Incidence of and risks associated with Giardia infections in herds on dairy farms in the New York City Watershed

Background

The primary aims of this study were to determine the incidence of Giardia infections in dairy herds on farms in the New York City Watershed region and to evaluate risk factors associated with infections. Because co-infections of Giardia and Cryptosporidium spp. are common in this population, we also evaluated the effect of herd infection status on Giardia infections.

Methods

Farms were grouped into three cohorts based on their prior infection status with Giardia and/or Cryptosporidium spp. The sampling plan included collecting fecal samples from all calves below 30 days of age and proportional sampling of calves, young stock, and adults. A total of 10,672 fecal samples were collected and analyzed for the presence of Giardia cysts using zinc sulfate flotation. Herds enrolled in the study were sampled seasonally for a study period of two years. The probability of shedding cysts past a certain age and the factors that influenced the likelihood of shedding were evaluated using survival analysis. Linear regression was used to evaluate factors that were associated with the intensity of shedding.

Results

The majority of Giardia infections occurred in calves within their first 180 days of age, with the most number of calves shedding Giardia cysts between 11 and 20 days of age. The incidence of shedding of Giardia cysts ranged from 0.0004 per animal day for cattle in the low risk cohort to 0.0011 per animal day for cattle in the high risk cohort. The likelihood of shedding was influenced by the prior infection status of the herd and the season of collection. Infected animals shed on average 9,658 cysts/gram and the intensity of shedding Giardia cysts varied significantly with the age (p < 0.0001) and the season of collection (p = 0.0151 for Spring).

Conclusion

Giardia infections are common in dairy herds in the New York City watershed, particularly in calves less than 6 months of age. Seasonality may be an important factor in the perpetuation of infections based on changes in management practices corresponding to weather patterns of a particular season. A dairy herd''s prior infection status with Cryptosporidium influences the likelihood of infection with Giardia.     

Successful drug development despite adverse preclinical findings part 1: processes to address issues and most important findings

Unexpected adverse preclinical findings (APFs) are not infrequently encountered during drug development. Such APFs can be functional disturbances such as QT prolongation, morphological toxicity or carcinogenicity. The latter is of particular concern in conjunction with equivocal genotoxicity results. The toxicologic pathologist plays an important role in recognizing these effects, in helping to characterize them, to evaluate their risk for man, and in proposing measures to mitigate the risk particularly in early clinical trials. A careful scientific evaluation is crucial while termination of the development of a potentially useful drug must be avoided. This first part of the review discusses processes to address unexpected APFs and provides an overview over typical APFs in particular classes of drugs. If the mode of action (MoA) by which a drug candidate produces an APF is known, this supports evaluation of its relevance for humans. Tailor-made mechanistic studies, when needed, must be planned carefully to test one or several hypotheses regarding the potential MoA and to provide further data for risk evaluation. Safety considerations are based on exposure at no-observed-adverse-effect levels (NOAEL) of the most sensitive and relevant animal species and guide dose escalation in clinical trials. The availability of early markers of toxicity for monitoring of humans adds further safety to clinical studies. Risk evaluation is concluded by a weight of evidence analysis (WoE) with an array of parameters including drug use, medical need and alternatives on the market. In the second part of this review relevant examples of APFs will be discussed in more detail.     

In Vitro Biomechanical Evaluation and Comparison of FiberWire,FiberTape, OrthoFiber,and Nylon Leader Line for Potential Use During Extraarticular Stabilization Of Canine Cruciate Deficient Stifles

Objective— To compare biomechanical properties of 3 new generation polyethylene sutures (FiberTape [FT], FiberWire [FW], and OrthoFiber [OF]) with nylon leader line (NL) for use during extraarticular fixation of cranial cruciate deficient stifles. Study Design— In vitro biomechanical testing of suture loops under monotonic tensile and cyclical loading until failure. Sample Population— Constructs of FT, FW, OF, and NL. Methods— Twenty loops of each of 12 combinations of fixation and suture had monotonic tensile and cyclical loading. Two knotting techniques (square knot [SQ], slip knot [SL]) and a crimp clamp (CR) system were evaluated. Elongation, stiffness, and strength of constructs was tested. The main effects of group, loop material, and their interaction were evaluated. Results— Knotted FT, FW, and OF had less elongation than knotted NL under monotonic tensile and cyclical loading. Under monotonic tensile loading, knotted FT and OF were stiffer than knotted NL. CR FT, CR FW, and CR OF were stiffer than CR NL and CR FT, CR FW, and CR OF were stiffer than knotted FT, FW, and OF. FW and OF knotted loops were weaker than knotted NL. CR FT was stronger than CR NL. CR FT and CR OF were weaker than knotted FT and OF. Conclusions— Polyethylene sutures are stronger, stiffer and elongate less than nylon leader. Crimping suture alters the biomechanical properties of the loop. Clinical Relevance— FW, FT, and OF may perform better in reconstructive procedures, where increased strength and stiffness are considered to be beneficial.     

Comparison of chemistry analytes between 2 portable, commercially available analyzers and a conventional laboratory analyzer in reptiles

Background: Advantages of handheld and small bench‐top biochemical analyzers include requirements for smaller sample volume and practicality for use in the field or in practices, but little has been published on the performance of these instruments compared with standard reference methods in analysis of reptilian blood. Objective: The aim of this study was to compare reptilian blood biochemical values obtained using the Abaxis VetScan Classic bench‐top analyzer and a Heska i‐STAT handheld analyzer with values obtained using a Roche Hitachi 911 chemical analyzer. Methods: Reptiles, including 14 bearded dragons (Pogona vitticeps), 4 blue‐tongued skinks (Tiliqua gigas), 8 Burmese star tortoises (Geochelone platynota), 10 Indian star tortoises (Geochelone elegans), 5 red‐tailed boas (Boa constrictor), and 5 Northern pine snakes (Pituophis melanoleucus melanoleucus), were manually restrained, and a single blood sample was obtained and divided for analysis. Results for concentrations of albumin, bile acids, calcium, glucose, phosphates, potassium, sodium, total protein, and uric acid and activities of aspartate aminotransferase and creatine kinase obtained from the VetScan Classic and Hitachi 911 were compared. Results for concentrations of chloride, glucose, potassium, and sodium obtained from the i‐STAT and Hitachi 911 were compared. Results: Compared with results from the Hitachi 911, those from the VetScan Classic and i‐STAT had variable correlations, and constant or proportional bias was found for many analytes. Bile acid data could not be evaluated because results for 44 of 45 samples fell below the lower linearity limit of the VetScan Classic. Conclusions: Although the 2 portable instruments might provide measurements with clinical utility, there were significant differences compared with the reference analyzer, and development of analyzer‐specific reference intervals is recommended.     

Reprogramming cellular behavior with RNA controllers responsive to endogenous proteins

Synthetic genetic devices that interface with native cellular pathways can be used to change natural networks to implement new forms of control and behavior. The engineering of gene networks has been limited by an inability to interface with native components. We describe a class of RNA control devices that overcome these limitations by coupling increased abundance of particular proteins to targeted gene expression events through the regulation of alternative RNA splicing. We engineered RNA devices that detect signaling through the nuclear factor κB and Wnt signaling pathways in human cells and rewire these pathways to produce new behaviors, thereby linking disease markers to noninvasive sensing and reprogrammed cellular fates. Our work provides a genetic platform that can build programmable sensing-actuation devices enabling autonomous control over cellular behavior.     

ANXITANE® tablets reduce fear of human beings in a laboratory model of anxiety-related behavior

Anxiety and fear are common underlying factors in many canine behavior problems that impair the human–pet bond and often result in abandonment, relinquishment, or euthanasia. A combination of behavioral and pharmacological interventions is used to ameliorate the behavioral signs associated with anxiety-related behaviors in dogs, but there continues to be need for effective interventions. The current study examined the effects of the nutraceutical ANXITANE^® (l-Theanine) chewable tablets on fear of unfamiliar human beings. We first characterized dogs as anxious on the basis of the existence of a fear response to human beings in their home-pen. We then demonstrated that dogs characterized as anxious (N = 10) showed reduced interaction with an unknown human being as compared with normal controls (N = 7). The effect of an administration of ANXITANE^® tablets (N = 5) on these anxious Beagle dogs was compared with placebo (N = 5). Objective behavioral measures of anxiety were obtained using an open-field test, a human interaction test, and an actiwatch protocol that allowed monitoring of activity over 24-hours. The ANXITANE^® tablets-treated dogs showed greater human interaction and approach than the placebo control group, and no side effects related to treatment, including motor stimulant or sedative effects, were seen. The current study suggests that ANXITANE^® tablets are effective for reducing fearful behavior toward unfamiliar human beings in dogs and supports their use for treating anxiety-related behaviors.