Sexual behaviour of young rams is improved and less stressful after intranasal administration of oxytocin.

The aim of this study was to determine if intranasal administration of oxytocin modifies sexual behaviour and the stress response in young rams during sexual tests with ewes in oestrus. Ten rams were used in a cross-over design. At Day 0, the control group (CG, n = 5) received isotonic saline spray intranasally, and the treated group (OTG, n = 5) received oxytocin (24 IU) intranasally, 40 min before the sexual test. At Day 15, the groups were reversed. In each sexual test (20 min) with an oestrous-induced ewe, the sexual behaviour of the young rams was recorded. Serum cortisol concentrations were determined before and after the test. Less flehmen was observed in the OTG, but mounts with ejaculation were increased. The OTG presented lower serum cortisol concentration than the CG. In conclusion, intranasal administration of oxytocin modified the sexual behaviour of rams, evidenced by a decrease in flehmen behaviour and an increase in mounts with ejaculation, making sexual activity more efficacious. In addition, the treatment decreased the stress response of the rams in the sexual tests. Therefore, intranasal administration of oxytocin could be used to increase sexual activity in rams, and with less stress, providing better welfare conditions.

Syringe immersion test as in vitro bioassay against Rhipicephalus microplus: Macrocyclic lactones dose-response relationship.

Background: For the diagnosis of tick sensitivity against different acaricides, there are in vitro and in vivo methods. The main in vivo method, the stable test, is considered a defining methodology. In Uruguay, the Rhipicephalus microplus (R. microplus) strain Mozo is used as the standard susceptible strain by the regulatory authorities. In vitro techniques applied both on adult and larvae stages are validated by FAO and can serve as an orientation diagnosis of the resistance profile developed in field conditions. An alternative was proposed as a modification of the larval immersion test (LIT), where syringes were used seeking to reduce the work necessary to perform the original technique, resulting in the syringe immersion test (SIT). Aim: The aim of this study was to expand the SIT for the characterization of sensitivity to Macrocyclic Lactones (MLs) in R. microplus and provide information on field strain sensitivity of R. microplus larvae. Methods: Log-logistic dose-response model for Ivermectin (IVM), Doramectin (DRM), and Moxidectin (MOX) were performed using concentrations ranging from 0.01 to 20.0 ppm (n = 6, 3 replicates per level on each drug). Larvae sensitivity results were determined after 24 hours of incubation at 27°C/90% RH, counting live/dead larvae. The final model will be decided as the best fit according to the model selection AIC criteria for each drug. Pharmacodynamic parameters [lower limit, slope, and effective dose at different levels (ED20, ED50, ED80, and ED95)] and its 95% confidence interval were considered for drug comparison. Results: Dose-response models were fitted for IVM, DRM, and MOX. MOX had the lowest ED50 of the three drugs, implying that MOX is of higher potency (two folds) when compared to IVM and DRM on R. microplus larvae using SIT. DRM had a different slope compared to IVM and MOX (p < 0.05), while IVM and MOX showed a similar slope (p > 0.05). Conclusion: This study allowed us to standardize the technique for larvae immersion for each ML, granting a new tool for in vitro test as a screening technique for tick sensitivity.

Clinical signs associated with prostatic disorders in canines: Retrospective study in Uruguay (2011-2019).

Background: Prostate disease represents about 0.7% of diseases in canines. The main diagnosed pathology is benign prostatic hyperplasia (BPH). However, the reports that study the association of a certain clinical sign with a specific prostate disease are scarce. Aim: The main objective of this study was to evaluate the clinical relevance of the most commonly observed clinical signs associated with the different prostatic disorders in canines admitted to the hospital of the Facultad de Veterinaria-Universidad de la República between 2011 and 2019. Methods: This retrospective study included 7,729 male canines treated at the hospital de la Facultad de Veterinaria-Universidad de la República (Montevideo, Uruguay) between 2011 and 2019. 289 canines with a presumptive/definitive diagnosis of prostate diseases were selected, recording the presence/absence of associated clinical signs. Results were reported in terms of odds ratios (ORs) using logistic regression (p < 0.05). Results: The five most frequently reported clinical signs were tenesmus (34%), anorexia (32%), lethargy (27%), prostatomegaly or pain during rectal examination (25%), and abdominal pain from palpation (22%). Diarrhea (3.39 vs. 0.33 OR), anorexia (2.07 vs. 0.39 OR), weight loss (2.27 vs. 0.27 OR), hematuria (3.25 vs. 0.44 OR), and urinary incontinence (2.96 vs. 0.33 OR) indicated a highest predictive value (p < 0.05) with prostatitis versus BPH, respectively. Being weight loss, the clinical sign is more frequently associated with neoplasia (20.2 OR, p = 0.002). Conclusion: This study shows that there are clinical signs with a higher degree of association for certain canine prostatic disorders than others.

Therapeutic advantages of the combined use of closantel and moxidectin in lambs parasitized with resistant gastrointestinal nematodes.

The serious widespread development of nematode resistance has motivated the use of combined anthelmintic formulations. However, the advantages/disadvantages of the combined use of anthelmintics require further scientific characterization. The goals of the current trial were a) to characterize the pharmacokinetics of closantel (CLO) and moxidectin (MXD) administered both subcutaneously (sc) and orally either separately or co-administered (CLO + MXD) to lambs; b) to compare the nematodicidal activity of both molecules given individually or co-administered to lambs infected with resistant nematodes. Seventy (70) Corriedale lambs naturally infected with multiple resistant gastrointestinal nematodes were involved in the pharmacokinetic and efficacy trials. The animals were allocated into six groups (n = 10) and treated with either CLO, MXD, or with the CLO + MXD combined formulation by both the oral and sc routes. Additionally, an untreated control group (n = 10) was included for the efficacy trial. The efficacy was estimated by the faecal egg count reduction test (FECRT). Higher systemic exposure of both CLO and MXD was observed after the sc compared to the oral administration in lambs. The combined administration of CLO + MXD did not markedly alter their disposition kinetics. At 13 days post-treatment, the administration of both molecules as a single active principle reached efficacy levels ranging between 80% (MXDoral), 84% (CLOoral), 85% (CLOsc), and 92% (MXDsc). The combined oral and sc treatments reached 99% efficacy. No adverse effects were observed after the combined treatment of CLO + MXD, and their co-administration did not show any adverse pharmacokinetic interaction. The combined effect of CLO + MXD successfully restored the maximum efficacy levels, which were not reached by the individual active ingredients.

Characterization of the Domestic Cat Population of Uruguay: Breeds, Coat Colors, Hair Length, Lifestyle, Sex and Spay/Neuter Status According to Guardian Report.

The objective of this study was to characterize the domestic cat population of Uruguay in relation to breed, coat color, hair length, lifestyle (indoor vs. outdoor), age, sex, and spay/neuter status according to a survey completed by their owners or guardians. An online survey, distributed to residents of Uruguay, was completed in full by 2561 cat guardians. Descriptive statistics and Chi-squared tests were performed. The population of cats with guardians in Uruguay is characterized by the following data: higher frequency of female cats (53%), most of the cats were between two and six years old (49%), most of them were neutered (84%, mainly those older than one year of age), most of them have outdoor access (87%), a very low percentage (6%) are purebred (Siamese being the most frequent: 86%), and within the non-pure breeds, short hair cats were the most frequent (79%). This study, in addition to expanding the information on the characteristics of cats with guardians from other countries and continents, is the first study in Latin America to describe some key demographic aspects such as cat breeds, coat color, hair length, lifestyles, and frequency by age, sex, and spay/neuter status (spayed/neutered or not) at the country level.

Characterization of Raid Hipico Uruguayo Competencies by Ride Type: Causes of Death and Risk Factors.

RHU is the oldest endurance sport in Uruguay. However, despite 80 years of racing, there are no studies to characterize this type of competition, explore rates and causes of death, and identify the associated risk factors. The aim was to characterize the Raid Hipico Uruguayo (RHU) competencies according to the distance (short (SR, 60 km) vs. long (LR, 80-115 km)), the causes of deaths, and the associated risk factors. The study population comprised horses (n = 16,856) that participated in RHU rides from 2007 to 2018. LR were more frequent than SR (p < 0.001). The average speed of winners was higher in SR (32.12 km/h) than in LR (28.14 km/h) (p < 0.001). There were 99 fatalities (5.9 per 1000 starts). SR had greater frequency of high comfort index (CI = Temp [°F] + Humidity [%]) than LR, and LR had greater frequency of low CI than SR (p < 0.001). The percentage of inexperienced horses and those who completed the ride was greater in SR than in LR (p < 0.001). In both types of rides, more horses died during than after the ride, and inexperienced horses were more likely to suffer fatalities than horses with prior experience in the sport (p < 0.05). SR were associated with increased risk of sudden death, while LR were associated with increased risk of death due to metabolic alterations. The high fatality index shown in this work warrants urgent investigation in this sport to minimize mortality associated with RHU-specific diseases.

Hydroelectrolytic and Acid-Base Parameters after 80 to 115 km Endurance Races (Raid Uruguayo) and Their Association with the Comfort Index.

The Raid Uruguayo (RAID) is an equestrian endurance competition. This study characterized the hydroelectrolytic parameters (Na+, K+, Cl-, tCa++, and iCa++), hematocrit (Ht), total plasma protein (TPP), and blood pH from 900 equine athletes (finishers and non-finishers) competing over distances of 80 to 115 km under different climate conditions. Paired blood samples were taken prior to the start of the competition (sample 1) and at the end of the race or at the time of leaving the competition (sample 2). The association of the comfort index (CI: low, moderate, and high) with blood parameters was evaluated. Of the 900 horses included, 550 were not able to finish the trial. The comfort index was not associated with success in completing the race. In the horses that finished the race, the CI was not associated with Ht, pH, TPP, or Na+ concentrations in samples taken after finishing the RAID. In contrast, the decreases in chloride, K+, tCa++, and iCa++ concentrations found after the race were more pronounced at moderate and high CI values when compared with low CI values. In horses that did not finish the race, the CI was associated with all variables except for Ht. The data confirmed the relevance of considering the impact of the comfort index in hydroelectrolytic losses in the RAID, as it influence ssuccess or failure in the performance of endurance horses finishing the competition.

Caenorhabditis elegans as a valuable model for the study of anthelmintic pharmacodynamics and drug-drug interactions: The case of ivermectin and eprinomectin.

Caenorhabditis elegans is a free-living nematode that has been validated for anthelmintic drug screening. However, this model has not been used to address anthelmintic dose-response-time and drug-drug interactions through matrix array methodology. Eprinomectin (EPM) and Ivermectin (IVM) are macrocyclic lactones widely used as anthelmintics. Despite being very similar, EPM and IVM are combined in commercial formulations or mixed by farmers, under the assumption that the combination would increase their efficacy. However, there is no data reported on the pharmacological evaluation of the combination of both drugs. In this study, we assessed the pharmacodynamics and drug-drug interactions of these two anthelmintic drugs. Since the action of these drugs causes worm paralysis, we used an infrared motility assay to measure EPM and IVM effects on worm movement over time. The results showed that EPM was slightly more potent than IVM, that drug potency increased with drug time exposure, and that once paralyzed, worms did not recover. Different EPM/IVM concentration ratios were used and synergy and combination sensitivity scores were determined at different exposure times, applying Highest Single Agent (HSA), Loewe additivity, Bliss and Zero Interaction Potency (ZIP) models. The results clearly indicate that there is neither synergy nor antagonism between both macrocyclic lactones. This study shows that it is more relevant to prioritize the exposure time of each individual drug than to combine them to improve their effects. The results highlight the utility of C. elegans to address pharmacodynamics studies, particularly for drug-drug interactions. Models in vitro can be integrated to facilitate preclinical and clinical translational studies and help researchers to understand drug-drug interactions and achieve rational therapeutic regimes.

The potential of bioprinting for preparation of nanoparticle-based calibration standards for LA-ICP-ToF-MS quantitative imaging.

This paper discusses the feasibility of a novel strategy based on the combination of bioprinting nano-doping technology and laser ablation-inductively coupled plasma time-of-flight mass spectrometry analysis for the preparation and characterization of gelatin-based multi-element calibration standards suitable for quantitative imaging. To achieve this, lanthanide up-conversion nanoparticles were added to a gelatin matrix to produce the bioprinted calibration standards. The features of this bioprinting approach were compared with manual cryosectioning standard preparation, in terms of throughput, between batch repeatability and elemental signal homogeneity at 5 µm spatial resolution. By using bioprinting, the between batch variability for three independent standards of the same concentration of 89Y (range 0-600 mg/kg) was reduced to 5% compared to up to 27% for cryosectioning. On this basis, the relative standard deviation (RSD) obtained between three independent calibration slopes measured within 1 day also reduced from 16% (using cryosectioning) to 5% (using bioprinting), supporting the use of a single standard preparation replicate for each of the concentrations to achieve good calibration performance using bioprinting. This helped reduce the analysis time by approximately 3-fold. With cryosectioning each standard was prepared and sectioned individually, whereas using bio-printing it was possible to have up to six different standards printed simultaneously, reducing the preparation time from approximately 2 h to under 20 min (by approximately 6-fold). The bio-printed calibration standards were found stable for a period of 2 months when stored at ambient temperature and in the dark.

Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic: Chilean Air Force Experience in the Air Transport of Critically Ill Patients-The First 100 Cases.

OBJECTIVE: Critical care air transport has played an important role during the coronavirus disease 2019 (COVID-19) pandemic. The goal of this article is to analyze results and lessons learned from the evacuation of the first 100 COVID-19 patients transported between medical facilities in Chile. METHODS: We reviewed prospective data of patients who were referred for air transport between March 27, 2020, and July 9, 2020. RESULTS: Of 115 referred patients, 100 were transported by air. All patients were intubated and mechanically ventilated. Hypertension, diabetes, and obesity were the most commonly observed comorbidities. Our service did not experience any major problems in patient care en route or among the crewmembers. We did not observe any severe acute respiratory syndrome coronavirus 2 infections among our flight team members during the study period. Twelve (12%) patients died at their destination intensive care unit, whereas the remaining 88 patients (88%) returned to their primary hospitals after recovery. CONCLUSIONS: Air transport of mechanically ventilated patients with COVID-19 infection has been shown to be a safe way of transport, with no in-flight deaths and an in-hospital mortality of 12%, which compares favorably with the in-hospital mortality of similar patients who did not undergo air transport.

How do Time, Tannin, and Moisture Content Influence Toxicogenic Fungal Populations during the Storage of Sorghum Grains?

ABSTRACT: Cereal grains are usually ensiled to improve their nutritional value and are one of the main sources of feed for dairy cattle. However, during storage, grains can be contaminated with toxicogenic fungi. Sorghum is one of the most economically important cereals in the world. Therefore, the aim of this work was to evaluate the influence of storage duration and tannin and moisture content (MC) on toxicogenic fungal populations in sorghum grain storage. Samples that were prepared with varieties high in tannins (genotypes Morgan 108 and ACA 558, >5 g/kg dry matter) and with varieties low in tannin content (genotypes Flash 10 and ACA 546, <1 g/kg dry matter) were collected and manually compacted in experimental laboratory silos where they received different MC treatments: low (15 to 25%), medium (26 to 32%), and high (33 to 42%). Freshly harvested grains were analyzed at time 0, and stored grains were analyzed at 30, 90, and 180 days. Fungal isolation and identification were performed following conventional mycological methods. Penicillium citrinum (34%), Aspergillus flavus (60%), and Fusarium nygamai (68%) were the most abundant species. Rapid detection of aflatoxins and fumonisins in each sample was performed using enzyme-linked immunosorbent assay according to the AOAC method, and the quantification of aflatoxin B1 was performed using high-performance liquid chromatography. In four samples of pre- and poststorage grains, aflatoxins were detected with levels of 6.7 to 28.8 µg/kg and aflatoxin B1 with a level of 2 to 14 µg/kg. Fumonisins were only detected in two freshly harvested samples, with levels of 500 to 900 µg/kg. In general, storage time favored the increase of Penicillium populations and reduced Aspergillus and Fusarium. Conversely the abundance of the three populations was not affected by the MC. The results of this study show that fungal populations must be analyzed at different times.

Modeling human migration driven by changing mindset, agglomeration, social ties, and the environment.

Migration is an adaptation strategy to unfavorable conditions and is governed by a complex set of socio-economic and environmental drivers. Here we identified important drivers relatively underrepresented in many migration models-CHanging mindset, Agglomeration, Social ties, and the Environment (CHASE)-and asked: How does the interplay between these drivers influence transient dynamics and long-term outcomes of migration? We addressed this question by developing and analyzing a parsimonious Markov chain model. Our findings suggest that these drivers interact in nonlinear and complex ways. The system exhibits legacy effects, highlighting the importance of including migrants' changing priorities. The increased characteristic population size of the system counter-intuitively leads to fewer surviving cities, and this effect is mediated by how fast migrants change their mindsets and how strong the social ties are. Strong social ties result in less diverse populations across cities, but this effect is influenced by how many cities remain. To our knowledge, this is the first time that these drivers are incorporated in one coherent, mechanistic, parsimonious model and the effects of their interplay on migration systematically studied. The complex interplay underscores the need to incorporate these drivers into mechanistic migration models and implement such models for real-world cases.

Circulating Tumor Cells Enumeration from the Portal Vein for Risk Stratification in Early Pancreatic Cancer Patients.

BACKGROUND: Effective biomarkers are needed to enable personalized medicine for pancreatic cancer patients. This study analyzes the prognostic value, in early pancreatic cancer, of single circulating tumor cell (CTC) and CTC clusters from the central venous catheter (CVC) and portal blood (PV). METHODS: In total, 7 mL of PV and CVC blood from 35 patients with early pancreatic cancer were analyzed. CTC were isolated using a positive immunomagnetic selection. The detection and identification of CTC were performed by immunocytochemistry (ICC) and were analyzed by Epi-fluorescence and confocal microscopy. RESULTS: CTC and the clusters were detected both in PV and CVC. In both samples, the CTC number per cluster was higher in patients with grade three or poorly differentiated tumors (G3) than in patients with well (G1) or moderately (G2) differentiated. Patients with fewer than 185 CTC in PV exhibited a longer OS than patients with more than 185 CTC (24.5 vs. 10.0 months; p = 0.018). Similarly, patients with fewer than 15 clusters in PV showed a longer OS than patients with more than 15 clusters (19 vs. 10 months; p = 0.004). These significant correlations were not observed in CVC analyses. CONCLUSIONS: CTC presence in PV could be an important prognostic factor to predict poor prognosis in early pancreatic cancer. In addition, the number of clustered-CTC correlate to a tumor negative differentiation degree and, therefore, could be used as a diagnostic biomarker for pancreatic cancer.

Is the suckling period and application pattern relevant for fluazuron against tick infestation in cows and their suckling calves?

BACKGROUND: Fluazuron is a chitin synthesis inhibitor administered as a pour-on formulation in cattle for tick control. This study analyzes under endemic tick infestation, the incidence of the pour-on application pattern on the plasma levels of fluazuron in calves and cows in the lactation period of the beef cow. Two hundred and ninety-two beef cows around parturition were treated with a commercial pour-on formulation of fluazuron at a rate of 2.5 mg/kg of body weight. A total of 4 treatments were carried out on days 0, 32, 77, and 117. At each administration time, the cows were grouped according to the pour-on administration pattern: long (~ 60 cm pour-on application surface) and short (~ 30 cm pour-on application surface). Fluazuron levels in cows and calves plasma were determined before the third and fourth application for each subgroup (n = 10) by HPLC-MS/MS. During the entire study, cow-calf pairs were maintained under field conditions and qualitatively examined for tick infestation on the day of each treatment. Both treatments (long and short) schemes were designed to prevent the annual persistence of ticks. RESULTS: No animals with presence of ticks were identified during the first 117 days of the study, except for three cows and one calf at the time of the third application (day 77). There were no differences after 40 days (day 77) post-treatment of the second application (30 ± 5 ppb vs. 28.5 ± 12 ppb, p > 0.05) and 45 days (day 117) after the third application (147 ± 55 ppb vs 140 ± 46 ppb, p > 0.05) between groups of cows treated with the long or short pour-on application, respectively. Plasma concentration of fluazuron at second and third application was increased (3.3 and 2.9 times, respectively) in calves under free suckling compared to cows. Nevertheless, both groups of cows and calves showed a significant increase in plasma concentration of fluazuron between times (4.9 times, p < 0.0001 and 2.8 times, p < 0.0001, respectively). In both groups, tick prevalence was 0% throughout the trial, except for day 77, which reached 1%. CONCLUSIONS: The main conclusions of this study were the following: 1) Different administration patterns (long vs. short) did not differ in plasma levels of fluazuron.; 2) Given that only the cows were treated and lactating calves presented higher plasma levels of fluazuron than cows, passage through milk appears to be relevant and possibly due to a cumulative effect and continuous drug intake.

How public reaction to disease information across scales and the impacts of vector control methods influence disease prevalence and control efficacy.

With the development of social media, the information about vector-borne disease incidence over broad spatial scales can cause demand for local vector control before local risk exists. Anticipatory intervention may still benefit local disease control efforts; however, infection risks are not the only focal concerns governing public demand for vector control. Concern for environmental contamination from pesticides and economic limitations on the frequency and magnitude of control measures also play key roles. Further, public concern may be focused more on ecological factors (i.e., controlling mosquito populations) or on epidemiological factors (i.e., controlling infection-carrying mosquitoes), which may lead to very different control outcomes. Here we introduced a generic Ross-MacDonald model, incorporating these factors under three spatial scales of disease information: local, regional, and global. We tailored and parameterized the model for Zika virus transmitted by Aedes aegypti mosquito. We found that sensitive reactivity caused by larger-scale incidence information could decrease average human infections per patch breeding capacity, however, the associated increase in total control effort plays a larger role, which leads to an overall decrease in control efficacy. The shift of focal concerns from epidemiological to ecological risk could relax the negative effect of the sensitive reactivity on control efficacy when mosquito breeding capacity populations are expected to be large. This work demonstrates that, depending on expected total mosquito breeding capacity population size, and weights of different focal concerns, large-scale disease information can reduce disease infections without lowering control efficacy. Our findings provide guidance for vector-control strategies by considering public reaction through social media.

Therapeutic equivalence of ivermectin 1% and two novel formulations combined of ivermectin 1% + fluazuron 12.5% for the control of Rhipicephalus (Boophilus) microplus in beef cattle from Uruguay.

Background: Novel combinations of ivermectin (IVM) and fluazuron (FLU) are presented as an alternative for the control of ticks in cattle. Applying a combination of drugs with the aim to affect different stages of the parasite's life cycle is established as a potential measure to achieve the control of ticks in cattle. Aim: To determine the therapeutic equivalence between two novel formulations of IVM 1% combined with FLU 12.5% tested on bovines naturally infested with Rhipicephalus (Boophilus) microplus. Methods: Forty adult beef cattle were randomized into four groups (n = 10): IVM [1% (0.2 mg/kg)], combinations groups A and B [IVM 1% (0.2 mg/kg) + FLU 12.5% (2.5 mg/kg), each], and control [untreated]). On days 14, 27, and 49 after administration, the presence of ticks was ranked as null, low, medium, and high; a cumulative link model was adjusted to evaluate treatment response. Results: Although all groups had some animals with the presence of ticks until day 27, on day 14 IVM [odds ratios (OR) 0.013, CI95%: 0.001-0.014, p < 0.01], A (OR 0.01, CI95%: 0.00-0.07, p < 0.01) and B (OR 0.01, CI95%: 0.00-0.148, p < 0.01) groups were different when compared to the control group, unlike on day 27 where only groups A (OR 0.02, CI95%: 0.00-0.17, p < 0.01) and B (OR 0.06, CI95%: 0.00-0.46, p < 0.01) remained different from the control group. On day 49 post-administration, IVM and B did not differ from the control group, with 0.95 probability (CI95% 0.92-1.02) of high parasite burden. At day 49 post-administration, group A was the only group free of ticks (OR 0.01, CI95%: 0.00-0.13, p < 0.01). Conclusions: Pharmacotechnical differences in combined formulations should be considered in therapeutic equivalence studies.

Pharmacokinetic study of oral amitriptyline in horses.

The purpose of this study was to evaluate the pharmacokinetics of oral amitriptyline in horses. Oral amitriptyline (1 mg/kg) was administered to six horses. Blood samples were collected from jugular and lateral thoracic vein at predetermined times from 0 to 24 hr after administration. Plasma concentrations were determined by high-performance liquid chromatography and analyzed using noncompartmental methods. Pharmacodynamic parameters including heart rate, respiration rate, and intestinal motility were evaluated, and electrocardiographic examinations were performed in all subjects. The mean maximum plasma concentration (Cmax ) of amitriptyline was 30.7 ng/ml, time to maximum plasma concentration (Tmax ) 1-2 hr, elimination half-life (t1/2 ) 17.2 hr, area under plasma concentration-time curve (AUC) 487.4 ng ml-1  hr-1 , apparent clearance (Cl/F) 2.6 L hr-1  kg-1 , and apparent volume of distribution (Vd/F) 60.1 L/kg. Jugular vein sampling overestimated the amount of amitriptyline absorbed and should not be used to study uptake following oral administration. Heart rate and intestinal motility showed significant variation (p < .05). Electrocardiography did not provide conclusive results. Further studies are required to discern if multiple dose treatment would take the drug to steady state as expected, consequently increasing plasma concentrations.

Mating strategy is determinant of adenovirus prevalence in European bats.

Adenoviruses are double-strained DNA viruses found in a great number of vertebrates, including humans. In order to understand their transmission dynamics, it is crucial, even from a human health perspective, to investigate how host traits influence their prevalence. Bats are important reservoirs for adenoviruses, and here we use the results of recent screenings in Western Europe to evaluate the association between characteristic traits of bat species and their probability of hosting adenoviruses, taking into account their phylogenetic relationships. Across species, we found an important phylogenetic component in the presence of adenoviruses and mating strategy as the most determinant factor conditioning the prevalence of adenoviruses across bat species. Contrary to other more stable mating strategies (e.g. harems), swarming could hinder transmission of adenoviruses since this strategy implies that contacts between individuals are too short. Alternatively, bat species with more promiscuous behavior may develop a stronger immune system. Outstandingly high prevalence of adenoviruses was reported for the Iberian species Pipistrellus pygmaeus, P. kuhlii and Nyctalus lasiopterus and we found that in the latter, males were more likely to be infected by adenoviruses than females, due to the immunosuppressing consequence of testosterone during the mating season. As a general trend across species, we found that the number of adenoviruses positive individuals was different across localities and that the difference in prevalence between populations was correlated with their geographic distances for two of the three studied bat species (P. pygmaeus and P.kuhlii). These results increase our knowledge about the transmission mechanisms of adenoviruses.

A generic arboviral model framework for exploring trade-offs between vector control and environmental concerns.

Effective public health measures must balance potentially conflicting demands from populations they serve. In the case of infectious disease risks from mosquito-borne infections, such as Zika virus, public concern about the pathogen may be counterbalanced by public concern about environmental contamination from chemical agents used for vector control. Here we introduce a generic framework for modeling how the spread of an infectious pathogen might lead to varying public perceptions, and therefore tolerance, of both disease risk and pesticide use. We consider how these dynamics might impact the spread of a vector-borne disease. We tailor and parameterize our model for direct application to Zika virus as spread by Aedes aegypti mosquitoes, though the framework itself has broad applicability to any arboviral infection. We demonstrate how public risk perception of both disease and pesticides may drastically impact the spread of a mosquito-borne disease in a susceptible population. We conclude that models hoping to inform public health decision making about how best to mitigate arboviral disease risks should explicitly consider the potential public demand for, or rejection of, chemical control of mosquito populations.

The egg hatch test: A useful tool for albendazole resistance diagnosis in Fasciola hepatica.

In the current study, the egg hatch test (EHT) has been evaluated as an in vitro technique to detect albendazole (ABZ) resistance in Fasciola hepatica. The intra- and inter-assay variations of the EHT were measured by means of the coefficient of variation in different fluke isolates and over time; then, the results of the EHT were compared with the "gold standard" controlled efficacy test, which assesses the in vivo anthelmintic efficacy. The EHT was used later to evaluate the intra-herd variability regarding the level of ABZ resistance in calves infected by the same fluke isolate. Finally, several factors of the initial protocol were modified to improve the simplicity of the assay, including the incubation time of eggs with the drug and the use of eggs collected from faeces. The greatest uniformity between results within the assay and over time until 8 weeks after gallbladder collection (the deadline proposed for egg analysis) was obtained with an ABZ concentration of 0.5 µM. The length of exposure to ABZ was shown to be critical, as prolonged incubation (15 days) led to a change of ovicidal activity. The ABZ concentration of 0.5 µM is suggested as a possible discriminating dose to predict ABZ resistance, due to the close agreement between the results of the EHT at an ABZ concentration of 0.5 µM and those of the in vivo assays.