Effects of the dose of erythropoiesis stimulating agents on cardiovascular events, quality of life, and health-related costs in hemodialysis patients: the clinical evaluation of the dose of erythropoietins (C.E. DOSE) trial protocol

<p>Abstract</p> <p>Background</p> <p>Anemia is a risk factor for death, adverse cardiovascular outcomes and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are commonly used to increase hemoglobin levels in this population. In observational studies, higher hemoglobin levels (around 11-13 g/dL) are associated with improved survival and quality of life compared to hemoglobin levels around 9-10 g/dL. A systematic review of randomized trials found that targeting higher hemoglobin levels with ESA causes an increased risk of adverse vascular outcomes. It is possible, but has never been formally tested in a randomized trial, that ESA dose rather than targeted hemoglobin concentration itself mediates the increased risk of adverse vascular outcomes. The Clinical Evaluation of the DOSe of Erythropoietins (C.E. DOSE) trial will assess the benefits and harms of a high versus a low fixed ESA dose for the management of anemia in patients with end stage kidney disease.</p> <p>Methods/Design</p> <p>This is a randomized, prospective open label blinded end-point (PROBE) trial due to enrol 2204 hemodialysis patients in Italy. Patients will be randomized 1:1 to 4000 IU/week versus 18000 IU/week of intravenous epoietin alfa or beta, or any other ESA in equivalent doses. The dose will be adjusted only if hemoglobin levels fall outside the 9.5-12.5 g/dL range. The primary outcome will be a composite of all-cause mortality, non fatal stroke, non fatal myocardial infarction and hospitalization for cardiovascular causes. Quality of life and costs will also be assessed.</p> <p>Discussion</p> <p>The C.E.DOSE study will help inform the optimal therapeutic strategy for the management of anemia of hemodialysis patients, improving clinical outcomes, quality of life and costs, by ascertaining the potential benefits and harms of different fixed ESA doses.</p> <p>Trial registration</p> <p>Clinicaltrials.gov NCT00827021</p

Bioactive Molecules Released in Food by Lactic Acid Bacteria: Encrypted Peptides and Biogenic Amines

Lactic acid bacteria (LAB) can produce a huge amount of bioactive compounds. Since their elective habitat is food, especially dairy but also vegetal food, it is frequent to find bioactive molecules in fermented products. Sometimes these compounds can have adverse effects on human health such as biogenic amines (tyramine and histamine), causing allergies, hypertensive crises, and headache. However, some LAB products also display benefits for the consumers. In the present review article, the main nitrogen compounds produced by LAB are considered. Besides biogenic amines derived from the amino acids tyrosine, histidine, phenylalanine, lysine, ornithine, and glutamate by decarboxylation, interesting peptides can be decrypted by the proteolytic activity of LAB. LAB proteolytic system is very efficient in releasing encrypted molecules from several proteins present in different food matrices. Alpha and beta-caseins, albumin and globulin from milk and dairy products, rubisco from spinach, beta-conglycinin from soy and gluten from cereals constitute a good source of important bioactive compounds. These encrypted peptides are able to control nutrition (mineral absorption and oxidative stress protection), metabolism (blood glucose and cholesterol lowering) cardiovascular function (antithrombotic and hypotensive action), infection (microbial inhibition and immunomodulation) and gut-brain axis (opioids and anti-opioids controlling mood and food intake). Very recent results underline the role of food-encrypted peptides in protein folding (chaperone-like molecules) as well as in cell cycle and apoptosis control, suggesting new and positive aspects of fermented food, still unexplored. In this context, the detailed (transcriptomic, proteomic, and metabolomic) characterization of LAB of food interest (as starters, biocontrol agents, nutraceuticals, and probiotics) can supply a solid evidence-based science to support beneficial effects and it is a promising approach as well to obtain functional food. The detailed knowledge of the modulation of human physiology, exploiting the health-promoting properties of fermented food, is an open field of investigation that will constitute the next challenge

Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (&gt;= 65 years; estimated glomerular filtration rate &lt;= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off &lt;= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

THE ROLE OF MINERAL NUTRITION ON YIELDS AND FRUIT QUALITY IN GRAPEVINE, PEAR AND APPLE

ABSTRACT Fertilization of temperate fruit trees, such as grapevine ( Vitis spp.), apple ( Malus domestica), and pear ( Pyrus communis) is an important tool to achive maximum yield and fruit quality. Fertilizers are provided when soil fertility does not allow trees to express their genetic potential, and time and rate of application should be scheduled to promote fruit quality. Grapevine berries, must and wine quality are affected principally by N, that regulate the synthesis of some important compounds, such as anthocyanins, which are responsible for coloring of the must and the wine. Fermenation of the must may stop in grapes with low concentration of N because N is requested in high amount by yeasts. An N excess may increase the pulp to peel ratio, diluting the concentration of anthocyanins and promoting the migration of anthocyanins from berries to the growing plant organs; a decrease of grape juice soluble solid concentration is also expected because of an increase in vegetative growth. Potassium is also important for wine quality contributing to adequate berry maturation, concentration of sugars, synthesis of phenols and the regulation of pH and acidity. In apple and pear, Ca and K are important for fruit quality and storage. Potassium is the most important component of fruit, however, any excess should be avoided and an adequate K:Ca balance should be achieved. Adequate concentration of Ca in the fruit prevents pre- and post-harvest fruit disorders and, at the same time, increases tolerance to pathogens. Although N promotes adequate growth soil N availability should be monitored to avoid excessive N uptake that may decrease fruit skin color and storability

EFFECT OF TIMING OF NITROGEN APPLICATION ON NITROGEN UPTAKE AND PARTITIONING IN POTTED WALNUT (JUGLANS REGIA L.) TREES

We evaluated the effect of the time of nitrogen (N) application on N uptake efficiency (NUE), partitioning and remobilization in walnut trees of cv Chandler grafted on seedlings. In February 2007, thirty, 2-year-old, trees were planted in 40-L pots and divided in 3 groups of 10 each, according to the time of N application: April 21 (bud burst), May 25 (pistillate flower maturity), September 12 (late summer). Each tree was addressed with 1 g of N (dissolved in water) as ammonium nitrate in which both ammonium and nitrate N were 15N enriched (5% atm.). One week after fertilization, 5 trees for each set were harvested and divided in: current growing shoots, leaves, stem and roots. All organs were dried, weighed milled and analyzed for 15N. At the end of the season the other 5 trees, for each set, were removed from the soil and two trees each group were harvested as above, while the other 3 trees were planted in fresh, 15N-uncontaminated soil until harvest (May 2008), when trees were divided into roots, stem, twigs, shoots, leaves and developing fruits. One week after fertilization the percentage of N derived from fertilizer (NDFF) was higher in trees fertilized in late summer followed by pistillate flower maturity and bud burst. At the end of the trial, the percentage of NDFF and NUE were unaffected by time of fertilization; shoot, leaves and developing fruits presented a higher percentage of NDFF than stem and roots, with no difference induced by timing of N application

Ultrasonography: Ariadne's Thread in the Diagnosis of the Cardiorenal Syndrome

The term cardiorenal syndrome (CRS) describes a broad spectrum of clinical conditions with four combinations of acute and chronic heart and kidney failure. Based on the pathophysiological primum movens, the actual classification recognizes five CRS types: in type I and II CRS, the initiating event is heart failure (acute or chronic), while it is kidney failure in type III and IV CRS; type V is linked to systemic diseases. Ultrasound techniques (echocardiography and ultrasonography of the kidney, inferior vena cava and chest) can be extremely helpful in establishing a prompt diagnosis and a correct CRS classification. Basic echocardiography allows evaluation of ventricular diastolic and systolic functions, investigates pulmonary congestion and pericardial effusion, and describes volume overload. On the other hand, renal ultrasound helps clinicians to distinguish between acute and chronic renal failure, excludes urinary tract dilation or pathological bladder repletion, and provides crucial information regarding kidney volume or echogenicity. Applying basic knowledge of echocardiography and renal ultrasound, nephrologists may be in a better position for patient treatment and management, bearing in mind that doctors can properly use a stethoscope although not being a cardiologist

Pest categorisation of Colletotrichum gossypii

23siThe Panelon Plant Health performed a pest categorisation of Colletotrichumgossypii, the fungal agent of anthracnose and ramulosis diseases of cotton, for the EU. The identity of the pest is well established and reliable methods exist for its detection/identification. The pest is present in most of the cotton-growing areas worldwide, including Bulgaria and Romania in the EU. Colletotrichumgossypii is listed as Glomerellagossypii in Annex IIB of Directive 2000/29/EC and is not known to occur in Greece, which is a protected zone (PZ). The only hosts are Gossypium species, with G.hirsutum and G.barbadense being the most susceptible. The pest could potentially enter the PZ on cotton seeds originating in infested third countries or EU infested areas. Entry into PZ by natural means from EU infested areas is possible, although there is uncertainty on the maximum distance the pest can travel by wind or insects. Bolls and unginned cotton are minor pathways of entry. Pest distribution and climate matching suggest that the pest could establish and spread in cotton-producing areas of northern Greece. In the infested areas, the pest causes damping-off, leaf/boll spotting, boll rot, witches' broom symptoms and stunting resulting in yield and quality losses. It affects also the lint and seeds reducing fibres quality and seed germinability. It is expected that its introduction and spread in the EU PZ would impact cotton yield and quality. The agricultural practices and control methods currently applied in Greece would not prevent pest establishment and spread. Colletotrichumgossypii meets all the criteria assessed by EFSA for consideration as potential quarantine pest for the EU PZ of Greece. The criteria for considering C.gossypii as a potential Union regulated non-quarantine pest are also met since cotton seeds are the main means of spread.openopenJeger, Michael; Bragard, Claude; Caffier, David; Candresse, Thierry; Chatzivassiliou, Elisavet; Dehnen‐Schmutz, Katharina; Gilioli, Gianni; Grégoire, Jean‐Claude; Jaques Miret, Josep Anton; MacLeod, Alan; Navajas Navarro, Maria; Niere, Björn; Parnell, Stephen; Potting, Roel; Rafoss, Trond; Urek, Gregor; Van Bruggen, Ariena; Van der Werf, Wopke; West, Jonathan; Winter, Stephan; Vloutoglou, Irene; Bottex, Bernard; Rossi, VittorioJeger, Michael; Bragard, Claude; Caffier, David; Candresse, Thierry; Chatzivassiliou, Elisavet; Dehnen‐schmutz, Katharina; Gilioli, Gianni; Grégoire, Jean‐claude; Jaques Miret, Josep Anton; Macleod, Alan; Navajas Navarro, Maria; Niere, Björn; Parnell, Stephen; Potting, Roel; Rafoss, Trond; Urek, Gregor; Van Bruggen, Ariena; Van der Werf, Wopke; West, Jonathan; Winter, Stephan; Vloutoglou, Irene; Bottex, Bernard; Rossi, Vittori