Dietary management of chronic enteropathy in dogs.

Chronic idiopathic enteropathy is a clinical condition defined by the exclusion of infectious, metabolic or neoplastic causes of gastrointestinal signs and is categorised by a response to treatment including management with diet change, immunosuppressant medication or interventions that directly target the microbiome (e.g. antibiotics, faecal transplantation or probiotics). Animals that fail these therapies are categorised as non-responsive or refractory chronic idiopathic enteropathy. This specific categorisation implies that nutritional intervention is only needed for a subset of patients with enteropathy. However, often dogs with chronic idiopathic enteropathy are malnourished, have nutrient malabsorption or have gastrointestinal inflammation that occurs as a result of a breakdown in tolerance to luminal antigens including microorganism or dietary components. Thus, all dogs with chronic idiopathic enteropathy benefit from a nutritional assessment and targeted nutritional intervention. Among dogs presenting for chronic idiopathic enteropathy, the response rate to diet alone is roughly 50% in the referral population giving the impression that the overall response could be even higher especially when more than one nutritional intervention is attempted and strict adherence is maintained. The objectives of this review article are to outline the nutritional approach to a dog with chronic idiopathic enteropathy, including the nutritional assessment, and to highlight areas for nutritional intervention.

Impact of feeding method on overall activity of indoor, client-owned dogs.

OBJECTIVE: To compare the total daily activity time, walking time and running time using food-dispensing toys versus bowls in a group of client-owned, primarily indoor dogs. MATERIALS AND METHODS: A two-way, two period, randomised repeated measures mixed-effects crossover study performed on 26 client-owned, primarily indoor dogs. RESULTS: Toy feeding increased average daily total activity time by 12% and walking time by 26%. Average daily total activity time and walking time were reduced by 8 and 7% respectively with each increase in year of age. Gender, body condition and muscle condition had no significant effect on average daily total activity or walking time. Toy feeding, time, their interaction, age, gender, body condition and muscle condition had no significant effect on average daily running time. CLINICAL SIGNIFICANCE: Feeding toys may be helpful during weight loss programs to achieve the goal of increasing daily exercise duration in dogs that need to lose weight.

The Role of Sulfur Dioxide in Stratospheric Aerosol Formation Evaluated Using In-Situ Measurements in the Tropical Lower Stratosphere.

Stratospheric aerosols (SAs) are a variable component of the Earth's albedo that may be intentionally enhanced in the future to offset greenhouse gases (geoengineering). The role of tropospheric-sourced sulfur dioxide (SO2) in maintaining background SAs has been debated for decades without in-situ measurements of SO2 at the tropical tropopause to inform this issue. Here we clarify the role of SO2 in maintaining SAs by using new in-situ SO2 measurements to evaluate climate models and satellite retrievals. We then use the observed tropical tropopause SO2 mixing ratios to estimate the global flux of SO2 across the tropical tropopause. These analyses show that the tropopause background SO2 is about 5 times smaller than reported by the average satellite observations that have been used recently to test atmospheric models. This shifts the view of SO2 as a dominant source of SAs to a near-negligible one, possibly revealing a significant gap in the SA budget.

Equine model for soft-tissue regeneration.

Soft-tissue regeneration methods currently yield suboptimal clinical outcomes due to loss of tissue volume and a lack of functional tissue regeneration. Grafted tissues and natural biomaterials often degrade or resorb too quickly, while most synthetic materials do not degrade. In previous research we demonstrated that soft-tissue regeneration can be supported using silk porous biomaterials for at least 18 months in vivo in a rodent model. In the present study, we scaled the system to a survival study using a large animal model and demonstrated the feasibility of these biomaterials for soft-tissue regeneration in adult horses. Both slow and rapidly degrading silk matrices were evaluated in subcutaneous pocket and intramuscular defect depots. We showed that we can effectively employ an equine model over 6 months to simultaneously evaluate many different implants, reducing the number of animals needed. Furthermore, we were able to tailor matrix degradation by varying the initial format of the implanted silk. Finally, we demonstrate ultrasound imaging of implants to be an effective means for tracking tissue regeneration and implant degradation.

Evaluation of UT/LS hygrometer accuracy by intercomparison during the NASA MACPEX mission.

Acquiring accurate measurements of water vapor at the low mixing ratios (< 10 ppm) encountered in the upper troposphere and lower stratosphere (UT/LS) has proven to be a significant analytical challenge evidenced by persistent disagreements between high-precision hygrometers. These disagreements have caused uncertainties in the description of the physical processes controlling dehydration of air in the tropical tropopause layer and entry of water into the stratosphere and have hindered validation of satellite water vapor retrievals. A 2011 airborne intercomparison of a large group of in situ hygrometers onboard the NASA WB-57F high-altitude research aircraft and balloons has provided an excellent opportunity to evaluate progress in the scientific community toward improved measurement agreement. In this work we intercompare the measurements from the Midlatitude Airborne Cirrus Properties Experiment (MACPEX) and discuss the quality of agreement. Differences between values reported by the instruments were reduced in comparison to some prior campaigns but were nonnegligible and on the order of 20% (0.8 ppm). Our analysis suggests that unrecognized errors in the quantification of instrumental background for some or all of the hygrometers are a likely cause. Until these errors are understood, differences at this level will continue to somewhat limit our understanding of cirrus microphysical processes and dehydration in the tropical tropopause layer.

Optical pacing of the adult rabbit heart.

Optical pacing has been demonstrated to be a viable alternative to electrical pacing in embryonic hearts. In this study, the feasibility of optically pacing an adult rabbit heart was explored. Hearts from adult New Zealand White rabbits (n = 9) were excised, cannulated and perfused on a modified Langendorff apparatus. Pulsed laser light (λ = 1851 nm) was directed to either the left or right atrium through a multimode optical fiber. An ECG signal from the left ventricle and a trigger pulse from the laser were recorded simultaneously to determine when capture was achieved. Successful optical pacing was demonstrated by obtaining pacing capture, stopping, then recapturing as well as by varying the pacing frequency. Stimulation thresholds measured at various pulse durations suggested that longer pulses (8 ms) had a lower energy capture threshold. To determine whether optical pacing caused damage, two hearts were perfused with 30 µM of propidium iodide and analyzed histologically. A small number of cells near the stimulation site had compromised cell membranes, which probably limited the time duration over which pacing was maintained. Here, short-term optical pacing (few minutes duration) is demonstrated in the adult rabbit heart for the first time. Future studies will be directed to optimize optical pacing parameters to decrease stimulation thresholds and may enable longer-term pacing.

Antibodies to OspC, OspF and C6 antigens as indicators for infection with Borrelia burgdorferi in horses.

REASONS FOR PERFORMING STUDY: Lyme disease is caused by Borrelia burgdorferi, which is transmitted by infected ticks (Ixodes spp.). Reports on Lyme disease in horses have increased in recent years. Nevertheless, the diagnosis of Lyme disease in horses is still challenging owing to its vague clinical presentation and the limitations of diagnostic tests. OBJECTIVES: This study used a new serological Lyme multiplex assay to examine antibody responses to 3 antigens of B. burgdorferi, outer surface protein (Osp) C, OspF and C6, and to verify their use as markers for early and late infection stages in horses. METHODS: Multiplex analysis of antibodies to OspC, OspF and C6 in equine patient sera (n = 191) was performed. A subset of the sera (n = 90) was also tested using a commercial C6-based Lyme test. RESULTS: Antibodies to OspF and C6 highly correlate as reliable markers of infection with B. burgdorferi in horses. Antibodies to OspC, which have been confirmed as early infection markers in man and dogs, were only detected in some patient sera, suggesting that OspC antibodies are indicators of early infection in horses. Commercial C6 testing identified most infected horses but also resulted in false positive and false negative interpretations. CONCLUSIONS: Serological multiplex testing is a rapid and quantitative diagnostic method to confirm infection with B. burgdorferi and to identify the stage of infection. In horses with risk of exposure and clinical signs, multiplex testing supports the diagnosis of Lyme disease. POTENTIAL RELEVANCE: Antimicrobial treatment of B. burgdorferi is time sensitive. Treatment success decreases with time of persistent infection, while the risk of developing chronic disease increases. The ability to identify early infection with B. burgdorferi provides practitioners and clinicians with a tool to improve the diagnosis of equine Lyme disease and make treatment decisions.

Evidence for NO(x) control over nighttime SOA formation.

Laboratory studies have established a number of chemical pathways by which nitrogen oxides (NO(x)) affect atmospheric organic aerosol (OA) production. However, these effects have not been directly observed in ambient OA. We report measurements of particulate organic nitrates in Bakersfield, California, the nighttime formation of which increases with NO(x) and is suppressed by high concentrations of organic molecules that rapidly react with nitrate radical (NO(3))--evidence that multigenerational chemistry is responsible for organic nitrate aerosol production. This class of molecules represents about a third of the nighttime increase in OA, suggesting that most nighttime secondary OA is due to the NO(3) product of anthropogenic NO(x) emissions. Consequently, reductions in NO(x) emissions should reduce the concentration of organic aerosol in Bakersfield and the surrounding region.

Altering embryonic cardiac dynamics with optical pacing.

Several studies have shown that altering blood flow early in development leads to congenital heart defects. In these studies the perturbations to hemodynamics were very gross manipulations (vessel ligation, conotruncal banding, etc.) that would be inappropriate for probing the delicate mechanisms responsible for mechanically-transduced signaling. Also, these perturbations lacked feedback from a monitoring system to determine the exact degree of alteration and the location of its effect. Here, we employed optical pacing (OP) to alter the heart rate in quail embryos and optical coherence tomography (OCT) to measure the resultant shear forces on the endocardium. OP is a new technique utilizing pulsed 1.851 µm infrared laser light to noninvasively capture the heart rate to the pulse frequency of the laser without the use of exogenous agents. To measure shear stress on the endocardium, we extended our previous OCT algorithms to enable the production of 4-D shear maps. 4-D shear maps allowed observation of the spatial and temporal distribution of shear stress. Employing both OCT and OP, we were able to develop perturbation protocols that increase regurgitant flow and greatly modify the oscillatory shear index (OSI) in a region of the heart tube where future valves will develop. Regurgitant flow has been linked with valve development and precise perturbations may allow one to determine the role of hemodynamics in valvulogenesis.

Intracoronary optical coherence tomography, basic theory and image acquisition techniques.

Optical coherence tomography (OCT) imaging is showing great potential as an alternative or complementary tool to intravascular ultrasound (IVUS) for aiding in stent procedures and future diagnosis/treatment of atherosclerosis. Here, we describe the basic theory behind OCT imaging and explain important parameters such as axial resolution, lateral resolution and sensitivity. Also, we describe several image acquisition techniques that have been adopted for OCT imaging.

A fluorescent bead-based multiplex assay for the simultaneous detection of antibodies to B. burgdorferi outer surface proteins in canine serum.

Lyme disease is a zoonotic, vector-borne disease affecting humans, dogs, horses and other species. It is caused by infection with spirochetes of the Borrelia burgdorferi sensu lato group which are transmitted to the mammalian host by infected ticks (Ixodes). Exposure to B. burgdorferi is commonly diagnosed by serological testing. The gold standard for the detection of antibodies to B. burgdorferi is a two-step procedure of an ELISA followed by confirmatory Western blotting (WB). Here, we developed and validated a new bead-based multiplex assay for the detection of antibodies to B. burgdorferi in canine serum which combined the testing by ELISA and WB in a single quantitative test. B. burgdorferi outer surface protein A (OspA), OspC and OspF were expressed in E. coli. The recombinant proteins were coupled to fluorescent beads providing the matrix of the assay. Two sets of canine sera were used for validation of the multiplex assay. First, sera from 79 dogs with known ELISA and WB results were used to establish the conditions of the assay. These samples were selected to provide similar numbers of pre-tested sera ranging from negative to high positive results and included sera from vaccinated and/or naturally infected dogs. A high correlation was observed for detection of antibodies to B. burgdorferi in the single and multiplex assays (n=79). Spearman's rank correlations were 0.93, 0.88 and 0.96 for OspA, OspC and OspF, respectively. Second, a total of 188 canine serum samples that were not tested previously were used for further multiplex assay validation. All samples were also blindly analyzed for antibodies to B. burgdorferi antigens by WB. The WB results provided a 'relative gold standard' for each antigen and were used to perform a receiver operating curve analysis. The areas under the curves were 0.93 for OspA, 0.82 for OspC, and 0.89 for OspF. Multiplex assay interpretation ranges for antibodies to all three B. burgdorferi antigens in canine serum were established by likelihood analysis. The diagnostic sensitivities of the individual OspA, OspC and OspF bead-based assays were 83%, 62% and 82%, respectively, and the diagnostic specificities were 90%, 89% and 86%, respectively. The new multiplex assay provides a sensitive and fully quantitative platform for the simultaneous evaluation of antibodies to B. burgdorferi OspA, OspC and OspF antigens and distinguishes between antibodies that originated from vaccination or natural exposure to B. burgdorferi.

Optical pacing of the embryonic heart.

Light has been used to noninvasively alter the excitability of both neural and cardiac tissue 1-10. Recently, pulsed laser light has been shown to be capable of eliciting action potentials in peripheral nerves and in cultured cardiomyocytes 7-10. Here, we demonstrate for the first time optical pacing (OP) of an intact heart in vivo. Pulsed 1.875 µm infrared laser light was employed to lock the heart rate to the pulse frequency of the laser. A laser Doppler velocimetry (LDV) signal was used to verify the pacing. At low radiant exposures, embryonic quail hearts were reliably paced in vivo without detectable damage to the tissue, indicating that OP has great potential as a tool to study embryonic cardiac dynamics and development. In particular, OP can be utilized to control the heart rate, and thereby alter stresses and mechanically transduced signaling.

Ultrahigh-speed optical coherence tomography imaging and visualization of the embryonic avian heart using a buffered Fourier Domain Mode Locked laser.

The embryonic avian heart is an important model for studying cardiac developmental biology. The mechanisms that govern the development of a four-chambered heart from a peristaltic heart tube are largely unknown due in part to a lack of adequate imaging technology. Due to the small size and rapid motion of the living embryonic avian heart, an imaging system with high spatial and temporal resolution is required to study these models. Here, an optical coherence tomography (OCT) system using a buffered Fourier Domain Mode Locked (FDML) laser is applied for ultrahigh-speed non-invasive imaging of embryonic quail hearts at 100,000 axial scans per second. The high scan rate enables the acquisition of high temporal resolution 2D datasets (195 frames per second or 5.12 ms between frames) and 3D datasets (10 volumes per second). Spatio-temporal details of cardiac motion not resolvable using previous OCT technology are analyzed. Visualization and measurement techniques are developed to non-invasively observe and quantify cardiac motion throughout the brief period of systole (less than 50 msec) and diastole. This marks the first time that the preseptated embryonic avian heart has been imaged in 4D without the aid of gating and the first time it has been viewed in cross section during looping with extremely high temporal resolution, enabling the observation of morphological dynamics of the beating heart during systole.

4D embryonic cardiography using gated optical coherence tomography.

Simultaneous imaging of very early embryonic heart structure and function has technical limitations of spatial and temporal resolution. We have developed a gated technique using optical coherence tomography (OCT) that can rapidly image beating embryonic hearts in four-dimensions (4D), at high spatial resolution (10-15 mum), and with a depth penetration of 1.5 - 2.0 mm that is suitable for the study of early embryonic hearts. We acquired data from paced, excised, embryonic chicken and mouse hearts using gated sampling and employed image processing techniques to visualize the hearts in 4D and measure physiologic parameters such as cardiac volume, ejection fraction, and wall thickness. This technique is being developed to longitudinally investigate the physiology of intact embryonic hearts and events that lead to congenital heart defects.

Real-time optical coherence tomography of the anterior segment at 1310 nm.

BACKGROUND: Recent advances in high-speed scanning technology have enabled a new generation of optical coherence tomographic (OCT) systems to perform imaging at video rate. Here, a handheld OCT probe capable of imaging the anterior segment of the eye at high frame rates is demonstrated for the first time. OBJECTIVE: To demonstrate real-time OCT imaging of anterior segment structures. DESIGN: Survey of anterior segment structures in normal human subjects. SETTING: Laboratory. MAIN OUTCOME MEASURES: Achieving real-time imaging of the anterior segment, satisfactory image quality, and convenience of a handheld probe. RESULTS: Optical coherence tomographic imaging of the anterior segment of the eyes of human subjects was performed using 1310-nm wavelength light with an image rate of 8 frames per second. Imaging trials demonstrated clear resolution of corneal epithelium and stroma, sclerocorneal junction, sclera, iris pigment epithelium and stroma, and anterior lens capsule. The anterior chamber angle was clearly visualized. Limited imaging of the ciliary body was performed. Real-time imaging of pupillary constriction in response to light stimulus was also performed. CONCLUSION: High-speed OCT at 1310-nm wavelength is a potentially useful technique for noninvasive assessment of anterior segment structures. CLINICAL RELEVANCE: Our results suggest that real-time OCT has potential applications in glaucoma evaluation and refractive surgery.

High-resolution endoscopic imaging of the GI tract: a comparative study of optical coherence tomography versus high-frequency catheter probe EUS.

BACKGROUND: Both optical coherence tomography (OCT) and catheter probe EUS (CPEUS) are candidates for high-resolution imaging of the GI wall, but their potential roles in this clinical context have not been investigated. METHODS: OCT and CPEUS were used to image normal-appearing portions of the GI tract at the same sites. CPEUS was performed with a 20-MHz or a new 30-MHz catheter probe. RESULTS: Forty-four histologically confirmed normal sites in 27 patients were evaluated. With OCT, mucosa and muscularis mucosa were clearly seen at all sites. Except for stomach, OCT demonstrated the submucosa in all sites. OCT penetration ranged from 0.7 to 0.9 mm. Microscopic structures such as esophageal glands, intestinal villi, colonic crypts, and blood vessels were easily identified. CPEUS penetration ranged from 10 mm to 20 mm, and 5 to 7 distinct layers were discernible. However, both mucosa and submucosa were seen as thin layers without microscopic detail. CONCLUSION: OCT resolution is superior to high-frequency CPEUS, but depth of penetration is limited to mucosa and submucosa. OCT images the major structural components of the mucosa and submucosa whereas CPEUS does not. Potentially, OCT and high-frequency CPEUS may be complementary for clinical imaging.

Photothermal coagulation of blood vessels: a comparison of high-speed optical coherence tomography and numerical modelling.

Optical-thermal models that can accurately predict temperature rise and damage in blood vessels and surrounding tissue may be used to improve the treatment of vascular disorders. Verification of these models has been hampered by the lack of time- and depth-resolved experimental data. In this preliminary study, an optical coherence tomography system operating at 4-30 frames per second was used to visualize laser irradiation of cutaneous (hamster dorsal skin flap) blood vessels. An argon laser was utilized with the following parameters: pulse duration 0.1-2.0 s, spot size 0.1-1.0 mm, power 100-400 mW. Video microscopy images were obtained before and after irradiations, and optical-thermal modelling was performed on two irradiation cases. Time-resolved optical coherence tomography and still images were compared with predictions of temperature rise and damage using Monte Carlo and finite difference techniques. In general, predicted damage agreed with the actual blood vessel and surrounding tissue coagulation seen in images. However, limitations of current optical-thermal models were identified, such as the inability to model the dynamic changes in blood vessel diameter that were seen in the optical coherence tomography images.

Potential new endoscopic techniques for the earlier diagnosis of pre-malignancy.

Light interacts with tissue in a variety of ways, including absorption, fluorescence, elastic scattering and Raman scattering. These interactions enable a number of promising technologies for endoscopic diagnosis of pre-malignancy, including chromoscopy; fluorescence, scattering and Raman spectroscopies; and optical coherence tomography. Although still in various stages of technical development and clinical trials, these optical diagnostic techniques are demonstrating strong potential to significantly enhance the clinical endoscopist's ability to detect dysplasia in gastrointestinal mucosae.

Simplified method for polarization-sensitive optical coherence tomography.

We report a method for extracting the birefringence properties of biological samples with micrometer-scale resolution in three dimensions, using a new form of polarization-sensitive optical coherence tomography. The method measures net retardance, net fast axis, and total reflectivity as a function of depth into the sample. Polarization sensing is accomplished by illumination of the sample with at least three separate polarization states during consecutive acquisitions of the same pixel, A scan, or B scan. The method can be implemented by use of non-polarization-maintaining fiber and a single detector. In a calibration test of the system, net retardance was measured with an average error of 7.5 degrees (standard deviation 2.2 degrees ) over the retardance range 0 degrees to 180 degrees , and a fast axis with average error of 4.8 degrees over the range 0 degrees to 180 degrees .

High-resolution endoscopic imaging of the GI tract using optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) has demonstrated the microscopic structure of the gastrointestinal (GI) tract mucosa and submucosa in vitro. We evaluated a prototype OCT system and assessed the feasibility of OCT in the human GI tract. METHODS: The 2.4 mm diameter prototype OCT probe, inserted through an endoscope, provides a 360-degree radial scan. Images (6.7 frames/sec) are displayed on a television monitor. Tissue contact is not required. In patients undergoing elective endoscopy, OCT images were obtained of normal mucosa (confirmed by biopsy). RESULTS: Seventy-two sites were imaged (38 patients): esophagus (21), stomach (12), duodenum (11), terminal ileum (4), colon (15), and rectum (9). Varying the distance between the probe and the mucosal surface produced images of the GI wall of varying depth. When held about 1 mm above the mucosal surface, the images consisted of mucosal structures such as colonic crypts, gastric pits, and duodenal villi. With the probe held against the wall, the OCT image comprised several layers interpreted as mucosa, muscularis mucosae, and submucosa. Structures including blood vessels were evident within the submucosa. A probe with a 0.5 mm working distance to the focal point provided the best images. Reducing the frame rate to 4.0 per second facilitated image interpretation. CONCLUSIONS: OCT is feasible in the human GI tract and provides interpretable high-resolution images of mucosa and submucosa.