Search

Abstract Anti-Stokes photoluminescence (PL) is light emission at a higher photon energy than the excitation, with applications in optical cooling, bioimaging, lasing, and quantum optics. Here, we show how plasmonic nano-cavities activate anti-Stokes PL in WSe2 monolayers through resonant excitation of a dark exciton at room temperature. The optical near-fields of the plasmonic cavities excite the out-of-plane transition dipole of the dark exciton, leading to light emission from the bright exciton at higher energy. Through statistical measurements on hundreds of plasmonic cavities, we show that coupling to the dark exciton leads to a near hundred-fold enhancement of the upconverted PL intensity. This is further corroborated by experiments in which the laser excitation wavelength is tuned across the dark exciton. We show that a precise nanoparticle geometry is key for a consistent enhancement, with decahedral nanoparticle shapes providing an efficient PL upconversion. Finally, we demonstrate a selective and reversible switching of the upconverted PL via electrochemical gating. Our work introduces the dark exciton as an excitation channel for anti-Stokes PL in WSe2 and paves the way for large-area substrates providing nanoscale optical cooling, anti-Stokes lasing, and radiative engineering of excitons.

Abstract Chagas cardiomyopathy, caused by the protozoal parasite Trypanosoma cruzi, is characterized by arrhythmias, myocardial damage, heart failure, and sudden death. We describe 2 dogs with severe, symptomatic Chagas cardiomyopathy characterized by myocardial dysfunction and electrocardiographic abnormalities that were managed with a combination of cardiac medications and antiparasitic treatment with itraconazole and amiodarone. Both dogs died suddenly within 6 months of diagnosis. These cases highlight the need for early detection of Chagas disease in dogs and continued research to develop effective antiparasitic treatment protocols.

Abstract Background Transesophageal echocardiography (TEE) is useful in the assessment and procedural monitoring of congenital heart disease (CHD) with a relatively low complication rate in humans. Objectives To evaluate the safety of TEE and report complications in dogs. Animals Forty client‐owned dogs with CHD. Methods Prospective observational study including gastroesophagoscopy before and after TEE imaging. TEE was planned with a GE 6VT‐D adult probe in dogs weighing ≥4 kg and a GE 10T‐D microprobe alternating with an intracardiac echocardiography probe placed in the esophagus in dogs

Trypanosoma cruzi naturally infects a wide variety of wild and domesticated mammals, in addition to humans. Depending on the infection dose and other factors, the acute infection can be life-threatening, and in all cases, the risk of chagasic heart disease is high in persistently infected hosts. Domestic, working, and semi-feral dogs in the Americas are at significant risk of T. cruzi infection and in certain settings in the southern United States, the risk of new infections can exceed 30% per year, even with the use of vector control protocols. In this study, we explored whether intermittent low-dose treatment with the trypanocidal compound benznidazole (BNZ) during the transmission season, could alter the number of new infections in dogs in an area of known, intense transmission pressure. Preliminary studies in mice suggested that twice-weekly administration of BNZ could prevent or truncate infections when parasites were delivered at the mid-point between BNZ doses. Pre-transmission season screening of 126 dogs identified 53 dogs (42.1%) as T. cruzi infection positive, based upon blood PCR and Luminex-based serology. Serial monitoring of the 67 uninfected dogs during the high transmission season (May to October) revealed 15 (22.4%) new infections, 6 in the untreated control group and 9 in the group receiving BNZ prophylaxis, indicating no impact of this prophylaxis regimen on the incidence of new infections. Although these studies suggest that rigorously timed and more potent dosing regimen may be needed to achieve an immediate benefit of prophylaxis, additional studies would be needed to determine if drug prophylaxis reduced disease severity despite this failure to prevent new infections.

Abstract Background The protozoal parasite Trypanosoma cruzi causes myocarditis in dogs. Objectives To describe the cardiac diagnostic test results and outcomes of dogs naturally infected with T. cruzi. Animals Forty‐four client‐owned dogs. Methods Medical records were retrospectively reviewed to identify dogs with an indirect fluorescent antibody test result for T. cruzi ≥1 : 80. Data collected included signalment, cardiac diagnostic test results (ECG, echocardiography, cardiac troponin I) and outcome. Outcomes were categorized as alive, dead (cardiac or noncardiac) or lost to follow up. Results ECG abnormalities were present in 41 dogs with ventricular arrhythmias (n = 28) and atrioventricular block (AVB) (n = 15) most commonly identified. Echocardiographic chamber enlargement was present in 28 dogs and most often included the right ventricle (RV) (n = 15) and left atrium (n = 12). Troponin was ≥2 times the reference range in 20/36 (56%) dogs. In univariate analysis using nonparametric Kaplan‐Meier, ventricular arrhythmias with a modified Lown score ≥2 (P = .02), presence of AVB (P = .04), and RV enlargement (P = .006) were associated with decreased survival times. Right ventricular enlargement (HR 3.6; 95% confidence interval [CI] 1.4‐9.3; P = .007) and higher body weight at presentation (HR 1.0; 95% CI 1.0‐1.1; P = .04) were associated with decreased time to death in the final explanatory multivariable model. Conclusions and Clinical Importance Cardiac abnormalities were common and variable, and RV enlargement was associated with shorter survival time. A diagnostic evaluation that includes screening for arrhythmias, echocardiography, and cTnI can provide useful information related to the characterization of heart disease in dogs seropositive for T. cruzi.

Abstract Background Heartworms, a cause of pulmonary hypertension (PH) in dogs, can migrate from the pulmonary arteries into the heart resulting in life‐threatening caval syndrome (CS). Objectives To describe clinical and echocardiographic characteristics in dogs with intracardiac heartworms including estimated heartworm burden and frequency of PH and pigmenturia. Animals Seventy‐two client‐owned dogs with heartworms. Methods Retrospective study. Data collected from an electronic medical records search for dogs with intracardiac heartworms included clinicopathologic, echocardiographic, and procedural findings. Dogs with heartworms isolated to the pulmonary arteries were excluded. Results Estimated intracardiac heartworm burden was low in 14 of 72 (19%) and high in 58 of 72 (81%) dogs. The majority were small breed (54/72; 75%; 29/72; 40% Chihuahuas) and had a high likelihood of PH (67/72; 93%). Pigmenturia was the second most common clinical finding (31/72; 43%) after lethargy (32/72; 44%). Anemia (37/55; 36%), pigmenturia (30/58; 52%), and bilirubinuria (28/36; 78%) were significantly more common in dogs with a high worm burden (P

Abstract Background The Evaluation of pimobendan in dogs with cardiomegaly caused by preclinical myxomatous mitral valve disease (EPIC) study monitored dogs with myxomatous mitral valve disease (MMVD) as they developed congestive heart failure (CHF). Objectives To describe the changes in clinical and radiographic variables occurring as dogs with MMVD and cardiomegaly develop CHF, compared to similar dogs that do not develop CHF. Animals One hundred and thirty‐five, and 73 dogs that did or did not develop CHF, respectively. Materials and methods The following variables were evaluated in 2 groups of dogs (dogs that did or did not develop CHF): Heart rate (HR), clinic respiratory rate (RR), home‐measured resting respiratory rate (RRR), rectal temperature (RT), body weight (BW), and vertebral heart sum (VHS). Absolute value and rate of change of each variable were calculated for each day a dog was in study. Daily means were calculated and plotted against time. The onset of CHF or last visit before leaving the study were set as reference time points. Results The most extreme values and rate of change occurred in variables immediately before onset of CHF. Vertebral heart sum increased earliest. Heart rate, RR, and RRR also increased. Rectal temperature and BW decreased. Increases in RR and RRR were most extreme and occurred immediately before CHF. Conclusions and Clinical Importance Dogs with MMVD and cardiomegaly experience increases in HR, RR, RRR, and VHS, and decreases in BW and RT as they develop CHF. The variables with highest absolute change and rate of change were RR and RRR. These findings reinforce the value of RR and RRR as indicators of impending or incipient CHF.

Abstract Background Chagas disease is increasingly recognized in the southern U.S., where triatomine vectors transmit Trypanosoma cruzi among wildlife and domestic dogs with occasional vector spillover to humans. As in humans, clinical outcome in dogs is variable, ranging from acute death to asymptomatic infections or chronic heart disease. In order to characterize cardiac manifestations of T. cruzi infections, we tracked a cohort of naturally-infected dogs and a matched cohort of uninfected dogs. We hypothesized that selected measures of cardiac disease (abnormal rate, abnormal rhythm, and elevated cardiac troponin I (cTnI; a biomarker of cardiac injury)) would occur more commonly in infected than uninfected dogs matched by age, breed, sex and location. In addition to the clearly positive and negative dogs, we specifically tracked dogs with discordant test results across three independent serological assays to gather clinical data that might elucidate the infection status of these animals and inform the utility of the different testing approaches. Results We placed an ambulatory ECG monitor (Holter) on 48 government working dogs and analyzed 39 successful recordings that met length and quality criteria from 17 T. cruzi-infected, 18 uninfected dogs and 4 dogs with discordant results. Overall, 76.5% of positive, 100.0% of discordant, and 11.1% of negative dogs showed > 1 ECG abnormality (p

Canine Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is increasingly recognized as a health concern for dogs in the USA, and infected dogs may signal geographic regions of risk for human disease. Dogs living in multi-dog kennel environments (kennels with more than one dog) where triatomine vectors are endemic may be at high risk for infection. We monitored a cohort of 64 T. cruzi-infected and uninfected dogs across 10 kennels in Texas, USA, to characterize changes in infection status over one year. We used robust diagnostic criteria in which reactivity on multiple independent platforms was required to be considered positive. Among the 30 dogs enrolled as serologically- and/or PCR-positive, all but one dog showed sustained positive T. cruzi diagnostic results over time. Among the 34 dogs enrolled as serologically- and PCR-negative, 10 new T. cruzi infections were recorded over a 12-month period. The resulting incidence rate for dogs initially enrolled as T. cruzi-negative was 30.7 T. cruzi infections per 100 dogs per year. This study highlights the risk of T. cruzi infection to dogs in kennel environments. To protect both dog and human health, there is an urgent need to develop more integrated vector control methods as well as prophylactic and curative antiparasitic treatment options for T. cruzi infection in dogs.

Abstract Background Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, causes sudden death and chronic heart disease with no currently approved treatment. Objective To report epidemiologic and select cardiac characteristics associated with T. cruzi infection in dogs presenting to a teaching hospital in Texas. Animals Three hundred seventy‐five client‐owned dogs. Methods A retrospective search of medical records identified dogs tested for T. cruzi antibodies or with histologic T. cruzi parasites. Data retrieved included signalment, location of residence, reported reason for testing, cardiac troponin I (cTnI) concentration, and ECG abnormalities. Results Trypanosoma cruzi‐infected dogs (N = 63, 16.8%) were significantly younger than negative dogs (N = 312) (mean, 5.9 ± 3.8 versus 7.4 ± 4.0 years; P = .007) with no difference by sex or breed. Ninety‐one breeds were tested; the highest percent infected were non‐sporting (10/35; 29%) and toy breed (10/42; 24%) groups. The odds of infection were 13 times greater among dogs with an infected housemate or littermate (95% confidence interval [CI], 3.94‐50.45; P < .001). Infected dogs were more likely to have ventricular arrhythmias (odds ratio [OR], 2.19; 95% CI, 1.15‐4.33, P = .02), combinations of ECG abnormalities (OR, 2.91; 95% CI, 1.37‐5.99; P = .004), and cTnI >0.129 ng/mL (ADVIA; OR, 10.71; 95% CI, 1.60‐212.21; P = .035). Conclusions and Clinical Importance Dogs infected with T. cruzi were identified in Texas in many breed groups including breeds affected by well‐described heart diseases that mimic Chagas disease suggesting a need for increased awareness, including knowledge of when to consider testing.

Background Accurately assessing the morphology and shape of the patent ductus arteriosus (PDA) and obtaining measurements are important to avoid procedural complications. Objectives To characterize and compare PDA morphology, shape, and dimensions with angiography and echocardiography. Animals 25 client‐owned dogs with echocardiographically confirmed PDA. Methods Prospective case series. Imaging consisted of single plane angiography, transthoracic echocardiography from the right (TTE‐R) and left (TTE‐L), and two‐dimensional, biplane, and three‐dimensional transesophageal echocardiography (TEE‐2D and TEE‐3D). Measurements included angiographic minimal ductal diameter (MDD), echocardiographic pulmonary ostium in a single dimension (TTE‐R, TTE‐L, and TEE‐2D) and in perpendicular dimensions (TEE‐3D) with similar measurements of the ampulla 3 mm above the MDD or pulmonary ostium. The morphology and shape of the PDA were characterized. Results Catheter‐based occlusion (N = 20) and surgical ligation (N = 5) were performed without complication. Angiographic morphology was classified as type II (N = 19), type III (N = 1), and other (N = 1). Angiographic MDD and TEE‐2D pulmonary ostium measurements were significantly (P = .008) but weakly correlated (r = .56); similar relationships were found for ampulla diameter measurements (P

Abstract Trypanosoma cruzi infection in dogs can cause heart failure and sudden death with few treatment options available. A litter of 4 dogs living in a T cruzi endemic area were randomized to prophylaxis and nonprophylaxis groups as part of a study evaluating a modified benznidazole dosing regimen administered twice weekly to prevent T cruzi infection during a vector transmission season. The 2 dogs that received prophylaxis remained healthy without T cruzi infection or cardiac disease for >2 years. One dog that did not receive prophylaxis died unexpectedly with acute T cruzi–induced pancarditis, and the second dog tested positive for T cruzi and developed complex arrhythmias with markedly increased cardiac troponin I and improved with a higher benznidazole treatment dose. Although the small sample size precludes definitive conclusions, we describe the potential clinical benefit of prophylactic and early treatment with modified benznidazole dosing regimens for dogs with T cruzi infection.

Trypanosoma cruzi , the protozoan parasite and cause of Chagas disease, is widely distributed in many vertebrate and triatomine species throughout North, Central, and South America. Variations in housing quality largely determines human infection risk in the Americas. However, the southern U.S. contains widespread, infected triatomine vectors and captive species and domesticated animals with active T. cruzi infection or at high risk of becoming infected and developing Chagas disease. There is a critical need for better detection and intervention strategies, principally focused on human infection throughout the Americas, but mainly in the U.S., for high-value dogs employed in government and other work. In addition to this economic impact, the concentration of largely unavoidable T. cruzi infections in U.S. dogs provides an incomparable opportunity to answer questions related to T. cruzi infection and Chagas disease that are impossible or unethical to address in humans. As the course of T. cruzi infection and Chagas disease, the immune response to infection, and the response to therapeutics are highly similar across the range of mammalian host species, information obtained from studies in other species can directly inform researchers on how to best detect, manage, and treat T. cruzi infection and Chagas disease in humans.

Introduction:Geroscience studies of low-dose rapamycin in laboratory species have identified numerous benefits, including reversing age-related cardiac dysfunction. Cardiovascular benefits have been observed in dogs with 10 weeks of treatment, raising questions about possible benefits and adverse effects of long-term use of low-dose rapamycin. The objectives of this study were to assess the impact of 6 months of low-dose rapamycin on echocardiographic indices of cardiac function in healthy dogs and to document the occurrence of adverse events.Methods:Seventeen client-owned dogs aged 6–10 years, weighing 18–36 kg, and without significant systemic disease were included in a prospective, randomized, placebo-controlled, masked clinical trial. Low-dose rapamycin (0.025 mg/kg) or placebo was administered three times per week for 6 months. Baseline, 6-month, and 12-month evaluation included physical examination, cardiology examination, and clinicopathology. Three-month evaluation included physical examination and clinicopathology. Owners completed online questionnaires every 2 weeks.Results:There were no statistically significant differences in echocardiographic parameters between rapamycin and placebo groups at 6 or 12 months. No clinically significant adverse events occurred. In 26.8% of the bi-weekly surveys owners whose dogs received rapamycin reported perceived positive changes in behavior or health, compared to 8.1% in the placebo group (p = 0.04).Discussion:While no clinically significant change in cardiac function was observed in dogs treated with low-dose rapamycin, the drug was well-tolerated with no significant adverse events.

BackgroundTriatomine insects, vectors of the etiologic agent of Chagas disease (Trypanosoma cruzi), are challenging to locate in sylvatic habitats. Collection techniques used in the United States often rely on methods to intercept seasonally dispersing adults or on community scientists' encounters. Neither method is suited for detecting nest habitats likely to harbor triatomines, which is important for vector surveillance and control. Furthermore, manual inspection of suspected harborages is difficult and unlikely to reveal novel locations and host associations. Similar to a team that used a trained dog to detect sylvatic triatomines in Paraguay, we worked with a trained scent detection dog to detect triatomines in sylvatic locations across Texas.Principle methodology/findingsZiza, a 3-year-old German Shorthaired Pointer previously naturally infected with T. cruzi, was trained to detect triatomines. Over the course of 6 weeks in the fall of 2017, the dog and her handler searched at 17 sites across Texas. The dog detected 60 triatomines at 6 sites; an additional 50 triatomines were contemporaneously collected at 1 of these sites and 2 additional sites without the assistance of the dog. Approximately 0.98 triatomines per hour were found when only humans were conducting searches; when working with the dog, approximately 1.71 triatomines per hour were found. In total, 3 adults and 107 nymphs of four species (Triatoma gerstaeckeri, Triatoma protracta, Triatoma sanguisuga, and Triatoma indictiva) were collected. PCR testing of a subset revealed T. cruzi infection, including DTUs TcI and TcIV, in 27% of nymphs (n = 103) and 66% of adults (n = 3). Bloodmeal analysis of a subset of triatomines (n = 5) revealed feeding on Virginia opossum (Didelphis virginiana), Southern plains woodrat (Neotoma micropus), and eastern cottontail (Sylvilagus floridanus).Conclusion/significanceA trained scent detection dog enhanced triatomine detections in sylvatic habitats. This approach is effective at detecting nidicolous triatomines. Control of sylvatic sources of triatomines is challenging, but this new knowledge of specific sylvatic habitats and key hosts may reveal opportunities for novel vector control methods to block the transmission of T. cruzi to humans and domestic animals.

Borzoi are large, relatively uncommon sighthounds anecdotally reported to suffer from sudden death. This multicenter retrospective cohort study aimed to describe the sample of Borzoi presenting to veterinary cardiologists for evaluation, with records searched from 14 centers across a study period of up to 20 years. The study sample was comprised of 152 client-owned Borzoi, with dogs most commonly presenting for pre-breed screening in 87/152 (52%), followed by evaluation of an arrhythmia in 28/152 (18%). Of the 131/152 (86%) dogs that had an echocardiogram performed, 85/131 (65%) were structurally normal, with 40/85 (47%) structurally normal dogs having trace or mild atrioventricular valve regurgitation. Tricuspid valve dysplasia was the most commonly diagnosed congenital cardiac disease (n = 6). Myxomatous mitral valve disease (n = 12) and dilated cardiomyopathy (n = 13) were diagnosed at similar frequencies, though 92% of valve disease cases were mild. Only 48/152 (32%) Borzoi had a diagnostic electrocardiogram (ECG) and/or a Holter monitor for arrhythmia screening. Despite this, ventricular arrhythmias were identified during the entirety of the available cardiac evaluation including diagnostic ECG, contemporaneous ECG monitoring during the echocardiogram, and/or Holter monitor in 25/131 (19%) dogs in which an echocardiographic diagnosis was available. Of these 25 Borzoi, 76% had minimal or no structural cardiac disease identified, and five had a family history of sudden death. A sudden death outcome was reported in 3/55 (5%) Borzoi with long-term outcome data available. In conclusion, Borzoi commonly have trace or mild atrioventricular valve insufficiencies, and may develop ventricular arrhythmias and dilated cardiomyopathy.

Trypanosoma cruzi infection causes inflammation and fibrosis, resulting in cardiac damage in dogs. The objectives of this study were to describe cardiac magnetic resonance imaging (CMR) in naturally infected dogs with chronic Chagas disease and the frequency of abnormalities for CMR and cardiac diagnostic tests. Ten asymptomatic, client-owned dogs seropositive for T. cruzi were prospectively enrolled in an observational study evaluating echocardiography, ECG (standard and ambulatory), cardiac troponin I (cTnI), and CMR. Standard ECG measurements (3/10) and cTnI concentration (1/10) outside the reference range were uncommon. Ambulatory ECG abnormalities were documented more frequently (6/10 dogs) than with standard ECG and included ventricular arrhythmias (4), supraventricular premature beats (3), second-degree atrioventricular block (2), and sinus arrest (1). Echocardiographic abnormalities were documented in 6/10 dogs including mildly increased left ventricular internal dimension in diastole (1) and decreased right ventricular (RV) systolic function based on reductions in tricuspid annular plane systolic excursion (3) and RV S’ (4). Abnormalities were detected with CMR in 7/10 dogs including delayed myocardial enhancement in 5 of which 2 also had increased extracellular volume, abnormal wall motion in 5, and loss of apical compact myocardium in 1. In conclusion, CMR abnormalities were common, and the results of this study suggest CMR can provide useful information in dogs with T. cruzi infection and may support naturally infected dogs for future clinical investigation as an animal model for Chagas disease.