Effects of feeding Saccharomyces cerevisiae fermentation products on the health and growth performance of Holstein dairy calves.

It is essential to reduce antibiotic use in the livestock industry, which leads to a need for alternatives to antibiotics that reduce illness and promote growth in dairy calves. The objective of this study was to evaluate the effect of feeding dairy calves Saccharomyces cerevisiae fermentation products (SCFP) on average daily gain (ADG) and antibiotic use in dairy calves through 4 mo of age. Holstein bull calves (n = 60; 5 ± 3 d old) were blocked by body weight (BW) and serum total protein (STP) and assigned to 1 of 2 treatments. The control treatment (CON) fed a 24% crude protein (CP):17% fat milk replacer (MR), calf starter, grower #1, and grower #2 with no SCFP added. The SCFP treatment fed the same MR with 1 g/d of SCFP, calf starter with 0.8% (dry matter; DM) SCFP, grower #1 with 0.44% (DM) SCFP, and grower #2 with 0.275% (DM) SCFP. Calves were offered 2.84 L (12.5% solids) of MR twice daily (0630 and 1630 h) through d 51 and MR once daily (0630 h) from d 52 to 56, and were weaned on d 57. From d 1 to 56, calves also received ad libitum access to calf starter and water. On d 57, calves were switched to grower #1 and on d 84, calves were switched to grower #2, which contained a lower level of CP and a higher level of neutral detergent fiber (NDF). Individual calf BW, body condition score (BCS), hip height (HH), and hip width (HW) were measured biweekly from d 0 to 112. Feed intake was recorded daily, and feed efficiency (gain:feed) and ADG were calculated. Daily fecal and respiratory scores were recorded for each calf through d 56, and all medical interventions were recorded for the duration of the study and grouped based on illness. We found no effect of treatment on STP, BW, BCS, HH, or HW at d 0 or 56, nor effects on preweaning ADG and feed efficiency. No treatment effect was observed for BCS or HH at d 112; however, BW and HW were increased in SCFP calves at d 112. A treatment tendency was observed for postweaning ADG, with SCFP calves being larger than CON calves and SCFP calves having improved feed efficiency compared with CON calves after weaning. A treatment effect was observed for respiratory treatments postweaning, with SCFP calves being treated less frequently than CON calves. Our results suggest that feeding SCFP to calves improves postweaning growth and feed efficiency, and reduces postweaning respiratory disease interventions.

Research Note: Orange corn altered the cecal microbiome in laying hens.

Carotenoids, which are pigments known to have many health benefits, such as their antioxidant properties, are being researched for their potential as a feed additive for production animals. These pigments are found in varying quantities in different breeds of corn, and their impact on the chicken microbiome requires further investigation. This 35 d laying hen (Novagen White) feeding trial involved varying the levels and composition of carotenoids by changing the corn source: white (0.9 µg total carotinoids/g total diet), yellow (5.7 µg/g), and orange (24.9 µg/g). For each of the three corn diet treatments, 6 replicate cages were randomly assigned. The cecal microbial community composition of the hens was then studied by 16S rRNA gene amplicon sequencing. The composition of the cecal bacterial community, as determined by Bray-Curtis dissimilarity, was different (P < 0.05) in chickens fed the orange corn diet, compared to chickens on the white corn diet, but there was no statistical difference between animals fed yellow corn compared to the white or orange corn groups. There was no change in the alpha diversity between any of the groups. Within Lactobacillus, which is one of the most abundant genera, 2 amplicon sequence variants (ASVs) were decreased and one ASV was increased in the orange corn group compared to both the white and yellow corn groups. While previous studies showed that orange corn did not alter the community composition in broilers, it appears that orange corn based feed may alter the community composition of laying hens.

Orange corn diets associated with lower severity of footpad dermatitis in broilers.

Footpad dermatitis (FPD), damage and inflammation of the plantar surface of the foot, is of concern for poultry because FPD affects the birds' welfare and production value. Footpad dermatitis is painful and causes costly chicken paw downgrades, carcass condemnations, and reduced live weights. However, a universal preventative has not been found. The hypothesis was that diets containing orange corn, when compared with diets containing yellow or white corn, would reduce the severity of footpad dermatitis in broiler chickens on wet litter. When compared with yellow and white corn, orange corn contains higher quantities of carotenoids, antioxidant pigments, believed to play a role in skin and feather health. This experiment was a randomized block, 3 × 2 factorial design: orange, yellow, and white corn diets with birds raised on wet or dry litter (control group). Female Ross 708 broilers (n = 960) were used to create 4 replicates of each diet x litter treatment combination. Footpads were scored at day 19, 27, 35, and 42, following the Global Animal Partnership standard's 0-2 scale of visual increasing severity: 0 indicates minimal damage and 1 and 2 indicate mild to severe lesions and ulceration, dark papillae, and/or bumble foot. At 42 d of age, birds on the wet litter had greater severity of FPD, scores 1 and 2, compared with the control group (88 vs. 13% respectively; P < 0.0001). At 42 d of age, prevalence of more severe footpad scores, 1 or 2, was lowest on the orange corn diet (33%), followed by white corn (56%) and yellow corn (63%). Birds fed the orange corn diet had higher BW throughout the study (P = 0.004) and had fat pads and livers with higher yellow pigment deposition (P < 0.005). Litter moisture content altered microbiome composition but corn type did not. In conclusion, the main determinant of FPD in this study was exposure to wet litter. When compared with yellow and white corn, orange corn was associated with improved bird growth and reduced severity of footpad dermatitis, especially at later time points.

Enhanced Electron-Phonon Coupling for Charge-Density-Wave Formation in La_{1.8-x}Eu_{0.2}Sr_{x}CuO_{4+δ}.

Charge density wave (CDW) correlations are prevalent in all copper-oxide superconductors. While CDWs in conventional metals are driven by coupling between lattice vibrations and electrons, the role of the electron-phonon coupling (EPC) in cuprate CDWs is strongly debated. Using Cu L_{3} edge resonant inelastic x-ray scattering, we study the CDW and Cu-O bond-stretching phonons in the stripe-ordered cuprate La_{1.8-x}Eu_{0.2}Sr_{x}CuO_{4+δ}. We investigate the interplay between charge order and EPC as a function of doping and temperature and find that the EPC is enhanced in a narrow momentum region around the CDW ordering vector. By detuning the incident photon energy from the absorption resonance, we extract an EPC matrix element at the CDW ordering vector of M≃0.36 eV, which decreases to M≃0.30 eV at high temperature in the absence of the CDW. Our results suggest a feedback mechanism in which the CDW enhances the EPC which, in turn, further stabilizes the CDW.

Evaluation of different Campylobacter jejuni isolates to colonize the intestinal tract of commercial turkey poults and selective media for enumeration.

Consumption of contaminated poultry products is the main source of human campylobacteriosis, for which Campylobacter jejuni is responsible for 90% of human cases. Although chickens are believed to be a main source of human exposure to C. jejuni, turkeys also contribute to cases of human infection. Little is known about the kinetics of C. jejuni intestinal colonization in turkeys, or best selective media for their recovery. Enumeration of C. jejuni from intestinal samples can be challenging because most selective Campylobacter media support the growth of non-Campylobacter organisms. In this study, we sought to compare a) C. jejuni isolates that persistently colonize different compartments of the poult intestinal tract, and b) selective media to enumerate C. jejuni from turkey intestinal samples. Three-week-old poults were orally colonized with C. jejuni isolates NCTC 11168 or NADC 20827 (isolated from a turkey flock). Mock-colonized poults were orally gavaged with uninoculated media. Poults were euthanized at d 3, 7, and 21 post colonization and direct plated on different selective Campylobacter media [Campy Line agar with sulfamethoxazole (CLA-S), CHROMagar Campylobacter (CAC) and Campy Cefex] for enumeration. Isolates NCTC 11168 and NADC 20827 poorly colonized the distal ileum. Both isolates colonized the colon, but the number of NADC 20827 significantly decreased at d 21. Isolates NCTC 11168 and NADC 20827 persistently colonized the cecum for up to 21 days. There was no significant difference in the Campylobacter amount recovered on CLA-S and CAC. Campy Cefex failed to prevent growth of background microbes to enumerate C. jejuni from turkey samples. Two independent PCR assays (multiplex PCR and qPCR) confirmed that colonies grown on CLA-S or CAC were C. jejuni. Data from this study demonstrated that isolates NCTC 11168 and NADC 20827 persistently colonized the cecum, and CLA-S or CAC were successful to enumerate Campylobacter from intestinal samples. These findings will be useful to evaluate the host response by C. jejuni in turkeys, and test pre-harvest strategies to reduce its colonization and promote food safety.

Genome-wide association study identifies pharmacogenomic loci linked with specific antihypertensive drug treatment and new-onset diabetes.

We conducted a discovery genome-wide association study with expression quantitative trait loci (eQTL) annotation of new-onset diabetes (NOD) among European Americans, who were exposed to a calcium channel blocker-based strategy (CCB strategy) or a ß-blocker-based strategy (ß-blocker strategy) in the INternational VErapamil SR Trandolapril STudy. Replication of the top signal from the SNP*treatment interaction analysis was attempted in Hispanic and African Americans, and a joint meta-analysis was performed (total 334 NOD cases and 806 matched controls). PLEKHH2 rs11124945 at 2p21 interacted with antihypertensive exposure for NOD (meta-analysis P=5.3 × 10-8). rs11124945 G allele carriers had lower odds for NOD when exposed to the ß-blocker strategy compared with the CCB strategy (Odds ratio OR=0.38(0.24-0.60), P=4.0 × 10-5), whereas A/A homozygotes exposed to the ß-blocker strategy had increased odds for NOD compared with the CCB strategy (OR=2.02(1.39-2.92), P=2.0 × 10-4). eQTL annotation of the 2p21 locus provides functional support for regulating gene expression.

Growth and developmental outcome of infants with in-utero exposure to methadone vs buprenorphine.

OBJECTIVE: To compare early growth and developmental outcome of infants with in-utero exposure to low-dose methadone (<100 mg per day), high-dose methadone (⩾100 mg per day) and buprenorphine. STUDY DESIGN: A retrospective review of infants with in-utero methadone and buprenorphine exposure who were evaluated at the Southcoast Developmental Pediatric clinic in New Bedford, MA, USA was completed. Growth data and developmental testing results during infancy were compared among the groups. RESULT: Infants in the high-dose methadone group had lower head circumference z scores and a lower mean score on the Alberta Infant Motor Scale (AIMS). Regression results confirmed an association between methadone dose and head circumference z score and AIMS score. CONCLUSION: Exposure to maternal methadone dose in excess of 100 mg is associated with a reduction in infant head circumference when compared with buprenorphine or lower dose methadone, and may have a negative impact on motor skill development during early infancy.

Clinical immunology of the sphingosine 1-phosphate receptor modulator fingolimod (FTY720) in multiple sclerosis.

The oral sphingosine 1-phosphate (S1P) receptor (S1PR) modulator fingolimod has been shown to be effective in the treatment of patients with relapsing multiple sclerosis (MS). The drug binds with high affinity to 4 of the 5 G-protein-coupled S1P receptors (S1P(1-5)). After binding, the receptors are internalized, degraded, and thus functionally antagonized by fingolimod. Under physiologic conditions, S1P(1) mediates the egress of lymphocytes from secondary lymphoid organs to the peripheral circulation. Functional antagonism of S1P(1) by fingolimod results in a reduction in peripheral lymphocyte counts by inhibiting egress of lymphocytes, including potentially encephalitogenic T cells and their naïve progenitors that would otherwise be present within the circulation. Despite the fingolimod-mediated reduction of lymphocyte counts, fingolimod-treated patients with MS have been shown to have few infections and related complications and were able to mount antigen-specific immune responses in vaccination studies.

Demonstration of a neutral atom controlled-NOT quantum gate.

We present the first demonstration of a CNOT gate between two individually addressed neutral atoms. Our implementation of the CNOT uses Rydberg blockade interactions between neutral atoms held in optical traps separated by >8 microm. Using two different gate protocols we measure CNOT fidelities of F=0.73 and 0.72 based on truth table probabilities. The gate was used to generate Bell states with fidelity F=0.48+/-0.06. After correcting for atom loss we obtain an a posteriori entanglement fidelity of F=0.58.

Rabi oscillations between ground and Rydberg states with dipole-dipole atomic interactions.

We demonstrate Rabi oscillations of small numbers of 87Rb atoms between ground and Rydberg states with n< or =43. Coherent population oscillations are observed for single atoms, while the presence of two or more atoms decoheres the oscillations. We show that these observations are consistent with van der Waals interactions of Rydberg atoms.

Potential management strategies for the linden borer (Coleoptera: Cerambycidae) in urban landscapes and nurseries.

The linden borer, Saperda vestita Say (Coleoptera: Cerambycidae), is a native insect species that is common throughout north central and northeastern North America. Over the past decade, increasing occurrence of damage associated with the linden borer has been reported on Tilia spp. in city street trees and nurseries throughout Wisconsin, probably because of increased use of these trees. Our objective was to gain a better understanding of the seasonal biology and potential management strategies for this important pest. We evaluated the effectiveness of three systemic insecticides, imidacloprid, thiamethoxam, and disulfoton, and a mechanical control method of chipping linden borer-infested wood as a means of reducing S. vestita larval survival, subsequent emergence, and oviposition. Autumn and spring soil injections of imidacloprid to linden borer-infested Tilia cordata'Greenspire' nursery stock (< 11.4 cm in diameter at breast height [dbh]) provided >90% control. Autumn soil injections of imidacloprid and thiamethoxam and a spring granular soil application treatment of disulfoton applied to larger (>22 cm dbh) Tilia spp. did not effectively control linden borer at the application rates tested. Chipping infested Tilia spp. effectively destroyed linden borer larvae, pupae, and adults. Arborists and landscape managers should consider chipping felled Tilia spp. trees infested with S. vestita to prevent adults from potentially attacking nearby susceptible trees.

Members of the Toll-like receptor family of innate immunity pattern-recognition receptors are abundant in the male rat reproductive tract.

Protecting developing and maturing spermatozoa and reproductive tissues from microbial damage is an emerging aspect of research in reproductive physiology. Bacterial, viral, and yeast infections of the testis and epididymis can hinder maturation and movement of spermatozoa, resulting in impaired fertility. Toll-like receptors (TLRs) are a broad family of innate immunity receptors that play critical roles in detecting and responding to invading pathogens. Objectives of this study were to determine if organs of the rat male reproductive tract express mRNAs for members of the TLR family, to characterize expression patterns for TLRs in different regions of the epididymis, and to determine if TLR adaptor and target proteins are present in the male reproductive tract. Messenger RNA for Tlr1-Tlr9 was abundantly expressed in testis, epididymis, and vas deferens, as determined by RT-PCR, while Tlr10 and Tlr11 were less abundantly expressed. Tlr mRNA expression showed no region-specific patterns in the epididymis. Immunoblot analysis revealed relatively equal levels of protein for TLRs 1, 2, 4, and 6 in testis, all regions of the epididymis and vas deferens, and lower levels of TLRs 3, 5, and 9-11. TLR7 was primarily detected in the testis. The TLR adapter proteins, myeloid differentiation primary response gene 88 and TLR adaptor molecule 1, as well as v-rel reticuloendotheliosis viral oncogene homolog and NFKBIA, were prominent in testis, epididymis, and vas deferens. The abundant expression of a majority of TLR family members together with expression of TLR adaptors and activation targets provides strong evidence that TLRs play important roles in innate immunity of the male reproductive tract.

Fast ground state manipulation of neutral atoms in microscopic optical traps.

We demonstrate Rabi flopping at MHz rates between ground hyperfine states of neutral 87Rb atoms that are trapped in two micron sized optical traps. Using tightly focused laser beams we demonstrate high fidelity, site specific Rabi rotations with cross talk on neighboring sites separated by 8 microm at the level of 10(-3). Ramsey spectroscopy is used to measure a dephasing time of 870 micros, which is approximately 5000 longer than the time for a pi/2 pulse.

A LabVIEW model incorporating an open-loop arterial impedance and a closed-loop circulatory system.

While numerous computer models exist for the circulatory system, many are limited in scope, contain unwanted features or incorporate complex components specific to unique experimental situations. Our purpose was to develop a basic, yet multifaceted, computer model of the left heart and systemic circulation in LabVIEW having universal appeal without sacrificing crucial physiologic features. The program we developed employs Windkessel-type impedance models in several open-loop configurations and a closed-loop model coupling a lumped impedance and ventricular pressure source. The open-loop impedance models demonstrate afterload effects on arbitrary aortic pressure/flow inputs. The closed-loop model catalogs the major circulatory waveforms with changes in afterload, preload, and left heart properties. Our model provides an avenue for expanding the use of the ventricular equations through closed-loop coupling that includes a basic coronary circuit. Tested values used for the afterload components and the effects of afterload parameter changes on various waveforms are consistent with published data. We conclude that this model offers the ability to alter several circulatory factors and digitally catalog the most salient features of the pressure/flow waveforms employing a user-friendly platform. These features make the model a useful instructional tool for students as well as a simple experimental tool for cardiovascular research.

Electrical properties and conduction in reperfused papillary muscle.

The reversibility of ischemia-induced changes of extracellular K(+) concentration ([K(+)](o)), resting membrane potential (E(M)), and passive cable-like properties, ie, extracellular resistance and cell-to-cell electrical coupling, and their relationship to recovery of conduction and contraction is described in 25 reperfused rabbit papillary muscles. No-flow ischemia caused extracellular K(+) accumulation, depolarization of E(M), an increase in whole-tissue (r(t)), external (r(o)), and internal (r(i)) longitudinal resistances, and failure of conduction and contraction. Muscles were reperfused 10 minutes after the onset of ischemia related cell-to-cell electrical uncoupling, ie, 26+/-1 minutes after arrest of perfusion. In 11 muscles, incomplete reflow occurred with only partial recovery of [K(+)](o) and r(t). In the remaining 14 muscles, reperfusion caused a rapid and parallel decrease in [K(+)](o), r(t), and r(o). When complete tissue reperfusion occurred, cell-to-cell electrical uncoupling was largely reversible. Thus, cell-to-cell electrical uncoupling did not indicate irreversible injury. Reperfusion induced a depolarizing current widening the difference between the K(+) equilibrium potential and the E(M). This difference decreased after longer periods of reperfusion. Conduction was restored and conduction velocity approached preischemic values as cell-to-cell electrical interaction was reestablished and E(M) recovered. The recovery of r(o) preceded r(i), decreasing the ratio of the extracellular to intracellular resistance early in reperfusion, an effect predicted to influence the amplitude of the extracellular voltage field and electrocardiographic ST segments during reperfusion.

Modulation of pituitary somatostatin receptor subtype (sst1-5) messenger ribonucleic acid levels by changes in the growth hormone axis.

The role of individual components of the hypothalamic-pituitary-GH axis in the modulation of pituitary somatostatin (SRIF) receptor subtype (sst1-5) synthesis was assessed using multiplex RT-PCR to measure receptor messenger RNA (mRNA) levels in normal rats and spontaneous dwarf rats (SDRs). In SDRs, a strain with no immunodetectable GH, pituitary sst1 and sst2 mRNA levels were elevated, sst5 mRNA levels were reduced, and sst3 and sst4 mRNA levels did not significantly differ from those in normal controls. Treatment of SDRs with GH (72 h), but not insulin-like growth factor I, significantly decreased sst2 mRNA levels and increased sst4 and sst5 mRNA levels above vehicle-treated control levels. To test whether more rapid changes in circulating GH levels could alter SRIF receptor subtype expression, normal rats were infused (iv) with GH-releasing hormone (GHRH) for 4 h in the presence or absence of SRIF antiserum. GHRH infusion increased pituitary sst1 and sst2 and decreased sst5, but had no effect on sst3 and sst4 mRNA levels. Immunoneutralization of SRIF, which produced a rise in circulating GH levels, did not alter basal or GHRH-mediated SRIF receptor subtype expression. These observations indicate that acute suppression of SRIF tone does not regulate pituitary SRIF receptor subtype mRNA levels in vivo. The possibility that elevated circulating GH concentrations induced by GHRH infusion were responsible for the observed changes in SRIF receptor subtype mRNA levels was examined by infusing SDRs with GHRH for 4 h. GHRH did not increase sst1 mRNA levels in SDRs above their already elevated value. However, GHRH infusion produced an increase in sst2 and a decrease in sst5 mRNA levels similar to those observed in normal rats, indicating that the acute effects of GHRH on SRIF receptor subtype expression are independent of circulating GH levels. Primary rat pituitary cell cultures were incubated with GHRH (10 nM) or forskolin (10 microM) for 4 h to determine whether GHRH could directly mediate SRIF receptor subtype mRNA. GHRH treatment increased sst1 and sst2 mRNA levels and decreased sst5 mRNA levels, but had no effect on sst3 and sst4, similar to the results in vivo. The effect of forskolin mimicked that of GHRH on sst1, sst2, and sst5 mRNA, suggesting that GHRH acts through cAMP to directly mediate gene transcription or mRNA stability of these SRIF receptor subtypes. In addition, forskolin reduced sst3 and sst4 expression. These results strongly suggest that rat pituitary sst1, sst2, and sst5 mRNA levels are regulated both in vivo and in vitro by GHRH. The stimulatory action of GHRH on sst1 and sst2 and the inhibitory action on sst5 indicate that these receptor subtypes have independent and unique roles in the modulation of pituitary GH release.

Therapy of B-cell lymphomas with monoclonal antibodies and radioimmunoconjugates: the Seattle experience.

Monoclonal antibodies (mAbs) and radioimmunoconjugates targeting B-cell differentiation antigens have emerged as promising new treatments for patients with relapsed non-Hodgkin's lymphoma. This review focuses on our experience in Seattle over the past decade treating relapsed B-cell non-Hodgkin's lymphomas. In initial pilot studies, we administered escalating doses of the unmodified murine anti-CD20 mAb 1F5 to four patients with multiply relapsed lymphoma and-documented the dose-dependent penetration of antibody into the bone marrow and lymph nodes. The two patients who received the higher doses (1032 mg and 2380 mg) had remissions of brief duration, including one minor response lasting 2 weeks and one partial response lasting 6 weeks. Sequential phase-I and -II trials with myeloablative doses of iodine-131-mAbs have documented complete responses in 30 of 36 (83%) patients treated and, most importantly, many of these responses have been durable. A recent long-term follow-up study of the 29 patients treated with myeloablative doses of the I-131-labeled murine anti-B1 (anti-CD20) antibody has documented estimated overall and progression-free survival rates of 68% and 42%, respectively, with a median follow-up time of 42 months. To optimize the durability of responses, we are currently conducting a phase-I/II trial studying the toxicity and efficacy of I-131-anti-B1 antibody given in combination with high-dose etoposide and cyclophosphamide and autologous hematopoietic stem cell rescue.

Effect of rates of perfusion on dominant frequency and defibrillation energy in isolated fibrillating hearts.

This study assessed the influence of rates of reperfusion on excitability of the myocardium using dominant frequency (DF) (in Hz) of VF and the relationship of DF to the minimum defibrillation energy (MDE) (in J). Our hypothesis was that increasing flow during reperfusion increases DF that raises MDE. Initially, six Langendorff perfused swine hearts were serially fibrillated and perfusion arrested for 4 minutes followed by reperfusion and defibrillation to establish reproducibility of the model. The epicardial ECG was analyzed for DF. In subsequent studies (n = 8), no flow VF was followed by 1-minute reperfusion at normal flow or 10% flow (low flow) and shocked with increasing energy via epicardial pads until defibrillation. The DF at onset of no flow VF was 9.5 +/- 1.4 and decreased to 3.6 +/- 1.4 after 4 minutes. Reperfusion at normal flow increased the DF of VF compared to low flow after 1 minute (10.8 +/- 1.1 vs 4.5 +/- 1.1 Hz, P = 0.0002) and was associated with increased defibrillation energy requirements (13.5 +/- 5.0 vs 7.3 +/- 6.2 J, P = 0.047). In summary, defibrillation energy requirements are lower when myocardial excitability is reduced during low flow reperfusion.