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SAR on NRF2 inhibitor MSU38225 has led to a compound that inhibits expression of NRF2 target genes, reduces proliferation of lung cancer cells through G2/M arrest, and lowers cell migration.

Liquid crystalline elastomers (LCEs) are crosslinked polymer networks that combine the elastic properties of rubber with the anisotropic properties of liquid crystals. Multifunctionality and responsivity can be programmed into LCEs by patterning their local orientation, which is difficult to achieve in other monolithic material systems. Advances in the synthesis and alignment of LCEs have paved the way for their functional integration in robotics, optics, consumer products, energy and healthcare devices. In this Review, we discuss recent advances in materials chemistry and processing that have contributed to the resurgence in LCE research. We examine the mechanical response of LCEs to stimuli and survey approaches for mechanical alignment, surface-enforced alignment, field-induced alignment and rheological alignment. The Review concludes with an over-the-horizon outlook discussing current challenges and emerging research opportunities. Liquid crystalline elastomers are stimuli-responsive polymeric materials whose mechanical properties can be programmed by patterning their local orientation, making them promising candidates to serve as low-density actuators and functional elements in various applications. This Review discusses the synthesis and processing of liquid crystalline elastomers, with a focus on alignment methods and potential applications.

Activation of myosin light-chain kinase (MLCK) by calcium ions (Ca2+) and calmodulin (CaM) plays an important role in numerous cellular functions including vascular smooth muscle contraction and cellular motility. Despite extensive biochemical analysis of this system, aspects of the mechanism of activation remain controversial, and competing theoretical models have been proposed for the binding of Ca2+and CaM to MLCK. The models are analytically solvable for an equilibrium steady state and give rise to distinct predictions that hold regardless of the numerical values assigned to parameters. These predictions form the basis of a recently proposed, multi-part experimental strategy for model discrimination. Here we implement this strategy by measuring CaM-MLCK binding using anin vitroFRET system. This system uses the CaM-binding region of smooth muscle MLCK protein to link two fluorophores to form an MLCK FRET Reporter (FR). Biochemical and biophysical experiments have established that FR can be reliably used to analyze MLCK-CaM binding. We assessed the binding of either wild-type CaM, or mutant CaM with one or more defective EF-hand domains, to FR. Interpretation of binding data in light of the mathematical models suggests a partially ordered mechanism for binding of CaM to MLCK. Complementary data collected using orthogonal approaches that directly quantify CaM-MLCK binding further supports our conclusions.

Background: Bone–patellar tendon–bone (BTB) and hamstring autografts are the most common grafts used for anterior cruciate ligament (ACL) reconstruction. Patient preferences should be accounted for as a part of shared decision making. Purpose/Hypothesis: The purpose of this study was to perform a discrete choice experiment that evaluated patient preferences toward ACL autografts. We hypothesized that there would be no difference in patient preferences between groups. Study Design: Cross-sectional study. Methods: Patients aged 18 to 25 years who underwent shoulder arthroscopy at a single institution between 2013 and 2019 were included in the study as a proxy for healthy controls. Patients with a history of ACL tear were excluded. A discrete choice experiment was developed from a literature search and used the following data points as they pertain to BTB or hamstring autograft: risk of developing a significant complication, return-to-play rate, risk of anterior knee pain with kneeling, and risk of additional surgery due to graft failure. Included patients completed a custom survey in which they were asked to choose between “surgery A” (hamstring) and “surgery B” (BTB). Results: A total of 107 participants were included in the analysis. Of these participants, 39 (36.5%) chose surgery A (hamstring) and 68 (63.6%) chose surgery B (BTB). When comparing the hamstring group with the BTB group, there was no significant difference in age, sex, body mass index, race, level of education, or employment status. However, 80.5% of self-reported athletes preferred BTB ( P = .008). When controlling for age, sex, and body mass index, patients in the BTB group were more likely to rate return to sport (risk ratio [RR] = 1.49 [95% CI, 1.18-1.98]; P = .001) and the risk of requiring additional surgery due to graft failure (RR = 1.26 [95% CI, 1.02-1.58]; P = .037) as highly important. Conversely, they were less likely than patients in the hamstring group to rate pain while kneeling (RR = 0.65 [95% CI, 0.98-1.05]; P < .001) and complication risk (RR = 0.75 [95% CI, 0.59-0.94]; P = .013) as important. Conclusion: The study hypothesis was rejected, as patient values did affect ACL graft choice preference. Utilizing patient-selected values in a quantifiable way can benefit the shared decision-making process before ACL reconstruction.

Disruptions to the maternally inherited allele UBE3A, encoding for an E3 ubiquitin ligase, leads to the manifestation of Angelman Syndrome (AS). While this disorder is rare, the symptoms are severe and lifelong including but not limited to: intractable seizures, abnormal EEG's, ataxic gait, lack of speech, and most notably an abnormally happy demeanor with easily provoked laughter. Currently, little is known about the neurophysiological underpinnings of UBE3A leading to such globally severe phenotypes. Utilizing the newest AS rat model, comprised of a full UBE3A deletion, we aimed to elucidate novel mechanistic actions and potential therapeutic targets. This report demonstrates for the first time that catalytically active UBE3A protein is detectable within cerebrospinal fluid (CSF) of wild type rats but distinctly absent in AS rat CSF. Microdialysis within the rat hippocampus also showed that UBE3A protein is located in the interstitial fluid of wild type rat brains but absent in AS animals. This protein maintains catalytic activity and appears to be regulated in a dynamic activity-dependent manner. LAY SUMMARY: Angelman syndrome (AS) is a rare genetic disorder caused by the loss of the UBE3A gene within the central nervous system. Although we have identified the gene responsible for AS, we still have a long way to go to fully understand its function in vivo. Here we report that UBE3A is present within normal cerebrospinal fluid (CSF) but distinctly absent in AS CSF. Furthermore, we demonstrate that UBE3A is secreted and that this may occur in a dynamic activity-dependent fashion. Extracellular UBE3A maintained its ubiquitinating activity, thus suggesting that UBE3A may have a novel role outside of neurons. Autism Res 2021, 14: 645-655. © 2021 International Society for Autism Research and Wiley Periodicals LLC.

A total of 710 pigs (Line 400 × 200, DNA, Columbus, net energy (NE)) were used in two experiments (Exp. 1: initially, 6.3 ± 0.05 kg; Exp. 2: initially, 6.8 ± 0.05 kg) to evaluate the effects of two medium-chain fatty acid (MCFA) based products on nursery pig growth performance. Following their arrival at the nursery facility, pigs were randomized to pens (five pigs per pen) and allowed a 4-d acclimation period. Thereafter, pens of pigs were blocked by initial weight and randomized to dietary treatment. In Exp. 1, the dietary treatments were a dose titration of: 0%, 0.5%, 1.0%, or 2.0% MCFA-based additive, as well as a diet including 1.0% MCFA from a 1:1:1 blend of C6:0, C8:0, and C10:0. In Exp.2, dietary treatments consisted of a basal diet containing no MCFA (control), the control diet with a 1.0% inclusion of four different blends of MCFA, lactic acid, and monolaurin or a diet with 1.0% added MCFA (a 1:1:1 blend of C6:0, C8:0, and C10:0). The four blends consisted of 50% C6:0, 20% lactic acid, and increasing levels of monolaurin (0%, 10%, 20%, and 30%) at the expense of C12:0 (30%, 20%, 10%, and 0%). Treatment diets were formulated and manufactured in two dietary phases. Data were analyzed as a randomized complete block design with pen as the experimental unit. In Exp. 1, overall (days 0–34), increasing CaptiSURE increased (linear, P ≤ 0.014) average daily gain (ADG) and average daily feed intake (ADFI). Feed efficiency improved (quadratic, P = 0.002) with increasing CaptiSURE up to 1.0% of the diet with no benefit thereafter. There was no evidence for differences between pigs fed 1.0% CaptiSURE and pigs fed the 1.0% MCFA blend of C6:0, C8:0, and C10:0. In Exp. 2, overall (days 0–35), pigs fed the 1.0% 1:1:1 MCFA blend had increased (P < 0.034) ADFI and ADG resulting in 0.9 kg greater final weight (P = 0.014) compared with the control group. There was no evidence that the mean performance of pigs fed the four blends of MCFA, lactic acid, and monolaurin were different from the pigs fed the control diet. In summary, the addition of a 1.0% 1:1:1 blend of C6:0, C8:0, and C10:0 in nursery pig diets improved ADG, ADFI, and gain to feed ratio (G:F) compared with pigs fed the control diet. In addition, providing nursery pigs with the MCFA product CaptiSURE, up to 2% of the diet, resulted in linear improvements in ADG and ADFI. Altering the C12:0 to monolaurin ratio and adding lactic acid did not improve growth performance compared with pigs fed the control diet.

Isolation of Shigella in the bloodstream is a rare sequela of Shigella infections. Shigellemia typically occurs in patients with immature immune responses or in immunocompromised adults. Herein, we present a case of shigellemia in a 40-year-old male who presented with diabetic ketoacidosis (DKA), severe diarrhea, hypovolemic hyponatremia, and altered mental status. Stool cultures were found to be positive for Shigella, and broad-spectrum antibiotic therapy was initiated. Because of the patient’s reported sexual exposures, a rapid HIV point of care test was done and returned negative. In spite of intervention, the patient’s vitals, labs, and symptoms failed to improve, and he developed septic shock requiring pressor support in the intensive care unit. Further workup for the etiology of the patient’s sepsis included a CT abdomen and pelvis which showed findings concerning infectious colitis. Blood cultures later returned positive for Shigella, which was found to be resistant to multiple antibiotics. The patient was started on IV ceftriaxone with an improvement of and eventual resolution of symptoms. Shigellemia is a rare complication of infection with Shigella and necessitates further workup to avoid overlooking potential predisposing factors such as HIV or other immunocompromising conditions. Its susceptibilities should also be evaluated, as Shigella strains are more frequently becoming resistant to antibiotics that had previously been the therapies of choice.

Broadcast-spawning scleractinian corals undergo mass spawning annually, the timing of which is determined by a series of environmental and chemical cues. Flower Garden Banks reefs (FGB, NW Gulf of Mexico) have high coral cover compared to the rest of the Tropical Western Atlantic and exhibit highly synchronous coral spawning, although spawning observations have been largely limited to shallower depths (17–24 m). Using a remotely operated vehicle (ROV), we report observations of mesophotic (39–42 m) broadcast spawning of three major reef-building coral species at East FGB. We observed spawning of 20 Montastraea cavernosa colonies, an order of magnitude more than has been previously reported for this population at mesophotic depths. Spawning times of the three target species (M. cavernosa, Orbicella franksi, and Pseudodiploria strigosa) ranged from 45 min prior to sunset up to 1 h, 33 min after sunset, consistent with shallow conspecifics. We place these observations in the context of other spawning reports of the same species at the FGB and throughout the Tropical Western Atlantic. In addition, the ROV was directed to collect eight genetically unique fragments of gravid Orbicella faveolata and employed a novel gamete collection device designed to capture gametes from actively spawning colonies in situ. These data and collection techniques highlight the benefits of using ROV technology for coral-spawning research, particularly for mesophotic coral reef ecosystems, where gamete release occurs across time ranges exceeding limits imposed by recreational diving. Finally, our observations of overlap in the timing of spawning along the shallow to mesophotic continuum at the FGB suggest—at least for the corals monitored here—that the potential for cross fertilization across depths exists.

Objective: To assess the acceptability, safety and efficacy of the PPH Butterfly, a new uterine compression device, in women with postpartum haemorrhage (PPH). Design: A phase two clinical device trial using matched historical controls, with accompanying grounded theory study. Setting: UK university consultant obstetric unit. Population: women with PPH after vaginal birth unresponsive to initial oxytocin therapy. Outcomes were compared to historical controls matched on blood loss, parity and type of birth. Methods: after oral consent, trained staff used the device in additional to normal care. Main Outcome Measures: The primary outcome was additional blood loss >1000mls. Qualitative interviews assessed device feasibility and acceptability. Results: Of the 57 recruits, two-thirds were primiparous and almost half had undergone operative birth. Two percent of recruited women had additional blood loss of over 1000mls compared to 8% of 113 controls (adjusted odds ratio 0.13, 95% CI (0.02 to 1.09)). Women treated with the device received significantly more additional treatments and had higher rates of exclusive breast-feeding at discharge. There were no serious adverse events related to the device. In 47 interviews, participants, birth partners, clinicians and attending midwives viewed the device positively. Clinicians found it useful to stop blood loss and diagnose the source of bleeding. Conclusions: the PPH Butterfly is acceptable and may have clinical benefits: it is a promising device for PPH management. Funding: National Institute for Health Research invention for innovation (i4i) program (II-LA-0715-200008) Keywords: postpartum haemorrhage, childbirth, oxytocin, third stage of labour, uterine compression. Registration: prospective ISRCTN (15452399); www.isrctn.com/ISRCTN15452399

Modern feed quality sorghum grain has been bred to reduce anti-nutrients, most conspicuously condensed tannins, but its inclusion in the diets of monogastric animals can still result in variable performance that is only partially understood. Sorghum grain contains several negative intrinsic factors, including non-tannin phenolics and polyphenols, phytate, and kafirin protein, which may be responsible for these muted feed performances. To better understand the non-tannin phenolic and polyphenolic metabolites that may have negative effects on nutritional parameters, the chemical composition of sorghum grain polyphenol extracts from three commercial varieties (MR-Buster, Cracka, and Liberty) was determined through the use of an under-studied, alternative analytical approach involving Fourier-transform infrared (FT-IR) spectroscopy and direct ionization mass spectrometry. Supervised analyses and interrogation of the data contributing to variation resulted in the identification of a variety of metabolites, including established polyphenols, lignin-like anti-nutrients, and complex sugars, as well as high levels of fatty acids which could contribute to nutritional variation and underperformance in monogastrics. FT-IR and mass spectrometry could both discriminate among the different sorghum varieties indicating that FT-IR, rather than more sophisticated chromatographic and mass spectrometric methods, could be incorporated into quality control applications.

Introduction. The clinical course of Coronavirus Disease 2019 (COVID-19) is highly heterogenous, ranging from asymptomatic to fatal forms. The identification of clinical and laboratory predictors of poor prognosis may assist clinicians in monitoring strategies and therapeutic decisions. Materials and Methods. In this study, we retrospectively assessed the prognostic value of a simple tool, the complete blood count, on a cohort of 664 patients ( F 260; 39%, median age 70 (56-81) years) hospitalized for COVID-19 in Northern Italy. We collected demographic data along with complete blood cell count; moreover, the outcome of the hospital in-stay was recorded. Results. At data cut-off, 221/664 patients (33.3%) had died and 453/664 (66.7%) had been discharged. Red cell distribution width (RDW) ( χ 2 10.4; p < 0.001 ), neutrophil-to-lymphocyte (NL) ratio ( χ 2 7.6; p = 0.006 ), and platelet count ( χ 2 5.39; p = 0.02 ), along with age ( χ 2 87.6; p < 0.001 ) and gender ( χ 2 17.3; p < 0.001 ), accurately predicted in-hospital mortality. Hemoglobin levels were not associated with mortality. We also identified the best cut-off for mortality prediction: a NL ratio > 4.68 was characterized by an odds ratio for in-hospital mortality OR = 3.40 (2.40-4.82), while the OR for a RDW > 13.7 % was 4.09 (2.87-5.83); a platelet count > 166,000 /μL was, conversely, protective (OR: 0.45 (0.32-0.63)). Conclusion. Our findings arise the opportunity of stratifying COVID-19 severity according to simple lab parameters, which may drive clinical decisions about monitoring and treatment.

Two experiments were conducted to evaluate the effects of Fe injection timing after birth on suckling and subsequent nursery and growing-finishing pig performance. The injectable Fe source used in both experiments was GleptoForte (Ceva Animal Health, LLC., Lenexa, KS). GleptoForte contains gleptoferron which is a Fe macromolecule complex. In Exp. 1, a total of 324 newborn pigs (DNA 241 × 600, initially 1.6 ± 0.04 kg body weight [BW]) within 27 litters were used. Two days after birth, all piglets were weighed, and six barrows and six gilts per litter were allotted to 1 of 6 treatments consisting of no Fe injection or 200 mg of injectable Fe provided in a single injection on d 2, 4, 6, 8, or 10 of age. Pigs were weaned (~21 d of age) and allotted to nursery pens with all pigs in each pen having received the same Fe treatment. In Exp. 2, a total of 1,892 newborn pigs (PIC 359 × C40; initially 1.5 ± 0.02 kg BW) within 172 litters were used. One day after birth, piglets were weighed, and 11 pigs within each litter were allotted to 1 of 6 treatments consisting of no Fe injection or 200 mg of injectable Fe provided on d 1, 3, 5, or 7 of age, or 200 mg on d 1 plus 200 mg on d 12 of age. Pigs were weaned (19 d of age) and placed in a commercial wean-to-finish facility in a total of 15 pens with equal representation of treatments in each pen. In both experiments, not providing an Fe injection after birth decreased (P < 0.05) preweaning average daily gain (ADG), weaning weight, and hemoglobin and hematocrit values compared with all other treatments. In Exp. 1, increasing the age that piglets received an Fe injection until 4 or 6 d after birth provided marginal evidence for an improvement (quadratic; P = 0.070) in preweaning ADG. For the nursery period, increasing the age that piglets received an Fe injection improved (quadratic; P = 0.013) d 80 BW, but there was no evidence of a difference (P > 0.10) in d 173 BW at the end of the grow-finish period. In Exp. 2, increasing the age that piglets received a 200 mg Fe injection showed no evidence of difference (P > 0.10) for subsequent nursery and growing-finishing ADG. In both experiments, hemoglobin and hematocrit values were decreased (linear; P < 0.05) at weaning with increasing age when pigs received an Fe injection. These experiments suggest that providing a 200 mg Fe injection within 7 d after farrowing is sufficient for optimizing preweaning and subsequent growth performance.

Weaned pigs (n=1,722; 5.9 kg BW) were used in a 53-d study evaluating the effects of Fe injection timing on subsequent nursery pig performance. Treatments consisted of a negative control for piglets receiving no Fe injection or 200-mg of injectable Fe (GleptoForte, Ceva Animal Health, Lenexa, KS) provided on d 1, 3, 5, or 7 of age, or 200-mg on d 1 plus an additional 200-mg injection on d 12. At weaning, pigs were placed in a commercial wean-to-finish facility in a total of 15 pens with equal representation of treatments in each pen. Pigs were weighed on d 73 after birth to determine subsequent nursery growth performance. Growth data were analyzed (GLIMMIX procedure of SAS) as a completely randomized design with individual pig as the experimental unit and pen as a random effect. Increasing the age that piglets received a 200-mg Fe injection showed no evidence of difference (P >0.10) for subsequent nursery ADG (Table 1). Not providing an Fe injection after birth decreased (P=0.0001) subsequent nursery ADG and decreased (P=0.0001) d 73 BW compared to all other treatments. Providing a 200-mg injection of Fe on d 1 plus a 200-mg injection on d 12 decreased (P=0.010) subsequent nursery ADG and decreased (P=0.024) d 73 BW compared to pigs receiving a 200-mg injection on d 1 only. There was no evidence of difference (P >0.10) for nursery mortality amongst the treatments. These results suggest that providing a 200-mg Fe injection within 7 d after farrowing is sufficient for optimizing subsequent nursery growth performance. The additional 200-mg Fe injection at d 12 decreased subsequent nursery growth performance and ending BW.

Modern feed quality sorghum grain has been bred to reduce anti-nutrients, most conspicuously condensed tannins, but its inclusion in the diets of monogastric animals can still result in variable performance that is only partially understood. Sorghum grain contains several negative intrinsic factors, including non-tannin phenolics and polyphenols, phytate, and kafirin protein, which may be responsible for these muted feed performances. To better understand the non-tannin phenolic and polyphenolic metabolites that may have negative effects on nutritional parameters, the chemical composition of sorghum grain polyphenol extracts from three commercial varieties (MR-Buster, Cracka, and Liberty) was determined through the use of an under-studied, alternative analytical approach involving Fourier-transform infrared (FT-IR) spectroscopy and direct ionization mass spectrometry. Supervised analyses and interrogation of the data contributing to variation resulted in the identification of a variety of metabolites, including established polyphenols, lignin-like anti-nutrients, and complex sugars, as well as high levels of fatty acids which could contribute to nutritional variation and underperformance in monogastrics. FT-IR and mass spectrometry could both discriminate among the different sorghum varieties indicating that FT-IR, rather than more sophisticated chromatographic and mass spectrometric methods, could be incorporated into quality control applications.

A total of 140 weanling pigs (241 × 600, DNA, Columbus, NE; initially 5.5 ± 0.79 kg body weight) were used in a 32-d study evaluating the effects of increasing dietary Fe from either iron sulfate (FeSO4) or iron carbonate (FeCO3) on nursery pig growth performance and blood Fe status. The pigs used for this trial did not receive an Fe injection after birth in order to increase the sensitivity to added dietary Fe after weaning. Pigs were weaned at approximately 21 d and allotted to pens based on the initial weight in a completely randomized block design with five pigs in each pen and four pens per treatment. Experimental treatments were arranged as a 2 × 3 + 1 factorial with main effects of dietary Fe source (FeSO4 vs. FeCO3) and level (10, 30, or 50 mg/kg of added Fe) plus a negative control with no additional dietary Fe. The basal diet contained 40 mg/kg total dietary Fe based on ingredient contributions and was formulated with an Fe-free trace mineral premix. Experimental diets were formulated below the pigs recommended Fe requirement based on NRC (2012) estimates. Experimental diets were fed in pellet form in a single phase for the duration of the trial. From day 0 to 32, there was no evidence for source × level interactions for growth performance, hemoglobin (Hb), or hematocrit (Hct) values. There was no evidence for a difference (P > 0.10) in dietary Fe source. Providing increasing Fe levels in the diet from either FeSO4 or FeCO3 improved (P < 0.05) average daily gain, average daily feed intake, gain-to-feed ratio, and increased (P < 0.05) Hb and Hct values. A day effect (P = 0.001) was observed for both Hb and Hct with values increasing throughout the study. Increasing dietary Fe levels in the diet from either FeSO4 or FeCO3 increased (linear; P < 0.05) Hb and Hct values on days 14, 21, and 32. In summary, these data suggest that the micronized form of FeCO3 is a source of Fe that can be added to nursery diets to yield similar responses to those observed from FeSO4 supplementation. Similar to previous research, increasing dietary Fe improved the growth performance and increased Hb and Hct values when pigs have low Fe status at weaning.

Background Two experiments were conducted to determine the effects of increasing amounts of soybean meal (SBM) in swine diets and estimate the energy value of SBM. Methods A total of 2233 pigs (PIC 337 × 1050, Hendersonville, TN) and 3796 pigs (PIC 359 × C40), initially 11.0 kg and 17.6 kg body weight (BW), were used in Exp. 1 and 2, respectively. In Exp. 1, pigs were placed in 92 pens each containing 20 to 27 pigs. In Exp. 2, pigs were placed in 84 pens each containing 37 to 43 pigs. Treatments were assigned in a randomized complete block design with BW as the blocking factor. Dietary treatments consisted of 21%, 27%, 33%, or 39% SBM in Exp. 1 and 17.5%, 22%, 26.5%, 31%, 35.5%, or 40% SBM in Exp. 2, obtained by changing the inclusion rate of feed-grade amino acids and corn grain. For Exp. 1, representative samples of corn grain, SBM, and distillers dried grains with solubles were analyzed for total AA content prior to diet formulation. For Exp. 2, diets were formulated using NRC (2012) nutrient loadings. Treatment diets were fed for 21 and 22 d (Exp. 1 and 2) and there were 23 replicates in Exp. 1 and 14 replicates in Exp. 2. Pigs were weighed and feed disappearance measured weekly to calculate average daily gain (ADG), average daily feed intake (ADFI), gain-to-feed ratio (G:F), and caloric efficiency (CE). Data were analyzed with block as a random effect and treatment as a fixed effect, and contrasts were constructed to test the linear and quadratic effects of increasing SBM. Results In Exp. 1, there was a tendency (linear, P = 0.092) for a decrease in ADFI as SBM increased. There was a tendency (P = 0.090) for a quadratic response for ADG, with a decrease in ADG observed with 39% SBM inclusion. Pigs fed diets with increasing SBM had a tendency (quadratic, P = 0.069) for an increase in G:F up to 33% SBM and an improvement (linear, P = 0.001; quadratic, P = 0.063) in CE with increasing SBM. Using CE to estimate the energy of SBM relative to corn, a value of 105.4% of corn energy or 2816 kcal/kg NE was determined using all data points. When removing the CE value of the 39% SBM treatment due to the quadratic tendency, SBM was estimated to have 121.1% of corn energy or 3236 kcal/kg NE. In Exp. 2, there was a decrease (linear, P = 0.001) in ADFI. Pigs fed increasing SBM had a tendency (linear, P = 0.065) for reduced ADG but an improvement (linear, P = 0.001) in G:F and CE as SBM increased. The energy value of SBM was estimated as 124.7% of corn energy or 3332 kcal/kg NE. Conclusions The results suggest that feeding increasing levels of SBM improves G:F and CE. The energy value of SBM was estimated to be between 105% and 125% of corn, which is much greater than the NRC (2012) would indicate.

A total of 336 newborn pigs (DNA 241 × 600, initially 1.75 ± 0.05 kg bodyweight [BW]) from 28 litters were used in a 63-d study evaluating the effects of increasing injectable Fe dose on suckling and subsequent nursery pig performance and blood Fe status. GleptoForte (Ceva Animal Health, LLC, Lenexa, KS) contains gleptoferron which is an Fe macromolecule complex that is commercially used as an injectable Fe source for suckling piglets. On the day of processing (day 3 after birth), all piglets were weighed and 6 barrows and 6 gilts per litter were allotted within sex to 1 of 6 treatments in a completely randomized design. Treatments consisted of a negative control receiving no Fe injection and increasing injectable Fe to achieve either 50, 100, 150, 200 mg, or 200 mg plus a 100 mg injection on day 11 after birth. Pigs were weaned (~21 d of age) and allotted to nursery pens based on BW and corresponding treatment in a completely randomized design. During lactation, increasing injectable Fe up to 100 mg improved (quadratic; P < 0.05) average daily gain (ADG) and day 21 BW with no further improvement thereafter. There was no evidence of differences (P > 0.10) observed between the 200 mg and 200 mg + 100 mg treatments for growth. For the nursery period, increasing Fe dosage increased (linear; P < 0.05) ADG, average daily feed intake, and day 42 BW. There was no evidence of differences (P > 0.10) between the 200 mg and 200 mg + 100 mg treatments for nursery growth. For blood criteria, significant treatment × day interactions (P = 0.001) were observed for hemoglobin (Hb) and hematocrit (Hct). The interactions occurred because pigs that had

Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, lack of speech, and ataxia. The gene responsible for AS was identified as Ube3a and it encodes for E6AP, an E3 ubiquitin ligase. Currently, there is very little known about E6AP's mechanism of action in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. Elucidating the mechanistic action of E6AP would enhance our understanding of AS and drive current research into new avenues that could lead to novel therapeutic approaches that target E6AP's various functions. To facilitate the study of AS, we have generated a novel rat model in which we deleted the rat Ube3a gene using CRISPR. The AS rat phenotypically mirrors human AS with loss of Ube3a expression in the brain and deficits in motor coordination as well as learning and memory. This model offers a new avenue for the study of AS. Autism Res 2020, 13: 397-409. © 2020 International Society for Autism Research,Wiley Periodicals, Inc. LAY SUMMARY: Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, difficulty speaking, and ataxia. The gene responsible for AS was identified as UBE3A, yet very little is known about its function in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. To facilitate the study of AS, we have generated a novel rat model in which we deleted the rat Ube3a gene using CRISPR. The AS rat mirrors human AS with loss of Ube3a expression in the brain and deficits in motor coordination as well as learning and memory. This model offers a new avenue for the study of AS.

Programming the local orientation of liquid crystal elastomers (LCEs) is a differentiated approach to prepare monolithic material compositions with localized deformation. Our prior efforts prepared LCEs with surface-enforced spatial variations in orientation to localize deformation when the LCEs were subjected to directional load. However, because these surface alignment methods included regions of planar orientation, the deformation of these programmed LCEs is inherently directional. The absence of macroscopic orientation in polydomain LCEs results in uniform, nonlinear deformation in all axes (omnidirectional soft elasticity). Here, we exploit the distinct mechanical response of polydomain LCEs prepared with isotropic or nematic genesis. By localizing the polydomain genesis via masked photopolymerizations conducted at different temperatures, we detail the preparation of main-chain, polydomain LCEs that are homogeneous in composition but exhibit spatially localized programmability in their mechanical response that is uniform in all directions.

Three studies evaluated the effects of added dietary salt on growth performance of pigs weighing 7 to 10, 11 to 30, and 27 to 65 kg. In experiment 1, 325 pigs were used with 5 pigs per pen and 13 pens per treatment. Pigs were fed a diet (0.39% Na and 0.78% Cl) for 7 d after weaning, then randomly assigned to diets with either 0, 0.20, 0.40, 0.60, or 0.80% added salt for 14 d. All diets were corn-soybean meal-based with 10% dried whey. Calculated Na concentrations were 0.11, 0.19, 0.27, 0.35, and 0.43% and calculated Cl concentrations were 0.23, 0.35, 0.47, 0.59, and 0.70%, respectively. Increasing salt increased (linear, P < 0.05) average daily gain (ADG) and gain to feed ratio (G:F). For ADG, the linear, quadratic polynomial (QP), and broken-line linear (BLL) models were competing with the breakpoint for the BLL at 0.59% salt. For G:F, the BLL reported a breakpoint at 0.33% while the QP indicated maximum G:F at 0.67% added salt. In experiment 2, 300 pigs were used in a 34-d trial with 5 pigs per pen and 12 pens per treatment. Pigs were weaned at 21 d of age and fed a phase 1 diet (0.50% Na and 0.67% Cl) for 11 d and then a phase 2 diet (0.35% Na and 0.59% Cl) for 14 d. Then pens of pigs were randomly assigned to corn-soybean meal-based diets containing 0.20, 0.35, 0.50, 0.65, or 0.80% added salt. Calculated dietary Na concentration were 0.10, 0.16, 0.22, 0.28, and 0.34% and calculated Cl concentrations were 0.23, 0.32, 0.41, 0.50, and 0.59%, respectively. Overall, ADG and G:F increased (quadratic, P < 0.07) with increasing added salt. For ADG, the QP and BLL had similar fit with the breakpoint for BLL at 0.51% added salt. For G:F, the BLL model predicted a break point at 0.35% added salt. In experiment 3, 1,188 pigs were used in a 44-d study with 27 pigs per pen and 11 pens per treatment. Pens of pigs were randomly assigned to corn-soybean meal-based diets containing 0.10, 0.33, 0.55, or 0.75% added salt. Calculated dietary Na concentrations were 0.10, 0.19, 0.28, and 0.36% and calculated Cl concentrations were 0.23, 0.36, 0.49, and 0.61%, respectively. Overall, there was no evidence to indicate that added salt above 0.10% of the diet affected growth. In conclusion, the BLL models suggested to maximize ADG for 7 to 10 and 11 to 30 kg pigs was 0.59% (0.34% Na and 0.58% Cl) and 0.51% added salt (0.22% Na and 0.42% Cl), respectively. There was no evidence that growth of 27 to 65 kg pigs was improved beyond 0.10% added salt (0.11% Na and 0.26% Cl).

The integration of soft, stimuli-responsive materials in robotic systems is a promising approach to introduce dexterous and delicate manipulation of objects. Electrical control of mechanical response offers many benefits in robotic systems including the availability of this energy input, the associated response time, magnitude of actuation, and opportunity for self-regulation. Here, a materials chemistry is detailed to prepare liquid crystal elastomers (LCEs) with a 14:1 modulus contrast and increase in dielectric constant to enhance electromechanical deformation. The inherent modulus contrast of these LCEs (when coated with compliant electrodes) directly convert an electric field to a directional expansion of 20%. The electromechanical response of LCE actuators is observed upon application of voltage ranging from 0.5 to 6 kV. The deformation of these materials is rapid, reaching strain rates of 18% s-1 . Upon removal of the electric field, little hysteresis is observed. Patterning the spatial orientation of the nematic director of the LCEs results in a 2D-3D shape transformation to a cone 8 mm in height. Individual and sequential addressing of an array of LCE actuators is demonstrated as a haptic surface.

Newborn pigs (n=1,892; 1.5 kg BW) were used in a 20-d study evaluating the effects of Fe injection timing after birth on preweaned pig performance and blood criteria. A total of 172 litters were used. One d after farrowing, piglets were weighed, and 11 pigs within each litter were allotted to 1 of 6 treatments in a CRD. Treatments consisted of pigs receiving no Fe injection or 200-mg of injectable Fe (GleptoForte, Ceva Animal Health, Lenexa, KS) provided on d 1, 3, 5, or 7 of age, or 200-mg on d 1 plus 200-mg on d 12. 1 pig/litter received no Fe injection and 2 pigs/litter were placed on all other treatments. Piglets were weighed on d 1 and 20 after birth to determine growth performance and bled on d 20 to determine Fe status. Increasing the age that piglets received the Fe injection tended to decrease (linear; P=0.080) ADG. Not providing an Fe injection decreased (P=0.0001) overall ADG and d 20 BW compared to all other treatments. Hemoglobin and Hct decreased (linear; P< 0.05) with increasing age when pigs received an Fe injection. There was no evidence of differences (P >0.10) between the pigs receiving a 200-mg injection on d 1 and d 12 compared to those receiving the Fe on d 1 only. Pigs not provided an Fe injection had decreased (P=0.0001) Hb and Hct values compared to pigs receiving an Fe injection. Pigs receiving the 200-mg injection on d 1 and 12 had increased (P=0.0001) Hb and Hct values compared to pigs receiving 200-mg on d 1 only. Results suggest that providing a 200-mg Fe injection within 7 d after farrowing is sufficient for optimizing preweaning growth performance. The additional 200-mg Fe injection at d 12 did not influence growth performance but does increase Hb and Hct at weaning.

Recent research has reported that increasing standardized ileal digestible (SID) Trp:Lys ratio above 20% in finishing pigs fed Ractopamine HCL (RAC) resulted in improved growth and carcass performance, however this response has been inconsistent. Therefore, the objective of this study was to evaluate the effects of feeding high SID Trp:Lys ratios with RAC on growth and carcass performance. A total of 1,791 finishing pigs (PIC 1050×337; initially 110 kg BW) were used in a 27-d study. Pens of 25 or 26 pigs were allotted by initial BW and randomly assigned to 1 of 5 dietary treatments in a RCBD with 14 replications per treatment. The dietary treatments consisted of 5 SID Trp:Lys ratios (20, 22, 24, 26, and 28%). Corn-soybean meal-based diets were formulated to 0.90% SID Lys and contained 10 ppm ractopamine. At d 27, pigs were transported to a packing plant for processing and carcass data collection. Growth data were analyzed (GLIMMIX procedure of SAS) as a RCBD with pen as the experimental unit and initial BW as a covariate. Carcass data were analyzed with pen as the experimental unit and block × treatment as the random effect. Hot carcass weight served as a covariate for analysis of backfat, loin depth, and lean percentage. For overall growth performance, increasing SID Trp:Lys increased (linear, P< 0.0001) SID Trp g/kg of gain and SID Trp intake (Table 1); however, there were no evidence of treatment differences (P >0.10) for ADG or G:F. For carcass characteristics, increasing SID Trp:Lys decreased (linear; P=0.002) carcass yield and tended to decrease (P=0.078) lean percentage. There was no evidence of treatment differences (P >0.10) for HCW, loin depth, carcass ADG, or carcass feed efficiency. In summary, increasing SID Trp:Lys ratios above 20% in pigs fed RAC did not improve growth or carcass performance.

A total of 710 pigs (Line 400 × 200, DNA, Columbus, net energy (NE)) were used in two experiments (Exp. 1: initially, 6.3 ± 0.05 kg; Exp. 2: initially, 6.8 ± 0.05 kg) to evaluate the effects of two medium-chain fatty acid (MCFA) based products on nursery pig growth performance. Following their arrival at the nursery facility, pigs were randomized to pens (five pigs per pen) and allowed a 4-d acclimation period. Thereafter, pens of pigs were blocked by initial weight and randomized to dietary treatment. In Exp. 1, the dietary treatments were a dose titration of: 0%, 0.5%, 1.0%, or 2.0% MCFA-based additive, as well as a diet including 1.0% MCFA from a 1:1:1 blend of C6:0, C8:0, and C10:0. In Exp.2, dietary treatments consisted of a basal diet containing no MCFA (control), the control diet with a 1.0% inclusion of four different blends of MCFA, lactic acid, and monolaurin or a diet with 1.0% added MCFA (a 1:1:1 blend of C6:0, C8:0, and C10:0). The four blends consisted of 50% C6:0, 20% lactic acid, and increasing levels of monolaurin (0%, 10%, 20%, and 30%) at the expense of C12:0 (30%, 20%, 10%, and 0%). Treatment diets were formulated and manufactured in two dietary phases. Data were analyzed as a randomized complete block design with pen as the experimental unit. In Exp. 1, overall (days 0–34), increasing CaptiSURE increased (linear, P ≤ 0.014) average daily gain (ADG) and average daily feed intake (ADFI). Feed efficiency improved (quadratic, P = 0.002) with increasing CaptiSURE up to 1.0% of the diet with no benefit thereafter. There was no evidence for differences between pigs fed 1.0% CaptiSURE and pigs fed the 1.0% MCFA blend of C6:0, C8:0, and C10:0. In Exp. 2, overall (days 0–35), pigs fed the 1.0% 1:1:1 MCFA blend had increased (P < 0.034) ADFI and ADG resulting in 0.9 kg greater final weight (P = 0.014) compared with the control group. There was no evidence that the mean performance of pigs fed the four blends of MCFA, lactic acid, and monolaurin were different from the pigs fed the control diet. In summary, the addition of a 1.0% 1:1:1 blend of C6:0, C8:0, and C10:0 in nursery pig diets improved ADG, ADFI, and gain to feed ratio (G:F) compared with pigs fed the control diet. In addition, providing nursery pigs with the MCFA product CaptiSURE, up to 2% of the diet, resulted in linear improvements in ADG and ADFI. Altering the C12:0 to monolaurin ratio and adding lactic acid did not improve growth performance compared with pigs fed the control diet.

Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, lack of speech, and ataxia. The gene responsible for AS was identified as Ube3a and it encodes for E6AP, an E3 ubiquitin ligase. Currently, there is very little known about E6AP's mechanism of action in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. Elucidating the mechanistic action of E6AP would enhance our understanding of AS and drive current research into new avenues that could lead to novel therapeutic approaches that target E6AP's various functions. To facilitate the study of AS, we have generated a novel rat model in which we deleted the rat Ube3a gene using CRISPR. The AS rat phenotypically mirrors human AS with loss of Ube3a expression in the brain and deficits in motor coordination as well as learning and memory. This model offers a new avenue for the study of AS. Autism Res 2020, 13: 397-409. © 2020 International Society for Autism Research,Wiley Periodicals, Inc. LAY SUMMARY: Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, difficulty speaking, and ataxia. The gene responsible for AS was identified as UBE3A, yet very little is known about its function in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. To facilitate the study of AS, we have generated a novel rat model in which we deleted the rat Ube3a gene using CRISPR. The AS rat mirrors human AS with loss of Ube3a expression in the brain and deficits in motor coordination as well as learning and memory. This model offers a new avenue for the study of AS.

Weaned pigs (n = 308; 5.7 kg BW) were used in a 42-d study evaluating the effects of increasing injectable Fe dose at processing (d 3 after farrowing) on subsequent nursery pig performance and hematological criteria. Pigs were weaned on d 21 and allotted to pens based on previous Fe treatment with BW balanced across pens within a treatment with 5 or 6 pigs/pen and 10 pens/treatment. Treatments applied at processing were a negative control receiving no Fe injection or increasing injectable Fe (Gleptoforte, Ceva Animal Health, Lenexa, KS) to provide 50, 100, 150, 200-mg, or 200-mg plus 100-mg on d 11 post-farrowing. All pigs were fed the same diets after weaning containing 110 mg/kg of Fe from FeSO4 provided from the trace mineral premix. Growth data were analyzed as a CRD with pen as the experimental unit. Hematological criteria were analyzed as a repeated measure with pig as the experimental unit. Overall, increasing injectable Fe improved (linear; P < 0.05) ADG and ADFI (Table 1). Increasing injectable Fe up to 150 mg improved (quadratic; P = 0.011) G:F with a worsening G:F thereafter. There was no evidence of difference in growth performance (P > 0.10) between the 200-mg and the 200 + 100 mg injectable Fe treatments. Significant treatment×day interactions (P < 0.001) were observed for Hgb and Hct because pigs receiving an Fe injection less than 150-mg had increasing values through nursery while all other pigs had values remaining constant until d 63 after birth with no evidence of difference (P > 0.10) amongst all treatments at d 63 after birth. These results suggest that providing a 200-mg Fe injection at processing provides the greatest growth performance in the nursery and Fe in the diet is sufficient to meet the pigs’ Fe requirement to restore blood Fe status at the end of the nursery.

A total of 350 pigs (DNA 400×200, initial BW=6.3 kg) were used in a 34-d growth trial to evaluate the effects of a medium chain fatty acid (MCFA)-based feed additive in nursery pig diets. Following arrival to the nursery facility, pigs were randomized to pens (5 pigs per pen) and allowed a 4-d acclimation period. Thereafter, pens of pigs were blocked by BW and randomized to 1 of 5 dietary treatments (14 pens per treatment). Treatments were a dose response of 0, 0.5, 1.0, or 2.0% MCFA-based additive (CaptiSURE, Kemin Industries, Inc.; Des Moines, IA) as well as a treatment including 1.0% MCFA from a 1:1:1 blend of C6, C8, and C10 (Sigma Aldrich, St. Louis, MO). Treatment diets were formulated and manufactured in two dietary phases (d 0 to 13 and 13 to 34). Data were analyzed as a randomized complete block design with pen serving as the experimental unit. Overall (d 0 to 34), increasing CaptiSURE increased (linear, P ≤ 0.014) ADG and ADFI. Feed efficiency improved (quadratic, P = 0.002) with increasing CaptiSURE up to 1% of the diet with no benefit thereafter. As a result of the linear improvement in ADG, pigs fed 2.0% CaptiSURE were 1.8 kg heavier (P = 0.05) than pigs fed diets without MCFA at d 34. There was no evidence for differences between pigs fed 1.0% CaptiSURE and pigs fed the 1.0% MCFA blend of C6, C8, and C10 in phase 1, phase 2 or in overall performance. In summary, the addition of up to 2% of this MCFA-based additive in nursery pig diets resulted in linear improvements in ADG and ADFI. The MCFA-based feed additive also resulted in a similar improvement in growth performance as the C6, C8, and C10 MCFA blend when both were added at 1% of the diet.

Nursery pigs (n = 3,796; 17.6 kg BW) were used in a 22-d study evaluating the effects of increasing soybean meal on nursery pig performance. At 8 weeks of age, pens were allotted to treatment based on location in a randomized complete block design with 39 to 40 pigs per pen. Ten pens were placed on the positive control treatment and 12 pens placed on all other treatments. Experimental diets were fed in one phase (d 0 to 22) in meal form. Treatments included a positive control diet with 40% soybean meal and 1.8% choice white grease. Six diets were formulated with increasing soybean meal (17.5 to 40%) without added fat. Pigs were weighed on d 0, 13, and 22 to determine ADG, ADFI, G:F and NE efficiency. Growth data were analyzed as a randomized complete block design with pen as the experimental unit. Growth data were evaluated using linear and quadratic effects of soybean meal level and a pairwise comparison of the 40% soybean meal treatments with and without added fat. An outbreak of E. coli-associated disease was noted in the first 2 weeks of the experiment. Overall, increasing soybean meal tended to decrease (linear; P = 0.070) ADG, decreased (linear; P = 0.0001) ADFI, improved (linear; P = 0.0001) G:F and caloric efficiency, and reduced (linear; P = 0.050) removal rate (Table 1). Pigs fed the positive control had decreased (P = 0.019) ADFI and improved (P = 0.001) G:F compared to pigs fed the 40% soybean meal diet without added fat. These results suggest the net energy value for soybean meal was underestimated in diet formulation. Increasing soybean meal level in the diet reduced removal rate, suggesting soybean meal may provide added health benefits beside amino acids and energy.

Weaned pigs (n = 311; 5.9 kg BW) were used in a 59-d study evaluating the effects of Fe injection timing after birth on nursery pig performance and hematological criteria. Pigs were weaned at 21 d and allotted to pens based on preweaning Fe treatment with BW balanced across pens within a treatment with 5 or 6 pigs/pen and 10 pens/treatment. The preweaning treatments were a negative control receiving no Fe injection or 200-mg of injectable Fe (Gleptoforte, Ceva Animal Health, Lenexa, KS) provided in a single injection on d 2, 4, 6, 8, or 10 after birth. All pigs were fed common diets after weaning that contained 110 mg/kg of added Fe as FeSO4 provided from the trace mineral premix. Growth data were analyzed as a completely randomized design with pen as the experimental unit. Hematological criteria were measured as a repeated measure with pig as the experimental unit. Overall, increasing the age of pigs receiving a 200-mg Fe injection from 2 to 4 or 6 d after birth increased (quadratic; P = 0.013) d 80 ending BW with a decrease in BW when Fe was provided on d 8 or 10 (Table 1). Not providing an Fe injection after birth worsened (P < 0.05) ADG, ADFI, and d 80 ending BW. Significant treatment×day interactions (P < 0.001) were observed for Hgb and Hct values. These interactions occurred because pigs not receiving an Fe injection after birth had values that increased from d 21 to 35 while pigs receiving an Fe injection had values that decreased from d 21 to 35. While it is common practice to provide an Fe injection within the first 48 hours of birth, these results suggest delaying injection until d 4 or 6 may increase nursery final weight.

Liquid crystal elastomers (LCEs) are anisotropic polymeric materials. When subjected to an applied stress, liquid crystalline (LC) mesogens within the elastomeric polymer network (re)orient to the loading direction. The (re)orientation during deformation results in nonlinear stress-strain dependence (referred to as soft elasticity). Here, we uniquely explore mechanotropic phase transitions in elastomers with appreciable mesogenic content and compare these responses to LCEs in the polydomain orientation. The isotropic (amorphous) elastomers undergo significant directional orientation upon loading, evident in strong birefringence and x-ray diffraction. Functionally, the mechanotropic displacement of the elastomers to load is also nonlinear. However, unlike the analogous polydomain LCE compositions examined here, the isotropic elastomers rapidly recover after deformation. The mechanotropic orientation of the mesogens in these materials increase the toughness of these thiol-ene photopolymers by nearly 1300 % relative to a chemically similar elastomer prepared from wholly isotropic precursors.

Hayden E Hundley,1 Mark E Hudson,2,3 Ajay D Wasan,3,4 Trent D Emerick3,4 1Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 2Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; 3University of Pittsburgh Physicians, Pittsburgh, PA, USA; 4Division of Chronic Pain, Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Objective: The aim of this study is to identify scheduling inefficiencies and to develop a personalized schedule based on diagnosis, service time (face-to-face time between the patient and the provider), and patient wait time using a Gantt diagram in a chronic pain clinic.Design: This is an observational prospective cohort quality improvement (QI) study.Setting: This study was carried out at a single outpatient multidisciplinary pain management clinic in a university teaching hospital.Subjects: New and established chronic pain patients at the University of Pittsburgh Medical Center (UPMC) Montefiore Chronic Pain Clinic were recruited for this study.Methods: Time tracking data for each phase of clinic visit and pain-related diagnoses were collected from 81 patients on 5 clinic days in March 2016 for patient flow analysis.Results: A Gantt diagram was created using Microsoft Excel® software. Areas of overbooking and underbooking were identified. Median service times (minutes) differed dramatically based on the diagnosis and were highest for facial pain (23 [IQR, 15–31]) and chronic abdominal and/or pelvic pain (21.5 [IQR, 16–27]) and lowest for myalgia. Abdominal and/or pelvic pain and facial pain median service times consistently exceeded the 15-minute allocation for return visits.Conclusion: Schedule efficiency analysis using the Gantt diagram identified trends of overbooking and underbooking and inefficiencies in examination room utilization. A 15-minute appointment for all return patients is unrealistic due to variation of service times for some diagnoses. Scheduling appointments based on the diagnosis is an innovative approach that may reduce scheduling inefficiencies and improve patient satisfaction and the overall quality of care. To the best of our knowledge, this type of scheduling diagram has not been used in a chronic pain clinic. Keywords: quality of health care, chronic pain, outcome assessment, pain management, physician performance, referral and consultation, satisfaction, strategic planning&nbsp

A total of 2,673 mixed sex pigs (DNA 600 × PIC 1050; initially 21.4 kg BW) were used in a 117-d study to evaluate the effects of increasing SID Lysine:Calorie NE ratio on the growth performance and carcass characteristics of DNA sired pigs. Pens of pigs (30 pigs/pen) were blocked by BW and location and allotted to 1 of 4 dietary treatments with 18 pens per treatment. Treatments were 90%, 95%, 100%, or 105% of the 2016 PIC recommended SID Lysine:Calorie NE ratio for finishing gilts. Data were analyzed as a randomized complete-block design with pen as the experimental unit. Overall (d 0-117), increasing Lysine:Calorie NE tended to improve ADG (Linear; P = 0.077) and G:F (Linear; P = 0.053). Although there was an increase in ADG with increasing SID Lysine:Calorie NE, there was no evidence for a difference (P > 0.100) in final BW. The lack of BW response is most likely due to the lower (Quadratic; P < 0.008) removal rate as SID Lysine:Calorie NE increased. Carcass ADG (Linear; P < 0.064) tended to improve as SID Lysine: Calorie NE increased. An improvement in carcass G:F (Quadratic; P < 0.004) was observed as SID Lysine:Calorie NE increased to 100% PIC (2016) recommendations, with little improvement observed thereafter. No significant differences were observed in carcass yield, loin depth, back fat, or % lean. These results suggests that DNA sired pigs fed increasing SID Lysine:Calorie NE ratios tended to have improved growth performance with no impact on carcass quality.

Hypothalamic orexin neurons project to numerous brain areas, including the ventral tegmental area (VTA), which is involved in motivation and food-seeking behavior. Here we address how exogenously administered orexin-A and endogenous orexin 1 receptor (OX1R) activation in the VTA affects feeding behavior. We hypothesized that orexin-A and OX1R antagonist SB334867 delivered to the VTA, at doses that were subthreshold for effect when injected into the ventricle, would affect intake of palatable foods in multiple test situations. We first used a hedonic feeding model in which satiated rats selectively consume a high-fat diet (HFD). Intra-VTA orexin-A stimulated additional consumption of chow and increased HFD intake in this model. In ad libitum-fed rats given daily 30-min test sessions, intra-VTA orexin-A also increased intake of HFD and 0.1 M sucrose. Further analysis of licking patterns revealed that that VTA orexin-A increased meal size and licking burst size only toward the end of the meal. Consistent with this finding, a subthreshold dose of VTA orexin-A prevented intake suppression induced by gastrointestinal nutrient infusion. Surprisingly, intra-VTA orexin-A had no effect on operant responding for sucrose pellets on a progressive ratio schedule of reinforcement. A role for endogenous VTA OX1R stimulation is supported by our finding that bilateral VTA injection of the selective OX1R antagonist SB334867 suppressed 0.1 M sucrose intake. Together, our data suggest that OX1R activity in the VTA facilitates food intake, potentially by counteracting postingestive negative feedback that would normally suppress feeding later in a meal.

Phytases are important commercial enzymes that catalyze the dephosphorylation of myo-inositol hexakisphosphate (phytate) to its lower inositol phosphate (IP) esters, IP6 to IP1. Digestion of phytate by Citrobacter braakii 6-phytase deviates significantly from monophasic Michaelis-Menten kinetics. Analysis of phytate digestion using isothermal titration calorimetry (ITC) using the single injection method produced a thermogram with two peaks consistent with two periods of high enzyme activity. Continuous-flow electrospray ionization time-of-flight mass spectroscopy (ESI-ToF-MS) provided real-time analysis of phytase catalysis. It was able to show that the first two cleavage steps were rapid and concurrent but the third cleavage step from IP4 to IP3 was slow. The third (IP4 to IP3), fourth (IP3 to IP2) and fifth (IP2 to IP1) cleavages were effectively sequential due to the preferred association of the more phosphorylated species with the phytase catalytic site. This created a bottleneck during the cleavage of IP4 to IP3 until the point at which IP4 was exhausted and was followed by the rapid cleavage of IP3 to IP2, which was observed as the second peak in the ITC thermogram. This work illustrates the importance of an orthogonal approach when studying non-specific or complex enzyme catalyzed reactions.

A total of 300 nursery pigs (initially 5.9 ± 0.05 kg BW) were used in a 42-d growth trial to evaluate the effects of feeding a therapeutic level of chlortetracycline (CTC) with or without direct fed microbials (DFM) on growth performance and antimicrobial resistance (AMR) of fecal Escherichia coli. CTC is a broad-spectrum in-feed antibiotic commonly used in the swine industry. Weaned pigs (~21 d of age) were allotted to pens based on initial BW and fed a common starter diet for 4 d. Pens were then blocked by BW and allotted to dietary treatments in a completely randomized block design. Dietary treatments were arranged in a 2 × 3 factorial consisting of combinations of CTC (none vs. 400 mg/kg from days 0 to 42) and DFM (0 vs. 0.05% DFM 1 vs. 0.05% DFM 2). Fecal samples were collected from three randomly selected pigs from each pen on days 0, 21, and 42 for E. coli isolation and AMR determination. Overall, pigs fed diets containing CTC had improved (P < 0.001) ADG, ADFI, and BW compared to those not fed CTC with no evidence for any effect of either DFM 1 or DFM 2. Regardless of CTC, inclusion of DFM 2 in diets improved (P < 0.05) ADFI from days 0 to 14 and on day 14 BW compared to diets that did not include DFM 2. The addition of CTC with or without DFMs to nursery pig diets increased (P < 0.05) the probability of AMR to tetracycline and ceftiofur of fecal E. coli isolates, but this resistance generally decreased (P < 0.05) over time. A decrease (P < 0.05) in AMR to ampicillin and tetracycline (TET) throughout the trial was observed, while resistance to ceftriaxone decreased (P < 0.020) from days 0 to 21 and increased from days 21 to 42 amongst dietary treatments regardless of CTC or DFM inclusion in the diet. A CTC × DFM × day interaction (P < 0.015) was observed for streptomycin, whereby from days 21 to 42 AMR increased in diets containing either CTC or DFM 1 alone, but the combination decreased resistance. There was no evidence for any effect of DFMs on AMR of fecal E. coli isolates to any other antibiotics evaluated. In conclusion, therapeutic levels of added CTC with or without DFM inclusion improved nursery pig performance, but increased AMR of fecal E. coli isolates to TET and ceftiofur. A moderate improvement in intake and day 14 BW was observed when DFM 2 was included in the diet with or without CTC, but, except for streptomycin, there was no evidence that added dietary DFMs affected resistance of fecal E. coli to antibiotics.

Three studies evaluated the effects of added dietary salt on growth performance of pigs weighing 7 to 10, 11 to 30, and 27 to 65 kg. In experiment 1, 325 pigs were used with 5 pigs per pen and 13 pens per treatment. Pigs were fed a diet (0.39% Na and 0.78% Cl) for 7 d after weaning, then randomly assigned to diets with either 0, 0.20, 0.40, 0.60, or 0.80% added salt for 14 d. All diets were corn-soybean meal-based with 10% dried whey. Calculated Na concentrations were 0.11, 0.19, 0.27, 0.35, and 0.43% and calculated Cl concentrations were 0.23, 0.35, 0.47, 0.59, and 0.70%, respectively. Increasing salt increased (linear, P < 0.05) average daily gain (ADG) and gain to feed ratio (G:F). For ADG, the linear, quadratic polynomial (QP), and broken-line linear (BLL) models were competing with the breakpoint for the BLL at 0.59% salt. For G:F, the BLL reported a breakpoint at 0.33% while the QP indicated maximum G:F at 0.67% added salt. In experiment 2, 300 pigs were used in a 34-d trial with 5 pigs per pen and 12 pens per treatment. Pigs were weaned at 21 d of age and fed a phase 1 diet (0.50% Na and 0.67% Cl) for 11 d and then a phase 2 diet (0.35% Na and 0.59% Cl) for 14 d. Then pens of pigs were randomly assigned to corn-soybean meal-based diets containing 0.20, 0.35, 0.50, 0.65, or 0.80% added salt. Calculated dietary Na concentration were 0.10, 0.16, 0.22, 0.28, and 0.34% and calculated Cl concentrations were 0.23, 0.32, 0.41, 0.50, and 0.59%, respectively. Overall, ADG and G:F increased (quadratic, P < 0.07) with increasing added salt. For ADG, the QP and BLL had similar fit with the breakpoint for BLL at 0.51% added salt. For G:F, the BLL model predicted a break point at 0.35% added salt. In experiment 3, 1,188 pigs were used in a 44-d study with 27 pigs per pen and 11 pens per treatment. Pens of pigs were randomly assigned to corn-soybean meal-based diets containing 0.10, 0.33, 0.55, or 0.75% added salt. Calculated dietary Na concentrations were 0.10, 0.19, 0.28, and 0.36% and calculated Cl concentrations were 0.23, 0.36, 0.49, and 0.61%, respectively. Overall, there was no evidence to indicate that added salt above 0.10% of the diet affected growth. In conclusion, the BLL models suggested to maximize ADG for 7 to 10 and 11 to 30 kg pigs was 0.59% (0.34% Na and 0.58% Cl) and 0.51% added salt (0.22% Na and 0.42% Cl), respectively. There was no evidence that growth of 27 to 65 kg pigs was improved beyond 0.10% added salt (0.11% Na and 0.26% Cl).

Formaldehyde-based feed additives are approved in the US for Salmonella control and reducing bacterial contamination in animal feed. However, we hypothesize formaldehyde inclusion in swine diets may influence gut microbial composition due to its antimicrobial properties which might negatively influence microbial populations and pig growth performance. Also, formaldehyde inclusion in diets is known to reduce the dietary availability of amino acids. Therefore, our study was conducted to characterize if the effects of feed formaldehyde-treatment are due to influences on microbial population or diet amino acid (AA) sources. Dietary treatments were arranged in a (2 × 2) + 1 factorial with formaldehyde treatment (none vs. 1000 ppm formaldehyde) and crystalline AA inclusion (low vs. high) with deficient AA content plus a positive control diet to contain adequate AA content without dietary formaldehyde. Treating diets with formaldehyde reduced growth rate (P = 0.001) while the AA inclusion had no evidence of impact. Formaldehyde reduced feed bacterial content and altered fecal microbial communities (P

A total of 300 nursery pigs (initially 5.9 ± 0.05 kg BW) were used in a 42-d growth trial to evaluate the effects of feeding a therapeutic level of chlortetracycline (CTC) with or without direct fed microbials (DFM) on growth performance and antimicrobial resistance (AMR) of fecal Escherichia coli. CTC is a broad-spectrum in-feed antibiotic commonly used in the swine industry. Weaned pigs (~21 d of age) were allotted to pens based on initial BW and fed a common starter diet for 4 d. Pens were then blocked by BW and allotted to dietary treatments in a completely randomized block design. Dietary treatments were arranged in a 2 × 3 factorial consisting of combinations of CTC (none vs. 400 mg/kg from days 0 to 42) and DFM (0 vs. 0.05% DFM 1 vs. 0.05% DFM 2). Fecal samples were collected from three randomly selected pigs from each pen on days 0, 21, and 42 for E. coli isolation and AMR determination. Overall, pigs fed diets containing CTC had improved (P < 0.001) ADG, ADFI, and BW compared to those not fed CTC with no evidence for any effect of either DFM 1 or DFM 2. Regardless of CTC, inclusion of DFM 2 in diets improved (P < 0.05) ADFI from days 0 to 14 and on day 14 BW compared to diets that did not include DFM 2. The addition of CTC with or without DFMs to nursery pig diets increased (P < 0.05) the probability of AMR to tetracycline and ceftiofur of fecal E. coli isolates, but this resistance generally decreased (P < 0.05) over time. A decrease (P < 0.05) in AMR to ampicillin and tetracycline (TET) throughout the trial was observed, while resistance to ceftriaxone decreased (P < 0.020) from days 0 to 21 and increased from days 21 to 42 amongst dietary treatments regardless of CTC or DFM inclusion in the diet. A CTC × DFM × day interaction (P < 0.015) was observed for streptomycin, whereby from days 21 to 42 AMR increased in diets containing either CTC or DFM 1 alone, but the combination decreased resistance. There was no evidence for any effect of DFMs on AMR of fecal E. coli isolates to any other antibiotics evaluated. In conclusion, therapeutic levels of added CTC with or without DFM inclusion improved nursery pig performance, but increased AMR of fecal E. coli isolates to TET and ceftiofur. A moderate improvement in intake and day 14 BW was observed when DFM 2 was included in the diet with or without CTC, but, except for streptomycin, there was no evidence that added dietary DFMs affected resistance of fecal E. coli to antibiotics.