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Journal articles on the topic 'Modelli murino'

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Author: Grafiati

Published: 10 March 2023

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1

Matarrese, Paola, and Giuseppe Marano. "Modulazione dei recettori β-adrenergici e differenze di genere." CARDIOLOGIA AMBULATORIALE 30, no. 1 (May 31, 2022): 20–24. http://dx.doi.org/10.17473/1971-6818-2022-1-5.

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Lo scompenso cardiaco (SC), processo evolutivo comune di più malattie cardiovascolari a differente eziologia (ad es. infarto del miocardio, ipertensione, cardiomiopatie, disturbi valvolari e altre), è diventato sempre più comune nella popolazione anziana, influenzando drasticamente il tasso di sopravvivenza e la qualità della vita. L’iperattività del sistema nervoso simpatico (SNS) che si associa allo SC determina un aumento delle catecolamine circolanti epinefrina e norepinefrina che, attraverso l’attivazione dei recettori beta-adrenergici (β-AR), svolgono un ruolo critico nella regolazione della funzione del sistema cardiovascolare. Una caratteristica distintiva dello SC è la diminuzione o la desensibilizzazione dei recettori β1-adrenergici (β1-AR) sulla membrana delle cellule cardiache. Le catecolamine e lo stress ossidativo sono coinvolti nella regolazione della densità dei β-AR. Lo stress ossidativo associato alla disfunzione mitocondriale sembra giocare un ruolo importante nella fisiopatologia dello SC. Infatti, una condizione di stress ossidativo è stata osservata sia in pazienti con SC che in modelli animali, e un’eccessiva esposizione a specie reattive dell’ossigeno (ROS) diminuisce l’espressione di β1-AR in cardiomiociti murini, sebbene i meccanismi sottostanti rimangano ancora non chiari. Recentemente, è stato scoperto che il recettore periferico delle benzodiazepine (PBR) svolge un ruolo chiave oltre che nell’energetica cellulare, nella regolazione della fisiologia mitocondriale e dell’equilibrio redox nei cardiomiociti. Nel presente studio, abbiamo valutato gli effetti delle catecolamine e dei ligandi del PBR sulla densità dei β1- e β2-AR nei monociti umani isolati da sangue periferico, che sono noti per esprimere entrambi i β-AR. La densità dei β-AR è stata misurata mediante citometria a flusso utilizzando anticorpi selettivi diretti contro un epitopo extracellulare di β1-AR o β2-AR. Il trattamento dei monociti con benzodiazepine induceva una riduzione della densità del β1-AR, ma non del β2-AR, sulla membrana dei monociti che veniva ripristinata utilizzando [1-(2-chlorophenyl)-N-methyl-(1-meth-ylpropyl)-3 isoquinolinecarboxamide] (PK11195), un antagonista del PBR. Questi risultati suggeriscono un possibile ruolo del PBR nella regolazione della densità del β1-AR proponendo i monociti isolati dal sangue periferico sia come modello in vitro utile per lo studio del sistema recettoriale β-adrenergico che come potenziali biomarcatori di progressione della malattia e risposta alla terapia.

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Hauck, Fabian. "Angeborene autoinflammatorische Störungen der cGAS-STING- und OASRNase-L-vermittelten Nukleinsäure-Immunität." Translationale Immunologie 5, no. 3 (October 28, 2021): 160–65. http://dx.doi.org/10.47184/ti.2021.03.04.

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Typ-I-Interferonopathien sind autoinflammatorische Störungen der angeborenen Nukleinsäure-Immunität, die zusätzlich zu Epitop-spezifischer Autoimmunität prädispositionieren. In der Immunbiologie ist die Nukleinsäure-Immunität vermittelt durch die cGAS-STING- und OAS-RNase-L-Signalwege weitgehend verstanden. In der translationellen und klinischen Immunologie zeigen angeborene Störungen dieser Signalwege deren physiologische Relevanz an der Schnittstelle zwischen Selbst- und Fremd-Nukleinsäure-Erkennung und führen zu einem neuen Verständnis von seit Langem bekannten Krankheitsbildern. Dieser Übersichtsartikel fasst aktuelle pathophysiologische Konzepte und deren klinische Implikationen zur unkontrollierten cGAS- und OAS1-Aktivierung durch biallelische LSM11 und RNU7-1-loss-of-function-, monoallelische ATAD3A dominant-negative und monoallelische OAS1-gain-of-function-Varianten zusammen. Eine murine monoallelische dominante Oas2-Variante wird als Modell für eine mögliche Organ-spezifische humane Typ-I-Interferonopathie diskutiert.

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Pozo, M. A., N. Hernández-Martín, P. Bascuñana, R. Fernández de la Rosa, F. Gómez, E. D. Martín, and L. García-García. "Experimental models in the study of epileptogenesis." ANALES RANM 139, no. 139(02) (August 2022): 140–49. http://dx.doi.org/10.32440/ar.2022.139.02.rev04.

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Epilepsy is a chronic neurological disease characterized by spontaneous recurrently occurring epileptic seizures as a consequence of abnormal, excessive and synchronous neuronal activity in the brain. Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy in adults, being characterized by hippocampal sclerosis, reactive gliosis, neurodegeneration, and synaptic reorganization. Animal models of TLE based on the administration of convulsive agents trigger a status epilepticus (SE) that progresses towards the occurrence of spontaneous recurrent seizures. Among these models are those induced by the systemic administration of pilocarpine or by intrahippocampal injection of kainic acid, both being characterized by 3 clearly defined phases: (i) acute SE seizures; (ii) latent period and (iii) occurrence of recurrent spontaneous seizures. These models not only reproduce most of the neuropathological TLE features but also allow for the identification of biomarkers of epileptogenesis and potential pharmacological targets. The use of neuroimaging techniques such as positron emission tomography (PET) with the radiotracer 18F-Fluorodeoxyglucose (18F-FDG) identifies brain hypometabolism in the latent period that not only localizes the epileptic focus but is also an biomarker of early diagnosis. Other neuroimaging techniques allow for detecting, among others, biomarkers of neuroinflammation, alterations in the permeability of the blood-brain barrier and astrocytic activation, all of them associated with epileptogenesis. Finally, the use of chemogenetics through DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) technology in murine models leads to targeted modulation of astrocytic activity, being a novel tool that considers the contribution of the astrocytes role in brain metabolic alterations in epileptogenesis.

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4

Javazon, Elisabeth H., Mohamed Radhi, Bagirath Gangadharan, Jennifer Perry, and David R. Archer. "Hematopoietic Stem Cell Function in a Murine Model of Sickle Cell Disease." Anemia 2012 (2012): 1–9. http://dx.doi.org/10.1155/2012/387385.

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Previous studies have shown that the sickle environment is highly enriched for reactive oxygen species (ROS). We examined the oxidative effects of sickle cell disease on hematopoietic stem cell function in a sickle mouse model.In vitrocolony-forming assays showed a significant decrease in progenitor colony formation derived from sickle compared to control bone marrow (BM). Sickle BM possessed a significant decrease in the KSL (c-kit+, Sca-1+, Lineage−) progenitor population, and cell cycle analysis showed that there were fewer KSL cells in the G0phase of the cell cycle compared to controls. We found a significant increase in both lipid peroxidation and ROS in sickle-derived KSL cells.In vivoanalysis demonstrated that normal bone marrow cells engraft with increased frequency into sickle mice compared to control mice. Hematopoietic progenitor cells derived from sickle mice, however, demonstrated significant impairment in engraftment potential. We observed partial restoration of engraftment by n-acetyl cysteine (NAC) treatment of KSL cells prior to transplantation. Increased intracellular ROS and lipid peroxidation combined with improvement in engraftment following NAC treatment suggests that an altered redox environment in sickle mice affects hematopoietic progenitor and stem cell function.

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5

Guo, Beining, Kamilia Abdelraouf, Kimberly R. Ledesma, Kai-Tai Chang, Michael Nikolaou, and Vincent H. Tam. "Quantitative Impact of Neutrophils on Bacterial Clearance in a Murine Pneumonia Model." Antimicrobial Agents and Chemotherapy 55, no. 10 (August 1, 2011): 4601–5. http://dx.doi.org/10.1128/aac.00508-11.

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ABSTRACTThe rapid increase in the prevalence of antibiotic-resistant pathogens is a global problem that has challenged our ability to treat serious infections. Currently, clinical decisions on treatment are often based onin vitrosusceptibility data. The role of the immune system in combating bacterial infections is unequivocal, but it is not well captured quantitatively. In this study, the impact of neutrophils on bacterial clearance was quantitatively assessed in a murine pneumonia model.In vitrotime-growth studies were performed to determine the growth rate constants ofAcinetobacter baumanniiATCC BAA 747 andPseudomonas aeruginosaPAO1. The absolute neutrophil count in mice resulting from different cyclophosphamide preparatory regimens was determined. The dynamic change of bacterial (A. baumanniiBAA 747) burden in mice with graded immunosuppression over 24 h was captured by a mathematical model. The fit to the data was satisfactory (r2= 0.945). The best-fit maximal kill rate (Kk) of the bacterial population by neutrophils was 1.743 h−1, the number of neutrophils necessary for 50% maximal killing was 190.8/μl, and the maximal population size was 1.8 × 109CFU/g, respectively. Using these model parameter estimates, the model predictions were subsequently validated by the bacterial burden change ofP. aeruginosaPAO1 at 24 h. A simple mathematical model was proposed to quantify the contribution of neutrophils to bacterial clearance and predict the bacterial growth/suppression in animals. Our results provide a novel framework to linkin vitroandin vivoinformation and may be used to improve clinical treatment of bacterial infections.

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van Oers, Nicolai S., Angela Moses, Pratibha Bhalla, Christian Wysocki, Christine Seroogy, M. Louise Markert, and M. Teresa de la Morena. "Characterization of Human FOXN1 Mutations Uncovers both Loss- and Gain-of-Function Outcomes." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 159.10. http://dx.doi.org/10.4049/jimmunol.208.supp.159.10.

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Abstract Thymus hypoplasia is reported for individuals with autosomal recessive, compound heterozygous and single allelic FOXN1 mutations. FOXN1 is the master transcriptional regulator of thymus epithelial cell development. Autosomal recessive mutations in FOXN1 lead to a Nude/SCID phenotype due to the ensuing T cell lymphopenia and impaired hair follicle extrusion. Targeted exome and whole genome sequencing for patients with low TRECs (measure of T cell output) has increased the number of diverse FOXN1 mutations to over 40. The consequence of these FOXN1 mutations on patients is varied and somewhat complicated by some individuals having only a transient delay in T cell development that corrects over time. We compared the functions of the FOXN1 mutants with luciferase reporter assays and nuclear localization experiments. For selected FOXN1 mutations, mice were developed to genocopy these to assess impacts on thymopoiesis. We identify partial and complete loss-of-function mutations along with gain-of-function and dominant negatives. Comparative analyses of murine thymopoiesis reveal some compound het Foxn1 mutations cause a transient thymus hypoplasia while others cause a permanent small thymus. Taken together, our findings establish FOXN1 genotype-phenotype relationships and suggest rapid functional screening approaches can be used to define the impact of different mutations of clinical relevance. Supported by grants from NIH (R01AI114523, R21AI144140) and the Jeffrey Modell Foundation (MdlM, CAW)

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Moreno-Indias, Isabel, Marta Torres, Josep M. Montserrat, Lidia Sanchez-Alcoholado, Fernando Cardona, Francisco J. Tinahones, David Gozal, et al. "Intermittent hypoxia alters gut microbiota diversity in a mouse model of sleep apnoea." European Respiratory Journal 45, no. 4 (December 23, 2014): 1055–65. http://dx.doi.org/10.1183/09031936.00184314.

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We assessed whether intermittent hypoxia, which emulates one of the hallmarks of obstructive sleep apnoea (OSA), leads to altered faecal microbiome in a murine model.In vivo partial pressure of oxygen was measured in colonic faeces during intermittent hypoxia in four anesthetised mice. 10 mice were subjected to a pattern of chronic intermittent hypoxia (20 s at 5% O2 and 40 s at room air for 6 h·day−1) for 6 weeks and 10 mice served as normoxic controls. Faecal samples were obtained and microbiome composition was determined by 16S rRNA pyrosequencing and bioinformatic analysis by Quantitative Insights into Microbial Ecology.Intermittent hypoxia exposures translated into hypoxia/re-oxygenation patterns in the faeces proximal to the bowel epithelium (<200 μm). A significant effect of intermittent hypoxia on global microbial community structure was found. Intermittent hypoxia increased the α-diversity (Shannon index, p<0.05) and induced a change in the gut microbiota (ANOSIM analysis of β-diversity, p<0.05). Specifically, intermittent hypoxia-exposed mice showed a higher abundance of Firmicutes and a smaller abundance of Bacteroidetes and Proteobacteria phyla than controls.Faecal microbiota composition and diversity are altered as a result of intermittent hypoxia realistically mimicking OSA, suggesting the possibility that physiological interplays between host and gut microbiota could be deregulated in OSA.

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8

Wahlsten, Adam, Marco Pensalfini, Alberto Stracuzzi, Gaetana Restivo, Raoul Hopf, and Edoardo Mazza. "On the compressibility and poroelasticity of human and murine skin." Biomechanics and Modeling in Mechanobiology 18, no. 4 (February 26, 2019): 1079–93. http://dx.doi.org/10.1007/s10237-019-01129-1.

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9

Wehr, Claudia, Julia Schüler, Claudia Nitschke, Kerstin Klingner, Fabian Müller, Heinz-Herbert Fiebig, Roland H. Mertelsmann, and Martin Trepel. "In Vivo Efficacy of Peptide-Derived B Cell Receptor (BCR) Targeted Therapy In a Disseminated Burkitt′s Lymphoma Xenograft Modell." Blood 116, no. 21 (November 19, 2010): 3924. http://dx.doi.org/10.1182/blood.v116.21.3924.3924.

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Abstract Abstract 3924 Targeted therapies in terms of monoclonal antibodies have become standard in the treatment of various lymphomas. Albeit being more specific than conventional therapy, the used antibodies target surface receptors both present on polyclonal and monoclonal hematopoietic cells. Due to its specificity for the malignant B-cell clone the B-cell receptor (BCR) is an ideal therapeutic target in lymphoma therapy. Moreover, using peptides has several advantages over whole antibodies: reduced immunogenicity, better epitope mimicry and tissue penetration, easier synthesis and more favourable pharmacokinetics (no uptake into the reticulo-endothelial system). Peptides mimicking the epitope recognized by lymphoma BCRs have therefore been praised as promising therapeutic tools for years (Lam, West J Med., 1993) but a proof-of-concept has only been published recently in mice bearing subcutaneous A20 lymphoma (Palmieri et al., Blood, 2010). In the current study, we have established a human cell line-derived disseminated Burkitt′s lymphoma model (SUP-B8) in NOD/SCID mice by intravenous injection. Our active principle was the tetramerized BCR binding peptide YSFEDLYRRGGK-biotin (termed T-peptide, Renschler et al., PNAS, 1994) which was applied intravenously on day (d) 12, 14, 16 and 19 after injection of the tumor cells, respectively. The therapeutic efficacy was evaluated in comparison to several control groups (tetramerized control peptide (termed C-peptide, RDYSYERLFGGK-biotin), vehicle (0.8% ACN in water, 200μl/d) and untreated animals). Tumor cell engraftment was monitored via daily surveillance of disease symptoms, FACS (anti-human lambda, CD19, anti-murine CD45) and fluorescence-based in vivo imaging system (FI, Kodak FX, Alexa750 labeled anti-human CD45) on days 12 and 21. SUP-B8 engrafted predominantly in the bone marrow (BM, take rate = 100%) and marrow infiltration increased in untreated mice between start and end of therapy from 1 ± 0.4% (d 12) to 39.8 ± 9.4% (d 21). Other sites of engraftment were subcutis (38%) and spleen (8%). The examined compounds were well tolerated in tumor-bearing mice, no acute toxicity could be observed and maximal body weight loss was below 15%. Treatment of xenograft mice with the tetramerized BCR-binding peptide significantly reduced bone marrow infiltration compared to controls (T-peptide 8.1 ± 4.6%, C-peptide: 32.8 ± 8%, p=0.037, vehicle: 30.5 ± 7.9%, p=0.029). Considering the short half-life of uncoupled peptides and the injection schedule every second day, this is a remarkable reduction. For further optimization of this promising therapeutic approach we plan to couple peptides to effector molecules via acid labile linkers; this is based on the evidence that confocal imaging of Burkitt lymphoma cell lines showed the processing of specific BCR binding peptides in acidic organelles of the cell. In summary, we conclude that BCR targeted peptide-based therapy is a feasible method with remarkable therapeutic results in vivo and future studies will focus on coupling specific peptides to appropriate effector molecules or combinational therapeutic approaches using conventional chemotherapeutics. Disclosures: No relevant conflicts of interest to declare.

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10

Puxeddu, Efisio. "La combinazione di un inibitore di BRAF e di un anticorpo anti-PD-L1 potenzia drammaticamente la regressione tumorale e l’immunità anti-tumorale in un modello murino immunocompetente di carcinoma anaplastico della tiroide." L'Endocrinologo 17, no. 6 (December 2016): 334–35. http://dx.doi.org/10.1007/s40619-016-0254-2.

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11

Bersi, Matthew R., Chiara Bellini, Jay D. Humphrey, and Stéphane Avril. "Local variations in material and structural properties characterize murine thoracic aortic aneurysm mechanics." Biomechanics and Modeling in Mechanobiology 18, no. 1 (September 24, 2018): 203–18. http://dx.doi.org/10.1007/s10237-018-1077-9.

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Emadi, Alireza, Sarvin Zamanzad-Ghavidel, Reza Sobhani, and Ali Rashid-Niaghi. "Multivariate modeling of groundwater quality using hybrid evolutionary soft-computing methods in various climatic condition areas of Iran." Journal of Water Supply: Research and Technology-Aqua 70, no. 3 (March 10, 2021): 328–41. http://dx.doi.org/10.2166/aqua.2021.150.

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Abstract In the current study, several soft-computing methods including artificial neural networks (ANNs), adaptive neuro-fuzzy inference system (ANFIS), gene expression programming (GEP), and hybrid wavelet theory-GEP (WGEP) are used for modeling the groundwater's electrical conductivity (EC) variable. Hence, the groundwater samples from three sources (deep well, semi-deep well, and aqueducts), located in six basins of Iran (Urmia Lake (UL), Sefid-rud (SR), Karkheh (K), Kavir-Markazi (KM), Gavkhouni (G), and Hamun-e Jaz Murian (HJM)) with various climate conditions, were collected during 2004–2018. The results of the WGEP model with data de-noising showed the best performance in estimating the EC variable, considering all types of groundwater resources with various climatic conditions. The Root Mean Squared Error (RMSE) values of the WGEP model were varied from 162.068 to 348.911, 73.802 to 171.376, 29.465 to 351.489, 118.149 to 311.798, 217.667 to 430.730, and 76.253 to 162.992 μScm−1 in the areas of UL, SR, K, KM, G, and HJM basins. The WGEP model's performance (R-values) for deep wells, semi-deep wells, and aqueducts of the areas of the KM basin associated with the arid steppe cold (Bsk) dominant climate classification was the best. Also, the WGEP's extracted mathematical equations could be used for EC estimating in other basins.

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Christen, Patrik, Bert van Rietbergen, Floor M. Lambers, Ralph Müller, and Keita Ito. "Bone morphology allows estimation of loading history in a murine model of bone adaptation." Biomechanics and Modeling in Mechanobiology 11, no. 3-4 (July 7, 2011): 483–92. http://dx.doi.org/10.1007/s10237-011-0327-x.

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14

bi, Yuanhong, Quansheng Liu, Lixin Wang, Wuritu Yang, and Xinwei Wu. "Bifurcation and Potential Landscape of p53 Dynamics Depending on PDCD5 Level and ATM Degradation Rate." International Journal of Bifurcation and Chaos 30, no. 09 (July 2020): 2050134. http://dx.doi.org/10.1142/s0218127420501345.

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The dynamic behavior of the tumor suppressor p53 as an important signal in response to various stresses can influence cellular fate decisions. Programmed cell death 5 (PDCD5) and wild type p53-induced phosphatase 1 (Wip1) regulate p53 dynamics as its activator and inhibitor, respectively. In the present study, we add Wip1 to p53-Mdm2 (Murine double minute 2) module with PDCD5 and focus on p53 dynamics depending on PDCD5 and ataxia telangiectasia mutated (ATM) degradation rate regulated by Wip1. The bifurcation results reveal that p53 dynamics varies with these two parameters. p53 exhibits monostability and bistabiltiy for smaller and larger PDCD5 level while p53 shows oscillation or coexistence of oscillation and steady states in a narrow parameter range. These dynamics are further explored by time series and potential landscapes. Our results may be useful for regulating cell fate upon DNA damage.

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15

Yeh, Chen-Hao, Jong-Kai Hsiao, Jaw-Lin Wang, and Fuu Sheu. "Immunological impact of magnetic nanoparticles (Ferucarbotran) on murine peritoneal macrophages." Journal of Nanoparticle Research 12, no. 1 (February 6, 2009): 151–60. http://dx.doi.org/10.1007/s11051-009-9589-y.

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Pissuwan, Dakrong, Stella M. Valenzuela, Murray C. Killingsworth, Xiaoda Xu, and Michael B. Cortie. "Targeted destruction of murine macrophage cells with bioconjugated gold nanorods." Journal of Nanoparticle Research 9, no. 6 (February 13, 2007): 1109–24. http://dx.doi.org/10.1007/s11051-007-9212-z.

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17

Ferreira, G. M. N., K. D. Hammond, and D. A. Gilbert. "Insulin stimulation of high frequency phosphorylation dynamics in murine erythroleukemia cells." Biosystems 33, no. 1 (January 1994): 31–43. http://dx.doi.org/10.1016/0303-2647(94)90059-0.

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18

Damiano, David B., and Melissa R. McGuirl. "A topological analysis of targeted In-111 uptake in SPECT images of murine tumors." Journal of Mathematical Biology 76, no. 6 (October 5, 2017): 1559–87. http://dx.doi.org/10.1007/s00285-017-1184-8.

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19

Kahler, Amy M., Theresa L. Cromeans, Jacquelin M. Roberts, and Vincent R. Hill. "Source water quality effects on monochloramine inactivation of adenovirus, coxsackievirus, echovirus, and murine norovirus." Water Research 45, no. 4 (February 2011): 1745–51. http://dx.doi.org/10.1016/j.watres.2010.11.026.

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Saatchi, Sanaz, Nishey Wanchoo, Junya Azuma, Stephen J. Smith, Philip S. Tsao, Paul G. Yock, and Charles A. Taylor. "The Use of Immunofluorescent Array Tomography to Study the Three-Dimensional Microstructure of Murine Blood Vessels." Cellular and Molecular Bioengineering 4, no. 2 (April 21, 2011): 311–23. http://dx.doi.org/10.1007/s12195-011-0165-z.

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Lara, Giovanna G., Olesja Hazenbiller, Tia Gareau, Robert D. Shepherd, Michael S. Kallos, Derrick E. Rancourt, and Kristina D. Rinker. "Fluid Flow Modulation of Murine Embryonic Stem Cell Pluripotency Gene Expression in the Absence of LIF." Cellular and Molecular Bioengineering 6, no. 3 (July 16, 2013): 335–45. http://dx.doi.org/10.1007/s12195-013-0287-6.

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22

Suzuki, Natsuki, Kazuhiro Aoki, Petr Marcián, Libor Borák, and Noriyuki Wakabayashi. "A threshold of mechanical strain intensity for the direct activation of osteoblast function exists in a murine maxilla loading model." Biomechanics and Modeling in Mechanobiology 15, no. 5 (November 17, 2015): 1091–100. http://dx.doi.org/10.1007/s10237-015-0746-1.

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23

Koivisto, Antti J., Maija Mäkinen, Elina M. Rossi, Hanna K. Lindberg, Mirella Miettinen, Ghita C. M. Falck, Hannu Norppa, et al. "Aerosol characterization and lung deposition of synthesized TiO2 nanoparticles for murine inhalation studies." Journal of Nanoparticle Research 13, no. 7 (January 7, 2011): 2949–61. http://dx.doi.org/10.1007/s11051-010-0186-x.

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24

Clerkin, James, Kate Connor, Kieron White, Kieron Sweeney, Liam Shiels, Thomas Van Brussel, Ingrid Arijs, et al. "MODL-27. PRECLINICAL INTERROGATION OF IMMUNOTHERAPY TREATMENT STRATEGIES IN GLIOBLASTOMA (GBM) USING A CLINICALLY RELEVANT DISEASE MODEL." Neuro-Oncology 24, Supplement_7 (November 1, 2022): vii296—vii297. http://dx.doi.org/10.1093/neuonc/noac209.1154.

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Abstract Clinically faithful pre-clinical models are essential for screening therapies and studying resistance mechanisms. Historically models have failed to predict response in the clinical setting. Current models seldom incorporate surgical resection, and commonly use young animals whose immune contexture differs from older patients. Here, we have established an orthotopic model, employing the syngeneic, mesenchymal-NFpp10a-cell line, in both young and aged mice. We have characterised the model's response to standard of care resection and temozolomide (TMZ) treatment. We have further studied response to anti-PD1 therapy (adjuvant and neoadjuvant). NFpp10a-Luc2 expressing cells were orthotopically implanted into C57BL/6 mice (aged { > 18months} and young {6-8weeks}) and weekly bioluminescence imaging (BLI) performed to monitor tumour growth. Several therapeutic interventions were assessed to study tumour growth and survival: (1)surgical resection, (2)TMZ, (3)anti-PD1 (4)neoadjuvant anti-PD1. RNAseq, murine microenvironment cell population (mMCP) counter and gene ontology analyses characterised treatment related changed in the TME. We demonstrated survival advantage in aged mice undergoing resection (Resection:33.5 days vs Non-Resection:18 days;p=0.0166). Subsequently, we observed that TMZ and anti-PD1 monotherapy had no impact on NFpp10a-Luc2 growth (TMZ-overall:p=0.9001, and anti-PD1-overall:p = 0.7933) or survival (TMZ-overall:p = 0.3035, anti-PD1-overall:p= 0.6328). Neoadjuvant anti-PD1 treated mice demonstrated no survival advantage compared to IgG control (33-days vs 35-days:p = 0.9429). or BLI signal (p = 0.1703). NFpp10a-Luc2 forms immune-cold TME relative to commonly employed models. mMCP counter analysis demonstrates neoadjuvant anti-PD1 induced influx of CD8+-T cells, B cells, and monocytes into the TME compared to IgG control, and was associated with significantly upregulated CXCR3 chemokine receptor binding pathway on gene ontology analysis (p = 0.0045). Overall, we have, for the first time established and characterised response of the NFpp10a-Luc2-C57BL/6 model to resection, TMZ and anti-PD1 therapies. NFpp10a-Luc2 tumours demonstrate similar therapeutic resistance and TME profile compared to human mesenchymal GBM. The model may therefore be employed in future pre-clinical studies to guide clinical trials in mesenchymal GBM.

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Mochan, Ericka, David Swigon, G. Bard Ermentrout, Sarah Lukens, and Gilles Clermont. "A mathematical model of intrahost pneumococcal pneumonia infection dynamics in murine strains." Journal of Theoretical Biology 353 (July 2014): 44–54. http://dx.doi.org/10.1016/j.jtbi.2014.02.021.

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26

Ferreira, G. M. N., K. D. Hammond, and D. A. Gilbert. "Oscillatory variations in the amount of protein extractable from murine erythroleukemia cells: stimulation by insulin." Biosystems 32, no. 3 (January 1994): 183–90. http://dx.doi.org/10.1016/0303-2647(94)90041-8.

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Markowetz, Florian, Klaas W. Mulder, Edoardo M. Airoldi, Ihor R. Lemischka, and Olga G. Troyanskaya. "Mapping Dynamic Histone Acetylation Patterns to Gene Expression in Nanog-Depleted Murine Embryonic Stem Cells." PLoS Computational Biology 6, no. 12 (December 16, 2010): e1001034. http://dx.doi.org/10.1371/journal.pcbi.1001034.

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Mikolajewicz, Nicholas, Delaney Smith, Svetlana V. Komarova, and Anmar Khadra. "High-affinity P2Y2 and low-affinity P2X7 receptor interaction modulates ATP-mediated calcium signaling in murine osteoblasts." PLOS Computational Biology 17, no. 6 (June 21, 2021): e1008872. http://dx.doi.org/10.1371/journal.pcbi.1008872.

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The P2 purinergic receptor family implicated in many physiological processes, including neurotransmission, mechanical adaptation and inflammation, consists of ATP-gated non-specific cation channels P2XRs and G-protein coupled receptors P2YRs. Different cells, including bone forming osteoblasts, express multiple P2 receptors; however, how P2X and P2Y receptors interact in generating cellular responses to various doses of [ATP] remains poorly understood. Using primary bone marrow and compact bone derived osteoblasts and BMP2-expressing C2C12 osteoblastic cells, we demonstrated conserved features in the P2-mediated Ca2+ responses to ATP, including a transition of Ca2+ response signatures from transient at low [ATP] to oscillatory at moderate [ATP], and back to transient at high [ATP], and a non-monotonic changes in the response magnitudes which exhibited two troughs at 10−4 and 10−2 M [ATP]. We identified P2Y2 and P2X7 receptors as predominantly contributing to these responses and constructed a mathematical model of P2Y2R-induced inositol trisphosphate (IP3) mediated Ca2+ release coupled to a Markov model of P2X7R dynamics to study this system. Model predictions were validated using parental and CRISPR/Cas9-generated P2Y2 and P2Y7 knockouts in osteoblastic C2C12-BMP cells. Activation of P2Y2 by progressively increasing [ATP] induced a transition from transient to oscillatory to transient Ca2+ responses due to the biphasic nature of IP3Rs and the interaction of SERCA pumps with IP3Rs. At high [ATP], activation of P2X7R modulated the response magnitudes through an interplay between the biphasic nature of IP3Rs and the desensitization kinetics of P2X7Rs. Moreover, we found that P2Y2 activity may alter the kinetics of P2X7 towards favouring naïve state activation. Finally, we demonstrated the functional consequences of lacking P2Y2 or P2X7 in osteoblast mechanotransduction. This study thus provides important insights into the biophysical mechanisms underlying ATP-dependent Ca2+ response signatures, which are important in mediating bone mechanoadaptation.

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Husi, Holger, Maria Sanchez-Niño, Christian Delles, William Mullen, Antonia Vlahou, Alberto Ortiz, and Harald Mischak. "A combinatorial approach of Proteomics and Systems Biology in unravelling the mechanisms of acute kidney injury (AKI): involvement of NMDA receptor GRIN1 in murine AKI." BMC Systems Biology 7, no. 1 (2013): 110. http://dx.doi.org/10.1186/1752-0509-7-110.

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Gevertz, Jana L., and Joanna R. Wares. "Developing a Minimally Structured Mathematical Model of Cancer Treatment with Oncolytic Viruses and Dendritic Cell Injections." Computational and Mathematical Methods in Medicine 2018 (October 30, 2018): 1–14. http://dx.doi.org/10.1155/2018/8760371.

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Mathematical models of biological systems must strike a balance between being sufficiently complex to capture important biological features, while being simple enough that they remain tractable through analysis or simulation. In this work, we rigorously explore how to balance these competing interests when modeling murine melanoma treatment with oncolytic viruses and dendritic cell injections. Previously, we developed a system of six ordinary differential equations containing fourteen parameters that well describes experimental data on the efficacy of these treatments. Here, we explore whether this previously developed model is the minimal model needed to accurately describe the data. Using a variety of techniques, including sensitivity analyses and a parameter sloppiness analysis, we find that our model can be reduced by one variable and three parameters and still give excellent fits to the data. We also argue that our model is not too simple to capture the dynamics of the data, and that the original and minimal models make similar predictions about the efficacy and robustness of protocols not considered in experiments. Reducing the model to its minimal form allows us to increase the tractability of the system in the face of parametric uncertainty.

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Lin, Chen, Shaohua Chen, Lijian Yang, Yubo Tan, Xue Bai, and Yangqiu Li. "The Feature of TCR Vβ Subfamily T Cells Expansion in NOD/SCID Mice Transplanted with Human Cord Blood Hematopoietic Stem Cell." Blood 108, no. 11 (November 16, 2006): 3872. http://dx.doi.org/10.1182/blood.v108.11.3872.3872.

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Abstract Reconstitute of functional human lymphocytes in some mouse strains has been intensely explored because this approach could provide a valuable means of assessing human immunity or of preclinical testing of vaccines, pathogens, and new therapeuticstrategies. The NOD/SCID mouse strain was found to be an efficient recipient for the reconstitution of human hematopoietic cells. In these xenogenic transplantation models, growth of human lymphocytes has been demonstrated in bone marrow, peripheral blood and spleen of the mice after i.v. inoculation. These mouse models showed the multilineage differentiation of human hematopoietic cells to varying degrees. Moreover, the engraftment of human hematopoietic cells is highly variable. Complete multilineage differentiation, especially T cells, has not been achieved using this strain. Examination of T cell receptor (TCR) gene repertoire is important to analysis the immune status of models, because clonal expansion of T cells permit the identification of specific antigen response of T cells. Little is known about the feature of T-cell immunity in the humanized NOD/SCID mouse model.In order to investigate the distribution and clonal expansion of TCR Vβsubfamily T cells in NOD/SCID mice transplanted with human cord blood hematopoietic stem cell. TCR Vβ repertoire usage and clonality were analyzed. The NOD/SCID mice were sublethally irradiated (60Co, 300cGy) to eliminate residual innate immunity in the host. The experimental mice were transplanted intravenously with cord blood CD34+ cells sorted by MACS. After 6 weeks, RNA was obtained from peripheral blood, bone marrow, thymus of model. The gene expression and clonality of TCR Vβ repertoire were detected by RT-PCR and GeneScan technique. A certain range of TCR Vβ usage was exhibited in the bone marrow of mice, which included TCR Vβ1, 2, 9, 13, 19. Further, oligoclonal expression of some TCR Vβ subfamilies (Vβ9, 13, 19) were identified by GeneScan technique. To investigate the reason involving oligoclonal expansion of TCR Vβ subfamily T cells from cord blood in mouse models, the T-cell culture with tissue-antigen of NOD/SCID mouse was performed in vitro. The cells from peripheral blood mononuclear cells and bone marrow, spleen, thymus in NOD/SCID mice were wiped off by freeze thawing and served as tissue-antigen. Cord blood mononuclear cells were separately cultured with the component from those murine cells for 15 to 20 days. Oligoclonal expression or oligoclonal trend of some TCR Vβ subfamilies (Vβ10, 11 and Vβ2, 15, 16, 19) was detected in T cells after stimulation with tissue-antigen of NOD/SCID mouse. Interesting, the similar clonal expansion of TCR Vβ11 subfamily was found in T cells cultured with peripheral blood, bone marrow and spleen respectively. The results indicate that the TCR Vβ subfamily T cells could be reconstituted in humanized NOD/SCID mouse transplanted with CD34+cells from cord blood. The restricted expression and clonal expansion of some CB T cell clones might be induced by tissue-antigens of NOD/SCID mice.

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Pinky, Lubna, Crystal W. Burke, Charles J. Russell, and Amber M. Smith. "Quantifying dose-, strain-, and tissue-specific kinetics of parainfluenza virus infection." PLOS Computational Biology 17, no. 8 (August 12, 2021): e1009299. http://dx.doi.org/10.1371/journal.pcbi.1009299.

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Human parainfluenza viruses (HPIVs) are a leading cause of acute respiratory infection hospitalization in children, yet little is known about how dose, strain, tissue tropism, and individual heterogeneity affects the processes driving growth and clearance kinetics. Longitudinal measurements are possible by using reporter Sendai viruses, the murine counterpart of HPIV 1, that express luciferase, where the insertion location yields a wild-type (rSeV-luc(M-F*)) or attenuated (rSeV-luc(P-M)) phenotype. Bioluminescence from individual animals suggests that there is a rapid increase in expression followed by a peak, biphasic clearance, and resolution. However, these kinetics vary between individuals and with dose, strain, and whether the infection was initiated in the upper and/or lower respiratory tract. To quantify the differences, we translated the bioluminescence measurements from the nasopharynx, trachea, and lung into viral loads and used a mathematical model together a nonlinear mixed effects approach to define the mechanisms distinguishing each scenario. The results confirmed a higher rate of virus production with the rSeV-luc(M-F*) virus compared to its attenuated counterpart, and suggested that low doses result in disproportionately fewer infected cells. The analyses indicated faster infectivity and infected cell clearance rates in the lung and that higher viral doses, and concomitantly higher infected cell numbers, resulted in more rapid clearance. This parameter was also highly variable amongst individuals, which was particularly evident during infection in the lung. These critical differences provide important insight into distinct HPIV dynamics, and show how bioluminescence data can be combined with quantitative analyses to dissect host-, virus-, and dose-dependent effects.

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Fayez, R., A. AlMuntashery, G. Bodie, A. Almamar, R. S. Gill, I. Raîche, C. L. Mueller, et al. "Canadian Surgery Forum1 Is laparoscopic sleeve gastrectomy a reasonable stand-alone procedure for super morbidly obese patients?2 Postoperative monitoring requirements of patients with obstructive sleep apnea undergoing bariatric surgery3 Role of relaparoscopy in the diagnosis and treatment of bariatric complications in the early postoperative period4 Changes of active and total ghrelin, GLP-1 and PYY following restrictive bariatric surgery and their impact on satiety: comparison of sleeve gastrectomy and adjustable gastric banding5 Prioritization and willingness to pay for bariatric surgery: the patient perspective6 Ventral hernia at the time of laparoscopic gastric bypass surgery: Should it be repaired?7 Linear stapled gastrojejunostomy with transverse handsewn enterotomy closure significantly reduces strictures for laparoscopic Roux-en-Y bypass8 Laparoscopic biliopancreatic diversion with duodenal switch as second stage for super super morbidly obese patients. Do all patients benefit?9 Sleeve gastrectomy in the super super morbidly obese (BMI > 60 kg/m²): a Canadian experience10 Laparoscopic gastric bypass for the treatment of refractory idiopathic gastroparesis: a report of 2 cases11 Duodeno-ileal switch as a primary bariatric and metabolic surgical option for the severely obese patient with comorbidities: review of a single-institution case series of duodeno-ileal intestinal bypass12 Management of large paraesophageal hernias in morbidly obese patients with laparoscopic sleeve gastrectomy: a case series13 Early results of the Ontario bariatric surgical program: using the bariatric registry14 Improving access to bariatric surgical care: Is universal health care the answer?15 Early and liberal postoperative exploration can reduce morbidity and mortality in patients undergoing bariatric surgery16 Withdrawn17 Identification and assessment of technical errors in laparoscopic Roux-en-Y gastric bypass18 A valid and reliable tool for assessment of surgical skill in laparoscopic Roux-en-Y gastric bypass19 Psychiatric predictors of presurgery drop-out following suitability assessment for bariatric surgery20 Predictors of outcomes following Roux-en-Y gastric bypass surgery at The Ottawa Hospital21 Prophylactic management of cholelithiasis in bariatric patients: Is routine cholecystectomy warranted?22 Early outcomes of Roux-en-Y gastric bypass in a publicly funded obesity program23 Similar incidence of gastrojejunal anastomotic stricture formation with hand-sewn and 21 mm circular stapler techniques during Roux-en-Y gastric bypass24 (CAGS Basic Science Award) Exogenous glucagon-like peptide-1 improves clinical, morphological and histological outcomes of intestinal adaptation in a distal-intestinal resection piglet model of short bowel syndrome25 (CAGS Clinical Research Award) Development and validation of a comprehensive curriculum to teach an advanced minimally invasive procedure: a randomized controlled trial26 Negative-pressure wound therapy (iVAC) on closed, high-risk incisions following abdominal wall reconstruction27 The impact of seed granting on research in the University of British Columbia Department of Surgery28 Quality of surgical care is inadequate for elderly patients29 Recurrence of inguinal hernia in general and hernia specialty hospitals in Ontario, Canada30 Oncostatin M receptor deficiency results in increased mortality in an intestinal ischemia reperfusion model in mice31 Laparoscopic repair of large paraesophageal hernias with anterior gastropexy: a multicentre trial32 Response to preoperative medical therapy predicts success of laparoscopic splenectomy for immune thrombocytopenic purpura33 Perioperative sepsis, but not hemorrhagic shock, promotes the development of cancer metastases in a murine model34 Measuring the impact of implementing an acute care surgery service on the management of acute biliary disease35 Patient flow and efficiency in an acute care surgery service36 The relationship between treatment factors and postoperative complications after radical surgery for rectal cancer37 Risk of ventral hernia after laparoscopic colon surgery38 Urinary metabolomics as a tool for early detection of Barrett’s and esophageal cancer39 Construct validity of individual and summary performance metrics associated with a computer-based laparo-scopic simulator40 Impact of a city-wide health system reorganization on emergency department visits in hospitals in surrounding communities41 Transcatheter aortic valve implantation for the nonoperative management of aortic stenosis: a cost-effectiveness analysis42 Breast cancer: racial differences in age of onset. A potential confounder in Canadian screening recommendations43 Risk taking in surgery: in and out of the comfort zone44 A tumour board in the office: Track those cancer patients!45 Increased patient BMI is not associated with advanced colon cancer stage or grade on presentation: a retrospective chart review46 Consensus statements regarding the multidisciplinary care of limb amputation patients in disasters or humanitarian emergencies. Report of the 2011 Humanitarian Action Summit Surgical Working Group on amputations following disasters or conflict47 Learning the CanMEDS role of professional: a pilot project of supervised discussion groups addressing the hidden curriculum48 Assessing the changing scope of training in Canadian general surgery programs: expected versus actual experience49 Predicting need for surgical management for massive gastrointestinal hemorrhage50 International health care experience: using CanMEDS to evaluate learning outcomes following a surgical mission in Mampong, Ghana51 The open abdomen: risk factors for mortality and rates of closure52 How surgeons think: an exploration of mental practice in surgical preparation53 The surgery wiki: a novel method for delivery of under-graduate surgical education54 Understanding surgical residents’ postoperative practices before implementing an enhanced recovery after surgery (ERAS) guideline at the University of Toronto55 From laparoscopic transabdominal to posterior retroperitoneal adrenalectomy: a paradigm shift in operative approach56 A retrospective audit of outcomes in patients over the age of 80 undergoing acute care abdominal surgery57 Canadian general surgery residents’ perspectives on work-hour regulations58 Timing of surgical intervention and its outcomes in acute appendicitis59 Preparing surgical trainees to deal with adverse events. An outline of learning issues60 Acute care surgical service: surgeon agreement at the time of handover61 Predicting discharge of elderly patients to prehospitalization residence following emergency general surgery62 Morbidity and mortality after emergency abdominal surgery in octo- and nonagenarians63 The impact of acute abdominal illness and urgent admission to hospital on the living situation of elderly patients64 A comparison of laparoscopic versus open subtotal gastrectomy for antral gastric adenocarcinoma: a North American perspective65 Minimally invasive excision of ectopic mediastinal parathyroid adenomas66 Perioperative outcomes of laparoscopic hernia repair in a tertiary care centre: a single institution’s experience67 Evaluation of a student-run, practical and didactic curriculum for preclerkship medical students68 Joseph Lister: Father of Modern Surgery69 Comparisons of melanoma sentinel lymph node biopsy prediction nomograms in a cohort of Canadian patients70 Local experience with myocutaneous flaps after extensive pelvic surgery71 The treatment of noncirrhotic splanchnic vein thrombosis: Is anticoagulation enough?72 Implementation of an acute care surgery service does not affect wait-times for elective cancer surgeries: an institutional experience73 Use of human collagen mesh for closure of a large abdominal wall defect, after colon cancer surgery, a case report74 The role of miR-200b in pulmonary hypoplasia associated with congenital diaphragmatic hernia75 Systematic review and meta-analysis of electrocautery versus scalpel for incising epidermis and dermis76 Accuracy of sentinel lymph node biopsy for early breast cancer in the community setting in St. John’s, New-foundland: results of a retrospective review77 Acute surgical outcomes in the 80 plus population78 The liberal use of platelets transfusions in the acute phase of trauma resuscitation: a systematic review79 Implementation of an acute care surgical on call program in a Canadian community hospital80 Short-term outcomes following paraesophageal hernia repair in the elderly patient81 First experience with single incision surgery: feasibility in the pediatric population and cost evaluation82 The impact of the establishment of an acute care surgery unit on the outcomes of appendectomies and cholecystectomies83 Description and preliminary evaluation of a low-cost simulator for training and evaluation of flexible endoscopic skills84 Tumour lysis syndrome in metastatic colon cancer: a case report85 Acute care surgery service model implementation study at a single institution86 Colonic disasters approached by emergent subtotal and total colectomy: lessons learned from 120 consecutive cases87 Acellular collagen matrix stent to protect bowel anastomoses88 Lessons we learned from preoperative MRI-guided wire localization of breast lesions: the University Health Network (UHN) experience89 Interim cost comparison for the use of platinum micro-coils in the operative localization of small peripheral lung nodules90 Routine barium esophagram has minimal impact on the postoperative management of patients undergoing esophagectomy for esophageal cancer91 Iron deficiency anemia is a common presenting issue with giant paraesophageal hernia and resolves following repair92 A randomized comparison of different ventilation strategies during thoracotomy and lung resection93 The Canadian Lung Volume Reduction Surgery study: an 8-year follow-up94 A comparison of minimally invasive versus open Ivor-Lewis esophagectomy95 A new paradigm in the follow-up after curative resection for lung cancer: minimal-dose CT scan allows for early detection of asymptomatic cancer activity96 Predictors of lymph node metastasis in early esophageal adenocarcinoma: Is endoscopic resection worth the risk?97 How well can thoracic surgery residents operate? Comparing resident and program director opinions98 The impact of extremes of age on short- and long-term outcomes following surgical resection of esophageal malignancy99 Epidermal growth factor receptor targeted gold nanoparticles for the enhanced radiation treatment of non–small cell lung cancer100 Laparoscopic Heller myotomy results in excellent outcomes in all subtypes of achalasia as defined by the Chicago classification101 Neoadjuvant chemoradiation versus surgery in managing esophageal cancer102 Quality of life postesophagectomy for cancer!103 The implementation, evolution and translocation of standardized clinical pathways can improve perioperative outcomes following surgical treatment of esophageal cancer104 A tissue-mimicking phantom for applications in thoracic surgical simulation105 Sublobar resection compared with lobectomy for early stage non–small cell lung cancer: a single institution study106 Not all reviews are equal: the quality of systematic reviews and meta-analyses in thoracic surgery107 Do postoperative complications affect health-related quality of life after video-assisted thoracoscopic lobectomy for patients with lung cancer? A cohort study108 Thoracoscopic plication for palliation of dyspnea secondary to unilateral diaphragmatic paralysis: A worthwhile venture?109 Thoracic surgery experience in Canadian general surgery residency programs110 Perioperative morbidity and pathologic response rates following neoadjuvant chemotherapy and chemoradiation for locally advanced esophageal carcinoma111 An enhanced recovery pathway reduces length of stay after esophagectomy112 Predictors of dysplastic and neoplastic progression of Barrett’s esophagus113 Recurrent esophageal cancer complicated by tracheoesophageal fistula: management by means of palliative airway stenting114 Pancreaticopleural fistula-induced empyema thoracis: principles and results of surgical management115 Prognostic factors of early postoperative mortality following right extended hepatectomy116 Optimizing steatotic livers for transplantation using a cell-penetrating peptide CPP-fused heme oxygenase117 Video outlining the technical steps for a robot-assisted laparoscopic pancreaticoduodenectomy118 Establishment of a collaborative group to conduct innovative clinical trials in Canada119 Hepatic resection for metastatic malignant melanoma: a systematic review and meta-analysis120 Acellular normothermic ex vivo liver perfusion for donor liver preservation121 Pancreatic cancer and predictors of survival: comparing the CA 19–9/bilirubin ratio with the McGill Brisbane Scoring System122 Staged liver resections for bilobar hepatic colorectal metastases: a single centre experience123 Economic model of observation versus immediate resection of hepatic adenomas124 Resection of colorectal liver metastasis in the elderly125 Acceptable long-term survival in patients undergoing liver resection for metastases from noncolorectal, non-neuroendocrine, nonsarcoma malignancies126 Patient and clinicopathological features and prognosis of CK19+ hepatocellular carcinomas: a case–control study127 The management of blunt hepatic trauma in the age of angioembolization: a single centre experience128 Liver resections for noncolorectal and non-neuroendocrine metastases: an evaluation of oncologic outcomes129 Developing an evidence-based clinical pathway for patients undergoing pancreaticoduodenectomy130 Hepatitis C infection and hepatocellular carcinoma in liver transplant: a 20 year experience131 The effect of medication on the risk of post-ERCP pancreatitis132 Temporal trends in the use of diagnostic imaging for patients with hepato-pancreato-biliary (HPB) conditions: How much ionizing radiation are we really using?196 A phase II study of aggressive metastasectomy for intra-and extrahepatic metastases from colorectal cancer133 Why do women choose mastectomy for breast cancer treatment? A conceptual framework for understanding surgical decision-making in early-stage breast cancer134 Synoptic operative reporting: documentation of quality of care data for rectal cancer surgery135 Learning curve analysis for cytoreductive surgery: a useful application of the cumulative sum (CUSUM) method136 Pancreatic cancer is strongly associated with a unique urinary metabolomic signature137 Concurrent neoadjuvant chemo/radiation in locally advanced breast cancer138 Impact of positron emission tomography on clinical staging of newly diagnosed rectal cancer: a specialized single centre retrospective study139 An evaluation of intraoperative Faxitron microradiography versus conventional specimen radiography for the excision of nonpalpable breast lesions140 Comparison of breast cancer treatment wait-times in the Southern Interior of British Columbia in 2006 and 2010141 Factors affecting lymph nodes harvest in colorectal carcinoma142 Laparoscopic adrenalectomy for metastases143 You have a message! Social networking as a motivator for fundamentals of laparoscopic surgery (FLS) training144 The evaluation and validation of a rapid diagnostic and support clinic for women assessment for breast cancer145 Oncoplastic breast surgery: oncologic benefits and limitations146 A qualitative study on rectal cancer patients’ preferences for location of surgical care147 The effect of surgery on local recurrence in young women with breast cancer148 Elevated IL-6 and IL-8 levels in tumour microenvironment is not associated with increased serum levels in humans with Pseudomyxoma peritonei and peritoneal mesothelioma149 Conversion from laparoscopic to open approach during gastrectomy: a population-based analysis150 A scoping review of surgical process improvement tools (SPITs) in cancer surgery151 Splenectomy during gastric cancer surgery: a population-based study152 Defining the polo-like kinase 4 (Plk4) interactome in cancer cell protrusions153 Neoadjuvant imatinib mesylate for locally advanced gastrointestinal stromal tumours154 Implementing results from ACOSOG Z0011: Practice-changing or practice-affirming?155 Should lymph node retrieval be a surgical quality indicator in colon cancer?156 Long-term outcomes following resection of retroperitoneal recurrence of colorectal cancer157 Clinical research in surgical oncology: an analysis of clinicaltrials.gov158 Radiation therapy after breast conserving surgery: When are we missing the mark?159 The accuracy of endorectal ultrasound in staging rectal lesions in patients undergoing transanal endoscopic microsurgery160 Quality improvement in gastrointestinal cancer surgery: expert panel recommendations for priority research areas161 Factors influencing the quality of local management of ductal carcinoma in situ: a cohort study162 Papillary thyroid microcarcinoma: Does size matter?163 Hyperthermic isolated limb perfusion for extremity soft tissue sarcomas: systematic review of clinical efficacy and quality assessment of reported trials164 Adherence to antiestrogen therapy in seniors with breast cancer: How well are we doing?165 Parathyroid carcinoma: Challenging the surgical dogma?166 A qualitative assessment of the journey to delayed breast reconstruction195 The role of yoga therapy in breast cancer patients167 Outcomes reported in comparative studies of surgical interventions168 Enhanced recovery pathways decrease length of stay following colorectal surgery, but how quickly do patients actually recover?169 The impact of complications on bed utilization after elective colorectal resection170 Impact of trimodal prehabilitation program on functional recovery after colorectal cancer surgery: a pilot study171 Complex fistula-in-ano: Should the plug be abandoned in favour of the LIFT or BioLIFT?172 Prognostic utility of cyclooxygenase-2 expression by colon and rectal cancer173 Laparoscopic right hemicolectomy with complete mesocolic excision provides acceptable perioperative outcomes but is complex and time-consuming: analysis of learning curves for a novice minimally invasive surgeon174 Intraoperative quality assessment following double stapled circular colorectal anastomosis175 Improving patient outcomes through quality assessment of rectal cancer care176 Are physicians willing to accept a decrease in treatment effectiveness for improved functional outcomes for low rectal cancer?177 Turnbull-Cutait delayed coloanal anastomosis for the treatment of distal rectal cancer: a prospective cohort study178 Preoperative high-dose rate brachytherapy in preparation for sphincter preservation surgery for patients with advanced cancer of the lower rectum179 Impact of an enhanced recovery program on short-term outcomes after scheduled laparoscopic colon resection180 The clinical results of the Turnbull-Cutait delayed coloanal anastomosis: a systematic review181 Is a vertical rectus abdominus flap (VRAM) necessary? An analysis of perineal wound complications182 Fistula plug versus endorectal anal advancement flap for the treatment of high transsphincteric cryptoglandular anal fistulas: a systematic review and meta-analysis183 Maternal and neonatal outcomes following colorectal cancer surgery184 Transanal drainage to treat anastomotic leaks after low anterior resection for rectal cancer: a valuable option185 Trends in colon cancer in Ontario: 2002–2009186 Validation of electronically derived short-term outcomes in colorectal surgery187 A population-based assessment of transanal and endoscopic resection for adenocarcinoma of the rectum188 Laparoscopic colorectal surgery in the emergency setting: trends in the province of Ontario from 2002 to 2009189 Prevention of perineal hernia after laparoscopic and robotic abdominoperineal resection: review with case series of internal hernia through pelvic mesh which was placed in attempt to prevent perineal hernia190 Effect of rectal cancer treatments on quality of life191 The use of antibacterial sutures as an adjunctive preventative strategy for surgical site infection in Canada: an economic analysis192 Impact of socioeconomic status on colorectal cancer screening and stage at presentation: preliminary results of a population-based study from an urban Canadian centre193 Initial perioperative results of the first transanal endoscopic microsurgery (TEM) program in the province of Quebec194 Use of negative pressure wound therapy decreases perineal wound infections following abdominal perineal resection." Canadian Journal of Surgery 55, no. 4 Suppl 1 (August 2012): S63—S135. http://dx.doi.org/10.1503/cjs.016712.

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Scherf, Wiebke, G??nther Richter, Jana Bergmann, Stefan Burdach, and Gesine Hansen. "Nasal DNA vaccination with an Interleukin-10 cDNA vector in a murine asthma modell." GBM Annual Fall meeting Halle 2002 2002, Fall (September 2002). http://dx.doi.org/10.1240/sav_gbm_2002_h_000219.

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Köse, Şükran, Tuba Tatlı Kış, Gülden Diniz, İlkay Akbulut, Başak Göl Serin, Canberk Yılmaz, Mine Özyazıcı, Mesut Arıcı, Aysu Yurdasiper, and Osman Yılmaz. "A New Experimental Allergic Rhinitis Model in Mice." Journal of Dr. Behcet Uz Children s Hospital, 2021. http://dx.doi.org/10.5222/buchd.2021.86658.

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Objective: Allergic rhinitis (AR) is an inflammatory disease of the nasal mucosa mediated by IgE after exposure to an allergen. The most well known related comorbidity of AR is asthma. This study was planned due to the need for an animal model for studies on AR-asthma coexistence. In this study, the frequency of AR accompanying in the asthma model created in mice,and the usability of the related model in AR studies will be investigated. Methods: In our study, 6-8 week-old, 18-20 g BALB/c mice were used. Chicken egg ovalbumin (OVA Grade V, Sigma) was administered through intraperitoneal (IP) route at doses of 10 μg on days 0 and 14. Mice were exposed to aerosolized 2.5% ovalbumin solution in sterile saline for 30 minutes 3 days a week for 8 weeks, starting 7 days after the last IP administration (21st day). After exposure to OVA, mice were observed for typical signs of AR including sneezing, runny nose, and nasal itching. The final diagnosis of AR was made by histopathological examination of the rhinotracheal tissues of mice. Results: In our study, all mice exposed to ovalbumin received histopathologic diagnosis of AR. Increased number of capillaries lymphocytes, polymorphonuclear leukocytes and eosinophilsper square millimetre of rhinotracheal tissues were calculated in the murine model of AR compared to the the control group. Conclusion: This study introduced a new AR model, not cited in the literature, and induced with the longest-term ovalbumin exposure in the literature. It was concluded that this model, known as the asthma model, can also be used to induce an AR model and can be used in studies investigating coexistence of allergic rhinitis and asthma.

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Ngamskulrungroj, Popchai, Yun Chang, Edward Sionov, and Kyung J. Kwon-Chung. "The Primary Target Organ of Cryptococcus gattii Is Different from That of Cryptococcus neoformans in a Murine Model." mBio 3, no. 3 (May 8, 2012). http://dx.doi.org/10.1128/mbio.00103-12.

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ABSTRACTCryptococcosis is caused by the opportunistic pathogenCryptococcus neoformansor by the primary pathogenCryptococcus gattii. Epidemiological studies suggest that patients infected withC. gattiimainly present with pulmonary disease, while those infected withC. neoformanscommonly manifest meningoencephalitis. We compared the pathogenesis of the two species using theC. neoformansH99 andC. gattiiR265 strains in a murine inhalation model.C. neoformansgrew faster in the brain and caused death by meningoencephalitis, whileC. gattiigrew faster in the lungs and caused death without producing fulminating meningoencephalitis. Despite the consistent failure to recover R265 cells from blood, a fraction of the R265 population was detected in the extrapulmonary organs, including the brain. Upon intravenous (i.v. ) inoculation of 104cells via the tail vein, however,C. gattiiproduced severe meningoencephalitis, demonstrating thatC. gattiicells can efficiently cross the blood-brain barrier. Interestingly, i.v. inoculation with five cells caused brain infection in only 10% ofC. gattii-infected mice, compared to 60% of mice infected withC. neoformans. In mice that had been initially inoculated via the pulmonary route and subsequently challenged intravenously, a protective effect was observed only in mice infected withC. gattii.C. neoformanscells grew 10 to 100 times faster thanC. gattiicells in blood or serum collected from naive mice. The paucity of meningoencephalitis upon inhalation ofC. gattii, therefore, may be partly due to an unknown factor(s) in the host’s blood coupled with immune protection that reduces dissemination to the brain and fosters lung infection.IMPORTANCEWhileCryptococcus neoformansis the most common cause of fatal meningoencephalitis, especially in HIV patients,Cryptococcus gattiicauses disease mainly in non-HIV patients. Clinical studies revealed that most patients infected withC. gattiiVGII strains have lung infections with minimal brain involvement. Despite extensive clinicopathological studies on cryptococcosis in animal models, only a few have includedC. gattii. We compared the pathogenesis of the two species in mice using an inhalation model. Similar to infection in humans, even thoughC. gattiican cross the blood-brain barrier, it failed to cause fatal meningoencephalitis but caused fatal lung infection. We show that growth ofC. gattiiin mouse blood is significantly slower than that ofC. neoformansand that a secondary protective phenomenon, though weak, manifests itself only inC. gattiiinfection. Our study provides a model for understanding the clinicopathological differences between these two closely genetically related pathogens.

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Pike, Daniel, Yan-Ting Shiu, Maheshika Somarathna, Lingling Guo, Tatyana Isayeva, John Totenhagen, and Timmy Lee. "High resolution hemodynamic profiling of murine arteriovenous fistula using magnetic resonance imaging and computational fluid dynamics." Theoretical Biology and Medical Modelling 14, no. 1 (March 20, 2017). http://dx.doi.org/10.1186/s12976-017-0053-x.

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Pike, Daniel, Yan-Ting Shiu, Maheshika Somarathna, Lingling Guo, Tatyana Isayeva, John Totenhagen, and Timmy Lee. "Correction to: High resolution hemodynamic profiling of murine arteriovenous fistula using magnetic resonance imaging and computational fluid dynamics." Theoretical Biology and Medical Modelling 16, no. 1 (April 9, 2019). http://dx.doi.org/10.1186/s12976-019-0104-6.

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Upadhya, Rajendra, Lorina G. Baker, Woei C. Lam, Charles A. Specht, Maureen J. Donlin, and Jennifer K. Lodge. "Cryptococcus neoformansCda1 and Its Chitin Deacetylase Activity Are Required for Fungal Pathogenesis." mBio 9, no. 6 (November 20, 2018). http://dx.doi.org/10.1128/mbio.02087-18.

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ABSTRACTChitin is an essential component of the cell wall ofCryptococcus neoformansconferring structural rigidity and integrity under diverse environmental conditions. Chitin deacetylase genes encode the enyzmes (chitin deacetylases [Cdas]) that deacetylate chitin, converting it to chitosan. The functional role of chitosan in the fungal cell wall is not well defined, but it is an important virulence determinant ofC. neoformans. Mutant strains deficient in chitosan are completely avirulent in a mouse pulmonary infection model.C. neoformanscarries genes that encode three Cdas (Cda1, Cda2, and Cda3) that appear to be functionally redundant in cells grown under vegetative conditions. Here we report thatC. neoformansCda1 is the principal Cda responsible for fungal pathogenesis. Point mutations were introduced in the active site of Cda1 to generate strains in which the enzyme activity of Cda1 was abolished without perturbing either its stability or localization. When used to infect CBA/J mice, Cda1 mutant strains produced less chitosan and were attenuated for virulence. We further demonstrate thatC. neoformansCda genes are transcribed differently during a murine infection from what has been measuredin vitro.IMPORTANCECryptococcus neoformansis unique among fungal pathogens that cause disease in a mammalian host, as it secretes a polysaccharide capsule that hinders recognition by the host to facilitate its survival and proliferation. Even though it causes serious infections in immunocompromised hosts, reports of infection in hosts that are immunocompetent are on the rise. The cell wall of a fungal pathogen, its synthesis, composition, and pathways of remodelling are attractive therapeutic targets for the development of fungicides. Chitosan, a polysaccharide in the cell wall ofC. neoformansis one such target, as it is critical for pathogenesis and absent in the host. The results we present shed light on the importance of one of the chitin deacetylases that synthesize chitosan during infection and further implicates chitosan as being a critical factor for the pathogenesis ofC. neoformans.

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Joseph, Susan, Joseph Aduse-Opoku, Ahmed Hashim, Eveliina Hanski, Ricarda Streich, Sarah C. L. Knowles, Amy B. Pedersen, William G. Wade, and Michael A. Curtis. "A 16S rRNA Gene and Draft Genome Database for the Murine Oral Bacterial Community." mSystems 6, no. 1 (February 23, 2021). http://dx.doi.org/10.1128/msystems.01222-20.

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Mouse model studies are frequently used in oral microbiome research, particularly to investigate diseases such as periodontitis and caries, as well as other related systemic diseases. We have reported here the details of the development of a curated reference database to characterize the oral microbial community in laboratory and some wild mice.

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Field, Sarah L., Tathagata Dasgupta, Michele Cummings, Richard S. Savage, Julius Adebayo, Hema McSara, Jeremy Gunawardena, and Nicolas M. Orsi. "Bayesian modeling suggests that IL-12 (p40), IL-13 and MCP-1 drive murine cytokine networks in vivo." BMC Systems Biology 9, no. 1 (November 9, 2015). http://dx.doi.org/10.1186/s12918-015-0226-3.

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Munguia-Lopez, Jose G., Rodrigo Juarez, Emilio Muñoz-Sandoval, Marco A. Kalixto-Sanchez, Joseph Matthew Kinsella, and Antonio De Leon-Rodriguez. "Biocompatibility of nitrogen-doped multiwalled carbon nanotubes with murine fibroblasts and human hematopoietic stem cells." Journal of Nanoparticle Research 21, no. 8 (August 2019). http://dx.doi.org/10.1007/s11051-019-4637-8.

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