Effects of feeding sainfoin proanthocyanidins to lactating ewes on intake, milk production and plasma metabolites; 34996024

There is increasing interest in using sainfoin (Onobrychis viciifolia) to feed sheep, but it contains proanthocyanidins (PACs), and the associated effects of PAC on sheep production are not well-known. The aim of the study was to assess the effect of the presence of PAC from sainfoin, through the inclusion of polyethylene glycol (PEG), on the intake and productive parameters of local ewes bearing one male lamb. For the experiment, 20 ewes and their newborn male lambs were placed in individual indoor cages. All ewes were fed ad libitum fresh sainfoin plus 200 g/d barley. Twice daily, half of the ewes were orally dosed with only water (Sainfoin Group; n = 10), and the other half were orally dosed with 100 g/d PEG 4000 per ewe (Sainfoin + PEG Group; n = 10). Sucking lambs were permanently housed with their dams until they reached 10–12 kg BW. The intake of sainfoin was recorded daily, and its chemical composition was analysed. Weekly, the BW, body condition score (BCS), milk yields and individual milk and blood samples were recorded. At the beginning and end of the experiment, faecal samples were collected from ewes and analysed for the anthelmintic role of PAC. The chemical composition, polyphenol content and antioxidant capacity of the diet and milk were analysed. The presence of PAC did not affect the intake, BW, BCS or milk yield of the dams (P > 0.05); however, all parameters were affected by the week of lactation (P 0.05). The presence of PAC had no effect on parasitism (P > 0.05). In conclusion, the presence of PAC had no relevant effects on milk production, although it affected protein metabolism, as indicated by the urea contents in milk and plasma. © 2021 The Author

Effects of condensed tannins from sainfoin on the milk fatty acid profile of ewes.

Abstract M136 There is an increased interest in using local fodder legumes to improve the self-sufficiency of feed for livestock. Sainfoin (Onobrychis viciifolia) is a typical high-quality crop of Mediterranean areas with a medium-high content of condensed tannins (CT), however their effects on milk composition are not well known. The aim of the study was to evaluate the effect of CT from fresh sainfoin on milk production, chemical composition, and fatty acids during 4 wk of lactation. Twenty pairs dam-lamb were individually fed fresh sainfoin ad libitum plus 200 g/d of barley. The distribution of pairs dam-lamb were done according to ewe’s BW (60.7 ± 6.15 kg BW) and BCS (3.3 ± 0.57), lambing date (06/04/2019 ± 0.95) and lamb weight at birth (4.1 ± 0.64 kg BW). Half of the ewes were daily orally dosed 100 g of PEG 4000/200 mL water per ewe as a tannin-binding agent (SF+PEG) and the other half received only water (SF). Once a week, ewes were milked and samples of sainfoin and milk were obtained and analyzed for chemical composition and individual fatty acids (FAs). The total saturated FA (SFA), monounsaturated FA (MUFA), polyunsaturated FA (PUFA), PUFA n-3 and PUFA n-6 were calculated. The sums and the major FA were analyzed using mixed models, with week of lactation as fixed and ewe as random effects using the SAS statistical software (SAS v.9.3)..

An EORTC Phase II study of caspofungin as first-line therapy of invasive aspergillosis in haematological patients

Objectives Caspofungin was evaluated as first-line monotherapy of invasive aspergillosis (IA) in patients with haematological malignancies and undergoing autologous transplants. Methods Adults with proven or probable IA, defined strictly according to EORTC-MSG criteria, were eligible. Those with possible IA were enrolled, but were not evaluable for efficacy unless upgraded to proven/probable disease within 7 days of registration based on investigations performed within 48 h after enrolment. Caspofungin dosage was 70 mg (day 1) followed by 50 mg/day. The primary endpoint was the proportion of patients with complete or partial response at the end of caspofungin therapy in the modified intention to treat (MITT) group; secondary endpoints were response and survival at day 84 and safety. Results In the MITT group (n = 61), 75% of patients had cancer not in remission (relapsing or refractory), 85% were neutropenic at enrolment and 49% had a Karnofsky score of ≤50. At end of treatment, 1 and 19 patients had complete and partial response, respectively [success rate 33% (20/61)], 9 (15%) achieved stabilization and 31 (51%) had disease progression. One patient was not evaluable. The 6 and 12 week survival rates were 66% (40/61) and 53% (32/60), respectively. Baseline characteristics associated with survival at day 84 were an underlying disease in remission (not relapsing or refractory) and Karnofsky score. Recovery from neutropenia at the end of treatment was also significantly associated with survival. No serious drug-related adverse events or discontinuations due to drug-related adverse events were observed. Conclusions Caspofungin provided an observed response rate compatible with the null hypothesis of a true response rate of ≤35%. Underlying disease-related factors had a major impact on result

The effects of high-intensity interval training on glucose metabolism, cardiorespiratory fitness and weight control in subjects with diabetes: systematic review a meta-analysis

Aim: The objective of this meta-analysis was to explore the effects of high-intensity interval training (HIIT) compared with control conditions (CON) or moderate intensity continuous training (MICT) on glycemic parameters in diabetes subjects. Methods: Pubmed, Embase and Google Scholar databases were searched for HIIT interventions that were carried out in diabetic subjects and exploring fasting glucose, glycated haemoglobin (HbA1c), fasting insulin and/or HOMA-IR. Results: This systematic review retrieved a total of 1741 studies of which 32 articles fulfilled the eligibility criteria. Nineteen trials were included in the meta-analysis since they compared HIIT intervention with CON or MICT group. There was a significantly reduction of fasting glucose of 13.3 mg/dL (p < 0.001), Hb1Ac -0.34% (p < 0.001), insulin -2.27 UI/L (p = 0.003), HOMA-IR -0.88 (p = 0.005) in the HIIT-group compared with CON-group. Nevertheless, this reduction was not significantly different when comparing HIIT with MICT (p = 0.140, p = 0.315, p = 0.520 and p = 0.389). Besides, there was a significant increase of absolute VO2max of 0.21 L/min (p < 0.001) and relative VO2max of 2.94 ml/kg/min (p < 0.001) in the HIIT-group compared with the CON-group and the MICT-group (0.22 L/min, p = 0.025) and (0.97 ml/kg/min, p = 0.045). Conclusions: These findings revealed that HIIT intervention led to significant improvement in glycemic control and insulin resistance in subjects with diabetes compared with CON-group

STARD1 promotes NASH-driven HCC by sustaining the generation of bile acids through the alternative mitochondrial pathway

Background & Aims Besides their physiological role in bile formation and fat digestion, bile acids (BAs) synthesised from cholesterol in hepatocytes act as signalling molecules that modulate hepatocellular carcinoma (HCC). Trafficking of cholesterol to mitochondria through steroidogenic acute regulatory protein 1 (STARD1) is the rate-limiting step in the alternative pathway of BA generation, the physiological relevance of which is not well understood. Moreover, the specific contribution of the STARD1-dependent BA synthesis pathway to HCC has not been previously explored. Methods STARD1 expression was analyzed in a cohort of human non-alcoholic steatohepatitis (NASH)-derived HCC specimens. Experimental NASH-driven HCC models included MUP-uPA mice fed a high-fat high-cholesterol (HFHC) diet and diethylnitrosamine (DEN) treatment in wild-type (WT) mice fed a HFHC diet. Molecular species of BAs and oxysterols were analyzed by mass spectrometry. Effects of NASH-derived BA profiles were investigated in tumour-initiated stem-like cells (TICs) and primary mouse hepatocytes (PMHs). Results Patients with NASH-associated HCC exhibited increased hepatic expression of STARD1 and an enhanced BA pool. Using NASH-driven HCC models, STARD1 overexpression in WT mice increased liver tumour multiplicity, whereas hepatocyte-specific STARD1 deletion (Stard1ΔHep) in WT or MUP-uPA mice reduced tumour burden. These findings mirrored the levels of unconjugated primary BAs, β-muricholic acid and cholic acid, and their tauroconjugates in STARD1-overexpressing and Stard1ΔHep mice. Incubation of TICs or PMHs with a mix of BAs mimicking this profile stimulated expression of genes involved in pluripotency, stemness and inflammation. Conclusions The study reveals a previously unrecognised role of STARD1 in HCC pathogenesis, wherein it promotes the synthesis of primary BAs through the mitochondrial pathway, the products of which act in TICs to stimulate self-renewal, stemness and inflammation. Lay summary Effective therapy for hepatocellular carcinoma (HCC) is limited because of our incomplete understanding of its pathogenesis. The contribution of the alternative pathway of bile acid (BA) synthesis to HCC development is unknown. We uncover a key role for steroidogenic acute regulatory protein 1 (STARD1) in non-alcoholic steatohepatitis-driven HCC, wherein it stimulates the generation of BAs in the mitochondrial acidic pathway, the products of which stimulate hepatocyte pluripotency and self-renewal, as well as inflammation.We acknowledge support from grants PID2019-111669RB-100, SAF2017-85877R and SAF2015-73579-JIN from Plan Nacional de I+D funded by the Agencia Estatal de Investigación (AEI), the Fondo Europeo de Desarrollo Regional (FEDER) and CIBEREHD; the center grant P50AA011999 Southern California Research Center for ALPD and Cirrhosis funded by NIAAA / NIH; as well as support from AGAUR of the Generalitat de Catalunya SGR-2017-1112, European Cooperation in Science & Technology (COST) ACTION CA17112 Prospective European Drug-Induced Liver Injury Network, the ‘ER stress-mitochondrial cholesterol axis in obesity-associated insulin resistance and comorbidities’-Ayudas FUNDACION BBVA and the Red Nacional 2018-102799-T de Enfermedades Metabólicas y Cáncer, and Project 201916/31 "Contribution of mitochondrial oxysterol and bile acid metabolism to liver carcinogenesis" 2019 by Fundació Marato TV3. We also acknowledge the support from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI16/00598, co-funded by European Regional Development Fund / European Social Fund, ‘Investing in your future’) and Centro Internacional sobre el Envejecimiento (OLD-HEPAMARKER, 0348_CIE_6_E), Spain. We also acknowledge support from R01 CA2344128 and U01 AA022614 grants to M.K.Peer reviewe

Feel4Diabetes healthy diet score: Development and evaluation of clinical validity

Background: The aim of this paper is to present the development of the Feel4Diabetes Healthy Diet Score and to evaluate its clinical validity. Methods: Study population consisted of 3268 adults (63% women) from high diabetes risk families living in 6 European countries. Participants filled in questionnaires at baseline and after 1 year, reflecting the dietary goals of the Feel4Diabetes intervention. Based on these questions the Healthy Diet Score was constructed, consisting of the following components: breakfast, vegetables, fruit and berries, sugary drinks, whole-grain cereals, nuts and seeds, low-fat dairy products, oils and fats, red meat, sweet snacks, salty snacks, and family meals. Maximum score for each component was set based on its estimated relative importance regarding T2DM risk, higher score indicating better quality of diet. Clinical measurements included height, weight, waist circumference, heart rate, blood pressure, and fasting blood sampling, with analyses of glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglycerides. Analysis of (co) variance was used to compare the Healthy Diet Score and its components between countries and sexes using baseline data, and to test differences in clinical characteristics between score categories, adjusted for age, sex and country. Pearson''s correlations were used to study the association between changes from baseline to year 1 in the Healthy Diet Score and clinical markers. To estimate reproducibility, Pearson''s correlations were studied between baseline and 1 year score, within the control group only. Results: The mean total score was 52.8 ± 12.8 among women and 46.6 ± 12.8 among men (p < 0.001). The total score and its components differed between countries. The change in the Healthy Diet Score was significantly correlated with changes in BMI, waist circumference, and total and LDL cholesterol. The Healthy Diet Score as well as its components at baseline were significantly correlated with the values at year 1, in the control group participants. Conclusion: The Feel4Diabetes Healthy Diet Score is a reproducible method to capture the dietary information collected with the Feel4Diabetes questionnaire and measure the level of and changes in the adherence to the dietary goals of the intervention. It gives a simple parameter that associates with clinical risk factors in a meaningful manner

International descriptive and interventional survey for oxycholesterol determination by gas- and liquid-chromatographic methods

Increasing numbers of laboratories develop new methods based on gas-liquid and high-performance liquid chromatography to determine serum concentrations of oxygenated cholesterol metabolites such as 7α-, 24(S)-, and 27-hydroxycholesterol. We initiated a first international descriptive oxycholesterol (OCS) survey in 2013 and a second interventional survey 2014 in order to compare levels of OCS reported by different laboratories and to define possible sources of analytical errors. In 2013 a set of two lyophilized serum pools (A and B) was sent to nine laboratories in different countries for OCS measurement utilizing their own standard stock solutions. In 2014 eleven laboratories were requested to determine OCS concentrations in lyophilized pooled sera (C and D) utilizing the same provided standard stock solutions of OCS. The participating laboratories submitted results obtained after capillary gas-liquid chromatography-mass selective detection with either epicoprostanol or deuterium labelled sterols as internal standards and high-performance liquid chromatography with mass selective detection and deuterated OCS as internal standard. Each participant received a clear overview of the results in form of Youden-Plots and basic statistical evaluation in its used unit. The coefficients of variation of the concentrations obtained by all laboratories using their individual methods were 58.5–73.3% (survey 1), 56.8–60.3% (survey 2); 36.2–35.8% (survey 1), 56.6–59.8, (survey 2); 61.1–197.7% (survey 1), 47.2–74.2% (survey 2) for 24(S)-, 27-, and 7α-hydroxycholesterol, respectively. We are surprised by the very great differences between the laboratories, even under conditions when the same standards were used. The values of OCS's must be evaluated in relation to the analytical technique used, the efficiency of the ample separation and the nature of the internal standard used. Quantification of the calibration solution and inappropriate internal standards could be identified as major causes for the high variance in the reported results from the different laboratories. A harmonisation of analytical standard methods is highly needed

First international descriptive and interventional survey for cholesterol and non-cholesterol sterol determination by gas- and liquid- chromatography–Urgent need for harmonisation of analytical methods

Serum concentrations of lathosterol, the plant sterols campesterol and sitosterol and the cholesterol metabolite 5α-cholestanol are widely used as surrogate markers of cholesterol synthesis and absorption, respectively. Increasing numbers of laboratories utilize a broad spectrum of well-established and recently developed methods for the determination of cholesterol and non-cholesterol sterols (NCS). In order to evaluate the quality of these measurements and to identify possible sources of analytical errors our group initiated the first international survey for cholesterol and NCS. The cholesterol and NCS survey was structured as a two-part survey which took place in the years 2013 and 2014. The first survey part was designed as descriptive, providing information about the variation of reported results from different laboratories. A set of two lyophilized pooled sera (A and B) was sent to twenty laboratories specialized in chromatographic lipid analysis. The different sterols were quantified either by gas chromatography-flame ionization detection, gas chromatography- or liquid chromatography-mass selective detection. The participants were requested to determine cholesterol and NCS concentrations in the provided samples as part of their normal laboratory routine. The second part was designed as interventional survey. Twenty-two laboratories agreed to participate and received again two different lyophilized pooled sera (C and D). In contrast to the first international survey, each participant received standard stock solutions with defined concentrations of cholesterol and NCS. The participants were requested to use diluted calibration solutions from the provided standard stock solutions for quantification of cholesterol and NCS. In both surveys, each laboratory used its own internal standard (5α-cholestane, epicoprostanol or deuterium labelled sterols). Main outcome of the survey was, that unacceptably high interlaboratory variations for cholesterol and NCS concentrations are reported, even when the individual laboratories used the same calibration material. We discuss different sources of errors and recommend all laboratories analysing cholesterol and NCS to participate in regular quality control programs