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Emphysema is a respiratory disease that causes the progressive loss of lung extracellular matrix (ECM) organisation, subsequently undermining lung integrity and reducing lung function. Fibroblasts must constantly repair damage to the lungs to preserve lung health, however, fibroblast ECM repair is reduced during emphysema, causing ECM damage to outweigh fibroblast ECM maintenance. Current treatments for emphysema fail to address the root causes of emphysematous progression, highlighting the need for novel methods of treating emphysema. Nitrofurantoin is a broad-spectrum antibiotic indicated for the treatment of urinary tract infections that also displays potential as a novel avenue of emphysema treatment. Nitrofurantoin is known to potentially cause fibrotic effects that could be repurposed to increase fibroblast repair and outweigh the progressive ECM damage of the emphysematous lung. Therefore, this study examined the effects of nitrofurantoin treatment on primary human lung fibroblasts derived from emphysema patients to determine if the drug holds potential as a novel treatment for emphysema. Nitrofurantoin was shown to stimulate migration and alter fibroblast morphology by increasing cell area and reducing roundness, suggesting that it could induce an ECM-repair primed phenotype in fibroblasts. Interestingly, nitrofurantoin treatment did not alter collagen-IV, perlecan, periostin or tenascin-C deposition, though fibronectin deposition was significantly upregulated at a higher dosage (20 μg/mL). This study highlighted the nitrofurantoin induced changes to fibroblast motility and morphology that facilitate ECM repair. Thus, nitrofurantoin induced pulmonary fibrosis could be caused by a change in cell phenotype that subsequently upregulates ECM repair, indicating its potential as a treatment for emphysema.

Factors defining wheat stem rust pathogen (Pgt) virulence remain poorly characterized. Comparative population genomics based on Pgt haplotypes suggest that structural variation and admixture through somatic hybridization and sexual recombination play an important role in broadening Pgt virulence.

Brillouin microscopy has recently emerged as a new bio-imaging modality that provides information on the microscale mechanical properties of biological materials, cells and tissues. The data collected in a typical Brillouin microscopy experiment represents the high-dimensional set of spectral information, i.e. each pixel within a 2D/3D Brillouin image is associated with hundreds of points of spectral data. Its analysis requires non-trivial approaches due to subtlety in spectral variations as well as spatial and spectral overlaps of measured features. This article offers a guide to the application of Principal Component Analysis (PCA) for processing Brillouin imaging data. Being unsupervised multivariate analysis, PCA is well-suited to tackle processing of complex Brillouin spectra from heterogeneous biological samples with minimal a priori information requirements. We point out the importance of data pre-processing steps in order to improve outcomes of PCA. We also present a strategy where PCA combined with k -means clustering method can provide a working solution to data reconstruction and deeper insights into sample composition, structure and mechanics.

Strongyloides colitis is a gastrointestinal manifestation of the parasitic infection, Strongyloides stercoralis , which may be misdiagnosed and treated as ulcerative colitis (UC) in patients presenting in non-endemic regions. Treatment of Strongyloides colitis as UC can lead to a lethal hyperinfection syndrome. Therefore, prior to commencing immunosuppressive treatment of UC, it is essential to use diagnostic markers to differentiate the two etiologies. In this case series, we discuss two migrant patients who were previously diagnosed with UC and treated accordingly who presented to our clinic for further investigation of suspected parasitic infection.

In this study, two-phase non-Newtonian turbulent fluid flow in an inclined geothermal pipe with chemical reaction was considered. The governing nonlinear partial differential equations derived were solved numerically using Finite Difference Method. Influence of flow parameters on the temperature, concentration and velocity profiles were analyzed graphically. From the mathematical analysis of the model, it was established that the chemical reaction parameter significantly influenced the concentration distribution in both gaseous and liquid phases. Findings further revealed that decreasing the chemical reaction parameter resulted in decreased concentration of the geothermal fluid, which causes corrosion of geothermal pipes. These findings provide important information to engineers and researchers in making better decisions in terms of design, sizing and maintenance of flow systems in geothermal pipes.

A central characteristic of emphysematous progression is the continuous destruction of the lung extracellular matrix (ECM). Current treatments for emphysema have only addressed symptoms rather than preventing or reversing the loss of lung ECM. Nitrofurantoin (NF) is an antibiotic that has the potential to induce lung fibrosis as a side effect upon oral administration. Our study aims to repurpose NF as an inhalable therapeutic strategy to upregulate ECM expression, thereby reversing the disease progression within the emphysematous lung. Spray-dried (SD) formulations of NF were prepared in conjunction with a two-fluid nozzle (2FN) and three-fluid nozzle (3FN) using hydroxypropyl methylcellulose (HPMC) and NF at 1:1 w/w. The formulations were characterized for their physicochemical properties (particle size, morphology, solid-state characteristics, aerodynamic behaviour, and dissolution properties) and characterized in vitro with efficacy studies on human lung fibroblasts. The 2FN formulation displayed a mass mean aerodynamic diameter (MMAD) of 1.8 ± 0.05 µm and fine particle fraction (FPF) of 87.4 ± 2.8% with significantly greater deposition predicted in the lower lung region compared to the 3FN formulation (MMAD: 4.4 ± 0.4 µm; FPF: 40 ± 5.8%). Furthermore, drug dissolution studies showed that NF released from the 2FN formulation after 3 h was significantly higher (55.7%) as compared to the 3FN formulation (42.4%). Importantly, efficacy studies in human lung fibroblasts showed that the 2FN formulation induced significantly enhanced ECM protein expression levels of periostin and Type IV Collagen (203.2% and 84.2% increase, respectively) compared to untreated cells, while 3FN formulations induced only a 172.5% increase in periostin and a 38.1% increase in type IV collagen. In conclusion, our study highlights the influence of nozzle choice in inhalable spray-dried formulations and supports the feasibility of using SD NF prepared using 2FN as a potential inhalable therapeutic agent to upregulate ECM protein production.

Nasal mass in the pediatric population is most commonly benign and thus treated with low suspicion for malignancy. Ewing's sarcoma is the most common pediatric malignancy and usually arises in the diaphysis of long bones. Only 1–2% of Ewing's sarcoma cases are in the head and neck region and even fewer in the nasal cavity. Here we report and extremely rare case of nasal cavity Ewing's sarcoma, the differential diagnosis, and review of treatment considerations.

Abstract Background Radiation therapy is a standard form of treating non-small cell lung cancer, however, local recurrence is a major issue with this type of treatment. A better understanding of the metabolic response to radiation therapy may provide insight into improved approaches for local tumour control. Cyclic hypoxia is a well-established determinant that influences radiation response, though its impact on other metabolic pathways that control radiosensitivity remains unclear. Methods We used an established Raman spectroscopic (RS) technique in combination with immunofluorescence staining to measure radiation-induced metabolic responses in human non-small cell lung cancer (NSCLC) tumour xenografts. Tumours were established in NOD.CB17-Prkdcscid/J mice, and were exposed to radiation doses of 15 Gy or left untreated. Tumours were harvested at 2 h, 1, 3 and 10 days post irradiation. Results We report that xenografted NSCLC tumours demonstrate rapid and stable metabolic changes, following exposure to 15 Gy radiation doses, which can be measured by RS and are dictated by the extent of local tissue oxygenation. In particular, fluctuations in tissue glycogen content were observed as early as 2 h and as late as 10 days post irradiation. Metabolically, this signature was correlated to the extent of tumour regression. Immunofluorescence staining for γ–H2AX, pimonidazole and carbonic anhydrase IX (CAIX) correlated with RS-identified metabolic changes in hypoxia and reoxygenation following radiation exposure. Conclusion Our results indicate that RS can identify sequential changes in hypoxia and tumour reoxygenation in NSCLC, that play crucial roles in radiosensitivity.

The emphysema death toll has steadily risen over recent decades, causing the disease to become the third most common cause of death worldwide in 2019. Emphysema is currently incurable and could be due to a genetic condition (Alpha-1 antitrypsin deficiency) or exposure to pollutants/irritants, such as cigarette smoke or poorly ventilated cooking fires. Despite the growing burden of emphysema, the mechanisms behind emphysematous pathogenesis and progression are not fully understood by the scientific literature. A key aspect of emphysematous progression is the destruction of the lung parenchyma extracellular matrix (ECM), causing a drastic shift in the mechanical properties of the lung (known as mechanobiology). The mechanical properties of the lung such as the stiffness of the parenchyma (measured as the elastic modulus) and the stretch forces required for inhalation and exhalation are both reduced in emphysema. Fibroblasts function to maintain the structural and mechanical integrity of the lung parenchyma, yet, in the context of emphysema, these fibroblasts appear incapable of repairing the ECM, allowing emphysema to progress. This relationship between the disturbances in the mechanical cues experienced by an emphysematous lung and fibroblast behaviour is constantly overlooked and consequently understudied, thus warranting further research. Interestingly, the failure of current research models to integrate the altered mechanical environment of an emphysematous lung may be limiting our understanding of emphysematous pathogenesis and progression, potentially disrupting the development of novel treatments. This review will focus on the significance of emphysematous lung mechanobiology to fibroblast activity and current research limitations by examining: (1) the impact of mechanical cues on fibroblast activity and the cell cycle, (2) the potential role of mechanical cues in the diminished activity of emphysematous fibroblasts and, finally, (3) the limitations of current emphysematous lung research models and treatments as a result of the overlooked emphysematous mechanical environment.

The oxidative degradation of biphenyl and polychlorinated biphenyls (PCBs) is initiated in Pandoraea pnomenusa B-356 by biphenyl dioxygenase (BPDO(B356)). BPDO(B356), a heterohexameric (αβ)(3) Rieske oxygenase (RO), catalyzes the insertion of dioxygen with stereo- and regioselectivity at the 2,3-carbons of biphenyl, and can transform a broad spectrum of PCB congeners. Here we present the X-ray crystal structures of BPDO(B356) with and without its substrate biphenyl 1.6-Å resolution for both structures. In both cases, the Fe(II) has five ligands in a square pyramidal configuration: H233 Nε2, H239 Nε2, D386 Oδ1 and Oδ2, and a single water molecule. Analysis of the active sites of BPDO(B356) and related ROs revealed structural features that likely contribute to the superior PCB-degrading ability of certain BPDOs. First, the active site cavity readily accommodates biphenyl with minimal conformational rearrangement. Second, M231 was predicted to sterically interfere with binding of some PCBs, and substitution of this residue yielded variants that transform 2,2'-dichlorobiphenyl more effectively. Third, in addition to the volume and shape of the active site, residues at the active site entrance also apparently influence substrate preference. Finally, comparison of the conformation of the active site entrance loop among ROs provides a basis for a structure-based classification consistent with a phylogeny derived from amino acid sequence alignments.

Background: Surgery for degenerative spine pathologies is typically performed on a scheduled basis; however, worsening symptoms may warrant emergency surgery. An increasing number of patients requiring emergency surgery has been observed (22.6% in 2006 to 34.8% in 2019). We sought to compare the outcomes of patients who received scheduled surgery and those who required emergency surgery. Methods: All patients treated between Jan. 1, 2006, and Dec. 31, 2019, were included. Retrospective comparisons were made between patients who were scheduled (elective) for surgery and those requiring emergency surgery, patients who were scheduled for surgery and those who decompensated while on the surgical waitlist and patients who presented as de novo emergencies and those who decompensated while on the surgical waitlist. Results: Among the 6217 patients with degenerative pathologies, 4654 (74.9%) patients were scheduled (elective) for surgery and 1563 (25.1%) were patients requiring emergency surgery. Compared with patients who were scheduled, patients requiring emergency surgery had a longer length of stay (LOS) in hospital (5.1 d, interquartile range [IQR] 2.7-11.2 v. 3.6 d, IQR 1.3-6.4, p < 0.001) and lower rate of home discharge (78.6% v. 94.2%, p < 0.001). Patients requiring emergency surgery were 1.34 times more likely to have any adverse events (95% confidence interval [CI] 1.06-1.68, p = 0.01). When compared with patients who were scheduled for surgery, those who decompensated while on the surgical waitlist had longer LOS (7.0 d, IQR 3.3-15.0 v. 3.6 d, IQR 1.3-6.4, p < 0.001), less home discharge (77.6% v. 94.2%, p < 0.001) and were 2.5 times more likely to have any adverse events (95% CI 1.5-4.1, p < 0.001). Patients who decompensated had a 2.1 times higher risk of having any adverse events than patients who presented as de novo emergencies (95% CI 1.2-3.6, p< 0.001). Conclusion: We observed worse perioperative outcomes for patients requiring emergency surgery for degenerative spinal conditions than for patients who were scheduled for surgery. Patients who decompensated while on the surgical waitlist had the worst outcomes. Contexte: Le traitement chirurgical des pathologies dégénératives de la colonne vertébrale est généralement planifié; l'aggravation des symptômes peut toutefois justifier une opération d'urgence. On constate d'ailleurs qu'un pourcentage croissant de patients ont besoin d'une telle intervention (22,6% en 2006 comparativement à 34,8% en 2019). Nous avons cherché à comparer les issues des patients ayant subi une intervention planifiée avec celles des patients nécessitant une opération d'urgence. Méthodes: Tous les patients traités entre le 1er janvier 2006 et le 31 décembre 2019 ont été inclus. Nous avons établi des comparaisons rétrospectives entre les patients allant subir une intervention planifiée (non urgente) et ceux ayant besoin d'une opération d'urgence, entre les patients allant subir une intervention planifiée et ceux ayant subi une décompensation alors qu'ils étaient sur une liste d'attente, et entre les patients nécessitant une opération urgente pour une pathologie de novo et ceux ayant subi une décompensation alors qu'ils étaient sur une liste d'attente. Résultats: Parmi les 6217 patients présentant des pathologies dégénératives, 4654 (74,9%) allaient subir une intervention planifiée (non urgente) et 1563 (25,1%) avaient besoin d'une opération d'urgence. Comparativement aux premiers, ces derniers restaient plus longtemps à l'hôpital (5,1 jours [écart interquartile (EI) 2,7-11,2] c. 3,6 jours [EI 1,3-6,4], p < 0,001) et présentaient un taux de congé plus faible (78,6% c. 94,2%, p < 0,001). Ils étaient 1,34 fois plus susceptibles d'être victimes d'un événement indésirable (intervalle de confiance [IC] de 95% 1,06-1,68, p = 0,01). Comparativement aux patients pour lesquels une intervention était prévue, ceux ayant subi une décompensation alors qu'ils étaient sur une liste d'attente restaient plus longtemps à l'hôpital (7,0 jours [EI 3,3-15,0] c. 3,6 jours [EI 1,3-6,4], p < 0,001), présentaient un taux de congé plus faible (77,6% c. 94,2%, p < 0,001) et étaient 2,5 fois plus susceptibles de subir un événement indésirable (IC de 95% 1,5-4,1, p < 0,001). Les patients ayant subi une décompensation présentaient un risque 2,1 fois plus élevé d'être victimes d'un événement indésirable, comparativement aux patients nécessitant une opération urgente pour une pathologie de novo (IC de 95% 1,2-3,6, p < 0,001). Conclusion: Nous avons observé des issues périopératoires moins favorables chez les patients ayant besoin de se faire opérer d'urgence pour des pathologies dégénératives de la colonne vertébrale, comparativement à ceux pour lesquels une intervention était prévue. Les patients ayant subi une décompensation alors qu'ils étaient sur une liste d'attente présentaient les pires issues., Older age demographics have increased the demand for spinal surgery, creating an ever-increasing burden for the health care system. (1) This is especially true for degenerative spinal pathologies such as [...]

In this introduction to the forum Quirk Historicism, the editors describe the recent tendency of music scholars, in the wake of New Historicism, to avail themselves of objets trouvés and historical micronarratives for interpretation. Fall 2015