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1.
Nano Lett ; 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38578061

RESUMEN

Monolayer 2D semiconductors, such as WS2, exhibit uniquely strong light-matter interactions due to exciton resonances that enable atomically thin optical elements. Similar to geometry-dependent plasmon and Mie resonances, these intrinsic material resonances offer coherent and tunable light scattering. Thus far, the impact of the excitons' temporal dynamics on the performance of such excitonic metasurfaces remains unexplored. Here, we show how the excitonic decay rates dictate the focusing efficiency of an atomically thin lens carved directly out of exfoliated monolayer WS2. By isolating the coherent exciton radiation from the incoherent background in the focus of the lens, we obtain a direct measure of the role of exciton radiation in wavefront shaping. Furthermore, we investigate the influence of exciton-phonon scattering by characterizing the focusing efficiency as a function of temperature, demonstrating an increased optical efficiency at cryogenic temperatures. Our results provide valuable insights into the role of excitonic light scattering in 2D nanophotonic devices.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38597362

RESUMEN

The prevalence of anatomical-based subtypes of feline congenital extrahepatic portosystemic shunts (EHPSS) has not been completely elucidated. The goal of this study was to use CT angiography to create an anatomical-based nomenclature system for feline congenital EHPSS. Additionally, subjective portal perfusion scores were generated to determine if intrinsic portal vein development was associated with different shunt conformations or patient age at the time of CT. The SVSTS and VIRIES list services were used to recruit cases. Data collected included patient DOB, gender, breed, weight, CT date, and reported diagnosis. Shunts were classified based upon (1) the shunt portal vessel(s) of origin, (2) the shunt systemic vessel(s) of insertion, and (3) any substantial portal vessels contributing to the shunt. Additionally, hepatic portal perfusion was subjectively scored between 1 (poor/none) and 5 (good/normal) based on the caliber of the intrahepatic PVs. A total of 264 CT scans were submitted from 29 institutions. Due to exclusion criteria, 33 (13%) were removed, leaving 231 CT scans to be included. Twenty-five different EHPSS anatomies were identified with five classifications accounting for 78% of all shunts (LGP [53%], LGC-post [11%], LCG [7%], LGC-pre [4%], and PC [4%]). Shunt origin involved the left gastric vein in 75% of the described classifications. Significant differences were identified among the five most common shunt types with respect to age at the time of CT scan (P = .002), breed (P < .001), and subjective portal perfusion score (P < .001). This refined anatomical classification system for feline EHPSS may enable improved understanding, treatment comparisons, and outcome prediction for cats with these anomalies.

3.
CASE (Phila) ; 8(3Part A): 231-235, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38524971
5.
J Vet Intern Med ; 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38500407

RESUMEN

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.

6.
Sci Adv ; 10(4): eadj8819, 2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38266081

RESUMEN

Vertically stacked van der Waals (vdW) heterostructures exhibit unique electronic, optical, and thermal properties that can be manipulated by twist-angle engineering. However, the weak phononic coupling at a bilayer interface imposes a fundamental thermal bottleneck for future two-dimensional devices. Using ultrafast electron diffraction, we directly investigated photoinduced nonequilibrium phonon dynamics in MoS2/WS2 at 4° twist angle and WSe2/MoSe2 heterobilayers with twist angles of 7°, 16°, and 25°. We identified an interlayer heat transfer channel with a characteristic timescale of ~20 picoseconds, about one order of magnitude faster than molecular dynamics simulations assuming initial intralayer thermalization. Atomistic calculations involving phonon-phonon scattering suggest that this process originates from the nonthermal phonon population following the initial interlayer charge transfer and scattering. Our findings present an avenue for thermal management in vdW heterostructures by tailoring nonequilibrium phonon populations.

7.
Leuk Lymphoma ; 65(1): 109-117, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37917858

RESUMEN

Multiple myeloma (MM) is more common among Black/African American (AA) patients than White patients, but survival rate improvements are less pronounced for AA patients. This study evaluated treatment patterns and survival among 1810 AA and 5904 White adults in the United States with ≥1 MM treatment and ≥3 months of follow-up. Median time from diagnosis to systemic treatment was longer (37 [0-3053] vs. 35 [0-3664] days) and median time to stem cell transplant (SCT) was longer for AA than White patients (255 [1-2352] vs. 225 [1-3094] days), and AA patients were less likely to receive SCT (odds ratio [OR]: 0.66; 95% confidence interval [CI]: 0.58-0.76). Despite disparities in treatment between AA and White patients, AA patients demonstrated lower risk of death (OR: 0.89; 95% CI: 0.81-0.96). These data highlight the value of equal access to care for the improvement of health outcomes in underserved populations.


Asunto(s)
Mieloma Múltiple , Adulto , Humanos , Negro o Afroamericano , Disparidades en Atención de Salud , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/epidemiología , Mieloma Múltiple/terapia , Estados Unidos/epidemiología , Blanco
8.
Am J Vet Res ; : 1-10, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38154250

RESUMEN

OBJECTIVE: To develop breed-specific echocardiographic values for normal Borzoi and to report the prevalence of structural cardiac abnormalities. ANIMALS: 146 clinically healthy, adult Borzoi dogs. METHODS: Cardiac auscultation and standard echocardiograms were performed. Longitudinal follow-up was described in a subset of dogs (n = 25). RESULTS: Most Borzoi were structurally normal (119/146, 81.5%), with breed-specific echocardiographic values generated independently for each sex, as females weighed significantly less than males (30.4 ± 3.8 kg vs 38.3 ± 4.1 kg, respectively; P < .001), and a significant impact of sex was found on most measurements. Physiologic heart murmurs were identified in 64/119 (53.8%) normal dogs. Thirty-six (30.2%) structurally normal dogs had trace or mild mitral regurgitation, and 43 (36.1%) had trace or mild tricuspid regurgitation. Structural cardiac disease was identified in 21 dogs (14.4%), including 9 dogs (6.2%) with dilated cardiomyopathy (DCM), 9 dogs (6.2%) with stage B1 myxomatous mitral valve disease (MMVD), and 3 (2.1%) dogs with congenital abnormalities. Seven dogs (4.8%) had equivocal abnormalities. During follow-up, new dogs were diagnosed with occult DCM (n = 3), equivocal DCM (1), and stage B1 MMVD (2). Two dogs originally diagnosed with DCM (1 occult and 1 equivocal) normalized after diet change. CLINICAL RELEVANCE: Borzoi dogs commonly have physiologic heart murmurs and mild atrioventricular valve regurgitation. Both DCM and MMVD were identified at similar frequencies in healthy Borzoi, although dogs with MMVD all had normal heart sizes. Echocardiographic screening for DCM in Borzoi should be considered, with breed-specific echocardiographic values now available for improved diagnostic confidence.

9.
J Vet Diagn Invest ; 35(6): 704-709, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37670473

RESUMEN

The vector-borne protozoan parasite Trypanosoma cruzi causes Chagas disease in humans, dogs, and many other mammalian hosts. Canine Chagas disease is increasingly diagnosed in dogs of the southern United States where triatomine insect vectors occur, and there are limited veterinary testing options; only the indirect fluorescent antibody (IFA) test is offered at a single accredited diagnostic laboratory. We evaluated a multiplex microsphere immunoassay (MIA) for the detection of antibodies against T. cruzi in dogs and compared it with existing serologic methods to establish cutoff values and relative sensitivity and specificity. We tested 135 canine sera that had been characterized using the IFA and off-label use of 2 commercial rapid assays with our multiplex MIA against 12 antigens: 9 T. cruzi antigens, a negative control recombinant protein (green fluorescent protein, GFP), a Leishmania antigen, and a canine parvovirus antigen (used as an antibody control given near-ubiquitous parvoviral vaccination). The median fluorescence intensity (MFI) ratio between each T. cruzi antigen and GFP was calculated for every sample. Samples with an antigen:GFP MFI ratio > 4 SDs above the mean of 25 known-negative sera were considered positive to that antigen. Samples testing positive to ≥ 2 antigens were considered positive for T. cruzi antibodies. Compared to the IFA, our multiplex MIA had a relative sensitivity of 100% and specificity of 97.0%. Given its precision, high-throughput format, potential for automation, and lack of subjective interpretation, our multiplex MIA should be considered a valid and improved assay for T. cruzi antibodies in dogs.


Asunto(s)
Enfermedad de Chagas , Enfermedades de los Perros , Trypanosoma cruzi , Humanos , Animales , Perros , Microesferas , Enfermedad de Chagas/diagnóstico , Enfermedad de Chagas/veterinaria , Inmunoensayo/veterinaria , Inmunoensayo/métodos , Anticuerpos Antiprotozoarios , Mamíferos
10.
Nat Commun ; 14(1): 5726, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37714855

RESUMEN

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.

11.
PLoS One ; 18(7): e0288801, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37463140

RESUMEN

Cardiac troponin I (cTnI) is considered the gold standard biomarker for myocardial injury and shows a high degree of homology between humans and dogs. The ADVIA Centaur XP High-Sensitivity Troponin I (AC-cTnI-HS) assay has been validated for use in humans but not dogs. The study objectives were to analytically validate the AC-cTnI-HS assay in dogs, to assess correlation between the AC-cTnI-HS and a previous ADVIA Centaur TnI-Ultra (AC-cTnI-U) assay, to assess cTnI sample storage stability, and to clinically evaluate the AC-cTnI-HS assay in healthy dogs and dogs with cardiac disease. Canine serum samples were used for analytical validation. Intra- and inter-assay variability, dilutional parallelism, and spiking recovery were assessed. Samples from 196 client-owned dogs were evaluated (healthy dogs (n = 39) or dogs with congenital heart disease (n = 54), myxomatous mitral valve disease (n = 68), dilated cardiomyopathy (n = 15), or myocarditis (n = 20)). Inter- and intra-assay coefficient of variation (%CV) was between 2.8-41.4% and 3.8-30.2%, respectively, with pools with concentrations >20 pg/mL all having %CVs <10%. The observed to expected ratios for dilutional parallelism and spiking recovery experiments ranged between 92.3 and 266.7.0% and 84.3 and 108%, respectively. A strong correlation between the AC-cTnI-HS and AC-cTnI-U assays was observed (Spearman's ρ = 0.927), though a proportional bias existed, with AC-cTnI-HS assay concentrations being proportionally lower than AC-cTnI-U assay concentrations. Serum samples stored at -80°C had stable cTnI measurements for up to 2.7 years and after a single freeze-thaw cycle. Healthy dogs and dogs with congenital heart disease had significantly lower cTnI concentrations than dogs in the other three groups. The AC-cTnI-HS assay precisely, reproducibly, and accurately measures cTnI concentrations in dog serum with cTnI concentrations >20 pg/mL.


Asunto(s)
Cardiomiopatía Dilatada , Cardiopatías , Enfermedades de las Válvulas Cardíacas , Humanos , Animales , Perros , Troponina I , Cardiopatías/veterinaria , Inmunoensayo , Biomarcadores
12.
Front Vet Sci ; 10: 1168711, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37275618

RESUMEN

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.

13.
Future Oncol ; 19(11): 763-773, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37161798

RESUMEN

Aim: To define ruxolitinib failure and develop parameters to guide transition to next-line therapy for patients with myelofibrosis. Methods: A modified Delphi panel with 14 hematologists-oncologists. Survey concepts included defining primary refractory status, loss of response, disease progression, intolerance and transition to next-line therapy. Results: Ruxolitinib failure may be defined as no improvement in symptoms or spleen size, progressive disease or ruxolitinib intolerance, following a maximally tolerated dose for ≥3 months. Loss of spleen response 1 month after initial response may prompt discontinuation. Lack of evidence to inform transition to next-line therapy was noted; tapering ruxolitinib should be considered according to ruxolitinib dose and patient characteristics. Conclusion: Expert consensus was provided on defining ruxolitinib failure and transition to next-line therapy as summarized in this position paper, which may support considerations in the development of future clinical practice guidelines.


People with myelofibrosis who receive treatment with ruxolitinib may need to stop treatment because it is not working or they cannot tolerate the side effects. There is little good scientific information available about how and when to stop ruxolitinib treatment, and how to move to another treatment after stopping ruxolitinib. A group of clinical experts in hematology and oncology followed a scientific process, called the Delphi method, to discuss this topic and to reach agreement on the most important aspects of this challenge. The experts agreed that ruxolitinib failure may be defined as having no improvement in symptoms or spleen size, progressive disease or ruxolitinib intolerance, after the patient was receiving the highest dose they could tolerate for ≥3 months. The results of this expert discussion may support patients and their healthcare providers making decisions in real life, and development of future clinical practice guidelines.


Asunto(s)
Mielofibrosis Primaria , Humanos , Mielofibrosis Primaria/diagnóstico , Mielofibrosis Primaria/tratamiento farmacológico , Nitrilos/uso terapéutico , Pirimidinas/uso terapéutico , Pirazoles/efectos adversos
14.
Antimicrob Agents Chemother ; 67(5): e0013223, 2023 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-37039666

RESUMEN

Trypanosoma cruzi naturally infects a broad range of mammalian species and frequently results in the pathology that has been most extensively characterized in human Chagas disease. Currently employed treatment regimens fail to achieve parasitological cure of T. cruzi infection in the majority of cases. In this study, we have extended our previous investigations of more effective, higher dose, intermittent administration protocols using the FDA-approved drug benznidazole (BNZ), in experimentally infected mice and in naturally infected dogs and nonhuman primates (NHP). Collectively, these studies demonstrate that twice-weekly administration of BNZ for more than 4 months at doses that are ~2.5-fold that of previously used daily dosing protocols, provided the best chance to obtain parasitological cure. Dosing less frequently or for shorter time periods was less dependable in all species. Prior treatment using an ineffective dosing regimen in NHPs did not prevent the attainment of parasitological cure with an intensified BNZ dosing protocol. Furthermore, parasites isolated after a failed BNZ treatment showed nearly identical susceptibility to BNZ as those obtained prior to treatment, confirming the low risk of induction of drug resistance with BNZ and the ability to adjust the treatment protocol when an initial regimen fails. These results provide guidance for the use of BNZ as an effective treatment for T. cruzi infection and encourage its wider use, minimally in high value dogs and at-risk NHP, but also potentially in humans, until better options are available.


Asunto(s)
Enfermedad de Chagas , Nitroimidazoles , Tripanocidas , Trypanosoma cruzi , Ratones , Perros , Humanos , Animales , Tripanocidas/uso terapéutico , Tripanocidas/farmacología , Enfermedad de Chagas/tratamiento farmacológico , Enfermedad de Chagas/parasitología , Nitroimidazoles/uso terapéutico , Nitroimidazoles/farmacología , Protocolos Clínicos , Primates , Mamíferos
15.
Animals (Basel) ; 13(8)2023 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-37106957

RESUMEN

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.

16.
PLoS Negl Trop Dis ; 17(3): e0010813, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36940217

RESUMEN

BACKGROUND: Triatomine 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/FINDINGS: Ziza, 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/SIGNIFICANCE: A 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.


Asunto(s)
Enfermedad de Chagas , Lagomorpha , Triatoma , Trypanosoma cruzi , Humanos , Femenino , Animales , Perros , Preescolar , Texas/epidemiología , Perros de Trabajo , Enfermedad de Chagas/diagnóstico , Enfermedad de Chagas/veterinaria , Enfermedad de Chagas/epidemiología , Ecosistema , Ninfa
17.
Front Vet Sci ; 10: 1102494, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36777677

RESUMEN

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.

18.
bioRxiv ; 2023 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-36778432

RESUMEN

Trypanosoma cruzi naturally infects a broad range of mammalian species and frequently results in the pathology that has been most extensively characterized in human Chagas disease. Currently employed treatment regimens fail to achieve parasitological cure of T. cruzi infection in the majority of cases. In this study, we have extended our previous investigations of more effective, higher dose, intermittent administration protocols using the FDA-approved drug benznidazole (BNZ), in experimentally infected mice and in naturally infected dogs and non-human primates (NHP). Collectively these studies demonstrate that twice-weekly administration of BNZ for more than 4 months at doses that are ∻2.5-fold that of previously used daily dosing protocols, provided the best chance to obtain parasitological cure. Dosing less frequently or for shorter time periods was less dependable in all species. Prior treatment using an ineffective dosing regimen in NHPs did not prevent the attainment of parasitological cure with an intensified BNZ dosing protocol. Furthermore, parasites isolated after a failed BNZ treatment showed nearly identical susceptibility to BNZ as those obtained prior to treatment, confirming the low risk of induction of drug resistance with BNZ and the ability to adjust the treatment protocol when an initial regimen fails. These results provide guidance for the use of BNZ as an effective treatment for T. cruzi infection and encourage its wider use, minimally in high value dogs and at-risk NHP, but also potentially in humans, until better options are available.

19.
J Am Vet Med Assoc ; 261(5): 705-712, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36735504

RESUMEN

OBJECTIVE: To describe the clinical presentation and outcome in dogs diagnosed with Trypanosoma cruzi infection in nonendemic areas and to survey veterinary cardiologists in North America for Chagas disease awareness. ANIMALS: 12 client-owned dogs; 83 respondents from a veterinary cardiology listserv. PROCEDURES: A retrospective, multicenter medical records review to identify dogs diagnosed with American trypanosomiasis between December 2010 and December 2020. An anonymous online survey was conducted August 9 to 22, 2022. RESULTS: Diagnosis was made using indirect fluorescent antibody titer (n = 9), quantitative PCR assay (1), or postmortem histopathology (2). Time spent in Texas was < 1 year (n = 7) or 2 to 8 years (5). Time in nonendemic areas prior to diagnosis was < 1 year (n = 10) and > 3 years (2). Eleven had cardiac abnormalities. Of the 12 dogs, 5 had died unexpectedly (range, 1 to 108 days after diagnosis), 4 were still alive at last follow-up (range, 60 to 369 days after diagnosis), 2 were euthanized because of heart disease (1 and 98 days after diagnosis), and 1 was lost to follow-up. Survey results were obtained from 83 cardiologists in North America, of which the self-reported knowledge about Chagas disease was limited in 49% (41/83) and 69% (57/83) expressed interest in learning resources. CLINICAL RELEVANCE: Results highlight the potential for encountering dogs with T cruzi infection in nonendemic areas and need for raising awareness about Chagas disease in North America.


Asunto(s)
Enfermedad de Chagas , Enfermedades de los Perros , Trypanosoma cruzi , Animales , Perros , Estudios Retrospectivos , Enfermedad de Chagas/diagnóstico , Enfermedad de Chagas/epidemiología , Enfermedad de Chagas/veterinaria , Texas , Encuestas y Cuestionarios , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/epidemiología
20.
Vet Clin North Am Small Anim Pract ; 52(6): 1267-1281, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36336420

RESUMEN

Veterinary Chagas disease is a persistent threat to humans, dogs, and other wild or domestic mammals that live where infected triatomine "kissing bug" insect vectors occur across the Americas, including 28 states in the Southern United States. Animals infected with the Trypanosoma cruzi parasite may be asymptomatic or may develop myocarditis, heart failure, and sudden death. It is difficult to prevent animal contact with vectors because they are endemic in sylvatic environments and often disperse to domestic habitats. Challenges for disease management include imperfect diagnostic tests and limited antiparasitic treatment options.


Asunto(s)
Enfermedad de Chagas , Enfermedades de los Perros , Triatoma , Trypanosoma cruzi , Animales , Estados Unidos/epidemiología , Humanos , Perros , Enfermedad de Chagas/diagnóstico , Enfermedad de Chagas/epidemiología , Enfermedad de Chagas/terapia , Enfermedad de Chagas/veterinaria , Triatoma/parasitología , Trypanosoma cruzi/parasitología , Insectos Vectores/parasitología , Mamíferos/parasitología , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/terapia
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