FATAL SYSTEMIC FUNGAL INFECTION IN EASTERN BONGO ANTELOPE (TRAGELAPHUS EURYCERUS ISAACI): SIX CASES.

Over a span of 6 yr, six adult eastern bongo antelope (Tragelaphus eurycerus isaaci) from a single institution died due to systemic mycotic infections. All animals were of the same genetic lineage and in good body condition at the time of death. Gross findings in all cases included multifocal white-to-tan nodules up to 10 cm in diameter that were most numerous in the heart, lung, and kidney. Histologic examination identified these nodules as foci of granulomatous inflammation containing branching, septate, broad, undulating fungal elements. Identification of the fungal species was pursued using PCR with sequencing, immunohistochemistry, and culture. Multiple fungal species were identified using the various modalities, and commonality of species identification was limited to Cladosporium sp. in four of the cases. The clinical and postmortem findings in these cases were identical and were considered to be the same infectious disease. The Cladosporium sp. was considered a candidate as an emerging fatal infectious agent in this population of bongo antelopes. In all of these cases, death was attributed to conduction abnormalities associated with the cardiac lesions or euthanasia.

Curricular changes and interim posts during Covid-19: graduates' perspectives.

BACKGROUND: During the COVID-19 pandemic UK medical schools facilitated the early graduation of their final-year medical students to 'Foundation interim Year 1 (FiY1) doctors' through amendments made to curricula and final assessment. Such changes gave opportunity for evaluation. This study therefore aimed to explore 1) graduate perspective on the implementation of FiY1 and 2) how changes to course structures have affected self-reported preparedness for work. METHODS: Questionnaire surveys using Likert scale and free-text responses (n = 45), and semi-structured interviews (n = 7) were conducted with FiY1s from two UK medical schools contrasting in the amendments made to course structures. Data were analysed using quantitative methods and thematic analysis; 44% (n = 20) of respondents believed that governing health bodies had not communicated sufficiently prior to starting work. RESULTS: Graduates who had sat modified practical and written examinations reported 'legitimacy' and feeling more prepared compared to having not sat examinations (practical 100%, n = 17; written 88.3%, n = 15). Graduates from both schools agreed that carrying out assistantships as originally scheduled would have made them feel more prepared (91.1%, n = 41). CONCLUSIONS: The implementation of FiY1 was largely well received by graduates yet assistantship programmes may fulfil a similar role in normal times. Medical schools and governing bodies must ensure effective communication channels exist with students in order to better prepare them for their first posts, especially in times of crisis. Additionally, final examinations contribute to feelings of preparedness for work and instil a sense of legitimacy, a finding which is relevant to working within the current programmatic assessment structure.

Differential production and secretion of potentially toxigenic extracellular proteins from hypervirulent Aeromonas hydrophila under biofilm and planktonic culture.

BACKGROUND: Hypervirulent Aeromonas hydrophila (vAh) is an emerging pathogen in freshwater aquaculture that results in the loss of over 3 million pounds of marketable channel catfish, Ictalurus punctatus, and channel catfish hybrids (I. punctatus, ♀ x blue catfish, I. furcatus, ♂) each year from freshwater catfish production systems in Alabama, U.S.A. vAh isolates are clonal in nature and are genetically unique from, and significantly more virulent than, traditional A. hydrophila isolates from fish. Even with the increased virulence, natural infections cannot be reproduced in aquaria challenges making it difficult to determine modes of infection and the pathophysiology behind the devastating mortalities that are commonly observed. Despite the intimate connection between environmental adaptation and plastic response, the role of environmental adaption on vAh pathogenicity and virulence has not been previously explored. In this study, secreted proteins of vAh cultured as free-living planktonic cells and within a biofilm were compared to elucidate the role of biofilm growth on virulence. RESULTS: Functional proteolytic assays found significantly increased degradative activity in biofilm secretomes; in contrast, planktonic secretomes had significantly increased hemolytic activity, suggesting higher toxigenic potential. Intramuscular injection challenges in a channel catfish model showed that in vitro degradative activity translated into in vivo tissue destruction. Identification of secreted proteins by HPLC-MS/MS revealed the presence of many putative virulence proteins under both growth conditions. Biofilm grown vAh produced higher levels of proteolytic enzymes and adhesins, whereas planktonically grown cells secreted higher levels of toxins, porins, and fimbrial proteins. CONCLUSIONS: This study is the first comparison of the secreted proteomes of vAh when grown in two distinct ecological niches. These data on the adaptive physiological response of vAh based on growth condition increase our understanding of how environmental niche partitioning could affect vAh pathogenicity and virulence. Increased secretion of colonization factors and degradative enzymes during biofilm growth and residency may increase bacterial attachment and host invasiveness, while increased secretion of hemolysins, porins, and other potential toxins under planktonic growth (or after host invasion) could result in increased host mortality. The results of this research underscore the need to use culture methods that more closely mimic natural ecological habitat growth to improve our understanding of vAh pathogenesis.

Self-similar propagation of optical pulses in fibers with positive quartic dispersion.

We study the propagation of ultrashort pulses in optical fiber with gain and positive (or normal) quartic dispersion by self-similarity analysis of the modified nonlinear Schrödinger equation. We find an exact asymptotic solution, corresponding to a triangle-like T4/3 intensity profile, with a T1/3 chirp, which is confirmed by numerical simulations. This solution follows different amplitude and width scaling compared to the conventional case with quadratic dispersion. We also suggest, and numerically investigate, a fiber laser consisting of components with positive quartic dispersion that emits quartic self-similar pulses.

Hsp90 inhibition suppresses NF-κB transcriptional activation via Sirt-2 in human lung microvascular endothelial cells.

The ability of anti-heat shock protein 90 (Hsp90) drugs to attenuate NF-κB-mediated transcription is the major basis for their anti-inflammatory properties. While the molecular mechanisms underlying this effect are not clear, they appear to be distinct in human endothelial cells. We now show for the first time that type 2 sirtuin (Sirt-2) histone deacetylase binds human NF-κB target gene promoter and prevents the recruitment of NF-κB proteins and subsequent assembly of RNA polymerase II complex in human lung microvascular endothelial cells. Hsp90 inhibitors stabilize the Sirt-2/promoter interaction and impose a "transcriptional block," which is reversed by either inhibition or downregulation of Sirt-2 protein expression. Furthermore, this process is independent of NF-κB (p65) Lysine 310 deacetylation, suggesting that it is distinct from known Sirt-2-dependent mechanisms. We demonstrate that Sirt-2 is recruited to NF-κB target gene promoter via interaction with core histones. Upon inflammatory challenge, chromatin remodeling and core histone H3 displacement from the promoter region removes Sirt-2 and allows NF-κB/coactivator recruitment essential for RNA Pol II-dependent mRNA induction. This novel mechanism may have important implications in pulmonary inflammation.

Novel application of in vivo microdialysis in a rat Achilles tendon acute injury model.

Tendon injury and healing involve intricate changes to tissue metabolism, biology, and inflammation. Current techniques often require animal euthanasia or tissue destruction, limiting assessment of dynamic changes in tendon, including treatment response, disease development, rupture risk, and healing progression. Microdialysis, a minimally invasive technique, offers potential for longitudinal assessment, yet it has not been applied to rat tendon models. Therefore, the objective of this study is to adapt a novel application of an in vivo assay, microdialysis, using acute injury as a model for extreme disruption of the tendon homeostasis. We hypothesize that microdialysis will be able to detect measurable differences in the healing responses of acute injury with high specificity and sensitivity. Overall results suggest that microdialysis is a promising in vivo technique for longitudinal assessment for this system with strong correlations between extracellular fluid (ECF) and dialysate concentrations and reasonable recovery rates considering the limitations of this model. Strong positive correlations were found between dialysate and extracellular fluid (ECF) concentration for each target molecule of interest including metabolites, inflammatory mediators, and collagen synthesis and degradation byproducts. These results suggest that microdialysis is capable of detecting changes in tendon healing following acute tendon injury with high specificity and sensitivity. In summary, this is the first study to apply microdialysis to a rat tendon model and assess its efficacy as a direct measurement of tendon metabolism, biology, and inflammation.NEW & NOTEWORTHY This study adapts a novel application of microdialysis to rat tendon models, offering a minimally invasive avenue for longitudinal tendon assessment. Successfully detecting changes in tendon healing after acute injury, it showcases strong correlations between extracellular fluid and dialysate concentrations. The results highlight the potential of microdialysis as a direct measure of tendon metabolism, biology, and inflammation, bypassing the need for animal euthanasia and tissue destruction.

Decorin and/or biglycan knockdown in aged mouse patellar tendon impacts fibril morphology, scar area, and mechanical properties.

Small leucine-rich proteoglycans, such as decorin and biglycan, play pivotal roles in collagen fibrillogenesis during development, healing, and aging in tendon. Previous work has shown that the absence of decorin and biglycan affects fibril shape and mechanical properties during tendon healing. However, the roles of decorin and biglycan in the healing process of aged tendons are unclear. Therefore the objective of this study was to evaluate the differential roles of decorin and biglycan during healing of patellar tendon injury in aged mice. Aged (300 days old) female Dcn+/+/Bgn+/+ control (WT, n = 52), Dcnflox/flox (I-Dcn-/-, n = 36), Bgnflox/flox (I-Bgn-/-, n = 36), and compound Dcnflox/flox/Bgnflox/flox (I-Dcn-/-/Bgn-/-, n = 36) mice with a tamoxifen-inducible Cre were utilized. Targeted gene expression, collagen fibril diameter distributions, mechanical properties, and histological assays were employed to assess the effects of knockdown of decorin and/or biglycan at the time of injury. Knockdown resulted in alterations in fibril diameter distribution and scar area, but surprisingly did not lead to many differences in mechanical properties. Biglycan played a larger role in early healing stages, while decorin is more significant in later stages, particularly in scar remodeling. This study highlights some of the differential roles of biglycan and decorin in the regulation of fibril structure and scar area, as well as influencing gene expression during healing in aged mice.

A new species of Tritrichomonas (Sarcomastigophora: Trichomonida) from the domestic cat (Felis catus).

Feline trichomoniasis is an intestinal disease in cats resulting in chronic diarrhea, flatulence, tenesmus, and fecal incontinence. Bovine trichomoniasis is a sexually transmitted disease of cattle infecting the reproductive tract of cows causing pyometra and possible mid- to late-term abortions. The causative agent for both diseases has been reported to be the flagellated protozoan, Tritrichomonas foetus. However, several published reports support significant biological differences between T. foetus isolated from bovines and felines. In the present study, we describe Tritrichomonas blagburni n.sp. from the domestic cat (Felis catus) as the causative agent of feline intestinal trichomoniasis. We support our proposal based on results of experimental cross-infection studies between cats and cattle using both feline and bovine isolates of the parasite, differences in pathogenicity between the two parasites for the respective host species, and molecular gene sequencing differences between parasites obtained from domestic cats and parasites obtained from cattle.

Commissioning a CT-compatible LDR tandem and ovoid applicator using Monte Carlo calculation and 3D dosimetry.

PURPOSE: To determine the geometric and dose attenuation characteristics of a new commercially available CT-compatible LDR tandem and ovoid (T&O) applicator using Monte Carlo calculation and 3D dosimetry. METHODS: For geometric characterization, we quantified physical dimensions and investigated a systematic difference found to exist between nominal ovoid angle and the angle at which the afterloading buckets fall within the ovoid. For dosimetric characterization, we determined source attenuation through asymmetric gold shielding in the buckets using Monte Carlo simulations and 3D dosimetry. Monte Carlo code MCNP5 was used to simulate 1.5 × 10(9) photon histories from a (137)Cs source placed in the bucket to achieve statistical uncertainty of 1% at a 6 cm distance. For 3D dosimetry, the distribution about an unshielded source was first measured to evaluate the system for (137)Cs, after which the distribution was measured about sources placed in each bucket. Cylindrical PRESAGE(®) dosimeters (9.5 cm diameter, 9.2 cm height) with a central channel bored for source placement were supplied by Heuris Inc. The dosimeters were scanned with the Duke Large field of view Optical CT-Scanner before and after delivering a nominal dose at 1 cm of 5-8 Gy. During irradiation the dosimeter was placed in a water phantom to provide backscatter. Optical CT scan time lasted 15 min during which 720 projections were acquired at 0.5° increments, and a 3D distribution was reconstructed with a (0.05 cm)(3) isotropic voxel size. The distributions about the buckets were used to calculate a 3D distribution of transmission rate through the bucket, which was applied to a clinical CT-based T&O implant plan. RESULTS: The systematic difference in bucket angle relative to the nominal ovoid angle (105°) was 3.1°-4.7°. A systematic difference in bucket angle of 1°, 5°, and 10° caused a 1% ± 0.1%, 1.7% ± 0.4%, and 2.6% ± 0.7% increase in rectal dose, respectively, with smaller effect to dose to Point A, bladder, sigmoid, and bowel. For 3D dosimetry, 90.6% of voxels had a 3D γ-index (criteria = 0.1 cm, 3% local signal) below 1.0 when comparing measured and expected dose about the unshielded source. Dose transmission through the gold shielding at a radial distance of 1 cm was 85.9% ± 0.2%, 83.4% ± 0.7%, and 82.5% ± 2.2% for Monte Carlo, and measurement for left and right buckets, respectively. Dose transmission was lowest at oblique angles from the bucket with a minimum of 56.7% ± 0.8%, 65.6% ± 1.7%, and 57.5% ± 1.6%, respectively. For a clinical T&O plan, attenuation from the buckets leads to a decrease in average Point A dose of ∼3.2% and decrease in D(2cc) to bladder, rectum, bowel, and sigmoid of 5%, 18%, 6%, and 12%, respectively. CONCLUSIONS: Differences between dummy and afterloading bucket position in the ovoids is minor compared to effects from asymmetric ovoid shielding, for which rectal dose is most affected. 3D dosimetry can fulfill a novel role in verifying Monte Carlo calculations of complex dose distributions as are common about brachytherapy sources and applicators.

Hybrid interpenetrating hydrogel network favoring the bidirectional migration of tenocytes for rotator cuff tendon regeneration.

Replenishment of tenocytes to the injury site is an ideal strategy to improve healing response and accelerate the tendon ECM regeneration. The present study focused on the synthesis and characterization of a hybrid hydrogel scaffold system poly(propylene-fumarate)-alginate-polyvinyl alcohol-acrylic acid (PAPA) using poly(propylene-fumarate) (PPF), alginate, polyvinyl alcohol (PVA) and acrylic acid and the in vitro investigation of bidirectional mobility of swine shoulder tenocytes (SST) for its potential application in rotator-cuff tendon regeneration. IR analysis revealed the presence of alginate, PPF and PVA segments on the surface, SEM and AFM analyses revealed the porous and nano-topographical features of PAPA, respectively, swelling was 712.6 ± 84.21% with the EWC (%) of 87.59 ± 1.26 having the diffusional exponent and swelling constant 0.551 and 1.8, respectively. PAPA was biodegradable, cytocompatible and supported long-term survival of SSTs. SEM imaging revealed the adhesion, colonization, and sheet formation of SSTs within the PAPA hydrogel network. The SSTs seeded on the PAPA scaffolds were peculiar for their bidirectional migration as the anterograde movement was completed in 9 days whereas the retrograde infiltration occurred up to the depth of 198 µm. These findings suggest the promising translational potential of PAPA scaffold system in the management of rotator cuff tendon injury.

Commissioning and benchmarking a 3D dosimetry system for clinical use.

PURPOSE: A 3D dosimetry system is described which consists of two parts: a radiochromic plastic dosimeter PRESAGE (which responds to absorbed dose with a linear change in optical-density) and the Duke large-field-of-view optical-CT scanner (DLOS). The DLOS/PRESAGE system has recently been commissioned and benchmarked for clinical use and, in particular, for verification and commissioning of complex radiation treatments. METHODS: DLOS commissioning involved determining the dynamic range, spatial resolution, noise, temporal, and other characteristics of the light source and imaging components. Benchmarking tests were performed on the combined DLOS/PRESAGE system to establish baseline dosimetric performance. The tests consisted of delivering simple radiation treatments to PRESAGE dosimeters, and comparing the measured 3D relative dose distributions with the known gold standard. The gold standard distribution was obtained from machine beam-data or the treatment planning system (TPS). All studies used standardized procedures to ensure consistency. RESULTS: For commissioning, isotropic spatial resolution was submillimeter (MTF > 0.5 for frequencies of 1.5 lp/mm) and the dynamic range was -60 dB. Flood field uniformity was within 10% and stable after 45 min of warm-up. Stray-light is small, due to telecentricity, but even the residual can be removed through deconvolution by a point-spread-function. For benchmarking, the mean 3D passing NDD (normalized dose distribution) rate (3%, 3mm, 5% dose threshold) over the benchmark data sets was 97.3% +/- 0.6% (range 96%-98%), which is on par with other planar dosimeters used in external beam radiation therapy indicating excellent agreement. Noise was low at < 2% of maximum dose (4-12 Gy) for 2 mm reconstructions. The telecentric design was critical to enabling fast imaging with minimal stray-light artifacts. CONCLUSIONS: This work presents the first comprehensive benchmarking of a 3D dosimetry system for clinical use. The DLOS/PRESAGE benchmark tests show consistently good agreement to simple known distributions. The system produces accurate isotropic 2 mm dose data over clinical volumes (e.g., 16 cm diameter phantoms, 12 cm height), in under 15 min. It represents a uniquely useful and versatile new tool for commissioning and verification of complex therapy treatments.

Commissioning a small-field biological irradiator using point, 2D, and 3D dosimetry techniques.

PURPOSE: To commission a small-field biological irradiator, the XRad225Cx from Precision x-Ray, Inc., for research use. The system produces a 225 kVp x-ray beam and is equipped with collimating cones that produce both square and circular radiation fields ranging in size from 1 to 40 mm. This work incorporates point, 2D, and 3D measurements to determine output factors (OF), percent-depth-dose (PDD) and dose profiles at multiple depths. METHODS: Three independent dosimetry systems were used: ion-chambers (a farmer chamber and a micro-ionisation chamber), 2D EBT2 radiochromic film, and a novel 3D dosimetry system (DLOS∕PRESAGE®). Reference point dose rates and output factors were determined from in-air ionization chamber measurements for fields down to ∼13 mm using the formalism of TG61. PDD, profiles, and output factors at three separate depths (0, 0.5, and 2 cm), were determined for all field sizes from EBT2 film measurements in solid water. Several film PDD curves required a scaling correction, reflecting the challenge of accurate film alignment in very small fields. PDDs, profiles, and output factors were also determined with the 3D DLOS∕PRESAGE® system which generated isotropic 0.2 mm data, in scan times of 20 min. RESULTS: Surface output factors determined by ion-chamber were observed to gradually drop by ∼9% when the field size was reduced from 40 to 13 mm. More dramatic drops were observed for the smallest fields as determined by EBT∼18% and ∼42% for the 2.5 mm and 1 mm fields, respectively. PRESAGE® and film output factors agreed well for fields <20 mm (where 3D data were available) with mean deviation of 2.2% (range 1%-4%). PDD values at 2 cm depth varied from ∼72% for the 40 mm field, down to ∼55% for the 1 mm field. EBT and PRESAGE® PDDs agreed within ∼3% in the typical therapy region (1-4 cm). At deeper depths the EBT curves were slightly steeper (2.5% at 5 cm). These results indicate good overall consistency between ion-chamber, EBT2 and PRESAGE® measured OFs, PDDs, and profiles. CONCLUSIONS: The combination of independent 2D and 3D measurements was found to be valuable to ensure accurate and comprehensive commissioning. Film measurements were time consuming and challenging due to the difficulty of film alignment in small fields. PRESAGE® 3D measurements were comprehensive and efficient, because alignment errors are negligible, and all parameters for multiple fields could be obtained from a single dosimeter and scan. However, achieving accurate superficial data (within 4 mm) is not yet feasible due to optical surface artifacts.

Thrombotic microangiopathy secondary to recurrent prostate cancer.

An 86-year-old man returned to the UK from Spain with symptoms suggestive of gastrointestinal bleeding. He was found to have an acute kidney injury and thrombocytopenia. Further investigations identified the presence of a microangiopathic hemolytic anemia, supporting the diagnosis of a thrombotic microangiopathy. Differentials included atypical hemolytic uremic syndrome and secondary thrombotic microangiopathy. Thrombotic thrombocytopenic purpura (TTP) and STEC (Shiga toxin-producing E. coli) hemolytic uremic syndrome were excluded by a normal ADAMTS-13 and negative E. coli serology and stool PCR. The patient was treated with blood and platelet transfusions. He received eculizumab and hemodialysis whilst a screen for secondary causes was undertaken. Thrombotic microangiopathy was shown to be secondary to recurrence of prostate cancer, which had been treated 16 years previously. He later recovered his renal function and receives ongoing hormonal treatment for his prostate cancer.

Mechanical properties of the different rotator cuff tendons in the rat are similarly and adversely affected by age.

Rotator cuff tendon tears and tendinopathies are common injuries affecting a large portion of the population and can result in pain and joint dysfunction. Incidence of rotator cuff tears significantly increases with advancing age, and up to 90% of these tears involve the supraspinatus. Previous literature has shown that aging can lead to inferior mechanics, altered composition, and changes in structural properties of the supraspinatus. However, there is little known about changes in supraspinatus mechanical properties in context of other rotator cuff tendons. Alterations in tendon mechanical properties may indicate damage and an increased risk of rupture, and thus, the purpose of this study was to use a rat model to define age-related alterations in rotator cuff tendon mechanics to determine why the supraspinatus is more susceptible to tears due to aging than the infraspinatus, subscapularis, and teres minor. Fatigue, viscoelastic, and quasi-static properties were evaluated in juvenile, adult, aged, and geriatric rats. Aging ubiquitously and adversely affected all rotator cuff tendons tested, particularly leading to increased stiffness, decreased stress relaxation, and decreased fatigue secant and tangent moduli in geriatric animals, suggesting a common intrinsic mechanism due to aging in all rotator cuff tendons. This study demonstrates that aging has a significant effect on rotator cuff tendon mechanical properties, though the supraspinatus was not preferentially affected. Thus, we are unable to attribute the aging-associated increase in supraspinatus tears to its mechanical response alone.

Limited Scar Resection for Chronic Achilles Tendon Repair: Use of a Rat Model.

BACKGROUND: Achilles tendon rupture diagnosis is frequently missed, leading to the development of a chronic rupture that requires surgical intervention to remove scar tissue and return the elongated Achilles tendon to appropriate functional length. The limited scar resection (LSR) intervention strategy may provide an advantage over other techniques, as it is less invasive and nondestructive to other tissues, although there is little evidence comparing outcomes between intervention strategies. HYPOTHESIS: The LSR technique would be a viable treatment option for chronic Achilles tendon ruptures and would perform comparably with a more clinically accepted procedure, the gastrocnemius fascial turndown (GFT), in postintervention functional outcome measures and tendon mechanical and histological properties. STUDY DESIGN: Controlled laboratory study. METHODS: Chronic Achilles tendon ruptures were induced in the right hindlimb of Sprague-Dawley rats by Achilles tendon transection without repair, immobilization in dorsiflexion, and 5 weeks of cage activity. Animals were randomly divided between the intervention strategy groups (LSR and GFT), received 1 week of immobilization in plantarflexion, and were sacrificed at 3 or 6 weeks postintervention. In vivo functional outcome measures (gait kinetics, passive joint function, tendon vascular perfusion) were quantified during healing, and tendon mechanical and histological properties were assessed postsacrifice. RESULTS: When compared with the GFT, the LSR technique elicited a faster return to baseline in gait kinetics, although there were few differences between groups or with healing time in other functional outcome measures (passive joint function and vascular perfusion). Quasi-static mechanical properties were improved with healing in both surgical intervention groups, although only the LSR group showed an improvement in fatigue properties between 3 and 6 weeks postintervention. Histological properties were similar between intervention strategies, except for decreased cellularity in the LSR group at 6 weeks postintervention. CONCLUSION: The LSR technique is a viable surgical intervention strategy for a chronic Achilles tendon rupture in a rodent model, and it performs similarly, if not better, when directly compared with a more clinically accepted surgery, the GFT. CLINICAL RELEVANCE: This study supports the increased clinical use of the LSR technique for treating chronic Achilles tendon rupture cases.

Disseminated Toxoplasma gondii Infection in an Adult Osprey (Pandion haliaetus).

An adult female osprey (Pandion haliaetus) was found weak and unable to fly in Auburn, Alabama in August 2019. The bird was captured and submitted to the Southeastern Raptor Center of the Auburn University College of Veterinary Medicine for evaluation. On presentation, the bird was thin with a body condition score of approximately 1.5 out of 5. The bird died during the examination and was submitted for necropsy. At the necropsy, there was a severe loss of muscle mass over the body, and the keel was prominent. The liver and spleen were moderately enlarged with pale tan to red foci randomly scattered throughout the parenchyma. A histopathologic observation revealed multifocal to coalescing areas of necrosis and hemorrhage with intralesional protozoans in the liver, spleen, lungs, kidney, sciatic nerve, esophagus, cerebrum, heart, and proventriculus. Immunohistochemistry using anti-Toxoplasma gondii-specific antibodies showed a strong positive labeling of the parasite. Semi-nested PCR, specific for the B1 gene of T. gondii, successfully identified T. gondii. This is the first confirmed case of T. gondii infection in an osprey.

Randomized Trial of Aspirin Versus Warfarin After Transcatheter Aortic Valve Replacement in Low-Risk Patients.

BACKGROUND: The optimal antithrombotic regimen after transcatheter aortic valve replacement remains unclear. METHODS: In this randomized open-label study, low-risk patients undergoing transfemoral transcatheter aortic valve replacement at 7 centers in the United States were randomized 1:1 to low-dose aspirin or warfarin plus low-dose aspirin for 30 days. Patients who could not be randomized were enrolled in a separate registry. Computed tomography or transesophageal echocardiography was performed at 30 days. The primary effectiveness end point was a composite of the following at 30 days: hypoattenuated leaflet thickening, at least moderately reduced leaflet motion, hemodynamic dysfunction (mean aortic valve gradient ≥20 mm Hg, effective orifice area ≤1.0 cm2, dimensionless valve index <0.35, or moderate or severe aortic regurgitation), stroke, or transient ischemic attack. RESULTS: Between July 2018 and October 2019, 94 patients were randomly assigned, 50 to aspirin and 44 to warfarin plus aspirin, and 30 were enrolled into the registry. In the intention-to-treat analysis of the randomized cohort, the composite primary effectiveness end point was met in 26.5% for aspirin versus 7.0% for warfarin plus aspirin (P=0.014; odds ratio, 4.8 [95% CI, 1.3-18.3]). The rate of hypoattenuated leaflet thickening was 16.3% for aspirin versus 4.7% for warfarin plus aspirin (P=0.07; odds ratio, 4.0 [95% CI, 0.8-20.0]). There was no excess bleeding at 30 days with anticoagulation. In the as-treated analysis of pooled randomized and registry cohorts, the rate of hypoattenuated leaflet thickening was 16.7% for aspirin versus 3.1% for warfarin plus aspirin (P=0.011; odds ratio, 6.3 [95% CI, 1.3-30.6]). CONCLUSIONS: In low-risk transcatheter aortic valve replacement patients, anticoagulation with warfarin may prevent transcatheter heart valve dysfunction in the short term without excess bleeding. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03557242.

Balloon-Expandable Valve Geometry After Transcatheter Aortic Valve Replacement in Low-Risk Patients With Bicuspid Versus Tricuspid Aortic Stenosis.

BACKGROUND: Prospective bicuspid low-risk transcatheter aortic valve replacement (TAVR) registries' data demonstrated encouraging short-term results. Detailed data on transcatheter heart valve (THV) geometry after deployment using contemporary devices are lacking. This study sought to examine valve geometry after TAVR in patients with bicuspid aortic stenosis (AS). METHODS: The study population was patients from the LRT (Low Risk TAVR) trial who underwent TAVR using the SAPIEN 3 THV for bicuspid and tricuspid AS. THV geometry measured on 30-day computed tomography (CT) included valve height, angle, depth, and eccentricity. Additionally, THV hemodynamics and outcomes post-TAVR were compared among patients with bicuspid and tricuspid AS. RESULTS: A total of 107 patients from the LRT trial using the SAPIEN 3 THV were included in our analysis. On 30-day CT, the valve height ratio (1.07 vs. 1.07; p = 0.348), depths (right [5.6 mm vs. 6.2 mm; p = 0.223], left [5.3 mm vs. 4.4 mm; p = 0.082] and non [4.8 mm vs. 4.5 mm; p = 0.589] coronary cusps), eccentricities (1.08 vs. 1.07; p = 0.9550), and angles (except the right [3.9 degrees vs. 6.3 degrees; p = 0.003] and left [3.6 degrees vs. 6.0 degrees; p = 0.007]) were similar between bicuspid and tricuspid patients. Hemodynamics, stroke, and mortality were similar at 1 year. CONCLUSION: Despite challenging bicuspid anatomy of the aortic valve, our comprehensive CT analysis supports similar THV geometry between patients with bicuspid and tricuspid AS undergoing TAVR using the SAPIEN 3 THV in low-risk patients. This translated to excellent short-term clinical outcomes and THV hemodynamics in both aortic valve morphologies. TRIAL REGISTRY: NCT02628899, https://clinicaltrials.gov/ct2/show/NCT02628899.

Avian influenza vaccination in chickens and pigs with replication-competent adenovirus-free human recombinant adenovirus 5.

Protective immunity to avian influenza (AI) virus can be elicited in chickens by in ovo or intramuscular vaccination with replication-competent adenovirus (RCA)-free human recombinant adenovirus serotype 5 (Ad5) encoding AI virus H5 (AdTW68.H5) or H7 (AdCN94.H7) hemagglutinins. We evaluated bivalent in ovo vaccination with AdTW68.H5 and AdCN94.H7 and determined that vaccinated chickens developed robust hemagglutination inhibition (HI) antibody levels to both H5 and H7 AI strains. Additionally, we evaluated immune responses of 1-day-old chickens vaccinated via spray with AdCN94.H7. These birds showed increased immunoglobulin A responses in lachrymal fluids and increased interleukin-6 expression in Harderian gland-derived lymphocytes. However, specific HI antibodies were not detected in the sera of these birds. Because pigs might play a role as a "mixing vessel" for the generation of pandemic influenza viruses we explored the use of RCA-free adenovirus technology to immunize pigs against AI virus. Weanling piglets vaccinated intramuscularly with a single dose of RCA-free AdTW68.H5 developed strong systemic antibody responses 3 wk postvaccination. Intranasal application of AdTW68.H5 in piglets resulted in reduced vaccine coverage, i.e., 33% of pigs (2/6) developed an antibody response, but serum antibody levels in those successfully immunized animals were similar to intramuscularly vaccinated animals.