Adv Exp Med Biol
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Hemorrhagic shock (HS) is a severe complication of traumatic brain injury (TBI) that doubles mortality due to severely compromised microvascular cerebral blood flow (mvCBF) and oxygen delivery reduction, as a result of hypotension. Volume expansion with resuscitation fluids (RF) for HS does not improve microvascular CBF (mvCBF); moreover, it aggravates brain edema. We showed that the addition of drag-reducing polymers (DRP) to crystalloid RF (lactated Ringer's) significantly improves mvCBF, oxygen supply, and neuronal survival in rats suffering TBI+HS. ⋯ HES (p < 0.05). Thus, resuscitation after TBI+HS using HES-DRP effectively restores mvCBF and reduces hypoxia, microthrombosis, and neuronal necrosis compared to HES. HES-DRP is more neuroprotective than lactated Ringer's with DRP and requires an infusion of a smaller volume, which reduces the development of hypervolemia-induced brain edema.
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Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide and has garnered increasing attention in recent decades. NAFLD is characterized by a wide range of liver changes, from simple steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. The pathogenesis of NAFLD/NASH is very complicated and involves lipid accumulation, insulin resistance, inflammation, and fibrogenesis. ⋯ In particular, the clinical spectrum, pathophysiology, and therapeutic options of NAFLD share many things in common with diabetes. Insulin resistance is an underlying basis for the pathogenesis of diabetes and NAFLD. This chapter focuses on the molecular mechanism involved in the pathogenesis of insulin resistance, diabetes, and NASH/NAFLD including those that drive disease progression such as oxidative stress, genetic and epigenetic mechanisms, adiponectin, cytokines, and immune cells.
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There are several mechanisms that cause memory impairment, including motivated forgetting, active forgetting, natural decay, and memory interference. Interference occurs when one is attempting to recall something specific, but there is conflicting information making it more difficult to recall the target stimuli. In laboratory settings, it is common to measure memory interference with paired associate tasks-usually utilizing the AB-CD, AB-AC, AB-ABr, or AB-DE AC-FG method. ⋯ The memory effects of each condition differ, but are all related to alterations in brain physiology and general memory deterioration. Exercise, or physical activity, has been demonstrated to attenuate memory interference in some cases, but the mechanisms are still being determined. Further research is needed on memory interference, in regard to exercise and neuropsychiatric disorders.
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The field of cancer therapy has been revolutionized through the use of immunotherapy, and treatment with these therapies now spans from early to late stage, and even into prevention. However, there are still a significant proportion of patients who do not derive long-term benefit from monotherapy and even combined therapy regimens, and novel approaches are needed to enhance therapeutic responses. Additionally, ideal biomarkers of response to immunotherapy are lacking and are critically needed. ⋯ The field of microbiome research in immuno-oncology is quickly emerging, with the potential use of the microbiome (in the gut as well as in the tumor) as a biomarker for response to IO as well as a therapeutic target. Notably, the microbiome may even have a role in toxicity to therapy. The state of the science in microbiome and IO are discussed and caveats and future directions are outlined to provide insights as we move forward as a field.
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β-hemolytic streptococci are major causes of necrotizing soft tissue infections (NSTIs), Streptococcus pyogenes (group A streptococcus; GAS) in particular. NSTIs caused by Streptococcus dysgalactiae (SD) have also been reported. In the INFECT cohort of 409 NSTIs patients, more than a third of the cases were caused by GAS (31%) or SD (7%). ⋯ As in other studies, a significant microbial diversity was observed, but with predominance of a few emm types. Overall, the INFECT study gives a comprehensive and contemporary picture of the clinical characteristics and the microbes involved in streptococcal NSTIs. The reported severity of disease underscores the need for new efforts aimed at identifying novel diagnostic measures and improved treatment.