Short term treatment with a cocktail of rapamycin, acarbose and phenylbutyrate delays aging phenotypes in mice.

Pharmaceutical intervention of aging requires targeting multiple pathways, thus there is rationale to test combinations of drugs targeting different but overlapping processes. In order to determine if combining drugs shown to extend lifespan and healthy aging in mice would have greater impact than any individual drug, a cocktail diet containing 14 ppm rapamycin, 1000 ppm acarbose, and 1000 ppm phenylbutyrate was fed to 20-month-old C57BL/6 and HET3 4-way cross mice of both sexes for three months. Mice treated with the cocktail showed a sex and strain-dependent phenotype consistent with healthy aging including decreased body fat, improved cognition, increased strength and endurance, and decreased age-related pathology compared to mice treated with individual drugs or control. The severity of age-related lesions in heart, lungs, liver, and kidney was consistently decreased in mice treated with the cocktail compared to mice treated with individual drugs or control, suggesting an interactive advantage of the three drugs. This study shows that a combination of three drugs, each previously shown to enhance lifespan and health span in mice, is able to delay aging phenotypes in middle-aged mice more effectively than any individual drug in the cocktail over a 3-month treatment period.

Prevalence and Molecular Characteristics of Clostridium difficile in Retail Meats, Food-Producing and Companion Animals, and Humans in Minnesota.

Community-associated Clostridium difficile infection (CA-CDI) now accounts for approximately 50% of CDI cases in central Minnesota; animals and meat products are potential sources. From November 2011 to July 2013, we cultured retail meat products and fecal samples from food-producing and companion animals in central Minnesota for C. difficile by using standard methods. The resulting 51 C. difficile isolates, plus 30 archived local veterinary C. difficile isolates and 208 human CA-CDI case isolates from central Minnesota (from 2012) from the Minnesota Department of Health, were characterized molecularly, and source groups were compared using discriminant analysis. C. difficile was recovered from 0 (0%) of 342 retail meat samples and 51 (9%) of 559 animal fecal samples. Overall, the 81 animal source isolates and 208 human source isolates were highly diverse genetically. Molecular traits segregated extensively in relation to animal versus human origin. Discriminant analysis classified 95% of isolates correctly by source group; only five (2.5%) human source isolates were classified as animal source. These data do not support meat products or food-producing and companion animals as important sources of CA-CDI in the central Minnesota study region.

A New Preclinical Paradigm for Testing Anti-Aging Therapeutics.

Testing drugs for anti-aging effects has historically been conducted in mouse life-span studies, but are costly and time consuming, and more importantly, difficult to recapitulate in humans. In addition, life-span studies in mice are not well suited to testing drug combinations that target multiple factors involved in aging. Additional paradigms for testing therapeutics aimed at slowing aging are needed. A new paradigm, designated as the Geropathology Grading Platform (GGP), is based on a standardized set of guidelines developed to detect the presence or absence of low-impact histopathological lesions and to determine the level of severity of high-impact lesions in organs from aged mice. The GGP generates a numerical score for each age-related lesion in an organ, summed for total lesions, and averaged over multiple mice to obtain a composite lesion score (CLS). Preliminary studies show that the platform generates CLSs that increase with the age of mice in an organ-dependent manner. The CLSs are sensitive enough to detect changes elicited by interventions that extend mouse life span, and thus help validate the GGP as a novel tool to measure biological aging. While currently optimized for mice, the GGP could be adapted to any preclinical animal model.

Prioritization of Managed Pork Supply Movements during a FMD Outbreak in the US.

In the event of a foot-and-mouth disease (FMD) outbreak in the United States, local, state, and federal authorities will implement a foreign animal disease emergency response plan restricting the pork supply chain movements and likely disrupting the continuity of the swine industry business. To minimize disruptions of the food supply while providing an effective response in an outbreak, it is necessary to have proactive measures in place to ensure minimal disease spread and maximum continuation of business. Therefore, it is critical to identify candidate movements for proactive risk assessments: those that are both most likely to contribute to disease spread and most necessary for business continuity. To do this, experts from production, harvest, retail, and allied pork industries assessed 30 common pork supply movements for risk of disease spread and industry criticality. The highest priority movements for conducting a risk assessment included the movement of weaned pigs originating from multiple sow farm sources to an off-site nursery or wean to finish facility, the movement of employees or commercial crews, the movement of vaccination crews, the movement of dedicated livestock hauling trucks, and the movement of commercial crews such as manure haulers and feed trucks onto, off, or between sites. These critical movements, along with several others identified in this study, will provide an initial guide for prioritization of risk management efforts and resources to be better prepared in the event of a FMD outbreak in the United States. By specifically and proactively targeting movements that experts agree are likely to spread the disease and are critical to the continuity of business operations, potentially catastrophic consequences in the event of an outbreak can be limited.

High Prevalence of Covert Infection With Gastrointestinal Helminths in Cats.

Fecal flotation is routinely used to identify feline helminth infections in clinical practice, but it is known to have limitations of sensitivity, particularly for cestodes. To determine the prevalence of helminths in a contemporary population of cats and evaluate the ability of fecal flotation to detect these infections, helminths were recovered from intestinal tracts removed from 116 adult cats humanely euthanized by an animal control shelter in northeastern Oklahoma. Results were compared to those of fecal flotation performed using both passive and centrifugal techniques. Helminths were identified in 78/116 (67.2%) cats, including Toxocara cati (48/116; 41.4%), Ancylostoma tubaeforme (8/116; 6.9%), Dipylidium caninum (40/116; 34.5%), and Taenia taeniaeformis (30/116; 25.9%). Cats with T. cati were significantly more likely to harbor T. taeniaeformis (P = .001) than cats without ascarids. Centrifugal fecal flotation with sugar solution identified 37/48 (77.1%) T. cati infections, 8/30 (26.7%) T. taeniaeformis infections, and no D. caninum infections. Proglottids were detected on external examination in 19.0% (12/63) of cats with cestodes. Cestodes were present in over half of the cats examined in this study, but the majority of these infections were not evident by the detection of external proglottids or recovery of characteristic stages on fecal flotation.

Incorporating risk communication into highly pathogenic avian influenza preparedness and response efforts.

A highly pathogenic avian influenza (HPAI) outbreak in the United States will initiate a federal emergency response effort that will consist of disease control and eradication efforts, including quarantine and movement control measures. These movement control measures will not only apply to live animals but also to animal products. However, with current egg industry "just-in-time" production practices, limited storage is available to hold eggs. As a result, stop movement orders can have significant unintended negative consequences, including severe disruptions to the food supply chain. Because stakeholders' perceptions of risk vary, waiting to initiate communication efforts until an HPAI event occurs can hinder disease control efforts, including the willingness of producers to comply with the response, and also can affect consumers' demand for the product. A public-private-academic partnership was formed to assess actual risks involved in the movement of egg industry products during an HPAI event through product specific, proactive risk assessments. The risk analysis process engaged a broad representation of stakeholders and promoted effective risk management and communication strategies before an HPAI outbreak event. This multidisciplinary team used the risk assessments in the development of the United States Department of Agriculture, Highly Pathogenic Avian Influenza Secure Egg Supply Plan, a comprehensive response plan that strives to maintain continuity of business. The collaborative approach that was used demonstrates how a proactive risk communication strategy that involves many different stakeholders can be valuable in the development of a foreign animal disease response plan and build working relationships, trust, and understanding.

Effects of PBN and OKN007 in rodent glioma models assessed by 1H MR spectroscopy.

Gliomas, the most common primary brain tumors in adults, have a poor outcome. PBN (α-phenyl-tert-butylnitrone) and OKN007 (2,4-disulfophenyl-PBN) are nitrones that have demonstrated beneficial effects in many aging diseases. In this study, we evaluated the anti-tumor effects of PBN and OKN007 in several rodent glioma models (C6, RG2, and GL261) by assessing metabolite alterations with magnetic resonance spectroscopy (MRS). PBN or OKN007 was administered in drinking water before or after tumor formation. MR imaging and single-voxel point-resolved spectroscopy were done to assess tumor morphology and metabolites, after therapy. Major metabolite ratios (choline, N-acetylaspartate, and lipid (methylene or methyl), all compared to creatine), as well as quantification of individual metabolite concentrations, were assessed. Nitrones induced tumor metabolism changes that resulted in restoring major metabolite ratios close to their normal levels, in the glioma regression phase. Nitrone treatment decreased the lipid (methylene)-to-creatine ratio, as well as the estimated concentration of lipid (methylene) significantly. Alterations in lipids can be a useful marker for the evaluation of the efficacy associated with treatment and were found in this study to be related to the reduction of necrosis, but not apoptosis. OKN007 was more effective than PBN when administered after tumor formation in the C6 glioma model. In conclusion, (1)H MRS and conventional MRI are useful methods to assess and follow the response of varied glioma models to anti-tumor treatments.

Actinobacillus equuli as a primary pathogen in breeding sows and piglets.

The death of over 300 sows in 2 months on a 3000 sow farrow-to-isowean operation in Manitoba was attributed to infection with Actinobacillus equuli. This pathogen commonly infects foals, and is rarely reported in swine. Our report is the second recently published case of this pathogen in North American swine.