Effect of the method of preservation on the chemical composition and in vitro fermentation characteristics in two legumes rich in condensed tannins

The objective of the present study was to evaluate the effects of preservation (hay and silage) on the chemical composition and the in vitro fermentation characteristics in comparison with fresh forage in two legumes rich in condensed tannins (CT). Sainfoin (Onobrychis viciifolia) was collected at the late bloom stage and sulla (Hedysarum coronarium) at the early bloom stage. In each forage, a part was immediately freeze-dried, a part was dried at ambient temperature to obtain hay, and another part was ensiled in vacuum-packages for 82 days. An in vitro assay to study the fermentation was carried out with an Ankom system during 72 h. In both forages, the silages had different contents of polyphenols and condensed tannins fractions than fresh forage and hay (P<0.05). Sainfoin hay only had greater content of fibre-bound CT fraction (FBCT) than fresh sainfoin, whereas sulla hay had greater protein-bound CT and FBCT contents than fresh sulla (P<0.05). Sainfoin silage had lower gas and methane production than hay and fresh forage (P < 0.001), whereas fresh sulla had greater gas and methane production, followed by hay and silage, which produced the least (P<0.05). In both legumes, hay had lower in vitro organic matter digestibility (IVOMD) than silage and fresh forage (P<0.001). The method of preservation affected the total production of volatile fatty acids (VFA) only in sulla (P<0.05). Most of the proportions of individual VFA were affected by the method of preservation in both legumes (P<0.001). In conclusion, polyphenols content, total content and fractions of CT were more affected in the silages than in the hays when compared to fresh forages. However, according to gas and methane production and IVOMD, silage may have greater feed nutritive value than hay although further studies on animal performance are warranted before recommendation

Methane Production of Fresh Sainfoin, with or without PEG, and Fresh Alfalfa at Different Stages of Maturity is Similar, but the Fermentation End Products Vary (vol 9, 197, 2019)

The authors wish to make the following correction to their paper [1]. In Table 2, the production of methane in alfalfa at the start-flowering should be 38 mL/g dOM and not 3 mL/g dOM. Table 2. Effect of the substrate (S) and the stage of maturity 1 (SM) on gas and methane production (CH4), potential gas production (A), rate of gas production (c), in vitro organic matter degradability (IVOMD), ammonia (NH3-N), and volatile fatty acids (VFAs). Table The authors would like to apologize for any inconvenience caused

Carotenoids and liposoluble vitamins in the plasma and tissues of light lambs given different maternal feedings and fattening concentrates

The carotenoids and liposoluble vitamins in the plasma and tissues of the lambs under different maternal feedings and fattening concentrates was studied. During lactation, 21 lambs were housed with their dams, that received a total mixed ration (intensive); 21 ewe–lamb pairs grazed on alfalfa; and 21 pairs grazed on sainfoin. After weaning, half of the lambs in each maternal feeding group received a commercial concentrate (control) and the other half a concentrate with quebracho (Schinopsis balansae), as a source of condensed tannins, until they were slaughtered (23 kg). The analyte concentrations in the plasma of lambs at weaning reflected the content in the feedstuffs. Grazing during suckling more than doubled the contents of lutein in the liver and retinol in the tissues compared to the intensive feeding. The content of a-tocopherol in the tissues was greatest in sainfoin lambs, intermediate in alfalfa lambs, and lowest in the intensive lambs. The quebracho concentrate decreased a-tocopherol (by 41–81%) and ¿-tocopherol (by 65–89%) contents in the lamb tissues. The use of the analytes in the plasma at weaning correctly classified 100% of the lambs into the maternal feeding (intensive vs. grazing (alfalfa + sainfoin)) but has to be improved in the carcass and tissues separately

The Inclusion of Concentrate with Quebracho Is Advisable in Two Forage-Based Diets of Ewes According to the In Vitro Fermentation Parameters

Simple Summary In dry, mountainous areas, ewes are fed low-quality forages (hay or straw) indoors, although they also graze in high-quality pastures when available. Concentrate supplementation is recommended to cover high nutritional requirements during lactation. Condensed tannins (CT) of quebracho (Schinopsis balansae) can be included in the concentrate to reduce methane (CH4) emissions and ruminal degradation of protein, improving the fermentation’s efficiency. Furthermore, low levels of quebracho can improve some meat and milk quality traits. The effects of the inclusion of concentrate and CT in diets depend on the level of inclusion and the quality of forage. The aim of this study was to evaluate the in vitro fermentation characteristics of diets in order to identify the most suitable one to be fed to ewes under farming conditions. The diets examined differed in quality of the forage available, comparing hay versus fresh forage diets and forage alone versus 70:30 forage:concentrate with (quebracho) or without CT (control) in each type of forage. The fresh-forage-based diets had lower gas and CH4 production and greater in vitro organic matter degradability (IVOMD) than the hay-based diets. The inclusion of quebracho concentrate increased the IVOMD in hay-based diets and reduced ammonia content in fresh-forage-based diets. Abstract Ewes receive hay or graze on fresh pastures supplemented with concentrates to fulfil their lactation requirements. Quebracho (Schinopsis balansae) can be added to change the ruminal fermentation. Fermentation parameters of forages alone and 70:30 forage:concentrate diets with control and quebracho concentrate were compared after 24 h of in vitro incubation. Fresh forage diets produced less gas (p < 0.05) and had greater IVOMD (p < 0.001), ammonia (NH3-N) content, valeric acid, branched-chain volatile fatty acid proportions, and lower propionic acid proportion than the hay diets (p < 0.01). In the hay diets, methane production increased with control concentrate (p < 0.01) and tended to decrease with quebacho concentrate (p < 0.10). The inclusion of both concentrates increased the acetic:propionic ratio (p < 0.01), and only the inclusion of quebracho concentrate increased the IVOMD (p < 0.01). In the fresh forage diets, gas and methane production increased with the inclusion of the control concentrate (p < 0.05), but methane production decreased with quebracho concentrate (p < 0.01). The inclusion of quebracho concentrate reduced the NH3-N content and valeric acid proportion (p < 0.05). In conclusion, the inclusion of quebracho concentrate would be advisable to reduce the CH4 production and NH3-N content in fresh forage diets and to increase the IVOMD in hay diets in comparison with the forages alone

Proteomic profiling of urine for the detection of colon cancer.

BACKGROUND: Colorectal cancer is the second most common cause of cancer related death in the developed world. To date, no blood or stool biomarkers with both high sensitivity and specificity for potentially curable early stage disease have been validated for clinical use. SELDI and MALDI profiling are being used increasingly to search for biomarkers in both blood and urine. Both techniques provide information predominantly on the low molecular weight proteome (<15 kDa). There have been several reports that colorectal cancer is associated with changes in the serum proteome that are detectable by SELDI and we hypothesised that proteomic changes would also be detectable in urine. RESULTS: We collected urine from 67 patients with colorectal cancer and 72 non-cancer control subjects, diluted to a constant protein concentration and generated MALDI and SELDI spectra. The intensities of 19 peaks differed significantly between cancer and non-cancer patients by both t-tests and after adjusting for confounders using multiple linear regressions. Logistic regression classifiers based on peak intensities identified colorectal cancer with up to 78% sensitivity at 87% specificity. We identified and independently quantified 3 of the discriminatory peaks using synthetic stable isotope peptides (an 1885 Da fragment of fibrinogen and hepcidin-20) or ELISA (beta2-microglobulin). CONCLUSION: Changes in the urine proteome may aid in the early detection of colorectal cancer

Effect of the rate of inclusion of field pea in the concentrate of lambs on in vitro fermentation parameters

The replacement of soya by local protein sources, as the field pea (Pisum sativum), has been encouraged to reduce the dependency of Europe on soya imports. The aim of this study was to investigate the effect of increasing amounts of field pea in the lamb’s concentrate (0%Pea, 10%Pea, 20%Pea and 30%Pea) on in vitro fermentation. Gas production was determined with the Ankom system for 24 hours and the parameters of kinetics of fermentation were estimated. Methane, ammonia (NH3 -N) and in vitro organic matter degradability (IVOMD) were determined. Most of the parameters were affected by the rate of inclusion of pea. The 10%Pea concentrate had the lowest gas production and the NH3 -N content (P<0.05). Methane production was lower in 10%Pea than in 30%Pea (P<0.05), presenting 0%Pea and 20%Pea intermediate values. Regarding the IVOMD, the 10%Pea had greater degradability than 20%Pea and 30%Pea (P<0.05) presenting 0%Pea intermediate value (P>0.05). In conclusion, a partial substitution of soya by 10% field pea in lamb’s concentrate could be recommended because it reduced gas and methane production and NH3 -N content whereas it increased IVOMD.Le remplacement du soja par des sources de protéines locales, comme le pois de grande culture (Pisum sativum), a été encouragé afin de réduire la dépendance de l’Europe vis-à-vis des importations de soja. Le but de cette étude était d’étudier l’effet de l’augmentation des quantités de pois (0%de Pois, 10% de Pois, 20% de Pois et 30% de Pois) dans le concentré d’agneau sur la fermentation in vitro. La production de gaz a été déterminée avec le système Ankom pendant 24 heures et les paramètres de cinétique de fermentation ont été estimés. Le méthane, l’ammoniac (NH3 -N) et la dégradation de la matière organique in vitro (IVOMD) ont été déterminés. Le taux d’inclusion du pois a eu un effet sur la plupart des paramètres. Ainsi, le concentré de 10% de Pois a réduit la production de gaz et la teneur en NH3 -N par rapport au reste des concentrés (p <0,05). La production de méthane était plus faible pour le concentré de 10% de Pois que chez celui de 30% de Pois (P <0,05). Concernant l’IVOMD, le concentré de 10% de Pois avait une digestibilité supérieure à ceux de 20% et de30% de Pois (p 0,05). En conclusion, une substitution partielle du soja par 10% de Pois dans les concentrés d’agneau pourrait être recommandée car elle réduit la production de gaz, demethane et la teneur en NH3 -N, alors qu’elle augmenterait l’IVOMD.The authors gratefully acknowledge the staff of the CITA Research Centre for technical support, especially to Angelines Legua and Andrés Domínguez. Project RTA2014-00032-c02-01 and RZPP2017; INIA and ESF funded M. Blanco contractOvinePeaDegradability in vitroMethaneAmmoniaPoisDégradation in vitroOvineMethaneAmmoniacPublishe

Daratumumab plus lenalidomide and dexamethasone in relapsed/ refractory multiple myeloma: extended follow-up of POLLUX, a randomized, open-label, phase 3 study

In POLLUX, daratumumab (D) plus lenalidomide/dexamethasone (Rd) reduced the risk of disease progression or death by 63% and increased the overall response rate (ORR) versus Rd in relapsed/refractory multiple myeloma (RRMM). Updated efficacy and safety after >3 years of follow-up are presented. Patients (N = 569) with ≥1 prior line received Rd (lenalidomide, 25 mg, on Days 1–21 of each 28-day cycle; dexamethasone, 40 mg, weekly) ± daratumumab at the approved dosing schedule. Minimal residual disease (MRD) was assessed by next-generation sequencing. After 44.3 months median follow-up, D-Rd prolonged progression-free survival (PFS) in the intent-to-treat population (median 44.5 vs 17.5 months; HR, 0.44; 95% CI, 0.35–0.55; P < 0.0001) and in patient subgroups. D-Rd demonstrated higher ORR (92.9 vs 76.4%; P < 0.0001) and deeper responses, including complete response or better (56.6 vs 23.2%; P < 0.0001) and MRD negativity (10–5; 30.4 vs 5.3%; P < 0.0001). Median time to next therapy was prolonged with D-Rd (50.6 vs 23.1 months; HR, 0.39; 95% CI, 0.31–0.50; P < 0.0001). Median PFS on subsequent line of therapy (PFS2) was not reached with D-Rd versus 31.7 months with Rd (HR, 0.53; 95% CI, 0.42–0.68; P < 0.0001). No new safety concerns were reported. These data support using D-Rd in patients with RRMM after first relapse

Pharmacokinetics and Exposure–Response Analyses of Daratumumab in Combination Therapy Regimens for Patients with Multiple Myeloma

Introduction: Daratumumab, a human IgG monoclonal antibody targeting CD38, has demonstrated activity as monotherapy and in combination with standard-of-care regimens in multiple myeloma. Population pharmacokinetic analyses were conducted to determine the pharmacokinetics of intravenous daratumumab in combination therapy versus monotherapy, evaluate the effect of patient- and disease-related covariates on drug disposition, and examine the relationships between daratumumab exposure and efficacy/safety outcomes. Methods: Four clinical studies of daratumumab in combination with lenalidomide/dexamethasone (POLLUX and GEN503); bortezomib/dexamethasone (CASTOR); pomalidomide/dexamethasone, bortezomib/thalidomide/dexamethasone, and bortezomib/melphalan/prednisone (EQUULEUS) were included in the analysis. Using various dosing schedules, the majority of patients (684/694) received daratumumab at a dose of 16 mg/kg. In GEN503, daratumumab was administered at a dose of 2 mg/kg (n = 3), 4 mg/kg (n = 3), 8 mg/kg (n = 4), and 16 mg/kg (n = 34). A total of 650 patients in EQUULEUS (n = 128), POLLUX (n = 282), and CASTOR (n = 240) received daratumumab 16 mg/kg. The exposure–efficacy and exposure–safety relationships examined progression-free survival (PFS) and selected adverse events (infusion-related reactions; thrombocytopenia, anemia, neutropenia, lymphopenia, and infections), respectively. Results: Pharmacokinetic profiles of daratumumab were similar between monotherapy and combination therapy. Covariate analysis identified no clinically important effects on daratumumab exposure, and no dose adjustments were recommended on the basis of these factors. Maximal clinical benefit on PFS was achieved for the majority of patients (approximately 75%) at the 16 mg/kg dose. No apparent relationship was observed between daratumumab exposure and selected adverse events. Conclusion: These data support the recommended 16 mg/kg dose of daratumumab and the respective dosing schedules in the POLLUX and CASTOR pivotal studies. Funding: Janssen Research & Development