Why effect sizes are systematically larger for progression-free survival than overall survival in cancer drug trials: Prognostic scores as a way forward.

Cancer drugs have accumulated the most approvals over the past years. Overall survival (OS) is considered the gold standard for cancer trial outcomes. However, its use has declined over the past years, in favor of surrogate endpoints, such as progression-free survival (PFS).

IMI-Type Carbapenemase-Producing Enterobacter cloacae Complex, France and Overseas Regions, 2012-2022.

We characterized a collection of IMI-like-producing Enterobacter spp. isolates (n = 112) in France. The main clone corresponded to IMI-1-producing sequence type 820 E.

Evaluation of analytical performance of AQUIOS CL flow cytometer and method comparison with bead-based flow cytometry methods.

Objectives: Given that method validation is mandatory for compliance with the International Organization for Standardization (ISO) 15,189 standard requirements, we evaluated the analytical performance of the AQUIOS CL system (Beckman Coulter) and compared it with two bead-based flow cytometry (FCM) protocols (BD FACSCAntoII and Beckman Coulter DxFLEX). There are no comparative literature data on standardized protocols for counting lymphocyte subsets on the new-generation cytometer DxFLEX.

Methods: We evaluated the AQUIOS CL's performance with regard to accuracy, linearity and stability by using dedicated control cell samples and patient samples.

Associations between Forkhead Box O1 (FoxO1) Expression and Indicators of Hepatic Glucose Production in Transition Dairy Cows Supplemented with Dietary Nicotinic Acid.

Forkhead box protein O1 (FoxO1) is a transcription factor which promotes hepatic glucose production (HGP) by up-regulating the transcription of gluconeogenic enzymes in monogastric species. The activity of FoxO1 is inhibited by insulin-induced phosphorylation. The aims of the present study were to find associations between FoxO1 expression and variables associated with HGP as affected by feeding regimen in dairy cows during the transition period.

Insulin Signaling in Liver and Adipose Tissues in Periparturient Dairy Cows Supplemented with Dietary Nicotinic Acid.

The glucose homeostasis in dairy cattle is very well controlled, in line with the metabolic adaptation during the periparturient period. Former studies showed that nicotinic acid (NA) lowered plasma non-esterified fatty acids (NEFA) concentrations and increased insulin sensitivity in dairy cows. Thus, the purpose of this study was to investigate whether the expression of proteins involved in hepatic and adipose insulin signaling and protein expression of hepatic glucose transporter 2 (GLUT2) were affected by dietary NA and dietary concentrate intake in periparturient dairy cows.

Longitudinal changes in adipose tissue of dairy cows from late pregnancy to lactation. Part 2: The SIRT-PPARGC1A axis and its relationship with the adiponectin system.

The transition period in dairy cows is characterized by major changes in glucose and adipose tissue metabolism. The Sirtuin-1 (SIRT1) PPARγ co-activator 1α (PPARGC1A) axis might be related to the adiponectin (ADIPOQ) system to orchestrate the regulation of these processes. We aimed to assess the mRNA abundance of the aforementioned components in one visceral and one subcutaneous fat depot, together with the ADIPOQ concentrations in serum of dairy cows from late gestation to early lactation.

Longitudinal changes in adipose tissue of dairy cows from late pregnancy to lactation. Part 1: The adipokines apelin and resistin and their relationship to receptors linked with lipolysis.

The transition from pregnancy to lactation is characterized by major changes in glucose and adipose tissue metabolism. Anti- and prolipolytic pathways mediated via the hydroxycarboxylic acid receptors 1 (HCAR1) and 2 (HCAR2) and tumor necrosis factor-α receptor 1 (TNFR1), as well as the adipokines apelin and resistin, are likely involved in regulating these processes. This study aimed to determine the mRNA abundance of the aforementioned receptors in both subcutaneous and visceral adipose tissue, to characterize the adipokine concentrations in serum, and to test the effects of feeding diets with either high or low portions of concentrate and a concomitant niacin supplementation from late gestation to early lactation.

Haematological and immunological adaptations of non-pregnant, non-lactating dairy cows to a high-energetic diet containing mycotoxins.

Diet change and fatness are supposed to challenge the immune system of the cow. Therefore, immunological and haematological consequences of adaptation to and continued feeding of a high-energy diet were studied in eight non-pregnant, non-lactating Holstein cows over 16 weeks. Blood haptoglobin concentration remained unaltered, suggesting that an acute phase reaction was not induced.

Functional Dissection of the Nascent Polypeptide-Associated Complex in Saccharomyces cerevisiae.

Both the yeast nascent polypeptide-associated complex (NAC) and the Hsp40/70-based chaperone system RAC-Ssb are systems tethered to the ribosome to assist cotranslational processes such as folding of nascent polypeptides. While loss of NAC does not cause phenotypic changes in yeast, the simultaneous deletion of genes coding for NAC and the chaperone Ssb (nacΔssbΔ) leads to strongly aggravated defects compared to cells lacking only Ssb, including impaired growth on plates containing L-canavanine or hygromycin B, aggregation of newly synthesized proteins and a reduced translational activity due to ribosome biogenesis defects. In this study, we dissected the functional properties of the individual NAC-subunits (α-NAC, β-NAC and β'-NAC) and of different NAC heterodimers found in yeast (αβ-NAC and αβ'-NAC) by analyzing their capability to complement the pleiotropic phenotype of nacΔssbΔ cells.

Expression of metabolic sensing receptors in adipose tissues of periparturient dairy cows with differing extent of negative energy balance.

We recently showed that the mRNA expression of genes encoding for specific nutrient sensing receptors, namely the free fatty acid receptors (FFAR) 1, 2, 3, and the hydroxycarboxylic acid receptor (HCAR) 2, undergo characteristic changes during the transition from late pregnancy to lactation in certain adipose tissues (AT) of dairy cows. We hypothesised that divergent energy intake achieved by feeding diets with either high or low portions of concentrate (60% v. 30% concentrate on a dry matter basis) will alter the mRNA expression of FFAR 1, 2, 3, as well as HCAR2 in subcutaneous (SCAT) and retroperitoneal AT (RPAT) of dairy cows in the first 3 weeks postpartum (p.

Changes in lipid metabolism and β-adrenergic response of adipose tissues of periparturient dairy cows affected by an energy-dense diet and nicotinic acid supplementation.

Dairy cattle will mobilize large amounts of body fat during early lactation as an effect of decreased lipogenesis and increased lipolysis. Regulation of lipid metabolism involves fatty acid synthesis from acetate and β-adrenergic-stimulated phosphorylation of hormone-sensitive lipase (HSL) and perilipin in adipocytes. Although basic mechanisms of mobilizing fat storage in transition cows are understood, we lack a sufficiently detailed understanding to declare the exact regulatory network of these in a broad range of dairy cattle.

Effects of an energy-dense diet and nicotinic acid supplementation on production and metabolic variables of primiparous or multiparous cows in periparturient period.

It is well observed that feeding energy-dense diets in dairy cows during the dry period can cause metabolic imbalances after parturition. Especially dairy cows with high body condition score (BCS) and fed an energy-dense diet were prone to develop production diseases due to metabolic disturbances postpartum. An experiment was conducted to determine the effects of an energy-dense diet and nicotinic acid (NA) on production and metabolic variables of primiparous and multiparous cows in late pregnancy and early lactation which were not pre-selected for high BCS.

Changes of Adipose Tissue Morphology and Composition during Late Pregnancy and Early Lactation in Dairy Cows.

Dairy cows mobilize large amounts of body fat during early lactation to overcome negative energy balance which typically arises in this period. As an adaptation process, adipose tissues of cows undergo extensive remodeling during late pregnancy and early lactation. The objective of the present study was to characterize this remodeling to get a better understanding of adaptation processes in adipose tissues, affected by changing metabolic conditions including lipid mobilization and refilling as a function of energy status.

Diagnostic opportunities for evaluation of the exposure of dairy cows to the mycotoxins deoxynivalenol (DON) and zearalenone (ZEN): reliability of blood plasma, bile and follicular fluid as indicators.

To investigate the usefulness of follicular fluid (FF) in relation to blood plasma and bile as indicators of exposure of dairy cows to ZEN, DON and their metabolites, a dose-response study was performed with 30 dairy cows. The cows, 10 in each group (named CON; FUS-50, FUS-100), received a diet with three different concentrations of Fusarium toxin-contaminated maize. Thereby, the following dietary concentration were reached: CON (0.

Effect of increasing body condition on key regulators of fat metabolism in subcutaneous adipose tissue depot and circulation of nonlactating dairy cows.

In response to negative energy balance, overconditioned cows mobilize more body fat than thin cows and subsequently are prone to develop metabolic disorders. Changes in adipose tissue (AT) metabolism are barely investigated in overconditioned cows. Therefore, the objective was to investigate the effect of increasing body condition on key regulator proteins of fat metabolism in subcutaneous AT and circulation of dairy cows.

Description of a bovine model for studying digestive and metabolic effects of a positive energy balance not biased by lactation or gravidity.

Physiological consequences of adaptation to and continued feeding of a high-energetic diet were studied in eight non-pregnant, non-lactating dairy Holstein cows over a period of 16 weeks. The first six weeks served as an adaptation period from the low energetic straw-based diet (3.8 MJ NEL/kg DM) to the high-energetic ration (7.

Agonists of the G protein-coupled receptor 109A-mediated pathway promote antilipolysis by reducing serine residue 563 phosphorylation of hormone-sensitive lipase in bovine adipose tissue explants.

A balanced lipolytic regulation in adipose tissues based on fine-tuning of prolipolytic and antilipolytic pathways is of vital importance to maintain the metabolic health in dairy cows. Antilipolytic pathways, such as the G protein-coupled receptor 109A (GPR109A)-mediated pathway and the insulin signaling pathway in bovine adipose tissues may be involved in prohibiting excessive lipomobilization by reducing triglycerol hydrolysis. This study aimed to evaluate the in vitro antilipolytic potential of the mentioned pathways in bovine adipose tissue explants.

Effects of dexamethasone-21-isonicotinate on peripheral insulin action in dairy cows 5 days after surgical correction of abomasal displacement.

Background: Dexamethasone frequently is used for treatment of ketosis in dairy cows, but its effects are not fully understood.

Hypothesis: Dexamethasone treatment affects whole body insulin sensitivity.

Animals: Twelve German Holstein cows, 2-4 weeks postpartum, 5 days after omentopexy to correct left abomasal displacement.

Lipolysis in early lactation is associated with an increase in phosphorylation of adenosine monophosphate-activated protein kinase (AMPK)α1 in adipose tissue of dairy cows.

Adenosine monophosphate-activated protein kinase (AMPK)α1 is activated in the context of triacylglycerol hydrolysis in adipose tissue in monogastric animals. This study describes AMPKα1 protein expression and the occurrence of its phosphorylated form (pAMPKα1) in different adipose tissue depots as influenced by time and postpartum diet in dairy cows. Biopsy samples were obtained from subcutaneous (SCAT) and retroperitoneal (RPAT) adipose tissues of 20 Holstein cows 21 d prepartum (ap) and 1 and 21 d postpartum (pp).

[Relevance, measurement and assessment of the antioxidative status in farm animals].

Reactive oxygen species (ROS) are generated in living organisms under physiological and pathological conditions. They have to be neutralized by the antioxidative system which consists of enzymatic and non enzymatic antioxidants. Both, the activity of antioxidative enzymes and the capacity of non enzymatic antioxidants are known as the antioxidative status of the organism.

Hormone-sensitive lipase protein expression and extent of phosphorylation in subcutaneous and retroperitoneal adipose tissues in the periparturient dairy cow.

Lipomobilization is essential for dairy cows to balance the energy requirement for milk production in early lactation. This study aimed to determine the role of hormone-sensitive lipase (HSL) and its activation by phosphorylation at Ser 660 (HSLp660) and 563 (HSLp563) in different adipose tissue depots as influenced by time and postpartum diet in dairy cows. Biopsy samples were obtained from s.

Differentiation of viable, apoptotic and necrotic cells in bronchoalveolar lavage fluid of normal horses and horses with recurrent airway obstruction.

Proinflammatoric cytokines are released extracellularly during necrosis. These lead to inflammation and destruction of surrounding tissues. The aim of this study was to compare the number of viable, apoptotic and necrotic cells in the bronchoalveolar lavage fluid (BALF) of normal horses and horses with recurrent airway obstruction (RAO) and to determine if fluorescence microscopy is a reliable method for this examination.

Mutations in the C-terminal region of the HIV-1 reverse transcriptase and their correlation with drug resistance associated mutations and antiviral treatment.

Objective: replication of HIV-1 after cell entry is essentially dependent on the reverse transcriptase (RT). Antiretroviral drugs impairing the function of the RT currently aim at the polymerase subunit. One reason for failure of antiretroviral treatment is the evolvement of resistance-associated mutations in the viral genome.

[Testing for BTV, BVDV and BHV-1 in blood samples of new world camelids kept in middle Germany].

The susceptibility of camelids for infectious agents which may result in severe economic losses or which are strictly regulated for epidemiological reasons in farm animals potentially causes a mutual risk of transmission. This study aimed to investigate the presence of antibodies against bovine herpesvirus 1 (BHV-1), bluetongue virus (BTV) and bovine viral diarrhoea virus (BVDV) as well as the presence of pestivirus antigen in new world camelids in Central Germany. Therefore 107 serum samples from 93 alpacas and lamas from this region which had been obtained from 2007 to 2009 were examined using ELISA, serum neutralisation test, RT-PCR and a pestivirus specific gene probe.