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BACKGROUND: Double lumen endobronchial tubes (DLTs) are frequently used to employ single lung ventilation strategies during thoracic surgical procedures. Placement of these tubes can be challenging even for experienced clinicians. We hypothesized that airway anatomy, particularly of the glottis and proximal trachea, significantly impacts the ease or difficulty in placement of these tubes. METHODS: Images from 24 randomly selected Positron Emission Tomography - Computed Tomography (PET-CT) scans were evaluated for several anatomic aspects of the upper airway, including size and angulation of the glottis and proximal tracheal using calibrated CT measurements and an online digital protractor. The anatomic issues identified were confirmed in cadaveric anatomic models. RESULTS: Proximal tracheal diameter measurements in PET-CT scans demonstrated a mean ± standard deviation of 20.4 ± 2.5 mm in 12 males and 15.5 ± 0.98 mm in 12 females (p < 0.001), and both were large enough to accommodate 39 French and 37 French DLTs in males and females, respectively. Subsequent measurements of the posterior angulation of the proximal trachea revealed a mean angle of 40.8 ± 5.7 degrees with no sex differences. By combining the 24 individual posterior tracheal angles with the 16 angled distal tip measurements DLTs (mean angle 24.9 ± 2.1 degrees), we created a series of 384 patient intubation angle scenarios. This data clearly showed that DLT rotation to a full 180 degrees decreased the mean intubation angle between the DLT and the proximal trachea from a mean of 66.6 ± 5.9 to only 15.8 ± 5.9 degrees. CONCLUSIONS: Rotation of DLTs a full 180 instead of the recommended 90 degrees facilitates DLT intubations.

UNLABELLED: Coccidioidomycosis, also known as Valley fever, is a disease caused by the fungal pathogen Coccidioides. Unfortunately, patients are often misdiagnosed with bacterial pneumonia, leading to inappropriate antibiotic treatment. The soil Bacillus subtilis-like species exhibits antagonistic properties against Coccidioides in vitro; however, the antagonistic capabilities of host microbiota against Coccidioides are unexplored. We sought to examine the potential of the tracheal and intestinal microbiomes to inhibit the growth of Coccidioides in vitro. We hypothesized that an uninterrupted lawn of microbiota obtained from antibiotic-free mice would inhibit the growth of Coccidioides, while partial in vitro depletion through antibiotic disk diffusion assays would allow a niche for fungal growth. We observed that the microbiota grown on 2×GYE (GYE) and Columbia colistin and nalidixic acid with 5% sheeps blood agar inhibited the growth of Coccidioides, but microbiota grown on chocolate agar did not. Partial depletion of the microbiota through antibiotic disk diffusion revealed diminished inhibition and comparable growth of Coccidioides to controls. To characterize the bacteria grown and identify potential candidates contributing to the inhibition of Coccidioides, 16S rRNA sequencing was performed on tracheal and intestinal agar cultures and murine lung extracts. We found that the host bacteria likely responsible for this inhibition primarily included Lactobacillus and Staphylococcus. The results of this study demonstrate the potential of the host microbiota to inhibit the growth of Coccidioides in vitro and suggest that an altered microbiome through antibiotic treatment could negatively impact effective fungal clearance and allow a niche for fungal growth in vivo. IMPORTANCE: Coccidioidomycosis is caused by a fungal pathogen that invades the host lungs, causing respiratory distress. In 2019, 20,003 cases of Valley fever were reported to the CDC. However, this number

The development in interventional respiratory medicine entails the need of bronchial anatomical knowledge, whose variations assume their greatest importance nowadays. The aim of this study was to describe the frequency of these variations and to analyze the bronchial lengths, barely registered before in literature. This observational descriptive study (from June 2018 until April 2019) was conducted in a sample of 17 pairs of lungs, which were dissected and measured at the Cadaver Donation Centre (Universidad Complutense, Madrid), and a second sample of 50 bronchoscopies, performed at the San Carlos Clinic Hospital, which were analyzed during the procedure. Our results show that there are no significant differences in the incidence of variations by sex in any of both samples, and neither in the average length of any bronchus by sex nor lobar pattern. Left main bronchus presents the longest length and left upper lobe bronchus the shortest. The highest percentage of variations is contained in the right lower lobe (25.4%), and the most frequent variation in the subsuperior bronchus (B*) (19.4%). The middle lobe and the left lower lobe present the lowest percentage of variations (11.9%). Only 37.3% of the pairs of lungs/patients did not have any anatomical variation in the general sample. Despite of the small size of the sample, results show a high percentage of variations and a minority of completely normal pairs of lungs, which invites us to reflect about the probable high prevalence of variations in the general population. Further studies with greater samples are needed to confirm our hypothesis., Depto. de Anatomía y Embriología, Fac. de Medicina, TRUE, pub

Spiders represent an evolutionary successful group of chelicerate arthropods. The body of spiders is subdivided into two regions (tagmata). The anterior tagma, the prosoma, bears the head appendages and four pairs of walking legs. The segments of the posterior tagma, the opisthosoma, either lost their appendages during the course of evolution or their appendages were substantially modified to fulfill new tasks such as reproduction, gas exchange, and silk production. Previous work has shown that the homeotic Hox genes are involved in shaping the posterior appendages of spiders. In this paper, we investigate the expression of the posterior Hox genes in a tarantula that possesses some key differences of posterior appendages compared to true spiders, such as the lack of the anterior pair of spinnerets and a second set of book lungs instead of trachea. Based on the observed differences in posterior Hox gene expression in true spiders and tarantulas, we argue that subtle changes in the Hox gene expression of the Hox genes abdA and AbdB are possibly responsible for at least some of the morphological differences seen in true spiders versus tarantulas.

Introduction:Penetrating neck trauma is defined as injuries involving the platysma. Neck injuries are potentially lethal due to the presence of vascular and aerodigestive structures. Diagnosis of aerodigestive lesions requires a high index of suspicion, early diagnosis and treatment is essential. Clinical case: A male patient with penetrating neck trauma in zone II by gunshot, with torpid evolution during hospitalization, suspected esophageal perforation, communication of the digestive tract with the airway is identified by esophagogram, and an endoscopic study shows a lesion. of 80% of the circumference, once video-assisted thoracoscopy with pleural decortication was performed, a cervicotomy was performed with tracheoplasty, and end-to-end cervical esophageal anastomosis, postoperative course without complications. Conclusions: It is important to avoid inadvertent lesions in different anatomical elements when faced with entities that offer unspecific clinical and laboratory data. Knowing the treatment modalities that are available allows protocolization for early surgical intervention, thus avoiding complications, and opening up the possibility of reducing the mortality of these procedures., Introducción: Se define como traumatismo penetrante de cuello a las lesiones que involucran el platisma. Las lesiones en cuello son potencialmente letales dada la presencia de estructuras vasculares y aerodigestivas. El diagnóstico de lesiones aerodigestivas requiere un alto índice de sospecha, es imprescindible el diagnóstico y tratamiento temprano. Caso clínico: Se presenta paciente masculino con traumatismo penetrante de cuello en zona II por proyectil, con evolución tórpida durante hospitalización, bajo sospecha de perforación esofágica, se identifica comunicación del tracto digestivo con la vía aérea mediante esofagograma, y con estudio endoscópico se observa lesión de 80% de la circunferencia , una vez realizada toracoscopía video-asistida con decorticación pleural , se lleva a cabo cervicotomía realizando traqueoplastía, y anastomosis de esófago cervical termino-terminal, curso postoperatorio sin complicaciones. Conclusiones: Es importante evitar inadvertir lesiones en diferentes elementos anatómicos ante lesione que ofrecen datos clínicos y de laboratorios poco específicos. Conocer las modalidades de tratamiento de las que se disponen, permite protocolizar para la intervención quirúrgica temprana, evitando así complicaciones, y dar apertura a la posibilidad de reducir la mortalidad de estos procedimientos.

Critical to morphogenesis is the precise regulation of the activity of membrane receptors, which receive signals from the environment to trigger a spatio-temporally controlled cascade of events. Miss-regulation of receptor activities typically lead to malformations, fatal disease or malignant transformation. The tyrosine kinase FGFR1/Breathless (Btl) receptor plays a pivotal role during the formation of the tracheal system in Drosophila. The activation of Btl by binding of its ligand Branchless (Bnl) leads to the specification of terminal cells at the tip of tracheal tubes, which form the fine branches responsible to oxygenate the tissues. We found that Wengen (Wgn), a TNF receptor, is also required for terminal cell specification. Our results indicated that Wgn works in an unconventional manner during tracheal development, independent of its proposed canonical ligand, named Eiger (Egr) and its canonical signalling pathway, the JNK pathway. Our cellular approach indicated that Wgn is constitutively internalised and accumulates in endocytic vesicles, and colocalise with Btl in these vesicles. Our biochemical approach indicated that Wgn and Btl form a complex. Our genetic approach indicated that Wgn regulates the activity of Btl. Thus, we propose a model in which Wgn would regulate terminal cell specification by regulating the intracellular trafficking of Btl receptor modulating in this way its physiological activity. We have generated new tools to investigate in further detail Wgn activity in life conditions and the Btl/Wgn interactions. We are extending our analysis of Wgn requirements to other tissues in which Wgn is also expressed, in order to test whether this unconventional mechanism that we identified in the trachea is a general mechanism of activity of Wgn. This could suggest that the binding of TNFRs to unrelated proteins is a general strategy of TNFRs activity.

Polyploidy is an extended phenomenon in biology. However, its physiological significance and whether it defines specific cell behaviors is not well understood. Here we study its connection to macroautophagy/autophagy, using the larval respiratory system of Drosophila as a model. This system comprises cells with the same function yet with notably different ploidy status, namely diploid progenitors and their polyploid larval counterparts, the latter destined to die during metamorphosis. We identified an association between polyploidy and autophagy and found that higher endoreplication status correlates with elevated autophagy. Finally, we report that tissue histolysis in the trachea during Drosophila metamorphosis is mediated by autophagy, which triggers the apoptosis of polyploid cells.

Polyploidy is an extended phenomenon in biology. However, its physiological significance and whether it defines specific cell behaviors is not well understood. Here we study its connection to macroautophagy/autophagy, using the larval respiratory system of Drosophila as a model. This system comprises cells with the same function yet with notably different ploidy status, namely diploid progenitors and their polyploid larval counterparts, the latter destined to die during metamorphosis. We identified an association between polyploidy and autophagy and found that higher endoreplication status correlates with elevated autophagy. Finally, we report that tissue histolysis in the trachea during Drosophila metamorphosis is mediated by autophagy, which triggers the apoptosis of polyploid cells.

The tracheal epithelium is a primary target for pulmonary diseases as it provides a conduit for air flow between the environment and the lung lobes. The cellular and molecular mechanisms underlying airway epithelial cell proliferation and differentiation remain poorly understood. Hedgehog (HH) signaling orchestrates communication between epithelial and mesenchymal cells in the lung, where it modulates stromal cell proliferation, differentiation and signaling back to the epithelium. Here, we reveal a previously unreported autocrine function of HH signaling in airway epithelial cells. Epithelial cell depletion of the ligand sonic hedgehog (SHH) or its effector smoothened (SMO) causes defects in both epithelial cell proliferation and differentiation. In cultured primary human airway epithelial cells, HH signaling inhibition also hampers cell proliferation and differentiation. Epithelial HH function is mediated, at least in part, through transcriptional activation, as HH signaling inhibition leads to downregulation of cell type-specific transcription factor genes in both the mouse trachea and human airway epithelial cells. These results provide new insights into the role of HH signaling in epithelial cell proliferation and differentiation during airway development.

The mechanisms coupling fate specification of distinct tissues to their physical separation remain to be understood. The trachea and esophagus differentiate from a single tube of definitive endoderm, requiring the transcription factors SOX2 and NKX2-1, but how the dorsoventral site of tissue separation is defined to allocate tracheal and esophageal cell types is unknown. Here, we show that the EPH/EPHRIN signaling gene Efnb2 regulates tracheoesophageal separation by controlling the dorsoventral allocation of tracheal-fated cells. Ventral loss of NKX2-1 results in disruption of separation and expansion of Efnb2 expression in the trachea independent of SOX2. Through chromatin immunoprecipitation and reporter assays, we find that NKX2-1 likely represses Efnb2 directly. Lineage tracing shows that loss of NKX2-1 results in misallocation of ventral foregut cells into the esophagus, while mosaicism for Nkx2-1 generates ectopic NKX2-1/EPHRIN-B2 boundaries that organize ectopic tracheal separation. Together, these data demonstrate that NKX2-1 coordinates tracheal specification with tissue separation through the regulation of EPHRIN-B2 and tracheoesophageal cell sorting.

The immunological features that distinguish COVID-19-associated acute respiratory distress syndrome (ARDS) from other causes of ARDS are incompletely understood. Here, we report the results of comparative lower respiratory tract transcriptional profiling of tracheal aspirate from 52 critically ill patients with ARDS from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a "cytokine storm," we observe reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS is characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity. In silico analysis of gene expression identifies several candidate drugs that may modulate gene expression in COVID-19 ARDS, including dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 is characterized by impaired interferon-stimulated gene (ISG) expression. The relationship between SARS-CoV-2 viral load and expression of ISGs is decoupled in patients with COVID-19 ARDS when compared to patients with mild COVID-19. In summary, assessment of host gene expression in the lower airways of patients reveals distinct immunological features of COVID-19 ARDS.

[EN] The ideal tracheal substitute must have biomechanical properties comparable to the native trachea, but currently there is no standardised approach to evaluating these properties. Here we propose a novel method for evaluating and comparing the properties of tracheal substitutes, thus systematising both measurement and data curation. This system was tested by comparing native rabbit tracheas to frozen and decellularised specimens and determining the histological characteristics of those specimens. We performed radial compression tests on the anteroposterior tracheal axis and longitudinal axial tensile tests with the specimens anastomosed to the jaw connected to a measuring system. All calculations and results were adjusted according to tracheal size, always using variables relative to the tracheal dimensions, thus permitting comparison of different sized organs. The biomechanical properties of the decellularised specimens were only slightly reduced compared to controls and significant in regard to the maximum stress withstood in the longitudinal axis (-0.246 MPa CI [-0.248, -0.145] MPa) and the energy stored per volume unit (-0.124 mJ & BULL;mm(-3) CI [-0.195, -0.055] mJ & BULL;mm(-3)). The proposed method is suitable for the systematic characterisation of the biomechanical properties of different tracheal substitutes, regardless of the size or nature of the substitute, thus allowing for direct comparisons.

Purpose: Patients with tracheal lesions that exceed half of the trachea’s total length require a tracheal substitute. Tissue engineering, using either synthetic materials or decellularized tracheal tissue, opens up new possibilities for generating tracheal substitutes. Decellularization, a procedure in which the tissue's immunogenic cellular material is removed while the extracellular matrix (ECM) is preserved, seems the most promising approach. The majority of tracheal decellularization methods, however, are reliant on harsh chemicals and require lengthy wash procedures, resulting in damage to the ECM. To address these issues, a supercritical carbon dioxide (scCO2) decellularization approach has been suggested as an alternative solution due to its ability to both decellularize and sterilize tissues while leaving no toxic residues and requiring less treatment time. Therefore, the aim of this thesis was to compare scCO2 treatment with a chemical decellularization method, which is the current gold standard reported in literature, for creating a decellularized porcine tracheal scaffold with good cytocompatibility. Methods: A total of five different protocols were tested that varied in decellularization and sterilization methods used. Decellularization efficiency was evaluated in terms of DNA content, histological appearance, and retention of ECM components. Additionally, mechanical tensile testing and scanning electron microscopy were used to assess the effects of the different decellularization protocols. Further, decellularized scaffolds were recellularized with fibrin-encapsulated porcine adipose derived stem cells to assess the cytocompatibility of the scaffolds. Results: The highest reduction in DNA content was observed when samples were subjected to the detergent-enzymatic protocol, followed by sterilization with gamma irradiation, and when samples were subjected to scCO2 treatment, followed by washing with sodium hydroxide. The latter proto, Biomedical Engineering

Newcastle disease (ND) has a great impact on poultry health and welfare with its most virulent (velogenic) strain. In addition, issues exacerbated by the increase in global temperatures necessitates a greater understanding of the host immune response when facing a combination of biotic and abiotic stress factors in poultry production. Previous investigations have revealed that the host immune response is tissue-specific. The goal of this study was to identify genes and/or signaling pathways associated with immune response to NDV (Newcastle disease virus) in the trachea, an essential organ where NDV replicate after the infection, by profiling the tissue specific transcriptome response in two genetically distinct inbred chicken lines when exposed to both abiotic and biotic stressors. Fayoumis appear to be able to respond more effectively (lower viral titer, higher antibody levels, immune gene up-regulation) and earlier than Leghorns. Our results suggest NDV infection in Fayoumis appears to elicit proinflammatory processes, and pathways such as the inhibition of cell viability, cell proliferation of lymphocytes, and transactivation of RNA, more rapidly than in Leghorns. These differences in immune response converge at later timepoints which may indicate that Leghorns eventually regulate its immune response to infection. The profiling of the gene expression response in the trachea adds to our understanding of the chicken host response to NDV infection and heat stress on a whole genome level and provides potential candidate genes and signaling pathways for further investigation into the characterization of the time-specific and pathway specific responses in Fayoumis and Leghorns.

Introduction and objective: In low-income countries, the situation of foreign bodies is relatively poorly studied. Although the literature is relatively scarce, published studies show that they represent an increasingly important public health problem. Material and methods: A retrospective study was conducted that used the collection and analysis of data available in the operating room books diagnosed as tracheobronchial consecutively for a period of 26 years (1983-2009) in Maputo Central Hospital (Mozambique). Results: 118 patients were studied. Of these, 21 were in the trachea (17.80%) and 97 in the bronchi (82.20%). Most patients observed were men (59.30%). The average age of the patients in this study was 4.39 years (mode 2, median 2.50; standard deviation 6.004, the range was 2 months to 45 years). There were more cases in 2-year-old children (19.5%). The seeds were the most frequent (31.40%), followed by plastic (26.30%) and metal (22%). There were 5 cases of complications. Conclusions: Although this study provides evidence that can be considered important from the point of view of public health, it should be considered that it is a hospital study with its own limitations. However, this study presents a unique compilation of cases of patients with foreign bodies in the airway that covers a relatively long period, which is an important source of information on the subject., Introducción y objetivo: En los países de bajos ingresos, la situación de los cuerpos extraños está relativamente poco estudiada. Aunque la literatura es relativamente escasa, los estudios publicados muestran que representan un problema de salud pública cada vez más importante. Material y método: Se realizó un estudio retrospectivo que utilizó la recopilación y el análisis de los datos disponibles en los libros del registro del quirófano diagnosticados como cuerpos extraños traqueobronquial consecutivamente durante un período de 26 años (1983-2009) en Hospital Central de Maputo (Mozambique). Resultados: se estudiaron 118 pacientes. De estos, 21 se localizaron en la tráquea (17.80%) y 97 en los bronquios (82.20%). La mayoría de los pacientes observados fueron hombres (59.30%). La edad promedio de los pacientes en este estudio fue de 4.39 años (moda 2, mediana 2.50; desviación estándar 6.004, el rango fue de 2 meses a 45 años). Se observaron más casos en niños de 2 años (19.5%). Las semillas fueron los cuerpos extraños más frecuentes, responsables del 31.40% de todos los cuerpos extraños diagnosticadas, seguidas por el plástico (26.30%) y el metal (22%). Se presentaron 5 casos de complicaciones. Conclusiones: Aunque este estudio aporta evidencia que puede considerarse importante desde el punto de vista de la salud pública, debe tenerse en cuenta que se trata de una investigación hospitalaria con sus propias limitaciones. Sin embargo, este estudio presenta una compilación única de casos de pacientes con cuerpos extraños traqueobronquial que cubre un período relativamente largo, lo que constituye una importante fuente de información sobre el tema.

Epithelia grow and shape into functional structures during organogenesis. Although most of the focus on organogenesis has been drawn to the building of biological structures, the disassembly of pre-existing structures is also an important event to reach a functional adult organ. Examples of disassembly processes include the regression of the Müllerian or Wolffian ducts during gonad development and mammary gland involution during the post-lactational period in adult females. To date, it is unclear how organ disassembly is controlled at the cellular level. Here, we follow the Drosophila larval trachea through metamorphosis and show that its disassembly is a hormone-driven and precisely orchestrated process. It occurs in two phases: first, remodeling of the apical extracellular matrix (aECM), mediated by matrix metalloproteases and independent of the actomyosin cytoskeleton, results in a progressive shortening of the entire trachea and a nuclear-to-cytoplasmic relocalization of the Hippo effector Yorkie (Yki). Second, a decreased transcription of the Yki target, Diap1, in the posterior metameres and the activation of caspases result in the apoptotic loss of the posterior half of the trachea while the anterior half escapes cell death. Thus, our work unravels a mechanism by which hormone-driven ECM remodeling controls sequential tissue shortening and apoptotic cell removal through the transcriptional activity of Yki, leading to organ disassembly during animal development.

BACKGROUND Fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased postnatal survival among infants with severe pulmonary hypoplasia due to isolated congenital diaphragmatic hernia on the left side, but data are lacking to inform its effects in infants with moderate disease. METHODS In this open-label trial conducted at many centers with experience in FETO and other types of prenatal surgery, we randomly assigned, in a 1:1 ratio, women carrying singleton fetuses with a moderate isolated congenital diaphragmatic hernia on the left side to FETO at 30 to 32 weeks of gestation or expectant care. Both treatments were followed by standardized postnatal care. The primary outcomes were infant survival to discharge from a neonatal intensive care unit (NICU) and survival without oxygen supplementation at 6 months of age. RESULTS In an intention-to-treat analysis involving 196 women, 62 of 98 infants in the FETO group (63%) and 49 of 98 infants in the expectant care group (50%) survived to discharge (relative risk, 1.27; 95% confidence interval [CI], 0.99 to 1.63; twosided P = 0.06). At 6 months of age, 53 of 98 infants (54%) in the FETO group and 43 of 98 infants (44%) in the expectant care group were alive without oxygen supplementation (relative risk, 1.23; 95% CI, 0.93 to 1.65). The incidence of preterm, prelabor rupture of membranes was higher among women in the FETO group than among those in the expectant care group (44% vs. 12%; relative risk, 3.79; 95% CI, 2.13 to 6.91), as was the incidence of preterm birth (64% vs. 22%, respectively; relative risk, 2.86; 95% CI, 1.94 to 4.34), but FETO was not associated with any other serious maternal complications. There were two spontaneous fetal deaths (one in each group) without obvious cause and one neonatal death that was associated with balloon removal. CONCLUSIONS This trial involving fetuses with moderate congenital diaphragmatic hernia on the left side did not show a significant benefit of FETO

Tracheal cartilage provides architectural integrity to the respiratory airway, and defects in this structure during embryonic development cause severe congenital anomalies. Previous genetic studies have revealed genes that are critical for the development of tracheal cartilage. However, it is still unclear how crosstalk between these proteins regulates tracheal cartilage formation. Here we show a core regulatory network underlying murine tracheal chondrogenesis from embryonic day (E) 12.5 to E15.5, by combining volumetric imaging of fluorescence reporters, inhibitor assays, and mathematical modeling. We focused on SRY-box transcription factor 9 (Sox9) and extracellular signal-regulated kinase (ERK) in the tracheal mesenchyme, and observed a synchronous, inverted U-shaped temporal change in both Sox9 expression and ERK activity with a peak at E14.5, whereas the expression level of downstream cartilage matrix genes, such as collagen II alpha 1 (Col2a1) and aggrecan (Agc1), monotonically increased. Inhibitor assays revealed that the ERK signaling pathway functions as an inhibitory regulator of tracheal cartilage differentiation during this period. These results suggest that expression of the cartilage matrix genes is controlled by an incoherent feedforward loop via Sox9 and ERK, which is supported by a mathematical model. Furthermore, the modeling analysis suggests that a Sox9-ERK incoherent feedforward regulation augments the robustness against the variation of upstream factors. The present study provides a better understanding of the regulatory network underlying the tracheal development and will be helpful for efficient induction of tracheal organoids.

У статті наведено дані патоморфології органів курей за інфекційного бронхіту. Авторами встановлено, що ураження органів за інфекційного бронхіту курей має системний характер і проявляється залежно від віку птиці та форми захворювання: за респіраторної форми найбільше вражаються легені у курей 20-добового віку; за нефрозо-нефритної форми – нирки у 40, 90-добовому віці; за репродуктивної форми – яєчники та яйцепроводи у 285-добовому віці. При цьому, за респіраторної форми інфекційного бронхіту в легенях курей спостерігали гіперемію та набряк строми, у пневмокапілярах і навколо судин міститься набрякова рідина. Значна кількість пневмокапілярів заповнена десквамованим епітелієм і лімфоцитами. Окремі ділянки легеневої тканини і тканина навколо судин просочені транссудатом. У просвіті парабронхів відмічали наявність десквамованого епітелію, лімфоцитів та слизово-серозного ексудату. Зустрічалися великі ділянки ателектазу, які межували з ділянками компенсаторної емфіземи. Хвороба супроводжувалася катарально-геморагічним, крупозним запаленням бронхів. В багатьох випадках спостерігали гіперемію та крововиливи на слизовій оболонці трахеї, нерідко катаральний бронхіт. За нефрозонефритної форми інфекційного бронхіту у нирках курей реєстрували гіперемію та крововиливи в строму, зернисту дистрофію, некроз і десквамацію клітин епітелію канальців, у просвіті яких виявляли накопичення білкової маси, а також кровонаповнення капілярного сплетення судинного клубочка. За репродуктивної форми інфекційного бронхіту у яйцепроводі відмічали наявність кіст, особливо в передній його частині. Задня частина яйцепроводу переважно була атрофована. Яєчник був значно зменшений і вкритий жовтими тілами. Надалі наставала атрезія і дегенеративні зміни у яйцевих фолікулах., The article presents the data of pathomorphology of chicken organs for infectious bronchitis. The authors found that the lesions of the organs for infectious bronchitis of chickens are systemic in nature and manifests itself depending on the age of the bird and the form of the disease: in the respiratory form, the lungs are most affected in chickens of 20-day age; in the nephroso-nephritis form – kidneys at 40, 90-day age; in the reproductive form – ovaries and ovaries at 285-day age. In this case, the respiratory form of infectious bronchitis in the lungs of chickens was observed hyperemia and edema of stroma, in pnevmocapillar and around the vessel contains a transudate. A significant number of pneumocapillars filled desquamated epithelium and lymphocytes. Some parts of the lung tissue and the tissue around the vessels are impregnated with transudate. In the lumen of parabronchus the presence of desquamated epithelium, lymphocytes, and muco-serous exudate noted. There were large areas of atelectasis, which bordered on areas of compensatory emphysema. The disease was accompanied by catarrhal-hemorrhagic, croup inflammation of the bronchus. In many cases, hyperemia and hemorrhages on the mucous membrane of the trachea, often catarrhal bronchitis, were observed. For nephroso-nephritis forms of infectious bronchitis in the kidneys of chickens for infectious bronchitis, hyperemia and hemorrhages in the stroma, granular dystrophy, necrosis and desquamation of tubular epithelial cells were recorded, in the lumen of which the accumulation of protein mass was detected, as well as blood filling of the capillary plexus of the vascular glomerulus. According to the reproductive form of infectious bronchitis in the oviduct, the presence of cysts was noted, especially in the anterior part of it. The posterior part of the oviduct was predominantly atrophied. The ovary was significantly reduced and covered with yellow bodies. In the future, atresia and degenerative changes in the, В статье приведены данные патоморфологии органов кур при инфекционном бронхите. Авторами установлено, что поражение органов при инфекционном бронхите кур носит системный характер и проявляется в зависимости от возраста птицы и формы заболевания: при респираторной форме поражаются легкие у кур 20-суточного возраста; при нефрозо-нефритной форме - почки в 40, 90-суточном возрасте; при репродуктивной форме - яичники и яйцеводы в 285-суточном возрасте. При этом, при респираторной форме инфекционного бронхита в легких кур наблюдали гиперемию и отек стромы, в пневмокапилярах и вокруг сосудов содержится отечная жидкость. Значительное количество пневмокапиляров заполнено десквамированным эпителием и лимфоцитами. Отдельные участки легочной ткани вокруг сосудов пропитанные транссудатом. В просвете парабронхов отмечали наличие десквамированного эпителия, лимфоцитов и слизисто-серозного экссудата. Встречались большие участки ателектаза, которые граничили с участками компенсаторной эмфиземы. Болезнь сопровождалась катарально-геморрагическим, крупозным воспалением бронхов. Во многих случаях наблюдали гиперемию и кровоизлияния на слизистой оболочке трахеи, часто катаральный бронхит. При нефрозонефритной форме инфекционного бронхита в почках кур регистрировали гиперемию и кровоизлияния в строму, зернистую дистрофию, некроз и десквамацию клеток эпителия канальцев, в просвете которых отмечалили накопления белковой массы, а также кровенаполнения капиллярного сплетения сосудистого клубочка. При репродуктивной форме инфекционного бронхита в яйцеводе отмечали наличие кист, особенно в передней части. Задняя часть яйцевода преимущественно была атрофирована. Яичник был значительно уменьшен и покрыт желтыми телами. В дальнейшем наступала атрезия и дегенеративные изменения в яйцевых фолликулах.

Specification of the trachea and esophagus from the embryonic foregut is critical for the function of the respiratory and digestive systems. Congenital birth defects associated with improper tracheoesophageal development in humans are common and have severe consequences to respiration and feeding that require immediate surgical intervention. During development, tracheoesophageal specification is dependent on proper dorsoventral patterning of the foregut endoderm tube. This involves the establishment of ventral NKX2.1 and dorsal SOX2 expression domains that are thought to promote tracheal and esophageal fate, respectively. Loss of Nkx2.1 results in failed foregut separation, and adoption of SOX2 expression throughout the common foregut tube. Similarly, loss of Sox2 results in a common foregut tube expressing NKX2.1, leading to the previous conclusion that both of these transcription factors are master regulators of tracheal and esophageal fate, respectively. However, our understanding of tracheoesophageal fate specification is limited by a lack of information on dorsoventral foregut patterning at the transcriptome level. In this study, we use genome-wide methods to understand how tracheal and esophageal lineages are specified during mouse embryonic development. We use single cell RNA-sequencing to define transcriptomic profiles of early developing mouse trachea, lung, and esophagus, and discover a multitude of previously unknown markers of these tissues. Transcriptomic analysis of Nkx2.1-/- mutant foreguts reveals that NKX2.1 loss does not result in lineage conversion to esophagus as previously hypothesized and exposes an NKX2.1-independent tracheoesophageal program. Using ChIP-seq against NKX2.1, we identify direct NKX2.1 regulatory targets and interrogate their combinatorial regulation by NKX2.1 and SOX2 in compound mouse mutant analysis. Amongst the novel targets we identify are Shh and Wnt7b, which we demonstrate are regulated by NKX2.1 to control tracheal and es

Cells use motile cilia to generate force in the extracellular space. The structure of a cilium can be classified into three subdomains: the intracellular basal body (BB) that templates cilium formation, the extracellular axoneme that generates force, and the transition zone (TZ) that bridges them. While the BB is composed of triplet microtubules (TMTs), the axoneme is composed of doublet microtubules (DMTs), meaning the cilium must convert between different microtubule geometries. Here, we performed electron cryotomography to define this conversion, and our reconstructions reveal identifying structural features of the BB, TZ, and axoneme. Each region is distinct in terms of microtubule number and geometry, microtubule inner proteins, and microtubule linkers. TMT to DMT conversion occurs within the BB, and microtubule geometry changes to axonemal by the end of the TZ, followed by the addition of axoneme-specific components essential for cilium motility. Our results provide the highest-resolution images of the motile cilium to date and reveal how BBs template axonemes.

Background: The aetiology of post-partum chest pain range from benign to life-threatening. Concerning causes include pulmonary embolism, pneumothorax, myocardial infarction, peripar-tum cardiomyopathy, aortic dissection, and oesophageal rupture. Case: A 24-year-old primigravid, antenatally well lady arrived fully dilated in spontaneous labour. She commenced pushing and at 1 h suddenly developed right-sided facial, eyelid, and neck swelling. She progressed to deliver a male liveborn baby. Day 1 post-partum she developed worsening throat swelling, dysphonia, chest tightness, and subcutaneous emphysema along her trachea and anterior chest with normal air entry and vital signs. An ECG was norma and chest x-ray showed pneumomediastinum and bilateral supraclavicular subcutaneous emphysema. A follow-up CT scan showed a moderate to large volume pneumomediastinum encircling the oesophagus, trachea, and thyroid. Gas was also tracking bilaterally within the bronchovascular interstitium, the oblique and right horizontal fissure, lower cervical soft tissues and bilateral supraclavicular regions with no signs of oesophageal perforation. She was diagnosed with Hamman's syndrome (spontaneous pneumomediastinum and subcutaneous emphysema) and managed conservatively. The patient's condition gradually stabilized prior to discharge. Discussion(s): Hamman's syndrome is an uncommon cause of spontaneous pneumomediastinum and subcutaneous emphysema. Pneumomediastinum occurs when air leaks through smal alveolar ruptures, the upper respiratory, or gastrointestinal tracts. Predisposing factors include prolonged labour, forceful coughing or vomiting, or asthmatic bronchospasm. Common presenting symptoms of pneumomediastinum include chest pain, dyspnoea, cough, neck pain, odynophagia, dysphagia. Exclusion of other serous causes of pneumomediastinum including pneumothorax and Boerhaave's syndrome (spontaneous transmural perforation of the oesophagus) is essential.

Author Posting. © Company of Biologists, 2020. This article is posted here by permission of Company of Biologists for personal use, not for redistribution. The definitive version was published in Journal of Experimental Biology 223 (2020): jeb217885, doi:10.1242/jeb.217885., Assessment of the compressibility of marine mammal airways at depth is crucial to understanding vital physiological processes such as gas exchange during diving. Very few studies have directly assessed changes in cetacean and pinniped tracheobronchial shape, and none have quantified changes in volume with increasing pressure. A harbor seal, gray seal, harp seal, harbor porpoise and common dolphin were imaged promptly post mortem via computed tomography in a radiolucent hyperbaric chamber. Volume reconstructions were performed of segments of the trachea and bronchi of the pinnipeds and bronchi of the cetaceans for each pressure treatment. All specimens examined demonstrated significant decreases in airway volume with increasing pressure, with those of the harbor seal and common dolphin nearing complete collapse at the highest pressures. The common dolphin bronchi demonstrated distinctly different compression dynamics between 50% and 100% lung inflation treatments, indicating the importance of air in maintaining patent airways, and collapse occurred caudally to cranially in the 50% treatment. Dynamics of the harbor seal and gray seal airways indicated that the trachea was less compliant than the bronchi. These findings indicate potential species-specific variability in airway compliance, and cessation of gas exchange may occur at greater depths than those predicted in models assuming rigid airways. This may potentially increase the likelihood of decompression sickness in these animals during diving., This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors., 2021-02-10

Disease has large negative impacts on poultry production. A more comprehensive understanding of host-pathogen interaction can lead to new and improved strategies to maintain health. In particular, host genetic factors can lead to a more effective response to pathogens, hereafter termed resistance. Fayoumi and Leghorn chicken lines have demonstrated relative resistance and susceptibility, respectively, to the Newcastle disease virus (NDV) vaccine strain and many other pathogens. This biological model was used to better understand the host response to a vaccine strain of NDV across three tissues and time points, using RNA-seq. Analyzing the Harderian gland, trachea, and lung tissues together using weighted gene co-expression network analysis (WGCNA) identified important genes that were co-expressed and associated with parameters including: genetic line, days post-infection (dpi), challenge status, sex, and tissue. Pathways and driver genes, such as EIF2AK2, MPEG1, and TNFSF13B, associated with challenge status, dpi, and genetic line were of particular interest as candidates for disease resistance. Overall, by jointly analyzing the three tissues, this study identified genes and gene networks that led to a more comprehensive understanding of the whole animal response to lentogenic NDV than that obtained by analyzing the tissues individually.

The genome-scale transcriptional programs that specify the mammalian trachea and esophagus are unknown. Though NKX2-1 and SOX2 are hypothesized to be co-repressive master regulators of tracheoesophageal fates, this is untested at a whole transcriptomic scale and their downstream networks remain unidentified. By combining single-cell RNA-sequencing with bulk RNA-sequencing of Nkx2-1 mutants and NKX2-1 ChIP-sequencing in mouse embryos, we delineate the NKX2-1 transcriptional program in tracheoesophageal specification, and discover that the majority of the tracheal and esophageal transcriptome is NKX2-1 independent. To decouple the NKX2-1 transcriptional program from regulation by SOX2, we interrogate the expression of newly-identified tracheal and esophageal markers in Sox2/Nkx2-1 compound mutants. Finally, we discover that NKX2-1 binds directly to Shh and Wnt7b and regulates their expression to control mesenchymal specification to cartilage and smooth muscle, coupling epithelial identity with mesenchymal specification. These findings create a new framework for understanding early tracheoesophageal fate specification at the genome-wide level.

The respiratory system, which includes the trachea, airways, and distal alveoli, is a complex multi-cellular organ that intimately links with the cardiovascular system to accomplish gas exchange. In this review and as members of the NIH/NHLBI-supported Progenitor Cell Translational Consortium, we discuss key aspects of lung repair and regeneration. We focus on the cellular compositions within functional niches, cell-cell signaling in homeostatic health, the responses to injury, and new methods to study lung repair and regeneration. We also provide future directions for an improved understanding of the cell biology of the respiratory system, as well as new therapeutic avenues.

The conducting airway forms a protective mucosal barrier and is the primary target of airway disorders. The molecular events required for the formation and function of the airway mucosal barrier, as well as the mechanisms by which barrier dysfunction leads to early onset airway diseases, remain unclear. In this study, we systematically characterized the developmental landscape of the mouse airway using single-cell RNA sequencing and identified remarkably conserved cellular programs operating during human fetal development. We demonstrated that in mouse, genetic inactivation of chloride channel Ano1/Tmem16a compromises airway barrier function, results in early signs of inflammation, and alters the airway cellular landscape by depleting epithelial progenitors. Mouse Ano1-/-mutants exhibited mucus obstruction and abnormal mucociliary clearance that resemble the airway defects associated with cystic fibrosis. The data reveal critical and non-redundant roles for Ano1 in organogenesis, and show that chloride channels are essential for mammalian airway formation and function.

According to our previous reports, impaired oocyte pickup was observed in the oviductal infundibulum of an autoimmune disease (AD) mouse model, suggesting a relationship between female infertility and AD. This study examines the relationship between AD and infundibulum morphofunction by focusing on the epithelial cilia. Healthy MRL/MpJ and AD-prone MRL/MpJ-Fas(lpr/lpr) mice were examined at 3 and 6 months of age, representing early and late disease stages, respectively. Oocyte pickup indices decreased with AD progression indicated by splenomegaly, autoantibody production and increased T cell counts of infundibulum mucosa in MRL/MpJ-Fas(lpr/lpr) mice. Ciliary beating frequency (CBF) and height in the infundibulum were faster and higher in MRL/MpJ-Fas(lpr/lpr) mice than in MRL/MpJ mice at the early AD stages, although the absolute CBF values were lower at the late AD stage. At the late stage, ciliary height did not differ between mouse lines but the morphological index of cilia beating direction indicated randomized patterns in MRL/MpJ-Fas(lpr/lpr) mice. The tracheal mucosa was also examined as a representative example of cilia morphology; its CBF decreased at the late AD stage in MRL/MpJ-Fas(lpr/lpr); however, there were no AD-related morphological changes. Our results demonstrate altered cilia motility in systemic and reproductive organs, with such morphological changes of the infundibulum likely impairing function, including oocyte pickup.

Airway smooth muscle is best known for its role as an airway constrictor in diseases such as asthma. However, its function in lung development is debated. A prevalent model, supported by in vitro data, posits that airway smooth muscle promotes lung branching through peristalsis and pushing intraluminal fluid to branching tips. Here, we test this model in vivo by inactivating Myocardin, which prevented airway smooth muscle differentiation. We found that Myocardin mutants show normal branching, despite the absence of peristalsis. In contrast, tracheal cartilage, vasculature, and neural innervation patterns were all disrupted. Furthermore, airway diameter is reduced in the mutant, counter to the expectation that the absence of smooth muscle constriction would lead to a more relaxed and thereby wider airway. These findings together demonstrate that during development, while airway smooth muscle is dispensable for epithelial branching, it is integral for building the tracheal architecture and promoting airway growth.

Objectives: To test the feasibility, safety, and efficacy of intratracheal delivery of nitric oxide (NO) generated from air by pulsed electrical discharge via a Scoop catheter. Study design: We studied healthy 3- to 4-month-old lambs weighing 34 ± 4 kg (mean ± SD, n = 6). A transtracheal Scoop catheter was inserted through a cuffed tracheostomy tube. U46619 was infused to increase mean pulmonary arterial pressure (mPAP) from 16 ± 1 to 32 ± 3 mmHg (mean ± SD). Electrically generated NO was delivered via the Scoop catheter to awake lambs. A sampling line, to monitor NO and nitrogen dioxide (NO2) levels, was placed in the distal trachea of the lambs. The effect of varying doses of electrically generated NO, produced continuously, on pulmonary hypertension was assessed. Results: In awake lambs with acute pulmonary hypertension, NO was continuously delivered via the Scoop catheter at 400 ml/min. NO induced pulmonary vasodilation. NO2 levels, measured in the trachea, were below 0.5 ppm at intratracheal NO doses of 10–80 ppm. No changes were detected in the levels of methemoglobin in blood samples before and after 5 min of NO breathing. Conclusions: Continuously delivering electrically generated NO through a Scoop catheter produces vasodilation of the pulmonary vasculature of awake lambs with pulmonary hypertension. Transtracheal NO delivery may provide a long-term treatment for patients with chronic pulmonary hypertension as an outpatient without requiring a mask or tracheal intubation.

Cells use motile cilia to generate force in the extracellular space. The structure of a cilium can be classified into three subdomains: the intracellular basal body (BB) that templates cilium formation, the extracellular axoneme that generates force, and the transition zone (TZ) that bridges them. While the BB is composed of triplet microtubules (TMTs), the axoneme is composed of doublet microtubules (DMTs), meaning the cilium must convert between different microtubule geometries. Here, we performed electron cryotomography to define this conversion, and our reconstructions reveal identifying structural features of the BB, TZ, and axoneme. Each region is distinct in terms of microtubule number and geometry, microtubule inner proteins, and microtubule linkers. TMT to DMT conversion occurs within the BB, and microtubule geometry changes to axonemal by the end of the TZ, followed by the addition of axoneme-specific components essential for cilium motility. Our results provide the highest-resolution images of the motile cilium to date and reveal how BBs template axonemes.

The original article [1] contains two errors in Fig. 1: 1) Fig. 1A mistakenly shows a tracheoesophageal fistula instead of the intended image of a tracheal agenesis. 2) There is a small omission in Fig. 1C whereby arrows intended to annotate the image are missing. The correct versions of Figs. 1A and 1C can be viewed ahead in this correction article. (Figure Presented).

Background: Tracheal agenesis (TA) is a rare disorder usually diagnosed prenatally when a congenital high airway obstruction syndrome (CHAOS) is identified. We present a case of unexpected TA in a neonate without prenatal diagnosis of airway obstruction, with a difficult management at birth. Moreover, we discuss about differential diagnosis, classification and treatment issues. Case presentation: A 2280 g female neonate was born at 35 week gestational age (GA) with prenatal diagnosis of aortic coarctation, polyhydramnios and diffuse hyperechogenicity of the right lung. At birth, the neonate had no audible cry, no air entry to the lungs, and hypotonia. Tracheal intubation was unsuccessful, and no visualization of the trachea was obtained when tracheostomy was attempted. Post-mortem examination showed tracheal agenesis associated with tracheoesophageal fistula and revealed no cardiologic malformations. Aortic coarctation had been suspected prenatally because of the first portion of the descendent thoracic aorta being compressed by a fibrous band connecting the proximal and distal tracheal branches. CHAOS had not developed due to the tracheoesophageal fistula (TOF). Conclusions: TA is not always diagnosed in the fetus and it may present unexpectedly making the neonate's management at birth critical. An effective rescue temporary oxygenation may be obtained with mask ventilation or oesophageal intubation in those cases of TA associated with a TOF. We suggest to consider a fetal magnetic resonance imaging (MRI) when the association polyhydramnios/lung hyperechogenicity occurs, even in the absence of CHAOS or other malformations. Once a diagnosis is provided, the mother should be transferred to selected centres where an ex-utero intrapartum procedure (EXIT) can be attempted. Moreover, despite high mortality, different surgical management are described to improve survival.

Oxygen- and capacity-limited thermal tolerance (OCLTT) is a controversial hypothesis claiming to explain variation in, and mechanistically determine, animal thermal limits. The lack of support from Insecta is typically argued to be a consequence of their high-performance respiratory systems. However, no studies have reported internal body oxygen levels during thermal ramping so it is unclear if changes in ambient gas are partially or fully offset by a compensatory respiratory system. Here we provide such an assessment by simultaneously recording haemolymph oxygen (pO(2)) levels-as an approximation of tissue oxygenation-while experimentally manipulating ambient oxygen and subjecting organisms to thermal extremes in a series of thermolimit respirometry experiments using pupae of the butterfly Pieris napi. The main results are that while P. napi undergo large changes in haemolymph pO(2) that are positively correlated with experimental oxygen levels, haemolymph pO(2) is similar pre-and post-death during thermal assays. OCLTT predicts that reduction in body oxygen level should lead to a reduction in CTmax. Despite finding the former, there was no change in CTmax across a wide range of body oxygen levels. Thus, we argue that oxygen availability is not a functional determinant of the upper thermal limits in pupae of P. napi.

Background: Management of the difficult airway in ENT surgery can be challenging, particularly because conventional difficult airway algorithms often are not applicable. Awake tracheostomies are now less frequently performed by surgeons, and in some cases may not be feasible due to the location and spread of pathology. Transtracheal jet ventilation (TTJV) offers a safe, feasible alternative that can be performed with minimal discomfort on the awake patient, yet is rarely practiced in Australian healthcare centers due to lack of familiarity.1 To our knowledge, no audit has been performed on TTJV in Australia on this scale for ENT surgery. Method(s): We report a retrospective audit of the use of TTJV in a tertiary healthcare centre in Melbourne, Victoria, over the past 7 years, with a total of 50 patients with severe airway compromise undergoing pharynolar-yngeal surgery. Result(s): TTJV was successful in 98% of patients. Only one patient required further postoperative attention for possible airway compromise, but recovered uneventfully. Minor complications occurred in 12% of patients, which is a substantial improvement compared to other cases in the literature. Rates of complications and ease of insertion (measured by number of needle passes) demonstrated improvement. Conclusion(s): TTJV should always be performed using a high-frequency jet ventilator (HFJV). Imaging prior to TTJV is highly recommended. Cannulation of the trachea below the cricothyroid membrane is feasible but more challenging to the inexperienced anaesthetist. Apnoeic oxygenation through the TTJV cannula is delays desaturation in the well-preoxygenated patient.

Introduction/Aim. Limited attention has been paid to laryngeal and tracheal ('middle airway') dysfunction in asthma and COPD. We have demonstrated that vocal cord dysfunction (VCD) can be detected in up to 20% of symptomatic asthma but this has never been studied in COPD. Moreover, excessive dynamic airway collapse (EDAC) occurs frequently in COPD (Leong, Resp Res, 2017) and in asthma (unpublished observations), thus it is possible that laryngeal instabilty and dysfunction predispose to VCD. The aim of current studies was to determine the prevalence of VCD and EDAC in symptomatic asthma and COPD and to examine links between VCD and EDAC. Methods. Patients with symptomatic asthma (n = 125) and COPD (n = 101) suspected of having VCD (total n = 226) as well as healthy control individuals (n = 35) were assessed using dynamic 320-slice CT larynx and trachea. VCD was diagnosed only if detected during inspiration using a validated algorithym described by Low et al. (AJRCCM 2011). EDAC was diagnosed by CT if tracheal area during expiration was <50% of maximal tracheal area during inspiration. Groups were compared using appropriate statistical methods. Results. VCD and EDAC were absent in controls. VCD was diagnosed in 50/226 ((22.1%) cases and EDAC in 58/226 (25.7%) overall. VCD was present in asthma in 18/125 (14.4%) patients and in 32/101 (31.6%) patients with COPD (P < 0.01). EDAC was detected in asthma in 22/125 (17.6%) and in 36/101 (35.6%) cases with COPD (P < 0.01). Both VCD and EDAC together occurred in only 18/226 (8.0%) cases; more often in COPD (13/101, 12.9%) than in asthma (5/125, 4%; P < 0.01). Conclusion. Surprisingly VCD was more frequently detected in COPD than in asthma and more patients had EDAC. However, a minority of patients with VCD had coexisting EDAC suggesting that a pathological link between VCD and tracheal dysfunction may be unlikely. These observations merit further study.

Introduction: Cystic fibrosis (CF) predominantly affects young adults. Accurate radiological assessment of pulmonary disease is vital for predicting exacerbations, one of the leading causes of morbidity and mortality. We evaluated the image quality of model-based iterative reconstruction (MBIR) ultra-low-dose CT chest (ULD-CT) in CF evaluation. Method(s): We compared ULD-CT with standard adaptive statistical iterative reconstruction (ASIR) low-dose CT (LD-CT). Subjective assessment of contrast and noise were performed for each study. Background noise, signal to noise ratio (SNR) and contrast to noise ratio (CNR) were calculated and compared between the CT studies. Conspicuity of major structures was assessed. These aspects of image quality were compared to determine whether ULD-CT was superior to LD-CT in assessment of CF. Result(s): The ULD-CT achieved median effective dose of 0.073 mSv, comparable to one standard chest radiograph and significantly lower than the median LD-CT dose of 1.22 mSv. ULD-CT had lower subjective contrast and higher subjective noise when compared to LD-CT. Objectively measured background noise was lower in ULD-CT (16.33 HU vs 38.53 HU, P < 0.0001) compared to LD-CT. ULD-CT had higher median CNR (52.65 vs 22.09, P < 0.0001) and SNR in lung (9.08 vs 7.29, P = 0.002) compared to LD-CT. ULD-CT was equal to LD-CT in identification of trachea, bronchi, pleural and pericardium. Interobserver reliability showed agreement of 80-92%. Conclusion(s): The image quality of ULD-CT is similar to LD-CT, at 1/16th the dose. MBIR constructed ULD-CT is an effective imaging modality for CF surveillance, with potential applications in other disease settings.Copyright © 2019 The Royal Australian and New Zealand College of Radiologists

A new trainee in clinical genetics is confronted with a number of eponymous syndromes which need to be learned. Many of these are outlined in the FRACP clinical genetics syllabus and the Oxford Desk Reference in Clinical Genetics. A trainee needs to be able to discuss these conditions intelligently and consider them as part of a differential diagnosis, despite never having seen the condition. As well as eponymous syndromes, there are a number of conditions named after the main signs and symptoms, such as VACTERL association (vertebral defects, anal atresia, cardiac defects, trachea-oesophageal-fistula, renal anomalies and limb abnormalities. Acronyms can be a good way to learn a large of amount of information for some people, but should not be made mandatory. We previously introduced new acronyms to help memorize the clinical features of common clinical genetics conditions with the following rules (1) avoid pejoratives, (2) common conditions, (3) use the eponymous name if possible, (4) avoid 'ABCE...' etc. and (5) include scoring systems if possible. Here, we further extend upon that work and introduce thirty new acronyms: ADAM Syndr, APERT, BARDET BIEDL, BATTEN, CANTU, LOWRY Syndr, COHEN, DIAMOND blackfan, ELLIS VAN C, FABRY S, FEINGOLD, FETAL alcohol, GAUCHER, GOLDENHAR, GORLIN, GRIEG, HIPPEL, MECP2, MOEBIUS, MUCOPOLYSACCharidosis, DySTROPIA, PEARSON, Poland, POMPE, PROTUES, STEINER, STICKLER, TRECHER, TUBEROUS and WEAVER. With these new acronyms, pre-existing acronyms for named conditions (i.e., VACTERL) and acronyms available on the internet (i.e., MUSCLES for Duchenne Muscular Dystrophy) we hope to cover 100 common clinical genetics conditions.

Avibacterium paragallinarum is the causative agent of infectious coryza, a highly contagious respiratory disease in chickens. Given its fastidious nature, this bacterium is difficult to recover and identify, particularly from locations colonized by normal bacterial flora. Standard PCR methods have been utilized for detection but are labor-intensive and not feasible for high-throughput testing. We evaluated a real-time PCR (rtPCR) method targeting the HPG-2 region of A. paragallinarum, and validated a high-throughput extraction for this assay. Using single-tube extraction, the rtPCR detected 4 A. paragallinarum (ATCC 29545T and 3 clinical) isolates with a limit of detection (LOD) of 10 cfu/mL and a PCR efficiency of 89-111%. Cross-reaction was not detected with 33 non-A. paragallinarum, all close relatives from the family Pasteurellaceae. Real-time PCR testing on extracts of 66 clinical samples (choana, sinus, or trachea) yielded 98.2% (35 of 36 on positives, 30 of 30 on negatives) agreement with conventional PCR. Duplicate samples tested in a 96-well format extraction in parallel with the single-tube method produced equivalent LOD on all A. paragallinarum isolates, and 96.8% agreement on 93 additional clinical samples extracted with both procedures. This A. paragallinarum rtPCR can be utilized for outbreak investigations and routine monitoring of susceptible flocks.

Tricellular adherens junctions are points of high tension that are central to the rearrangement of epithelial cells. However, the molecular composition of these junctions is unknown, making it difficult to assess their role in morphogenesis. Here, we show that Sidekick, an immunoglobulin family cell adhesion protein, is highly enriched at tricellular adherens junctions in Drosophila. This localization is modulated by tension, and Sidekick is itself necessary to maintain normal levels of cell bond tension. Loss of Sidekick causes defects in cell and junctional rearrangements in actively remodeling epithelial tissues like the retina and tracheal system. The adaptor proteins Polychaetoid and Canoe are enriched at tricellular adherens junctions in a Sidekick-dependent manner; Sidekick functionally interacts with both proteins and directly binds to Polychaetoid. We suggest that Polychaetoid and Canoe link Sidekick to the actin cytoskeleton to enable tricellular adherens junctions to maintain or transmit cell bond tension during epithelial cell rearrangements.

OBJECTIVES: Latest trials failed to confirm merits of nebulized amikacin for critically ill patients with nosocomial pneumonia. We studied various nebulized and IV antibiotic regimens in a porcine model of severe Pseudomonas aeruginosa pneumonia, resistant to amikacin, fosfomycin, and susceptible to meropenem. DESIGN: Prospective randomized animal study. SETTING: Animal Research, University of Barcelona, Spain. SUBJECTS: Thirty female pigs. INTERVENTIONS: The animals were randomized to receive nebulized saline solution (CONTROL); nebulized amikacin every 6 hours; nebulized fosfomycin every 6 hours; IV meropenem alone every 8 hours; nebulized amikacin and fosfomycin every 6 hours; amikacin and fosfomycin every 6 hours, with IV meropenem every 8 hours. Nebulization was performed through a vibrating mesh nebulizer. The primary outcome was lung tissue bacterial concentration. Secondary outcomes were tracheal secretions P. aeruginosa concentration, clinical variables, lung histology, and development of meropenem resistance. MEASUREMENTS AND MAIN RESULTS: We included five animals into each group. Lung P. aeruginosa burden varied among groups (p < 0.001). In particular, IV meropenem and amikacin and fosfomycin + IV meropenem groups presented lower P. aeruginosa concentrations versus amikacin and fosfomycin, amikacin, CONTROL, and fosfomycin groups (p < 0.05), without significant difference between these two groups undergoing IV meropenem treatment. The sole use of nebulized antibiotics resulted in dense P. aeruginosa accumulation at the edges of the interlobular septa. Amikacin, amikacin and fosfomycin, and amikacin and fosfomycin + IV meropenem effectively reduced P. aeruginosa in tracheal secretions (p < 0.001). Pathognomonic clinical variables of respiratory infection did not differ among groups. Resistance to meropenem increased in IV meropenem group versus amikacin and fosfomycin + meropenem (p = 0.004). CONCLUSIONS: Our findings corroborate that amikacin and

Background: We previously showed that pretreatment with intratracheal delivery (ITD) of alloantigen induced prolonged cardiac allograft survival and generated regulatory T cells (Tregs) in mice. In this study, we examined the role of splenic dendritic cells (DCs) in the ITD model. Methods: CBA mice were treated with ITD from C57BL/10 splenocytes and 7 days later received transplantation of C57BL/10 hearts. In adoptive transfer studies, splenic DCs from ITD-treated mice were transferred into naive CBA recipients that received C57BL/10 hearts immediately after the transfer. In addition, to determine the role of splenic DCs isolated from ITD-treated mice, the cells were incubated under stimulation with lipopolysaccharide (LPS). Results: ITD-treated CBA recipients had markedly prolonged allograft survival (median survival time [MST], 67 days) while naive recipients rejected allografts acutely (MST, 8 days). In adoptive transfer studies, CBA recipients of the transfer of splenic DCs from ITD-treated mice had prolonged allograft survival (MST, 85 days), while CBA recipients of the transfer of splenic DCs from naive mice did not have prolonged allograft survival (MST, 8 days). In another transfer study, CBA recipients of the transfer of splenic CD8α+ DCs from ITD-treated mice had prolonged allograft survival (MST, 79 days), while those receiving splenic CD8α- DCs from ITD-treated mice did not have prolonged allograft survival (MST, 8 days). In vitro studies showed that ITD-treated splenic DCs produced more IL-10 and less IL-12 than naive splenic DCs under stimulation with LPS. Conclusions: ITD pretreatment induces regulatory DCs, which produce high amounts of IL-10 resulting in the prolongation of graft survival in our model.

Development of effective rescue countermeasures for toxic inhalational industrial chemicals, such as methyl isocyanate (MIC), has been an emerging interest. Nonetheless, current methods for studying toxin-induced airway injuries are limited by cost, labor time, or accuracy, and only provide indirect or localized information. Optical Coherence Tomography (OCT) endoscopic probes have previously been used to visualize the 3-D airway structure. However, gathering such information in small animal models, such as rat airways after toxic gas exposure, remains a challenge due to the required probe size necessary for accessing the small, narrow, and partially obstructed tracheas. In this study, we have designed a 0.4 mm miniature endoscopic probe and investigated the structural changes in rat trachea after MIC inhalation. An automated 3D segmentation algorithm was implemented so that anatomical changes, such as tracheal lumen volume and cross-sectional areas, could be quantified. The tracheal region of rats exposed to MIC by inhalation showed significant airway narrowing, especially within the upper trachea, as a result of epithelial detachment and extravascular coagulation within the airway. This imaging and automated reconstruction technique is capable of rapid and minimally-invasive identification of airway obstruction. This method can be applied to large-scale quantitative analysis of in vivo animal models.