Lysozyme M deficiency leads to an increased susceptibility to Streptococcus pneumoniae-induced otitis media

<p>Abstract</p> <p>Background</p> <p>Lysozyme is an antimicrobial innate immune molecule degrading peptidoglycan of the bacterial cell wall. Lysozyme shows the ubiquitous expression in wide varieties of species and tissues including the tubotympanum of mammals. We aim to investigate the effects of lysozyme depletion on pneumococcal clearance from the middle ear cavity.</p> <p>Methods</p> <p>Immunohistochemistry was performed to localize lysozyme in the Eustachian tube. Lysozyme expression was compared between the wild type and the lysozyme M^-/-mice using real time quantitative RT-PCR and western blotting. Muramidase activity and bactericidal activity of lysozyme was measured using a lysoplate radial diffusion assay and a liquid broth assay, respectively. To determine if depletion of lysozyme M increases a susceptibility to pneumococal otitis media, 50 CFU of <it>S. pneumoniae </it>6B were transtympanically inoculated to the middle ear and viable bacteria were counted at day 3 and 7 with clinical grading of middle ear inflammation.</p> <p>Results</p> <p>Immunolabeling revealed that localization of lysozyme M and lysozyme P is specific to some/particular cell types of the Eustachian tube. Lysozyme P of lysozyme M^-/-mice was mainly expressed in the submucosal gland but not in the tubal epithelium. Although lysozyme M^-/-mice showed compensatory up-regulation of lysozyme P, lysozyme M depletion resulted in a decrease in both muramidase and antimicrobial activities. Deficiency in lysozyme M led to an increased susceptibility to middle ear infection with <it>S. pneumoniae </it>6B and resulted in severe middle ear inflammation, compared to wild type mice.</p> <p>Conclusion</p> <p>The results suggest that lysozyme M plays an important role in protecting the middle ear from invading pathogens, particularly in the early phase. We suggest a possibility of the exogenous lysozyme as an adjuvant therapeutic agent for otitis media, but further studies are necessary.</p

Patient Selection in One Anastomosis/Mini Gastric Bypass—an Expert Modified Delphi Consensus

Purpose: One anastomosis/mini gastric bypass (OAGB/MGB) is up to date the third most performed obesity and metabolic procedure worldwide, which recently has been endorsed by ASMBS. The main criticisms are the risk of bile reflux, esophageal cancer, and malnutrition. Although IFSO has recognized this procedure, guidance is needed regarding selection criteria. To give clinicians a daily support in performing the right patient selection in OAGB/MGB, the aim of this paper is to generate clinical guidelines based on an expert modified Delphi consensus. Methods: A committee of 57 recognized bariatric surgeons from 24 countries created 69 statements. Modified Delphi consensus voting was performed in two rounds. An agreement/disagreement among ≥ 70.0% of the experts was considered to indicate a consensus. Results: Consensus was achieved for 56 statements. Remarkably, ≥ 90.0% of the experts felt that OAGB/MGB is an acceptable and suitable option "in patients with Body mass index (BMI) > 70, BMI > 60, BMI > 50 kg/m2 as a one-stage procedure," "as the second stage of a two-stage bariatric surgery after Sleeve Gastrectomy for BMI > 50 kg/m2 (instead of BPD/DS)," and "in patients with weight regain after restrictive procedures. No consensus was reached on the statement that OAGB/MGB is a suitable option in case of resistant Helicobacter pylori. This is likely as there is a concern that this procedure is associated with reflux and its related long-term complications including risk of cancer in the esophagus or stomach. Also no consensus reached on OAGB/MGB as conversional surgery in patients with GERD after restrictive procedures. Consensus for disagreement was predominantly achieved "in case of intestinal metaplasia of the stomach" (74.55%), "in patients with severe Gastro Esophageal Reflux Disease (GERD)(C,D)" (75.44%), "in patients with Barrett's metaplasia" (89.29%), and "in documented insulinoma" (89.47%). Conclusion: Patient selection in OAGB/MGB is still a point of discussion among experts. There was consensus that OAGB/MGB is a suitable option in elderly patients, patients with low BMI (30-35 kg/m2) with associated metabolic problems, and patients with BMIs more than 50 kg/m2 as one-stage procedure. OAGB/MGB can also be a safe procedure in vegetarian and vegan patients. Although OAGB/MGB can be a suitable procedure in patients with large hiatal hernia with concurrent hiatal hernia, it should not be offered to patients with grade C or D esophagitis or Barrett's metaplasia.info:eu-repo/semantics/publishedVersio

Neural cytoskeleton capabilities for learning and memory

This paper proposes a physical model involving the key structures within the neural cytoskeleton as major players in molecular-level processing of information required for learning and memory storage. In particular, actin filaments and microtubules are macromolecules having highly charged surfaces that enable them to conduct electric signals. The biophysical properties of these filaments relevant to the conduction of ionic current include a condensation of counterions on the filament surface and a nonlinear complex physical structure conducive to the generation of modulated waves. Cytoskeletal filaments are often directly connected with both ionotropic and metabotropic types of membrane-embedded receptors, thereby linking synaptic inputs to intracellular functions. Possible roles for cable-like, conductive filaments in neurons include intracellular information processing, regulating developmental plasticity, and mediating transport. The cytoskeletal proteins form a complex network capable of emergent information processing, and they stand to intervene between inputs to and outputs from neurons. In this manner, the cytoskeletal matrix is proposed to work with neuronal membrane and its intrinsic components (e.g., ion channels, scaffolding proteins, and adaptor proteins), especially at sites of synaptic contacts and spines. An information processing model based on cytoskeletal networks is proposed that may underlie certain types of learning and memory

Bayesian registration of models using finite element eigenmodes.

This paper is concerned with registering three-dimensional wire-frame organ models. This involves finding correspondences between points on the models of two different examples of the same organ. Such registration is widely used in the processing of medical data; for example in segmentation, or to superimpose functional information on a more detailed structural map. The algorithm described in this paper is based on matching the modes of deformation of organ shapes. Modes with lower spatial frequency characterise large scale organ features whereas small scale variations determine the high frequency modes. First, the organ sizes are normalised using a generalised version of the centroid size metric. The axes of the fundamental frequency modes are then aligned to provide initial rigid-body registration. The registration is refined by matching increasingly high frequency modes using the 'Highest confidence first' algorithm. The matches are evaluated using a Bayesian combination of local prior and likelihood functions. The prior is derived from the Gompertz metric of biological growth and ensures that physically impossible matches are not accepted. The likelihood function is a measure of the similarity between local modal deformation components. The registration algorithm has been applied by the authors in the analysis of three dimensional ultrasound data. Results are presented showing the registration of two liver models derived from 3D ultrasound

Interactive segmentation of 3d ultrasound using deformable solid models and active contours

This paper presents a prototype segmentation system for three-dimensional ultrasound data. 3D ultrasound is cheap and noninvasive but the data has a low signal-to-noise ratio and contains artifacts. To overcome these difficulties we have developed a system which uses a prior model, initialised by a clinician, to provide the starting point for a data-driven segmentation algorithm based on active contours. Results are presented showing how the technique can facilitate the segmentation of a gall-bladder