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In South Africa, mycobacterial culture is regarded as the gold standard for the detection of Mycobacterium tuberculosis complex (MTBC) infection in wildlife even though it is regarded as “imperfect.” We compared a novel decontamination and mycobacterial culture technique (TiKa) to the conventional mycobacterium growth indicator tube (MGIT) system using known amounts of bacilli and clinical samples from MTBC-infected African buffaloes ( Syncerus caffer), white rhinoceros ( Ceratotherium simum), and African elephants ( Loxodonta africana). Use of the TiKa-KiC decontamination agent on samples spiked with 10,000 to 10 colony forming units (cfu) of M. bovis (SB0121) and M. tuberculosis (H37Rv) had no effect on isolate recovery in culture. In contrast, decontamination with MGIT MycoPrep resulted in no growth of M. bovis samples at concentrations

Objectives The objective of this study was to investigate predictors and develop risk equations for stage-3 chronic kidney disease (CKD) in Thai patients with type 2 diabetes mellitus (DM). Methods A retrospective cohort study was conducted in patients with type 2 DM. The outcome was the development of stage-3 CKD. The data set was randomly split into training and validation data sets. Cox proportional hazard regression was used for model development. Discrimination (Harrell’s C statistic) and calibration (the Hosmer-Lemeshow chi-square test and survival probability curve) were applied to evaluate model performance. Results In total, 2178 type 2 DM patients without stage-3 CKD, visiting the hospital from January 1, 2008, to December 31, 2017, were recruited, with median follow-up time of 1.29 years (interquartile range, 0.5-2.5 years); 385 (17.68%) subjects had developed stage-3 CKD. The final predictors included age, male sex, urinary albumin to creatinine ratio, estimated glomerular filtration rate, and hemoglobin A1c. Two 3-year stage-3 CKD risk models, model 1 (laboratory model) and model 2 (simplified model), had the C statistic in validation data sets of 0.890 and 0.812, respectively. Conclusions Two 3-year stage-3 CKD risk models were developed for Thai patients with type 2 DM. Both models have good discrimination and calibration. These stage-3 CKD prediction models could equip health providers with tools for clinical management and supporting patient education.

Herein we qualitatively examine the relationship between reaction rate and reaction selectivity in iridium-catalysed hydrogen isotope exchange (HIE) reactions directed by Lewis basic functional groups. We have recently developed a directing group scale that allows semi-quantitative predictions of Lewis base directed selectivity in HIE, formally ranking 'relative rates' determined from a structured set of competition experiments. Here, we show that selectivity and rate are in fact not correlated, but that different types of behaviour emerge in competition experiments and that the observed behaviour can be predicted from our established selectivity scale.

Nutrients excreted from animals affect the nutritive value of manure as a soil amendment as well as the composition of gases emitted from manure storage facilities. There is a dearth of information, however, on how diet type in combination with dietary particle size affects nutrients deposited into manure storage facilities and how this affects manure composition and gas emissions. To fill this knowledge gap, an animal feeding trial was performed to evaluate potential interactive effects between feed particle size and diet composition on manure characteristics and manure-derived gaseous emissions. Forty-eight finishing pigs housed in individual metabolism crates that allowed for daily collection of urine and feces were fed diets differing in fiber content and particle size. Urine and feces were collected and stored in 446-L stainless steel containers for 49 d. There were no interactive effects between diet composition and feed particle size on any manure or gas emission parameter measured. In general, diets higher in fiber content increased manure nitrogen (N), carbon (C), and total volatile fatty acid (VFA) concentrations and increased manure VFA emissions but decreased manure ammonia emissions. Decreasing the particle size of the diet lowered manure N, C, VFAs, phenolics, and indole concentrations and decreased manure emissions of total VFAs. Neither diet composition nor particle size affected manure greenhouse gas emissions.

Herein we report the rational, computationally-guided design of an iridium(I) catalyst system capable of enabling directed hy-drogen isotope exchange (HIE) with the challenging sulfone directing group. Substrate binding energy was used as a parame-ter to guide rational ligand design via an in-silico catalyst screen, resulting in a lead series of chelated iridium(I) NHC-phosphine complexes. Subsequent preparative studies show that the optimal catalyst system displays high levels of activity in HIE, and we demonstrate the labeling of a broad scope of substituted aryl sulfones. We also show that the activity of the cata-lyst is maintained at low pressures of deuterium gas, and apply these conditions to tritium radiolabeling, including the expedi-ent synthesis of a tritium-labeled drug molecule.

Background The benefits of using the oxidized oils from rendering and recycling as an economic source of lipids and energy in animal feed always coexist with the concerns that diverse degradation products in these oxidized oils can negatively affect animal health and performance. Therefore, the quality markers that predict growth performance could be useful when feeding oxidized oils to non-ruminants. However, the correlations between growth performance and chemical profiles of oxidized oils have not been well examined. In this study, six thermally oxidized soybean oils (OSOs) with a wide range of quality measures were prepared under different processing temperatures and processing durations, including 45 °C-336 h; 67.5 °C-168 h; 90 °C-84 h; 135 °C-42 h; 180 °C-21 h; and 225 °C-10.5 h. Broilers and nursery pigs were randomly assigned to diets containing either unheated control soybean oil or one of six OSOs. Animal performance was determined by measuring body weight gain, feed intake, and gain to feed ratio. The chemical profiles of OSOs were first evaluated by common indicative tests, including peroxide value, thiobarbituric acid reactive substances, p-anisidine value, free fatty acids, oxidized fatty acids, unsaponifiable matter, insoluble impurities, and moisture, and then analyzed by the liquid chromatography-mass spectrometry-based chemometric analysis. Results Among common quality indicators, p-anisidine value (AnV), which reflects the level of carbonyl compounds, had the greatest inverse correlation with the growth performance of both broilers and pigs, followed by free fatty acids and oxidized fatty acids. Among the 17 aldehydes identified in OSOs, C9-C11 alkenals, especially 2-decenal and 2-undecenal, had stronger inverse correlations (r Conclusions As the major lipid oxidation products contributing to the AnV, individual C9-C11 unsaturated aldehydes in heavily-oxidized oils could function as effective prediction markers of growth and feed intake in feeding non-ruminants.

Background Oxidized feed lipids have been shown to have detrimental effects on food animal growth and metabolism. The present study aimed to measure classes of lipid oxidation products (LOP) in feed-grade oils at temperatures representing production and storage conditions. Results There were significant oil type × time interactions in the accumulation of primary and secondary LOP. At 22.5 °C, peroxide value (PV), a marker for the primary phase of lipid oxidation, increased most in fish oil (FO), followed by tallow (TL), soybean oil (SO), linseed oil (LO) and modified algae oil (MAO), whereas palm oil (PO) showed no appreciable increase in PV. Secondary LOP, such as p-anisidine value, hexanal, 2,4,-decadienal, polymerized triacylglycerols and total polar compounds, increased only in FO. At 45 °C, FO and SO produced both primary and secondary LOP, whereas MAO, PO and TL had slower rates of PV increase and no secondary LOP. At 90 °C and 180 °C, all oils except for FO accumulated both primary and secondary LOP. Conclusions Higher polyunsaturated fatty acid:saturated fatty acid oils and higher temperatures produced greater quantities of primary and secondary LOP. However, unrefined TL was more prone to oxidation at 22.5 °C than predicted, whereas LO was more stable than predicted, indicating that pro-oxidant and antioxidant compounds can markedly influence the rate of oxidation. Measuring both primary and secondary LOP will provide better information about the oxidative status of feed oils and provide better information about which classes of LOP are responsible for detrimental health effects in animals. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.

Background Drug-drug interactions between feminizing hormone therapy (FHT) and antiretroviral therapy (ART) are a major concern among transgender women (TGW), which may lead to suboptimal ART adherence and inappropriate FHT dosage. To evaluate potential drug-drug interactions between FHT and ART, we performed intensive measurements of the pharmacokinetic (PK) parameters of blood tenofovir (TFV), efavirenz (EFV), and estradiol (E2). Methods Twenty TGW with newly diagnosed human immunodeficiency virus (HIV) infection were enrolled. FHT (E2 valerate 2 mg/d and cyproterone acetate 25 mg/d) was prescribed at baseline until week 5 and restarted at week 8. ART (TFV disoproxil fumarate/emtricitabine/EFV at 300/200/600 mg) was initiated at week 3. The E2 PK parameters were measured intensively at weeks 3 (without ART) and 5 (with ART), and TFV and EFV PK parameters were measured intensively at weeks 5 (with FHT) and 8 (without FHT). Results The median (interquartile range) age and body mass index were 25.5 (22.5–31.0) years and 20.6 (19.3–23.1) kg/m2, respectively. The differences in geometric mean ratios between weeks 3 and 5 were as follows for E2 area under the curve, maximum concentration, and concentration at 24 hours (C24), respectively: 0.72 (90% confidence interval, .64–.81; P < .001), 0.81 (.72–.92; P = .006), and 0.64 (.50–.83; P = .004). The differences in geometric mean ratios between weeks 5 and 8 were as follows for TFV AUC, TFV C24, and EFV C24: 0.86 (90% confidence interval, .80–.93; P = .002), 0.83 (.75–.93; P = .006), and 0.91 (.85–.97; P = .02). Conclusions Among HIV-positive TGW, E2 PK parameters were significantly lower in the presence of TFV disoproxil fumarate/emtricitabine/EFV, and some TFV and EFV PK parameters were lower in the presence of FHT. Further studies should determine whether these reductions are clinically significant and whether they occur with other FHT or ART regimens.

[3 H]Genipin was synthesized in a single step by Ir(I) catalyzed hydrogen isotope exchange. Conditions for selective exchange of the sp2 CH bond ortho to the methyl ester functionality were developed through deuterium modeling studies through a catalyst screen. Optimized conditions so obtained were then utilized with tritium gas to generate [3 H]genipin at a specific activity of 18.5 Ci/mmol. Racemic [14 C]genipin was prepared in eight steps in overall 5.4% radiochemical yield from potassium [14 C]cyanide.

This chapter provides an overview of recent developments in the Pauson–Khand reaction. The work that is discussed herein is selected from the time period 2013–2018, and only cobalt‐mediated versions of the Pauson–Khand reaction are considered. This review is focused on the discussion of developments in the areas of reaction promotion, novel substrates, asymmetric variants, mechanistic studies, and applications in total synthesis. The quantity and range of work published within the review period reflects the continued and sustained interest in the Pauson–Khand reaction and the application of this annulation protocol in organic synthesis. Notable advances in the review period include the use of flow chemistry, techniques of enhanced efficiency for use with electron‐poor alkenes and internal alkynes, further insight into the reaction mechanism, and remarkable applications in complex natural product synthesis.

The objectives of this study were to determine if feeding thermally processed (TP, heated at 100°C for 120 h) spray-dried egg whites (SDEW) to nursery pigs would impact growth performance, apparent total tract digestibility (ATTD) of GE, N, and S, and oxidative stress. Thirty-two barrows, (initial BW 7.1 kg) were randomly assigned to dietary treatments with 1 pig per pen. In a preliminary study, thermally processing SDEW at 100°C for 120 h increased protein carbonyls (PC) from 6 µmol/g to 19.4 µmol/g (P ≤ 0.01). Diets included either 12% SDEW, 6% TP-SDEW plus 6% SDEW, or 12% TP-SDEW. The experiment lasted 24 d for collection of growth performance data, while plasma was collected on d 21 and liver tissue harvested on d 24 to analyze for markers of oxidative stress. Feces were collected on d 22 for measures of ATTD. Daily gain, daily feed intake, feed efficiency, and ATTD of GE were not found to be different among dietary treatments (P ≥ 0.57). In contrast, ATTD of N (P = 0.11) and S (P = 0.03) were found to increase with increasing protein oxidation in the diet. There was no change in the plasma or liver F2-isoprostanes and 8-hydroxy-2’-deoxyguanosine among dietary treatments (P ≥ 0.28). An increase in plasma PC (P = 0.02) was observed in pigs fed 12% TP-SDEW compared to pigs fed 12% SDEW and pigs fed 6% TP-SDEW. In contrast, a decrease in liver tissue PC (P = 0.04) was observed in pigs fed 6% TP-SDEW compared to pigs fed 12% SDEW and 12% TP-SDEW. These results indicate that feeding TP-SDEW does not affect growth performance, ATTD of GE, and oxidative stress as indicated by F2-isoprostanes or 8-hydroxy-2’-deoxyguanosine; but appeared to have variable effects on oxidative stress as measured by PC.

An experiment was conducted to evaluate the effects of age and supplemental xylanase in corn- or wheat-based diets on cecal volatile fatty acid (VFA) concentrations of Ross × Ross 708 male broilers during weekly intervals from 14 to 42 d of age. Day-old chicks (1,500) were randomly distributed into 60 floor pens (25 chicks/pen; 0.078 m2/bird) and fed 1 of 4 dietary treatments (TRT) throughout the starter (1 to 14 d of age), grower (15 to 28 d of age), and finisher (29 to 42 d of age) phases with 15 replicates per TRT. Dietary TRT consisted of a 2 × 2 factorial arrangement with 2 diet types (corn- or wheat-based) and 2 xylanase inclusions (0 or 16,000 BXU/kg) as the main factors. At 14, 21, 28, 35, and 42 d of age, cecal contents were collected (4 birds/pen) for VFA analysis. Main effects of cereal grain source (P

An experiment was conducted to evaluate the effects of feeding diets varying in cereal grain source and supplemental xylanase concentrations on growth performance and cecal volatile fatty acid (VFA) concentrations of Ross × Ross 708 male broilers from 1 to 40 d of age. A total of 1,536 day-old chicks were randomly distributed into 64 floor pens (24 chicks/pen; 0.08 m2/bird) and fed 1 of 8 dietary treatments (TRT) with 8 replicates per TRT. Experimental TRT were of either corn- (TRT 1 to 4) or wheat-based (TRT 5 to 8) origins. The 4 dietary TRT for each cereal grain source consisted of a positive control (PC) reference diet and 3 reduced AMEn diets (AMEn reduced 66 kcal/kg below PC) with supplemental xylanase at either 0 (negative control), 12,000, or 24,000 BXU/kg. Birds and feed were weighed at 1, 14, 26, and 40 d of age to determine BW gain, feed intake, and feed conversion ratio. At 26 and 40 d of age, cecal contents were collected and pooled per pen (7 birds/pen; 5 replicate pens/TRT) for VFA concentrations. No TRT differences (P > 0.05) in cumulative growth performance were observed. Likewise, no TRT differences (P > 0.05) in acetic or total VFA concentrations were observed at 26 or 40 d of age. However, cereal grain source (P < 0.05) influenced propionic, isobutyric, butyric, and isovaleric concentrations at 26 and 40 d of age with birds receiving the corn-based diets having higher (P < 0.05) cecal propionic, isobutyric, and isovaleric concentrations, and lower (P < 0.05) butyric acid concentrations than those fed the wheat-based diets. These results indicate that dietary cereal grain source may influence individual cecal VFA concentrations. However, supplemental xylanase did not affect broiler growth performance or cecal VFA concentrations. Therefore, future research evaluating factors limiting xylanase responses on broiler growth performance and cecal VFA production is warranted.

Objective The objective was to determine the DE of various lipids and compare these values with predicted values based on published equations. Materials and Methods Pigs (480) weaned at 24 d of age were fed a common diet for 7 d after which they were fed a basal or lipid-based diet for 28 d. Lipids (7.13%) were added in place of the basal diet, and all diets were pelleted and offered ad libitum. Fecal samples were collected on d 25 from 2 pigs per pen and pooled for subsequent analysis. Apparent total-tract digestibility of GE of the diet was determined by the indirect method and the DE content of each lipid source using the difference procedure. Results and Discussion The DE for butter fat, canola oil, coconut oil, fish oil, flaxseed oil, lard, olive oil, palm oil, soybean oil, and tallow was 8,911, 9,474, 9,380, 9,464, 8,584, 8,648, 9,606, 8,304, 9,979, and 8,071 kcal/kg, respectively. Using these values and the chemical composition of each lipid, the best fit prediction equation was DE, kcal/kg = 10,267 − (110.3 × FFA, %) − (41.8 × C16:0, %) − (39.7 × C18:0, %) − (98.0 × unsaturated:saturated ratio) + (6.4 × iodine value), SE = 164, R2 = 0.97, P = 0.01. Implications and Applications The determined DE herein were approximately 12% greater than predicted based on published equations, indicating the refining of published prediction equations is needed. These results indicate that DE of lipids can vary depending on their fatty acid composition, which consequently affects pig performance.

The objectives of this experiment were to evaluate the effect of oil source and peroxidation status on broiler performance and oxidative stress. Broilers (initial BW 85.1 ± 7.8 g) were allotted to 40 cages with 5 birds per cage in a completely randomized design. The 4 × 2 factorial arrangement of treatments consisted of oil source (palm oil, soybean oil, flaxseed oil, and fish oil) and peroxidation status (fresh or peroxidized). Broilers were fed experimental diets for 20 d to measure growth performance; on day 21 of the experiment, plasma and liver samples were harvested for analysis of oxidative stress including thiobarbituric acid reactive substances (TBARS), protein carbonyls (PC), 8-hydroxy-2'-deoxyguanosine (8- OH-2dG), glutathione peroxidase activity (GPx) and superoxide dismutase and catalase (CAT). An interaction occurred between oil source and peroxidation status where broilers fed peroxidized oils had reduced ADFI, ADG, G:F, and plasma GPx in all oil sources except for fish oil (P ≤ 0.04). Plasma 8-OH-2dG was increased by feeding peroxidized oils (P = 0.01). An interaction occurred in liver TBARS where broilers fed peroxidized palm oil had greater liver TBARS compared to fresh palm oil (P = 0.09). An interaction was noted for liver PC where broilers fed palm, flaxseed, and fish oil had similar liver PC regardless of peroxidation status, while broilers fed peroxidized soybean oil had increased liver PC compared to the fresh soybean oil diet (P = 0.04). Oil source affected plasma TBARS and 8-OH-2dG (P = 0.01), plasma PC (P = 0.09), liver 8-OH-2dG (P = 0.08), and liver CAT (P = 0.02). Correlations between oil composition with growth performance and oxidative stress markers imply that oil UFA:SFA, p-anisidine value, DDE, total polar compounds, and polymerized triglycerides should be measured as an indicator of oil quality, with growth performance being correlated to plasma TBARS, PC, and GPx. In conclusion, the degree of unsaturation and peroxidation status of dietary oils affected growth performance and markers of oxidative stress in poultry.

Given the prevalence of skin cancer, sunscreens are recommended by dermatologists including the American Academy of Dermatology to protect skin from harmful ultraviolet rays. Unfortunately, this leads to an estimated 14,000 tons of sunscreen entering waterways each year. Many of the chemicals in sunscreens, such as oxybenzone and benzophenone-2, are indicated to have adverse effects on corals and other aquatic life. As an eco-conscious alternative, physical barrier sunscreens, such as non-nano-titanium dioxide (TiO2), have been suggested as a replacement. This study examines the impact of a non-nano-TiO2-based sunscreen over a nationally sold brand of sunscreen containing oxybenzone, on clownfish (Amphiprion ocellaris). Animals were evaluated for mortality, swimming behavior, and feeding behavior. Our data indicate that at an exposure level of 100 mg/L oxybenzone-containing sunscreen had a negative impact on mortality, leading to 25% death by the end of the 97-h testing period. Negative impacts on behavior were even more dramatic for the 100 mg/L oxybenzone-containing sunscreen, with 100% of the animals failing to feed over the first 49 h of testing and 100% of animals demonstrating abnormal swimming behavior over the entire testing period. By comparison, the non-nano-(TiO2) sunscreen at 100 mg/L had little (6.7%) negative impact on mortality and feeding. While swimming behavior was disrupted during the first 25 h of testing (26.7% abnormal movement), animals recovered well over the remainder of the testing period (out to 97 h).

IntroductionThe shape of the glucose curve during an oral glucose tolerance test (OGTT) reflects β-cell function in populations without diabetes but has not been as well studied in those with diabetes. A monophasic shape has been associated with higher risk of diabetes, while a biphasic pattern has been associated with lower risk. We sought to determine if phenotypic or metabolic characteristics were associated with glucose response curve shape in adults with type 2 diabetes treated with metformin alone.Research design and methodsThis is a cross-sectional analysis of 3108 metformin-treated adults with type 2 diabetes diagnosed ResultsThe monophasic profile was the most common (67.8% monophasic, 5.5% biphasic, 26.7% continuous rise). The monophasic subgroup was younger, more likely male and white, and had higher body mass index (BMI), while the continuous rise subgroup was more likely female and African American/black. HOMA2-S and fasting glucose did not differ among the subgroups. The biphasic subgroup had the highest early, late, and total insulin and C peptide responses (all pConclusionsBased on the large multiethnic GRADE cohort, sex, race, age, and BMI were found to be important determinants of the shape of the glucose response curve. A pattern of a continuously rising glucose at 2 hours reflected reduced β-cell function and may portend increased glycemic failure rates.Trial registration numberNCT01794143.

Cement and water within the concrete mass create a hydrated phase which acts as the glue for holding the sand and coarse aggregates in place to develop a strong construction material. The most important phase within the cement matrix is that of calcium silicate hydrate (CSH), which is largely responsible for the concrete strength. Decomposition of the CSH phase due to high temperatures will affect compressive strength of the concrete. Raman bands at 1083, 709 and 276 cm−1, which are representative of the CaCO3 and CSH presence in the concrete matrix phases can be used to assess changes in compressive strength as a result of thermal decomposition. The ratio between 1083/709 cm−1 bands was calculated and correlated to the compression strength of the concrete. The results show there is a rapid decline in strength around a critical peak ratio of 8.78 and a residual compressive strength of 0.62, closely following a polynomial curve. The tool developed here allows an indirect evaluation of the temperature the concrete has been exposed to by studying the band. A case study from a fire scene taken from a warehouse in Kingston (Jamaica) is also presented with the conclusion and results compared. The study showed that Raman spectroscopy has the potential to provide in-situ non-destructive testing of fire damaged concrete rapidly and accurately.

Weissella paramesenteroides has potential as an industrial biocatalyst due to its ability to produce lactic acid. A novel strain of W. paramesenteroides was isolated from ensiled sorghum. The genome was sequenced using a hybrid assembly of Oxford Nanopore and Illumina data to produce a 2-Mbp genome and 22-kbp plasmid sequence.

Rendered products from the meat industry provide quality proteins in diets for companion animals. These proteins are exposed to extreme temperatures during processing leading to the potential for decreased diet digestibility and subsequent growth performance. While this would impact production efficiency in livestock species, oxidized ingredients in companion animal diets may impact health and longevity. The objective of this study was to determine the extent to which a feedstuff containing oxidized protein and lipid affect diet digestibility, growth performance, and oxidative stress in nursery pigs. A total of 56 male pigs (21 d of age, initial body weight 5.51 ± 0.65 kg) were randomly assigned to one of the four dietary treatments in a 2 × 2 factorial arrangement with two levels of heat and two levels of antioxidant (AOX). Diets were fed for 35 d and growth performance was measured, while total tract digestibility and nitrogen (N) balance was determined during the trial on day 18–20. Blood plasma was collected on day 34 and jejunum, colon, and liver tissues were collected on day 35 to analyze for markers of oxidative stress. Average daily feed intake (ADFI) was reduced in pigs fed diets without AOXs (P = 0.02). Additionally, pigs consuming diets containing heated chicken byproduct (CBP) meal had decreased gain:feed (GF; P = 0.02). There was an interaction between heat and AOX (P = 0.02) where heating CBP reduced N digestibility in the presence of an AOX but did not have an impact when AOX was not present. The removal of AOX resulted in reduced GE digestibility (P < 0.01). Dry matter (P < 0.01), ash (P < 0.01), and protein (P < 0.01) digestibility were reduced (P < 0.01) as a result of heating. Furthermore, heating (P =0.01) as well as absence of AOX (P =0.01) resulted in reduced digestible energy. No difference was detected in N retention suggesting that oxidation reduces digestibility but has no impact on N utilization. This is supported by the fact that systemic oxidative stress was not consistently affected by heating or AOX inclusion. These results suggest that feeding pigs CBP containing oxidized proteins and lipids did not induce oxidative stress. However, feeding young pigs CBP containing oxidized proteins and lipids did result in reduced energy and nutrient digestibility as well as negatively affected feed efficiency. Because CBP is commonly used in companion animal diets, it is reasonable to revisit their impacts on those species.

Used restaurant oil offers a sustainable and affordable energy source in broiler diets but variable lipid composition and the presence of harmful peroxidation products may alter intestinal immunity. The objective of this study was to evaluate the effects of feeding different lipid sources with variable peroxidation statuses on immune cell populations producing interleukin-6 (IL6) and interferon-γ (IFNG) in the broiler ileum. Two hundred broilers were fed diets with 5% inclusion of control or peroxidized palm, soybean, flaxseed or fish oil in a 4 × 2 factorial treatment design. At 21d, 2 birds/ treatment were euthanized for ileum collection and immune cell populations were analyzed by RNAscope- in situ hybridization (ISH). Ileal production of IL6 increased 85.8% by feeding peroxidized flaxseed oil while IFNG-producing cells were increased 55.1-59.9% by feeding either control or peroxidized soybean oil (P ≤ 0.05). Feeding peroxidized lipid generally reduced CD3+ T cells not producing either IL6 or IFNG by 14.9-39.0% (P ≤ 0.05). Overall, these results suggest that IL6 and IFNG have differential responses to lipid source and peroxidation while lipid peroxidation negatively impacts T cell presence in the broiler chicken ileum. Inflammatory outcomes observed in broilers fed peroxidized flaxseed oil suggest that yellow grease containing this type of oil may detrimentally impact broilers, while soybean oil generally contributes to intestinal inflammation regardless of heat exposure

Remote directing groups in a bifunctional molecule do not always behave independently of one another in C–H activation chemistries. A combined DFT and experimental mechanistic study to provide enhanced Ir catalysts for chemoselective C–H deuteration of bifunctional aryl primary sulfonamides is described. This provides a pharmaceutically-relevant and limiting case study in using binding energies to predict intramolecular directing group chemoselectivity. Rational catalyst design, guided solely by qualitative substrate–catalyst binding free energy predictions, enabled intramolecular discrimination between competing ortho-directing groups in C–H activation and delivered improved catalysts for sulfonamide-selective C–H deuteration. As a result, chemoselective binding of the primary sulfonamide moiety was achieved in the face of an intrinsically more powerful pyrazole directing group present in the same molecule. Detailed DFT calculations and mechanistic experiments revealed a breakdown in the applied binding free energy model, illustrating the important interconnectivity of ligand design, substrate geometry, directing group cooperativity, and solvation in supporting DFT calculations. This work has important implications around attempts to predict intramolecular C–H activation directing group chemoselectivity using simplified monofunctional fragment molecules. More generally, these studies provide insights for catalyst design methods in late-stage C–H functionalisation., In C–H activation chemistries, the interpretation of the influence of remote directing groups in a bifunctional molecule depends on the in silico method used to inform catalyst design.

Three experiments were conducted to evaluate oil source and peroxidation status (experiment 1) or peroxidized soybean oil (SO; experiments 2 and 3) on growth performance, oxidative stress, and digestibility of dietary ether extract (EE). In experiment 1, palm oil (PO), poultry fat (PF), canola oil (CO), and SO were evaluated, while in experiments 2 and 3, only SO was evaluated. Lipids were either an unheated control (CNT) or thermally processed at 90 °C for 72 hr, being added at 10%, 7.5%, or 3% of the diet in experiments 1, 2, and 3, respectively. In experiment 1, 288 pigs (body weight, BW, 6.1 kg) were fed 1 of 8 factorially arranged treatments with the first factor being lipid source (PO, PF, CO, and SO) and the second factor being peroxidation status (CNT or peroxidized). In experiment 2, 216 pigs (BW 5.8 kg) were fed 1 of 6 treatments consisting of 100%, 90%, 80%, 60%, 20%, and 0% CNT SO blended with 0%, 10%, 20%, 40%, 80%, and 100% peroxidized SO, respectively. In experiment 3, 72 pigs (BW 5.8 kg) were fed either CNT or peroxidized SO. Pigs were fed 21 d with feces collected on day 12 or 14 and pigs bled on day 12 blood collection. In experiment 1, an interaction between oil source and peroxidation status was observed for averaged daily gain (ADG) and average daily feed intake (ADFI; P = 0.10) which was due to no impact of feeding pigs peroxidized PO, PF, or SO on ADG or ADFI compared with feeding pigs CNT PO, PF, or SO, respectively; while pigs fed peroxidized CO resulted in reduced ADG and ADFI compared with pigs fed CNT CO. There was no interaction between oil source and peroxidation status, and no lipid source effect on gain to feed ratio (GF; P ≥ 0.84), but pigs fed the peroxidized lipids had a lower GF compared with pigs fed the CNT lipids (P = 0.09). In experiment 2, feeding pigs diets containing increasing levels of peroxidized SO resulted in reduced ADG (quadratic, P = 0.03), ADFI (linear, P = 0.01), and GF (quadratic, P = 0.01). In experiment 3, feeding peroxidized SO at 3% of the diet reduced ADG (P = 0.11) and ADFI (P = 0.13), with no observed change in GF (P = 0.62). Differences in plasma protein carbonyls, glutathione peroxidase, and vitamin E due to feeding peroxidized lipids were inconsistent across the 3 experiments. Digestibility of dietary EE was reduced in pigs fed peroxidized PO or SO (P = 0.01, experiment 1) and peroxidized SO in experiments 2 and 3 (P ≤ 0.02). In conclusion, the peroxidation status of dietary lipids consistently affects growth performance and EE digestibility but has a variable effect on measures of oxidative stress.

A palette of commonly used directing groups, including various pharmaceutically relevant nitrogen-containing heterocycles, are quantitatively ranked based on the results of intermolecular hydrogen isotope exchange competition reactions using two iridium complexes: [Ir(COD)(IMes)(PPh3)][BArF24] and [IrCl(COD)(IMes)]. The directing group power scales that have been constructed from these data reveal a wide range of reactivity covering four orders of magnitude. Intramolecular competition experiments have demonstrated that the obtained reactivity scale provides accurate predictions of regioselectivity within molecules with multiple competing directing groups. This work contributes to our understanding and control of regioselectivity in metal-catalysed C–H activation reactions.

Mycotoxins (MTX) such as deoxynivalenol (DON), fumonisins (FUM), and zearalenone (ZEN) are a few of the most prevalent mycotoxins in livestock feed. Effects of MTX can vary based on contamination and type, but include losses in performance, immune function and reproduction impacting profitability. Effectiveness of mitigation strategies for MTX can greatly vary depending on type and contamination level. Therefore, the trial objective was to evaluate an in-feed mitigation strategy [Biofix® Plus (BPL), 1.5 kg/MT inclusion, BIOMIN America, Inc., Overland Park, KS] on nursery pig performance during a natural mixed MTX challenge. A total of 105 newly weaned pigs (BW = 5.5 ± 0.2 kg) were allotted to 1 of 4 treatments in a 2 × 2 factorial design with 2 MTX contamination levels [low (L-MTX) and high (H-MTX); Table 1] and 2 BPL levels [without (Control) and with (BPL)] with 3 pigs per pen and 8 to 9 pens per treatment for a 5-week trial. Data were analyzed using the GLIMMIX procedure of SAS with main effects of MTX and BPL and their interaction. There was no interaction of MTX and BPL on any of the cumulative 5-week performance metrics, therefore only main effects will be discussed. Average pig BW at 5-week was reduced (P < 0.05) in H-MTX compared with L-MTX diets (21.5 vs 18.5 kg, respectively). Similarly, ADG and ADFI were reduced (P < 0.05) in H-MTX pigs compared with L-MTX pigs. Feed efficiency was numerically reduced (P = 0.050) in H-MTX pigs compared with L-MTX pigs. However, BPL fed pigs had increased (P < 0.05) feed efficiency compared with pigs not fed BPL. Thus, MTX did effect BW, ADG, and ADFI and BPL was able to increase feed efficiency regardless of MTX level suggesting that BPL should be considered as a mitigation strategy to address mixed MTX challenges.

The bromodomain and extraterminal domain (BET) family of epigenetic regulators comprises four proteins (BRD2, BRD3, BRD4, BRDT), each containing tandem bromodomains. To date, small molecule inhibitors of these proteins typically bind all eight bromodomains of the family with similar affinity, resulting in a diverse range of biological effects. To enable further understanding of the broad phenotype characteristic of pan-BET inhibition, the development of inhibitors selective for individual, or sets of, bromodomains within the family is required. In this regard, we report the discovery of a potent probe molecule possessing up to 150-fold selectivity for the N-terminal bromodomains (BD1s) over the C-terminal bromodomains (BD2s) of the BETs. Guided by structural information, a specific amino acid difference between BD1 and BD2 domains was targeted for selective interaction with chemical functionality appended to the previously developed I-BET151 scaffold. Data presented herein demonstrate that selective inhibition of BD1 domains is sufficient to drive anti-inflammatory and antiproliferative effects.

Background Restaurant oil in poultry diets increases energy content, reduces production costs, and promotes sustainability within the food supply chain. However, variable oil composition and heating temperatures among restaurant oil sources can impact broiler chicken health due to heat-induced lipid modifications. Objectives A 21-d experiment was conducted to evaluate ileal morphology, liver cytokine gene expression, and ileal immune cell populations in broilers fed control or peroxidized lipids with varying chain and saturation characteristics. Methods Day-old broilers were housed in battery cages (5 birds per cage) and fed diets containing 5% control or peroxidized oils. Eight diets were randomly assigned in a 4 × 2 factorial arrangement consisting of oil source (palm, soybean, flaxseed, or fish) and peroxidation status (control or peroxidized). At day 21, samples were collected for ileal histomorphology [villus height (VH), crypt depth (CrD), and the VH:CrD ratio], and liver cytokine expression (qPCR). Ileum cytokine expression and T-cell markers were analyzed by RNAscope in situ hybridization (ISH). Data were analyzed as a mixed model (SAS 9.4) with fixed effects of lipid source, peroxidation, and lipid × peroxidation interaction. Results CD3+ T-cells in the ileum decreased 16.2% due to peroxidation (P = 0.001) with 30.3% reductions observed in birds fed peroxidized flaxseed oil (P = 0.01). Peroxidation increased IL6+ and IL1B+ cells by 62.0% and 40.3%, respectively (P = 0.01). Soybean oil increased IFNG+ cells by 55.1% compared with palm oil, regardless of peroxidation status (P = 0.007). Lipid source and peroxidation did not alter ileal histomorphology or liver cytokine expression. Conclusions Lipid peroxidation increased ileal IL1B and IL6 in broiler chickens, whereas soybean oil diets increased IFNG. Generally, peroxidation decreased overall CD3+ T-cell populations, suggesting impaired T-cell presence or recruitment. These results identify potential immunomodulatory lipid profiles in restaurant oil while supporting RNAscope-ISH as a method to describe avian tissue-level immune responses.

Despite dramatic increases in new drugs and regimens, a combination of two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) remains the backbone of many regimens to treat HIV.This article summarizes the pharmacokinetic characteristics of approved NRTIs that are currently in the international treatment and prevention guidelines.Compared to other NRTIs, tenofovir alafenamide fumarate (TAF) is more advantageous in terms of potency and safety. It is therefore a preferred choice in combination with emtricitabine (FTC) in most HIV treatment guidelines. The efficacy of the two-drug combination of NRTI/Integrase strand-transfer inhibitor, i.e. lamivudine/dolutegravir has been approved as an option for initial therapy. This regimen however has some limitations in patients with HBV coinfection. The two NRTI combinations tenofovir disproxil fumarate (TDF)/FTC and TAF/FTC have also been approved for pre-exposure prophylaxis (PrEP). Interestingly, a promising long-acting nucleoside reverse transcriptase translocation inhibitor, islatravir, formulated for implant was well tolerated and remained effective for up to a year, suggesting its potential as a single agent for PrEP. In the next decade, it remains to be seen whether NRTI-based regimens will remain the backbone of preferred ART regimens, or if the treatment will eventually move toward NRTI-sparing regimens to avoid long-term NRTI-toxicity.

Adenosine triphosphate (ATP) test based on one nucleotide has been applied as point-of-care testing (POCT) for bacterial contamination in the medical and food industries. Hypothetically, testing three adenylate nucleotides (A3) may provide better detection of duodenoscope bacterial contamination than ATP test.To evaluate performance characteristics and optimal cut-off value of A3 and ATP tests in predicting bacterial contamination of duodenoscopes.Four hundred duodenoscope samples obtained after 100 endoscopic retrograde cholangiopancreatography procedures were randomized into group A (A3 test) or B (ATP test). Samples were collected from the elevator at the four-step cleaning process of duodenoscope. We defined the new cut-off value of the test for reaching 100% negative predictive value (NPV) from our receiver operating characteristic (ROC).Using the cultures from the four-step cleaning process as the reference, the areas under ROC (AUROC) were 0.83 and 0.84 for group A (N = 200) and group B (N = 200), respectively. Using the cultures from post-high-level disinfection (HLD) as the reference, the AUROC were 0.35 and 0.74 for group A (N = 50) and group B (N = 50), respectively. We investigated ATP as a POCT after HLD with a new cut-off value of 40 RLU. However, this threshold did not allow detection of low numbers of bacteria.A3 and ATP tests provide good performances in predicting bacterial contamination of duodenoscopes for the four-step cleaning process. The ATP40 RLU is helpful as a POCT after HLD; however, the limitation of this cut-off value is its inability to detect low numbers of bacteria.

Background Skin signs observed in morbid obesity may change as the weight reduces, especially post-bariatric surgery (BaS). Data concerning the skin findings exclusively in post-BaS patients remain limited. Methods Seventy post-BaS patients were examined for cutaneous abnormalities. The patients were divided into those with successful weight loss (% excessive body weight loss (EBWL) of at least 50%) and a non-successful group (%EBWL Results Forty-six patients with successful weight loss demonstrated a significantly lower prevalence of acanthosis nigricans on the neck, axillae and inguinal areas, keratosis pilaris (KP) and pebble fingers. However, a higher prevalence of alopecia was observed. After adjustment with patients’ factors, KP (adjusted odds ratio (aOR) = 0.21, 95%CI 0.06–0.74, p = 0.02) and pebble fingers (aOR = 0.09, 95%CI 0.01–0.89, p = 0.04) remained significantly less likely in patients with successful weight loss. Laboratory results comparing pre- and post-surgery values revealed significant decreases in fasting plasma glucose, hemoglobin A1c, and triglyceride and an increase of high-density lipoproteins in both groups. However, significant decreases of liver aminotransferases (AST and ALT) were observed only in the successful group (p = 0.04, 0.003). Nonetheless, a decrease in vitamin B12 (p = 0.01) was observed in the successful group. Conclusion Weight loss after BaS provided an improvement for metabolic profiles. Successful weight reduction resulted in better skin improvement. However, nutritional supplements may be necessary. Trial registration Thai Clinical Trials Registry TCTR20171003002. Registered October 3. 2017, retrospectively registered.

Rendered products from the meat industry can provide economical quality sources of proteins to the animal and feed industry. Similar to lipids, rendered proteins are susceptible to oxidation, yet the stability of these proteins is unclear. In addition, interest in understanding how oxidative stress can impact efficiency in production animals is increasing. Recent studies show that consumption of oxidized lipids can lead to a change in the oxidative status of the animal as well as decreases in production efficiency. To date, little is known about how consumption of oxidized proteins impacts oxidative status and growth performance. The objectives of this study were to determine if feeding diets high in oxidized protein to growing pigs would: 1) impact growth performance and 2) induce oxidative stress. Thirty pigs (42 d old; initial body weight [BW] 12.49 ± 1.45 kg) were randomly assigned to one of three dietary treatments with increasing levels of oxidized protein. Spray-dried bovine plasma was used as the protein source and was either unheated upon arrival, heated at 45 °C for 4 d, or heated at 100 °C for 3 d. Diets were fed for 19 d and growth performance was measured. Blood plasma (days 0 and 18), jejunum, colon, and liver tissues (day 19) were collected to analyze for markers of oxidative stress (e.g., protein oxidation, lipid oxidation, DNA damage, and glutathione peroxidase activity). Average daily gain (ADG;P < 0.01) and average daily feed intake (ADFI;P < 0.01) had a positive linear relationship to increased protein oxidation, but there was no effect on gain to feed ratio. Furthermore, protein (P = 0.03) and fat (P < 0.01) digestibility were reduced with increased protein oxidation in the diet. Crypt depth showed a positive linear relationship with dietary protein oxidation levels (P = 0.02). A trend was observed in liver samples where pigs fed the plasma heated to 45 °C had increased lipid oxidation compared with pigs fed the plasma either unheated or heated to 100 °C (P = 0.09). DNA damage in the jejunum tended to have a linear relationship with the dietary protein oxidation level (P = 0.07). Even though results suggest dietary oxidized protein did not induce oxidative stress during short-term feeding, differences in performance, gut morphology, and digestibility are likely a result of reduced protein availability.

Background Bovine tuberculosis and tuberculosis are chronic infectious diseases caused by the Mycobacterium tuberculosis complex members, Mycobacterium bovis and Mycobacterium tuberculosis, respectively. Infection with M. bovis and M. tuberculosis have significant implications for wildlife species management, public health, veterinary disease control, and conservation endeavours. Results Here we describe the first use of the VetMAX™ Mycobacterium tuberculosis complex (MTBC) DNA quantitative real-time polymerase chain reaction (qPCR) detection kit for African wildlife samples. DNA was extracted from tissues harvested from 48 African buffaloes and MTBC DNA was detected (test-positive) in all 26 M. bovis culture-confirmed animals with an additional 12 PCR-positive results in culture-negative buffaloes (originating from an exposed population). Of six MTBC-infected African rhinoceros tested, MTBC DNA was detected in antemortem and postmortem samples from five animals. The PCR was also able to detect MTBC DNA in samples from two African elephants confirmed to have M. bovis and M. tuberculosis infections (one each). Culture-confirmed uninfected rhinoceros and elephants’ samples tested negative in the PCR assay. Conclusions These results suggest this new detection kit is a sensitive screening test for the detection of MTBC-infected African buffaloes, African elephants and white rhinoceros.

Two experiments were conducted to determine the effect of oven drying (OD) or freeze drying (FD) on apparent ileal digestibility (AID) of AA in diets fed to pigs. In experiment 1, 15 barrows (88.4 ± 6.4 kg) were allotted to either a corn starch–soybean meal (CST), potato starch–soybean meal (PST), or corn–soybean meal (CSBM) diet, over 2 collection periods. Following collection, samples were pooled within pig and subdivided into either OD or FD, resulting in 10 observations per diet by drying-method combination. In experiment 2, 11 barrows (63.3 ± 3.8 kg) were fed a CST diet, and, following collection, samples were pooled within pig and subdivided and either adjusted to pH 4 or remain unadjusted. Subsets of these samples were then subdivided to be either FD or OD, resulting in 11 observations per pH level by drying-method combination. OD was accomplished by drying samples in a forced air oven at either 100 °C (experiment 1) or 75 °C (experiment 2). In experiment 1, there was no diet type by drying-method interactions noted for any of the AA (P > 0.10).OD resulted in a higher AID of AA compared with samples which were FD (P ≤ 0.10), for all AA except for Gly and Tyr. Averaged across all AA, AID of AA was 3.3% greater if the sample was OD compared with FD. Differences in AID of AA among the 3 diets were noted for all AA (P ≤ 0.07), except for Cys (P = 0.33), due to the fact that CST and PST diets only contained soybean meal (SBM) as an AA-providing ingredient while the CSBM diet contained both corn and SBM. Pigs fed the PST diet had greater SID for all AA compared with pigs fed the CST diet (P ≤ 0.05), except for His, Lys, Cys, and Glu. In experiment 2, there were no pH-adjustment by drying-method interactions noted on AID for any of the AA (P > 0.10). Adjusting ileal digesta to a pH of 4.0 had little effect on AID for most of the AA, except for a lowered AID of Arg, His, Lys, Trp, and Ser (P ≤ 0.10). OD resulted in a higher AID for all AA (P ≤ 0.09) except for Ile, Thr, Val, Ala, Asp, Glu, and Gly. Averaged across all AA, the increase in AID of AA was 1.7% greater if the sample was OD compared with FD. On average, OD of ileal digesta resulted in a 2.5% greater estimate of AID of AA compared with samples that were FD, and was not diet-, pH-, or AA-dependent. Because the majority of the data on AA digestibility are based on FD, a bias factor may be necessary to adjust AA digestibility data obtained on an OD-basis relative to an FD-basis for use in feed formulation.

The objectives of the current experiments were to evaluate the effect of feeding soybean oil (SO) with different levels of peroxidation on lipid, N, and GE digestibility, gut integrity, oxidative stress, and growth performance in nursery pigs. Treatments consisted diets containing 10% fresh SO (22.5 °C) or thermally processed SO (45 °C for 288 h, 90 °C for 72 h, or 180 °C for 6 h), each with an air infusion of 15 L/min, with postprocessing peroxide values of 7.6, 11.5, 19.1, and 13.4 mEq/kg and p-anisidine values of 1.92, 6.29, 149, and 159, for the 22.5 °C, 45 °C, 90 °C and 180 °C processed SO, respectively. In experiment 1, 64 barrows (7.1 ± 0.9 kg initial BW) were randomly allotted into 2 rooms of 32 pens and individually fed their experimental diets for 21 d, with a fresh fecal sample collected on day 20 for determination of GE and lipid digestibility. In experiment 2, 56 barrows (BW 9.16 ± 1.56 kg) were placed into individual metabolism crates for assessment of GE, lipid, and N digestibility and N retention. Urinary lactulose to mannitol ratio was assessed to evaluate in vivo small intestinal integrity, and urine and plasma were collected to analyze for markers of oxidative stress. Pigs were subsequently euthanized to obtain liver weights and analyze the liver for markers of oxidative stress. In experiment 1, pigs fed the SO thermally processed at 90 °C had reduced ADG (P = 0.01) and ADFI (P = 0.04) compared to pigs fed the other SO treatment groups, with no differences noted among pigs fed the 22.5 °C, 45 °C, and 180 °C SO treatments. No effects of feeding thermally processing SO on dietary GE or lipid digestibility (P > 0.10) were noted in either experiment. In experiment 2, there was no dietary effect of feeding peroxidized SO on the DE:ME ratio, N digestibility, or N retained as a percent of N digested, on the urinary ratio of lactulose to mannitol, on serum, urinary, or liver thiobarbituric acid reactive substances, on plasma protein carbonyls, or on urinary or liver 8-OH-2dG (P > 0.10). In experiment 2, pigs fed the SO thermally processed at 90 °C had the greatest isoprostane concentrations in the serum (P ≤ 0.01) and urine (P ≤ 0.05) compared to pigs fed the unprocessed SO. These results indicate that the change in fatty acid composition and/or the presence of lipid peroxidation products in peroxidized SO may reduce ADG and ADFI in nursery pigs, but appears to have no impact on GE, lipid, or N digestibility, or gut permeability. These data suggest that the presence of lipid peroxidation products may affect certain markers of oxidative stress.

Herein we target the total synthesis of 2-epi-α-cedren-3-one, a natural compound isolated from the essential oil of Juniperus thurifera. Overall, our synthetic sequence presents an optimised and robust series of chemical transformations, with prominent features including a low temperature and highly (Z)-selective Wittig olefination reaction, which is vital for the establishment of the relative stereochemistry within the final natural product, and a microwave-assisted, catalytic, intramolecular Pauson-Khand cyclisation reaction, which is used to construct the intriguing tricyclic core of the target molecule. Our optimum cyclisation protocol utilises only 20 mol% of transition metal, and delivers the complex tricyclic structure in just 10 min. Further manipulations of the annulation product culminate in the first total synthesis of the described natural target.

Consumption of thermally oxidized oil is associated with metabolic disorders, but oxidized oil-elicited changes in the metabolome are not well defined. In this study, C57BL/6 mice were fed the diets containing either control soybean oil or heated soybean oil (HSO) for 4 weeks. HSO-responsive metabolic events were examined through untargeted metabolomics-guided biochemical analysis. HSO directly contributed to the presence of new HSO-derived metabolites in urine and the decrease of polyunsaturated fatty acid-containing phospholipids in serum and the liver. HSO disrupted redox balance by decreasing hepatic glutathione and ascorbic acid. HSO also activated peroxisome proliferator-activated receptors, leading to the decrease of serum triacylglycerols and the changes of cofactors and products in fatty acid oxidation pathways. Most importantly, multiple metabolic changes, including the decrease of tryptophan in serum; the increase of NAD+ in the liver; the increases of kynurenic acid, nicotinamide and nicotinamide N-oxide in urine; and the decreases of the metabolites from pyridine nucleotide degradation in the liver indicated that HSO activated tryptophan-NAD+ metabolic pathway, which was further confirmed by the upregulation of gene expression in this pathway. Because NAD+ and its metabolites are essential cofactors in many HSO-induced metabolic events, the activation of tryptophan-NAD+ pathway should be considered as a central metabolic response to the exposure of HSO.

Consumption of peroxidized lipids has been shown to reduce pig performance and energy and lipid digestibility. Objectives of the current study were to evaluate the effect of feeding soybean oil (SO) with different levels of peroxidation on growth performance, lipid, N, and GE digestibility, plasma Trp, and gut integrity in finishing pigs. Fifty-six barrows (46.7 ± 5.1 kg initial BW) were randomly assigned to one of four diets in each of two dietary phases, containing either 10% fresh SO (22.5 °C) or thermally processed SO (45 °C for 288 h, 90 °C for 72 h, or 180 °C for 6 h), each infused with of 15 L/min of air. Peroxide values were 2.0, 17.4, 123.6, and 19.4 mEq/kg; 2,4-decadienal values were 2.07, 1.90, 912.15, and 915.49 mg/kg; and 4-hydroxynonenal concentrations were 0.66, 1.49, 170.48, and 82.80 mg/kg, for the 22.5, 45, 90, and 180 °C processed SO, respectively. Pigs were individually housed and fed ad libitum for 81 d to measure growth performance, including a metabolism period to collect urine and feces for determination of GE, lipid, N digestibility, and N retention. Following the last day of fecal and urine collection when pigs were in the metabolism crates, lactulose and mannitol were fed and subsequently measured in the urine to evaluate gut permeability, while markers of oxidative stress were evaluated in plasma, urine, and liver. There were no differences observed in ADFI (P = 0.91), but average daily gain (ADG) and gain:feed G:F were decreased in pigs fed 90 °C SO diet (P ≤ 0.07) compared to pigs fed the other SO diets. Pigs fed the 90 and 180 °C SO had the lowest (P = 0.05) DE as a % of GE compared to pigs fed the 22.5 °C SO, with pigs fed the 45 °C SO being intermediate. Lipid digestibility was similarly affected (P = 0.01) as energy digestibility, but ME as a % of DE was not affected by dietary treatment (P = 0.16). There were no effects of lipid peroxidation on N digested, N retained, or the urinary lactulose:mannitol ratio (P ≥ 0.25). Pigs fed the SO processed at 90 and 180 °1C had lower concentrations (P < 0.01) of plasma Trp compared to pigs fed the 22.5 and 45 °C SO treatments. Pigs fed 90 °C SO had the greatest (P < 0.01) concentrations of F(2)-isoprostane in plasma and urine thiobarbituric acid reactive substances compared to the other SO treatments. These results indicate that the change in FA composition and/or the presence of lipid peroxidation products in peroxidized SO may reduce ADG, G:F, and digestibility of GE and ether extract, but has little impact on N digestibility and balance or on gut permeability.

Objectives were to evaluate effects of feeding soybean oil (SO) with varying levels of peroxidation on fresh belly characteristics, processing yields, and shelf life of commercially manufactured bacon stored under food-service-style conditions. Fifty-six barrows were randomly assigned to 1 of 4 diets containing 10% fresh SO (22.5 °C) or thermally processed SO (45 °C for 288 h, 90 °C for 72 h, or 180 °C for 6 h), each infused with air at a rate of 15 L/min. Individually housed pigs were provided ad libitum access to feed for 81 d. On day 82, pigs were slaughtered, and on day 83, carcasses were fabricated and bellies collected for recording of weight, dimensions, and flop distance. Belly adipose tissue cores were collected for the analysis of iodine value (IV) by near-infrared spectroscopy (NIR-IV). Bacon was manufactured at a commercial processing facility, and sliced bacon was subsequently transferred to food-service-style packaging and subjected to 0-, 30-, 60-, or 90-d storage at -20 °C. Stored bacon was evaluated for thiobarbituric acid reactive substances (TBARS) and trained sensory evaluation of oxidized odor and flavor. Fresh belly and bacon processing traits were analyzed as a 1-way ANOVA with the fixed effect of SO, whereas shelf life traits were analyzed as a 1-way ANOVA repeated in time. There was no effect (P ≥ 0.30) of SO on belly weight, length, width, or thickness, but bellies of pigs fed 90 °C SO had greater (P ≤ 0.04) flop distance (more firm) than all other SO treatments. Belly fat NIR-IV of pigs fed 90 °C SO were 10.22 units less (P < 0.0001) than pigs fed 180 °C SO, which were 2.99 and 3.29 units less than belly adipose tissue of pigs fed 22.5 and 45 °C SO, respectively. There was no effect of SO on brine uptake or cooking yield of commercially manufactured bacon. There was a trend (P = 0.09) for bacon manufactured from bellies of pigs fed 45 and 90 °C SO to have greater slicing yields than those from pigs fed 22.5 and 180 °C SO. There were no SO × storage time interactions (P ≥ 0.27) for any shelf life trait. There was no difference in TBARS, oxidized odor, or oxidized flavor among the 4 SO treatments, although all 3 shelf life metrics increased (P < 0.0001) with storage time. Overall, feeding SO thermally processed at 90 and 180 °C reduced belly adipose tissue IV, but feeding peroxidized SO did not affect processing yields or shelf life characteristics of commercially manufactured bacon.

An experiment was conducted to determine the effect of feeding finishing pigs a corn-soybean (CSBM) diet or a CSBM diet supplemented with 30% dried distillers grains with solubles (DDGS), in combination with or without a growth-promoting ionophore (0 or 30 mg narasin/kg of diet), has on manure composition, microbial ecology, and gas emissions. Two separate groups of 24 gilts (initial BW = 145.1 kg, SD = 7.8 kg) were allotted to individual metabolism crates that allowed for total but separate collection of feces and urine during the 48-d collection period. After each of the twice-daily feedings, feces and urine from each crate was collected and added to its assigned enclosed manure storage tank. Each tank contained an individual fan system that pulled a constant stream of air over the manure surface for 2 wk prior to air (day 52) and manure sampling (day 53). After manure sampling, the manure in the tanks was dumped and the tanks cleaned for the second group of pigs. Except for total manure Ca and P output as a percent of intake and for manure methane product rate and biochemical methane potential (P ≤ 0.08), there were no interactions between diet composition and narasin supplementation. Narasin supplementation resulted in increased manure C (P = 0.05), increased manure DM, C, S, Ca, and phosphorus as a percent of animal intake (P ≤ 0.07), and increased manure volatile solids and foaming capacity (P ≤ 0.09). No effect of narasin supplementation was noted on manure VFA concentrations or any of the gas emission parameters measured (P ≥ 0.29). In contrast, feeding finishing pigs a diet containing DDGS dramatically affected manure composition as indicated by increased concentration of DM, C, ammonia, N, and total and volatile solids (P = 0.01), increased manure DM, N, and C as a percent of animal intake (P = 0.01), increased manure total VFA and phenols (P ≤ 0.05), decreased gas emissions of ammonia and volatile sulfur compounds (VSC; P = 0.01), increased emissions of phenols and indoles (P ≤ 0.06), decreased methane production rate (P = 0.01), and slight differences in microbial ecology (R ≤ 0.47). In conclusion, feeding a diet which contains an elevated level of indigestible fiber (i.e., DDGS) resulted in more fiber in the manure which therefore dramatically affected manure composition, gas emissions, and microbial ecology, while narasin supplementation to the diet did not exhibit a significant effect on any of these parameters in the resultant swine manure.

Background The phosphoinositide 3 kinase (PI3K) pathway is important in the oncogenic function of HER2. Aberrent activation of PI3K is implicated in resistance to trastuzumab and other HER2-targeted therapies and is frequent, with up to 22% of HER2 positive breast cancer having a PIK3CA mutation. Copanlisib is a pan-class 1 PI3K inhibitor that shows particular activity against PI3Kα, the isoform encoded by the PIK3CA gene. Copanlisib has been shown to re-sensitise trastuzumab resistant cell lines to trastuzumab with synergism seen in some cell lines between copanlisib and HER2 targeted therapy. Trial design The study is a phase Ib/II open label, single arm adaptive, multi-centre trial of copanlisib in combination with trastuzumab. Eligible patients are treated with a dose escalation schedule of copanlisib IV on Days 1, 8 and 15 of a 28 day cycle with trastuzumab 2 mg/kg weekly (loading dose of 4 mg/kg in cycle 1). The phase II dose will be based on the maximum tolerated dose (MTD) established in Phase Ib. Patients are treated until radiologic or symptomatic progression, unacceptable toxicity, consent withdrawal or physician's decision. Eligibility criteria Eligible patients must have recurrent incurable or metastatic HER2-positive breast cancer that has progressed on at least one prior line of trastuzumab or T-DM1-based treatment regimen in this setting. Patients with treated and controlled brain metastases are eligible. Participants must have adequate organ function and ECOG PS ≤ 2. Patients recruited for the Phase II part of the study must have a PIK3CA mutation. Patients with uncontrolled arterial hypertension, uncontrolled diabetes or recent clinically serious infections are excluded. Specific aims The primary end point for the phase Ib part of this study is to determine the MTD for the combination. For the phase II study is anti-tumour efficacy, measured by Clinical Benefit Rate (CBR). Secondary end points are evaluation of safety and tolerability, progression-free survival, time to treatment failure, duration of response and overall survival. Incorporated translational endpoints include examination of molecular tumor adaptation in tissue and blood. Given the role of PI3K in cellular glucose metabolism, an additional exploratory objective is to determine if quantitive reduction in metabolic signal on Positron Emission Tomography-Computed Tomography (PET-CT) is predictive of benefit from therapy. Statistical methods To establish the MTD, we use a modified 3+3 design where 3 additional patients will be accrued even if the first 3 patients accrued experience no dose limiting toxicities (DLT) in sequential cohorts for a planned 12 patients. To determine the CBR, a one sample exact binomial test with a one sided significance level of 5%, 19 evaluable patients will provide >80% power to detect a difference between the null hypothesis proportion of 30% for CBR versus the alternative hypothesis proportion of 65%. Present accrual and target accrual There are 9 patients recruited so far to the phase Ib part of this study. Target accrual is 12 and for phase II is 19 patients. Contact information for people with a specific interest in the trial Prof Bryan Hennessy, Beaumont Hospital, Dublin Ireland Funded by Bayer Citation Format: Keegan NM, Walshe J, Gullo G, Kennedy J, Bulger K, Kelly CM, Crown J, Toomey S, Egan K, Kerr J, Given M, Hernando A, Teiserskiene A, Grogan L, Breathnach O, Morris PG, Keane M, Hennessy BT. A phase Ib/II trial of coPANlisib in combination with tratuzumab in pretreated recurrent or metastatic HER2-positive breast cancer “PantHER” [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT3-06-05.

The varied applications of hydrogen isotopes (deuterium, D, and tritium, T) in the physical and life sciences demands a range of methods for their installation in an array of molecular architectures. In this review, we describe recent advances in synthetic C–H functionalization for hydrogen isotope exchange.

Hydrogen isotopes are unique tools for identifying and understanding biological and chemical processes. Hydrogen isotope labelling allows for the traceless and direct incorporation of an additional mass or radioactive tag into an organic molecule with almost no changes in its chemical structure, physical properties, or biological activity. Using deuterium-labelled isotopologues to study the unique mass-spectrometric patterns generated from mixtures of biologically relevant molecules drastically simplifies analysis. Such methods are now providing unprecedented levels of insight in a wide and continuously growing range of applications in the life sciences and beyond. Tritium (3 H), in particular, has seen an increase in utilization, especially in pharmaceutical drug discovery. The efforts and costs associated with the synthesis of labelled compounds are more than compensated for by the enhanced molecular sensitivity during analysis and the high reliability of the data obtained. In this Review, advances in the application of hydrogen isotopes in the life sciences are described.

The wide range of applications involving hydrogen isotopes in drug discovery and beyond dictates that their selective and efficient installation continues to present an important and continuing challenge to synthetic chemists. In this review advances in the field of hydrogen isotope exchange over the last ten years and related hydrogen isotope applications in a broad spectrum of disciplinary areas are brought together.

Energy is an expensive component of poultry diets with lipids providing a concentrated energy source to meet these needs. Three separate experiments with broilers (15 d of age), turkeys (15 d of age) and laying hens (60 wk of age) were conducted to determine the AMEn content of 10 lipids with varying fatty acid and free fatty acid concentrations and to compare these values to predicted values based on previously published equations. A corn-soybean meal (broilers and turkeys) or corn-soybean meal-distillers dried grains with solubles (layers) control diet was formulated with test diets created by mixing the control diet with 0, 3, 6, or 9% (broilers and turkeys) or 0, 2, 4, and 6% (laying hens) lipid. Experimental diets were fed over a 5-d acclimation period followed by a 48 h total excretion collection period with AMEn of the diets calculated based upon the GE, nitrogen, and titanium dioxide in the feed and excreta samples. The pen-mean AMEn of each diet was regressed on percentage lipid inclusion level using linear regression with the slope of the line representing the AMEn of each lipid source. As expected, the AMEn values varied widely among lipid sources and species, with broilers having a greater AME compared to turkeys and layers. In general, saturated fatty acids (C14:0, C16:0, and C18:0) were negatively correlated to AMEn while unsaturated fatty acids (namely C18:2) were positively correlated to AMEn. Consequently, the unsaturated: saturated ratio, the polyunsaturated fatty acids: saturated and monounsaturated fatty acids ratio, and iodine value tended to be positively related to AMEn. Compared to broilers and turkeys that were able to efficiently utilize energy from corn oil (purified and crude DDGS corn oil) relative to soybean oil, laying hen AMEn values for corn oils were reduced in comparison to soybean oil. These data indicate that energy values of lipid differ widely due to source and appear to differ relative to a particular species.

Two 21-d experiments were conducted to determine the optimum standardized ileal digestible (SID) Trp:Lys ratio for growing pigs; 1 experiment fed diets supplemented with or without an antibiotic. The primary response variables in both experiments were ADG, ADFI, G:F, and plasma urea N (PUN) concentrations with the optimum SID Trp:Lys ratio detected using broken-line analysis. Experiment 1 evaluated the optimum SID Trp:Lys ratio in growing pigs fed diets supplemented with an antibiotic. This experiment used 120 crossbred pigs that were blocked by sex and initial BW (24.13 ± 2.72 kg) and allotted to 6 SID Trp:Lys ratios in 4 replicates. Dietary treatments were formulated by the addition of crystalline Trp to create 6 SID Trp:Lys ratios (13.08%, 14.06%, 15.04%, 17.00%, 18.95%, and 20.91%) with a constant SID Lys level of 0.655%. As SID Trp:Lys ratios increased, ADG, ADFI, and G:F increased, and PUN concentrations decreased linearly ( 0.49) and no interactions between antibiotics and Trp:Lys ratios ( > 0.29). When the data for all pigs were pooled for the various Trp:Lys ratios, the optimum SID Trp:Lys ratios for ADG and PUN based on linear broken-line analysis were 14.58% ( < 0.001) and 14.54% ( < 0.001), respectively, resulting in an optimum SID Trp:Lys ratio of 14.56% as the mean of the determined optima for ADG and PUN responses. These results demonstrate that the optimum SID Trp:Lys ratio for 30- to 50-kg growing pigs is not impacted by the dietary inclusion of an antibiotic as long as the diets are formulated on an SID AA basis.

The consequences of high ambient temperature for broiler chickens collectively results in poorer productivity, prostration and even death. As they approach processing weight, broilers are particularly sensitive to heat stress as they produce large amounts of metabolic heat. Transport from farm to the processing site is a stress for broilers. So, the combination of high ambient temperature prior to transport and the stress associated with transport to processing have unwanted effects on broiler performance and meat quality. In two experiments (summer and winter) the effect of supplementing the water of Ross-308 broiler chickens with electrolytes, with or without betaine for 2 days before processing, on performance and breast muscle meat quality were investigated. In the summer experiment broilers were exposed to a cyclic high temperature protocol over the two days (9 h at 28–29 °C and 14 h at 22–24 °C). In the winter experiment the shed temperature ranged between 14 and 18 °C. The growth performance of birds during supplementation and then the breast muscle meat quality 24–72 h post-mortem were determined. In both experiments betaine had no effect on any performance or meat quality measure and the electrolyte supplementation had no effect on growth performance. In the summer experiment, electrolyte supplementation had significant effects on some measures of meat quality. Breast muscle from supplemented birds had lower 24 h post-mortem pH and based on meat ‘lightness’, lower levels of PSE meat. The 72 h drip loss was significantly lower in meat from birds that had been supplemented with electrolytes. The electrolyte supplements had no effects on meat ‘redness’ or ‘yellowness’, on shear force or cooking losses. In the winter experiment, the electrolyte supplementation had no effect on growth performance or breast muscle meat quality. In this experiment, the average shed temperature was approximately 16 °C with peak values of approximately 18 °C. The growth rate of the birds was approximately 40% higher than that identified in industry performance standards for the Ross-308 strain. The data suggest that the temperature for best performance of the Ross-308 is lower than the 18–24 °C currently accepted as ideal. In all experiments there were significant effects of bird gender on performance and meat quality measures. While electrolyte supplementation supported improvements in meat quality during periods of moderately high ambient temperature, the commercial benefit of these would need to be assessed. The value of electrolyte supplementation is likely to be more substantial when broiler chickens experience heat wave conditions with temperatures > 32 °C, but this remains to be evaluated.

Beef longissimus lumborum muscles (24) were each portioned into 6 steaks, and these were held at ~0.5 °C for up to 14 weeks. Total volatile basic nitrogen (TVB-N) data was compared against other measures of quality and freshness: total viable microbial count (TVC), ultimate pH, drip loss, purge, moisture content, cook loss, shear force, particle size, vitamin E, intramuscular fat content (IMF) and colour parameters. There was an association between TVB-N and colour parameters; and between TVB-N and several parameters for microbial load, tenderness and moisture. IMF and vitamin E were not correlated to TVB-N. TVB-N of 5.1 mg/100 g (95% confidence intervals: 4.6–5.5 mg/100 g) was estimated as equivalent to a TVC of log 7 cfu/g. When beef samples were categorised as either spoilt or fresh using this TVC recommendation, TVB-N was correct in 77.9% of its assignments. Additional investigation is necessary to confirm this result against a larger sample population with a broader range of TVB-N values.

The objective of this study was to evaluate the effect of feeding hydrogenated palm kernel oil (PKO), palm oil (PO), or soybean oil (SO) relative to unhydrogenated PKO, PO, and SO on apparent total tract digestibility (ATTD) of gross energy (GE) and ether extract (EE), and on pig performance, in to 20 to 40 kg pigs. One hundred and fifty-four pigs (39.5 ± 3.6 kg BW) were randomly assigned to one of 9 diets composed of a basal diet, or test diets containing 94% of the basal diet and 6% added lipid. Lipids consisted of either unhydrogenated or hydrogenated PKO, PO, or SO in a factorial arrangement. The basal diet contained titanium dioxide as an inert maker and was used to determine the ATTD of GE or EE of each lipid using the difference method. There were 2 pigs per pen with pigs ad libitum fed for 25 d to measure growth performance. On d 23 and 24, a fresh fecal sample was obtained from each pen to measure ATTD of GE and EE. There was an interaction between lipid source and hydrogenation for ATTD of GE and EE of the lipid (P ≤ 0.01), where hydrogenation of PKO had no effect on ATTD of GE or EE of the lipid, while hydrogenation of PO and SO resulted in a reduction in the ATTD of GE and EE compared to their unhydrogenated counterparts. There was also an interaction between lipid source and hydrogenation on GF (P ≤ 0.01) where hydrogenation of PKO had no effect on GF while hydrogenation of PO and SO resulted in a reduction in GF compared to their unhydrogenated counterparts. The data show that hydrogenation of PKO has no impact on ATTD of GE and EE of the lipid, or on GF, but hydrogenation of PO or SO reduce ATTD of GE and EE of the lipid, and GF, due to their fatty acids being longer in carbon chain length.