Association between quantitative bacterial culture of bronchoalveolar lavage fluid and antibiotic requirement in dogs with lower respiratory tract signs

BackgroundHistorically, positive bacterial cultures from the lower respiratory tract (LRT) have been considered clinically relevant when quantitative bacterial cultures of bronchoalveolar lavage fluid (BALF) were >1700 colony forming units (cfu)/mL. However, this threshold might not accurately predict a requirement for antibiotics.ObjectivesTo study whether quantitative BALF bacterial culture results were predictive of antibiotic requirement in dogs with LRT signs.AnimalsThirty‐three client‐owned dogs.MethodsCross‐sectional study. Dogs with positive quantitative bacterial culture of BALF were included. Dogs were divided into 2 groups, depending on whether they had a LRT infection requiring antibiotics (LRTI‐RA) or LRT disease not requiring antibiotics (LRTD‐NRA), based on thoracic imaging features, presence of intracellular bacteria on BALF cytology, and response to treatment. Predictive effect of cfu/mL and BALF total nucleated cell count (TNCC) on antibiotic requirement, adjusting for ongoing or prior antibiotic therapy and age, were studied using logistic regression.ResultsTwenty‐two and 11 dogs were included in the LRTI‐RA and LRTD‐NRA groups, respectively. The cfu/mL was not significantly predictive of antibiotic requirement, independent of ongoing or prior antibiotic treatment and age (LRTI‐RA: median, 10 000 cfu/mL; range, 10‐3 × 10⁸; LRTD‐NRA: median, 10  000 cfu/mL; range, 250‐1.3 × 10⁹; P = .27). The TNCC was not significantly predictive of antibiotic requirement when only dogs with bronchial disease were considered (LRTI‐RA: median, 470 cells/μL; range, 240‐2260; LRTD‐NRA: median, 455 cells/μL; range, 80‐4990; P = .57).Conclusion and Clinical ImportanceThe cfu/mL is an inappropriate measure for determining whether antibiotics are of benefit in dogs with LRT signs.     

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.     

Drilling to gabbro in intact ocean crust

Sampling an intact sequence of oceanic crust through lavas, dikes, and gabbros is necessary to advance the understanding of the formation and evolution of crust formed at mid-ocean ridges, but it has been an elusive goal of scientific ocean drilling for decades. Recent drilling in the eastern Pacific Ocean in Hole 1256D reached gabbro within seismic layer 2, 1157 meters into crust formed at a superfast spreading rate. The gabbros are the crystallized melt lenses that formed beneath a mid-ocean ridge. The depth at which gabbro was reached confirms predictions extrapolated from seismic experiments at modern mid-ocean ridges: Melt lenses occur at shallower depths at faster spreading rates. The gabbros intrude metamorphosed sheeted dikes and have compositions similar to the overlying lavas, precluding formation of the cumulate lower oceanic crust from melt lenses so far penetrated by Hole 1256D.     

Biscrolling nanotube sheets and functional guests into yarns

Multifunctional applications of textiles have been limited by the inability to spin important materials into yarns. Generically applicable methods are demonstrated for producing weavable yarns comprising up to 95 weight percent of otherwise unspinnable particulate or nanofiber powders that remain highly functional. Scrolled 50-nanometer-thick carbon nanotube sheets confine these powders in the galleries of irregular scroll sacks whose observed complex structures are related to twist-dependent extension of Archimedean spirals, Fermat spirals, or spiral pairs into scrolls. The strength and electronic connectivity of a small weight fraction of scrolled carbon nanotube sheet enables yarn weaving, sewing, knotting, braiding, and charge collection. This technology is used to make yarns of superconductors, lithium-ion battery materials, graphene ribbons, catalytic nanofibers for fuel cells, and titanium dioxide for photocatalysis.     

Survival and growth of upland oak and co-occurring competitor seedlings following single and repeated prescribed fires

Studies within and outside the U.S. indicate recurring oak (Quercus spp.) regeneration problems. In deciduous forests of the eastern U.S., a prevailing explanation for this trend is fire suppression leading to high competitor abundance and low understory light. In response, prescribed fire is increasingly used as a management tool to remedy these conditions and encourage future oak establishment and growth. Within eastern Kentucky, we implemented single and repeated (3×) prescribed fires over a 6-yr period (2002–2007). Pre- and post-burn, we quantified canopy cover and oak seedling survival and growth compared to other woody seedlings deemed potential competitors, primarily red maple (Acer rubrum L.) and sassafras (Sassafras albidum (Nutt.) Nees.). Burning temporarily decreased canopy cover 3–10%, but cover rebounded the subsequent growing season. Repeated burning ultimately produced canopy cover about 6% lower than sites unburned and burned once, suggesting a cumulative effect on understory light. Red maple exhibited low survival (∼40%) following single and repeated burns, but growth remained similar to unburned seedlings. Burning had little impact on sassafras survival and led to total height and basal diameters 2× greater than unburned seedlings. A single burn had no impact on red oak (Erythrobalanus spp.) survival and increased height and basal diameters 25–30%, but this positive growth response was driven by seedlings on several plots which experienced high burn temperatures and consequently high overstory mortality. White oaks (Leucobalanus spp.), however, exhibited twice as high mortality compared to those unburned, with no change in growth parameters. Repeated burning negatively impacted survival and growth of both oak groups compared to unburned seedlings. With both burn regimes, oaks with smaller pre-burn basal diameters exhibited the lowest post-burn survival. Thus, despite the ability of prescribed burns to temporarily increase understory light and reduce red maple survival, neither single or repeated burns placed oaks in an improved competitive position. These findings result from a combination of highly variable yet interdependent factors including the (1) life history traits of oaks compared to their co-occurring competitors, (2) pre-burn stature of pre-existing oak seedlings, and (3) variability in fire temperature and effects on understory light.     

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.     

Effects on plasma endotoxin and eicosanoid concentrations and serum cytokine activities in horses competing in a 48-, 83-, or 159-km endurance ride under similar terrain and weather conditions

OBJECTIVE: To determine plasma endotoxin concentration in horses competing in a 48-, 83-, or 159-km endurance race and its importance with regard to physical, hematologic, or serum and plasma biochemical variables. ANIMAL: 3 horses. PROCEDURE: Weight and rectal temperature measurements and blood samples were obtained before, during, and after exercise. Blood samples were analyzed for plasma endotoxin concentration; serum antiendotoxin antibody titers; thromboxane B2 (TxB2) and 6-keto-prostaglandin F1alpha (PGF1alpha) concentrations; tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6) activities; WBC, plasma protein, lactate, serum electrolyte, and calcium concentrations; PCV; and creatine kinase activity. RESULTS: Detection of plasma endotoxin increased during exercise for horses competing at all distances but occurred more frequently in the 48- and 83-km groups. Plasma lactate concentration was significantly greater when endotoxin was concurrently detected. Endotoxin in plasma was not significantly associated with success of race completion. Plasma TxB2 and PGF1alpha concentrations and serum IL-6 activity significantly increased with exercise. Horses that had an excellent fitness level (as perceived by their owners) had greater decreases in serum antiendotoxin antibody titers during exercise than did horses perceived as less fit. In horses with better finish times, TxB2 and PGF1alpha concentrations were significantly greater and TNFalpha activity was significantly less than that of slower horses. CONCLUSIONS AND CLINICAL RELEVANCE: Endotoxemia developed during endurance racing, but was significantly correlated with increased plasma lactate concentration and not with other variables indicative of endotoxemia. Plasma TxB2 and PGF1alpha concentrations and serum TNFalpha activity may be associated with performance success.     

Relative bioavailability of organic bis-glycinate bound copper relative to inorganic copper sulfate in beef steers fed a high antagonist growing diet

To assess the relative bioavailability of bis-glycinate bound Cu, 90 Angus-cross steers (265 ± 21 kg) were blocked by body weight (BW) to pens with GrowSafe bunks and randomly assigned to dietary treatments (14 to 18 steers/treatment): 0 mg supplemental Cu/kg dry matter (DM; CON), 5 or 10 mg supplemental Cu/kg DM as Cu sulfate (CS5; CS10) or bis-glycinate bound Cu (GLY5; GLY10). Steers received a high antagonist growing diet (analyzed 4.9 mg Cu/kg DM, 0.48% S, and 5.3 mg Mo/kg DM). Steers were weighed at the beginning (days 1 and 0) and end (days 125 and 126) of the trial to determine average daily gain (ADG) and gain:feed (G:F). Blood was collected from all steers on days 0, 28, 56, 84, and 126. Liver samples were collected on days −3 or −2 and day 123 or 124. Data were analyzed using ProcMixed of SAS (experimental unit = steer; fixed effect = treatment and block). Plasma Cu was analyzed as repeated measures (repeated effect = day). Plasma and liver Cu concentrations were regressed against total Cu intake using ProcGLM to calculate relative bioavailability of GLY. Final BW and overall ADG were greatest for CS5 and CS10 and least for CON and GLY5 (P = 0.01). Overall, DMI was not affected by treatment (P = 0.14), but overall G:F tended to be greatest for CS5, CS10, and GLY5 and least for CON (P = 0.08). Total and supplemental Cu intake was greatest for steers supplemented either source at 10 mg Cu/kg DM and least for CON (P < 0.01). However, total and supplemental Cu intake was greater for CS5 than GLY5 (P < 0.01). Final liver Cu concentrations were greatest for CS10, least for CON, CS5, and CS10, and intermediate for GLY10 (P < 0.01). Final plasma Cu was greatest for steers supplemented either source at 10 mg Cu/kg DM (P < 0.01). Relative bioavailability of GLY was 82% compared to CS based on liver Cu (P < 0.01) but did not differ based on plasma Cu (P = 0.60). The lesser bioavailability of GLY relative to CS could be due to a high concentration of dietary antagonists and lower solubility of GLY (68.9% relative to CS) in pH conditions (5.2) similar to the ruminal pH of a beef animal consuming a high concentrate diet. Future studies should examine the effects of bis-glycinate bound Cu fed in blended combination with inorganic Cu sulfate to determine the most effective blend of sources for feedlot cattle experiencing varying amounts of dietary Cu antagonists.