Modified Mouse Model of Clostridioides difficile Infection as a Platform for Probiotic Efficacy Studies.

Probiotics may represent a promising approach for reducing Clostridioides (Clostridium) difficile infections (CDIs). A clinical trial conducted by our group demonstrated that CDI patients undergoing adjunctive treatment with Lactobacillus and Bifidobacterium probiotics had a reduction in diarrheal duration and compositional changes in their stool microbiomes. Here, we modified a CDI mouse model to represent clinical outcomes observed in patients and employed this model to identify evidence for the prevention of primary CDI and relapse with the same probiotic. Mice (n = 80) were administered 0.25 mg/ml cefoperazone over 5 days and subsequently challenged with 102C. difficile VPI 10463 spores. A subset of mice (n = 40) were administered 108 CFU of probiotics daily alongside cefoperazone pretreatment and until experimental endpoints were reached. Clinical scoring was performed daily on mice and used to evaluate CDI onset and severity. Moderate CDI in mice was defined by survival beyond day 3 postinfection, while mice with severe CDI were those who succumbed to infection prior to day 3 postinfection. Sequencing and analysis of 16S rRNA from stool content were performed to determine compositional alterations to the microbiota. Using total clinical scores, we identified an association between probiotic treatment and delayed onset of primary CDI and relapse by approximately 12 to 24 h (P < 0.001). The stool microbiome of mice with moderate CDI receiving probiotic treatment was significantly enriched with Lachnospiraceae during primary CDI (P < 0.05). The outcomes observed present an opportunity to use this modified CDI mouse model to examine the efficacy of nonantibiotic options for CDI management.

Technical note: Validation of an ear-tag accelerometer to identify feeding and activity behaviors of tiestall-housed dairy cattle.

The objective of this study was to validate the CowManager SensOor ear-tag accelerometer (Agis Automatisering BV, Harmelen, the Netherlands) against visual observations of feeding, rumination, resting, and active behaviors of tiestall-housed dairy cows. Prior validation of the sensor has been published for freestall and grazing dairy herds. However, the behavioral differences that exist among these and a tiestall system necessitate additional validation. Lactating Holstein cows (n = 10) at different lactation stages and parities were included in the study. Cows were monitored both visually and with the sensor for 10 h/d for 4 consecutive days (10 cows × 10 h × 4 d = 400 h of observation total). A single trained observer classified each minute of visual observation into 1 of 13 behaviors and then summarized them into the 4 behavioral categories of eating, rumination, not active, or active. The sensor registered ear movements continuously and, based on a proprietary model, converted them into the behavioral categories. Multivariate mixed models were run to obtain covariance estimates, from which correlation coefficients were computed to assess agreement between visual observation and sensor data. The models included the percentage of time spent performing each behavior per day as the dependent variable and technology (visual observation versus sensor) and day as fixed effects. The models also included the random effects of technology and the repeated effects of technology and day. The correlation strength between visual observation and sensor data varied from poor to almost perfect by behavioral category (eating: r = 0.27; rumination: r = 0.69; eating-rumination: r = 0.83; not active: r = 0.95; and active: r = 0.89). The results suggest that the sensor can be used to accurately monitor active and not-active behaviors of tiestall-housed dairy cows. The results also suggest that although the sensor shows promise for identifying feeding behaviors in general, the independent classification of rumination and eating requires additional sensitivity.

Oral probiotic combination of Lactobacillus and Bifidobacterium alters the gastrointestinal microbiota during antibiotic treatment for Clostridium difficile infection.

Perturbations in the gastrointestinal microbiome caused by antibiotics are a major risk factor for Clostridium difficile infection (CDI). Probiotics are often recommended to mitigate CDI symptoms; however, there exists only limited evidence showing probiotic efficacy for CDI. Here, we examined changes to the GI microbiota in a study population where probiotic treatment was associated with significantly reduced duration of CDI diarrhea. Subjects being treated with standard of care antibiotics for a primary episode of CDI were randomized to probiotic treatment or placebo for 4 weeks. Probiotic treatment consisted of a daily multi-strain capsule (Lactobacillus acidophilus NCFM, ATCC 700396; Lactobacillus paracasei Lpc-37, ATCC SD5275; Bifidobacterium lactis Bi-07, ATCC SC5220; Bifidobacterium lactis B1-04, ATCC SD5219) containing 1.7 x 1010 CFUs. Stool was collected and analyzed using 16S rRNA sequencing. Microbiome analysis revealed apparent taxonomic differences between treatments and timepoints. Subjects administered probiotics had reduced Verrucomicrobiaceae at week 8 compared to controls. Bacteroides were significantly reduced between weeks 0 to 4 in probiotic treated subjects. Ruminococcus (family Lachnospiraceae), tended to be more abundant at week 8 than week 4 within the placebo group and at week 8 than week 0 within the probiotic group. Similar to these results, previous studies have associated these taxa with probiotic use and with mitigation of CDI symptoms. Compositional prediction of microbial community function revealed that subjects in the placebo group had microbiomes enriched with the iron complex transport system, while probiotic treated subjects had microbiomes enriched with the antibiotic transport system. Results indicate that probiotic use may impact the microbiome function in the face of a CDI; yet, more sensitive methods with higher resolution are warranted to better elucidate the roles associated with these changes. Continuing studies are needed to better understand probiotic effects on microbiome structure and function and the resulting impacts on CDI.

Effects of alternative deep bedding options on dairy cow preference, lying behavior, cleanliness, and teat end contamination.

Cows spend more time lying down when stalls are soft and dry, and bedding plays a key role in the comfort of the lying surface. The first objective of this study (experiment 1) was to compare cow preference for 2 types of alternative deep-bedding materials, switchgrass and switchgrass-lime, using wheat straw on a rubber mat as a control. Nine Holstein lactating cows were submitted in trios to a 3-choice preference test over 14 d (2 d of adaptation, 3 d of restriction to each stall, and 3 d of free access to all 3 stalls). Cows were housed individually in pens containing 3 stalls with different lying surfaces: (1) rubber mat with chopped wheat straw (WS); (2) deep-bedded switchgrass (SG); and (3) deep-bedded switchgrass, water, and lime mixture (SGL). The second objective (experiment 2) was to test, in freestall housing, the effects of these 3 types of bedding on lying behavior, cow cleanliness, and teat end bacterial contamination. Bedding treatments were compared in a 3 × 3 Latin square design using 24 cows split into groups of 8, with bedding materials being switched every 4 wk. Lying behavior was measured with data loggers in both studies. During experiment 1, cows chose to spend more time lying and had more frequent lying bouts on SG (9.4 h/d; 8.2 bouts/d) than on SGL (1.0 h/d; 0.9 bouts/d). They also spent more time standing and stood more frequently in stalls with SG (2.0 h/d; 10.1 bouts/d) than in those with SGL (0.6 h/d; 2.6 bouts/d), and stood longer in stalls with SG than with WS (0.6 h/d). In experiment 2, the total lying time, frequency of lying bouts, and mean lying bout duration were, on average, 9.7 ± 1.03 h/d, 8.2 ± 0.93 bouts/d, and 1.2 ± 0.06 h/bout, respectively, and did not differ between treatments. No treatment effects were found for cow cleanliness scores. Bedding dry matter was highest for SG (74.1%), lowest for SGL (63.5%), and intermediate for WS (68.6%) [standard error of the mean (SEM) = 1.57%]. This may explain the higher teat end count of coliforms for cows on SGL (0.92 log10 cfu/g) compared with WS (0.13 log10 cfu/g) (SEM = 0.144 log10 cfu/g). In conclusion, cows preferred the deep-bedded switchgrass surface over the other 2 surfaces, and deep-bedded switchgrass appears to be a suitable bedding alternative for dairy cows.

Experimental assessment of gold nanoparticle-mediated dose enhancement in radiation therapy beams using electron spin resonance dosimetry.

In this work, we aim to experimentally assess increments of dose due to nanoparticle-radiation interactions via electron spin resonance (ESR) dosimetry performed with a biological-equivalent sensitive material.We employed 2-Methyl-Alanine (2MA) in powder form to compose the radiation sensitive medium embedding gold nanoparticles (AuNPs) 5 nm in diameter. Dosimeters manufactured with 0.1% w/w of AuNPs or no nanoparticles were irradiated with clinically utilized 250 kVp orthovoltage or 6 MV linac x-rays in dosimetric conditions. Amplitude peak-to-peak (App) at the central ESR spectral line was used for dosimetry. Dose-response curves were obtained for samples with or without nanoparticles and each energy beam. Dose increments due to nanoparticles were analyzed in terms of absolute dose enhancements (DEs), calculated as App ratios for each dose/beam condition, or relative dose enhancement factors (DEFs) calculated as the slopes of the dose-response curves.Dose enhancements were observed to present an amplified behavior for small doses (between 0.1-0.5 Gy), with this effect being more prominent with the kV beam. For doses between 0.5-5 Gy, dose-independent trends were observed for both beams, stable around (2.1 ± 0.7) and (1.3 ± 0.4) for kV and MV beams, respectively. We found DEFs of (1.62 ± 0.04) or (1.27 ± 0.03) for the same beams. Additionally, we measured no interference between AuNPs and the ESR apparatus, including the excitation microwaves, the magnetic fields and the paramagnetic radicals.2MA was demonstrated to be a feasible paramagnetic radiation-sensitive material for dosimetry in the presence of AuNPs, and ESR dosimetry a powerful experimental method for further verifications of increments in nanoparticle-mediated doses of biological interest. Ultimately, gold nanoparticles can cause significant and detectable dose enhancements in biological-like samples irradiated at both kilo or megavoltage beams.

Optimistic update bias increases in older age.

BACKGROUND: Healthy older adults report greater well-being and life satisfaction than their younger counterparts. One potential explanation for this is enhanced optimism. We tested the influence of age on optimistic and pessimistic beliefs about the future and the associated structural neural correlates. METHOD: Eighteen young and 18 healthy older adults performed a belief updating paradigm, measuring differences in updating beliefs for desirable and undesirable information about future negative events. These measures were related to regional brain volume, focusing on the anterior cingulate cortex (ACC) because this region is strongly linked to a positivity bias in older age. RESULTS: We demonstrate an age-related reduction in updating beliefs when older adults are faced with undesirable, but not desirable, information about negative events. This greater 'update bias' in older age persisted even after controlling for a variety of variables including subjective rating scales and poorer overall memory. A structural brain correlate of this greater 'update bias' was evident in greater grey matter volume in the dorsal ACC in older but not in young adults. CONCLUSIONS: We show a greater update bias in healthy older age. The link between this bias and relative volume of the ACC suggests a shared mechanism with an age-related positivity bias. Older adults frequently have to make important decisions relating to personal, health and financial issues. Our findings have wider behavioural implications in these contexts because an enhanced optimistic update bias may skew such real-world decision making.

Ureteroscopy with laser lithotripsy for urolithiasis in the spinal cord injury population.

STUDY DESIGN: Retrospective study. OBJECTIVES: The purpose of this investigation was to review the outcomes and safety of retrograde ureteroscopic laser lithotripsy (URS) for the treatment of urolithiasis in the spinal cord injury (SCI) population. SETTING: Virginia, USA. METHODS: All patients with SCI who underwent URS with holmium:YAG laser lithotripsy for urolithiasis over a 15-year period were identified. Stone size, location and number at presentation were recorded. Information regarding patient characteristics, intra-operative complications, surgical efficacy, stone clearance, peri-operative complications, and follow-up stone events was collected and analyzed. RESULTS: A total of 67 URS procedures were performed on 29 SCI patients during the study period with an average follow-up of 3.4 years. Patients had an average of 2.3 ipsilateral ureteroscopies. The majority (85.1%) used indwelling catheters for long-term bladder management, and complete stone clearance after the first procedure was 34.3%. Of the 44 cases with residual stones >4 mm, 20 (45.5%) were secondary to technical or procedural limitations. The intra-operative complication rate was comparable to non-SCI studies at 1.5%, but peri-operative complications were significantly higher at 29.9% with the majority due to urosepsis. Factors associated with peri-operative complications include chronic obstructive pulmonary disease, motor incomplete injuries and lack of a pre-operative ureteral stent. CONCLUSION: URS in the SCI population is an effective treatment for ureteral or renal stones but may be associated with greater risks and reduced efficacy.

Past, present, and future of endovascular stroke therapies.

Endovascular therapy in the acute management of ischemic stroke has become more common with technologic advances, such as easier navigation into the intracranial circulation and improved treatment efficacy with the advent of revascularization devices. This select review outlines milestones in the application of endovascular therapy in acute ischemic stroke (AIS) and offers some insight into important factors influencing the future directions of endovascular AIS treatment. In particular, we discuss the evolution of endovascular devices for AIS and how ingenuity continues to offer novel treatments. With these advances, the future of endovascular AIS treatment is promising.

Ethnoveterinary application of Morinda citrifolia fruit puree on a commercial heifer rearing facility with endemic salmonellosis.

We have previously reported that Morinda citrifolia (noni) puree modulates neonatal calves developmental maturation of the innate and adaptive immune system. In this study, the effect of noni puree on respiratory and gastrointestinal (GI), health in preweaned dairy calves on a farm with endemic salmonellosis was examined. Two clinical trials were conducted whereby each trial evaluated one processing technique of noni puree. Trials 1 and 2 tested noni versions A and B, respectively. Puree analysis and trial methods were identical to each other, with the calf as the experimental unit. Calves were designated to 1 of 3 treatment groups in each trial and received either: 0, 15 or 30 mL every 12 hr of noni supplement for the first 3 weeks of life. Health scores, weaning age, weight gain from admission to weaning, and weaned by 6 weeks, were used as clinical endpoints for statistical analysis. In trial 1, calves supplemented with 15 mL noni puree of version A every 12 hr had a higher probability of being weaned by 6 weeks of age than control calves (P = 0.04). In trial 2, calves receiving 30 mL of version B every 12 hr had a 54.5% reduction in total medical treatments by 42 days of age when compared to controls (P = 0.02). There was a trend in reduced respiratory (61%), and GI (52%) medical treatments per calf when compared to controls (P = 0.06 and 0.08, respectively). There were no differences in weight gain or mortality for any treatment group in either trial.

Bone-invasive oral squamous cell carcinoma in cats: pathology and expression of parathyroid hormone-related protein.

Feline oral squamous cell carcinoma (OSCC) is the most common oral tumor in cats. There is no effective treatment, and the average duration of survival after diagnosis is only 2 months. Feline OSCC is frequently associated with osteolysis; however, the mechanisms responsible are unknown. The objective of this study was to characterize the epidemiology and pathology of bone-invasive OSCC in cats and to determine the expression of select bone resorption agonists. In sum, 451 cases of feline OSCC were evaluated. There was no sex or breed predisposition, although there were more intact cats in the OSCC group compared to the control group. Gingiva was the most common site, followed by the sublingual region and tongue. Cats with lingual OSCC were younger (mean, 11.9 years) compared to cats with gingival OSCC (mean, 13.6 years). In addition to osteolysis, there was periosteal new bone formation, osseous metaplasia of tumor stroma, and direct apposition of OSCC to fragments of bone, suggestive of bone-binding behavior. Eighty-two cases were selected for immunohistochemical detection of parathyroid hormone-related protein (PTHrP). Specimens with osteolysis had increased PTHrP expression and nuclear localization, compared to OSCC without osteolysis. Thirty-eight biopsies of OSCC with osteolysis were evaluated for tumor necrosis factor α expression, and only 4 biopsies had such expression in a small proportion of tumor cells. Increased tumor expression of PTHrP and increased localization of PTHrP to the nucleus were associated with osteolysis and may play an important role in bone resorption and tumor invasion in cats with OSCC.

Diagnostic cerebral angiography: the interventional neurology perspective.

BACKGROUND/OBJECTIVE: Cerebral angiography (CA) is increasingly used in clinical practice with advances in neurointerventional therapy. We present our CA experience performed by neurologists at an academic institution. METHOD: CA performed between July 2005 and March 2008 was reviewed. Major neurological outcome was defined as a new neurological deficit lasting >24 hours or worsening of pre-existing neurological deficit by 4 points on the National Institutes of Health Stroke Scale. Major non-neurological outcomes were defined as any death within 24 hours of the procedure, vascular injury requiring surgery, arteriovenous fistula, or pseudo-aneurysm formation and access site hematoma >5 cm, and/or requiring blood transfusion. RESULTS: In total 661 angiograms were performed over 30 months. CA indications were ischemic stroke in 210/661 (31.7%), hemorrhagic stroke in 321/661 (48.6%), trauma for 16/661 (2.4%), presurgical epilepsy workup 95/661 (14.3%), and other conditions 19/661 (2.9%). Mean age of the group was 49 +/- 18 years. Permanent neurological deficit occurred in .2% (1 patient) and reversible neurological deficits occurred in .2% (1/661). Major non-neurological complications occurred in .9% (6/661). All these rates were less than established guidelines. CONCLUSIONS: The safety and efficacy of CA performed by interventional neurologists is acceptable by current guidelines.

Measurement of antiplatelet inhibition during neurointerventional procedures: the effect of antithrombotic duration and loading dose.

BACKGROUND/OBJECTIVE: Symptomatic thromboembolic events are the most common complications associated with aneurysm coiling, and carotid and intracranial stenting. Our objective is to assess the effect of aspirin (ASA) and clopidogrel dose and duration on platelet inhibition using a point of care assay in neurointerventional (NI) suite. METHOD: The dose, duration, and point of care platelet function assay data for clopidogrel and aspirin therapy were prospectively collected between February 2006 and November 2007. Inadequate platelet inhibition for ASA was defined as >or=550 ASA reaction units (ARU), and for clopidogrel was defined as or=7 days, 300 mg for 24 hours, and 600 mg same day load had a mean P2Y12/ADP inhibition of 45%, 35% (P-value = .09), and 16%, respectively (P-value = .005). CONCLUSION: Premedication with clopidogrel, in contrast to aspirin, does not achieve adequate platelet inhibition in about two-third of the patients. Same day antiplatelet loading may be insufficient to achieve adequate platelet inhibition and should be avoided if clinically feasible.

Long term clinical and angiographic outcomes with the Wingspan stent for treatment of symptomatic 50-99% intracranial atherosclerosis: single center experience in 51 cases.

BACKGROUND AND AIM: Two independent post-approval registries have reported favorable periprocedural and short term outcomes with the use of the Wingspan stent for treatment of intracranial arterial stenosis. Data on long term clinical and imaging outcomes after Wingspan stent placement are limited. METHODS: All patients treated with the Wingspan stent in a single academic center from January 2006 to February 2008 were identified. Data on stenting indication, severity of stenosis, technical success, re-stenosis and clinical outcome were collected. RESULTS: 51 patients were treated with the Wingspan stent system for a symptomatic intracranial atherosclerotic stenosis of 50-99%. The technical success rate was 98%. The mean pre- and post-stent stenoses were 73 (11)% and 21 (7)%. Any stroke or death within 24 h of the procedure occurred in 1/51 (2%). The frequency of any stroke or death within 30 days or ipsilateral stroke beyond 30 days was 5/51 (10.0%) at a mean follow-up time of 14.6 months (range 8-30). The frequency of ≥ 50% re-stenosis on follow-up imaging was 7/29 (24%) at 8.6 (4.4) months (range 3-20); all were detected on the initial imaging within 3-6 months, and only one was symptomatic. CONCLUSION: The use of the Wingspan stent in patients with ≥50% symptomatic intracranial stenosis is associated with good long term clinical outcome. One stroke occurred after the first 30 days, suggesting a significant stabilization of the adverse event rate after the first month.

Effects of additional milk replacer feeding on calf health, growth, and selected blood metabolites in calves.

The objective of the experiment was to evaluate effects of increased milk replacer feeding on growth, intake, feed efficiency, and health parameters in stressed calves. Holstein bull calves (n = 120; approximately 3 to 8 d of age) were purchased from sale barns and dairy farms and housed in fiberglass hutches. In addition, wood shavings contaminated with coronavirus were mixed with clean shavings and added to each hutch before the start of the experiment. Calves were fed either a fixed amount (454 g/d) of a 20% crude protein (CP), 20% fat milk replacer to weaning at 28 d or a variable amount (454, 681, 908, and 454 g/d on d 0 to 7, 8 to 14, 15 to 31, and 32 to 41, respectively) of a milk replacer containing 28% CP and 17% fat without or with added dietary supplement containing bovine serum. Calves were also fed commercial calf starter and water ad libitum. Plasma IgG concentration in most calves on arrival at the facility was < 10 g/L. Intake, change in body weight, feed efficiency, morbidity and mortality, and selected plasma metabolites were determined. Body weight at 28 d, 56 d, daily body weight gain, intake of milk replacer, fecal scores, days with diarrhea, and days treated with antibiotics were increased with feeding variable amount of milk replacer over the 56-d study. Starter intake from d 1 to 56 was reduced from 919 to 717 g/d in calves fed fixed and variable amounts of milk replacer, respectively. Morbidity, measured as the number of days that calves had diarrhea, was increased by 53% when a variable amount of milk replacer was fed. Calves fed variable milk replacer were treated with antibiotics for 3.1 d compared with 1.9 d for calves fed 454 g of milk replacer/d. Concentrations of plasma glucose, urea N, and insulin-like growth factor-I were increased when calves were fed variable amount of milk replacer. Dietary supplement containing bovine serum had no effect on any parameter measured. There was no effect of milk replacer feeding on concentrations of nonesterified fatty acids, total protein, or growth hormone concentrations. Plasma tumor necrosis factor-alpha was highest in calves with the highest plasma IgG concentrations on the day of arrival and might be related to the calf's ability to identify pathogens in the environment. Under conditions of this study, calves fed variable amount of milk replacer and exposed to immunological challenge before weaning had greater BW gain, but also increased incidence of diarrhea that required added veterinary treatments.

Coupling of oral human or porcine insulin to the B subunit of cholera toxin (CTB) overcomes critical antigenic differences for prevention of type I diabetes.

Our earlier investigations have demonstrated a critical difference in the efficacy of orally administered porcine compared to human or mouse insulin (no effect) in preventing type I diabetes in two distinct experimental models. Based on these findings one has to assume that certain insulins might not be suitable for the induction of oral 'tolerance'/bystander suppression, which might be one cause for recent failures in human oral antigen trials. Here we demonstrate that coupling to the non-toxic subunit of cholera toxin (CTB) can abolish these differences in efficacy between human and porcine insulin. As expected, an added benefit was the much smaller oral antigen dose required to induce CD4+ insulin-B specific regulatory cells that bystander-suppress autoaggressive responses. Mechanistically we found that uptake or transport of insulin-CTB conjugates in the gut occurs at least partially via binding to GM-1, which would explain the enhanced clinical efficacy. Both B chains bound well to major histocompatibility complex (MHC) class II, indicating comparable immunological potential once uptake and processing has occurred. Thus, our findings delineate a pathway to overcome issues in oral antigen choice for prevention of type I diabetes.

The cholera toxin B subunit is a mucosal adjuvant for oral tolerance induction in type 1 diabetes.

When conjugated to various proteins, the nontoxic B-chain of cholera toxin (CTB) significantly increases the ability of these proteins to induce immunological tolerance after oral administration. Here, we investigated if a nonconjugated form of CTB enhances the induction of immune tolerance after oral insulin administration. Induction of immunological tolerance was studied after oral administration of insulin preparations in three mouse models; an insulin/ovalbumin coimmunization model, a model of virus-induced diabetes in transgenic RIP-LCMV-NP mice and in nonobese diabetic (NOD) mice serving as a model of spontaneous diabetes. In the immunization model, we demonstrate that mixing with CTB increases the tolerogenic potential of insulin, approximately 10 fold. Titration of the CTB concentration in this system revealed that an insulin : CTB ratio of 100 : 1 was optimal for the induction of bystander suppression. Further studies revealed that this insulin : CTB ratio also was optimal for the prevention of diabetes in a virus-induced, transgenic diabetes model. In addition, the administration of this optimal insulin-CTB preparation significantly prevented the onset of diabetes in old NOD mice with established islet infiltration. The data presented here demonstrate that CTB, even in its unconjugated form, functions as a mucosal adjuvant, increasing the specific tolerogenic effect of oral insulin.

Infection-triggered regulatory mechanisms override the role of STAT 4 in control of the immune response to influenza virus antigens.

Accurate control of the balance of the T1 and T2 cells during antiviral immunity is essential for optimizing immune effector functions and for avoiding potentially severe immunopathology. We examined the in vivo role of the signal transducer and activator of transcription (STAT) 4 in regulating the T1/T2 balance during the response to live influenza virus and isolated viral proteins. We found that the differentiation of gamma interferon (IFN-gamma)-producing Th1 and Tc1 cells after inoculation of live virus occurred independently of STAT 4 expression. Influenza virus-specific T2 and Tc2 responses were well controlled in such STAT 4-deficient mice unless IFN-gamma was eliminated as well. In contrast, the STAT 4-dependent signaling pathway played a more essential role in regulating the T1/T2 balance after immunization with viral proteins and, in particular, inactivated nonreplicating virus. Pulmonary infection was cleared even in the absence of both functional STAT 4 genes and functional IFN-gamma genes because virus-neutralizing antibodies were still generated, consistent with a substantial redundancy in different antiviral effector pathways. Thus, replicating agents such as live influenza virus can elicit IFN-gamma and control T2 immunity independently of STAT 4, whereas the profile of immunity to isolated proteins is more reliant on an intact STAT 4 signaling pathway.

Effects of spray-dried animal plasma in calf milk replacer on health and growth of dairy calves.

Male Holstein calves (n = 120) purchased from local dairy farms were fed one of three calf milk replacers for 42 d. Experimental milk replacers were formulated to contain whey protein concentrate (WPC) as the primary protein source or WPC plus 5% spray-dried bovine plasma (SDBP) or spray-dried porcine plasma (SDPP). The SDPP was heated to remove heat-insoluble materials and provide products with similar IgG content. Calves were also fed commercial calf starter and water for ad libitum consumption. Intake, change in body weight (BW), feed efficiency, morbidity and mortality were determined. Mortality was 10, 3, and 2 in calves fed WPC, SDBP, and SDPP treatments, respectively. Morbidity, measured as the number of days that calves had diarrhea was reduced by 30% when SDBP or SDPP were fed. Calves had diarrhea for 6.9, 3.9, and 4.7 d during the 42-d study when fed commercial calf milk replacer containing WPC, SDBP, and SDPP, respectively. Fecal scores tended to be reduced and feed efficiency tended to be improved when SDBP or SDPP were fed. Mean intakes of total dry matter during the 42-d study were greater when calves were fed SDBP or SDPP and were 661, 710, and 684 g/d for calves fed WPC, SDBP, and SDPP, respectively. Mean BW gains from d0 to 42 were 231,261, and 218 g/d, respectively. Calves fed SDPP tended to have lower BW gain during the first 28 d of the study. However, difference in daily BW gain from d 1 to 28 was only 39 g/d. Inclusion of SDBP or SDPP in milk replacer reduced morbidity and mortality of milk-fed dairy calves.

Absorption of protein and IgG in calves fed a colostrum supplement or replacer.

Newborn Holstein bull calves (n = 32) were assigned to receive a colostrum supplement (CS) containing defibrinated bovine plasma or a colostrum replacer (CR) containing an immunoglobulin concentrate obtained by concentrating the immunoglobulin (Ig)G fraction of bovine plasma. The CS and CR contained 11.1 and 21.2% of dry matter as IgG, respectively. Each animal was fed two 454-g feedings at 1 and 8 h of age. The two feedings of CS and CR provided 95 and 187 g of IgG, respectively. Mean plasma IgG at 24 h of age was 8.0 and 13.6 g/L in calves fed CS and CR, respectively, indicating acceptable absorption of Ig from both sources. Mean apparent efficiency of IgG absorption in calves fed CS and CR were 33 and 30%, respectively, and did not differ between treatments. Mean plasma total protein at 24 h in calves fed CS and CR were 4.99 and 4.98 g/dl and did not differ between treatments. Increased plasma protein concentration from 0 to 24 h (4.5 g/L) was lower than the mean increase in plasma IgG concentration during the same period (10.3 g/L), indicating altered protein profile in the blood during the first 24 h of life. Correlation between plasma IgG and total protein at 24 h of age was significant within treatment, but the relationship between IgG and protein in plasma at 24 h varied between treatments. Predicted plasma total protein concentrations at 10 g of IgG/L of plasma at 24 h were 5.4 and 4.2 g/dl, in calves fed CS and CR, respectively. Prediction of plasma IgG concentration using total plasma protein may be inappropriate when calves are fed CS or CR.