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Always smile : Carley Allison's secrets for laughing, loving and living
\"Carley Allison was an up-and-coming young figure skater and singer who died tragically at the age of 18 of a cancer so rare there were only seven cases in the world. In this book, you will come to know Carley in her own words and in the words of the people who knew and loved her. Award-winning author Alice Kuipers weaves the memories of Carley's friends, family, and boyfriend with the blog Carley kept throughout her journey, from the moment she was diagnosed until her final months of searching for treatment that would keep the disease at bay. Kuipers also recreates pivotal moments from Carley's point of view, acting as ventriloquist for a voice lost too young. This book is built around the words she lived by, both in sickness and in health. Above all, again and again, she summed up her philosophy in two words: always smile.\"-- Provided by publisher.
Book
3D bioprinted silk fibroin hydrogels for tissue engineering
The development of biocompatible and precisely printable bioink addresses the growing demand for three-dimensional (3D) bioprinting applications in the field of tissue engineering. We developed a methacrylated photocurable silk fibroin (SF) bioink for digital light processing 3D bioprinting to generate structures with high mechanical stability and biocompatibility for tissue engineering applications. Procedure 1 describes the synthesis of photocurable methacrylated SF bioink, which takes 2 weeks to complete. Digital light processing is used to fabricate 3D hydrogels using the bioink (1.5 h), which are characterized in terms of methacrylation, printability, mechanical and rheological properties, and biocompatibility. The physicochemical properties of the bioink can be modulated by varying photopolymerization conditions such as the degree of methacrylation, light intensity, and concentration of the photoinitiator and bioink. The versatile bioink can be used broadly in a range of applications, including nerve tissue engineering through co-polymerization of the bioink with graphene oxide, and for wound healing as a sealant. Procedure 2 outlines how to apply 3D-printed SF hydrogels embedded with chondrocytes and turbinate-derived mesenchymal stem cells in one specific in vivo application, trachea tissue engineering, which takes 2–9 weeks.
Park and colleagues describe the synthesis of methacrylated photocurable silk fibroin bioink for digital light processing 3D bioprinting as well as fabrication of biocompatible organ-mimicking hydrogel structures for trachea tissue engineering.
Journal Article
Tissue-engineered trachea from a 3D-printed scaffold enhances whole-segment tracheal repair
Long segmental repair of trachea stenosis is an intractable condition in the clinic. The reconstruction of an artificial substitute by tissue engineering is a promising approach to solve this unmet clinical need. 3D printing technology provides an infinite possibility for engineering a trachea. Here, we 3D printed a biodegradable reticular polycaprolactone (PCL) scaffold with similar morphology to the whole segment of rabbits’ native trachea. The 3D-printed scaffold was suspended in culture with chondrocytes for 2 (Group I) or 4 (Group II) weeks, respectively. This
in vitro
suspension produced a more successful reconstruction of a tissue-engineered trachea (TET), which enhanced the overall support function of the replaced tracheal segment. After implantation of the chondrocyte-treated scaffold into the subcutaneous tissue of nude mice, the TET presented properties of mature cartilage tissue. To further evaluate the feasibility of repairing whole segment tracheal defects, replacement surgery of rabbits’ native trachea by TET was performed. Following postoperative care, mean survival time in Group I was 14.38 ± 5.42 days, and in Group II was 22.58 ± 16.10 days, with the longest survival time being 10 weeks in Group II. In conclusion, we demonstrate the feasibility of repairing whole segment tracheal defects with 3D printed TET.
Journal Article
Randomized Trial of Fetal Surgery for Severe Left Diaphragmatic Hernia
In this trial involving fetuses with severe left congenital diaphragmatic hernia, fetoscopic endoluminal tracheal occlusion at 27 to 29 weeks of gestation significantly increased survival to discharge, but it resulted in an increased incidence of preterm, prelabor rupture of membranes and preterm birth.
Journal Article
Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State: a case series
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic, with increasing deaths worldwide. To date, documentation of the histopathological features in fatal cases of the disease caused by SARS-CoV-2 (COVID-19) has been scarce due to sparse autopsy performance and incomplete organ sampling. We aimed to provide a clinicopathological report of severe COVID-19 cases by documenting histopathological changes and evidence of SARS-CoV-2 tissue tropism.
In this case series, patients with a positive antemortem or post-mortem SARS-CoV-2 result were considered eligible for enrolment. Post-mortem examinations were done on 14 people who died with COVID-19 at the King County Medical Examiner's Office (Seattle, WA, USA) and Snohomish County Medical Examiner's Office (Everett, WA, USA) in negative-pressure isolation suites during February and March, 2020. Clinical and laboratory data were reviewed. Tissue examination was done by light microscopy, immunohistochemistry, electron microscopy, and quantitative RT-PCR.
The median age of our cohort was 73·5 years (range 42–84; IQR 67·5–77·25). All patients had clinically significant comorbidities, the most common being hypertension, chronic kidney disease, obstructive sleep apnoea, and metabolic disease including diabetes and obesity. The major pulmonary finding was diffuse alveolar damage in the acute or organising phases, with five patients showing focal pulmonary microthrombi. Coronavirus-like particles were detected in the respiratory system, kidney, and gastrointestinal tract. Lymphocytic myocarditis was observed in one patient with viral RNA detected in the tissue.
The primary pathology observed in our cohort was diffuse alveolar damage, with virus located in the pneumocytes and tracheal epithelium. Microthrombi, where observed, were scarce and endotheliitis was not identified. Although other non-pulmonary organs showed susceptibility to infection, their contribution to the pathogenesis of SARS-CoV-2 infection requires further examination.
None.
Journal Article
Sensitive bioluminescence imaging of fungal dissemination to the brain in mouse models of cryptococcosis
Cryptococcus neoformans is a leading cause of fungal brain infection, but the mechanism of dissemination and dynamics of cerebral infection following pulmonary disease are poorly understood. To address these questions, non-invasive techniques that can study the dynamic processes of disease development and progression in living animal models or patients are required. As such, bioluminescence imaging (BLI) has emerged as a powerful tool to evaluate the spatial and temporal distribution of infection in living animals. We aimed to study the time profile of the dissemination of cryptococcosis from the lung to the brain in murine models by engineering the first bioluminescent C. neoformans KN99α strain, expressing a sequence-optimized red-shifted luciferase. The high pathogen specificity and sensitivity of BLI was complemented by the three-dimensional anatomical information from micro-computed tomography (μCT) of the lung and magnetic resonance imaging (MRI) of the brain. These non-invasive imaging techniques provided longitudinal readouts on the spatial and temporal distribution of infection following intravenous, intranasal or endotracheal routes of inoculation. Furthermore, the imaging results correlated strongly with the fungal load in the respective organs. By obtaining dynamic and quantitative information about the extent and timing of brain infections for individual animals, we found that dissemination to the brain after primary infection of the lung is likely a late-stage event with a timeframe that is variable between animals. This novel tool in Cryptococcus research can aid the identification of host and pathogen factors involved in this process, and supports development of novel preventive or therapeutic approaches.
Journal Article
Randomized Trial of Fetal Surgery for Moderate Left Diaphragmatic Hernia
In this randomized trial involving fetuses with moderate left congenital diaphragmatic hernia, fetoscopic endoluminal tracheal occlusion at 30 to 32 weeks of gestation did not significantly increase survival to discharge from a NICU or reduce the need for oxygen supplementation at 6 months, and it increased the risks of preterm, prelabor rupture of membranes and preterm birth. The surgical technique is shown in an animated video.
Journal Article
Neutrophil trails guide influenza-specific CD8+T cells in the airways
T cells constantly circulate throughout the body until an invading pathogen calls them into action. Microbes often cause localized infections, so how do T cells know where to go? Lim et al. explore this question in a mouse model of influenza infection and find that immune cells called neutrophils help guide the way (see the Perspective by Kiermaier and Sixt). Upon infection, neutrophils quickly traffic to the trachea. There, they lay down “tracks” enriched in proteins called chemokines, especially the chemokine CXCL12, which guide CD8 + T cells to the infected organ. Mice whose neutrophils could not lay down such tracks exhibited defects in CD8 + T cell recruitment and viral clearance. Science , this issue 10.1126/science.aaa4352 ; see also p. 1055 Trails of chemokines left behind by neutrophils guide T cells to sites of viral infection. [Also see Perspective by Kiermaier and Sixt ] During viral infections, chemokines guide activated effector T cells to infection sites. However, the cells responsible for producing these chemokines and how such chemokines recruit T cells are unknown. Here, we show that the early recruitment of neutrophils into influenza-infected trachea is essential for CD8 + T cell–mediated immune protection in mice. We observed that migrating neutrophils leave behind long-lasting trails that are enriched in the chemokine CXCL12. Experiments with granulocyte-specific CXCL12 conditionally depleted mice and a CXCR4 antagonist revealed that CXCL12 derived from neutrophil trails is critical for virus-specific CD8 + T cell recruitment and effector functions. Collectively, these results suggest that neutrophils deposit long-lasting, chemokine-containing trails, which may provide both chemotactic and haptotactic cues for efficient CD8 + T cell migration and localization in influenza-infected tissues.
Journal Article
CFAP53 regulates mammalian cilia-type motility patterns through differential localization and recruitment of axonemal dynein components
Motile cilia can beat with distinct patterns, but how motility variations are regulated remain obscure. Here, we have studied the role of the coiled-coil protein CFAP53 in the motility of different cilia-types in the mouse. While node (9+0) cilia of Cfap53 mutants were immotile, tracheal and ependymal (9+2) cilia retained motility, albeit with an altered beat pattern. In node cilia, CFAP53 mainly localized at the base (centriolar satellites), whereas it was also present along the entire axoneme in tracheal cilia. CFAP53 associated tightly with microtubules and interacted with axonemal dyneins and TTC25, a dynein docking complex component. TTC25 and outer dynein arms (ODAs) were lost from node cilia, but were largely maintained in tracheal cilia of Cfap53 -/- mice. Thus, CFAP53 at the base of node cilia facilitates axonemal transport of TTC25 and dyneins, while axonemal CFAP53 in 9+2 cilia stabilizes dynein binding to microtubules. Our study establishes how differential localization and function of CFAP53 contributes to the unique motion patterns of two important mammalian cilia-types.
Journal Article
Assessing Changes in Airflow and Energy Loss in a Progressive Tracheal Compression Before and After Surgical Correction
The energy needed to drive airflow through the trachea normally constitutes a minor component of the work of breathing. However, with progressive tracheal compression, patient subjective symptoms can include severe breathing difficulties. Many patients suffer multiple respiratory co-morbidities and so it is important to assess compression effects when evaluating the need for surgery. This work describes the use of computational prediction to determine airflow resistance in compressed tracheal geometries reconstructed from a series of CT scans. Using energy flux analysis, the regions that contribute the most to airway resistance during inhalation are identified. The principal such region is where flow emerging from the zone of maximum constriction undergoes breakup and turbulent mixing. Secondary regions are also found below the tongue base and around the glottis, with overall airway resistance scaling nearly quadratically with flow rate. Since the anatomical extent of the imaged airway varied between scans—as commonly occurs with clinical data and when assessing reported differences between research studies—the effect of sub-glottic inflow truncation is considered. Analysis shows truncation alters the location of jet breakup and weakly influences the pattern of pressure recovery. Tests also show that placing a simple artificial glottis in the inflow to a truncated model can replicate patterns of energy loss in more extensive models, suggesting a means to assess sensitivity to domain truncation in tracheal airflow simulations.
Journal Article