Emerging Variants of Canine Enteric Coronavirus Associated with Outbreaks of Gastroenteric Disease.

A 2022 canine gastroenteritis outbreak in the United Kingdom was associated with circulation of a new canine enteric coronavirus closely related to a 2020 variant with an additional spike gene recombination. The variants are unrelated to canine enteric coronavirus-like viruses associated with human disease but represent a model for coronavirus population adaptation.

Outbreak of Severe Vomiting in Dogs Associated with a Canine Enteric Coronavirus, United Kingdom.

The lack of population health surveillance for companion animal populations leaves them vulnerable to the effects of novel diseases without means of early detection. We present evidence on the effectiveness of a system that enabled early detection and rapid response a canine gastroenteritis outbreak in the United Kingdom. In January 2020, prolific vomiting among dogs was sporadically reported in the United Kingdom. Electronic health records from a nationwide sentinel network of veterinary practices confirmed a significant increase in dogs with signs of gastroenteric disease. Male dogs and dogs living with other vomiting dogs were more likely to be affected. Diet and vaccination status were not associated with the disease; however, a canine enteric coronavirus was significantly associated with illness. The system we describe potentially fills a gap in surveillance in neglected populations and could provide a blueprint for other countries.

Use of vaccines and factors associated with their uptake variability in dogs, cats and rabbits attending a large sentinel network of veterinary practices across Great Britain.

Vaccination remains a mainstay of companion animal population health. However, how vaccine use at a population level complies with existing guidelines is unknown. Here we use electronic health records to describe vaccination in dogs, cats and rabbits attending a large sentinel network of UK veterinary practices. In total, 77.9% (95% CI: 77.6-78.1) of animals had recorded vaccinations. The percentage of animals with recorded vaccinations was higher in dogs, neutered animals, in insured dogs and cats and in purebred dogs. Vaccination rates varied in different regions of Great Britain in all species. Dogs and cats belonging to owners living in less deprived areas of England and Scotland were more likely to be recorded as vaccinated. In the vaccinated population, cats received more core vaccines per year of life (0.86) than dogs (0.75), with feline leukaemia vaccines almost as frequent as core vaccines. In dogs, leptospira vaccines were more frequent than core vaccines. This descriptive study suggests a substantial proportion of animals are not benefiting from vaccine protection. For the first time, we identify potential factors associated with variations in recorded vaccination frequency, providing a critical baseline against which to monitor future changes in companion animal vaccination and evidence to inform future targeted health interventions.

Assessment of the treatment efficiency of an urban stormwater pond and its impact on the natural downstream watercourse.

During the last few decades, stormwater ponds have become an alternative management practice in order to avoid flooding and to contain rainwater and runoff in urban areas where impervious land cover has increased. A second purpose of stormwater ponds is to improve the quality of runoff water that is usually contaminated with nitrogen, phosphorus, metals and organic micropollutants. Processes used are based on natural methods such as settlement and contribute to minimize the impact of these inputs to the natural aquatic system. This study aims to better understand the behavior of a wet stormwater pond, Heron Lake (33 ha) located in the city of Villeneuve d'Ascq in northern France through various indicators [trace metals, PAHs, PCBs, caffeine (CAF), carbamazepine (CBZ), nutrients and pathogens]. For that purpose, water quality was monitored for 1 year, mainly at the entrance and at the outlet of the lake. Sampling have also been done in the downstream aquatic environment, the Marque River. Sediments were sampled in the lake to evaluate the pollution trapped during sedimentation. Our results of both water and sediment sampling highlight: (i) the wastewater input into the Heron Lake is estimated to be equivalent to that of roughly 3800 inhabitants; (ii) the removal rates observed at the outlet, relative to concentrations at the entrance channel, vary as follows for these dissolved species: 24% for NO3- and PO43-, 28% for CBZ, 35% for Cu, 63% for Pb, 78% for CAF, 84% for Zn and up to 93% for NH4+; (iii) there are high levels of sediment contamination with metals, PAHs and PCBs at the entrance channel; (iv) the eutrophication of this pond is attributed to persistent high nutrient concentrations in both water and sediment, and has contributed to the development of an invasive macrophyte, the Elodea nuttallii; and (v) there appears to be only a negligible impact of the discharge from the lake to the natural watercourse, contributing annual loads of <2 up to 6% of the total amount of Cu, Pb, Zn, CAF, CBZ and nutrients measured in the Marque River, and having a slight diluting effect on concentrations in the Marque River.

The Role of TGF-ß in the Association Between Primary Graft Dysfunction and Bronchiolitis Obliterans Syndrome.

Primary graft dysfunction (PGD) is a possible risk factor for bronchiolitis obliterans syndrome (BOS) following lung transplantation; however, the mechanism for any such association is poorly understood. Based on the association of TGF-ß with acute and chronic inflammatory disorders, we hypothesized that it might play a role in the continuum between PGD and BOS. Thus, the association between PGD and BOS was assessed in a single-center cohort of lung transplant recipients. Bronchoalveolar lavage fluid concentrations of TGF-ß and procollagen collected within 24 h of transplantation were compared across the spectrum of PGD, and incorporated into Cox models of BOS. Immunohistochemistry localized expression of TGF-ß and its receptor in early lung biopsies posttransplant. We found an association between PGD and BOS in both bilateral and single lung recipients with a hazard ratio of 3.07 (95% CI 1.76-5.38) for the most severe form of PGD. TGF-ß and procollagen concentrations were elevated during PGD (p < 0.01), and associated with increased rates of BOS. Expression of TGF-ß and its receptor localized to allograft infiltrating mononuclear and stromal cells, and the airway epithelium. These findings validate the association between PGD and the subsequent development of BOS, and suggest that this association may be mediated by receptor/TGF-ß biology.

Gonadectomy increases neurogenesis in the male adolescent rhesus macaque hippocampus.

New neurons are continuously produced in the subgranular zone of the adult hippocampus and can modulate hippocampal plasticity across life. Adolescence is characterized by dramatic changes in sex hormone levels, and social and emotional behaviors. It is also an age for increased risk of psychiatric disorders, including schizophrenia, which may involve altered hippocampal neurogenesis. The extent to which testosterone and other testicular hormones modulate hippocampal neurogenesis and adolescent behavioral development is unclear. This study aimed to determine if removal of testicular hormones during adolescence alters neurogenesis in the male rhesus macaque hippocampus. We used stereology to examine levels of cell proliferation, cell survival and neuronal differentiation in late adolescent male rhesus macaques (4.6-yrs old) that had previously been gonadectomized or sham operated prior to puberty (2.4-yrs old). While the absence of adolescent testicular hormones had no effect on cell proliferation, cell survival was increased by 65% and indices of immature neuronal differentiation were increased by 56% in gonadectomized monkeys compared to intact monkeys. We show for the first time that presence of circulating testicular hormones, including testosterone, may decrease neuronal survival in the primate hippocampus during adolescence. Our findings are in contrast to existing studies in adults where testosterone tends to be a pro-survival factor and demonstrate that testicular hormones may reduce hippocampal neurogenesis during the age typical of schizophrenia onset.

Recording of suspected adverse drug reaction reporting in veterinary free-text clinical narratives.

OBJECTIVES: To use text mining approaches to identify instances of suspected adverse drug reactions recorded in first opinion veterinary free-text clinical narratives, and to evaluate whether these were also reported to either the Veterinary Medicines Directorate or the relevant Marketing Authorisation holder in order to derive an estimate of the suspected adverse drug reaction (sADR) minimum under-reporting rate. To characterise sADR reports and explore whether particular features are associated with report submission. MATERIALS AND METHODS: Two regular expressions were developed to identify mentions of "adverse drug reactions" and "side effects" in the free-text clinical narratives of electronic health records contained within the Small Animal Veterinary Surveillance Network database. Consultations containing a match for the developed regular expressions were manually reviewed for inclusion and further classified to determine the suspected product, seriousness and expectedness of the event, and an indication of whether the event had been reported. The associations between event characteristics and reporting were explored using Fisher's exact tests. RESULTS: A total of 10,565 records were manually reviewed from which 827 sADRs were identified. Approximately 90% of these sADRs were not recorded as reported. Suspected adverse drug reactions that were not considered "expected" were recorded as reported more frequently than "expected" sADRs. However, clinical severity did not appear to impact on whether there was a record of reporting. CLINICAL SIGNIFICANCE: This is the first estimate of under reporting sADRs based on real world evidence from veterinary clinical records. The under-reporting rate implied by this study highlights that further interventions are required to improve reporting rate within the veterinary profession in order to support pharmacovigilance activities and improve drug safety.

High levels of cleaved caspase-3 in colorectal tumour stroma predict good survival.

AIM: The primary aim was to determine the prognostic significance of apoptosis in colorectal tumour cells and tumour-associated stroma. A secondary aim was to determine whether apoptosis was related to immune surveillance. METHODS: Immunohistochemistry was performed using monoclonal antibodies recognising cleaved caspase-3 (CC3), cleaved poly (ADP-ribose) polymerase (PARP), p53, Bcl2, MHC-II, B cells (CD16), macrophages (CD68) and T cells (CD3), on a tissue microarray of 462 colorectal tumours. RESULTS: Kaplan-Meier analysis demonstrated that patients with high expression of CC3 in the tumour or CC3 or cleaved PARP in tumour-associated stroma have a good prognosis. This suggests that tumour stroma is promoting tumourigenesis and that high levels of death within the stroma breaks this link. CC3 levels in the tumour correlated with cleaved PARP and MHC-II expression but not with CD16, CD68, CD3, p53 or Bcl2 expression. CC3 levels on tumour-associated stroma also correlated with cleaved PARP and MHC-II expression but not with CD16, CD68, CD3, p53 or Bcl2 expression. Tumour cells express MHC-II in response to IFN-γ, suggesting that this may be one of the initiators of apoptosis within the good prognosis tumours. Although 73% of the MHC-II-positive tumour had high levels of apoptosis, many tumours had high levels of apoptosis in the absence of MHC-II, implying that this is only one of many causes of apoptosis within tumours. On multivariate analysis, using Cox's proportional hazards model, tumour stage, vascular invasion and expression of CC3 in tumour-associated stroma were shown to be independent markers of prognosis. CONCLUSION: This study shows that a high level of apoptosis within colorectal tumour-associated stroma is an independent marker of good prognosis.

Immunology in the clinic review series; focus on cancer: glycolipids as targets for tumour immunotherapy.

Research into aberrant glycosylation and over-expression of glycolipids on the surface of the majority of cancers, coupled with a knowledge of glycolipids as functional molecules involved in a number of cellular physiological pathways, has provided a novel area of targets for cancer immunotherapy. This has resulted in the development of a number of vaccines and monoclonal antibodies that are showing promising results in recent clinical trials.

Therapeutic response to bronchial thermoplasty: toward feasibility of patient selection based on modeling predictions.

Bronchial thermoplasty (BT) is a treatment for moderate-to-severe asthma in which the airway smooth muscle layer is targeted directly using thermal ablation. Although it has been shown to be safe and effective in long-term follow-up, questions remain about its mechanism of action, patient selection, and optimization of protocol based on structural phenotype. Using a cohort of 20 subjects who underwent thermoplasty and assessment by computed tomography (CT), we demonstrate that response to BT can be feasibly predicted based on pretreatment airway dimensions that inform a subject-specific computational model. Analysis revealed the need for CT assessment at total lung capacity, rather than functional residual capacity, which was less sensitive to the effects of BT. Final model predictions compared favorably with observed outcomes in terms of airway caliber and asthma control, suggesting that this approach could form the basis of improved clinical practice.NEW & NOTEWORTHY Bronchial thermoplasty is a treatment for asthma that targets the airway smooth muscle directly. We demonstrate the feasibility and constraints of predicting patient-specific response to thermoplasty using a computational model informed by pretreatment CT scans at different lung volumes. Predictions are compared with functional outcomes and posttreatment CT scans. This has the potential to form the basis for improved clinical practice.

The cam-type deformity of the proximal femur arises in childhood in response to vigorous sporting activity.

BACKGROUND: The prevalence of a cam-type deformity in athletes and its association with vigorous sports activities during and after the growth period is unknown. QUESTIONS/PURPOSES: We therefore compared the prevalence and occurrence of a cam-type deformity by MRI in athletes during childhood and adolescence with an age-matched control group. PATIENTS AND METHODS: We retrospectively reviewed 72 hips in 37 male basketball players with a mean age of 17.6 years (range, 9-25 years) and 76 asymptomatic hips of 38 age-matched volunteers who had not participated in sporting activities at a high level. RESULTS: Eleven (15%) of the 72 hips in the athletes were painful and had positive anterior impingement tests on physical examination. Internal rotation of the hip averaged 30.1° (range, 15°-45°) in the control group compared with only 18.9° (range, 0°-45°) in the athletes. The maximum value of the alpha angle throughout the anterosuperior head segment was larger in the athletes (average, 60.5° ± 9°), compared with the control group (47.4° ± 4°). These differences became more pronounced after closure of the capital growth plate. Overall, the athletes had a 10-fold increased likelihood of having an alpha angle greater than 55° at least at one measurement position. CONCLUSIONS: Our observations suggest a high intensity of sports activity during adolescence is associated with a substantial increase in the risk of cam-type impingement. These patients also may be at increased risk of subsequent development of secondary coxarthrosis. LEVEL OF EVIDENCE: Level II, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Seasonality and risk factors for grass seed foreign bodies in dogs.

Grass seed foreign bodies (GSFBs) are a familiar presentation, especially in dogs, associated with a variety of clinical signs depending on site of penetration and extent of migration. Seasonality and risk factors for GSFB occurrence were investigated using electronic health records from a sentinel voluntary network of 245 veterinary practices in the United Kingdom between 17th March 2014 and 18th September 2020. Clinical narrative text mining of 4,580,503 canine consultations produced a final case dataset of 1,037 consultations where GSFBs had been recorded in individual dogs. Cases of GSFBs were recorded in all months, with 940 (90.6 %) recorded between June and September. In particular, the odds of GSFBs in July was almost 176 times more than that of January (Odds ratio, OR, 175.6, 95 % Confidence interval, CI, 43.5-707.7, P < 0.001). Compared to the retriever breed type, spaniel breed types were 7.7 times more likely to present with a GSFB (CI 5.4-11.0, P < 0.001). Other significant risk factors associated with recorded GSFBs for this population included being male (OR = 1.4, CI 1.2-1.6, P < 0.001), and geographical location. When compared to the South East of England, risk was lowest in Wales (OR = 0.1, CI 0.0-0.3, P=<0.001), and highest in the East of England (OR = 1.9, 1.2-2.9, P = 0.003), and overall risk in urban areas was reduced (OR = 0.8, CI 0.7-1.0, P = 0.024). These observations provide a number of areas for temporally targeted health campaigns at specific types of dogs, to reduce the impact of GSFBs on canine welfare.

A text-mining based analysis of 100,000 tumours affecting dogs and cats in the United Kingdom.

Cancer is a major reason for veterinary consultation, especially in companion animals. Cancer surveillance plays a key role in prevention but opportunities for such surveillance in companion animals are limited by the lack of suitable veterinary population health infrastructures. In this paper we describe a pathology-based animal tumour registry (PTR) developed within the Small Animal Veterinary Surveillance Network (SAVSNET) built from electronic pathology records (EPR) submitted to this network. From an original collection of 180232 free text (non-structured) EPRs reported between April 2018 and June 2019, we used specific text-mining methodologies to identify 109895 neoplasias. These data were normalized to describe both the tumour (type and location) and the animal (breed, neutering status and veterinary practice postcode). The resulting PTR, the largest of its kind for companion animals to date, is an important research resource being able to facilitate a wide array of research in areas including surveillance, clinical decision making and comparative cancer biology.

Temporal, Spatial, and Genomic Analyses of Enterobacteriaceae Clinical Antimicrobial Resistance in Companion Animals Reveals Phenotypes and Genotypes of One Health Concern.

BACKGROUND: Antimicrobial resistance (AMR) is a globally important one health threat. The impact of resistant infections on companion animals, and the potential public health implications of such infections, has not been widely explored, largely due to an absence of structured population-level data. OBJECTIVES: We aimed to efficiently capture and repurpose antimicrobial susceptibility test (AST) results data from several veterinary diagnostic laboratories (VDLs) across the United Kingdom to facilitate national companion animal clinical AMR surveillance. We also sought to harness and genotypically characterize isolates of potential AMR importance from these laboratories. METHODS: We summarized AST results for 29,330 canine and 8,279 feline Enterobacteriaceae isolates originating from companion animal clinical practice, performed between April 2016 and July 2018 from four VDLs, with submissions from 2,237 United Kingdom veterinary practice sites. RESULTS: Escherichia coli (E. coli) was the most commonly isolated Enterobacteriaceae in dogs (69.4% of AST results, 95% confidence interval, CI, 68.7-70.0) and cats (90.5%, CI 89.8-91.3). Multi-drug resistance was reported in 14.1% (CI 13.5-14.8) of canine and 12.0% (CI 11.1-12.9) of feline E. coli isolates. Referral practices were associated with increased E. coli 3rd generation ≤ cephalosporin resistance odds (dogs: odds ratio 2.0, CI 1.2-3.4). We selected 95 E. coli isolates for whole genome analyses, of which seven belonged to sequence type 131, also carrying the plasmid-associated extended spectrum ß-lactamase gene bla CTX-M- 15. The plasmid-mediated colistin resistance gene mcr-9 was also identified for the first time in companion animals. CONCLUSIONS: Linking clinical AMR data with genotypic characterization represents an efficient means of identifying important resistance trends in companion animals on a national scale.

Hyaluronan fragments activate an NF-kappa B/I-kappa B alpha autoregulatory loop in murine macrophages.

Macrophages play an important role in the acute tissue inflammatory response through the release of cytokines and growth factors in response to stimuli such as lipopolysaccharide (LPS). Macrophage inflammatory effector functions are also influenced by interactions with the extracellular matrix (ECM). Such macrophage-ECM interactions may be important in regulating chronic inflammatory responses. Recent evidence has suggested that hyaluronan (HA), a glycosaminoglycan (GAG) component of ECM can induce inflammatory gene expression in murine macrophages. HA exists in its native form as a large polymer, but is found as smaller fragments under inflammatory conditions. The NF-kappa B/I-kappa B transcriptional regulatory system has been shown to be a critical component of the host inflammatory response. We examined the effects of high molecular weight HA and lower molecular weight HA fragments on NF-kappa B activation in mouse macrophages. Only the smaller HA fragments were found to activate NF-kappa B DNA binding activity. After HA stimulation, I-kappa B alpha mRNA was induced and I-kappa B alpha protein levels, which initially decreased, were restored. The induction of I-kappa Balpha expression was not observed for other GAGs. The time course of I-kappa B alpha protein regeneration in response to HA fragments was consistent with an autoregulatory mechanism. In support of this mechanism, in vitro translated murine I-kappa B alpha inhibited HA fragment-induced NF-kappa B DNA binding activity. The NF-kappa B DNA binding complex in HA-stimulated extracts was found to contain p50 and p65 subunits. Activation of the NF-kappa B/I-kappa B system in macrophages by ECM fragments may be an important mechanism for propagating the tissue inflammatory response.

Interleukin-13 induces tissue fibrosis by selectively stimulating and activating transforming growth factor beta(1).

Interleukin (IL)-13 is a key mediator of tissue fibrosis caused by T helper cell type 2 inflammation. We hypothesized that the fibrogenic effects of IL-13 are mediated by transforming growth factor (TGF)-beta. To test this hypothesis we compared the regulation of TGF-beta in lungs from wild-type mice and CC10-IL-13 mice in which IL-13 overexpression causes pulmonary fibrosis. IL-13 selectively stimulated TGF-beta(1) production in transgenic animals and macrophages were the major site of TGF-beta(1) production and deposition in these tissues. IL-13 also activated TGF-beta(1) in vivo. This activation was associated with decreased levels of mRNA encoding latent TGF-beta-binding protein-1 and increased mRNA encoding urinary plasminogen activator, matrix metalloproteinase (MMP)-9, and CD44. TGF-beta(1) activation was abrogated by the plasmin/serine protease antagonist aprotinin. It was also decreased in progeny of crosses of CC10-IL-13 mice and MMP-9 null mice but was not altered in crosses with CD44 null animals. IL-13-induced fibrosis was also significantly ameliorated by treatment with the TGF-beta antagonist soluble TGFbetaR-Fc (sTGFbetaR-Fc). These studies demonstrate that IL-13 is a potent stimulator and activator of TGF-beta(1) in vivo. They also demonstrate that this activation is mediated by a plasmin/serine protease- and MMP-9-dependent and CD44-independent mechanism(s) and that the fibrogenic effects of IL-13 are mediated, in great extent, by this TGF-beta pathway.

Measuring airway dimensions during bronchoscopy using anatomical optical coherence tomography.

Airway dimensions are difficult to quantify bronchoscopically because of optical distortion and a limited ability to gauge depth. Anatomical optical coherence tomography (aOCT), a novel imaging technique, may overcome these limitations. This study evaluated the accuracy of aOCT against existing techniques in phantom, excised pig and in vivo human airways. Three comparative studies were performed: 1) micrometer-derived area measurements in 10 plastic tubes were compared with aOCT-derived area; 2) aOCT-derived airway compliance curves from excised pig airways were compared with curves derived using an endoscopic technique; and 3) airway dimensions from the trachea to subsegmental bronchi were measured using aOCT in four anaesthetised patients during bronchoscopy and compared with computed tomography (CT) measurements. Measurements in plastic tubes revealed aOCT to be accurate and reliable. In pig airways, aOCT-derived compliance measurements compared closely with endoscopic data. In human airways, dimensions measured with aOCT and CT correlated closely. Bland-Altman plots showed that aOCT diameter and area measurements were higher than CT measurements by 7.6% and 15.1%, respectively. Airway measurements using aOCT are accurate, reliable and compare favourably with existing imaging techniques. Using aOCT with conventional bronchoscopy allows real-time measurement of airway dimensions and could be useful clinically in settings where knowledge of airway calibre is required.

Long-term cost-effectiveness of weight management in primary care.

BACKGROUND: As obesity prevalence and health-care costs increase, Health Care providers must prevent and manage obesity cost-effectively. METHODS: Using the 2006 NICE obesity health economic model, a primary care weight management programme (Counterweight) was analysed, evaluating costs and outcomes associated with weight gain for three obesity-related conditions (type 2 diabetes, coronary heart disease, colon cancer). Sensitivity analyses examined different scenarios of weight loss and background (untreated) weight gain. RESULTS: Mean weight changes in Counterweight attenders was -3 kg and -2.3 kg at 12 and 24 months, both 4 kg below the expected 1 kg/year background weight gain. Counterweight delivery cost was pound59.83 per patient entered. Even assuming drop-outs/non-attenders at 12 months (55%) lost no weight and gained at the background rate, Counterweight was 'dominant' (cost-saving) under 'base-case scenario', where 12-month achieved weight loss was entirely regained over the next 2 years, returning to the expected background weight gain of 1 kg/year. Quality-adjusted Life-Year cost was pound2017 where background weight gain was limited to 0.5 kg/year, and pound2651 at 0.3 kg/year. Under a 'best-case scenario', where weights of 12-month-attenders were assumed thereafter to rise at the background rate, 4 kg below non-intervention trajectory (very close to the observed weight change), Counterweight remained 'dominant' with background weight gains 1 kg, 0.5 kg or 0.3 kg/year. CONCLUSION: Weight management for obesity in primary care is highly cost-effective even considering only three clinical consequences. Reduced healthcare resources use could offset the total cost of providing the Counterweight Programme, as well as bringing multiple health and Quality of Life benefits.

Prospective assessment of reproducibility of three-dimensional ultrasound for fetal biometry.

PURPOSE: To compare fetal ultrasound measurements performed by two observers with different levels of experience and evaluate the potential contribution of the use of three-dimensional (3D) ultrasound on repeatability, reproducibility and agreement of two-dimensional (2D) and 3D-derived measurements. MATERIALS AND METHODS: Two observers (one senior and one junior) measured head circumference (HC), abdominal circumference (AC) and femur length (FL) in 33 fetuses (20 to 40 weeks of gestation). Each observer performed two series of 2D measurements and two series of 3D measurements (i.e., measurements derived from triplane volume processing). Measurements were converted into Z-scores according to gestational age. Variability between the different series of measurements was studied using Bland-Altmann plots and intra-class correlation coefficients (ICC). RESULTS: Agreement with the 2D measurements of the senior observer was higher in 3D than in 2D for the junior observer (systematic differences of -0.4, -0.2 and -0.8 Z-score vs. -0.1, -0.1 and -0.6 for HC, AC and FL on 2D and 3D datasets, respectively). The use of 3D ultrasound improved junior observer repeatability (ICC=0.94, 0.88, 0.90 vs. 0.94, 0.94 and 0.96 for HC, AC and FL in 2D and 3D, respectively). The reproducibility was greater using the junior observer 3D datasets (ICC=0.75, 0.60 and 0.45 vs. 0.79, 0.89 and 0.63 for HC, AC and FL, respectively). CONCLUSION: The use of 3D ultrasound improves the consistency of the measurements performed by a junior observer and increases the overall repeatability and reproducibility of measurements performed by observers with different levels of experience.

Potent bronchodilation and reduced stiffness by relaxant stimuli under dynamic conditions.

Airway relaxation in response to isoprenaline, sodium nitroprusside (SNP) and electrical field stimulation (EFS) was compared under static and dynamic conditions. The capacity of relaxants to reduce airway stiffness and, thus, potentially contribute to bronchodilation was also investigated. Relaxation responses were recorded in fluid filled bronchial segments from pigs under static conditions and during volume oscillations simulating tidal and twice tidal manoeuvres. Bronchodilation was assessed from the reduction in carbachol-induced lumen pressure, at isovolume points in pressure cycles produced by volume oscillation, and stiffness was assessed from cycle amplitudes. Under static conditions, all three inhibitory stimuli produced partial relaxation of the carbachol-induced contraction. Volume oscillation alone also reduced the contraction in an amplitude-dependent manner. However, maximum relaxation was observed when isoprenaline or SNP were combined with volume oscillation, virtually abolishing contraction at the highest drug concentrations. The proportional effects of isoprenaline and EFS were not different under static or oscillating conditions, whereas relaxation to SNP was slightly greater in oscillating airways. All three inhibitory stimuli also strongly reduced carbachol-induced airway stiffening. The current authors conclude that bronchoconstriction is strongly suppressed by combining the inhibitory stimulation of airway smooth muscle with cyclical mechanical strains. The capacity of airway smooth muscle relaxants to also reduce stiffness may further contribute to bronchodilation.