Microbial pathogen-induced necrosis mediated by NLRP3 and ASC

NLRP3 and ASC are important components of the inflammasome, a multi-protein complex required for caspase-1 activation and IL-1[beta] production. NLRP3 mutations underlie autoinflammation characterized by excessive IL-1[beta] secretion. Disease-associated NLRP3 also causes a program of necrosis-like cell death in macrophages, the mechanistic details of which are unknown. We find that patient monocytes carrying disease-associated NLRP3 mutations exhibit excessive necrosis-like cell death by a process dependent on ASC and cathepsin B, resulting in spillage of the proinflammatory mediator HMGB1. Shigella flexneri and Klebsiella pneumoniae infection also cause NLRP3-dependent macrophage necrosis with features similar to the death caused by mutant NLRP3. This necrotic death is independent of caspase-1 and IL-1[beta], and thus independent of the inflammasome. While similar proteins mediate pathogen-induced cell death in plants, this report identifies NLRP3 as an important host regulator of pathogen-induced necrosis in animals, a process we term pyronecrosis

Exploratory analysis of the determinants of audit engagement resource allocations

https://egrove.olemiss.edu/dl_proceedings/1051/thumbnail.jp

Rootstock influences postharvest anthracnose development in 'Hass' avocado

Rootstock studies conducted on ‘Hass’ avocado found that rootstock had a significant impact on postharvest anthracnose susceptibility. This is the first record of such an effect for avocado. The severity and incidence of anthracnose was significantly lower on ‘Hass’ grafted to ‘Velvick’ Guatemalan seedling rootstock compared with the ‘Duke 6’ Mexican seedling rootstock. Differences in anthracnose susceptibility were related to significant differences in concentrations of antifungal dienes in the leaves and mineral nutrients in the leaves and fruits from trees grafted to different rootstocks. Leaf diene concentrations were up to 1.5 times higher in ‘Hass’ trees on the ‘Velvick’ than the ‘Duke 6’ rootstock. In ungrafted nursery stock trees, diene concentrations were around 3 times higher in ‘Velvick’ than ‘Duke 6’ leaves. The ‘Velvick’/‘Hass’ combination also had a significantly lower leaf N concentration, a significantly higher fruit flesh Mn concentration, and significantly lower and higher leaf N/Ca and Ca+Mg/K ratios, respectively. A significant correlation (r = 0.82) between anthracnose severity and skin N/Ca ratio was also evident

Cutting Edge: Inflammasome Activation by Alum and Alum's Adjuvant Effect Are Mediated by NLRP3

Alum is the only adjuvant approved for routine use in humans, although the basis for its adjuvanticity remains poorly understood. We have recently shown that Alum activates caspase-1 and induces secretion of mature IL-1β and IL-18. Here we show that in human and mice macrophages, alum-induced IL-1β, IL-18, and IL-33 secretion is mediated by the NLR protein NLRP3 and its adaptor ASC, but not by NLRC4. Other particulate adjuvants, such as QuilA and chitosan, induce inflammasome activation in a NLRP3-dependent fashion, suggesting that activation of the NLRP3-inflammasome may be a common mechanism of action of particulate adjuvants. Importantly, we demonstrate that antigen-specific antibody production elicited by vaccines that contain alum is significantly impaired in NLRP3-deficient mice. Our results demonstrate for the first time a role for the NLRP3-inflammasome during development of the immune response elicited by alum-enhanced vaccination. and suggest that therapeutic intervention aimed at NLRP3 may improve adjuvant efficacy

Sensitivity of selected organ dissection to diagnose Taenia solium cysticercosis in pigs from endemic areas

Taenia solium, also known as the pork tapeworm, is a neglected zoonotic parasite which is endemic in many developing countries, including Zambia. The tapeworm causes two disease conditions in humans: (1) taeniosis, which is the intestinal tapeworm infection, obtained after consumtion of raw/undercooked infected pork; and (2) cysticercosis, which is the metacestode larval stage infection, obtained after ingestion of tapeworm eggs. A human tapeworm carrier can excrete high numbers of eggs with the stool (100 000 eggs per day) and is thus an important source of environmental contamination. The transmission of cysticercosis is thus enhanced with poor sanitation and the lack of clean drinking water. After ingestion of the eggs, oncospheres hatch in the intestine and disseminate to several body tissues, including the central nervous system. Infection of the central nervous system with cysticerci is called neurocysticercosis, which is a major cause of acquired epilepsy worldwide

Improving Perioperative Knowledge and Confidence of Local Anesthetic Systemic Toxicity Management Through Education and Clinical Simulation

Local anesthetic systemic toxicity (LAST) is a life-threatening event that can occur after the administration of local anesthetics. Although LAST is a sparsely occurring event, reaction and recognition to the initial signs and symptoms followed by prompt treatment ensure effective, life-saving treatment. Providing perioperative staff with education and simulated LAST scenarios have shown to improve knowledge and confidence in LAST crisis management which translates to better preparedness if ever faced with this crisis. The purpose of this project was to provide clinical anesthesia providers and perioperative nursing staff with LAST education via simulation and case scenarios to improve awareness, confidence, knowledge, and responsiveness to a critical LAST crisis.A mixed-methods design was used to evaluate knowledge and confidence following the education and mock LAST scenario. Results provided information consistent with increased average mean scores of both knowledge and confidence across all categories. Participants’ post-evaluation questionnaires inferred information from the presentation and mock scenario were beneficial to practice and improved baseline knowledge and confidence.The results of this project have shown that knowledge and confidence improved for both RN and anesthesia providers. These findings may provide grounds for practice change for perioperative team members by changing the focus of assessments during local anesthetic administration. It is also recommended from the results of this project to incorporate LAST crisis management training into the new hire orientation program