International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Membrane fouling in an anaerobic membrane bioreactor: Differences in relative abundance of bacterial species in the membrane foulant layer and in suspension

A laboratory anaerobic membrane bioreactors (AnMBRs) (10L volume) was operated at 30°C and fed with artificial sewage containing 30% protein at COD loading rate 5.1kg/m3-d to investigate membrane fouling with two membranes. Biomass attached to the membrane surface and formed a foulant layer on the membrane. The foulant layers from polyvinylidene fluoride ultrafiltration membranes coated with PEBAX (cPVDF) and an uncoated polyetherimide (PEI) ultrafiltration membranes were analyzed and compared to suspended biomass in the reactor, using terminal restriction fragments (T-RFs) of the 16S rRNA gene and a clone library. One species of OP11 bacteria was present at high relative abundance in the foulant layers of both membranes. By contrast, Bacteroidetes and Firmicutes (LGC) species were present at low relative abundance in the foulant layers but high relative abundance in the suspended biomass. Similar differences were observed for other species. The results suggest that some minority species like OP11 play a direct role in fouling by attaching to the membrane surface while others, including some that likely play a major role in the metabolism of influent organics, play a less important or indirect role. In the AnMBR, the EPS was predominately proteinaceous. EPS and microbial cells of the foulant layer contributed to membrane fouling. The results also indicate that fouling of PEI was faster than cPVDF and this reaffirm the importance of the membrane material in fouling. © 2010 Elsevier B.V.link_to_subscribed_fulltex

Hydraulic characterization and design of a full-scale biocurtain

This paper describes the design and hydraulic characterization of a cost-effective biocurtain that is currently being used to remove carbon tetrachloride from an aquifer in Schoolcraft, Michigan, Novel aspects of the design are the use of closely spaced wells to recirculate solutes through a biocurtain, well screens spanning the vertical extent of contamination, and a semipassive mode of operation, with only six hours of low-level pumping per meek. This design was developed by coupling now and transport simulations with a cost optimization algorithm, based on initial hydraulic conductivity data and system design constraints from a previous pilot-scale experiment adjacent to the current site. The hydraulic conductivity of the site was characterized using permeameter analysis on more than 200 samples from continuous well cores that were collected during well installation. The subset of available conductivity data was used to predict tracer transport through the biocurtain during system operation. Observed tracer concentration arrival histol ies during initial system operation confirmed model predictions. Modeling also established that closely spaced wells operated for brief periods each week could effectively deliver the agents needed for remediation across the biocurtain, This was confirmed during long-term operation of the system, which has resulted in highly efficient contamination degradation. The delivery well design methodology is expected to be broadly applicable at other sites where flow can be recirculated between a series of delivery wells

Calcium signalling and pancreatic cell death: apoptosis or necrosis?

Secretagogues, such as cholecystokinin and acetylcholine, utilise a variety of second messengers (inositol trisphosphate, cADPR and nicotinic acid adenine dinucleotide phosphate) to induce specific oscillatory patterns of calcium (Ca2+) signals in pancreatic acinar cells. These are tightly controlled in a spatiotemporal manner, and are coupled to mitochondrial metabolism necessary to fuel secretion. When Ca2+ homeostasis is disrupted by known precipitants of acute pancreatitis, for example, hyperstimulation or non-oxidative ethanol metabolites, Ca2+ stores (endoplasmic reticulum and acidic pool) become depleted and sustained cytosolic [Ca2+] elevations replace transient signals, leading to severe consequences. Sustained mitochondrial depolarisation, possibly via opening of the mitochondrial permeability transition pore (MPTP), elicits cellular ATP depletion that paralyses energy-dependent Ca2+ pumps causing cytosolic Ca2+ overload, while digestive enzymes are activated prematurely within the cell; Ca2+-dependent cellular necrosis ensues. However, when stress to the acinar cell is milder, for example, by application of the oxidant menadione, release of Ca2+ from stores leads to oscillatory global waves, associated with partial mitochondrial depolarisation and transient MPTP opening; apoptotic cell death is promoted via the intrinsic pathway, when associated with generation of reactive oxygen species. Apoptosis, induced by menadione or bile acids, is potentiated by inhibition of an endogenous detoxifying enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1), suggesting its importance as a defence mechanism that may influence cell fate

Arsenic induced apoptosis in malignant melanoma cells is enhanced by menadione through ROS generation, p38 signaling and p53 activation

Introduction Resistance to apoptosis is a prominent feature of melanoma. Pharmacological concentration of arsenic in combination with a widely known oxidant, menadione was explored in this study to synergistically sensitize malignant melanoma cells to apoptosis. The molecular mechanism of apoptosis and the signalingpathways involved were thoroughly investigated. Materials methods and results Menadione synergized NaAsO2 to significantly increase ROS generation and facilitate the major apoptotic signaling events: alteration of mitochondrial membrane potential, cytochrome c release and anti-apoptotic protein Bcl-2 down-regulation and subsequent activation of caspase-9 and caspase-3 followed by poly-ADP-ribose polymerase-1 cleavage. Antioxidant N-acetyl-L-cysteine antagonized these events. Investigation of the signaling-pathway revealed significant suppression of AP-1 activity but not NF-jB upon NaAsO2 and menadione application. An increase in p38 phosphorylation and p53 protein expression did also dictate the apoptotic response. Suppression of p38 activation with SB203580 and inhibition of p53 expression by siRNA attenuated apoptosis. Transfection of p53, in p53 null HCT cells augmented the apoptotic events. Moreover, the treatment also led to tumor size reduction in BALB/c mice developed by intra-dermal B16 mouse melanoma cell injection;however, it had no detectable pro-proliferative or proapoptotic effect on non-tumor keratinocytes, normal fibroblasts or PBMC. Conclusion This study thus provides an insight into innovative mechanisms of melanoma sensitization, a proper cure against which is still elusive. Taken together, our data also provides the first evidence of arsenic activity accentuation by menadione through modulation of specific signaling-pathways