Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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Adrenal insufficiency (AI) remains a significant cause of morbidity and mortality in children with 1 in 200 episodes of adrenal crisis resulting in death. The goal of this working group of the Pediatric Endocrine Society Drug and Therapeutics Committee was to raise awareness on the importance of early recognition of AI, to advocate for the availability of hydrocortisone sodium succinate (HSS) on emergency medical service (EMS) ambulances or allow EMS personnel to administer patient's HSS home supply to avoid delay in administration of life-saving stress dosing, and to provide guidance on the emergency management of children in adrenal crisis. Currently, hydrocortisone, or an equivalent synthetic glucocorticoid, is not available on most ambulances for emergency stress dose administration by EMS personnel to a child in adrenal crisis. ⋯ In children with known AI, parents and care providers must be made familiar with the administration of maintenance and stress dose glucocorticoid therapy to prevent adrenal crises. Patients with known AI and their families should be provided an Adrenal Insufficiency Action Plan, including stress hydrocortisone dose (both oral and intramuscular/intravenous) to be provided immediately to EMS providers and triage personnel in urgent care and emergency departments. Advocacy efforts to increase the availability of stress dose HSS during EMS transport care and add HSS to weight-based dosing tapes are highly encouraged.
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Hepatocellular Carcinoma (HCC) is one of the most common malignancies in the world, and is well-known for its bad prognosis. Potassium calcium-activated channel subfamily N member 4 (KCNN4) is a type of intermediate conductance calcium-activated potassium channel, and increasing evidence suggests that KCNN4 contributes to the regulation of invasion and metastasis in a number of cancers. However, its clinical significance and biological function remain unclear in the HCC disease process. ⋯ The mitogen-activated protein kinase (MAPK) pathway is active in cell proliferation, differentiation, migration, senescence, and apoptosis. Matrix metallopeptidase 9 and extracellular signal regulated kinase 1/2 (ERK1/2) were important biomarkers of MAPK/ERK pathway, knockdown of KCNN4 reduced the expression of MMP9 and ERK1/2. These findings showed that KCNN4 promotes HCC invasion and metastasis through the MAPK/ERK pathway.
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Stable isotope tracers have been used to gain an understanding of integrative animal and human physiology. More commonly studied organ systems include hepatic glucose metabolism, lipolysis from adipose tissue, and whole body protein metabolism. Recent improvements in isotope methodology have included the use of novel physiologic methods/models and mathematical modeling of data during different physiologic states. ⋯ Second, we describe an adaptation of the established oral minimal model used to define postprandial glucose dynamics to include glycerol dynamics in an oral glucose tolerance test with a [2H5]-glycerol tracer to determine dynamic changes in lipolysis. Simulation results were optimized when parameters describing glycerol flux were determined with a hybrid approach using both tracer-based calculations and constrained parameter optimization. Both of these methodologies can be used to expand our knowledge of not only human physiology, but also the effects of various nutritional strategies and medications on metabolism.
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Renal failure is a challenging problem in patients with cirrhosis since mortality increases with worsening renal function, hence the inclusion of serum creatinine in calculating the Model for End-Stage Liver Disease score for liver transplant evaluation. Among the various causes, infection is the leading etiology of mortality associated with cirrhosis. Bacterial infection frequently precipitates renal failure in patients with cirrhosis with the reported prevalence around 34%. ⋯ Thus, the effects of endotoxemia on renal function in cirrhosis have become a major focus of research. The mechanisms of the damaging effects of endotoxin on renal function are complex but, in essence, involve dysregulated inflammation, circulatory dysfunction, poor clearance of endotoxin burden, as well as vasomotor nephropathy. In this article, we will review the mechanisms of endotoxemia-induced renal dysfunction in the setting of cirrhosis through the effects on renal blood flow, renal vascular endothelium, glomerular filtration rate, and tubular function.
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The journal impact factor (IF) is the leading method of scholarly assessment in today's research world. An important question is whether or not this is still a constructive method. For a specific journal, the IF is the number of citations for publications over the previous 2 years divided by the number of total citable publications in these years (the citation window). ⋯ Recently, alternatives to the IF have been emerging, such as the SCImago Journal & Country Rank, the Source Normalized Impact per Paper and the Eigenfactor Score, among others. However, all alternatives proposed thus far are associated with their own limitations as well. In conclusion, although IF contains its cons, until there are better proposed alternative methods, IF remains one of the most effective methods for assessing scholarly activity.