Articles: cations.
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Transient receptor potential vanilloid-1 (TRPV1), activated by heat, acidic pH, endogenous vanilloids and capsaicin, is essential for thermal hyperalgesia. Under inflammatory conditions, phosphorylation of TRPV1 by protein kinase C (PKC) can sensitize the channel and decrease the activation threshold. Src kinase also phosphorylates TRPV1, promoting channel trafficking to the plasma membrane. These post-translational modifications are important for several chronic pain conditions. This study presents a previously undescribed relationship between Src and PKC phosphorylation of TRPV1, influencing the thermal hypersensitivity associated with TRPV1 activation. ⋯ Src kinase-mediated phosphorylation of TRPV1 is a critical regulator of the PKC-induced sensitization induced by multiple inflammatory mediators. This suggest a new regulatory mechanism governing TRPV1 function and a potential therapeutic target for inflammatory type pain, including cancer pain where Src antagonists are currently utilized.
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Pediatric functional abdominal pain disorders (FAPD) are highly prevalent, difficult to diagnose, and challenging to treat. The brain systems supporting FAPD remain poorly understood. This investigation examined the neuromechanisms of FAPD during a well-tolerated visceral pain induction task, the water load symptom provocation task (WL-SPT). ⋯ Amygdala FC with the DMN in youth with FAPD also differed from healthy controls. Global cerebral blood flow changes were also noted between FAPD and healthy controls, but no significant differences in grey matter were detected either between groups or during the WL-SPT in youth with FAPD. Findings confirm youth with FAPD undergo changes in brain systems that could support the development of biomarkers to enhance understanding of the mechanisms of pain and treatment response.
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With increasing improvement in perioperative care, post-surgical complication and mortality rates have continued to decline in the United States. Nonetheless, not all racial groups have benefitted equally from this transformative improvement in postoperative outcomes. We tested the hypothesis that among a cohort of "sick" (ASA physical status 4 or 5) Black and White children, there would be no systematic difference in the incidence of postoperative morbidity and mortality. ⋯ In this cohort of children with high ASA physical status, Black children compared to their White peers experienced significantly higher rates of 30-day postoperative morbidity and mortality. These findings suggest that racial differences in postoperative outcomes among the sickest pediatric surgical patients may not be entirely explained by preoperative health status.
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Tobacco use will kill a projected 1 billion people in the 21st century in one of the deadliest pandemics in history. Tobacco use disorder is a disease with a natural history, pathophysiology, and effective treatment options. ⋯ Tobacco treatments that combine counseling and pharmacotherapy (e.g., nicotine replacement therapy) can further increase quit rates and reduce risk of morbidity such as pulmonary and wound-related complications. The perioperative setting provides a great opportunity to implement multimodal perianesthesia tobacco treatment, which combines multiple evidence-based tactics to implement the four core components of consistent ascertainment and documentation of tobacco use, advice to quit, access to pharmacotherapy, and referral to counseling resources.
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In little over a generation, the ingenuity of scientists and clinician researchers has developed inhaled medications and pathway-specific biological agents that control the inflammation and physiology of asthma. Unfortunately, whether it is because of cost or difficulty understanding why or how to use inhaled medications, patients often do not take these medications. The consequences of poor treatment adherence, loss of control and exacerbations, are the same as if the condition remained untreated. ⋯ In this article, we discuss the rationale for and the delivery of successful interventions to improve medication adherence in asthma. We contextualize these interventions by describing the causes of poor treatment adherence and how adherence is assessed. Finally, future perspectives on the design of new interventions are described.