Measuring the impact of maternal critical care admission on short- and longer-term maternal and birth outcomes.

PURPOSE: Factors increasing the risk of maternal critical illness are rising in prevalence in maternity populations. Studies of general critical care populations highlight that severe illness is associated with longer-term physical and psychological morbidity. We aimed to compare short- and longer-term outcomes between women who required critical care admission during pregnancy/puerperium and those who did not. METHODS: This is a cohort study including all women delivering in Scottish hospitals between 01/01/2005 and 31/12/2018, using national healthcare databases. The primary exposure was intensive care unit (ICU) admission, while secondary exposures included high dependency unit admission. Outcomes included hospital readmission (1-year post-hospital discharge, 1-year mortality, psychiatric hospital admission, stillbirth, and neonatal critical care admission). Multivariable Cox and logistic regression were used to report hazard ratios (HR) and odds ratios (OR) of association between ICU admission and outcomes. RESULTS: Of 762,918 deliveries, 1449 (0.18%) women were admitted to ICU, most commonly due to post-partum hemorrhage (225, 15.5%) followed by eclampsia/pre-eclampsia (133, 9.2%). Over-half (53.8%) required mechanical ventilation. One-year hospital readmission was more frequent in women admitted to ICU compared with non-ICU populations [24.5% (n = 299) vs 8.9% (n = 68,029)]. This association persisted after confounder adjustment (HR 1.93, 95% confidence interval [CI] 1.33, 2.81, p < 0.001). Furthermore, maternal ICU admission was associated with increased 1-year mortality (HR 40.06, 95% CI 24.04, 66.76, p < 0.001), stillbirth (OR 12.31, 95% CI 7.95,19.08, p < 0.001) and neonatal critical care admission (OR 6.99, 95% CI 5.64,8.67, p < 0.001) after confounder adjustment. CONCLUSION: Critical care admission increases the risk of adverse short-term and long-term maternal, pregnancy and neonatal outcomes. Optimizing long-term post-partum care may benefit maternal critical illness survivors.

Livestreaming Can Augment the Observation of Veterinary Post-mortem Examinations.

The creation of interactive livestreaming post-mortem examination sessions for veterinary students is described, including the technological and pedagogical issues that were considered and a detailed description of the solution developed. We used the Hero 7 Go Pro camera ( https://gopro.com/en/gb ) and livestreamed using Zoom ( https://explore.zoom.us/en/about/ ). We completed a thorough quantitative and qualitative analysis of the student perception of the value of the streaming platform and the sessions that were delivered to the second and third year students in the Bachelor of Veterinary Medicine and Surgery (BVMS) programme at the University of Glasgow. JISC Online surveys to BVMS2 and BVMS3 were central to the quantitative and qualitative analysis (MVLS Ethics reference 200,190,190).Students who responded to the survey found the material interesting, were able to interact effectively with the pathologists, enjoyed the "pathologists' eye" view that the system afforded, and enjoyed the ability to review and revise the video recording. The disadvantage some mentioned was not being in the appropriate professional space, i.e. the post-mortem facility, although a few students found this advantageous and suggested that this was a useful introduction to the post-mortem facility but without the cold/smell/noise to detract from their learning. In addition, a short explanation of additional uses of the Zoom Go Pro to teach BVMS4 and Veterinary Bioscience BSc Level 3 students and use for extracurricular student activities, e.g. Pathology Club, Student Chapter of the American Veterinary Medical Association at the University of Glasgow School of Veterinary Medicine, is given. The authors also consider other roles for the platform in the future, in particular the induction of students to the post-mortem facility environment.

Fusion Methods for Face Presentation Attack Detection.

Face presentation attacks (PA) are a serious threat to face recognition (FR) applications. These attacks are easy to execute and difficult to detect. An attack can be carried out simply by presenting a video, photo, or mask to the camera. The literature shows that both modern, pre-trained, deep learning-based methods, and traditional hand-crafted, feature-engineered methods have been effective in detecting PAs. However, the question remains as to whether features learned in existing, deep neural networks sufficiently encompass traditional, low-level features in order to achieve optimal performance on PA detection tasks. In this paper, we present a simple feature-fusion method that integrates features extracted by using pre-trained, deep learning models with more traditional colour and texture features. Extensive experiments clearly show the benefit of enriching the feature space to improve detection rates by using three common public datasets, namely CASIA, Replay Attack, and SiW. This work opens future research to improve face presentation attack detection by exploring new characterizing features and fusion strategies.

Detection of morphological changes caused by chemical stress in the cyanobacterium Planktothrix agardhii using convolutional neural networks.

The presence of harmful algal bloom in many reservoirs around the world, alongside the lack of sanitation law/ordinance regarding cyanotoxin monitoring (particularly in developing countries), create a scenario in which the local population could potentially chronically consume cyanotoxin-contaminated waters. Therefore, it is crucial to develop low cost tools to detect possible systems failures and consequent toxin release inferred by morphological changes of cyanobacteria in the raw water. This paper aimed to look for the best combination of convolutional neural network (CNN), optimizer and image segmentation technique to differentiate P. agardhii trichomes before and after chemical stress caused by the addition of hydrogen peroxide. This method takes a step towards accurate monitoring of cyanobacteria in the field without the need for a mobile lab. After testing three different network architectures (AlexNet, 3ConvLayer and 2ConvLayer), four different optimizers (Adam, Adagrad, RMSProp and SDG) and five different image segmentations methods (Canny Edge Detection, Morphological Filter, HP filter, GrabCut and Watershed), the combination 2ConvLayer with Adam optimizer and GrabCut segmentation, provided the highest median accuracy (93.33%) for identifying H2O2-induced morphological changes in P. agardhii. Our results emphasize the fact that the trichome classification problem can be adequately tackled with a limited number of learned features due to the lack of complexity in micrographs from before and after chemical stress. To the authors' knowledge, this is the first time that CNNs were applied to detect morphological changes in cyanobacteria caused by chemical stress. Thus, it is a significant step forward in developing low cost tools based on image recognition, to shield water consumers, especially in the poorest regions, against cyanotoxin-contaminated water.

Protease activated receptor 2 and matriptase expression in the joints of cats with and without osteoarthritis.

OBJECTIVES: The aim of this study was to determine the presence of protease-activated receptor 2 (PAR2) and matriptase proteins and quantify PAR2 and matriptase mRNA expression in the articular cartilage and synovial membrane of cats with and without osteoarthritis (OA). METHODS: A total of 28 articular cartilage samples from adult cats (14 OA and 14 normal), 10 synovial membranes from adult cats (five OA and five normal) and three cartilage samples from 9-week-old fetal cats were used. The presence of PAR2 and matriptase in the cartilage and synovial membrane of the adult samples was detected by immunohistochemical (IHC) staining, while real-time PCR was used for mRNA expression analyses in all samples. RESULTS: PAR2 was detected in all OA and normal articular cartilage and synovial membrane samples but confined to only a few superficial chondrocytes in the normal samples. Matriptase was only detected in OA articular cartilage and synovial membrane samples. PAR2 and matriptase mRNA expression were, however, detected in all cartilage and synovial membrane samples. PAR2 and matriptase mRNA expression levels in OA articular cartilage were five (P <0.001) and 3.3 (P <0.001) times higher than that of the healthy group, respectively. There was no significant difference (P = 0.05) in the OA synovial membrane PAR2 and matriptase mRNA expression compared with the normal samples. CONCLUSIONS AND RELEVANCE: Detection of PAR2 and matriptase proteins and gene expression in feline articular tissues is a novel and important finding, and supports the hypothesis that serine proteases are involved in the pathogenesis of feline OA. The consistent presence of PAR2 and matriptase protein in the cytoplasm of OA chondrocytes suggests a possible involvement of proteases in cartilage degradation. Further investigations into the PAR2 and matriptase pathobiology could enhance our understanding of the proteolytic cascades in feline OA, which might lead to the development of novel therapeutic strategies.

Diagnosis of non-effusive feline infectious peritonitis by reverse transcriptase quantitative PCR from mesenteric lymph node fine-needle aspirates.

OBJECTIVES: The aim of this study was to evaluate a feline coronavirus (FCoV) reverse transcriptase quantitative PCR (RT-qPCR) on fine-needle aspirates (FNAs) from mesenteric lymph nodes (MLNs) collected in sterile saline for the purpose of diagnosing non-effusive feline infectious peritonitis (FIP) in cats. METHODS: First, the ability of the assay to detect viral RNA in MLN FNA preparations compared with MLN biopsy preparations was assessed in matched samples from eight cats. Second, a panel of MLN FNA samples was collected from a series of cats representing non-effusive FIP cases (n = 20), FCoV-seropositive individuals (n = 8) and FCoV-seronegative individuals (n = 18). Disease status of the animals was determined using a combination of gross pathology, histopathology and/or 'FIP profile', consisting of serology, clinical pathology and clinical signs. RESULTS: Viral RNA was detected in 18/20 non-effusive FIP cases; it was not detected in two cases that presented with neurological FIP. Samples from 18 seronegative non-FIP control cats and 7/8 samples from seropositive non-FIP control cats contained no detectable viral RNA. Thus, as a method for diagnosing non-effusive FIP, MLN FNA RT-qPCR had an overall sensitivity of 90.0% and specificity of 96.1%. CONCLUSIONS AND RELEVANCE: In cases with a high index of suspicion of disease, RT-qPCR targeting FCoV in MLN FNA can provide important information to support the ante-mortem diagnosis of non-effusive FIP. Importantly, viral RNA can be reliably detected in MLN FNA samples in saline submitted via the national mail service. When applied in combination with biochemistry, haematology and serological tests in cases with a high index of suspicion of disease, the results of this assay may be used to support a diagnosis of non-effusive FIP.

Age-specific biological and molecular profiling distinguishes paediatric from adult acute myeloid leukaemias.

Acute myeloid leukaemia (AML) affects children and adults of all ages. AML remains one of the major causes of death in children with cancer and for children with AML relapse is the most common cause of death. Here, by modelling AML in vivo we demonstrate that AML is discriminated by the age of the cell of origin. Young cells give rise to myeloid, lymphoid or mixed phenotype acute leukaemia, whereas adult cells give rise exclusively to AML, with a shorter latency. Unlike adult, young AML cells do not remodel the bone marrow stroma. Transcriptional analysis distinguishes young AML by the upregulation of immune pathways. Analysis of human paediatric AML samples recapitulates a paediatric immune cell interaction gene signature, highlighting two genes, RGS10 and FAM26F as prognostically significant. This work advances our understanding of paediatric AML biology, and provides murine models that offer the potential for developing paediatric specific therapeutic strategies.

Proof of concept and feasibility studies examining the influence of combination ribose, adenine and allopurinol treatment on stroke outcome in the rat.

BACKGROUND: Cerebral ischaemia results in a rapid and profound depletion of adenosine triphosphate (ATP), the energy currency of the cell. This depletion leads to disruption of cellular homeostasis and cell death. Early replenishment of ATP levels might therefore have a neuroprotective effect in the injured brain. We have previously shown that the ATP precursors, D-ribose and adenine (RibAde), restored the reduced ATP levels in rat brain slices to values similar to those measured in the intact rodent brain. The aim of this study was to assess whether RibAde, either alone or in combination with the xanthine oxidase inhibitor allopurinol (RibAdeAll; to further increase the availability of ATP precursors), could improve outcome in an in vivo rodent model of transient cerebral ischaemia. METHODS: After 60 min occlusion of the middle cerebral artery, and upon reperfusion, rats were administered saline, RibAde, or RibAdeAll for 6 h. Baseline lesion volume was determined by diffusion-weighted MRI prior to reperfusion and final infarct volume determined by T2-weighted MRI at Day 7. Neurological function was assessed at Days 1, 3 and 7. RESULTS: Ischaemic lesion volume decreased between Days 1 and 7: a 50% reduction was observed for the RibAdeAll group, 38% for the RibAde group and 18% in the animals that received saline. Reductions in lesion size in treatment groups were accompanied by a trend for faster functional recovery. CONCLUSION: These data support the potential use of ribose, adenine and allopurinol in the treatment of cerebral ischaemic injury, especially since all compounds have been used in man.

Optimisation and validation of a PCR for antigen receptor rearrangement (PARR) assay to detect clonality in canine lymphoid malignancies.

PCR for antigen receptor gene rearrangements (PARR) analysis is being increasingly used to assist diagnosis of canine lymphoma. In this study, PARR was carried out on consecutive samples received as part of routine diagnostic practice from 271 patients: 195 with lymphoid malignancies, 53 with reactive conditions and 23 with other neoplasms. Initially, published primer sets were used but later minor primer modifications were introduced and primers were rationalised to give a PARR panel that provides a good compromise between sensitivity and cost. Results were compared to diagnoses made by histology or cytology, coupled with immunophenotyping by flow cytometry or immunohistochemistry where possible. After exclusion of 11 poor quality samples, 230/260 (88%) gave a clear result with 162/163 (99%) of samples classified as clonal and 56/67 (84%) classified as polyclonal giving results concordant with the cytological/histological diagnosis. Among 30 samples with equivocal results, 21 had clonal peaks in a polyclonal background and nine showed little amplification. These were from patients with a range of neoplastic and non-neoplastic conditions emphasising the need to interpret such results carefully in concert with other diagnostic tests. The combination of primer sets used in this study resulted in a robust, highly specific and sensitive assay for detecting clonality.

The skin is a significant but overlooked anatomical reservoir for vector-borne African trypanosomes.

The role of mammalian skin in harbouring and transmitting arthropod-borne protozoan parasites has been overlooked for decades as these pathogens have been regarded primarily as blood-dwelling organisms. Intriguingly, infections with low or undetected blood parasites are common, particularly in the case of Human African Trypanosomiasis caused by Trypanosoma brucei gambiense. We hypothesise, therefore, the skin represents an anatomic reservoir of infection. Here we definitively show that substantial quantities of trypanosomes exist within the skin following experimental infection, which can be transmitted to the tsetse vector, even in the absence of detectable parasitaemia. Importantly, we demonstrate the presence of extravascular parasites in human skin biopsies from undiagnosed individuals. The identification of this novel reservoir requires a re-evaluation of current diagnostic methods and control policies. More broadly, our results indicate that transmission is a key evolutionary force driving parasite extravasation that could further result in tissue invasion-dependent pathology.

Acute motor and sensory polyganglioradiculoneuritis in a cat: clinical and histopathological findings.

Polyneuropathies can have a variety of clinical presentations and tend to be rare in cats. In this report we describe a 6-year-old domestic shorthair cat with an acute and rapidly progressive onset of lower motor neuron and sensory signs affecting the spinal and cranial nerves. Histopathological examination revealed moderate-to-severe multifocal inflammatory infiltrates at the ventral and dorsal nerve roots, and dorsal spinal ganglia at the level of the L4 and cauda equina. The type and severity of inflammation varied between nerve roots, being composed of mainly neutrophils in some and mainly lymphocytes and macrophages in others. Immunohistochemistry showed a combination of neutrophils, macrophages and lymphocytes infiltrating the nerve roots and ganglia. The majority of the lymphocytes were T lymphocytes; only a few B lymphocytes were seen. Neurons within the affected ganglia showed central chromatolysis and necrosis. Wallerian-like degeneration and demyelination were observed in the nerve roots. A sensory and motor polyganglioradiculoneuritis was diagnosed. An autoimmune process similar to the acute motor and sensory neuropathy subtype of Guillain-Barré syndrome in humans or an infection by an unidentified agent were considered most likely.

Pre-denaturing transitions in human serum albumin probed using time-resolved phosphorescence.

The investigation of protein dynamics has long been of interest, since protein interactions and functions can be determined by their structure and changes in conformation. Although fluorescence, occurring on the nanosecond timescale, from intrinsic fluorescent amino acids has been extensively used, in order to fully access conformational changes longer timescales are required. Phosphorescence enables processes on the microsecond to second timescale to be accessed. However, at room temperature this emission can be weak and non trivial to measure. It requires the removal of oxygen - a common triplet state quencher and appropriate instrumentation. In this work we make use of a chemical deoxygenator to study room temperature phosphorescence from tryptophan in human serum albumin excited using a pulsed UV light emitting diode. This is extended to monitor the phosphorescence emission upon increasing temperature, allowing pre-denaturing transitions to be observed. Time-resolved data are analysed, both as the sum of exponential decays and using a distribution analysis based on non extensive decay kinetics. These results are compared to a fluorescence study and both the average lifetime and contribution of the different emitting components were found to give more dramatic changes on the phosphorescence timescale.

The chaperone protein clusterin may serve as a cerebrospinal fluid biomarker for chronic spinal cord disorders in the dog.

Chronic spinal cord dysfunction occurs in dogs as a consequence of diverse aetiologies, including long-standing spinal cord compression and insidious neurodegenerative conditions. One such neurodegenerative condition is canine degenerative myelopathy (DM), which clinically is a challenge to differentiate from other chronic spinal cord conditions. Although the clinical diagnosis of DM can be strengthened by the identification of the Sod1 mutations that are observed in affected dogs, genetic analysis alone is insufficient to provide a definitive diagnosis. There is a requirement to identify biomarkers that can differentiate conditions with a similar clinical presentation, thus facilitating patient diagnostic and management strategies. A comparison of the cerebrospinal fluid (CSF) protein gel electrophoresis profile between idiopathic epilepsy (IE) and DM identified a protein band that was more prominent in DM. This band was subsequently found to contain a multifunctional protein clusterin (apolipoprotein J) that is protective against endoplasmic reticulum (ER) stress-mediated apoptosis, oxidative stress, and also serves as an extracellular chaperone influencing protein aggregation. Western blot analysis of CSF clusterin confirmed elevated levels in DM compared to IE (p < 0.05). Analysis of spinal cord tissue from DM and control material found that clusterin expression was evident in neurons and that the clusterin mRNA levels from tissue extracts were elevated in DM compared to the control. The plasma clusterin levels was comparable between these groups. However, a comparison of clusterin CSF levels in a number of neurological conditions found that clusterin was elevated in both DM and chronic intervertebral disc disease (cIVDD) but not in meningoencephalitis and IE. These findings indicate that clusterin may potentially serve as a marker for chronic spinal cord disease in the dog; however, additional markers are required to differentiate DM from a concurrent condition such as cIVDD.

Osteoarthritis in the cat: 1. how common is it and how easy to recognise?

PRACTICAL RELEVANCE: Osteoarthritis (OA) is very common, particularly in older cats, but its clinical significance has largely gone unrecognised until recently. As in other species, OA is often painful and appropriate treatment is required to improve the animal's quality of life. Most cases appear to be primary or idiopathic. It is important for the clinician to actively seek these cases in the practice population. CLINICAL CHALLENGES: The recognition of chronic arthritic pain is a major challenge since most cats will not exhibit lameness. The main features of feline OA are changes in behaviour and lifestyle, which develop gradually and which owners tend to interpret as simply being the effects of old age. A meaningful physical orthopaedic examination can be difficult to achieve. A lack of familiarity with feline joint radiographs, and the fact that major cartilage pathology can be present in the absence of any bony change, mean that radiographic identification of OA in the cat can also be problematic. CLIENT QUESTIONNAIRE: The recognition of chronic arthritic pain in the cat is based on owner questionnaires designed to elicit information about changes in mobility, activity levels, grooming habits and general demeanour. EVIDENCE BASE: Several publications now report on the significance of behavioural and lifestyle changes as indicators of chronic arthritic pain in the cat. However, there is not as yet a fully validated owner-based questionnaire for recognising chronic pain in the cat. Furthermore, the aetiopathogenesis of feline OA still requires detailed investigation. Such studies are likely to make a major contribution to comparative rheumatology, since feline OA, more so than the canine disease, shows many similarities with human OA.

Osteoarthritis in the cat: 2. how should it be managed and treated?

PRACTICAL RELEVANCE: Osteoarthritis (OA) is very common in the cat and in many cases is associated with significant long-term pain, which limits mobility and activity, and severely compromises the animal's quality of life. CLINICAL CHALLENGES: The treatment of chronic arthritic pain is a major challenge and many analgesic drugs used in other species are not licensed, not available or not tested for use in the cat. Many older cats with painful OA have some degree of chronic kidney disease (CKD) and many clinicians are reluctant to use non-steroidal anti-inflammatory drugs (NSAIDs) in these animals because of the potential for nephrotoxicity. EVIDENCE BASE: There are several publications that show that meloxicam is an effective NSAID for the cat and can be used long-term. It is easy to administer and there is published evidence that meloxicam can actually slow the progression of CKD in this species. Many other drugs are used to treat chronic pain in the cat but there is no documented evidence of their efficacy in OA. Unlike the dog, there is limited evidence for the effectiveness of omega-3 fatty acid-rich diets in managing feline OA and further work is required. There is no published data as yet for the usefulness or otherwise of nutraceuticals (glucosamine and chondroitin) in managing feline OA; studies in the authors' clinic suggest some pain-relieving effect. Research into environmental enrichment as a way of improving quality of life in cats with painful OA is lacking, but it is an approach worth using where possible. Modifications to the environment (eg, provision of comfortable bedding and ramps) are also important.

Imaging diagnosis--Canine meningioangiomatosis.

Meningioangiomatosis is a rare proliferative disorder of the central nervous system. It occurs sporadically in dogs and is characterized by a leptomeningeal plaque that extends from the subarachnoid space along the perivascular spaces into the adjacent parenchyma. We describe the clinical presentation, magnetic resonance (MR) imaging and neuropathologic characteristics of two additional dogs with meningioangiomatosis, and document involvement of the thoracolumbar spinal cord, a site not previously described for this condition. MR imaging findings were different from those previously described, most likely reflecting the degree of vascularity and collagen deposition. The MR imaging features of meningioangiomatosis are not specific.

Undifferentiated carcinoma of the salivary gland in a chinchilla (Chinchilla lanigera).

A 12-year-old chinchilla (Chinchilla lanigera) developed a slow-growing, soft, fluctuating, nonpainful mass on the ventral neck with focally extensive alopecia over a period of approximately 8 months. On postmortem examination, an extensive, multilobulated, cystic, neoplastic mass extended subcutaneously over the ventral and lateral neck with metastatic spread to submandibular lymph nodes, spleen, liver, and lungs. Neoplastic cells were strongly positive for vimentin and pan-cytokeratin but were negative for alpha-smooth muscle actin, S100, and myosin; no intracytoplasmic myofibrils were detected on phosphotungstic acid hematoxylin staining. Histologic and immunohistochemical examination of the mass led to a diagnosis of undifferentiated carcinoma of the salivary gland and contributes to the paucity of knowledge concerning neoplasia in chinchillas.

Centrifugal migration of mesenchymal cells in embryonic lung.

Murine lung development begins at embryonic day (E) 9.5. Normal lung structure and function depend on the patterns of localization of differentiated cells. Pulmonary mesenchymal cell lineages have been relatively unexplored. Importantly, there has been no prior evidence of clonality of any lung cells. Herein we use a definitive genetic approach to demonstrate a common origin for proximal and distal pulmonary mesenchymal cells. A retroviral library with 3,400 unique inserts was microinjected into the airway lumen of E11.5 lung buds. After 7-11 days of culture, buds were stained for placental alkaline phosphatase (PLAP). Most PLAP+ cells are peribronchial smooth muscle cells, initially localized laterally near the hilum, then migrating down airways to the subpleural region. Laser-capture microdissection and polymerase chain reaction confirm the clonal identities of PLAP+ cells proximally and distally. Our observation of this fundamental process during lung development opens new avenues for investigation of maladaptive mesenchymal responses in lung diseases.

NPAS1 regulates branching morphogenesis in embryonic lung.

Drosophila trachealess (Trl), master regulator of tracheogenesis, has no known functional mammalian homolog. We hypothesized that genes similar to trachealess regulate lung development. Quantitative (Q)RT-PCR and immunostaining were used to determine spatial and temporal patterns of npas1 gene expression in developing murine lung. Immunostaining for alpha-smooth muscle actin demonstrated myofibroblasts, and protein gene product (PGP)9.5 identified neuroendocrine cells. Branching morphogenesis of embryonic lung buds was analyzed in the presence of antisense or sense oligodeoxynucleotides (ODN). Microarray analyses were performed to screen for changes in gene expression in antisense-treated lungs. QRT-PCR was used to validate the altered expression of key genes identified on the microarrays. We demonstrate that npas1 is expressed in murine embryonic lung. npas1 mRNA peaks early at Embryonic Day (E)10.5-E11.5, then drops to low levels. Sequencing verifies the identity of npas1 transcripts in embryonic lung. NPAS1 immunostaining occurs in nuclei of parabronchial mesenchymal cells, especially at the tracheal bifurcation. Arnt, the murine homolog of Tango (the heterodimerization partner for Trl) is also expressed in developing lung but at constant levels. npas1- or arnt-antisense ODN inhibit lung branching morphogenesis, with altered myofibroblast development and increased pulmonary neuroendocrine cells. On microarrays, we identify > 50 known genes down-regulated by npas1-antisense, including multiple genes regulating cell migration and cell differentiation. QRT-PCR confirms significantly decreased expression of the neurogenic genes RBP-Jk and Tle, and three genes involved in muscle development: beta-ig-h3, claudin-11, and myocardin. Npas1 can regulate myofibroblast distribution, branching morphogenesis, and neuroendocrine cell differentiation in murine embryonic lung.