KRASG12D inhibition reprograms the microenvironment of early and advanced pancreatic cancer to promote FAS-mediated killing by CD8+ T cells.

The KRASG12D mutation is present in nearly half of pancreatic adenocarcinomas (PDAC). We investigated the effects of inhibiting the KRASG12D mutant protein with MRTX1133, a non-covalent small molecule inhibitor of KRASG12D, on early and advanced PDAC and its influence on the tumor microenvironment. Employing 16 different models of KRASG12D-driven PDAC, we demonstrate that MRTX1133 reverses early PDAC growth, increases intratumoral CD8+ effector T cells, decreases myeloid infiltration, and reprograms cancer-associated fibroblasts. MRTX1133 leads to regression of both established PanINs and advanced PDAC. Regression of advanced PDAC requires CD8+ T cells and immune checkpoint blockade (ICB) synergizes with MRTX1133 to eradicate PDAC and prolong overall survival. Mechanistically, inhibition of KRASG12D in advanced PDAC and human patient derived organoids induces FAS expression in cancer cells and facilitates CD8+ T cell-mediated death. Collectively, this study provides a rationale for a synergistic combination of MRTX1133 with ICB in clinical trials.

Oncogenic Kras G12D specific non-covalent inhibitor reprograms tumor microenvironment to prevent and reverse early pre-neoplastic pancreatic lesions and in combination with immunotherapy regresses advanced PDAC in a CD8 + T cells dependent manner.

Pancreatic ductal adenocarcinoma (PDAC) is associated with mutations in Kras, a known oncogenic driver of PDAC; and the KRAS G12D mutation is present in nearly half of PDAC patients. Recently, a non-covalent small molecule inhibitor (MRTX1133) was identified with specificity to the Kras G12D mutant protein. Here we explore the impact of Kras G12D inhibition by MRTX1133 on advanced PDAC and its influence on the tumor microenvironment. Employing different orthotopic xenograft and syngeneic tumor models, eight different PDXs, and two different autochthonous genetic models, we demonstrate that MRTX1133 reverses early PDAC growth, increases intratumoral CD8 + effector T cells, decreases myeloid infiltration, and reprograms cancer associated fibroblasts. Autochthonous genetic mouse models treated with MRTX1133 leads to regression of both established PanINs and advanced PDAC. Regression of advanced PDAC requires CD8 + T cells and immune checkpoint blockade therapy (iCBT) synergizes with MRTX1133 to eradicate PDAC and prolong overall survival. Mechanistically, inhibition of mutant Kras in advanced PDAC and human patient derived organoids (PDOs) induces Fas expression in cancer cells and facilitates CD8 + T cell mediated death. These results demonstrate the efficacy of MRTX1133 in different mouse models of PDAC associated with reprogramming of stromal fibroblasts and a dependency on CD8 + T cell mediated tumor clearance. Collectively, this study provides a rationale for a synergistic combination of MRTX1133 with iCBT in clinical trials.

Dermal αSMA+ myofibroblasts orchestrate skin wound repair via ß1 integrin and independent of type I collagen production.

Skin wound repair is essential for organismal survival and failure of which leads to non-healing wounds, a leading health issue worldwide. However, mechanistic understanding of chronic wounds remains a major challenge due to lack of appropriate genetic mouse models. αSMA+ myofibroblasts, a unique class of dermal fibroblasts, are associated with cutaneous wound healing but their precise function remains unknown. We demonstrate that genetic depletion of αSMA+ myofibroblasts leads to pleiotropic wound healing defects, including lack of reepithelialization and granulation, dampened angiogenesis, and heightened hypoxia, hallmarks of chronic non-healing wounds. Other wound-associated FAP+ and FSP1+ fibroblasts do not exhibit such dominant functions. While type I collagen (COL1) expressing cells play a role in the repair process, COL1 produced by αSMA+ myofibroblasts is surprisingly dispensable for wound repair. In contrast, we show that ß1 integrin from αSMA+ myofibroblasts, but not TGFßRII, is essential for wound healing, facilitating contractility, reepithelization, and vascularization. Collectively, our study provides evidence for the functions of myofibroblasts in ß1 integrin-mediated wound repair with potential implications for treating chronic non-healing wounds.

Patients' perspectives regarding induction of labor in the absence of maternal and fetal indications: are our patients ready for the ARRIVE trial?

BACKGROUND: After careful review of the ARRIVE trial (A Randomized Trial of Induction Versus Expectant Management) data, induction of labor prior to one's due date in the absence of maternal and fetal indications (which the American College of Obstetricians and Gynecologists currently refers to as "elective") is now endorsed as a "reasonable" option by the American College of Obstetricians and Gynecologists (ACOG). As a result, there has been much discussion among providers regarding how best to operationalize this ACOG recommendation into shared decision making regarding delivery planning. However, we lack a formal understanding of the perspectives of patients themselves on this topic. OBJECTIVE: To assess patient understanding and preference for induction of labor prior to one's due date. MATERIALS AND METHODS: We conducted an anonymous, cross-sectional survey of women in their third trimester of pregnancy presenting for routine obstetric care in August 2018. The survey included a series of questions designed to assess basic demographics, obstetric history, and patient understanding and opinions about the practice of induction of labor, with a focus on induction of labor prior to one's due date in the absence of maternal and fetal indications. RESULTS: A total of 108 women were approached for participation, and 100 women participated in this survey (93% participation). Of the participants, 99% were supportive of induction of labor for fetal indications, and 96% were supportive for maternal indications prior to one's due date. In contrast, 54% of participants were not interested in induction of labor in the absence of maternal and fetal indications prior to one's due date. Women opposed to induction of labor in the absence of maternal and fetal indications were almost 4 times more likely to be concerned about the possibility that induction of labor in the absence of maternal and fetal indications could cause fetal harm (odds ratio, 3.9; confidence interval, 1.2-13.2). CONCLUSION: Nearly all women surveyed in our pilot study were interested in induction of labor prior to one's due date for maternal or fetal indications. 46% of those surveyed were interested in induction of labor in the absence of maternal and fetal indications prior to their due date. Concern about potential fetal harm was more likely among women opposed to induction of labor in the absence of maternal and fetal indications. As providers discuss delivery planning with their patients, these results may provide a useful context for operationalizing and individualizing the results of the ARRIVE trial for their patients.

Review: innovation through research in the North American pork industry.

This article involved a broad search of applied sciences for milestone technologies we deem to be the most significant innovations applied by the North American pork industry, during the past 10 to 12 years. Several innovations shifted the trajectory of improvement or resolved significant production limitations. Each is being integrated into practice, with the exception being gene editing technology, which is undergoing the federal approval process. Advances in molecular genomics have been applied to gene editing for control of porcine reproductive and respiratory syndrome and to identify piglet genome contributions from each parent. Post-cervical artificial insemination technology is not novel, but this technology is now used extensively to accelerate the rate of genetic progress. A milestone was achieved with the discovery that dietary essential fatty acids, during lactation, were limiting reproduction. Their provision resulted in a dose-related response for pregnancy, pregnancy maintenance and litter size, especially in maturing sows and ultimately resolved seasonal infertility. The benefit of segregated early weaning (12 to 14 days of age) was realized for specific pathogen removal for genetic nucleus and multiplication. Application was premature for commercial practice, as piglet mortality and morbidity increased. Early weaning impairs intestinal barrier and mucosal innate immune development, which coincides with diminished resilience to pathogens and viability later in life. Two important milestones were achieved to improve precision nutrition for growing pigs. The first involved the updated publication of the National Research Council nutrient requirements for pigs, a collaboration between scientists from America and Canada. Precision nutrition advanced further when ingredient description, for metabolically available amino acids and net energy (by source plant), became a private sector nutrition product. The past decade also led to fortuitous discoveries of health-improving components in ingredients (xylanase, soybeans). Finally, two technologies converged to facilitate timely detection of multiple pathogens in a population: oral fluids sampling and polymerase chain reaction (PCR) for pathogen analysis. Most critical diseases in North America are now routinely monitored by oral fluid sampling and prepared for analysis using PCR methods.

Effect of lower-energy, higher-fiber diets on pigs divergently selected for residual feed intake when fed higher-energy, lower-fiber diets.

Residual feed intake (RFI) is the difference between observed and predicted feed intake of an animal, based on growth and maintenance requirements. In Yorkshire pigs, divergent selection for increased (Low RFI) and decreased (High RFI) RFI was carried out over 10 generations (G) while feeding a corn- and soybean-meal-based, higher-energy, lower-fiber (HELF) diet. In G8 to G10, representing 4 replicates, barrows and gilts (n = 649) of the RFI lines were fed the HELF diet and a diet incorporating coproducts that were lower in energy and higher in dietary fiber (LEHF). The diets differed in ME, 3.32 vs. 2.87 Mcal/kg, and in neutral detergent fiber (NDF), 9.4% vs. 25.9%, respectively. The impact of the LEHF diet on 1) performance and growth, 2) diet digestibility, 3) genetic parameter estimates, and 4) responses to selection for RFI, when fed the HELF, was assessed. In general, the LEHF diet reduced the performance of both lines. When fed the HELF diet, the Low RFI pigs had lower (P < 0.05) ADFI (-12%), energy intake (-12%), ADG (-6%), and backfat depth (-12%); similar (P > 0.05) loin muscle area (LMA; +5%); and greater (P < 0.05) feed efficiency (i.e., 8% higher G:F and 7% lower RFI) than the High RFI line. These patterns of line differences were still present under the LEHF diet but differences for ADFI (-11%), energy intake (-10%), G:F (+2%), and RFI (-6%) were reduced compared to the HELF diet. Apparent total tract digestibility (ATTD) of the HELF and LEHF diets was assessed using 116 barrows and gilts from G8. When fed the HELF diet, ATTD of DM, GE, N, and NDF were similar between lines (P ≥ 0.27), but when fed the LEHF diet, the Low RFI pigs had greater digestibility (7%, 7%, 10%, and 32%) than the High RFI line (P ≤ 0.04). To measure responses to selection for RFI and estimate genetic parameters, data from all 10 generations were used (HELF; n = 2,310; LEHF, n = 317). Heritability estimates of performance traits ranged from 0.19 to 0.63, and genetic correlations of traits between diets were high and positive, ranging from 0.87 (RFI) to 0.99 (LMA). By G10, RFI in the Low RFI line was 3.86 and 1.50 genetic SD lower than in the High RFI line when fed the HELF and LEHF diets, respectively. Taken together, the results of this study demonstrate that responses to selection for RFI when fed a HELF diet are not fully realized when pigs are fed an extremely LEHF diet. Thus, feeding diets that differ from those used for selection may not maximize genetic potential for feed efficiency.

Effects of heat stress and insulin sensitizers on pig adipose tissue.

Heat stress (HS) negatively impacts several swine production variables, including carcass fat quality and quantity. Pigs reared in HS have more adipose tissue than energetically predicted, explainable, in part, by HS-induced hyperinsulinemia. Study objectives were to evaluate insulin's role in altering fat characteristics during HS via feeding insulin-sensitizing compounds. Forty crossbred barrows (113 ± 9 kg BW) were randomly assigned to one of five environment by diet treatments: 1) thermoneutral (TN) fed ad libitum (TNAL), 2) TN and pair-fed (TNPF), 3) HS fed ad libitum (HSAL), 4) HS fed ad libitum with sterculic oil (SO) supplementation (HSSO; 13 g/d), and 5) HS fed ad libitum with dietary chromium (Cr) supplementation (HSCr; 0.5 mg/d; Kemin Industries, Des Moines, IA). The study consisted of three experimental periods (P). During P0 (2 d), all pigs were exposed to TN conditions (23 ± 3 °C, 68 ± 10% RH) and fed ad libitum. During P1 (7 d), all pigs received their respective dietary supplements, were maintained in TN conditions, and fed ad libitum. During P2 (21 d), HSAL, HSSO, and HSCr pigs were fed ad libitum and exposed to cyclical HS conditions (28 to 33 °C, 58 ± 10% RH). The TNAL and TNPF pigs remained in TN conditions and were fed ad libitum or pair-fed to their HSAL counterparts. Rectal temperature (TR), respiration rate (RR), and skin temperature (TS) were obtained daily at 0600 and 1800 h. At 1800 h, HS exposed pigs had increased TR, RR, and TS relative to TNAL controls (1.13 °C, 48 bpm, and 3.51 °C, respectively; P < 0.01). During wk 2 and 3 of P2, HSSO pigs had increased 1800 h TR relative to HSAL and HSCr (~0.40 and ~0.42 °C, respectively; P ≤ 0.05). Heat stress decreased ADFI and ADG compared to TNAL pigs (2.24 vs. 3.28 and 0.63 vs. 1.09 kg/d, respectively; P < 0.01) and neither variable was affected by SO or Cr supplementation. Heat stress increased or tended to increase moisture content of abdominal (7.7 vs. 5.9%; P = 0.07) and inner s.c. (11.4 vs. 9.8%; P < 0.05) adipose depots compared to TNAL controls. Interestingly, TNPF pigs also had increased adipose tissue moisture content and this was most pronounced in the outer s.c. depot (15.0 vs. 12.2%; P < 0.01) compared to TNAL pigs. Heat stress had little or no effect on fatty acid composition of abdominal, inner, and outer s.c. adipose tissue depots. In summary, the negative effects of HS on fat quality do not appear to be fatty acid composition related, but may be explained by increased adipose tissue moisture content.

Impact of health challenges on pig growth performance, carcass characteristics, and net returns under commercial conditions.

Understanding how disease affects commercial production is imperative for pig producers to quantify its full impact on pig performance, carcass quality, and net returns. The objective of this experiment was to assess the productivity and economic importance of naturally occurring health challenges (HC) under commercial conditions. Three 1,000 pig grow-finish facilities received 936 pigs each. The experimental period started approximately 34 d post placement at an average start BW of 13.1 ± 0.2 kg. Barns were characterized based on the relative HC, determined by diagnostic assessments as the main characterization tool, along with other health indicators. Barns were characterized as low challenge health (LCh), moderate challenge health (MCh), and high challenge health (HCh). All barns tested positive for porcine reproductive and respiratory syndrome virus infection prior to the start of the experiment. Additionally, the MCh and HCh barns experienced influenza type A virus of swine. Similar to commercial production conditions, the disease challenge was not imposed but rather occurred naturally. Reduced ADG, ADFI, and G:F were observed with an increased HC (P < 0.001). Similarly, mortality was increased when the HC increased (P < 0.001). Decreased ADG increased days to achieve harvest BW, by 10 and 15 d in the MCh and HCh treatments compared with LCh, respectively (P < 0.001). No differences were observed for percent lean, loin depth, or fat depth (P > 0.10). The economic impact of the HC was assessed by applying these growth performance data to two economic models encompassing the two main marketing methods used by U.S. pig producers: fixed-weight and fixed-time. Financial losses attributed to the variation in disease severity that occurred in the present study ranged from $8.49 and $26.10 U.S. dollars (USD)/pig marketed using a fixed-market weight model, or between $11.02 and $29.82 USD/pig using a fixed-time model, depending on feed costs and market hog prices. In conclusion, increasing severity of HC under commercial conditions reduced ADG by 8% and 14% and resulted in mortality as high as 19.9%. Losses of $8.49 to $29.82/pig marketed underscore the potential magnitude of the economic impact of mixed etiology concurrent diseases in pork production.

The digestible energy, metabolizable energy, and net energy content of dietary fat sources in thirteen- and fifty-kilogram pigs.

The objective was to determine the energy concentration of a diverse array of dietary fat sources and, from these data, develop regression equations that explain differences based on chemical composition. A total of 120 Genetiporc 6.0 × Genetiporc F25 (PIC, Inc., Hendersonville, TN) individually housed barrows were studied for 56 d. These barrows (initial BW of 9.9 ± 0.6 kg) were randomly allotted to 1 of 15 dietary treatments. Each experimental diet included 95% of a corn-soybean meal basal diet plus 5% either corn starch or 1 of 14 dietary fat sources. The 14 dietary fat sources (animal-vegetable blend, canola oil, choice white grease source A, choice white grease source B, coconut oil, corn oil source A, corn oil source B, fish oil, flaxseed oil, palm oil, poultry fat, soybean oil source A, soybean oil source B, and tallow) were selected to provide a diverse and robust range of unsaturated fatty acid:SFA ratios (U:S). Pigs were limit-fed experimental diets from d 0 to 10 and from d 46 to 56, providing a 7-d adaption for fecal collection on d 7 to 10 (13 kg BW) and d 53 to 56 (50 kg BW). At 13 kg BW, the average energy content of the 14 sources was 8.42 Mcal DE/kg, 8.26 Mcal ME/kg, and 7.27 Mcal NE/kg. At 50 kg BW, the average energy content was 8.45 Mcal DE/kg, 8.28 Mcal ME/kg, and 7.29 Mcal NE/kg. At 13 kg BW, the variation of dietary fat DE content was explained by DE (Mcal/kg) = 9.363 + [0.097 × (FFA, %)] - [0.016 × omega-6:omega-3 fatty acids ratio] - [1.240 × (arachidic acid, %)] - [5.054 × (insoluble impurities, %)] + [0.014 × (palmitic acid, %)] ( = 0.008, = 0.82). At 50 kg BW, the variation of dietary fat DE content was explained by DE (Mcal/kg) = 8.357 + [0.189 × U:S] - [0.195 × (FFA, %)] - [6.768 × (behenic acid, %)] + [0.024 × (PUFA, %)] ( = 0.002, = 0.81). In summary, the chemical composition of dietary fat explained a large degree of the variation observed in the energy content of dietary fat sources at both 13 and 50 kg BW.

The composition of dietary fat alters the transcriptional profile of pathways associated with lipid metabolism in the liver and adipose tissue in the pig.

The objective was to investigate the of effect chemical composition of dietary fat on transcription of genes involved in lipid metabolism in adipose tissue and the liver via transcriptional profiling in growing pigs. A total of 48 Genetiporc 6.0 × Genetiporc F25 (PIC, Inc., Hendersonville, TN) barrows (initial BW of 44.1 ± 1.2 kg) were randomly allotted to 1 of 6 dietary treatments. Each experimental diet included 95% of a corn-soybean meal basal diet and 5% cornstarch (control; CNTR), animal-vegetable blend (AV), coconut oil (COCO), corn oil (COIL), fish oil (FO), or tallow (TAL). Pigs were sacrificed on d 10 (final BW of 51.2 ± 1.7 kg) to collect tissues. Expression normalization across samples was performed by calculating a delta cycle threshold (ΔCt) value using . Delta delta cycle threshold (ΔΔCt) values were expressed relative to the CNTR treatment. In adipose tissue, adding dietary fat, regardless of the source, decreased the mRNA abundance of compared with the CNTR ( = 0.014). Pigs fed a COIL-based diet tended to have greater adipose tissue expression of ( = 0.071) than pigs fed the other dietary fat sources tested. Abundance of mRNA was greater in adipose tissue of barrows a fed COIL-based diet than barrows fed CNTR or FO-based diets ( = 0.047). In the liver, adding dietary fat, regardless of source, increased the mRNA abundance of , , , , , and ( ≤ 0.020) and tended to increase the abundance of ( = 0.071) and ( = 0.086) compared with the CNTR. Pigs fed a TAL-based diet had greater hepatic transcription of than pigs fed CNTR-, COCO-, or FO-based diets ( = 0.013). Hepatic transcription of tended to be greater in pigs fed COCO than in pigs fed other dietary fat sources ( = 0.074). Dietary omega-3 fatty acid content tended to negatively correlate with mRNA abundance of ( = 0.065) in adipose tissue and ( = 0.063) in the liver. Dietary fat SFA content was negatively correlated with in the liver ( ≤ 0.039). Dietary fat MUFA content tended to be positively correlated with , , and mRNA abundance in the liver ( ≤ 0.100). To conclude, the intake of omega-3 fatty acids suppressed the mRNA abundance of genes involved in lipolysis in both adipose tissue and the liver. Dietary SFA are greater inhibitors of lipogenesis in adipose tissue than omega-6 fatty acids. Intake of medium-chain fatty acids alters hepatic lipid metabolism differently than intake of long-chain fatty acids.

SID lysine requirement of immunologically and physically castrated male pigs during the grower, early and late finisher periods.

The main objective of this experiment was to determine the standardized ileal digestible (SID) Lys requirement of immunologically castrated (IC) and physically castrated (PC) male pigs during 3 growth phases. An additional objective was to compare the ADFI of PC and IC after the second anti-gonadotropin releasing factor (GnRF) injection. Three hundred male pigs (PIC 359 × C29), 150 each of IC and PC, were allotted to 1 of 5 treatments: 80, 90, 100, 110, or 120% of the estimated Lys requirement using the modeling program. Pigs remained on the same treatment throughout each of the 3 phases. Lysine requirements were determined at 3 stages of growth starting at a BW of 30.0 ± 0.8, 64.7 ± 1.4, and 111.9 ± 1.9 kg for IC and 32.4 ± 0.6, 69.8 ± 1.0, and 114.5 ± 1.3 kg for PC. Anti-GnRF injections were administered to IC at 11.5 and 19 wk (average BW = 96.3 ± 1.8 kg) of age. The one-slope broken line regression and quadratic plateau models were used, and the best model was selected based on the Akaike information criterion. The IC SID Lys requirements based on ADG were 1.03, 0.97, and 0.55% and for G:F, the requirements were 0.99, 0.72, and 0.55% for phases 1, 2, and 3, respectively. For PC, the SID Lys requirements based on ADG were 0.86, 0.62, and 0.47% and for G:F were 0.86, 0.58, and 0.47% for phases 1, 2, and 3, respectively. Immunologically castrated pigs had greater SID Lys requirements for phases 1 and 2 compared to PC (0.17 and 0.35% points greater for ADG and 0.13 and 0.14% points greater for G:F for phases 1 and 2, respectively). After the second injection, when IC pigs are believed to become physiologically more similar to PC pigs, the SID Lys requirements continue to be greater for IC (0.55 vs. 0.47% for both ADG and G:F). The ADFI of IC increased 4 d after the second injection relative to PC. By 2 wk post second injection, the ADFI of IC exceeded that of PC ( < 0.05). Adopting immunological castration as a management tool requires an understanding that IC need to be fed differently compared to PC, to maximize growth performance. Immunologically castrated pigs have a greater SID Lys requirement throughout the grower and finishing periods compared to the PC.

Digestion and nitrogen balance using swine diets containing increasing proportions of coproduct ingredients and formulated using the net energy system.

Rising feed expenditures demand that our industry pursues strategies to lower the cost of production. One option is the adoption of the NE system, although many producers are hesitant to proceed without proof that NE estimates are reliable. The objective of this experiment was to compare the apparent total tract digestibility (ATTD) of energy and nutrients and the N retention (NR) of diets formulated using the NE system with increasing quantities of coproduct ingredients. The 5 dietary treatments included a control corn-soybean meal diet (CTL); the CTL plus 6% each of corn distiller's dried grains with solubles (DDGS), corn germ meal, and wheat middlings and NE equal to the CTL by adding soybean oil (CONS-18); the CONS-18 diet, without oil added, with NE content lower than the CTL (DECL-18); the CTL plus 12% each of corn DDGS, corn germ meal, and wheat middlings and NE equal to the CTL by adding soybean oil (CONS-36); and the CONS-36 diet, without oil added, with NE content lower than the CTL (DECL-36). Diets were formulated for both the growing period (GP; 40 to 70 kg) and the finishing period (FP; 70 to 110 kg). Forty gilts (PIC 337 × C22 or C29; 38.5 ± 0.4 kg initial BW) were randomly assigned to treatment and received feed and water ad libitum (8 pigs per treatment). For the last 13 d of the GP and FP, pigs were transferred to metabolism crates, where 2 total urine and fecal collections (d 4 to 6 and d 11 to 13) were performed. The GP fed diets with coproduct ingredients had lower ATTD of DM, N, and GE than those fed the CTL ( < 0.050). The ATTD of N and GE progressively decreased as coproduct inclusion increased from 0 to 18 to 36% in the FP ( < 0.010). In the GP and FP, there were no differences in ATTD of DM, N, or GE between CONS-18 and DECL-18 or between CONS-36 and DECL-36 ( > 0.050). The NR declined on all coproduct diets in the GP ( = 0.010) and tended to decline in the FP ( = 0.079). There were no differences in NR between CONS-18 and DECL-18 or between CONS-36 and DECL-36 ( > 0.050). In conclusion, digestion of diets containing up to 36% coproducts and formulated using NE resulted in expected DE and ME values; NR of diets with coproducts was lower than that of the simple CTL, which is not related to the accuracy of the energy estimations but rather to other factors such as imbalances in the AA concentrations or to postabsorptive energy metabolism, factors not accounted for by the current energy systems approach.

Porcine Reproductive and Respiratory Syndrome virus reduces feed efficiency, digestibility, and lean tissue accretion in grow-finish pigs.

Porcine reproductive and respiratory syndrome (PRRS) virus is a major swine virus that causes reproductive impairment in sows, as well as respiratory disease, reduction in growth rates, and mortalities in all ages of pigs. The objective of this study was to quantify the impact PRRS has on grower-finisher pig feed efficiency and tissue accretion rates. Thirty PRRS naïve, littermate pairs of maternal line Choice Genetics gilts (33.6 ± 0.58 kg BW) were selected and pairs split across 2 barns consisting of 5 pens (n = 6 pigs/pen per barn). Pigs in both barns were fed corn-soybean-DDGS diets ad libitum. All pigs in one barn were inoculated (CHAL) via an i.m. injection of a live PRRS strain isolated from the region (0 d post inoculation, dpi), while pigs in the other barn were given a saline control injection (CONT). Pig performance (ADG, ADFI, G:F) was assessed from 35 kg BW until each group reached market BW (128 kg). Additionally, longitudinal apparent total tract digestibility (ATTD) and body composition was assessed using Dual-energy X-ray absorptiometry (DXA) post inoculation (dpi) to estimate lean, protein, fat and bone accretion rates. Serological data from CHAL pigs showed that PRRS titers peaked 7 dpi and these pigs seroconverted by 35 dpi. According to both genomic and protein PRRS titers, CONT pigs were naïve to CHAL throughout the study. The PRRS infection reduced (P < 0.001) ATTD of dry matter, energy and nitrogen by 3 to 5% at 21 dpi and the reduction in ATTD persisted after 65 dpi. Compared to the CONT, CHAL pigs had decreased ADG (0.89 vs. 0.80 kg/d, P < 0.001), ADFI (2.05 vs. 1.93 kg/d, P < 0.001), and G:F (0.44 vs. 0.41 kg/d, P < 0.001) over the entire test period. The CHAL pigs also had attenuated DXA predicted whole body accretion of lean (547 vs. 633 g/d, P = 0.001), protein (109 vs. 126 g/d, P = 0.001) and fat (169 vs. 205 g/d, P = 0.001) compared to their CONT counterparts from dpi 0 to 80. Based on carcass data at slaughter (and consistent with the DXA data), CHAL pigs had leaner carcasses and reduced yields. These data clearly demonstrate that PRRS infection reduces digestibility, feed efficiency and protein accretion rates in grower-finisher pigs.

Effect of selection for residual feed intake during the grow/finish phase of production on sow reproductive performance and lactation efficiency.

As feed costs continue to rise and efficiency during finishing is emphasized, the impact of selecting for more efficient grow/finish pigs on reproductive performance and feed efficiency of sows must be evaluated. Therefore, the objectives of this study were to evaluate correlated responses for sow reproductive performance and lactation feed efficiency to selection for residual feed intake (RFI) during the grow/finish phase of production (RFI) in 2 selection lines of pigs developed at Iowa State University (Ames, IA) and to estimate heritabilities of these traits. One line was selected over 7 generations for decreased RFIG/F (low RFI [LRFI] line) and the other line was randomly selected for 5 generations and then selected for increased RFIG/F (high RFI [HRFI] line). After 7 generations of selection, LRFI sows had 1.0 more piglets farrowed ( = 0.11) compared with HRFI sows, 1.3 more pigs born alive ( < 0.05), similar farrowing survival, 0.4 fewer mummies ( < 0.01), and more piglets weaned, both by litter (1.6 more; < 0.01) and by sow (1.1 more; < 0.01). Low RFI sows consumed 25 kg less feed and lost 9.8 kg more BW, 7.0 kg more fat mass, and 3.1 mm more backfat than HRFI sows ( < 0.001) during lactation. Although LRFI sows had a greater negative energy balance (-19.8 vs. -8.0 MJ ME/d; < 0.001), they had better RFI during lactation (-28.6 vs. 8.2 kg; < 0.0001), and the trend was for LRFI sows to have better lactation efficiency (61.3 vs. 57.8%; = 0.47) than HRFI sows. Heritabilities for sow weights, sow body composition, sow maintenance requirements (estimated from BW), and piglet birth weight were high ( > 0.4, SE < 0.07). Traits pertaining to piglet growth during lactation and mobilization of body tissue of the sow were moderately heritable (0.2 < < 0.4, SE < 0.07). In conclusion, selection for decreased RFI has favorably affected piglet performance and lactation efficiency but has unfavorably affected sow body condition loss and energy balance during lactation. These results indicate that pigs selected for increased efficiency during grow-finish are better able to direct resources where needed during other life history phases, that is, reproduction and lactation.

Does heat stress alter the pig's response to dietary fat?

Heat stress (HS) results in major losses to the pork industry via reduced growth performance and, possibly, carcass fat quality. The experimental objective was to measure the effects of HS on the pig's response to dietary fat in terms of lipid digestion, metabolism, and deposition over a 35-d finishing period. A total of 96 PIC 337 × C22/C29 (PIC, Inc., Hendersonville, TN) barrows (initial BW of 100.4 ± 1.2 kg) were randomly allotted to 1 of 9 treatments arranged as a 3 × 3 factorial: thermoneutral (TN; constant 24°C; ad libitum access to feed), pair-fed thermoneutral (PFTN; constant 24°C; limit fed based on previous HS daily feed intake), or HS (cyclical 28°C nighttime, 33°C from d 0 to 7, 33.5°C from d 7 to 14, 34°C from d 14 to 21, 34.5°C from d 21 to 28, and 35°C from d 28 to 35 daytime; ab libitum access to feed) and diet (a corn-soybean meal-based diet with 0% added fat [CNTR], CNTR with 3% added tallow [TAL; iodine value {IV} = 41.8], or CNTR with 3% added corn oil [CO; IV = 123.0]). No interactions between environment and diet were evident for any major response criteria ( ≥ 0.063). Rectal temperature increased due to HS (39.0°C for HS, 38.1°C for TN, and 38.2°C for PFTN; < 0.001). Heat stress decreased ADFI (27.8%; < 0.001), ADG (0.72 kg/d for HS, 1.03 kg/d for TN, and 0.78 kg/d for PFTN; < 0.001), and G:F (0.290 for HS, 0.301 for TN, and 0.319 for PFTN; = 0.006). Heat stress barrows required 1.2 Mcal of ME intake more per kilogram of BW gain than PFTN ( < 0.001). Heat stress tended to result in the lowest apparent total tract digestibility of acid hydrolyzed ether extract (AEE; 59.0% for HS, 60.2% for TN, and 61.4% for PFTN; = 0.055). True total tract digestibility (TTTD) of AEE of CO-based diets (99.3%) was greater than that of CNTR (97.3%) and TAL-based diets (96.3%; = 0.012). Environment had no impact on TTTD of AEE ( = 0.118). Environment had no impact on jowl IV at market (69.2 g/100 g for HS, 69.3 g/100 g for TN, and 69.8 g/100 g for PFTN; = 0.624). Jowl IV at market increased with increasing degree of unsaturation of the dietary fat (68.5 g/100 g for CNTR, 68.2 g/100 g for TAL, and 71.5 g/100 g for CO; < 0.001). Heat stress decreased mRNA abundance of and ( ≤ 0.041). Heat stress and CO increased mRNA abundance of ( ≤ 0.047), and CO increased abundance of ( = 0.011). In conclusion, HS does not alter the pig's response to dietary fat. However, HS leads to reduced ADG, ADFI, G:F, and caloric efficiency and a suppression of mRNA abundance of genes involved in the lipolytic cascade, which resulted in a phenotype that was fatter than PFTN.

Defining the physical properties of corn grown under drought-stressed conditions and the associated energy and nutrient content for swine.

Historically high temperatures and low rainfall during the 2012 growing season resulted in drought-stressed conditions in much of the U.S. corn belt. The objective of this experiment was to investigate the impact of these conditions on the composition and energy content in corn and determine if relationships exist among corn quality measurements, chemical composition, and digestibility of energy. Twenty-eight samples of corn from the 2012 drought-stressed crop (DS), plus 2 representative corn samples from the 2011 crop (CNTRL), were collected in Iowa and Illinois using yield as an initial screen for drought impact. Yields ranged from 2.5 to 14.8 t/ha. Each sample was graded by an official of the U.S. grain inspection agency and analyzed for 1,000 kernel weight, kernel density, ether extract, starch, GE, NDF, and CP content. Diets were formulated using each of the 30 corn samples and were fed at 2.6 times the estimated maintenance energy requirement according to the . Sixty individually housed barrows (PIC 359 × C29; 34.2 ± 0.2 kg initial BW) were randomly allotted in an incomplete crossover design to 30 diets across 4 periods. Diet and fecal samples were analyzed to determine DE values. Both ME and NE values were then calculated from DE values using methods developed by and , respectively. Mean DE, ME, and NE values between the CNTRL and DS were not different (3.72 vs. 3.68 Mcal/kg, respectively, 3.66 vs. 3.62 Mcal/kg, respectively, and 2.92 vs. 2.87 Mcal/kg, respectively; > 0.10). Comparing CNTRL with DS, there were no differences ( > 0.10) in ether extract (4.07 vs. 3.96%), CP (8.56 vs. 9.18%), or starch (70.5 vs. 69.5%). However, ADF and NDF were higher in the DS (2.23 and 8.19%, respectively) when compared with CNTRL (1.89 and 6.92%, respectively; < 0.001 and = 0.015, respectively). Small but significant correlations were observed between DE and NDF ( = -0.51, = 0.008), kernel density ( = 0.51, = 0.007), and percent damaged kernels ( = 0.41, = 0.031). No statistically significant correlations were observed between DE and starch or ADF content or between DE and test weight. We can conclude that corn grown in drought-stressed conditions has energy content similar to corn grown under more favorable conditions and, therefore, can be successfully used in swine diets. Furthermore, NDF proved to be superior to fat, starch, and ADF content in explaining the variation in corn energy content.

Comparison of growth and efficiency of dietary energy utilization by growing pigs offered feeding programs based on the metabolizable energy or the net energy system.

The NE system describes the useful energy available for growth better than the ME system. The use of NE in diet formulation should maintain growth performance and carcass parameters when diets contain a diversity of ingredients. This study compared the growth performance of pigs on diets formulated using either the ME or the NE system. A total of 944 gilts and 1,110 castrates (40.8 ± 2.0 kg initial BW) were allotted to group pens and assigned to 1 of 5 different feeding programs according to a randomized complete block design. The 5 treatments included: a corn-soybean meal control diet (CTL), a corn-soybean meal diet plus corn distiller's dried grains with solubles (DDGS), formulated to be equal in ME to the CTL diet (ME-D), a corn-soybean meal diet plus corn DDGS, formulated to be equal in NE to the CTL diet (NE-D), a corn-soybean meal diet plus corn DDGS and corn germ meal, to be equal in ME to the CTL diet (ME-DC) and a corn-soybean meal diet plus corn DDGS and corn germ meal, formulated to be equal in NE to the CTL diet (NE-DC). When required, fat was added as an energy source. Pigs were harvested at an average BW of 130.3 ± 4.0 kg. Growth performance was not affected by treatment ( = 0.581, = 0. 177, and = 0.187 for ADG, ADFI, and G:F, respectively). However, carcass growth decreased with the addition of coproducts except for the NE-D treatment ( = 0.016, = 0.001, = 0.018, = 0.010, and = 0.010 for dressing percentage, HCW, carcass ADG, back fat, and loin depth, respectively). Carcass G:F and lean percentage did not differ among treatments ( = 0.109 and = 0.433, respectively). On the other hand, NE intake decreased ( = 0.035) similarly to that of carcass gain, suggesting a relationship between NE intake and energy retention. Calculations of NE per kilogram of BW gain differed among treatments ( = 0.010), but NE per kilogram of carcass was similar among treatments ( = 0.640). This suggests that NE may be better than ME at explaining the carcass results. Finally, ME intake and ME per kilogram of BW gain were not different among treatments ( = 0.112), but ME per kilogram of carcass gain was different among treatments ( = 0.048). In conclusion, the sequential addition of coproducts in diets formulated on an NE or ME basis can result in similar growth performance, but carcass parameters may be affected independently of the energy system used. However, formulating diets based on NE tended to improve predictability of growth, especially carcass parameters.

Effects of distillers' dried grains with solubles and soybean oil on dietary lipid, fiber, and amino acid digestibility in corn-based diets fed to growing pigs.

The use of corn coproducts increases the concentration of fiber and, often, the use of supplemental lipids in swine diets, which may affect energy and nutrient digestibility. An experiment was conducted to determine the effects of reduced-oil distillers' dried grains with solubles (DDGS) and soybean oil (SBO) on dietary AA, acid hydrolyzed ether extract (AEE), and NDF digestibility in corn-based diets fed to growing pigs. Eighteen growing pigs (33.8 ± 2.2 kg BW) were surgically fitted with a T-cannula in the distal ileum and allocated to 1 of 6 dietary treatment groups in a 3-period incomplete Latin square design, with 9 observations per treatment. Six dietary treatments were obtained by adding 0, 20, and 40% DDGS to corn-casein diets formulated with 2 and 6% SBO. Ileal digesta and fecal samples were collected and the apparent ileal digestibility (AID) and apparent total tract digestibility (ATTD) of AEE and NDF and the AID of AA were determined. Apparent values were corrected for endogenous losses of lipids, and true ileal (TID) and true total tract digestibility (TTTD) values of lipids were calculated. Results showed that the AID of Lys decreased ( < 0.001) with the inclusion of DDGS but was not affected ( = 0.63) by the inclusion of SBO. An interaction between DDGS and SBO on the AID ( = 0.002) and ATTD ( = 0.009) of NDF was observed, where the AID and ATTD of NDF decreased with DDGS at 6% SBO but no effect was observed at 2% SBO. The AID of NDF increased with SBO at 0% DDGS, but no effect was observed at 20 or 40% DDGS. An interaction between DDGS and SBO on the AID ( = 0.011) and ATTD ( = 0.008) of AEE was observed, where the AID and ATTD of AEE increased with SBO. The AID and ATTD of AEE increased with DDGS at 2% SBO, but no effect was observed at 6% SBO. Correction by ileal and fecal endogenous loss of AEE (9.5 and 13.6 g/kg of DMI, respectively) showed that increasing dietary AEE had no effect on the TID and TTD of AEE ( > 0.05). In conclusion, the AID of Lys decreased with DDGS and was not affected by lipids from SBO. The greatest AID and ATTD of NDF was observed in diets with a high AEE and low NDF content. Low values of apparent digestibility of AEE in lower-lipid diets are possibly the result of endogenous losses of lipids, because the true digestibility of AEE was not affected by the dietary increase of AEE.