In aerobiology, dose-response studies are used to estimate the risk of infection to a susceptible host presented by exposure to a specific dose of an airborne pathogen. In the research setting, host- and pathogen-specific factors that affect the dose-response continuum can be accounted for by experimental design, but the requirement to precisely determine the dose of infectious pathogen to which the host was exposed is often challenging. By definition, quantification of viable airborne pathogens is based on the culture of micro-organisms, but some airborne pathogens are transmissible at concentrations below the threshold of quantification by culture. In this paper we present an approach to the calculation of exposure dose at microbiologically unquantifiable levels using an application of the “continuous-stirred tank reactor (CSTR) model” and the validation of this approach using rhodamine B dye as a surrogate for aerosolized microbial pathogens in a dynamic aerosol toroid (DAT).

Objective—To determine the effects of advanced age on whole-body protein synthesis and activation of the mechanistic target of rapamycin (mTOR) signaling pathway in skeletal muscle of horses Animals—Six 22- to 26-year-old (aged) and six 7- to 14-year-old (mature) horses. Procedures—Whole-body protein synthesis was measured with a 2-hour primed constant infusion of 13C sodium bicarbonate, followed by a 4-hour primed constant infusion of 1-13C phenylalanine. After the infusions, a biopsy specimen was obtained from a gluteus medius muscle and activation of protein kinase B (Akt), p70 riboprotein S6 kinase (S6K1), riboprotein S6 (rpS6), and eukaryotic initiation factor 4E binding protein 1 (4EBP1) was determined with western immunoblot analysis. For all horses, inflammatory cytokine expression in muscle and blood samples was measured with quantitative real-time PCR analysis. Results—Advanced age had no effect on whole-body protein synthesis or the phosphorylation of Akt, rpS6, and 4EBP1; however, muscle specimens of aged horses had 42% lower phosphorylation of S6K1 than did those of mature horses. Aged and mature horses had similar inflammatory cytokine expression in muscle and blood samples. Conclusions and Clinical Relevance—The lower S6K1 activation for aged horses, compared with that for mature horses, could be indicative of low rates of muscle protein synthesis in aged horses. However, advanced age had no effect on any other indicators of whole-body or muscle protein synthesis or on measures of systemic or muscle inflammation, which suggested that protein metabolism and subsequently requirements may not differ between healthy mature and aged horses.

Bovine viral diarrhea virus (BVDV) is a widespread bovine pathogen capable of causing disease affecting multiple body systems. Previous studies have shown 2-(2-benzimidazolyl)-5-[4-(2-imidazolino)phenyl]furan dihydrochloride (DB772) effectively prevents BVDV infection in cell culture. The aim of this project was to assess the efficacy of DB772 for the prevention of acute BVDV infection. Four calves seronegative to BVDV were treated with DB772 and another 4 calves were treated with diluent only on the same dosing schedule. Each calf was subsequently challenged intranasally with BVDV. Virus was isolated consistently from untreated calves on days 4 to 8, while treated calves remained negative by virus isolation during this period. Azotemia was exhibited by all treated calves on day 4 resulting in the euthanasia of 1 calf on day 10 and the death of another on day 13. Virus was isolated from the 2 remaining treated calves on day 14 or 21. On day 21, both remaining treated calves and all 4 untreated calves had anti-BVDV antibody titers > 1:2048. This pilot study indicates that DB772 temporarily prevented acute disease due to BVDV, but carries a significant concern of renal toxicity.

Objective-To compare leakage and maximum intraluminal pressures of intestinal anastomoses with and without serosal patch supplementation in dogs. Sample-Healthy small intestine segments from cadavers of 2 dogs euthanized for reasons unrelated to the study. Procedures-12 enterectomy constructs were created by anastomosis of intestinal segments with a standard simple continuous suture pattern. Half of the constructs were randomly selected for additional serosal patch support. Leakage and maximum intraluminal pressures were measured in and compared between patch-supplemented and nonsupplemented constructs. Results-Mean +/- SD leakage pressure was significantly greater for the patch-supplemented anastomoses (81.8 +/- 6.7 mm Hg) than for the nonsupplemented anastomoses (28.0 +/- 6.7 mm Hg). Maximum intraluminal pressures were not significantly different between the groups. Conclusions and Clinical Relevance-Serosal patch–supplemented anastomoses were able to sustain a significantly higher pressure before leakage than were nonsupplemented anastomoses in intestinal specimens from canine cadavers. The serosal patch supplementation may protect against leakage immediately after enterectomy in dogs.

Objective—To assess biometric tools for gait analysis in healthy calves by use of pressure mat sensors, a handheld algometer, and serial circumferential measurements of selected joints. Animals—20 six- to eight-week-old healthy male Holstein calves. Procedures—Calves were evaluated over a 4-day period. Gait analysis was performed by training calves to walk over a pressure-sensitive mat, which recorded quantitative measurements. An algometer was applied perpendicular to each joint until an aversion response was observed or a preset limit of 50 N/cm2 was obtained. Circumference measurements of the carpal and tarsal joints were obtained by the application of a flexible measuring tape to defined areas of each limb. Variability between joint circumference measurements and pressure mat variables were analyzed with a standard least squares means model. Algometer measurements were dichotomized, and logistic regression was used to assess the probability that a calf reacted to algometer-applied pressure. Results—1 calf was removed from the study because of lameness. Mean carpal and tarsal joint circumference measurements were reliable and consistent among calves. Algometry results suggested that healthy calves were more sensitive to pressure applied to the elbow and stifle joints, compared with pressure applied to the carpal, tarsal, and metacarpophalangeal or metatarsophalangeal joints. Pressure mat variables of stance time and stride velocity varied greatly among calves, whereas impulse and maximum forces varied little. Conclusions and Clinical Relevance—Findings can serve as reference points for other studies and be used for comparison with results for calves with lameness or altered gaits.

Objective: To determine pharmacokinetic and pharmacodynamic properties of midazolam after IV and IM administration in alpacas. Animals: 6 healthy alpacas. Procedures: Midazolam (0.5 mg/kg) was administered IV or IM in a randomized crossover design. Twelve hours prior to administration, catheters were placed in 1 (IM trial) or both (IV trial) jugular veins for drug administration and blood sample collection for determination of serum midazolam concentrations. Blood samples were obtained at intervals up to 24 hours after IM and IV administration. Midazolam concentrations were determined by use of tandem liquid chromatography–mass spectrometry. Results: Maximum concentrations after IV administration (median, 1,394 ng/mL [range, 1,150 to 1,503 ng/mL]) and IM administration (411 ng/mL [217 to 675 ng/mL]) were measured at 3 minutes and at 5 to 30 minutes, respectively. Distribution half-life was 18.7 minutes (13 to 47 minutes) after IV administration and 41 minutes (30 to 80 minutes) after IM administration. Elimination half-life was 98 minutes (67 to 373 minutes) and 234 minutes (103 to 320 minutes) after IV and IM administration, respectively. Total clearance after IV administration was 11.3 mL/min/kg (6.7 to 13.9 mL/min/kg), and steady-state volume of distribution was 525 mL/kg (446 to 798 mL/kg). Bioavailability of midazolam after IM administration was 92%. Peak onset of sedation occurred at 0.4 minutes (IV) and 15 minutes (IM). Sedation was significantly greater after IV administration. Conclusions and Clinical Relevance: Midazolam was well absorbed after IM administration, had a short duration of action, and induced moderate levels of sedation in alpacas.

Objective: To compare the effect of extracorporeal shock wave therapy (ESWT) on expression of fibroblast growth factor-7 (FGF-7), transforming growth factor-β1 (TGF-β1), insulin-like growth factor-1 (IGF-1), platelet-derived growth factor-A (PDGF), and vascular endothelial growth factor-A (VEGF) in skin with surgically created skin wounds and intact skin in horses. Animals: 14 healthy horses. Procedure: 8 horses were treated with ESWT at 6 locations along the neck at 36, 24, 12, 6, 2, or 1 hour prior to collection of full-thickness biopsy specimens from each location; a control specimen was collected from a sham-treated location. In 6 horses, 5 full-thickness wounds were created in each forelimb. Wounds in 1 forelimb/horse received ESWT immediately after creation and subsequently on days 7, 14, and 21; wounds in the contralateral forelimb remained untreated. Biopsy specimens were collected from 1 wound on each forelimb on days 7, 14, 21, 28, and 35. Expression levels of FGF-7, TGF-β1, IGF-1, PDGF, and VEGF were assessed in tissue samples from the horses' necks and forelimbs. Results: In surgically created wounds, ESWT treatment was associated with reduced TGF-β1 expression, compared with expression in control wounds, during the entire study period. At 28 days following wound creation, IGF-1 expression was significantly increased for treated and untreated wounds, compared with findings on days 7, 14, 21, and 35. There was no significant effect of treatment on FGF-7, TGF-β1, IGF-1, PDGF, or VEGF expression in intact skin. Conclusions and Clinical Relevance: Intervention with ESWT to suppress TGF-β1 may decrease granulation tissue production, resulting in improved wound healing on the distal portion of horses' limbs.

Objective: To compare immune responses following modified-live virus (MLV) vaccination at weaning after intranasal or SC administration of an MLV vaccine to beef calves at 2 or 70 days of age. Animals: 184 calves. Procedures: Calves were allocated to 1 of 5 groups. The IN2 (n = 37) and IN70 (37) groups received an MLV vaccine containing bovine herpesvirus 1 (BHV1), bovine viral diarrhea virus (BVDV) types 1 and 2, bovine respiratory syncytial virus (BRSV), and parainfluenza 3 virus intranasally and a Mannheimia haemolytica and Pasteurella multocida bacterin SC at median ages of 2 and 70 days, respectively. The SC2 (n = 36) and SC70 (37) groups received a 7-way MLV vaccine containing BHV1, BVDV1, BVDV2, BRSV, parainfluenza 3 virus, M haemolytica, and P multocida SC at median ages of 2 and 70 days, respectively; the control group (37) remained unvaccinated until weaning. All calves received the 7-way MLV vaccine SC at median ages of 217 (weaning) and 231 days. Serum neutralizing antibody (SNA) titers against BHV1, BVDV1, and BRSV and intranasal IgA concentrations were determined at median ages of 2, 70, 140, 217, and 262 days. Cell-mediated immunity (CMI) against BHV1, BRSV, BVDV1, and P multocida was determined for 16 calves/group. Results: At median ages of 140 and 217 days, BVDV1 SNA titers were significantly higher for the SC70 group than those for the other groups. Intranasal IgA concentrations and CMI increased over time for all groups. Vaccination at weaning increased SNA titers and CMI in all groups. Conclusions and Clinical Relevance: SC administration of an MLV vaccine to 70-day-old calves significantly increased BVDV1 antibody titers before weaning.

Objective: To compare navicular bone marrow lesion (BML) conspicuity in the feet of horses as determined via 2 fat-suppressed MRI techniques, including standard short tau inversion recovery (STIR) and inversion recovery gradient echo (IRGE). Sample: Feet (n = 150) of horses with lameness referable to the distal portion of the digit. Procedures: STIR and IRGE sequences were obtained prospectively in all feet with a standing low-field equine MRI system. Presence of a BML was ascertained by identification of a characteristic combination of marrow alterations in T1-weighted, T2*-weighted, T2-weighted, and STIR images. Signal-to-noise and contrast-to-noise ratios were calculated on STIR and IRGE sequences in 56 feet with a navicular BML. Results: Signal-to-noise and contrast-to-noise ratios of both sequences correlated linearly (r = 0.87 and r = 0.92, respectively) but were significantly higher for STIR images (mean ± SD, 22.6 ± 12.7 and 12.4 ± 11.4, respectively), compared with IRGE images (13.7 ± 8.0 and 5.9 ± 7.2, respectively). Conclusions and Clinical Relevance: Results suggested that the IRGE sequence revealed BMLs significantly less conspicuously, compared with the standard STIR sequence. The 2 techniques cannot be used interchangeably, and IRGE is therefore not recommended as the sole fat-suppressed sequence for routine equine standing MRI protocols.

Objective: To determine the effects of 2 conjugated linoleic acid (CLA) isomers (cis-9, trans-11 and trans-10, cis-12) on synthesis of prostaglandin (PG) E2 and F2α and expression of prostaglandin H synthase-2 (PGHS-2) of adult and fetal bovine endometrial epithelial cells in vitro. Sample: Primary cultures of endometrial epithelial cells obtained from 4 adult cows and 4 fetal bovine carcasses. Procedures: Cells were exposed to 0, 50, 100, or 200μM cis-9, trans-11 or trans-10, cis-12 CLA isomers for 24 hours. Culture media collected before and after 6 hours of stimulation of cells with phorbol 12-myristate 13-acetate were assayed to detect PGE2 and PGF2α via ELISA. After stimulation, cells were collected for western blot analysis to quantify PGHS-2. Results: Concentrations of PGF2α and PGE2 were significantly lower in culture media of adult and fetal endometrial epithelial cells exposed to any concentration of either CLA than they were in media of cells not exposed to CLAs. The trans-10, cis-12 CLA isomer seemed to decrease PG production more markedly than did the cis-9, trans-11 CLA isomer. Most concentrations of both CLAs significantly reduced culture media PGE2:PGF2α concentration ratios of cells. Exposure of cells to CLAs did not affect expression of PGHS-2 protein. Conclusions and Clinical Relevance: Results of this study indicated CLAs significantly decreased PGF2α and PGE2 concentrations and PGE2:PGF2α concentration ratios for cultures of adult and fetal endometrial epithelial cells with no apparent effect on PGHS-2 expression. Similar effects in cows could have effects on maternal recognition of pregnancy and immune function.