAiD experience for involved families is rooted in complexity, ambiguity and ambivalence and thus resists easy categorisation. Families would benefit from structured psychosocial and spiritual supports that acknowledge this complexity, along with MAiD-specific bereavement support following the death.<br /><br />The nature of the MAiD experience for involved families is rooted in complexity, ambiguity and ambivalence and thus resists easy categorisation. Families would benefit from structured psychosocial and spiritual supports that acknowledge this complexity, along with MAiD-specific bereavement support following the death.