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The microstructure and tensile behavior of two heavy section castings that had chemical compositions typical of GJS400 were investigated. Conventional metallography, fractography, and micro-Computer Tomography (μ-CT) were employed, enabling the quantification of the volume fractions of eutectic cells with degenerated Chunky Graphite (CHG), which was identified as the major defect in the castings. The Voce equation approach was exploited to evaluate the tensile behaviors of the defective castings for integrity assessment. The results demonstrated that the Defects-Driven Plasticity (DDP) phenomenon, which refers to an unexpected regular plastic behavior related to defects and metallurgical discontinuities, was consistent with the observed tensile behavior. This resulted in a linearity of Voce parameters in the Matrix Assessment Diagram (MAD), which contradicts the physical meaning of the Voce equation. The findings suggest that the defects, such as CHG, contribute to the linear distribution of Voce parameters in the MAD. Furthermore, it is reported that the linearity in the MAD of Voce parameters for a defective casting is equivalent to the existence of a pivotal point in the differential data of the tensile strain hardening data. This pivotal point was exploited to propose a new material quality index assessing the integrity of castings.

The rapid spread of the finite element method has caused that it has become, among other methods, the standard tool for pre-clinical estimates of bone properties. This paper presents an application of this method for the calculation and prediction of strain and stress fields in the femoral head. The aim of the work is to study the influence of the considered anisotropy and heterogeneity of the modeled bone on the mechanical fields during a typical gait cycle. Three material models were tested with different properties of porous bone carried out in literature: a homogeneous isotropic model, a heterogeneous isotropic model, and a heterogeneous anisotropic model. In three cases studied, the elastic properties of the bone were determined basing on the Zysset-Curnier approach. The tensor of elastic constants defining the local properties of porous bone is correlated with a local porosity and a second order fabric tensor describing the bone microstructure. In the calculations, a model of the femoral head generated from high-resolution tomographic scans was used. Experimental data were drawn from publicly available database "Osteoporotic Virtual Physiological Human Project." To realistically reflect the load on the femoral head, main muscles were considered, and their contraction forces were determined based on inverse kinematics. For this purpose, the results from OpenSim packet were used. The simulations demonstrated that differences between the results predicted by these material models are significant. Only the anisotropic model allowed for the plausible distribution of stresses along the main trabecular groups. The outcomes also showed that the precise evaluation of the mechanical fields is critical in the context of bone tissue remodeling under mechanical stimulations., (© 2022. The Author(s).)

Aspirin, with its active compound acetylsalicylic acid (ASA), shows antiviral activity against rhino- and influenza viruses at high concentrations. We sought to investigate whether ASA and its metabolite salicylic acid (SA) inhibit SARS-CoV-2 since it might use similar pathways to influenza viruses. The compound-treated cells were infected with SARS-CoV-2. Viral replication was analysed by RTqPCR. The compounds suppressed SARS-CoV-2 replication in cell culture cells and a patient-near replication system using human precision-cut lung slices by two orders of magnitude. While the compounds did not interfere with viral entry, it led to lower viral RNA expression after 24 h, indicating that post-entry pathways were inhibited by the compounds.

Optical microscopy has been a basic and standard technique in cell biology research for decades. Microscopy techniques function well for thin, optically transparent cultures and allow for the imaging of thicker biological specimens. There is no better method of in vitro cell observation and analysis, hence microscopic techniques are extensively used and constitute an optimal tool for cell culture studies. This paper proposes an original methodology of optical microscopy data processing based on the phase contrast technique during cell culture monitoring. By exploiting images recorded during cell proliferation, a surface reconstruction was performed based on assumption, it can be considered that the local brightness of the image depends on the cells' thickness and thus the obtained results can be interpreted in the form of a surface that represents a three-dimensional structure, which allowed for a quantitative description of the cell evolution. The 3D data obtained enabled the investigation of parameters describing the morphology of the cells and the topology of their proliferation. These parameters included cell sizes in plane but also in the direction perpendicular to it, cell volume changes, their spatial distribution, as well as anisotropy and directivity. The method presented provides data carrying information similar to that obtained using a holographic microscope, e.g. A HoloMonitor (Phase Holographic Imaging PHI Inc.), or from confocal scanning microscopy with the "z-stack" mode. The techniques of bright field or phase contrast cell observation are, however, much cheaper, and widely available when compared to holographic microscopy, for instance. Besides, these also enable monitoring of cell activity over time, i.e. the study and quantitative description of dynamic changes in the cells. The proposed approach uses generally available free tools such as ImageJ software with BoneJ and Particle Analyzer plugins. The methodology is suitable for even a basic microscope, it can be easily implemented as a script, and thus data processing can be significantly shortened, the methodology can be automated, and also applied for data processing in real time., (Copyright © 2022. Published by Elsevier B.V.)

Chronic respiratory infections with the gram-negative bacterium Pseudomonas aeruginosa are an important co-morbidity for the quality of life and prognosis of people with cystic fibrosis (CF). Such long-term colonization, sometimes lasting up to several decades, represents a unique opportunity to investigate pathogen adaptation processes to the host. Our studies aimed to resolve if and to what extent the bacterial adaptation to the CF airways influences the fitness of the pathogen to grow and to persist in the lungs. Marker-free competitive fitness experiments of serial P. aeruginosa isolates differentiated by strain-specific SNPs, were performed with murine and human precision cut lung slices (PCLS). Serial P. aeruginosa isolates were selected from six mild and six severe CF patient courses, respectively. MPCLS or hPCLS were inoculated with a mixture of equal numbers of the serial isolates of one course. The temporal change of the composition of the bacterial community during competitive growth was quantified by multi-marker amplicon sequencing. Both ex vivo models displayed a strong separation of fitness traits between mild and severe courses. Whereas the earlier isolates dominated the competition in the severe courses, intermediate and late isolates commonly won the competition in the mild courses. The status of the CF lung disease rather than the bacterial genotype drives the adaptation of P. aeruginosa during chronic CF lung infection. This implies that the disease status of the lung habitat governed the adaptation of P. aeruginosa more strongly than the underlying bacterial clone-type and its genetic repertoire., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cramer, Nawrot, Wege, Dorda, Sommer, Danov, Wronski, Braun, Jonigk, Fischer, Munder and Tümmler.)

Bone presents the ability to adapt itself to the evolving mechanical environment. A simple anisotropic model for bone adaptation allowing reproducing the evolution of the elastic properties and the reorientation of the anisotropy frame is proposed is this work. The elastic properties are related to the value of the bone apparent density. The evolution law of the density is described via two functions reflecting the activities of the osteoclast and osteoblast cells. The anisotropy of the elastic properties of the bone is assumed evolving continuously between those of trabecular and compact tissues. The existence of a target material frame is assumed to describe its reorientation. The rate of rotation or spin of the material frame is supposed to be proportional to the target orientation angle and to the activity of the osteoclasts and osteoblasts. The mechanical stimulus governing the evolution of the apparent density is defined as the ratio between the current strain energy density and its critical value corresponding to the initiation of bone damage. The simulations showed that this simple model can reproduce some essential phenomena observed during bone adaptation process., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Geographic atrophy (GA), the advanced form of dry age-related macular degeneration, can result in irreversible blindness over time. We performed a systematic literature review to assess the humanistic and economic burden of GA., Methods: Predefined search terms were used to identify studies in PubMed, Embase, and Cochrane Library; conference abstracts also were searched., Results: Of 1111 unique studies identified, 25 studies on humanistic burden, 4 on economic burden, and 3 on both humanistic and economic burden of GA were included. Vision-related functioning and health-related quality of life (HRQOL) are poor in patients with GA. HRQOL is commonly measured using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25); patients with GA have significantly lower composite and subscale scores for near activities, distance activities, dependency, driving, social functioning, mental health, role difficulties, color vision, and peripheral vision than individuals without GA. Driving is a particular concern, and inability to drive affects dependency. Vision-related quality of life (VRQOL) declines as GA progresses. While we identified only 7 reports describing the economic burden of GA, its direct costs may be substantial. In a US study, mean cost to the payer per patient with GA was $11,533 in the year after diagnosis. A multinational study estimated annualized total direct costs of €1772 per patient with GA, mainly driven by diagnostic tests and procedures (€1071). Patients with GA are at increased risk of falls and fractures, potentially increasing direct costs. Only one study evaluated indirect costs, estimating ~$24.4 billion in yearly lost wages among people with severe vision loss due to GA or drusen ≥125 μm., Conclusion: GA represents a significant humanistic burden. Evidence on the economic impact of GA is limited; characterizing the economic burden of GA requires further research. Interventions that reduce GA-related disability may improve HRQOL and reduce indirect costs., Competing Interests: SPS, WC, MI, and DLJ are employees of Apellis. AH, MB, and TT are employees of RTI Health Solutions. SW was an employee of RTI Health Solutions when this research was conducted. The author reports no other conflicts of interest in this work., (© 2021 Sarda et al.)

Human rhinovirus (RV) is a major risk factor for chronic obstructive pulmonary disease (COPD) and asthma exacerbations. The exploration of RV pathogenesis has been hampered by a lack of disease-relevant model systems. We performed a detailed characterization of host responses to RV infection in human lung tissue ex vivo and investigated whether these responses are disease relevant for patients with COPD and asthma. In addition, impact of the viral replication inhibitor rupintrivir was evaluated. Human precision-cut lung slices (PCLS) were infected with RV1B with or without rupintrivir. At Days 1 and 3 after infection, RV tissue localization, tissue viability, and viral load were determined. To characterize host responses to infection, mediator and whole genome analyses were performed. RV successfully replicated in PCLS airway epithelial cells and induced both antiviral and proinflammatory cytokines such as IFNα2a, CXCL10, CXCL11, IFN-γ, TNFα, and CCL5. Genomic analyses revealed that RV not only induced antiviral immune responses but also triggered changes in epithelial cell-associated pathways. Strikingly, the RV response in PCLS was reflective of gene expression changes described in patients with COPD and asthma. Although RV-induced host immune responses were abrogated by rupintrivir, RV-triggered epithelial processes were largely refractory to antiviral treatment. Detailed analysis of RV-infected human PCLS and comparison with gene signatures of patients with COPD and asthma revealed that the human RV PCLS model represents disease-relevant biological mechanisms that can be partially inhibited by a well-known antiviral compound and provide an outstanding opportunity to evaluate novel therapeutics.

Smokers with apparently "healthy" lungs suffer from more severe and frequent viral respiratory infections, but the mechanisms underlying this observation are still unclear. Epithelial cells and dendritic cells (DC) form the first line of defense against inhaled noxes such as smoke or viruses. We therefore aimed to obtain insight into how cigarette smoke affects DCs and epithelial cells and how this influences the response to viral infection. Female C57BL/6J mice were exposed to cigarette smoke (CS) for 1 h daily for 24 days and then challenged i.n. with the viral mimic and Toll-like receptor 3 (TLR3) ligand poly (I:C) after the last exposure. DC subpopulations were analyzed 24 h later in whole lung homogenates by flow cytometry. Calu-3 cells or human precision-cut lung slices (PCLS) cultured at air-liquid interface were exposed to CS or air and subsequently inoculated with influenza H1N1. At 48 h post infection cytokines were analyzed by multiplex technology. Cytotoxic effects were measured by release of lactate dehydrogenase (LDH) and confocal imaging. In Calu-3 cells the trans-epithelial electrical resistance (TEER) was assessed. Smoke exposure of mice increased numbers of inflammatory and plasmacytoid DCs in lung tissue. Additional poly (I:C) challenge further increased the population of inflammatory DCs and conventional DCs, especially CD11b + cDCs. Smoke exposure led to a loss of the barrier function in Calu-3 cells, which was further exaggerated by additional influenza H1N1 infection. Influenza H1N1-induced secretion of antiviral cytokines (IFN-α2a, IFN-λ, interferon-γ-induced protein 10 [IP-10]), pro-inflammatory cytokine IL-6, as well as T cell-associated cytokines (e.g., I-TAC) were completely suppressed in both Calu-3 cells and human PCLS after smoke exposure. In summary, cigarette smoke exposure increased the number of inflammatory DCs in the lung and disrupted epithelial barrier functions, both of which was further enhanced by viral stimulation. Additionally, the antiviral immune response to influenza H1N1 was strongly suppressed by smoke. These data suggest that smoke impairs protective innate mechanisms in the lung, which could be responsible for the increased susceptibility to viral infections in "healthy" smokers., (Copyright © 2020 Danov, Wolff, Bartel, Böhlen, Obernolte, Wronski, Jonigk, Hammer, Kovacevic, Reuter, Krauss-Etschmann and Sewald.)

The usage of finite element method techniques gives a possibility to replace time-consuming experiments or imitate physical process in the ear by numerical simulation. Especially, the research of spatial motion of ossicular chain in the middle ear is of high interest for the oto-surgeons and engineers. It is known that the most affected bone from the ossicular chain is the incus. After the cholesteatoma operation and tympanoplasty, the affected incus is removed or sacrificed; thus, the possibility of transducing noise lays on the stapes, new titanium or other material prosthesis. In this case, the affected incus was removed because of the cholesteatoma that was lying in front of it in the tympanic cavity. The removed incus with the affected long process passed micro-computed tomography. The computer-aided design systems allowed redesigning a 'healthy' incus with an intact long process. In this way, it was possible to evaluate the influence of damaged long process of incus in the vibrational analysis. This article analyses the problems of mechanical behaviour of injured and healthy human incus. The numerical simulation has demonstrated that the features of healthy incus and analysed injured incus do not differ significantly, especially at low (about 500 Hz) frequencies. It explains why there is no impact of cholesteatoma on hearing for a long time in the audiogram.

The peptide sequence KKIRVRLSA was synthesized in a dimeric structure (SET-M33DIM) and evaluated as a candidate drug for infections due to multidrug-resistant (MDR) Gram-negative pathogens. SET-M33DIM showed significant antibacterial activity against MDR strains of Klebsiella pneumoniae, Acinetobacter baumannii, and Escherichia coli (Minimal Inhibitory Concentration [MICs], 1.5-11 µM), and less activity against Pseudomonas aeruginosa (MICs, 11-22 µM). It showed very low toxicity in vitro, ex vivo, and in vivo; in cytotoxicity tests, its EC 50 was as much as 22 times better than that of SET-M33, a peptide with the same amino-acid sequence, but synthesized in tetra-branched form (638 vs 28 µM). In in vivo and ex vivo experiments, SET-M33DIM cleared P. aeruginosa infection, significantly reducing signs of sepsis in animals, and restoring cell viability in lung tissue after bacterial challenge. It also quelled inflammation triggered by LPS and live bacterial cells, inhibiting expression of inflammatory mediators in lung tissue, cultured macrophages, and bronchial cells from a cystic fibrosis patient., (© 2019 Federation of American Societies for Experimental Biology.)

Background: Antiviral drugs such as rupintrivir may have an immune-modulatory effect in experimentally induced allergic asthma with subsequent RV infection. We infected lung slices of house-dust mite (HDM)-sensitized asthmatic mice ex vivo with human rhinovirus (RV) and investigated the effect of the antiviral drug rupintrivir on RV-induced cytokine response in lung tissue of HDM-sensitized mice ex vivo., Methods: Mice were sensitized with HDM. Precision-cut lung slices (PCLS) were prepared from HDM-sensitized or non-sensitized mice. Lung slices were infected ex vivo with RV or RV together with rupintrivir. Modulation of immune responses was evaluated by cytokine secretion 48 h post infection., Results: In vivo HDM sensitization resulted in a T H -2/T H -17-dominated cytokine response that persisted in PCLS ex vivo. RV infection of PCLS from non-sensitized mice resulted in the induction of an antiviral and pro-inflammatory immune response, as indicated by the secretion of IFN-α, IFN-β, IFN-γ, TNF-α, MCP-1, IP-10, IL-10, and IL-17A. In contrast, PCLS from HDM-sensitized mice showed an attenuated antiviral response, but exaggerated IL-4, IL-6, and IL-10 secretion upon infection. Rupintrivir inhibited exaggerated pro-inflammatory cytokine IL-6 and T H -2 cytokine IL-4 in HDM-sensitized mice., Conclusions: In summary, this study demonstrates that treatment with rupintrivir influences virus-induced IL-4 and IL-6 cytokine release under experimental conditions ex vivo.

Rhinovirus (RV) is the predominant virus causing respiratory tract infections. Bronchobini ® is a low dose multi component, multi target preparation used to treat inflammatory respiratory diseases such as the common cold, described to ease severity of symptoms such as cough and viscous mucus production. The aim of the study was to assess the efficacy of Bronchobini ® in RV infection and to elucidate its mode of action. Therefore, Bronchobini ® 's ingredients (BRO) were assessed in an ex vivo model of RV infection using mouse precision-cut lung slices, an organotypic tissue capable to reflect the host immune response to RV infection. Cytokine profiles were assessed using enzyme-linked immunosorbent assay (ELISA) and mesoscale discovery (MSD). Gene expression analysis was performed using Affymetrix microarrays and ingenuity pathway analysis. BRO treatment resulted in the significant suppression of RV-induced antiviral and pro-inflammatory cytokine release. Transcriptome analysis revealed a multifactorial mode of action of BRO, with a strong inhibition of the RV-induced pro-inflammatory and antiviral host response mediated by nuclear factor kappa B (NFkB) and interferon signaling pathways. Interestingly, this was due to priming of these pathways in the absence of virus. Overall, BRO exerted its beneficial anti-inflammatory effect by priming the antiviral host response resulting in a reduced inflammatory response to RV infection, thereby balancing an otherwise excessive inflammatory response.

The increasing number of severe infections with multi-drug-resistant pathogens worldwide highlights the need for alternative treatment options. Given the pivotal role of phagocytes and especially alveolar macrophages in pulmonary immunity, we introduce a new, cell-based treatment strategy to target bacterial airway infections. Here we show that the mass production of therapeutic phagocytes from induced pluripotent stem cells (iPSC) in industry-compatible, stirred-tank bioreactors is feasible. Bioreactor-derived iPSC-macrophages (iPSC-Mac) represent a highly pure population of CD45 + CD11b + CD14 + CD163 + cells, and share important phenotypic, functional and transcriptional hallmarks with professional phagocytes, however with a distinct transcriptome signature similar to primitive macrophages. Most importantly, bioreactor-derived iPSC-Mac rescue mice from Pseudomonas aeruginosa-mediated acute infections of the lower respiratory tract within 4-8 h post intra-pulmonary transplantation and reduce bacterial load. Generation of specific immune-cells from iPSC-sources in scalable stirred-tank bioreactors can extend the field of immunotherapy towards bacterial infections, and may allow for further innovative cell-based treatment strategies.

Objectives: In the context of cystic fibrosis, Pseudomonas aeruginosa biofilms often develop in the vicinity of airway mucus, which acts as a protective physical barrier to inhaled matter. However, mucus can also adsorb small drug molecules administered as aerosols, including antibiotics, thereby reducing their bioavailability. The efficacy of antibiotics is typically assessed by determining the MIC using in vitro assays. This widespread technique, however, does not consider either bacterial biofilm formation or the influence of mucus, both of which may act as diffusion barriers, potentially limiting antibiotic efficacy., Methods: We grew P. aeruginosa biofilms in the presence or absence of human tracheal mucus and tested their susceptibility to tobramycin and colistin., Results: A significant reduction of tobramycin efficacy was observed when P. aeruginosa biofilms were grown in the presence of mucus compared with those grown in the absence of mucus. Diffusion of tobramycin through mucus was reduced; however, this reduction was more pronounced in biofilm/mucus mixtures, suggesting that biofilms in the presence of mucus respond differently to antibiotic treatment. In contrast, the influence of mucus on colistin efficacy was almost negligible and no differences in mucus permeability were observed., Conclusions: These findings underline the important role of mucus in the efficacy of anti-infective drugs.

Background: Respiratory viruses such as respiratory syncytial virus (RSV) or rhinovirus are one of the major causes for respiratory tract infections causing common cold disease. Respiratory viral infections range from mild symptoms in adults to serious illness especially in the very young or elderly as well as patients suffering from lung diseases or being immunocompromised due to other reasons. Engystol (EGY-2) is a multicomponent, multitarget preparation consisting of Vincetoxicum hirundinaria and Sulfur in various dilutions. The study objective was to test the effect of EGY-2 on the innate immune response during the early onset of respiratory viral infection in vivo as exemplified in a mouse model of RSV-induced respiratory inflammation., Methods: Naïve BALB/c mice were infected with 1x106 infectious units RSV A2 intranasally to cause a mild respiratory infection. EGY-2 was administered daily per oral gavage starting seven days prior to RSV infection at doses of 0.4 to 5.1 tablets/kg. Control groups received placebo treatment. Animals were sacrificed 1 to 3 days post infection (p.i.) to analyse the infection and induced immune response in the lung. Viral load in bronchoalveolar lavage fluid (BALF) and lung homogenate was determined by TCID50 assay as well as immunofluorescence staining of BALF cells using anti-RSV antibody and microscopic analysis. The RSV induced immune response was assessed by evaluation of BALF differential cell count, BALF cytokine secretion and analysis of the phagocytic capacity of alveolar macrophages., Results: EGY-2 significantly reduced the RSV induced neutrophil and early lymphocyte influx on day 1 p.i. in BALF. EGY-2 treatment significantly diminished the RSV induced secretion of pro-inflammatory cytokines such as IFN-γ, IL-1β, IL-6, KC and TNF-α at day 1. EGY-2 treatment was not protective for RSV infection per se, as no alteration in the viral load in lung and BALF was detected. Enhanced numbers of phagocytic-active macrophages were observed in EGY-2 treated animals on day 1 and this macrophage population showed strongly enhanced phagocytic activity on day 1 and day 3., Conclusion: The data suggest a beneficial immunomodulatory effect of EGY-2 during early onset of respiratory viral infection in vivo, mediated by stimulation of macrophage phagocytosis, resulting in a reduced innate inflammatory response in terms of neutrophil and early lymphocyte infiltration as well as reduced inflammatory cytokine secretion.

Rationale: The pathogenesis of respiratory syncytial virus (RSV) bronchiolitis in infants remains poorly understood. Mouse models implicate pulmonary T cells in the development of RSV disease. T cell responses are initiated by dendritic cells (DCs), which accumulate in lungs of RSV-infected mice. In infants with RSV bronchiolitis, previous reports have shown that DCs are mobilised to the nasal mucosa, but data on lower airway DC responses are lacking., Objective: To determine the presence and phenotype of DCs and associated immune cells in bronchoalveolar lavage (BAL) and peripheral blood samples from infants with RSV bronchiolitis., Methods: Infants intubated and ventilated due to severe RSV bronchiolitis or for planned surgery (controls with healthy lungs) underwent non-bronchoscopic BAL. Immune cells in BAL and blood samples were characterised by flow cytometry and cytokines measured by Human V-Plex Pro-inflammatory Panel 1 MSD kit., Measurements and Main Results: In RSV cases, BAL conventional DCs (cDCs), NK T cells, NK cells and pro-inflammatory cytokines accumulated, plasmacytoid DCs (pDCs) and T cells were present, and blood cDCs increased activation marker expression. When stratifying RSV cases by risk group, preterm and older (≥4 months) infants had fewer BAL pDCs than term born and younger (<4 months) infants, respectively., Conclusions: cDCs accumulate in the lower airways during RSV bronchiolitis, are activated systemically and may, through activation of T cells, NK T cells and NK cells, contribute to RSV-induced inflammation and disease. In addition, the small population of airway pDCs in preterm and older infants may reveal a distinct endotype of RSV bronchiolitis with weak antiviral pDC responses., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objectives: Our previous data demonstrated that allergic airway inflammation induces migration of dendritic cells (DC) into airway sensory jugular and nodose ganglia (jugular-nodose ganglion complex; JNC). Here we investigated the effects of steroid treatment regarding the expression and migration of DC and calcitonin gene-related peptide (CGRP)-immunoreactive neurons of vagal sensory ganglia during allergic airway inflammation., Methods: A house dust mite (HDM) model for allergic airway inflammation was used. The mice received 0.3 mg fluticasone propionate per kilogram of body weight in the last 9 days. JNC slices were analyzed on MHC II, the neuronal marker PGP9.5, and the neuropeptide CGRP., Results: Allergic airway inflammation increased the numbers of DC and CGRP-expressing neurons in the JNC significantly in comparison to the controls (DC/neurons: HDM 44.58 ± 1.6% vs. saline 33.29 ± 1.6%, p < 0.05; CGRP-positive neurons/total neurons: HDM 30.65 ± 1.9% vs. saline 19.49 ± 2.3%, p < 0.05). Steroid treatment did not have any effect on the numbers of DC and CGRP-expressing neurons in the JNC compared to HDM-treated mice., Conclusions: The present findings indicate an important role of DC and CGRP-containing neurons in the pathogenesis of allergic airway inflammation. However, steroid treatment did not have an effect on the population of DC and neurons displaying CGRP in the JNC, whereas steroid treatment was found to suppress allergic airway inflammation., (© 2015 S. Karger AG, Basel.)

Background: Postoperative ileus (POI), a common postoperative complication, increases length of stay and costs. Although bowel rest and delayed oral intake were once thought to help prevent POI, newer evidence shows that chewing gum can be beneficial. METHODS--LITERATURE SEARCH: The literature was searched for the terms ileus, gum, chewing, and gum chewing for 2006 to 2013., Study Selection: All prospective randomized controlled trials comparing gum chewing in adults with a control treatment after abdominal surgery (except cesarean section) were included; an outcome measure was required as a dependent variable., Findings: Seven primary research studies from around the world were gathered., Results: Across all studies, patients in the gum-chewing experimental group both passed flatus and defecated before those in the non-gum-chewing control group. Where length of stay was studied, patients in all but one experimental group were in the hospital for less time., Limitations: These included small sample sizes, lack of blinding in all but one study, differences in standards of care among hospitals and countries represented, unspecified types of gum, and variable timing and frequency of gum chewing among studies., Discussion: Patients who chewed gum postoperatively had less POI, passed flatus sooner, had an earlier bowel movement and a shorter length of stay, and were more satisfied. Gum chewing is recommended as adjunctive therapy to reduce postoperative POI.

Background and Purpose: We conducted a phase II study combining induction chemotherapy with continuous hyperfractionated accelerated radiotherapy (CHART) in locally advanced non-small-cell lung cancer (NSCLC)., Materials and Methods: A total of 40 patients with stage III NSCLC were enrolled. All patients received 3 cycles of chemotherapy followed by CHART (56 Gy in 36 fractions over 12 days). The primary outcome measure was radiation toxicity. Secondary endpoints were response rate, overall survival, disease-free survival and loco-regional progression-free survival., Results: Acute radiation toxicity was minimal and there were no significant late toxicities. The response rate after completion of chemoradiation was 65%. The median and 2-year overall survival, progression-free survival and loco-regional progression-free survivals were 15.7 months, 28%; 12.1 months, 23%; and 26.4 months, 51%, respectively., Conclusions: Induction chemotherapy can be safely combined with CHART. The survival results are consistent with previous studies of chemotherapy followed by accelerated radiotherapy. This approach should be compared with synchronous chemoradiation to determine if it represents a less toxic alternative.